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3. A 46-year-old CKD 5 Afro-Caribbean on HD for the last 4 years secondary to IgAN presented to you in the transplant assessment clinic to consider suitability for kidney transplantation. His brother is willing to donate a kidney for him, 000 mismatch and no DSA. On routine examination this lesion was identified
- What is your differential diagnosis?
- Council this patient regarding kidney transplantation?
- What is your workup strategy?
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1. Differential diagnosis
Melanoma
Dysplastic nevus
2. Staging of lesion to assess prognosis and waiting time for transplantation
In situ no waiting
Stage IA,IIA IB 1 year
stage IIIA 1 to 2 years
Stage IIB,IIIB,IIC 2 to 4 years
Stage IIIC,IIID at least 5 years
3. History and examination
Biopsy and staging
Switch CNI to mTor inhibitors
Provisional Diagnosis:
Malignant melanoma
Differential diagnoses:
Points for patient counseling:
Work up strategy:
This patient first needs to stage the malignant melanoma then to decide when to go for transplantation
as melanoma with stage IA, IB, IIA, and IIIA is greater than 90%. Thus, a maximum of a 1-year wait time prior to transplantation for this group of patients, with 1- to 2-year wait time for stage IIIA patients.
The 5-year melanoma-specific survival for those with stage IIB, IIC, and IIIB is greater than 80%, with a plateau observed on the survival curve beyond.Therefore, we recommend a wait time of 2–4 years prior to transplantation for this group of patient.The 5-year melanoma-specific survival for those with stage IIIC and IIID is between 30% and 70%, with a plateau observed on the survival curve at 4–5 years. Furthermore, the 5-year overall survival rates for patients with metastatic melanoma is now over 35%, with long-lasting treatment responses even after discontinuation of active checkpoint inhibitor therapy. Institution of a wait time of at least 5 years prior to transplantation is optimal in these cases.
Malignant melanoma
Dysplastic navus
SCC
The characteristics of malignant melanoma arising in transplant patients are not clearly delineated. We describe clinical and histological features of malignant melanoma in five transplant patients. All transplant patients with melanoma arising post-transplantation had a previous history of skin cancer. Two had a history of internal organ malignancy. Three patients had thick malignant melanomas (Clark level III or higher, or >0.76 mm Breslow thickness). Lymph-node metastases occurred in one patient with cutaneous melanoma. Local cutaneous metastases occurred in one patient. Mean duration from transplantation to melanoma was 15.6 years. Two cases of aggressive metastatic melanoma responded well to cessation of immunosuppression. Three patients with nonmetastatic disease responded well to conventional complete excision and continuation of immunosuppression.
https://www.researchgate.net/publication/7004319_Malignant_melanoma_in_transplant_patients_Review_of_five_cases
This is most likely Malignant melanoma
Other differential may be
Council this patient regarding kidney transplantation?
He may need to wait for transplantation,depending upon stage of the melanoma.
The 5-year melanoma-specific survival for those with stage IA, IB, IIA, and IIIA is greater than 90%, thus, a maximum of a 1-year wait time prior to transplantation for this group of patients, with 1- to 2-year wait time for stage IIIA patients. The 5-year melanoma-specific survival for those with stage IIB, IIC, and IIIB is greater than 80%, with a plateau observed on the survival curve beyond.Therefore, we recommend a wait time of 2–4 years prior to transplantation for this group of patient.The 5-year melanoma-specific survival for those with stage IIIC and IIID is between 30% and 70%, with a plateau observed on the survival curve at 4–5 years. Furthermore, the 5-year overall survival rates for patients with metastatic melanoma is now over 35%, with long-lasting treatment responses even after discontinuation of active checkpoint inhibitor therapy. Institution of a wait time of at least 5 years prior to transplantation is optimal in these cases.
What is your workup strategy?
Biopsy of the lesion followed by staging of melanoma is needed .Treatment and transplantation willl depend upon the Stage of melanoma
Differential diagnosis could possibly be:
Tumours either benign or malignant (Melanoma or dysplastic nevus or squamous cell carcinoma or benign melanocytic lesions or Metastatic tumors to the skin or Epithelioid tumor or Pigmented spindle cell tumor)
Other lesions as blue nevus or Halo nevus or Pigmented actinic keratosis which might be precancerous.
Regarding renal transplantation, it is better to search for another donor or deceased donation program or dialysis as renal replacement therapy. There is a first degree relationship between them making the development of post renal transplant malignancy occurrence become more likely apart from the presence of other factors as immunosuppression and male gender. It is believed that skin cancers are the most associated post SOT malignant lesions, being aggressive and accompanied with high incidence of mortality.
The work up strategy:
Multidisciplinary team is required involving transplant professional, dermatologists and oncologists. Biopsy from the lesion determines the chemotherapeutic and other treatment options.
Full screening of internal organs is necessary especially to exclude visceral involvement.
If transplantation will be resumed after excluding the donor’s malignancy, low dose immunosuppression is needed. Better to avoid T and B cell depleting agents in induction. Maintenance immunosuppression would be based on low drug level i.e. the least dose required to avoid graft rejection as well as early switching to mTORi poses a better choice.
What is your differential diagnosis?
Council this patient regarding kidney transplantation?
What is your workup strategy?
What is your differential diagnosis?
· Malignant Melanoma
· benign melanocytic lesions
· blue nevus
· dysplastic nevus
· squamous cell carcinoma
· basal cell carcinoma
· Gangrenous lesion
Council this patient regarding kidney transplantation?
· I will break bad news that melanoma is the most likely diagnosis. However, biopsy and histology will confirm the diagnosis and the stage.
· I will inform him that there is a risk of recurrence and the need to be vigilant about that, but waiting for a period of time will help reduce risk of recurrence post-transplant.
· According to the American Joint Commission on Cancer-AJCC (Cancer Staging Manual) the defined time required before SOT:
stage 0: There is no need to defer SOT
stage 1a: wait for 2 years
stage 1b:wait for 5 years
stage IIa, IIb, IIIa: wait for 5 – 10 years
stage IIc, IIIb, IV: No SOT
· If transplant does happen, modifications of immunosuppression is required
What is your workup strategy?
References
The differential diagnosis include melanoma and squamous cell carcinoma.
There is excellent mismatch 0 0 0 and no DSA , but exclusion of malignant skin tumor is mandatory by skin biopsy and histopathology examination
What is your differential diagnosis?
The differential diagnosis is of Squamous cell carcinoma or melanoma. Tissue biopsy is recommended for the confirmation.
Council this patient regarding kidney transplantation?
Waiting period is suggested before the transplant.
What is your workup strategy?
First the lesion is screened for metastasis and then waiting period is calculated. mTOR inhibitors are used for immunosuppression.
What is your differential diagnosis?
Council this patient regarding kidney transplantation?
you can donate after you treat your skin cancer , but i would not advise you to do so as there is chance that he transmit the cancer to the brother(recipient ) hence he can have the cancer post transplant especially with the induction and immunosuppression.
we have to biopsy the lesion and check it staging accordingly we can decide when you can donate the kidney after 1 year if stage 1 or after 5 years if stage iv
melanoma initially present in the donor has a 74% transmission rate and a 58% mortality rate for organ transplant recipients.
in case the patient recieved the kidney from his brother, he should avoid CNI instead , mtor inhibitors should be part of him IS .
work up include:
a full-body examination to search for lesions or scars suspicious for melanoma else where, wide exision and staging.
the managment should be combined with dermatologist and oncologist.
Differential diagnosis for black discloration in the skin include: benign nevus or melanoma
tissue biopsy should done to confirm the diagnosis
if it is benign will proceed to transplant but if it is malignant we should counsel the patient about the waiting time before the transplant
Q1: The differential diagnosis includes:
· Melanoma
· dysplastic nevus
· SCC and melanocytic lesions
Q2: staging of the lesion is necessary before transplantation to calculate the outcome and waiting time for TX according to the AJCC.
In situ: no waiting.
stage IA, IB, IIA: 1 year
stage IIIA: 1-2 years
stage IIB, IIC, IIIB: 2-4 years
stage IIIC, IIID, IV: at least 5 years.
Immunosuppression includes mTOR inhibitors instead of CNIS.
Q3: we need a consultation with different specialists such as dermatologists and oncologists.
Different studies regarding spreading and staging such as CXR, PETscan, Excisional biopsy, and treatment strategies according to diagnoses such as pembrolizumab or immunotherapy.
Lesion at the heel of the foot in ESKD pt for DD calciphylaxis, gangrene, hematoma, PVD, skin cancer melanoma
Exact diagnosis and staging of melanoma if confirmed
Proper counselling of the patient for risk of recurrence post transplant with proper sun exposure protection.
Work up strategy :
Full history
Proper physical examination including dermatology consultation
Investigations :
Dupplex to exclude PVD
Biopsy of the lesion and oncologist consultation
a. Melanoma in situ: No wait-time
b. Class IA, IB, IIA: 1 year
c. Class IIB, IIC: 2-4 years
d. Class IIIA: 1-2 years
e. Class IIIB: 2-4 years
f. Class IIIC, IIID, IV: At least 5 years
mTOR may be used instead of tacrolimus for immunosuppression
Assalam o alaikum
1. What is your differential diagnosis?
o Malignant Melanoma
o Benign melanocytic lesions.
o Dysplastic nevus.
2. Counsel this patient regarding kidney transplantation?
o Breaking the news
o Discuss in detail the need to confirm diagnosis and evaluate for staging
o If it is confirmed then the patient might have to wait for a while to proceed for renal transplantation (depending on the AJCC stage)
(In situ = no waiting time, Stage IA, IB, IIA, = 1 year, Stage IIIA = 1-2 years, Stage IIB, IIC, IIIB = 2-4 years, Stage IIIC, IIID, IV = atleast 5 years)
o The risk of recurrence would be higher but waiting for a period of time will help reduce risk of recurrence post-transplant
o When transplant does happen, would need to have certain modifications of immunosuppression
3. What is your workup strategy?
o Clinical examination for satellite lesions
o Dermatology consult and dermoscopy to confirm diagnosis
o Excision biopsy for histopathology & immunohistochemistry
o Imaging (CECT chest, abdomen and pelvis) vs PET Scan
o Serum LDH
REFERENCES:
1. Watschinger B, Budde K, Crespo M, et al. Pre-existing malignancies in renal transplant candidates-time to reconsider waiting times. Nephrol Dial Transplant. 2019;34(8):1292-1300. doi:10.1093/ndt/gfz026
2. Al-Adra DP, Hammel L, Roberts J, et al. Preexisting melanoma and hematological malignancies, prognosis, and timing to solid organ transplantation: A consensus expert opinion statement. Am J Transplant. 2021;21(2):475-483. doi:10.1111/ajt.16324
Differential diagnosis
Counseling regarding kidney transplantation
The following will be put into consideration in counseling the patient
The result of the histological will help to make proper counseling on the waiting time before the kidney transplant can be done
According to American Joint Commission on Cancer Cancer Staging Manual; ITSCC, International Transplant Skin Cancer Collaborative
Stage of cancer recommended time to SOT
stage o no need to defer SOT
stage 1a 2 years
stage 1b 5 years
stage IIa, IIb, IIIa 5 – 10 years
stage IIc, IIIb, IV no need for SOT
Also, MDT will be set involving transplant physician, surgeon, oncologist, histopathologist, dermatologist, and clinical psychologist.
Work up strategy
Reference
Most likely malignant melanoma
Other D/D include
a) Dysplastic nevus
b) Squamous cell Carcinoma
c) Actinic Keratosis
2. Counselling regarding kidney transplantation?
I’ll counsel the patient regarding the possible D/D is malignant melanoma.
It must be investigated in detail and possibly managed before kidney transplant surgery.
Investigation and management requires a Nephrologist ,Oncologist, Pathologist, General Surgeon and Dermatologist)
-I’ll guide the patient regarding importance of Biopsy and The Staging of the disease which’ll decide the transplant decision depending on the result of the histopathology and the staging of the disease as following .
-Stage 0 No need to delay
-Stage Ia Delay for 2 years
-Stage Ib Delay for 5 years
-Stage IIa, IIb, IIIa Delay for 5-10 years
-Stages IIc, IIIb,
-IV Don’t go for Transplant
-I’ll counsel regarding risk of recurrence after kidney transplant and there’ll be more risk of de novo malignant melanoma .
3.What is your workup strategy?
I’ll take complete history to rule out family history of skin cancers, Previous cancers and other possible risk factors
I’ll do Complkete examination to determine the extent of disease
Ultrasound is the imaging modality of choice to diagnose nearby lymph node involvement and PET/CT is the best imaging study to look for other sites of metastasis.
Multidisciplinary team involvement with Nephrologist, Dermatologist, General Surgeons and Oncologists
Dermatologist opinion for diagnosis, for Excision biopsy and staging
Surgical and Oncology opinion for treatment and staging
Definitive treatment of Malignant Melanoma is surgery
Medical management is reserved for adjuvant therapy of patients with advanced melanoma
· By stage, standard treatment options for melanoma are as follows :
o Stage 0 – Excision
o Stage I – Excision, with or without lymph node management
o Stage II – Excision, with or without lymph node management
o Resectable stage III – Excision, with or without lymph node management; adjuvant therapy and immunotherapy
o Unresectable stage III, stage IV, and recurrent melanoma – Intralesional therapy, immunotherapy, signal transduction inhibitors, chemotherapy, palliative local therapy.
Post transplantation immunosuppressive therapy:
i) Reduction of immunosuppression ( early cyclosporin withdrawl)
ii) Consider mTOR inhibitor (sirolimus)-
This reduce cell growth & proliferation.
Advice the patient regarding avoidance of sun exposure, Sun Block usage & self examination.
REFERENCES :
1)D/D:
Malignant melanoma
Dysplastic Nevus.
2)Counselling Regarding Tx:
– Needs confirmation of lesion by MDT(Dermatologist, Histopathologist, radiologist)
– If melanoma, there is chances of recurrence.
– According to histopathology grade of
melanoma pt may have to wait for variable
period
Stage 0/ melanoma in situ:no need to wait
Stage Ia: 2years
Stage Ib: 5 years
Stage IIa, b and IIIa: 5-10 years
Stage IIc, IIIb and IV: not candidiate for
transplantation.
– Immunosuppressive: early shift from
calcineurin inhibitors to mTor to reduce
melanoma recurrence.
– To prevent recurrent and de Novo melanoma-.
avoid mid day sunexposure, use of brad
spectrum (high SPF & × ) sunblock, protective
Clothings
-Regarding primary disease: IgAN can recur in
30- 35% cases.
3) Work up strategy:
– MDT approches.
– H/O, Clinical Exam( Lymphadenopathy)
– Investigations:
Histopathologic confirmation and staging.
– LFT, KFT.
– Imaging: CXR, USG of W/A, if possible
PET-CT.
Treatment of lesion:
Wide excision with free margin.
Appropriate chemotherapy: according to
current dermatology and oncology protocol
What is your differential diagnosis?
# The differential diagnosis are:
Malignant melanoma
Benign melanocytic lesions
Dysplastic nevus or skin hematoma
Squamous cell carcinoma
# Council this patient regarding kidney transplantation?
This patient needs counseling regarding the risk of melanoma in SOT recipients, as they have a higher risk of melanoma than immunocompetent people, they have an even higher risk of squamous cell carcinoma (50- to- 250-fold increased risk) and basal cell carcinoma (10-fold increased risk). Melanoma is a highly immunogenic tumor and responds very well to new immunotherapies.
And also they need counseling about staging protocol biopsy to determine the suitable time for transplantation
Stage 0 No need to defer SOT
Stage 1a 2 Y
Stage 1b 5 Y
Stage 11a, 11b, 111a 5-10 Y
Stage 11c, 111b, 1V Not candidate for SOT
# What is your workup strategy?
History and physical exam
Removing a sample of tissue for testing (biopsy).
The best treatment for melanoma depends on the size and stage of cancer.
Treatment for early-stage melanomas usually includes surgery to remove the melanoma. A very thin melanoma may be removed entirely during the biopsy and require no further treatment. Removal of the cancer as well as a border of normal skin and a layer of tissue beneath the skin. For people with early-stage melanomas, this may be the only treatment needed.
If melanoma has spread beyond the skin, treatment options may include:
Surgery to remove affected lymph nodes
ImmunotherapyTargeted therapy
Radiation therapy.
Chemotherapy.
Stage 0 melanoma is almost always treated with surgery alone, usually a wide excision.
Stage I melanoma with surgical removal of the tumor and some of the healthy tissue around it, some lymph nodes may be removed.
Stage II melanoma is surgery to remove the tumor and some of the healthy tissue around it. While this surgery is being done, lymphatic mapping and sentinel lymph node biopsy may also be done. Stage IIB and stage IIC melanoma, treatment with 1 year of pembrolizumab is an option.
Stage III melanoma has spread locally or to a regional lymph node or to a skin site on the way to a lymph node. If the stage III melanoma can be removed with surgery, this typically will be the first treatment option. The lymph nodes may be checked for cancer and removed. After surgery, treatment with immunotherapy or targeted therapy may be recommended to help prevent the cancer from coming back. Advanced melanoma is a stage III melanoma that cannot be treated with surgery or stage IV melanoma.
1)AskMayoExpert. Melanoma, cutaneous, stage I to III: Diagnosis and treatment (adult). Mayo Clinic; 2018.
2)Cutaneous melanoma. National Comprehensive Cancer Network. https://www.nccn.org/professionals/physician_gls/default.aspx. Accessed Jan. 8, 2020.
3)Mitchell TC, Karakousis G, Schuchter L. Chapter 66: Melanoma. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa: Elsevier; 2020.
4)Malignant Melanoma Differential Diagnoses
Updated: Jan 26, 2023
Author: Winston W Tan, MD, FACP; Chief Editor: Dirk M Elston, MD
What is your differential diagnosis
This is pigmented skin lesion most likely malignant melanoma; the differential could be benign melanocytic lesion and pigmented actinic Keratosis.
Talk to The patient about the possible diagnosis is malignant melanoma which should be investigated and managed before the decision of kidney transplant. which should be MDT approach (nephrologist ,dermatologist , oncologist and histopathologist )
-Counseling regarding the need of biopsy and staging of the disease which may delay or even prohibit the transplant decision depending on the result of the histopathology and the staging of the disease as following .
-Stage 0 No need to defer SOT
-Stage Ia 2 y
-Stage Ib 5 y
-Stage IIa, IIb, IIIa 5-10 y
-Stages IIc, IIIb,
-IV Not candidates for SOT
-Another thing to talk about is the risk of recurrence after kidney transplant and even increased risk of de novo malignant melanoma .
– In early-stage melanoma, prognosis in SOT recipients is similar to that of the general population.
What is your workup strategy?
Reference:
1 . Am J Transplant. Author manuscript; available in PMC 2021 Oct 29.Published in final edited form as:Am J Transplant. 2021 Feb; 21(2): 475–483. Published online 2020 Oct 10. doi: 10.1111/ajt.16324
2. Recommendations for Solid Organ Transplantation for Transplant Candidates With a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma: A Consensus Opinion From the International Transplant Skin Cancer Collaborative (ITSCC) Am J Transplant, 16 (2016), pp. 407-413
3. Melanoma in Solid Organ Transplant Recipients https://www.binasss.sa.cr/marzo/22.pdf
What is your differential diagnosis ?
1.Benign melanocystic lesion
2.Dysplastic nevus
Council this patient regarding kidney transplantation?
1.Regarding the Skin lesion
2.Possibility of recurrence & de novo melanoma after transplantation
3.Regarding protection from recurrence or de novo
4.Regarding the Primary disease
Regarding the Skin lesion –
Stage 0/ melanoma in situ: no need to wait
· Stage Ia: 2years
· Stage Ib: 5 years
· Stage IIa, b and IIIa: 5-10 years
· Stage IIc, IIIb and IV: not candidiate for transplantation
Regarding protection from recurrence or de novo
1.Avoid intense sun exposure.
2. Avoid sun exposure for an hour or two on either side of mid-day.
3.Sun protective clothing: Long sleeve silk clothing, sunglass, cotton cricket hat is better.
4.Regular use of high factor sun block (SPF 50+ UVA)
5.Self examination before & after transplantation regularly.
Regarding the Primary disease
Risk of recurrence of IgAN after renal transplantation & chance of graft loss 30%.
What is your workup strategy?
1.Dermatology opinion for diagnosis, for punch biopsy and staging
2.Surgical and Oncology opinion regarding the staging and treatment
· By stage, standard treatment options for melanoma are as follows :
o Stage 0 – Excision
o Stage I – Excision, with or without lymph node management
o Stage II – Excision, with or without lymph node management
o Resectable stage III – Excision, with or without lymph node management; adjuvant therapy and immunotherapy
o Unresectable stage III, stage IV, and recurrent melanoma – Intralesional therapy, immunotherapy, signal transduction inhibitors, chemotherapy, palliative local therapy.
i) Reduction of immunosuppression( early cyclosporin withdrawl)
ii) Consider mTOR inhibitor (sirolimus)- This reduce cell growth & proliferation.
REFERENCES –
There is a large deep black pigmentation with irregular border present on sole of the foot. So my differential diagnosis are
a)Malignant melanoma
b)Non melanoma skin cancer
c)Melanocytic lesion
d)Dysplastic nevus
Counseling depends on definitive diagnosis of this lesion which needs skin biopsy.
a) Waiting time: In case of malignant melanoma needs appropriate treatment then council the patient regarding cancer free interval period prior to renal transplantation. This waiting time depends on staging of malignant melanoma-
Stage 0/in situ melanoma:no waiting time
Stage Ia: 2 years
Stage Ib: 5 years
Stage IIa, IIb, IIIa: 5 – 10 years
Stage IIc, IIIb & IV: contraindicated to transplantation.
b) Risk of recurrence of IgAN after renal transplantation & chance of graft loss 30%.
c) Risk of recurrence of malignant melanoma
d) Avoid sun:
i) Avoid intense sun exposure.
ii) Avoid sun exposure for an hour or two on either side of mid day.
e) Sun protective clothing: Long sleeve silk clothing, sunglass, cotton cricket hat is better.
f) Regular use of high factor sun block ( SPF 50)
g) Self examination before & after transplantation regularly.
a) Detail clinical examination: similar lesion in other site of body, lymphadenopathy
b) Skin biopsy
c) Staging workup: CT with contrast of chest, abdomen & pelvis.
d) Treatment of this lesion: Surgical excision, Topical 5 FU
e) Determine waiting time for transplantation.
f) Post transplantation immunosuppressive therapy:
i) Reduction of immunosuppression( early cyclosporin withdrawl)
ii) Consider mTOR inhibitor(sirolimus)- This reduce cell growth & proliferation.
g) Advice the patient regarding avoidance of sun exposure & self examination.
Clinical D/D include
Malignant melanoma
ischemic gangrene (arterial – due to calciphylaxis)
Blue naevus
It could be a form of malignant or premalignant lesion – needs evaluation and treatment
If it comes out to be a cancer, then adequate treatment involving Oncology team shall be required.
At present he is not fit to undergo transplant, needs to concentrate on treatment of cancer, along with dialysis and other supportive measures like nutrition.
After cure of the cancer with appropriate treatment regimen, a minimum observation period of 2-3 years (depending on type of malignancy) shall be required to look for any recurrence or metastatic lesion to appear. Once no recurrence or new lesion found after such observation period, he shall be reevaluated for fitness about transplant
Shall involve a Dermatologist for evaluation
Excision Biopsy of the lesion shall be required
If Melanoma – CT / MRI of Pelvis and Abdomen for lymphatic involvement with Inguinal / pelvis Lypmh-node biopsy.
Treatment of the lesion (malignancy) involving Oncology team, Dermatologist and Surgeon.
regular follow up (2-3 years) – to look recurrence or manifestation of occult mets.
Meanwhile regular dialysis, proper diet and supportive medications to continue
co-ordination with the dermatologist
-malignant melanoma
-naevus
-haematoma
-gangrene (arterial or venous ulcer)
-….etc
if it is a cancer ….require an interval between cancer management and transplantation depending on the type of cancer
also should inform about the possibility of recurrence after transplantation
What is your workup strategy?
an MDT discussion with the presence of dermatologist and oncologist
my 1st differential diagnosis is malignant melanoma in people with darker skin like Afriocarribeans but when it occurs it ysually affects the palms and soles.and its called acral lentigenous melanoms
other ddx:
I tell the patient that
so he requires careful evaluation to detect any cancer or precancerous lesion and get definitive treatment for it before transplantation.
and the waiting time afterwards will depend upon the type and stage of cancer.
and also perform regular self examination.
1.if the skin lesion is a melanoma then the donor’s risk of having melanoma is also increased
2.regarding the recurrence of IgAN after transplantion,several studies showed that live donor and related donor both increase the risk of recurrence and this could be explained by several points
◇ What is your differential diagnosis?
1) Malignant melanoma
2) melanocytic lesions.
3) Dysplastic nevus.
4) Squamous cell carcinoma.
5) Hematoma
◇Council this patient regarding kidney transplantation?
I will tell the patient that:
▪︎Organ transplant recipients, including kidney transplant recipients, have more skin cancers than the general population because the immunosuppressive medications that help to protect their transplanted organ also increase their risk for skin cancer.
▪︎ The importance of screening of skin cancers.
▪︎The waiting time before transplantation
with various groups recommending anywhere from no wait to 5 years (1)
▪︎Melanoma is an immune responsive malignancy and the need for immunosuppression for successful transplantation may lead to recurrent disease.
▪︎The importance of the usage of sunscreen.
▪︎I will tell the patient that, There are 3 important steps that you can take to reduce your risk of skin cancer:
1. Protect yourself from the sun.
2. Perform skin self-examinations
◇ Workup strategy:
Consult a dermatologist for a full skin examination.
The recommended waiting time is unknown (kidney transplantation isbsafe in patients with a prior history of localized melanoma and shorter waiting time. In malignant melanoma stage 0 and 1, waiting the recommended 5 years from the time of remission to kidney transplantation should be reconsidered. isolated renal transplantation is associated with the lowest risk of skin cancers when compared to heart, lung and pancreas-kidney transplant. The degree of immunosuppression which will also affect the risk.
◇ What is your workup strategy?
▪︎Proper history: to see if there is family history of melanoma.
▪︎Drug history (Immunosuppressio), if there is Excessive UV exposure, including tanning beds.
▪︎Examination:
– Use the 7-point weighted checklist for assessment of pigmented skin lesions:
– Major features of lesions (two points each): Change in size. Irregular shape. Irregular colour.
– Minor features of lesions (one point each): Largest diameter 7 mm or more. Inflammation. Oozing. Change in sensation ▪︎ Consult a dermatologist.
▪︎ Skin biopsy to reach a definite diagnosis ▪︎Treat the patient according to the diagnosis.
▪︎ Wait time before transplantation
If the biopsy showed melanoma in situ/lentigo maligna : excision and transplant with out waiting
if the biopsy confirmed . Patients Ia, Ib or IIa must wait for 2 to 5 years before transplantation,
patient with biopsy proven stage IIb or IIc should wait for 5 years.
we can not transplant ptients with metastasis Patient should void sun exposure especially in the mid-day and the use of sun screen with high protection (5 stars 50+ SPF) is recommended especially in the early period after transplantation (using of triple therapy)
▪︎ Reassur the patient since the patient will receive minimal immunosuppression
Notes:
Some studies demonstrates safety of kidney transplantation in patients with a prior history of localized melanoma and shorter waiting time. In malignant melanoma stage 0 and 1, waiting the recommended 5 years from the time of remission to kidney transplantation should be reconsidered (1).
_______________________
Ref
1) Shaker Qaqish et al. Listing Malignant Melanoma Patients for Renal Transplantation. Transplant Proc. 2020 . .
1- Malignant Melanoma
2- Dysplastic nevus
3- Squamous cell carcinoma
4- Metastatic tumors to the skin
5- Benign Melanocytic Lesion
6- Acquired perforating dermatosis
We need dermatological and oncology consultation to make a definite diagnosis , surly we need biopsy from this lesion , if its is benign we can proceed with transplantation , if its malignant we should inform the patient about the Waiting time..according to staging
From insitu to stage II c can be candidate for Tx. Stage III and IV are not for Tx.
Institute no delay time but follow up screening every 3 months. Two years for Ib up to 5 years in stage II b and II c. and Strategies for avoidance of sun.
immunosupression protocol changing cyclosporine and mTOR inhibitors.
there is a chance of tumor recurrence after transplant, even after waiting time . Precautions like sun screen, avoiding mid-day sun and using Sirolimus will reduce the likelihood of recurrence.
thanks
Uffing A, Pérez-Saéz MJ, Jouve T, Bugnazet M, Malvezzi P, Muhsin SA, Lafargue MC, Reindl-Schwaighofer R, Morlock A, Oberbauer R, Buxeda A, Burballa C, Pascual J, von Moos S, Seeger H, La Manna G, Comai G, Bini C, Russo LS, Farouk S, Nissaisorakarn P, Patel H, Agrawal N, Mastroianni-Kirsztajn G, Mansur J, Tedesco-Silva H, Ventura CG, Agena F, David-Neto E, Akalin E, Alani O, Mazzali M, Manfro RC, Bauer AC, Wang AX, Cheng XS, Schold JD, Berger SP, Cravedi P, Riella LV. Recurrence of IgA Nephropathy after Kidney Transplantation in Adults. Clin J Am Soc Nephrol. 2021 Aug;16(8):1247-1255. doi: 10.2215/CJN.00910121. PMID: 34362788; PMCID: PMC8455056.
1. Most likely Malignant melanoma, D/D( Dysplastic nevus, SCC, skin metastasis).
2. Councell about the risk of recurrence of the disease after transplantation & proper treatment with possibe waiting time before Tx.
3. Skin biopsy for confirmation, detailed systemic evaluation, dermatologist & oncologist consutation.
46 y old CKD stage 5 patient Afro-caribbean on HD since 4 years due to IGAN came for assessment having donor his brother 000 mismatched no DSA
while examination found the above lesion
differential diagnosis:
malignant melanoma (irregular border black lesion)
dysplastic nevus
sequamus cell carcinoma
metastatic tumor
council patient:
firstly diagnose the lesion :-
1-History and risk factors (when was lesion /size and shape/colour/symptom/ other family history/history of sun exposure or history of sever burn or cancer prone syndrome /if patient on immunosuppressive/ or received prolonged PUVA therapy.
2-skin examination:
-visual analysis and pattern recognition.
-comparative analysis of nevus pattern in an individual patient .
-dynamic analysis using ABCDE cretiria
Asymmetry (if a lesion is bisected, one half is not identical to other half)
Border irregularities.
Color variegation (presence of multiple shades of red, blue, black, gray, or white).
Diameter ≥6 mm.
Evolution (a lesion that is changing in size, shape, or color, or a new lesion).
*target education to motivate patient for skin examination.
* regular use of high factor sun blocker SPF + 50.
Work up:
-aggressive screening for skin cancer.
– aggressive management ‘ of precancerous skin lesion.
– changing of immunosuppressive protocols and dosing while achieving adequate therapy with decreased carcinogenicity.
– patient education regarding protection from sun exposure with self examination.
Malignant Melanoma
Squamous cell carcinoma
dermatology referral for skin biopsy & evaluation,
Counselling about the possibility of recurrence post-transplantation.
education for self-examination of the skin after transplantation and follow-up every three months are required.
detailed history about the lesion, any history of trauma, present of other lesions.
send skin biopsy, If the biopsy confirmed melanoma waiting list for renal transplantation 2-5 years about immunosuprestion early change CNI to sirolimus if there is no rejection risk.
references:
-Handbook of transplantation
2.Counsel the patient
Skin cancers have a variable risk for metastasis. However, if there is an active malignancy, this is a contraindication for transplant.If the risk for metastasis is minimal, transplantation can be done.
Pre transplantation basal cell carcional or squamous cell carcinoma is a marker for an increased likelihood of multiple de novo Non melanoma skin cancers after transplantation. It is not a contraindication for transplantation but requires aggresive preventive steps to be taken to prevent recurrence.
Primary basal cell carcinoma is not a contraindication to transplantation but a metastatic case in remission or not in remission is a contraindication and the patient should be reassessed after five years. This is the same with Squamous cell carcinoma.
Pre transplant melanoma insitu is not a contraindication for transplant, but Stages Ii,III and IV are, The patient have to be reassesed 3-10 years after the initial diagnosis.
3.Workup strategy
Investigate the lesion: with the aid of a dematologist, a detailed history and physical examination to be done to identify other lesions [related to this lesion or not]; and any lymph node enlargement. A history of prior cancers [with
A biopsy of the lesion for histology.
Imaging to look for sentinel lymph nodes, metastases and organ involvement.
Staging of the lesion if found to be malignant
REFERENCES
Skin Cancer as a Contraindication to organ Transplantation. Hiroseb et al. American Journal of Transplantation 2005; 5: 2079–2084
Skin Cancers as Contraindication to Organ Transplantation. Imko-Walczuk et al. Transplant Proc. 2015. Jul-Aug 47(6): 1547-52
What is your differential diagnosis?
There is a black dark pigmented macule or papule on the sole with asymmetric irregular border.
DD:
1-Malignant Melanoma.
2-Acral Lentiginous Melanoma.
2-Benign Melanocytic Lesion.
3-Dysplastic Nevus.
4-Squamous Cell Carcinoma.
5-Metastatic Cutaneous deposits.
6-Acquired Perforating Dermatosis.
7-Epitheliod tumour.
Council this patient regarding kidney transplantation?
Pre-transplantation counselling regarding the following points:
1- Diagnosis and treatment of this lesion will guide the discussion and will direct the team if the patient can proceed for renal transplantation or he needs to wait.
2- Waiting time between treatment and organ transplantation in cutaneous malignancy:
a-Melanoma in situ/Lentigo Maligna–à> no waiting time after wide excision.
b-Melanoma stage Ia/Ib—>> 1 year waiting time.
c-Melanoma stage IIb/IIc/IIIb——>> 2-4 years waiting time.
d-Melanoma stage IIIa/—–>> 1-2 years.
e-Melanoa stage IIIC/IIId—–>> 5 years waiting time.
f-Melanoma with distant metastasis—>> not eligible for TX.
3- Pre-transplant history of melanoma carries 10-12% risk of recurrence post-transplantation.
4- New primary Melanoma can develop after kidney transplantation in 2-3% of recipients.
5- Other types of cutaneous cancer can develop after renal transplantation.
6- Regular self-examination and annual dermatological examination are essential looking for recurrent or de-novo lesions.
7- Post-TX counselling regarding immunosuppression regimen and protection from sun exposure.
What is your workup strategy?
History and examination: local and systemic especially for other lesions, lymph nodes, distant metastasis, peripheral vascular disease.
Dermatology review for examination and excisional skin biopsy.
Oncology Review for staging (CT-chest abdomen and pelvis or PET-CT) and advice regarding any further management.
Waiting time will be decided according to diagnosis and staging as mentioned above.
If the patient is deemed suitable and safe for transplantation, immunosuppression protocol is recommended as follows: lower immunosuppression as low as possible. Consider switching CNI to m-TOR inhibitors, Azathioprine to MMF.
Regular self-examination and annual dermatological examination are essential looking for recurrent or de-novo lesions.
Protective sun exposure measures.
References;
Al-Adra DP, Hammel L, Roberts J, Woodle ES, Levine D, Mandelbrot D et al. Preexisting melanoma and hematological malignancies, prognosis, and timing to solid organ transplantation: A consensus expert opinion statement. American Journal of Transplantation. 2021 Feb;21(2):475-483. doi: 10.1111/ajt.16324.
Chadban, Steven et al. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation 2020.
Handbook of transplantation – 6th edition.
Rehnberg J, Ludvigsson JF, Carrero JJ, Emilsson L. Cancer risk in patients with immunoglobulin A nephropathy: a Swedish population-based cohort study. Nephrol Dial Transplant. 2022 Mar 25;37(4):749-759. doi: 10.1093/ndt/gfab322. PMID: 34788864.
Shaker Qaqish, Nakul Datta, Suphamai Bunnapradist, Erik L. Lum. Listing Malignant Melanoma Patients for Renal Transplantation.
Vajdic CM, van Leeuwen MT. Cancer incidence and risk factors after solid organ transplantation. International Journal of Cancer. 2009;125(8):1747–54.
Xing Y, Bronstein Y, Ross MI, Askew RL, Lee JE, Gershenwald JE, et al. Contemporary diagnostic imaging modalities for the staging and surveillance of melanoma patients: a meta-analysis. J Natl Cancer Inst. 2011 Jan 19. 103(2):129-42.
1-What is your differential diagnosis?
-Malignant Melanoma (most likely)
-Benign melanocytic lesions
-Dysplastic nevus
-Squamous cell carcinoma
-Metastatic tumors to the skin
-Acquired perforating dermatosis
2-Council this patient regarding kidney transplantation?
-Discuss with patient;According to a recent systematic review of the literature, patients with a history of melanoma before transplantation have a 10%-12% risk of recurrence of the original melanoma and a 2%-3% risk of developing a new primary melanoma.
–Should be counselling regarding risk of skin cancer post renal transplant and annual dermatological assessment is recommended for all renal transplant patients.
-Referral to a dermatologist and according to the staging of the melanoma, the management plan, and whether to proceed for transplantation or not.
-Should be treated before transplantation and we should be aware about the interval time to transplant and the other special considerations such as;
-Melanoma in situ/lentigo maligna, no waiting period is required after wide local excision but the patient should be followed up with regular skin exams.
-Stage Ia/Ib/IIa melanoma, 2-5 year wait time is required before transplantation. A 5-year delay is required for patients with stage IIb/IIc melanoma.
-Distant metastatic diseases are not eligible for transplantation in most circumstances.
-Counselling patients in case of procced for transplant the immunosuppression and sun exposure is a major risk factors for skin cancer so posttransplant surveillance is crucial,
-Frequent self examination of skin for any new skin lesion and use of sun screen with avoidance sun exposure.
3-What is your workup strategy?
-Detailed history about the lesion onset, history of trauma , any other lesions.
-Thorough examination looking for other lesions, lymph node examination.
-Assessment for PVD.
– A multidisciplinary team approach with dermatology consultation and further examination with a skin biopsy, LN involvement, and staging & Oncologist involvement.
-Skin biopsy for definitive diagnosis.
-If the biopsy confirmed melanoma, consider the waiting time based on the staging before considering transplantation.
-The choice of immunosuppressive therapy: minimal immunosuppression, switch from CNI to mToR as CNI increase the risk of skin cancer and use of MMF rather than azathioprine which increase the risk of skin cancer.
-Post transplant surveillance ( skin examination).
-The use of sun protective measures.
4-References;
*Melanoma.. infection.
*In case of melanoma transplant should be postponed after cure for a period depend on stage of the tumour.
*Dermatological consultation for biopsy to prove diagnosis, rule out other possibilities , and oncology involvement
This picture suggests malignant melanoma, with a subtype Acral lentiginous melanoma, which found most commonly on palmar, plantar, and subungual surfaces.
One or more of the following features may suggest melanoma: 1) asymmetry,2) irregular borders, 3) variegated color, and 4) diameter >6 mm.
Recommended wait time for Solid organ transplant candidates with a prior history of melanoma:
(According to Pathological Stage)
· In situ: No wait time necessary
· Stage IA (T1a) and Stage IB (T1b or T2a): 1 year
· Stage IIB (T3b or T4a) and Stage IIC (T4b): 2–4 years
· Stage IIIA (T1–2a, N1a or 2a): 1–2 years
· Stage IIIB (T0–3a and N1a/b/c, N2a/b): 2–4 years
· Stage IIIC (T3b-4b and N2b/c-N3b/c) and Stage IIID (T4b and N3a-3c): At least 5 years
· Stage IV: At least 5 years
SUPPORT TECHNIQUES FOR CLINICAL DIAGNOSIS
Can be used in not-clear definite malignant melanoma to improve the diagnosis.
· Dermoscopy
· Reflectance confocal microscopy
· Computer-assisted diagnosis
· Digital dermoscopy-based systems
· Multispectral imaging-based systems
· Convolutional neural networks-based systems
· Smartphone apps
· Adhesive patch genomic analysis
In this case, I will go for an excisional/complete biopsy without delay and send it for Histopathology.
Refer to Oncologist after the biopsy result, and he may need PET CT.
1) https://www.uptodate.com/contents/melanoma-clinical-features-and-diagnosis?search=melanoma&topicRef=4843&source=related_link#:~:text=Melanoma%3A%20Clinical%20features%20and%20diagnosis
2) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555431/#R28:~:text=Pre%2DExisting%20Melanoma%20and%20Hematological%20Malignancies%2C%20Prognosis%20and%20Timing%20to%20Solid%20Organ%20Transplantation%3A%20A%20Consensus%20Expert%20Opinion%20Statement
Dark lesion on the sole of the foot , irregular border , ulcerated center ( or may be that was the site of the biopsy taken ) , malignant melanoma should be excluded.
Differential diagnosis includes :
-squamous cell carcinoma
-benign melanoma
-blue nevus
-Epithelioid tumor
-Uremic skin lesions
-Dermatological consultation , biopsy and pathological examination should e done as soon as possible.
– Reassurance and management accordingly if malignant melanoma is diagnosed according to the stage detected .
-Proper staging should be done precisely as it will affect the management plan and the waiting time till transplantation ( may take from no wait at all to up to 5 years )
-Patient’s counseling should entail the possibility of recurrence or denovo
Our potential recipient is suffering from IgA nephropathy , Is it related in any way to malignant melanoma ?
-In a Swedish population-based cohort study they compared the risk of cancer among 3882 biopsy-verified IgAN patients diagnosed during 1974-2011 with 19341 reference individuals and followed them until 2015. Cox regression was used to estimate hazard ratios (HRs) for cancer in IgAN patients versus controls and conditional logistic regression assessed the risk of cancer before the IgAN was confirmed.
-During a median follow-up of 12.6 years, 488 (12.6%) patients with IgAN and 1783 (9.2%) matched reference individuals were diagnosed with cancer {HR 1.70 [95% confidence interval (CI), 1.52-1.89]}. The increased risk was only seen in IgAN patients developing end-stage renal disease (ESRD), with an HR of 4.01 (95% CI 3.33-4.82) for any cancer and HR of 2.22 (95% CI 1.79-2.75) when excluding non-melanoma skin cancer (NMSC). Non-ESRD IgAN patients did not have an increased overall cancer risk [HR 1.13 (95% CI 0.99-1.30)]. There was no increased risk of cancer preceding an IgAN diagnosis [odds ratio 1.10 (95% CI 0.92-1.32)].
Concluding that There was an increased risk of cancer in IgAN patients, but only for those with ESRD. Our results indicate ∼6 extra cancer cases per 100 IgAN patients with ESRD per 10 years, or >17 extra cases if including NMSC as well.
References:
1-Rehnberg J, Ludvigsson JF, Carrero JJ, Emilsson L. Cancer risk in patients with immunoglobulin A nephropathy: a Swedish population-based cohort study. Nephrol Dial Transplant. 2022 Mar 25;37(4):749-759. doi: 10.1093/ndt/gfab322. PMID: 34788864.
2-Shaker Qaqish, Nakul Datta, Suphamai Bunnapradist, Erik L. Lum. Listing Malignant Melanoma Patients for Renal Transplantation.
3-Handbook of transplantation – 6th edition.
– mostly a case of malignant melanoma
– dd: calciphylaxis (being on dialysis for a long duration), other skin lesions: SCC, blue nevus, benign melanocytic skin lesion, basal cell carcinoma & metastatic skin cancer.
Workup, strategy & counseling:
– dermatology referral for skin biopsy & evaluation.
– Staging will affect the decision & waiting time before transplantation ( table 1)
– Counselling about the possibility of recurrence post-transplantation.
– education for self-examination of the skin after transplantation and follow-up every three months are required.
– protective measures like protective clothing, sunscreen use & avoidance of prolonged sun exposure especially in peak hours should be instructed.
– In the presence of his brother as a donor with ooo mismatch & no DSA, minimization of immunosuppressive with mTORi based protocols will be preferable.
– Staging will affect the decision & waiting time before transplantation ( table 1)
We have a young male patient waiting for transplant due to chronic kidney disease IgA nephropathy…On examination there is black colored maculo papular lesion in the skin over the gluteal region which has irregular margin – most likely lesion is Malignant Melanoma…
The other differential diagnosis are blue nevus, melanocytic lesions, dysplastic nevus, squamous cell and basal cell carcinoma….
the patient has to be counselled before transplantation….According to American Joint commission on cancer, Melanoma fitness for cancer depends on the stage
In situ melanoma – Treated with wide local excision – no waiting time – follow up for 3 months
Stage 1a melanoma – Wide local excision – waiting time for transplant – 2 years
Stage 1b/IIa melanoma – treated with wide local excision + sentinel Lymph node biopsy – 2 to 5 years
Stage IIb/IIc – treated with wide local excision + sentinel lymph node biopsy – minimum is 5 years
Stage III or IV – transplant is contraindicated….
The patient should be counselled regarding the recurrence of the melanoma in the post transplant period..Vigilant self skin examination after transplant and follow up every 3 months in needed to detect new lesions…Protective clothing, avoiding peak day sun exposure, avoiding sun tanning should be taught to the patient…
Workup strategy includes skin biopsy and PET scan to decide the spread of the disease before deciding on renal transplantation…I will involve a multi disciplinary team with dermatologist and oncologist on board….
As the patient has a 6/6 match (complete 0 mismatch) with no DSA and the donor being his brother, I will minimize my immunosuppression strategy…Although KDIGO recommends IL2 receptor blockers as induction in all renal transplants, Many have been done without induction with good outcomes on the patient and graft especially in those with low immunogenic profile.. I will proceed with renal transplantation after the waiting time with no induction, steroid standard dose, Tacrolimus and MMF in early stages…An early switch after the wound healing to sirolimus is done as it is an mTOR inhibitor…
Williams GJ, Webster AC, Thompson JF. Organ transplantation and outcomes in patients with a past history of melanoma: A systematic review and meta-analysis. Clin Transplant. 2021;35(6):e14287.
What is your differential diagnosis?
Pictureshows single black skin lesion with
irregular border most probably malignant melanoma .
DD:
Squamous cell carcinoma
Blue nevus
Malignant melanoma.
Benign melanocytic lesions.
Dysplastic nevus.
Council this patient regarding kidney transplantation
Immunosuppression after transplantation greatly affect recurrence of malignancy,
the effects of an
inefficient immune system likely create a variety of pathways for cancer
recurrence.
One potential mechanism
is through decreased immune surveillance, where there is an accumulation of
oncogenic mutations or cells that would otherwise be identified and repaired by
the immune system.
This mechanism may be predominant in skin cancers, where
immunosuppression impairs the cells ability to repair ultraviolet
radiation-induced DNA damage through defective nucleotide excision repair.
Also Induction therapy with T cell depleting agents,
increases the risks of cancers, such as melanoma.
Therefore the patient must be be aware if possibilty of recurrence
Recommendations for wait times before transplantation
five-year melanoma-specific survival for those
with stage IA, IB, IIA, and IIIA is greater than 90%, so a maximum of a 1-year wait time prior to
transplantation for this group of patients, with one to two-year wait time for
stage IIIA patients.
The five-year melanoma-specific
survival for those with stage IIB, IIC, and IIIB is greater than 80%, with a
plateau observed on the survival curve beyond 5 years. Therefore, a wait
time of two to four years prior to transplantation for this group of patients.
Five-year melanoma-specific
survival for those with stage IIIC and IIID is between 30% and 70%,and for
patients with metastatic melanoma is now over 35%, with long-lasting treatment
responses even after discontinuation of active checkpoint inhibitor therapy, wait
time of at least five years prior to transplantation would be expected to
prevent transplantation of most of this group of patients who will develop
fatal melanoma recurrence
What is your workup strategy?
Skin biopsy for diagnosis and staging of the lesion.
Oncologist consultation
for ttt
Survey for metastasis with full body imaging.
Treatment surgical excision with LN if involved.
Proper waiting time before transplantation according to the stage.
Selection of good matching donor and avoid high risk transplantation
And induction with agents other than T cell depleting agents,
Low dose of Immunosuppression and switch to mTORi after 3
months.
Reference
David P. Al-Adra, Laura Hammel, John Roberts, E. Steve
Woodle. Preexisting melanoma and hematological malignancies, prognosis, and
timing to solid organ transplantation: A consensus expert opinion statement.American
Journal of TransplantationVolume 21, Issue 2 p. 475-483.
This patient should have a skin biopsy. This Could be a primary melanoma tumour.
A previous interrogation of the Cincinnati Transplant Tumour Registry (CTTR) identified 31 OTRs as having a diagnosis of melanoma prior to transplantation, of whom six developed recurrent disease and died 6 to 30 months post transplantation (32 month follow up), leading the author to recommend an interval of five years following treatment prior to considering solid organ transplantation.
The largest study of OTRs with a history of melanoma prior to transplantation suggests no increased risk of recurrence of local or metastatic melanoma (with mean follow up of 10.5 years after original melanoma diagnosis) compared to the control population. This study interrogated database records of the Mayo Clinic and identified melanoma in 59 patients (61 cases) prior to transplantation. These findings supported a smaller retrospective analysis of 9 melanomas by the skin care in organ transplant patients in Europe (SCOPE) group with no recurrences reported with a mean of 60 month follow up.
None of these studies provide conclusive evidence for recommending an optimal interval post melanoma prior to transplantation.
If skin biopsy-proven malignancy, and Based on KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation, candidates with active malignancy should be excluded from kidney transplantation except for those with indolent and low-grade cancers such as prostate cancer (Gleason score ≤ 6), superficial non-melanoma skin cancer, and incidentally detected renal tumors (≤ 1 cm in maximum diameter) (1B). Timing of kidney transplantation after potentially curative treatment for cancer is dependent on the cancer type and stage at initial diagnosis (Not Graded).
KDIGO recommend no waiting time for candidates with curatively treated (surgically or otherwise) non-metastatic basal cell and squamous cell carcinoma of the skin; melanoma in situ; small renal cell carcinoma (< 3 cm).
Ref:
Ali FR, Lear JT. Melanoma in organ transplant recipients: incidence, outcomes and management considerations. Journal of skin cancer. 2012 Jan 1;2012.
KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation
DDX
Benign melanocytic lesions.
Dysplastic nevus.
Squamous cell carcinoma.
The type, intensity, and duration of immunosuppressive therapy contribute to the risk of developing skin cancer, such as melanoma, after transplantation.
Carcinogenesis following SOT is due to a number of factors:
immunosuppressive therapy, UV exposure, genetic factors, viral infection
Immunosuppression has been shown to be a prominent risk factor for melanoma after transplantation because it impairs immune surveillance and has direct oncogenic activity
Counciling
Patient counseling regarding melanoma risk and adequate skin checks are necessary. Intensive screening for skin cancer in renal transplant recipients has been recommended.
Health care professionals should be aware of the necessity for regular skin screenings and early treatment of any suspicious pigmented lesions. Clinical practice guidelines from Kidney Disease Improving Global Outcomes include educating renal transplant recipients regarding the risk of skin and lip cancer, advising minimal sun exposure, use of UV-light blocking agents, self-examination of the skin and lips, and annual skin and lip examination by a dermatologist or experienced physician.
SOT recipients with a past history of melanoma reported an alarming recurrence rate of 19% and recommended leaving a period of at least 5 years between melanoma treatment and SOT.
Minimum Time From Melanoma Treatment to SOT According to the ITSCC.
Stage (AJCC CSM, 7th Edition)
Recommended Time to SOT
Stage 0
No need to defer SOT
Stage Ia
2 y
Stage Ib
5 y
Stage IIa, IIb, IIIa
5-10 y
Stages IIc, IIIb, IV
Not candidates for SOT
Dermatologists thus have an essential role in posttransplant follow-up as they are in a position to diagnose thin melanomas. Much work remains regarding the management of advanced melanoma in SOT recipients, who currently face a worse prognosis than immunocompetent patients with metastatic disease.
treatment decisions should be reached by a multidisciplinary committee, with the informed consent of the patient and knowing that there is a high risk of acute rejection.
Reference
Mona Ascha, MD1,2; Mustafa S. Ascha, BS, MS3; Joseph Tanenbaum, BA1; et al ,Risk Factors for Melanoma in Renal Transplant Recipients ,JAMA Dermatol. 2017;153(11):1130-1136. doi:10.1001/jamadermatol.2017.2291
C.González-CruzV.García-Patos Briones, Melanoma in Solid Organ Transplant RecipientsMelanoma en pacientes receptores de un trasplante de órgano sólido,Actas Dermo-Sifiliográficas (English Edition)
Volume 112, Issue 3, March 2021, Pages 216-224
1- What is your differnial diagnosis
a- malignant melanoma
b- seborrheic keratoses
c- melanocytic nevus
d- verruca vulgaris
e- condyloma acuminatum
f- fibroepithelial polyp
g- epidermal nevus
h- actinic keratoses
i- pigmented basal cell carcinomas,
j- squamous cell carcinomas.
2- Counsil this patient regarding kidney transplantation
As this lesion could be a benign lesion as seborrheic keratosis or malignant as melanoma ,so we need to diagnose and stage it first with skin biopsy and full skin cancer work up then we proceed accordingly. Melanoma is immune dependant malignant tumer and its main therapy is to booster immune response and recently , there was great improvement in survivalof patient with melanoma after treatment with immune check point inhibitors . However , its recurrence post transplantation is common and around 3 fo;ds higher than non transplant population . The 5 years survival in cases of
IA, IB, IIA, and IIIA is higher than 90 of cases. Listing for kidney transplantation in cases of melanoma depends on disease stage where stage I(a anb) ,IIa and III a can be listed for transplantation after maximum of a 1-year from melanoma treatment while waing for 1-2 years in case of stage IIIb and 2-4 years in case of stages IIB, IIC, and IIIB
3- Work up strategy for this patient
1- Full skin cancer work upincluding Skin biopsy for diagnosis and Radiological screening for any lymphadenopathy or distant metastasiswith CT (head , neck,chest and pelvi- abd).
2- Dermatological counseling for diagnosisi , treatment and annual evaluation for recurrence.
3- Correction of risk factor , minimize sun exposure.
ref
1- Shaker Qaqish, Nakul Datta, Suphamai Bunnapradist, Erik L. Lum. Listing Malignant Melanoma Patients for Renal Transplantation. Volume 52, Issue 10, 2020,Pages 3033-3037.
2- Al-Adra DP, Hammel L, Roberts J, Woodle ES, Levine D, Mandelbrot D, Verna E, Locke J, D’Cunha J, Farr M, Sawinski D, Agarwal PK, Plichta J, Pruthi S, Farr D, Carvajal R, Walker J, Zwald F, Habermann T, Gertz M, Bierman P, Dizon DS, Langstraat C, Al-Qaoud T, Eggener S, Richgels JP, Chang GJ, Geltzeiler C, Sapisochin G, Ricciardi R, Krupnick AS, Kennedy C, Mohindra N, Foley DP, Watt KD. Preexisting melanoma and hematological malignancies, prognosis, and timing to solid organ transplantation: A consensus expert opinion statement. Am J Transplant. 2021 Feb;21(2):475-483. doi: 10.1111/ajt.16324. Epub 2020 Oct 10. PMID: 32976703; PMCID: PMC8555431.
1.Malignant Melanoma.
2.Benign melanocytic lesions
3.blue nevus
4.squamous cell carcinoma
5.dysplastic nevus
most likely malignant Melanoma
Need diagnosis by biopsy.
Pretransplant melanoma recipients experienced a 30% increase in overall mortality and a 3% absolute risk difference for posttransplant melanoma. (1)
information regarding that waiting periods prior to transplantation.
The treatment needed for existing lesions,
Information regarding that waiting periods prior to transplantation, and the protocol of follow-up post-transplantation which will be dependent on the pathological stage (2)
1- In situ, wide local excision, No wait time necessary
2- Stage IA (T1a), wide local excision, waiting time 1 year.
3- Stage IB (T1b or T2a), wide local excision plus SLNB, waiting time 1 year.
4- Stage IIA (T2b or T3a), wide local excision plus SLNB, waiting time 1 year.
5- Stage IIB (T3b or T4a), wide local excision plus SLNB, waiting time 2–4 years
6- Stage IIC (T4b), wide local excision plus SLNB, waiting time 2–4 years.
7- Stage IIIA (T1-2a, N1a or 2a), Wide excision plus SLNB plus lymph node dissection, waiting time 1–2 years.
8- Stage IIIB (T0-3a and N1a/b/c, N2a/b), Wide excision plus SLNB plus lymph node dissection, Adjuvant therapy with CKI waiting time 2–4 years.
9- Stage IIIC (T3b-4b and N2b/c-N3b/c), Wide excision plus SLNB plus lymph node dissection, Adjuvant therapy with CKI, waiting time at least 5 years.
10- Stage IIID (T4b and N3a-3c), Wide excision plus SLNB plus lymph node dissection and adjuvant therapy with CKI, waiting time at least 5 years.
11- Stage IV, Wide excision plus SLNB plus lymph node dissection, adjuvant therapy with CKI, waiting time at least 5 years. (3)
The five-year melanoma-specific survival for those with stage IA, IB, IIA, and IIIA is greater than 90%, so a maximum of a 1-year wait time prior to transplantation, with one to two-year wait time for stage IIIA patients.
The five-year melanoma-specific survival for those with stage IIB, IIC, and IIIB is greater than 80%, with a plateau observed on the survival curve beyond 5 years, so a wait time of two to four years prior to transplantation.
Detailed history and examination
Skin biopsy to confirm and staging of the lesion.
MDT; including transplant nephrologist, plastic surgeon, oncologist and dermatologist.
Full body imaging including head, neck, chest, abdomen and pelvis screening of metastasis if needed.
Treatment by wide surgical excision with LN if involved.
Higher stages and metastatic tumor need for surgical and medical treatment.
induction with non-lymphocyte depleting agents,
Lower dose of Immunosuppression and switch to mTORi after 3 months period if there is no contraindication.
Avoid sun exposure, wearing protective clothing and use of sunscreen.
Proper self -skin examination and surveillance screening have a role in an early detection and diagnosis of any skin lesions.
Reference
1.Arron ST, Raymond AK, Yanik EL, et al. Melanoma outcomes in transplant recipients with pretransplant melanoma. Dermatol Surg. 2016;42(2):157–166.
2.Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472–492.
3.David P. Al-Adra, Laura Hammel, et al (2020). Preexisting Melanoma and Hematological Malignancies, Prognosis and Timing to Solid Organ Transplantation: A Consensus Expert Opinion Statement. American Journal of Transplantation, ajt.16324.doi:10.1111/ajt.16324.
DD :
-Malignant melanoma
-Benign melanocytic lesions
-Squamous cell carcinoma
-Dysplastic nevus
-blue nevus
Council this patient regarding kidney transplantation?
malignancy before transplantation has high risk of recurrence after transplantation due to immunosuppressive medications and decreases life expectancy.
Also we should council him regarding the waiting time after excision.
• melanoma in situs : wide excision and no need to wait but follow up post transplant for 3 months
• Stage Ia : needs wide local excision, and to wait for 2 years to transplant.
• Stage Ib/IIa: needs wide local excision with sentinel lymph node biopsy and must wait for 2 to 5 years.
• Stage IIb/IIc : needs wide local excision with sentinel lymph node biopsy and must wait for minimal 5 years.
• Any stage III or IV : need to be referred to oncology and they are not eligible for transplantation.
What is your workup strategy?
Needs to be managed as MDT between nephrologist, Dermatologist, and oncologist
Needs biopsy and she search for Mets.
Needs low immunosuppressive protocols : CNI free protocol and switch to mTOR after 3 months , induction with non-lymphocytic depleting agent
general measures:
avoid sun exposure
use protective clothes
What is your differential diagnosis?
Features of the lesion are mostly suggestive of malignant melanoma, which follows the ABCD characteristic features for melanoma. Asymmetry, Border irregularity, Color (more likely to be very dark black or blue), and Diameter >6 mm)
Differentials to consider;
· Benign melanocytic lesions
· Dysplastic nevus
· Squamous cell carcinoma
· Metastatic tumors to the skin
· Blue nevus
· Epithelioid (Spitz) tumor
· Pigmented spindle cell tumor
· Halo nevus
· Atypical fibroxanthoma
· Pigmented actinic keratosis
· Sebaceous carcinoma
· Histiocytoid hemangioma
Council this patient regarding kidney transplantation?
· Patient should be counseled and informed that after transplantation; immunosuppression is administered in order to prevent both acute and chronic rejections. Although the precise processes are unknown, an ineffective immune system can lead to a number of different cancer recurrence paths. (1)
· In transplant patients, melanoma-specific mortality is three times higher than in nontransplant recipients, and it is highest for localized-stage melanoma, indicating that de novo melanoma acts aggressively in the presence of immunosuppression. (2)
· Pretransplant melanoma recipients experienced a 30% increase in overall mortality and a 3% absolute risk difference for posttransplant melanoma (but not clearly or solely due to melanoma). (3)
· Patients should be advised that waiting periods prior to transplantation must take into account both the kinetics of response and the absolute risk of illness recurrence. The treatment of existing lesions, the period of waiting, and the protocol of follow-up post-transplantation are virtually dependent on the pathological stage (4)
What is your workup strategy?
The workup strategy should be with a multidisciplinary team approach with dermatologists and oncologists, including metastatic workup with imaging.
1- In situ, wide local excision, No wait time necessary
2- Stage IA (T1a), wide local excision, waiting time 1 year.
3- Stage IB (T1b or T2a), wide local excision plus SLNB, waiting time 1 year.
4- Stage IIA (T2b or T3a), wide local excision plus SLNB, waiting time 1 year.
5- Stage IIB (T3b or T4a), wide local excision plus SLNB, waiting time 2–4 years
6- Stage IIC (T4b), wide local excision plus SLNB, waiting time 2–4 years.
7- Stage IIIA (T1-2a, N1a or 2a), Wide excision plus SLNB plus lymph node dissection, waiting time 1–2 years.
8- Stage IIIB (T0-3a and N1a/b/c, N2a/b), Wide excision plus SLNB plus lymph node dissection, Adjuvant therapy with CKI waiting time 2–4 years.
9- Stage IIIC (T3b-4b and N2b/c-N3b/c), Wide excision plus SLNB plus lymph node dissection, Adjuvant therapy with CKI, waiting time at least 5 years.
10- Stage IIID (T4b and N3a-3c), Wide excision plus SLNB plus lymph node dissection and adjuvant therapy with CKI, waiting time at least 5 years.
11- Stage IV, Wide excision plus SLNB plus lymph node dissection, adjuvant therapy with CKI, waiting time at least 5 years. (5)
1- Kuschal C, Thoms KM, Boeckmann L, et al. Cyclosporin A inhibits nucleotide excision repair via downregulation of the xeroderma pigmentosum group A and G proteins, which is mediated by calcineurin inhibition. Exp Dermatol. 2011;20(10):795–799.
2- Robbins HA, Clarke CA, Arron ST, et al. Melanoma risk and survival among organ transplant recipients. J Invest Dermatol. 2015;135(11):2657–2665.
3- Arron ST, Raymond AK, Yanik EL, et al. Melanoma outcomes in transplant recipients with pretransplant melanoma. Dermatol Surg. 2016;42(2):157–166.
4- Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472–492.
5- David P. Al-Adra, Laura Hammel, et al (2020). Preexisting Melanoma and Hematological Malignancies, Prognosis and Timing to Solid Organ Transplantation: A Consensus Expert Opinion Statement. American Journal of Transplantation, ajt.16324.doi:10.1111/ajt.16324.
DD:
_ malignant melanoma. ,non melanoma skin cancer &organized hematoma.
Counselling:
_ Patient should be counseled regarding the cancer free interval :
In situ melanoma :wide local excision: No wait time , follow-up post transplantation for 3 months.
· Stage Ia melanoma :wide local excision: wait time for transplantation is 2 years.
· Stage Ib/IIa melanoma: wide local excision ± sentinel lymph node biopsy: to wait for 2 to 5 years.
· Stage IIb/IIc melanoma : wide local excision + sentinel lymph node biopsy: to wait for minimal 5 years.
· Any stage III or IV melanoma: referred for oncology opinion and they are not eligible for transplantation.
_ Treatment of malignant melanoma : surgical excision with adequate safety margin in addition systemic chemotherapy in case of metastasis.
_ Minimization of IS as avoidance of induction with ATG and use CNI free protocol and MMF based therapy (avoiding azathioprine).
_ Regular screening and self examination & examination by dermatologist.
_ avoidance of sun exposure 2 hours around midday & use of sun screen.
Use of sun protective clothes as silk and hats without holes.
_ plan of work up :
_ skin biopsy for diagnosis confirmation..
_ screening for metastasis : CT with contrast for chest, abdomen and pelvis.
This lesion is a melanocytic lesion with ulcer, irregular. Malignant melanoma must be ruled out. Excision and biopsy is mandatory. In the case of MM, we need to wait for about five years. As this is an immune-responsive malignancy, the immunosuppression will probably cause recurrence.
The patient should be consulted with a dermatologist and oncologist later on.
Qaqish S, Datta N, Bunnapradist S, Lum EL. Listing Malignant Melanoma Patients for Renal Transplantation. Transplant Proc. 2020 Dec;52(10):3033-3037. doi: 10.1016/j.transproceed.2020.04.1823. Epub 2020 Jul 9. PMID: 32654800.
Diagnosis:
This blackish skin lesion with irregular border highly suggestive of malignant melanoma
What is your differential diagnosis?
Council this patient regarding kidney transplantation?
After confirming the diagnosis by skin biopsy and staging ,the most important point to discuss with the patient is the survival outcome.
Active malignancy is contraindicated except for the non-melanoma skin cancer.
Also the patient must know the risk of immunosuppressant medication .
The patient must know the necessary wait time before transplantation.
According to the American joint commission on cancer –based model:
1-Melanoma in situ /No wait time is needed .
2- Stage Ia (treated with wide local excision) wait time is 2 years .
3-Stage Ib/IIa /wait time is 2-5 years .
4-Stage IIb/IIc /wait time is 5 years .
5-Stage III and IV melanoma are not eligible for transplantation and they should be referred for oncology opinion .
Work-up:
Detailed history and examination, Dermatology consultation for skin biopsy to confirm and staging of the lesion.
Full body imaging including head , neck, chest , abdomen and pelvis .
Treatment by wide surgical excision with LN if involved.
Higher stages and metastatic tumor need for surgical and medical treatment.
Lower the dose of IS and switch to mTORi
Stop CNIs as it the main cause of malignancies.
Avoid sun exposure, wearing protective clothing and use of sunscreen. Proper self -skin examination and surveillance screening have a role in an early detection and diagnosis of any skin lesions.
What is your differential diagnosis?
Malignant melanoma
Benign melanoctic lesion
Dysplastic nevus
Metastatic tumour
Council this patient regarding kidney transplantation
There are many possibilities here including malignant melanoma and we need to do surgical excision and histopathology in addition to full examination and imaging if indicated. Transplantation depends on the histopathology result and its staging. The risk of post transplant malignancy is high. No strong evidence supporting an increased risk of melanoma recurrence in patients who have a history of melanoma before transplant. Avoid sun exposure, do self examination and regular follow-up
What is your workup strategy?
MD approach including nephrologist, dermatologist, plastic surgeon, and oncologist
Full history, examination, investigations (and imaging accordingly)
Recommended wait time for SOT candidates with a prior history of melanoma:
1. In situ: Wide local excision, no wait time necessary, and follow up three months post SOT
2. Stage IA (T1a): Wide local excision and wait for one year
3. Stage IB (T1b or T2a): Wide local excision plus SLNB (sentinel lymph node biopsy) and wait for one year
4. Stage IIA (T2b or T3a): Wide local excision plus SLNB, and wait for one year
5. Stage IIB (T3b or T4a): Wide local excision plus SLNB, wait for 2–4 years
6. Stage IIC (T4b): Wide local excision plus SLNB, wait for 2–4 years
7. Stage IIIA (T1–2a, N1a or 2a): Wide excision plus SLNB plus lymph node dissection, wait for 1–2 years
8. Stage IIIB (T0–3a and N1a/b/c, N2a/b): Wide excision plus SLNB plus lymph node dissection and Adjuvant therapy with CKI (checkpoint inhibitor CAP: chest, abdomen and pelvis), wait 2–4 years
9. Stage IIIB (T3b-4b and N2b/c-N3b/c): Wide excision plus SLNB plus lymph node dissection and Adjuvant therapy with CKI, At least 5 years waitng
10. Stage IIID (T4b and N3a-3c): Wide excision plus SLNB plus lymph node dissection and Adjuvant therapy with CKI, wait for at least 5 years
11. Stage IV: Wide excision plus SLNB plus lymph node dissection and Adjuvant therapy with CKI, wait for at least 5 years
Stage IIIA, Stage IIIB, Stage IIIB, Stage IIID, and Stage IV need oncology referral
All patients with a pre-transplant melanoma diagnosis except for stage IIIC, IIID, and stage IV disease would be eligible following resection of disease (If one accepts an 80% five-year melanoma-specific survival as a threshold for transplantation)
References
1. Al-Adra DP, Hammel L, Roberts J, et al. Preexisting melanoma and hematological malignancies, prognosis, and timing to solid organ transplantation: A consensus expert opinion statement. Am J Transplant. 2021 Feb;21(2):475-483. doi: 10.1111/ajt.16324. Epub 2020 Oct 10. PMID: 32976703; PMCID: PMC8555431.
2. Brewer JD, Christenson LJ, Weaver AL, et al. Malignant Melanoma in Solid Transplant Recipients: Collection of Database Cases and Comparison With Surveillance, Epidemiology, and End Results Data for Outcome Analysis. Arch Dermatol. 2011;147(7):790–796. doi:10.1001/archdermatol.2011.159
3. Kubica AW, Brewer JD. Melanoma in immunosuppressed patients. Mayo Clin Proc. 2012 Oct;87(10):991-1003. doi: 10.1016/j.mayocp.2012.04.018. PMID: 23036673; PMCID: PMC3538393.
What is your differential diagnosis?
Hyperpegmented area at the sole of the foot for differntial diagnosis:
melanoma, blood collection after trauma and dysplastic navus
it follows the ABCD criteria for melanoma (asymmetry, border irregularity, color variegation, diameter >6 mm)
Council this patient regarding kidney transplantation? For Malignant melanoma
According to the stage of melanoma there may be wait prior to transplant according to the local transplant guidlines.
Post transplant there is a risk of recurrence that can occur 5-8 times higher than general populations and if that happens the outcome may be poor with high mortality (according to staging) thereofore it is important to monitor the skin for any new skin changes post transplant and limit sun exposure.
What is your workup strategy?
Refer to dermatology for consideration of skin biopsy and thourough examination. Look for metastatic lesions with appropriate image modality like PET scan
Reference:
1-What is your differential diagnosis?
——————————————————————
1- Malignant melanoma .
2- Benign melanocytic lesions.
3- Squamous cell carcinoma.
2-Council this patient regarding kidney transplantation?
—————————————————————————-
1-The patient should know the outcome of kidney transplant according to the available data and guidelines ;
a-The Transplant Cancer Match study determined recipients with pre-transplant melanoma had an absolute risk difference of 3% for post-transplant melanoma and a 30% increase in overall mortality .
b- Melanoma-specific mortality is elevated three-fold in transplant recipients compared with non-transplant recipients, and was strongest for localized stage melanoma, suggesting that de novo melanoma behaves aggressively in the setting of immunosuppression.
2-The patient must know the necessary wait time before transplantation;
According to the American joint commission on cancer –based model;
1-Melanoma in situ (treated with wide local excision ) No wait time is needed .
2- Stage Ia (treated with wide local excision) wait time is 2 years .
3-Stage Ib/IIa (treated with wide local excision ± sentinel lymph node biopsy ) wait time is 2-5 years .
4-Stage IIb/IIc (treated with wide local excision + sentinel lymph node biopsy) wait time is 5 years .
5-Stage III and IV melanoma are not eligible for transplantation and they should be referred for oncology opinion .
3-The candidate should know the effects of immunsuppressant ;
Concern for the effect of immunsuppression on the immune control incited by the checkpoint inhibitors is high in this population. In addition, given the potential for organ rejection with checkpoint inhibitor therapy in recurrent melanoma after transplantation . Consideration for the effect of immunosuppression effects on patients with node positive disease controlled by checkpoint inhibition, needs to be included in the decision.
4-The candidate must know the preventive measures ;
a-reducing sun exposure
b-wearing protective clothing .
c-practicing skin self examination .
What is your workup strategy?
——————————————————————
1-To determine transplant eligibility, prior consensus guidelines considered the AJCC survival curves for each melanoma stage in combination with the post-transplantation survival rate goal.
2-If one accepts an 80% five-year melanoma-specific survival as a threshold for transplantation, then all patients with a pre-transplant melanoma diagnosis except for stage IIIC, IIID, and stage IV disease would be eligible following resection of disease.
3-Imaging of the brain, chest, abdomen, and pelvis (and neck for those with a primary melanoma affecting the head or neck) are recommended for patients with a history of at least stage IIA melanoma prior to consideration for transplantation.
4-Recommendations for wait times prior to transplantation must take into consideration not only the absolute risk of disease recurrence, but also the kinetics of response .
5-Consideration for the effect of immunosuppression effects on patients with node positive disease controlled by checkpoint inhibition, needs to be included in the decision.
Reference ;
—————————–
1- Penn I Evaluation of the candidate with a previous malignancy. Liver Transpl Surg. 1996;2(5 Suppl 1):109–113. [PubMed] [Google Scholar].
2 -Arron ST, Raymond AK, Yanik EL, et al. Melanoma Outcomes in Transplant Recipients With Pretransplant Melanoma. Dermatol Surg. 2016;42(2):157–166. [PMC free article] [PubMed] [Google Scholar]
3- Robbins HA, Clarke CA, Arron ST, et al. Melanoma Risk and Survival among Organ Transplant Recipients. J Invest Dermatol. 2015;135(11):2657–2665. [PMC free article] [PubMed] [Google Scholar]
4-Zwald F, Leitenberger J, Zeitouni N, et al. Recommendations for Solid Organ Transplantation for Transplant Candidates With a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma: A Consensus Opinion From the International Transplant Skin Cancer Collaborative (ITSCC). Am J Transplant. 2016;16(2):407–413. [PubMed] [Google Scholar]
5- 12. Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472–492. [PMC free article] [PubMed] [Google Scholar]
DD.1. malignant melanoma
2.begnin melanocytic lesion
3. Dysplastic nervous.
4. NMSC
Counselling.
Should be after biopsy of lesion and staging
If malignant melanoma should inform about need for waitng time and risk of recurrence post transplant and aggressive behaviour because of IS
Workup strategy.
1. Diagnosis and staging by skin biopsy and regional LN Bx if involved. Check for mets by appropriate clinical and imaging.
2. Rx. Wide surgical excision with surgical margin according to depth of tumor. May need LN excision although no survival benefit. If metastatic surgical plus medical Rx eg BRAF inhibitors
3. Waiting time..according to staging
From insitu to stage II c can be candidate for Tx. Stage III and IV are not for Tx.
Institute no delay time but follow up screening every 3 months. Two years for Ib up to 5 years in stage II b and II c.
4. Strategies for avoidance of sun.
5. IS protocol avoid cyclosporine and MTOR inhibitors.
Important is self surveillance and clinical surveillance every 3 months.
There is a hyperpigmented lesion in the planter surface which is most likely a malignant melanoma
An informed consent should be discussed with the patient which include the following:
Survival outcome post kidney transplant:
The survival outcomes are commonly determined by staging according to the AJCC Melanoma Staging System:
· the thickness of the primary tumor
· presence of ulceration
· number of tumor-involved regional lymph nodes
· the presence of in-transit, satellite, and/or microsatellite metastases,
· distant organ metastasis.
With current therapeutic options, immunological checkpoint blockade as well as the approved MAPK inhibitor regimens for BRAF mutant melanoma, the five-year overall survival rate for patients with metastatic melanoma is now greater than 50%. in the post-resection setting, they decreased the risk of melanoma relapse of over 40%.
Melanoma-specific mortality is elevated three-fold in transplant recipients compared with non-transplant recipients, and was strongest for localized stage melanoma, suggesting that de novo melanoma behaves aggressively in the setting of immunosuppression. The Transplant Cancer Match study determined recipients with pre-transplant melanoma had an absolute risk difference of 3% for post-transplant melanoma and a 30% increase in overall mortality (but not clearly or solely due to melanoma). the five-year melanoma-specific survival for those with stage IIIC and IIID is between 30% and 70%, with a plateau observed on the survival curve at four to five years. Furthermore, the five-year overall survival rates for patients with metastatic melanoma is now over 35%, with long-lasting treatment responses even after discontinuation of active checkpoint inhibitor therapy.(1)
In a 191,471 subjects, 336 (0.18%) had pre-transplantation melanoma and the 5-year cumulative incidence of melanoma-specific death was 0.29% in patients with pre transplantation melanoma compared with 0.01% in patients without melanoma. Similarly, the 5-year cumulative incidence of incident primary melanoma was 0.75% in subjects with pre transplantation melanoma compared with 0.14% in subjects without pre transplantation melanoma, for an absolute risk difference of 0.61%. a history of thin melanoma (defined as Breslow thickness ≤ 1.50 to 2.00 mm, or as Clark level I, II) may not be associated with an increased recurrence or mortality risk in the post transplantation setting.
For post transplantation melanoma, thin melanoma (Clark level I, II) may behave comparably to melanoma in immunocompetent individuals, whereas thick melanoma ( Clark level III, IV) may behave more aggressively and be associated with increased mortality risk .(2)
Effect of immunosuppression:
Concern for the effect of immunosuppression on the immune control incited by the checkpoint inhibitors is high in this population. In addition, given the potential for organ rejection with checkpoint inhibitor therapy in recurrent melanoma after transplantation, so such cases should be discussed on an individual basis.
Possibility of cancer recurrence:
it is unclear if cancer recurrence will increase post-transplant if the immune response towards the cancer that was facilitated by checkpoint inhibition is diminished by immunosuppression. Additionally, data on the use of checkpoint inhibitors in the transplant patient population is still limited.
Induction therapy with T cell depleting agents, increases the risks of melanoma. In addition, T cell depleting agents used in the treatment of acute rejection of the kidney allograft also increase the risk of cancer development
Eligibility:
All patients with a pre-transplant diagnosis of locoregional melanoma (stages I, II, and possibly some patients with stage IIIa) may be transplant candidates. Imaging of the brain, chest, abdomen, and pelvis (and neck for those with a primary melanoma affecting the head or neck) are recommended for patients with a history of at least stage IIA melanoma prior to consideration for transplantation.
Wait times prior to transplantation:
· The five-year melanoma-specific survival for those with stage IA, IB, IIA, and IIIA is greater than 90%, so a maximum of a 1-year wait time prior to transplantation , with one to two-year wait time for stage IIIA patients.
· The five-year melanoma-specific survival for those with stage IIB, IIC, and IIIB is greater than 80%, with a plateau observed on the survival curve beyond 5 years, so a wait time of two to four years prior to transplantation.
· Institution of a wait time of at least five years prior to transplantation would be expected to prevent transplantation of most of this group of patients who will develop fatal melanoma recurrence.(1)
The routine use of SLN biopsy should be strongly considered in transplant candidates with melanoma <1.00 mm, as a negative SLN biopsy may justify curtailing transplantation wait times on a case-by-case basis. Last, patients considered noncandidates (stages IIc, IIIb, IIIc, and IV, after staging with PET/CT) may be considered as candidates following a wait time of 10 to 15 years. (2)
Ref
1-Al-Adra DP, Hammel L, Roberts J, Woodle ES, Levine D, Mandelbrot D, Verna E, Locke J, D’Cunha J, Farr M, Sawinski D, Agarwal PK, Plichta J, Pruthi S, Farr D, Carvajal R, Walker J, Zwald F, Habermann T, Gertz M, Bierman P, Dizon DS, Langstraat C, Al-Qaoud T, Eggener S, Richgels JP, Chang GJ, Geltzeiler C, Sapisochin G, Ricciardi R, Krupnick AS, Kennedy C, Mohindra N, Foley DP, Watt KD. Preexisting melanoma and hematological malignancies, prognosis, and timing to solid organ transplantation: A consensus expert opinion statement. Am J Transplant. 2021 Feb;21(2):475-483. doi: 10.1111/ajt.16324. Epub 2020 Oct 10. PMID: 32976703; PMCID: PMC8555431.
2-Zwald F, Leitenberger J, Zeitouni N, Soon S, Brewer J, Arron S, Bordeaux J, Chung C, Abdelmalek M, Billingsley E, Vidimos A, Stasko T. Recommendations for Solid Organ Transplantation for Transplant Candidates With a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma: A Consensus Opinion From the International Transplant Skin Cancer Collaborative (ITSCC). Am J Transplant. 2016 Feb;16(2):407-13. doi: 10.1111/ajt.13593. Epub 2016 Jan 28. PMID: 26820755.
The most probable diagnoses is malignant melanoma, typical lesion. Dark black, nodule.
Other differentials include:
1-Benign melanocytic lesions
2-Dysplastic nevus
3-Squamous cell carcinoma
4-Halo nevus
5-Pigmented actinic Keratosis
Malignant lesions before transplantation is a major concern because:
1-Immunosuppressive medications increase risk of malignancy
2-Malignancy reduces patient survival which is the major benefit of transplantation
Still, it is not an absolute contraindication. Patients with active malignancy are to be excluded from transplantation, except those with indolent or low-grade cancer.
Some types of malignant lesions require waiting time. This is dependent on the cancer type and its stage.
No waiting time is recommended for melanoma in situ and most non melanoma skin cancer and curatively treated malignancies.
Dermatology and oncology consultation.
Biopsy
Search for metastases.
References:
1-KDIGO guidelines 2020
2-Medscape
Can you please specify which KDIGO guidlines 2020, I would like to read it
Sorry, i didnot include the full name of the referece.
KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020;104: S1–S103.
differential diagnosis
most likely Malignant Melanoma
other causes could be
Counselling regarding transplantation
a)According to American Joint Commission on Cancer, stage–based model.
· In situ melanoma treated with wide local excision: No wait time is necessary for transplantation, follow-up post transplantation for 3 months.
· Stage Ia melanoma treated with wide local excision: wait time for transplantation is 2 years.
· Stage Ib/IIa melanoma treated with wide local excision ± sentinel lymph node biopsy: to wait for 2 to 5 years.
· Stage IIb/IIc melanoma treated with wide local excision + sentinel lymph node biopsy: to wait for minimal 5 years.
· Any stage III or IV melanoma: these stages to be referred for oncology opinion and they are not eligible for transplantation.
b) To be counseled and taught to remain vigilant of this potential problem and its recurrence.
c) The patients should receive counseling regarding the risk factors that can be controlled or manipulated. Counseling on other preventive behaviors such as wearing protective clothing, reducing excessive sun exposure, avoiding sun lamps/tanning beds, or practicing skin self-examination.
workup strategy
multidisciplinary approach including oncologist and plastic surgeon, and dermatologist.
biopsy of the lesion
extensive workup regarding spread of lesion by doing local and distant spread.
patient should be counselled about the possibility of post-transplant malignancy, and avoidance of sun exposure.
Ref;
Medscape; Malignant Melanoma Differential Diagnoses.
Williams GJ, Webster AC, Thompson JF. Organ transplantation and outcomes in patients with a past history of melanoma: A systematic review and meta-analysis. Clin Transplant. 2021;35(6):e14287.
Well done.
What is your differential diagnosis?
-This lesion with irregular margin and ulceration is most likely to be malignant melanoma.
Other differential diagnosis:
-Benign melanocytic lesions
-Dysplastic nevus
-Squamous cell carcinoma
-Basal cell carcinoma
-Metastatic tumors to the skin
-Blue nevus
-Epithelioid (Spitz) tumor
-Pigmented spindle cell tumor
-Halo nevus
-Atypical fibroxanthoma
-Pigmented actinic keratosis
-Sebaceous carcinoma
-Histiocytoid hemangioma
Council this patient regarding kidney transplantation?
-He needs dermatological consultation and excisional biopsy ,and according to the result ,we can proceed .if it localized melanoma waiting time at least 5 years ,while if it invasive contraindicated for transplantation.(1)
What is your workup strategy?
-Detail history and clinical examination.
-One meta-analysis of diagnostic tests used in staging melanoma has shown that ultrasonography is the best imaging study to diagnose lymph node involvement and that positron emission tomography computed tomography scanning (PET/CT) is the best imaging study to look for other sites of metastasis.(2)
-Definitive treatment of cutaneous melanoma is surgery, medical management is reserved for adjuvant therapy of patients with advanced melanoma. Less than one half of patients with deep primaries (> 4 mm) or regional lymph node involvement have long-term disease-free survival; consequently, these patients are classified as high risk and should be considered for adjuvant therapy.
By stage, standard treatment options for melanoma are as follows :
Stage 0 – Excision
Stage I – Excision, with or without lymph node management
Stage II – Excision, with or without lymph node management
Resectable stage III – Excision, with or without lymph node management; adjuvant therapy and immunotherapy
Unresectable stage III, stage IV, and recurrent melanoma – Intralesional therapy, immunotherapy, signal transduction inhibitors, chemotherapy, palliative local therapy.
References:
1.Chadban, Steven et al. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation 2020.
2. Xing Y, Bronstein Y, Ross MI, Askew RL, Lee JE, Gershenwald JE, et al. Contemporary diagnostic imaging modalities for the staging and surveillance of melanoma patients: a meta-analysis. J Natl Cancer Inst. 2011 Jan 19. 103(2):129-42. [QxMD MEDLINE Link]. [Full Text].
Very good but you need to discuss the waiting time with the patient so you need staging.
The ITSSC is simple and straight forward. Check your collegue;s Waid Zied ‘s answer.
Differential diagnosis?
Malignant melanoma
Melanocytic nevus
Counselling on kidney transplantation?
Kidney transplantation predisposes to cancers and therefore, presence of malignancies that are not cured or in remission is a contraindication to kidney transplantation. Patient with malignant melanoma needs to a tumor – free period of at least 5 yeras before they can be considered for transplantation.
Work up?
Thorugh history to rule out family history of skin cancers, previous cancers and premalignant skin lesions and other possible risk factor
Thorough examination to determine the extent of disease
Skin biospy and histologic analysis
Multidisciplinary team involvement with dermatologist, plastic surgeons, oncologists
You need to mention the wait time in the counselling process.
What is your differential diagnosis?
Malignant melanoma (MM)
Atypical nevus
De novo MM upon transplantation, pre-transplant MM, & donor-derived MM are the three different ways that MM manifests in OTRs.
De novo post-transplantation MM is the most typical MM presenting scenario in OTRs.
In OTRs, preexisting nevi should be thoroughly inspected. In comparison to the overall population (25%), atypical nevi & melanomas that develop in preexisting nevi are more common than in the general population.
============================
Council this patient regarding kidney transplantation?
============================
What is your workup strategy?
References
Mittal and Colegio, Skin Cancers in Organ Transplant Recipients, American Journal of Transplantation 2017; 17: 2509–2530, doi: 10.1111/ajt.14382
Thankyou but you missed the workup plan.!!!
What is your differential diagnosis?
This is most likely malignant melanoma.
Differentials to consider in the diagnosis of malignant melanoma include the following conditions(1):
Council this patient regarding kidney transplantation?
a) According to American Joint Commission on Cancer, stage–based model(2):
· In situ melanoma treated with wide local excision: No wait necessary, follow-up posttransplantation for 3 months.
· Stage Ia melanoma treated with wide local excision: to wait for 2 years.
· Stage Ib/IIa melanoma treated with wide local excision ± sentinel lymph node biopsy: to wait for 2 to 5 years.
· Stage IIb/IIc melanoma treated with wide local excision + sentinel lymph node biopsy: to wait for 5 years.
· Any stage III or IV melanoma: these stages to be refered for oncology opinion and they are not eligible for transplantation.
b) To be counseled and taught to remain vigilant of this potential problem and its recurrence. Pretransplant melanoma is associated with increased melanoma-specific mortality, overall mortality, and incident melanoma after transplant(3).
c) The patients should receive counseling regarding the risk factors that can be controlled or manipulated. Counseling on other preventive behaviors such as wearing protective clothing, reducing excessive sun exposure, avoiding sun lamps/tanning beds, or practicing skin self-examination.
What is your workup strategy?
· MDT; including transplant nephrologist, plastic surgeon, oncologist and dermatologist.
· Biopsy of skin lesion and staging.
· Screening for identification of distant metastasis.
· Surgical excision with safety margin.
· Tapering down immunosuppression and shifting CNIs to mTORi.
References
1. Medscape;Malignant Melanoma Differential Diagnoses.
2. Zwald F, Leitenberger J, Zeitouni N, Soon S, Brewer J, Arron S, Bordeaux J, Chung C, Abdelmalek M, Billingsley E, Vidimos A, Stasko T. Recommendations for Solid Organ Transplantation for Transplant Candidates With a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma: A Consensus Opinion From the International Transplant Skin Cancer Collaborative (ITSCC). Am J Transplant. 2016 Feb;16(2):407-13. doi: 10.1111/ajt.13593. Epub 2016 Jan 28. PMID: 26820755.
3. Arron ST, Raymond AK, Yanik EL, Castenson D, McCulloch CE, Clarke CA, Paddock LE, Niu X, Engels EA. Melanoma Outcomes in Transplant Recipients With Pretransplant Melanoma. Dermatol Surg. 2016 Feb;42(2):157-66. doi: 10.1097/DSS.0000000000000602. PMID: 26818209; PMCID: PMC6263147.
Well done.
DDx
Atypical mole
Basal cell carcinoma
Blue nevi
Haemangioma
cSSC
Dermatologic manifestation of metastatic carcinoma
Calcifylaxis
Work up :
Focused history including sun exposure other system affection review ,occupational, family history and drug history
Systemic Clinical exam
Lab investigations for serum level of calcium , PO4 and PTH
Dermatology opinion for diagnosis , for punch biopsy and staging
Surgical and Oncology opinion regarding the staging and treatment
Counseling the patient
Patient counseling regarding his future kidney transplantation should be preceded by good evaluation and staging The precise staging of melanoma is critical to recommendations regarding suitability; more advanced lesions require a wait of at least years, whereas superficial lesion may require no waiting period. In general, metastatic malignancies are contraindications to transplantation
Counseling should focus on the possibility of recurrency after transplantation ,DE novo melanoma after kidney transplantation and the need of immunosuppression
Importance of follow up and feeling free to ask question
Answering all patient concern
Ref.
C. González-Cruz, C. Ferrándiz-Pulido, V. García-Patos Briones, Melanoma in Solid Organ Transplant Recipients, Actas Dermo-Sifiliográficas (English Edition), Volume 112, Issue 3, 2021,Pages 216-224,
F. Zwald, J. Leitenberger, N. Zeitouni, S. Soon, J. Brewer, S. Arron, et al.
Recommendations for Solid Organ Transplantation for Transplant Candidates With a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma: A Consensus Opinion From the International Transplant Skin Cancer Collaborative (ITSCC) Am J Transplant, 16 (2016), pp. 407-413
Thank you ,theITSCC is very informative and clear
This patient need full work up of skin cancer including punsh biopsy ,adding to that will need to check his CA and Phosphor level
This patient need to be counselled for the possibility to post bond his transplant according to skin out come and according to the staging of his cancer
As we all know that early stages of cancer A,B,AND 111 A HAS GOOD PROGNISIS and can go for RTX after one year
If his cancer is agressive and with stage 111b or iv in this scenario we may waite for 5 years .
i will wait till find out the type and staging of this skin lesion
need to involve the dermatology .
The patient should be counselled about the possibility of post RTX malignenecy
advised to avoid sun exposure .
references
uptodate
Thankyou ,more staging details for the wait time could be more specific.
The differentials are.
Benign melanocytic lesion,
Malignant Melanoma,
Squamous cell carcinoma,
Basal cell carcinoma,
Hemangioma,
Calciphylaxis.
Blue nevus
The initial step should diagnosis of the lesion with punch biopsy, bone scan, Ca/phosphate product, than counselling of the patient, on exclusion, proceed for transplant workup. if any malignant lesion should be look workup for metastastatic disease and its staging.
Dermatologist opinion.
The 5 years survival for those if diagnosed with melanoma is 90% if stage 1A, B, IIA.
Stage IIb, IIIA >80%.
The waiting time is 2 years with localized disease, 2 to 5 year for stage III(AJCC, ITSCC).
The patient be counselled for de novo skin cancer which is the most common tumor post transplantation.
Post-transplant choice of immunosuppression.
Previous blood test like calcium, phosphate product, history of trauma, any skin cancers, excessive sun exposure, profession.
Physical examination,
Full body imaging,
punch biopsy, including skin full thickness, immunohistochemistry-fluorescence in situ hybridization.
dermatologist involvement may need dermoscopy.
References;
1.https://pubmed.ncbi.nlm.nih.gov/26853179/.
2.https://www.uptodate.com/contents/keratoacanthoma-epidemiology-risk-factors-and-diagnosis/abstract/1.
3.CJASN 16(8):p 1247-1255, August 2021. | DOI: 10.2215/CJN.00910121.
Well done.
Malignant melanoma
squamous cell carcinoma
Dysplastic nevus
The patient should be councelled regarding possibility of melanoma which needs to confirm first by biopsy.
I will do biopsy first to confirm diagnosis.
Consult with dermatologists
Avoid sun exposure and use of sun block.
Treatment according to biopsy
Differential diagnosis of melanoma;
1) Benign Melanocytic lesion.
2) Dysplastic nevus.
3)Squamous cell carcinoma.
Plan for kidney transplantation:
according to stage of melanoma set by AJCC, American joint committee on cancer which take into account thickness of primary tumor, presence of ulceration, number of tumor-involved regional lymph nodes and presence of satellite or microsatellite metastases as well as distant metastases, melanoma specific survival outcome is estimated.
It was agreed that a cut off 80% five-year survival rate of melanoma is acceptible for transplantation. Five-year graft survival for those with stage 1A,1B, IIA and IIIA are greater than 90%. therefore, its recommended that 1 year wait time prior to transplantation.For other categories, 5-year survival is 80%. Hence, its recommended to wait for two to 4 years prior to transplantation.
Your wait time is simple and acceptable but what about stage iv ,also stage 0??
Diagnosis and Differential diagnosis:
Malignant Melanoma
Blue Nevus
Basal cell carcinoma
Counselling of patient and workup strategy:
1. Identification of lesion by wide excision biopsy and staging by imaging of brain, chest, and abdomen.
2. Wait time to transplantation will depend on staging, with at least 5 years with stage IIIC and above.
3. Dermatology consult.
4. Council patient regarding increased risk of skin cancer post-transplant.
5. Avoidance of sun particularly at mid-day, use of SPF 50+ UVA 5* sunscreen.
6. Self-examination by patient.
7. Post-transplant reduction of immunosuppression with avoidance of AZA, and mTOR based IS regime.
46 year old presenting with a pigmented nodule that is more than 6 mm in diameter with irregular margins is suspicious for melanoma with differential diagnosis of non-melanoma skin cancer, and atypical nevus.
Patient needs to be counselled on the high risk that the lesion would be cancerous and that there is a high rate of recurrence of skin cancer post transplantation. Counselling on skin protective practises like use of sunscreen with SPF 50+/5 star, use of protective clothing and avoidance of the midday sun. They should also be counselled due to the poor HLA match they will require an aggressive induction and maintenance immunosuppressive therapy which predisposes them to a high risk of recurrence. Finally the patient needs to be counselled that the cancer stage will determine their eligibility for transplant whereby stage 4 will not be eligible while stage 2 and 3 transplant will be delayed for at least 5 years.
Workup should be in collaboration with dermatologist which include a full physical exam in good lighting looking for any other suspicious lesions. An excision biopsy to confirm the diagnosis. Imaging to rule out any metastasis in the chest, brain and abdomen.
Fine short answer,but this match can not be better 000 mismatch, no DSAs .
is there any drug preference?
Thank you prof.
Due to the poor match they will need induction with ATG.
Diagnosis:
Seeing asymmetry, border irregularities, color variegation with deep black pigmentation, and a large diameter (> 6 mm), it appears to be plantar melanoma (ABCD criteria). (1)
Differential diagnosis may include:
Atypical nevus
Pigmented basal cell carcinoma
Work up strategy in this case:
Counselling of this patient regarding kidney transplantation:
According to a recent systematic review of the literature, patients with a history of melanoma before transplantation have a 10%-12% risk of recurrence of the original melanoma and a 2%-3% risk of developing a new primary melanoma. (2)
He requires a stage-specific wait time following adequate melanoma treatment.
To the best of my knowledge, as per the available literature search, there are two recent recommendations published concerning minimum time from melanoma treatment to solid organ transplantation with minor differences (3, 4, 5).
The consensus expert opinion from American society of transplant surgeons recommends at least a wait time of 5 years even for stage III and stage IV( not suitable for transplant as per ITSCC) and based on latest AJCC TNM classification(8th)
References:
Well structured answer ,well done.
Thank you
What is your differential diagnosis?
Melanoma, non-melanoma skin cancer, and hematoma are among the top on the differential diagnosis
Council this patient regarding kidney transplantation?
Around 40% of malignancies in renal transplant patients are cutaneous, and the rate of cutaneous malignancy in renal transplant recipients is 20 times greater than in the general population.
SCC and BCC account for 90% of all cases whereas Melanoma, Kaposi sarcoma, and Merkel cell carcinoma are among the other cutaneous malignancies
It is SCC, not BCC, that predominates in renal transplants whereas BCC is more common in general population.
The more aggressive induction and maintenance immunosuppression, the higher the risk of skin malignancy. Renal transplantation is associated with the lowest risk compared to heart, lung, and pancreas-kidney transplant.
What is your workup strategy?
The initial step should start with preliminary diagnosis followed by confirmation. Consultation with a dermatologist is mandatory to determine the determine the most likely diagnosis followed by histological confirmation. Based on the diagnosis, the lesion should be treated accordingly.
For prevention of future skin lesions, patient is advised to use certified sun protection creams (high SPF/5 stars) and use protective cloths and avoid exposure to sun, in particular mid-day sun.
Renal recipient is advised to perform monthly self-examinations and a skilled dermatologist must perform annual examinations.
Timing of transplantation after a diagnosis of melanoma.
– If the biopsy confirmed the presence of melanoma in situ or lentigo maligna, we would be able to move directly from excision to transplantation.
– Transplantation should be delayed for 2-5 years for patients with stage Ia/Ib/IIa melanoma, and for 5 years for those with stage IIb/Ic melanoma.
– It is not contraindicated to transplant patients who have advanced stages of cancer.
Thankyou Mohamed but please explain your last statement about advanced cancer.!!!!
1_ The differential diagnosis includes:
_ malignant melanoma.
_ non melanoma skin cancer.
_Organized hematoma.
2_ counseling of the patient depends on the definitive diagnosis which needs skin biopsy.
_ in case of confirmed melanoma, the patient should be counseled regarding the cancer free interval as awaiting time prior to proceeding to renal transplantation.
In situ ….no waiting time.
Stages up to II 2 …wait for 1_5 years.
Stage more than IIa ….wait for 5 years
Metastasizing lesions ….not eligible for renal transplantation.
_ ttt of malignant melanoma by surgical excision with adequate safety margine plus systemic chemotherapy in case of metastasis.
_ In addition, minimization of IS protocol as avoidance of induction with ATG and use CNI free protocol and MMF based therapy (avoiding azathioprine which is a well known risk factor to develop skin malignancy).
_ regular screening and self examination with additional examination by an expert dermatologist.
_ avoidance of sun exposure 2 hours around midday and use of sun screen (SPF 50+ and 5* protection against UVA rays).
Use of sun protective clothes as silk and hats without holes.
3_ plan of work up :
_ skin biopsy to confirm diagnosis.
_ screening for metastasis as CT with contrast on chest, abdomen and pelvis.
Well done.
the diagnosis of this pigmented nodule is melanoma and most probably nodular melanoma which is account for 15 to 30% of all melanoma.
another differential diagnosis is
1-non melanoma skin CA.
2-melanoma syndrome
3- Blue nevus
4-familial typical mole.
5-xeroderma pigmentosum.
melanoma is the most serious form of skin cancer and has four morphological types include superficial spreading type, lentigomaligna, acral lentiginous and nodular type such as in our case.
The patient should be counseled about the possibility of melanoma which confirms by an excisional biopsy that extends to the subcutaneous fat and is the preferable producer for the diagnosis.
referral to a dermatologist and according to the staging of the melanoma, the management plan, and whether to proceed for transplantation or not.
counselling patients in case of procced for transplant the immunosuppression and sun exposure is a major risk factors for skin cancer so posttransplant surveillance is crucial
also frequent self examination of skin for any new skin lesion and use of sun screen with avoidance sun exposure
surgical excision extending into the subcutaneous fat followed by widening of the margin depending on Breslow depth , SLN biopsy is the preferable procedure for the diagnosis by a dermatologist.
proper staging is essential for management the worse the pronosis the more aggressive the
minimum time from melanoma treatment to SOT according to the ITSCC
stage 0 no need to defer SOT.
stage 1a 2 years
stage 1b 5 years
stage 11b,11b,111a 5 to 10 years
stage 11c,111b, and 1V are not candidates for SOT.
assessment for any metastasis by chemistry and images scanning.
screening for carcinogenic virus, avoiding sun exposure post-transplantation, avoiding ATG as induction therapy if possible
Reference
Thankyou well done.
46-years, Afro-Caribbean, proposed well matched donor with pigmented lesion at heel.
Differential diagnosis of skin lesion:
· Melanoma
· SCC
· Benign melanocystic lesion
· Dysplastic nevus
Counseling:
Importance about appropriate diagnosis of skin lesion then biopsy to confirm the diagnosis.
If the diagnosis is melanoma then counseling about waiting time is needed.
Stage 0/ melanoma in situ: no need to wait
Stage Ia: 2years
Stage Ib: 5 years
Stage IIa, b and IIIa: 5-10 years
Stage IIc, IIIb and IV: not candidiate for transplantation
Workup strategy:
According to confirmed diagnosis
Patients should be instructed to avoid excessive sun exposure and to use appropriate sunblock.
Detailed dermatologic surveillance.
Lower immunosuppression with sirolimus based protocol.
What are the IS drugs you should generally avoid.?
What is your differential diagnosis?
Council this patient regarding kidney transplantation?
The patient should be diagnosed first and exclusion of skin malignancy is must .
We should inform such patients about the risk of developing malignancies after transplantation and mainly skin cancer.
The above mentioned patient mostly has melanoma and MDT including dermatologist and oncologist must be involved in such case.
Staging of melanoma and the waiting period also should be mentioned to him
The five-year melanoma-specific survival for those with stage IA, IB, IIA, and IIIA is greater than 90%, thus, we recommend a maximum of a 1-year wait time prior to transplantation for this group of patients, with one to two-year wait time for stage IIIA patients. The five-year melanoma-specific survival for those with stage IIB, IIC, and IIIB is greater than 80%, with a plateau observed on the survival curve beyond 5 years.
Pathology stage Time interval to transplant
In situ No wait time necessary
Stage IA (T1a) 1 year
Stage IB (T1b or T2a ) 1 year
Stage IIA (T2b or T3a) 1 year
Stage IIB (T3b or T4a) 2–4 years
Stage IIC (T4b) 2-4 years
Stage IIIA (T1–2a, N1a or 2a) 1–2 years
Stage IIIB (T0–3a and N1a/b/c, N2a/b) 2–4 years
Stage IIIC (T3b-4b and N2b/c-N3b/c) At least 5 years
Stage IIID (T4b and N3a-3c) At least 5 years
Stage IV At least 5 years
What is your workup strategy?
History and risk factors — Key questions that should be asked to patients presenting with a lesion that is of concern or for a general examination of their nevi include:
When was the lesion (or a change in a pre-existing lesion) first noticed?Has the lesion changed over time in size, shape, color, and/or symptoms (eg, bleeding, itch)?Does the patient have a personal or family history of melanoma or other skin cancers¿
Does the patient have a history of excessive sun exposure and/or tanning bed use?
Did the patient suffer severe sunburns during their childhood or teenage years?
Does the patient have a cancer-prone syndrome (eg, familial atypical mole and melanoma syndrome or xeroderma pigmentosum)?
Is the patient immunosuppressed?
Did the patient receive prolonged psoralen plus ultraviolet A (PUVA) therapy?
Physical examination
The skin examination should be conducted under optimal lighting and include the entire body surface.
DIAGNOSIS CONFIRMATION
Biopsy — The definitive diagnosis of melanoma is histopathologic. A skin biopsy is the first step to establish the diagnosis of melanoma. Prebiopsy photographs are helpful for clinical-pathologic correlation and for preventing wrong site surgery
A complete full-thickness excisional biopsy of suspicious lesions with 1 to 3 mm margin of normal skin and extending to a depth to encompass the thickest portion of the lesion should be performed whenever possible. Partial incisional biopsy may be acceptable for very large lesions or for certain sites, including the face, palm or sole, ear, distal digit, or subungual lesions
Histopathology – The histopathologic diagnosis of melanoma is based upon a combination of architectural, cytologic, and host response features. Immunohistochemical stainings may be helpful in difficult cases .
Molecular techniques – Molecular techniques, including comparative genomic hybridization, fluorescence in situ hybridization (FISH), and gene expression profiling of tumors, may further aid in the diagnosis of equivocal melanocytic lesions.
Reference
Pre-Existing Melanoma and Hematological Malignancies, Prognosis and Timing to Solid Organ Transplantation: A Consensus Expert Opinion Statement
David P. Al-Adra, Laura Hammel, […], and Kymberly D. Watt
Uptodate Melanoma: Clinical features and diagnosis
Good detailed workup but as a tx .physicion you need to discuss and council him about immunosupresion drugs.
3. A 46-year-old CKD 5 Afro-Caribbean on HD for the last 4 years secondary to IgAN presented to you in the transplant assessment clinic to consider suitability for kidney transplantation. His brother is willing to donate a kidney for him, 000 mismatch and no DSA. On routine examination this lesion was identified.
• What is your differential diagnosis?
– Malignant melanoma
– Benign melanocytic lesions
– Squamous cell carcinoma
– Basal cell carcinoma
– Hemangioma
• Counsel this patient regarding kidney transplantation?
The discussion points will be centered around: –
– Skin biopsy – for histological diagnosis
– Proper treatment – to be initiated prior to kidney transplantation
– Wait time before proceeding to transplantation depends on the tumor type, tumor stage, presence/ absence of high-risk features, availability of a management approach alternative to transplantation (1, 2)
o Stage Ia/ Ib/ IIa melanoma have a 2-5 year wait time prior to transplantation
o Stage IIb/ IIc melanoma require a 5 year wait time
o Distant metastatic disease is considered a contraindication for kidney transplantation in most circumstances
– Sun protection (sun avoidance, sun-protective clothing, use of sunscreen) and practicing skin self-examination – sun protection decreases incidence of skin malignancies (3)
– Post-transplant surveillance appointments with a dermatologist – to monitor for development of new lesions, locally recurrent lesions and metastatic disease
– Pre-transplant melanoma is associated with increased all-cause mortality and melanoma-specific mortality and incident melanoma after transplantation. (4)
• What is your workup strategy?
– Detailed history and thorough physical examination to look for lesions elsewhere, lymphadenopathy
– Routine baseline investigations and evaluation for distant metastatic disease
– Skin biopsy for histopathologic examination
– Multidisciplinary approach – specific/ definitive treatment as guided by the oncologist
– Observe the appropriate wait-time prior to transplantation – depending on tumor stage
– Immunosuppressive therapy – it influences risk of post-transplant skin malignancies – mTORi are preferred to CNIs
– Reduction of immunosuppressive therapy – since increased intensity and duration of immunosuppression promotes development of skin malignancies (5)
– Chemoprevention – for patients with multiple and aggressive disease
References
1. Al-Adra DP, Hammel L, Roberts J, Woodle ES, Levine D, Mandelbrot D, et al. Preexisting melanoma and hematological malignancies, prognosis, and timing to solid organ transplantation: A consensus expert opinion statement. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2021 Feb;21(2):475-83. PubMed PMID: 32976703. Pubmed Central PMCID: PMC8555431. Epub 2020/09/26. eng.
2. Zwald F, Leitenberger J, Zeitouni N, Soon S, Brewer J, Arron S, et al. Recommendations for Solid Organ Transplantation for Transplant Candidates With a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma: A Consensus Opinion From the International Transplant Skin Cancer Collaborative (ITSCC). American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2016 Feb;16(2):407-13. PubMed PMID: 26820755. Epub 2016/01/29. eng.
3. Bangash HK, Colegio OR. Management of non-melanoma skin cancer in immunocompromised solid organ transplant recipients. Current treatment options in oncology. 2012 Sep;13(3):354-76. PubMed PMID: 22592596. Epub 2012/05/18. eng.
4. Arron ST, Raymond AK, Yanik EL, Castenson D, McCulloch CE, Clarke CA, et al. Melanoma Outcomes in Transplant Recipients With Pretransplant Melanoma. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al]. 2016 Feb;42(2):157-66. PubMed PMID: 26818209. Pubmed Central PMCID: PMC6263147. Epub 2016/01/29. eng.
5. Al-Adra D, Al-Qaoud T, Fowler K, Wong G. De Novo Malignancies after Kidney Transplantation. Clinical journal of the American Society of Nephrology : CJASN. 2022 Mar;17(3):434-43. PubMed PMID: 33782034. Pubmed Central PMCID: PMC8975024. Epub 2021/03/31. eng.
Thankyou.
What is your differential diagnosis?
Melanocytic nevi
Congenital nevus
keratinocyte carcinoma (non-melanoma skin cancer like SSC, BCC).
Melanoma
Council this patient regarding kidney transplantation?
This patient is a male black race, with this sole black naevus with the ulcerating center, needs to ask about the nature of this skin lesion and whether he had melanoma
The main factors to consider in organ-transplant candidates with a history of melanoma are tumor stage, presence or absence of residual disease, and time from diagnosis to transplantation(1)
pre-transplant melanoma should be taken seriously and get dermatology and oncology consultation for further confirmation and staging of the tumor according to the Melanoma Staging System, which takes into account the thickness of the primary tumor, presence of ulceration, number of tumor-involved regional lymph nodes, and the presence of in-transit, satellite, and/or microsatellite metastases, as well as distant organ metastasis.
Melanoma frequency in solid organ transplant recipients is about 2-3 folds higher than in the general population.
de novo melanomas size thicker than 2mm seem to have a worse outcome with a higher risk of death from metastatic melanoma, whereas those who develop a ≤2 mm thickness melanoma seems to have a prognosis similar to that of the general population (2).
the five-year overall survival rate for patients with metastatic melanoma is now greater than 50%. Given their efficacy in the metastatic setting, immunological checkpoint inhibition, as well as targeted therapy, have migrated to the post-resection setting, with a decrease in the risk of melanoma relapse of over 40% (4,5).
What is your workup strategy?
History and proper physical examination and high suspicion of melanoma will go for A multidisciplinary team approach with dermatology consultation and further examination with a skin biopsy, LN involvement, and staging
melanoma accounts for up to 80% of skin cancer deaths. Early diagnosis suggestively reduces melanoma-specific
mortality. Melanoma is a highly immunogenic tumor; it would be expected to be more common and
more aggressive in SOT. The available limited evidence from case series with diverse results, in one small series of 31 recipients with a history of melanoma reported a risk of relapse up to 19% due to their immune-suppressed state and it recommended waiting for at least 5 years from treatment time. while many studies did not confirm such high rate of recurrence, according to the European Skin Care in Organ Trans-plant Patients, (SCOPE) group stated no melanoma recurrences or deaths after SOT in a series of 9 recipients with a history of melanoma (6).
Risk factors for post-transplant skin cancers
oncogenic virus infections
increased photosensitivity, and UV radiation-induced DNA damage
Carcinogenicity of immunosuppressants Like induction with T cell depleting agents like ATG and also the intensity and duration of CNI, azathioprine Reduced host immunosurveillance also there is an accumulation of oncogenic mutations or cells that would otherwise be identified and repaired by the immune system, especially in skin tumors. in which the immunosuppression therapy diminished the ability of the cell to repair
Previous history of tumors before transplantation, tumor stage, any residual disease
Donor-derived melanoma has a poor prognosis and is difficult to treat, as melanoma considers an immunogenic tumor that can be affected by immunosuppression in fact donors with a history of invasive melanoma should be considered an absolute contraindication to donation.
References
1.González-Cruz C, Ferrándiz-Pulido C, García-Patos Briones V. Melanoma in Solid Organ Transplant Recipients. Actas Dermosifiliogr (Engl Ed). 2021 Mar;112(3):216-224.
2. Russo I, Piaserico S, Belloni-Fortina A, Alaibac M. Cutaneous melanoma in solid organ transplant patients. G Ital Dermatol Venereol. 2014 Aug;149(4):389-94.
3. Al-Adra DP, Hammel L, Roberts J, Woodle ES, Levine D, Mandelbrot D, Verna E, Locke J, D’Cunha J, Farr M, Sawinski D, Agarwal PK, Plichta J, Pruthi S, Farr D, Carvajal R, Walker J, Zwald F, Habermann T, Gertz M, Bierman P, Dizon DS, Langstraat C, Al-Qaoud T, Eggener S, Richgels JP, Chang GJ, Geltzeiler C, Sapisochin G, Ricciardi R, Krupnick AS, Kennedy C, Mohindra N, Foley DP, Watt KD. Preexisting melanoma and hematological malignancies, prognosis, and timing to solid organ transplantation: A consensus expert opinion statement. Am J Transplant. 2021 Feb;21(2):475-483
4. Eggermont AMM, Blank CU, Mandala M, et al. Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. N Engl J Med. 2018;378(19):1789–1801.
5. Eggermont AMM, Crittenden M, Wargo J. Combination Immunotherapy Development in Melanoma. Am Soc Clin Oncol Educ Book. 2018; 38:197–207.
6.Melanoma in Solid Organ Transplant RecipientsC. González-Cruz,∗ C. Ferrándiz-Pulido, V. García-Patos Briones , May 2020; accepted 2 November 2020 .Available online 22 January 2021
Exellent as usual ,thankyou for highlighting the relation of oncogenic viruses,specific IS drugs, and donor melanoma. You needed to mention the wait time.
***What is your differential diagnosis?
****Council this patient regarding kidney transplantation?
A-Out of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients-incidence of recurrence was 23% at 15 years -Graft loss was higher in patients with recurrence of IgA nephropathy , resulting in 32% graft loss at 8 years after diagnosis of recurrence
B-History of Pretransplant Melanoma
+Unfortunately for anyone whose survival depends on an a history of melanoma is a classic contraindication for SOT.
+There is little evidence on whether SOT recipients with a history of melanoma have an increased risk of recurrence rate and recommended leaving a period of at least 5 years between melanoma treatment and SOT.
+ the European Skin Care in Organ Trans-plant Patients reported no melanoma recurrences or deaths after SOT in a series of 9 recipients
+American Joint Commission on Cancer (AJCC) Cancer Staging Manual (7th Edition), the International Immunosuppression and Transplant Skin Cancer Collaborative (ITSCC) drew up a series of recommendations on the wait time between melanoma treatment and transplant Based on a5-year posttransplant survival rate of 60% and the AJCC 7th
****What is workup strategy?
Tests for Melanoma Skin Cancer lymph nodes examreferred to a dermatologist for dermoscopy (also known as dermatoscopy, epiluminescence microscopy [ELM], or surface microscopy) to see spots on the skin more clearly.
Skin biopsy (Shave-Punch-Excisional and incisional -“Optical” biopsies-Fine needle aspiration (FNA) biopsy-Surgical (excisional) lymph node biopsy-Sentinel lymph node biopsy) lab tests try to confirm the diagnosis.
Imaging testsChest x-ray- CT scan of the chest Ultrasound or CT scans guide a biopsy needle into a suspicious lymph node.MRI scans can be very helpful in looking at the brain and spinal cord.Positron emission tomography (PET) scan.for more advanced melanomas.
. If the melanoma has spread to distant parts of the body, a high LDH level is a sign that the cancer may be harder to treat. This can affect the stage of the cancer
References
1-CJASN 16(8):p 1247-1255, August 2021. | DOI: 10.2215/CJN.00910121
2-Mitchell TC, Karakousis G, Schuchter L. Chapter 66: Melanoma. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa: Elsevier; 2020.
3-National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Cutaneous Melanoma. Version 2.2019. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdfon June 11, 2019.
4-Ribas A, Read P, Slingluff CL. Chapter 92: Cutaneous Melanoma. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2019.
Swetter S, Geller AC. Melanoma: Clinical features and diagnosis. UpToDate. 2019. Accessed at
https://www.uptodate.com/contents/melanoma-clinical-features-and-diagnosis on June 10, 2019.
4-Swetter SM, Tsao H, Bichakjian CK, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2019;80:208-250.
DONATE
It is very well structured. I like that you have supported your arguments by uploading scientific evidence.
Ajay
-What is your differential diagnosis?
Melanoma
Benign melanocytic lesions
Dysplastic nevus
Squamous cell carcinoma
Metastatic tumors to the skin
Blue nevus
Epithelioid tumor
Pigmented spindle cell tumor
Halo nevus
Pigmented actinic keratosis
-Council this patient regarding kidney transplantation?
If the patient’s skin lesion is confirmed to be melanoma along with perfect donor match, counselling will be needed including a multidisciplinary team involving dermatologist and oncologist beside the transplanting team
Renal transplant recipients have a higher risk of melanoma than immunocompetent cases with higher mortality and difficult therapy.
A study involved 31 transplant recipients with a past history of melanoma revealed an alarming recurrence rate of 19% and adviced leaving a period of minimum 5 years between melanoma treatment and transplantation.
Dapprich et al.,found no cases of posttransplant recurrence or melanoma-specific mortality in 12 transplant recipients previously treated for melanoma (mean Breslow depth, 0.35 mm), also the European Skin Care in Organ Transplant Patients, Europe (SCOPE) group mentioned that no melanoma recurrences or deaths were noticed after transplantation in 9 recipients with a history of melanoma
Another study stated that 336 transplant recipients with a history of melanoma had a higher risk of posttransplant melanoma-specific mortality and incident melanoma than recipients without a history of melanoma. Inspite of these findings , the difference in 5-year mortality due to melanoma between recipients with and without pretransplant melanoma was 1.2%.
A 5-year posttransplant survival rate was 60% . It was recommended that melanoma stages Ia, Ib, IIa, IIb, or IIIa can be candidates for transplantion.
-What is your workup strategy?
Melanoma diagnosis is confirmed by excisional biopsy. Sentinel lymph node biopsy or gene profile assay has prognostic values for certain patients.
Dermatoscopy can assessing all nonpigmented and pigmented skin lesions.
Whole-body photography with sequential examinations for early melanoma detection in high-risk patients.
Lymph node involvement is best detected by US and PET/CT is the best imaging for other sites of metastasis ,PET is not indicated in early-stage disease (stage I or II), but can be benefical in staging patients with known lymph node affection.
Local Recurrence rate can be upto 40%, due to failure to perform a reexcision after biopsy of a melanoma so reexcision must be performed.
The International Immunosuppression and Transplant Skin Cancer Collaborative (ITSCC)recommendations for the time gap between melanoma treatment and transplant according to stages are
Stage 0—-No need to delay SOT ,Stage Ia—-2 y ,Stage Ib—5 y ,Stage IIa, IIb, IIIa—5-10 y,Stages IIc, IIIb, IV—-Not candidates for SOT
For immunosuppressive protocol m TOR inhibitors must be considered rather than CNI and MMF rendered to it’s anticarcinogenic effect
Behavioural counselling for sun protective measures and avoiding harmfull UV radiation is crucial
References
-Winston W Tan. Malignant Melanoma Differential Diagnoses.Medscape 2022
-C. González-Cruz, C. Ferrándiz-Pulido, V. García-Patos Briones,Melanoma in Solid Organ Transplant Recipients,Actas Dermo-Sifiliográficas (English Edition), 2021;112(3) ;216-224
That is a logical approach. I like your evidence to support your arguments.
Ajay
DD of pigmented skin lesion in dialysis patient:
1-acquired perforating dermatosis of dialysis
2-prurigo nodularis
3-folliculitis
4-keratosis pilaris
5-keratoacanthoma.it is a rapidly growing, dome-shaped, flesh-colored lesion, surrounded by a smooth wall of inflamed skin with a keratin plug in the center. this lesion may be malignant or benign as squamous cell carcinoma has been associated with this lesion. it is commonly arises on sun-exposed skin as evidence has shown UV rays to be a possible etiology. excisional skin biopsy should be done. Treatment consists of electrocautery and curettage.
after excisional biopsy and exclusion of malignant lesion, we can proceed for transplantation after counselling patient about risk factors for skin cancer especially squamous cell carcinoma, about sun exposure, protective clothes and use of sunscreen
workup strategy:
1- skin biopsy
2- dermatology consultation
3-treatment according to the result of biopsy
Tracey C. Vlahovic, Lion Sassoon. Diagnosing And Treating Pigmented Leg Lesions In A Dialysis Patient. Podiatry Today.2015.
That is a logical approach. I like your evidence to support your arguments.
Ajay
· What is your differential diagnosis?
1-Malignant melanoma (specially Acral lentiginous melanoma one of its morphological variants which is so common in Asians and individuals with darker skin tones and shows a particular predilection for the soles of the feet)(1).
2-Benign naves.
3-Squamous cell carcinoma.
·Council this patient regarding kidney transplantation?
Can proceed or transplantation after excluding malignant lesion, if its diagnosed as malignant melanoma .
1-Should be treated before transplantation and we should be aware about the interval time to transplant and the other special considerations such as
If its diagnosed as melanoma insitue no wait time necessary after wide local excision then as mentioned here.
Class IA, IB, IIA: 1 year
Class IIB, IIC: 2-4 years
Class IIIA: 1-2 years
Class IIIB: 2-4 years
Class IIIC, IIID, IV: At least 5 years.
What is your workup strategy?
1-Prevention by education, awareness and observation. ( about risk or recurrence).
2-Annual self-examination and examination by a physician.
3-Patients should be instructed to avoid excessive sun exposure and to use sunblock.
4-dermatologic surveillance on a regular basis.
5-De novo sirolimus based protocol should be priority.
References:
1-Handbook of Kidney Transplantation, Gabriel M. Danovitch, MD.
2-Al-Adra DP, Hammel L, Roberts J, et al. Preexisting melanoma and hematological malignancies, prognosis, and timing to solid organ transplantation: A consensus expert opinion statement. Am J Transplant. 2021;21(2):475-483. doi:10.1111/ajt.16324.
3-Melanoma: Clinical features and diagnosis, UP TO DATE 2022.
That is a logical approach that has been presented in a very well structured style. I like your evidence to support your arguments.
Ajay
• 46-year-old
• CKD 5 due to IgAN
• Afro-Caribbean
• HD for 4 years
• Suspected lesion on the sole of feet
• Very good match with related living donor 000 mismatch and no DSA.
● Patient has an oddly shaped and black discolored patch of raised skin surrounded by normal skin with irregular borders.
● Differential Diagnosis
▪︎Acral Lentiginous Melanoma
▪︎Other melanocytic neoplasms (tumors on the skin) such as lentigo, congenital acral nevi, and acquired acral nevi
▪︎Fungal and bacterial infections
▪︎Trauma-related hemorrhage
▪︎Chronic wounds Verrucae (warts)
▪︎Other skin cancers that may have secondary pigmentation (pigment transferred by another cell) such as squamous cell carcinoma or porocarcinoma, or cutaneous melanomas
● Council this patient regarding kidney transplantation?
Excellent match with his brother so we will proceed with transplantation after we confirm that the existing lesion is safe
But if the lesion is malignant we have to evaluate the case and the decision to proceed with transplantation will depend on the assessment of the severity of the condition.
● What is your workup strategy?
▪︎A full-body skin exam is done
▪︎A family history of skin cancer.
▪︎C.T scan for excluding metastasis and lymph node envolvement
▪︎MDT ( dermatologist , oncologist , surgeon)
▪︎Dermoscopy
Dermoscopy, or the use of a dermatoscope by a dermatologist
▪︎Biopsy
If the skin lesion is suspicious of acral lentiginous melanoma, it is best cut out as excision biopsy and the Pathology report should include a macroscopic description of the specimen and microscopic description
▪︎If the patient has melanoma in situ he is considered at a minimal risk for recurrence at transplantation, and therefore no wait time for transplantation has been recommended.
▪︎A minimum waiting time of 2 years before transplantation has been suggested for melanoma with a Breslow depth <1 mm and no clinical evidence of metastasis
▪︎Consideration could be given to a shorter waiting period with melanoma depth <1 mm if there is a negative SLN biopsy.
▪︎patients with MM <2 mm and negative sentinel node biopsy are eligible for transplant after a 2-year wait period.
▪︎Duration of the wait period should be discussed on a case by case
▪︎For most patients with MM >2 mm a 5-year wait is probably prudent.
▪︎Patients with lymph node involvement or metastatic disease generally should not receive a solid organ transplant.
▪︎Risk factors for developing melanoma included older age, male sex, recipient white race, living donors, sirolimus therapy, and cyclosporine therapy.
That is an excellent approach. I wish you could provide evidence to support your arguments. Please type headings and subheadings in bold or underline to make it easier to read.
Ajay
1.DIAGNOSIS;
Malignant Melanoma – Possibly based on location Acral lentiginous melanoma .
DDX;
Squamous Cell Carcinoma.
Benign Melanoctyic Lesion.
Calciphylaxis (Necrosis due to CUA)
Blue Naevi
2.COUNSELLING REGARDING KIDNEY TRANSPLANTATION;
If this is Malignant Melanoma, the following will be vital during counselling;
a. Wait Period before transplant;
-Stages 2b/2c – 5 yrs
-Stages 1a/1b/2a – 2 yrs
-In situ – No Wait Period.
-Metastatic – Transplantation plans aborted.
b. Risk factors;
-Immunosuppressive medication post transplant increases risk factors to other skin malignancies including SCC and BCC and regular surveillance post transplant is important.
-Sun exposure is a risk factor and minimized sun exposure is advised post transplant.
-Parkinsonism has been associated with increased risk to Malignant melanoma up to x 4 as evidenced by case control study analysis done at the Mayo clinic. Melanoma too have been associated with increased risk to parkinsonism and thus a multidisciplinary follow up will be needed in at risk patients.
-Family hx of Malignant Melanoma or Moles increases risk of the same and thus increased surveillance post transplant would be key here.
c. Recurrence risk;
-Pre transplant melanoma is the strongest risk factor to post transplant melanoma.
-Risk of recurrence is upto x8 and has poor outcomes post translant compared to general population.
-Though rare and mostly histological without graft failure,IGA nephropathy too is a possibility.
3.WORKUP STRATEGY.
-Multidisciplinary approach – Counselor, Dermatologist, Oncologist and a Nephrologist.
-Do baseline workups ;
a. FHG
b. UECS.
c. LFTS – Increased AST and ALT may show mets to the liver.
d. LDH – Increased levels may indicate a distant spread.
e. CXR/CHEST CT SCAN- Lungs are the first site of mets,This will be important in establishing baseline state.
f. CT ABD – to evaluate stage 3 disease.
Skin biopsy is diagnostic.
-Post transplant follow up;
a. Avoid sun exposure and use sunscreen 50 + SPF.
b. Use of triple immunosuppression – PDL/TAC/MMF in first 3-6/12 then switch to dual consisting of an antimetabolite + steroids as CNI have been shown to have more risk of skin cancer in at high risk patients. MTOR inhibitors preferred to CNIs in at risk patients.
-Involve the oncologist at the earliest stage and treat appropriately depending on stage.
REFERENCES;
1.Prof Halawa lecture.
2.Handbook of kidney transplantation by Gabriel Danovitch,6th edition.
3.Park CK et al; Incidence and Risk factors of keratinocyte carcinoma after solid organ transplantation, Ontario, Canada, JAMA, Dermatol 2019;155;1041;
4.David al dara et al -De novo malignancies after kidney transplantation
That is a logical approach that has been presented in a very well structured style. I like your evidence to support your arguments.
Ajay
1- DD:
melanoma
scc
benign melanocystic lesion
dysplastic nevus.
2- councelling:
First: patient should understand the importance of proper diagnosis of the present skin lesion. excisional biopsy is indicated to confirm the diagnosis.
If the diagnosis proved to be melanoma:
1- proper treatment according to recommended guideline by oncologist
2- wait time till transplantation: (according to the stage)
stage 0/ melanoma in situ: no need to wait
stage Ia: 2years
stage Ib: 5 years
stage IIa, b and IIIa: 5-10 years
stage IIc, IIIb and IV: not candidiate for transplantation
(recommendation of AJCC CSM)
second: regarding to original kidney disease: no contraindication of transplantation with no increased risk of recurrence. (risk of 10 years graft failure is 9.7%)
That is a logical approach. I wish you could provide evidence to support your arguments.
Ajay
1- González-Cruz C, Ferrándiz-Pulido C, Briones VG. Melanoma in solid organ transplant recipients. Actas Dermo-Sifiliográficas (English Edition). 2021 Mar 1;112(3):216-24.
2- Dahlke E, Murray CA, Kitchen J, Chan AW. Systematic review of melanoma incidence and prognosis in solid organ transplant recipients. Transplantation research. 2014 Dec;3:1-8.
Melanocytic nevi
Cutaneous squamous cell carcinoma
Should be counselling regarding risk of skin cancer post renal transplant and annual dermatological assessment is recommended for all renal transplant patients.
Skin biopsy and surgical removal
Consider free calcinurine inhibitors
Use of mTOR inhibitors
Sunscreen for skin protection
Reference:
Mona Ascha, Mustafa S, et al: Risk Factors for Melanoma in Renal Transplant Recipients: JAMA Dermatol. 2017 Nov; 153(11): 1130–1136.
That is a logical approach. Some more details in discussion would have been good.
Ajay
What is your differential diagnosis?
The patient has ESRD secondary to IgAN on HD, came for pre-transplant evaluation.
He has dark pigmented lesion over the heel.
DD:
· Benign melanocytic lesions
· Dysplastic nevus
· Melanoma
· Squamous cell carcinoma
· Metastatic tumors to the skin·
· Acquired perforating dermatosis
· Pigmented spindle cell tumor
. Hematoma.
The likely diagnosis in this case is melanoma.
Council this patient regarding kidney transplantation?
– Counseling about he finding of this suspicious lesion and the possible diagnosis.
– The work up required to diagnose this condition and multiple team involvement to diagnose and manage this condition.
– IF confirmed to be malignant melanoma.
SOT is associated with an increased risk of melanoma to general population, the risk has been increased by a factor of 1.6 to 3.4 in Europe and by a factor of 2 to 4 in Australia.
Melanoma accounts for 6.2 percent of post-transplantation skin cancers in adults and for 15 percent in children.
Risk factors:
The risk was higher in renal transplant recipients than in liver and lung recipients.
Male sex
Increasing age
Black race
The intensity and duration of immunosuppression.
Melanoma-specific mortality is higher in transplant recipients than in non-transplanted patients and is among the highest, compared with other cancers, even when stage and treatment are taken into account
The risk of recurrence after transplantation is high 20 %, even if the primary lesion occurred as long as 10 years before transplantation. For this reason, a prolonged waiting period before performing transplantation is advisable for a patient with antecedent melanoma (except for in situ melanoma).
The length of the waiting period should be weighed against other risks, especially for patients awaiting a heart, lung,
or liver transplant.
Melanoma may be transmitted from donors.
What is your workup strategy?
– Detailed history about the lesion onset, history of trauma , any other lesions.
– Thorough examination looking for other lesions, lymph node examination.
– Assessment for PVD.
– Dermatology consultation.
– Skin biopsy for definitive diagnosis.
– Evaluation for distant metastasis Pan- CT.
– Oncologist involvement.
– If the biopsy confirmed melanoma, consider the waiting time based on the staging before considering transplantation.
– The choice of immunosuppressive therapy: minimal immunosuppression, switch from CNI to mToR as CNI increase the risk of skin cancer and use of MMF rather than azathioprine which increase the risk of skin cancer.
– Post transplant surveillance ( skin examination).
– The use of sun protective measures.
References:
That is a logical approach that has been presented in a very well structured style. I like your evidence to support your arguments.
Ajay
What is your differential diagnosis?
Council this patient regarding kidney transplantation?
There is a need to investigate whether the lesion is neoplasm or vascular, to define immediate and subsequent care.
I would consult a dermatologist for a biopsy of the lesion if there are no blood dyscrasias or correct them to perform the procedure.
In case of confirming the main suspicion (melanoma), we must stage cancer to define the treatment and establish the possibility of transplantation.
If the lesion is in situ without major involvement, we can consider transplantation after removing the lesion. If not, we need a multidisciplinary definition to control the neoplastic disease before proceeding with the transplant.
What is your workup strategy?
That is an excellent approach. I wish you could provide evidence to support your arguments.
Ajay
Thank you, Professor.
I will improve myself
· What is your differential diagnosis?
The index patient is an ESRD patient on hemodialysis, now presenting for kidney transplant evaluation.
He is having a pigmented lesion over the heel of his foot.
Such a lesion could be either gangrene (due to peripheral vascular disease – PVD), a hematoma, lesion of calciphylaxis, or a skin cancer lesion (likely melanoma).
The diagnosis of this lesion involves:
a) Detailed history (regarding onset of the lesion, any history of trauma, waxing and waning lesions, claudication etc) and clinical examination, including skin examination, to look for any other lesion at any other site on body. Distal vessel examination should be done (for PVD).
b) Dermatology consultation.
· Council this patient regarding kidney transplantation?
If the index patient’s lesion is diagnosed as skin cancer- especially melanoma, the staging of the cancer is important. The disease-free interval (waiting period) prior to transplant should be followed as per the stage of the malignancy (1).
The patient needs to be counselled regarding the risk of recurrence of skin cancer post-transplant (as and when the transplant is performed) due to use of immunosuppressive medications (2).
The patient should also be counselled regarding the importance of behavioural interventions post-transplant in form of using measures for sun-protection like avoiding direct sunlight during peak hours, using protective clothing and sunscreen, as well as self-examination of skin (2).
· What is your workup strategy?
The strategy in the index case involves:
a) Detailed history (regarding onset of the lesion, any history of trauma, waxing and waning lesions, claudication etc)
b) Clinical examination, including skin examination, to look for any other lesion at any other site on body. Distal vessel examination should be done (for PVD).
c) Dermatology consultation.
d) Investigations:
a. Arterial Doppler to rule out PVD.
b. The lesion should be biopsied for definitive diagnosis (once hematoma and PVD ruled out)
e) Once the diagnosis of skin cancer is established, treatment should be initiated as per oncologists.
f) The decision regarding waiting period before transplant after treatment should be taken with respect to the type and stage of Melanoma (1):
a. Melanoma in situ: No wait-time
b. Class IA, IB, IIA: 1 year
c. Class IIB, IIC: 2-4 years
d. Class IIIA: 1-2 years
e. Class IIIB: 2-4 years
f. Class IIIC, IIID, IV: At least 5 years
g) Patient counselling: Regarding the disease, its treatment, wait-time before transplant, and emphasis on post-transplant self-examination of skin as well as sun-protective measures (2).
h) Choice of immunosuppression post-transplant: Switch from CNI to mTOR inhibitors (3).
References:
1. Al-Adra DP, Hammel L, Roberts J, Woodle ES, Levine D, Mandelbrot D, Verna E, Locke J, D’Cunha J, Farr M, Sawinski D, Agarwal PK, Plichta J, Pruthi S, Farr D, Carvajal R, Walker J, Zwald F, Habermann T, Gertz M, Bierman P, Dizon DS, Langstraat C, Al-Qaoud T, Eggener S, Richgels JP, Chang GJ, Geltzeiler C, Sapisochin G, Ricciardi R, Krupnick AS, Kennedy C, Mohindra N, Foley DP, Watt KD. Preexisting melanoma and hematological malignancies, prognosis, and timing to solid organ transplantation: A consensus expert opinion statement. Am J Transplant. 2021 Feb;21(2):475-483. doi: 10.1111/ajt.16324. Epub 2020 Oct 10. PMID: 32976703; PMCID: PMC8555431.
2. Baker RJ, Mark PB, Patel RK, Stevens KK, Palmer N. Renal association clinical practice guideline in post-operative care in the kidney transplant recipient. BMC Nephrol. 2017 Jun 2;18(1):174. doi: 10.1186/s12882-017-0553-2. PMID: 28571571; PMCID: PMC5455080.
3. Al-Adra D, Al-Qaoud T, Fowler K, Wong G. De Novo Malignancies after Kidney Transplantation. Clin J Am Soc Nephrol. 2022 Mar;17(3):434-443. doi: 10.2215/CJN.14570920. Epub 2021 Mar 29. PMID: 33782034; PMCID: PMC8975024.
That is a logical approach that has been presented in a very well structured style. I like your evidence to support your arguments.
Ajay
DIFFERENTIAL DIAGNOSIS
CUTANEOUS LESION WITH DARK POGMENTATION CAN BE
BENIGN NEVUS
MALIGNANAT MELANOMA ( my diagnosis in this case )
CUTANEOUS HEMANGIOMA
SCC AND BCC ARE LESS LIKELY AS THERE IS NO ULCER
PHYSICAL EXAMINATION FOR INGUINAL LYMPH NODES
COUNSELLING
CONSIDERING CKD 5 and IGAN , kidney transplant is a better alternative to HD with some post immunosuppression risk
skin malignancy are most common after tx and pre transplant lesion make them more prone for skin lesions/ malignancy
dermatologist and surgical oncology ref need to be done prior to tx
biopsy will be definitive in diagnosis and staging of melanoma
standard waiting time of 2 yrs and 5 yrs will be followed as per the stage of MM( malignant melanoma
IM after TX – mTOR inhibitor are known to have anti tumor effect and will be preferred over CNI
close follow up for recurrence is MUST
Differential diagnosis:
· Malignant melanoma
· Dysplastic nevus
· Sequmous cell carcinoma
· Bening melanocytic lesion
.Council this patient regarding kidney transplantation:
Melanoma is an immune responsive malignancy and the need for immunosuppressant for successful transplantation may lead to recurrent disease
This lesion is malignant melanoma and need work up pre kidney transplant
· Skin Biopsy
· Base line radiological imaging and laboratory studies
· Regular clinic follow up is recommended finding from history and examination should directed needed for further studies to detect local ,regional and distant metastasis
NCCN recommendation for baseline imaging
· Stage 0 1A 1B or 11 :cross sectional imaging is not recommended
· Stage 111 A cross sectional imaging is recommended
· Stage 111 B /C/D cross sectional imaging is recommended plus brain image
Patient with invasive melanoma should rarely be considered for transplant with out disease free period ranging from 3 to 10 years
Date from the Cincinnati transplant tumor registry :
Patient with history melanoma pre transplant wafting for 3 to 5 years
References :
1-American cancer society .
2- hand book of kidney transplant 6th ed
That is a logical approach. I wish you could provide more details of your evidence to support your arguments.
Ajay
This lesion is dark colored raised skin lesion
could be benign naevus or malignant melanoma
may be hemangioma
If this lesion is malignant melanoma workup should confirm with biopsy
then workup for metastasis as metastatic cancer is contraindication for malignancy
Then staging which includes 5year MS % ,appropriate treatment pre transplantattion , and sentinel lymph node
if Insitu >>>follow up post transplant 3months ,no wait time necessary .
Stage IA and B ,II A,III A>>should wait 1year before transplant after imaging brain ,CAP ,brain
Stage ll B and C ,lll b >>2-4 years wait +imaging + oncology referral
Stage lll C,D and stage lV>>>at least 5years wait +oncology referral +imaging
That is a logical approach. I like your evidence to support your arguments.
Ajay
What is your differential diagnosis?
Skin cancers including melanoma
Merkel cell carcinoma
Acral melanocytic nevi
Verrucous squamous cell carcinoma of sole
Hematoma
Council this patient regarding kidney transplantation?
Patient should be counseled in detail about the all the possibilities of the lesion and that melanoma seems to be likely . Multidisciplinary team including oncologist and dermatologist should be taken in loop .In order to confirm the diagnosis ,first biopsy of the lesion will be done and then further tests in order to check the status whether metastasis done or not as decision of treatment and renal transplantation will be dependent on the size and thickness and also on distant spread.. Metastatic melanoma is a contraindication to transplantation, however, 5 years waiting time is for IIb/IIc, and 2 years for Ia/Ib/IIa. Also given the advice of avoiding sun exposure and using sun blocks and sunscreens when going out especially and may need to switch from CNIs to Mtor post transplant.Recurrence of IgA Nephropathy should also be told to the patient.
What is your workup strategy?
Detailed history and complete clinical examination followed by CBC, ESR , viral serology including HIV, HSV-8, Hepatitis B and C profile, EBV and CMV,and cardiac assessment i.e., ECG,ECHO and CPET.Specific tests like skin biopsy –for diagnosis confirmation and CT chest/Abdomen/Pelvis-to check for distant spread should be done. Dermatologist and oncologist also to be involved .
REFERENCES:
Vajdic CM, van Leeuwen MT. Cancer incidence and risk factors after solid organ transplantation. International Journal of Cancer. 2009;125(8):1747–54.
Handbook of kidney transplantation by Gabriel Danovitch 6 edition
That is a logical approach I like your evidence to support your arguments.
Ajay
What is your differential diagnosis?
There is brown darkly pigmented raised lesion. It can be malignant melanoma, squamous cell carcinoma or hematoma.
Cutaneous malignancies are the most common cancers after kidney transplant. Incidence depends upon degree of sun exposure . There is 16 fold higher incidence of skin malignancy than aged matched controls. The common cancer after renal transplant include squamous cell carcinoma, Basal Cell carcinoma, malignant melanoma, Kaposi sarcoma and Merkel cell carcinoma.
Risk factors include , degree of immune suppression, type of transplant and degree of sun exposure
What is your work up strategy and counselling
This patient will require dermatology consultation and excision of skin lesion . Further management will depend upon histology. Patient should be advised about avoiding sun exposure and use of sunscreen .
If histology turns out to be malignant melanoma , then treatment will depend on stage.
Melanoma in situ or lentigo maligna – Proceed with transplant
Metastatic disease- Transplantation contra indicated
Stage 1 and 11a- wait 2-5 years
Stage 11b & 11c- wait 5 years
Post transplant careful surveillance and use of mTORi if no contraindication
Patient education about the disease and risk factors
Modification of immune suppression
That is an excellent approach. I wish your could provide evidence to support your arguments.
Ajay
Thank you Prof.
Davis LE, Shalin SC, Tackett AJ. Current state of melanoma diagnosis and treatment. Cancer Biol Ther. 2019;20(11):1366-1379.
Acral lentiginous melanoma:
Around half of all cases of melanoma that appear on the feet are acral lentiginous
melanoma,. this type of melanoma develops equally in all skin colors but represents melanomas in people with darker skin tones.
In the early stages, it can be hard to identify. It presents as a darker patch of
discoloration of the skin. It can also occur in the nail and appear as a wide, dark streak
on the nail. It is important to note, however, that not all dark streaks on the nail indicate
melanoma.
Differential Diagnosis:
Lentigo.
congenital acral nevi.
acquired acral nevi.
squamous cell carcinoma .
terra firma-forme dermatosis.
Theres risk of progress to malignancy and need close follow up with dermatologist
Follow up with consultation of dermatologist
CUBED” acronym which stands for colored lesions where any part is a different color,
uncertain diagnosis or a lesion without a clear clinical diagnosis, bleeding lesions,
enlargement of a lesion, and a delay in healing beyond two months.
The dermoscopic examination is a useful adjunct for pigmented acral lesions to help
identify worrisome pigment patterns.
lesions greater than 7 mm in diameter should be biopsied, and all lesions greater than 9
mm are likely to be melanoma..
References:
1-Kelly H. Hall; Ronald P. Rapini. Acral Lentiginous Melanoma. Stat Pearls Publishing;
2022 Jan-.
That is an excellent approach I like your evidence to support your arguments.
Ajay
References;
That is an excellent approach, but SCC (as you mention) is not a possibility here. I like your evidence to support your arguments.
Ajay
yes yes, thnx prof
Counseling the patient about kidney transplantation:
Workup strategy:
Hi Dr Wadi,
Calciphylaxis would not look like a lesion shown in this picture. Would you like to reconsider the 4th differential that you mentioned?
We expect you to provide evidence to support your arguments.
Ajay
History
Clinical image Melanoma of on the sole of a foot
====================================================================
What is your differential diagnosis?
====================================================================
Council this patient regarding kidney transplantation?
What is your workup strategy?
====================================================================
Reference
1- American Cancer Society and Natasha Buchanan Lunsford, PhD, from the Centers for Disease Control,July 23, 2019
2- Kalinova L, Majek O, Stehlik D, Krejci K, Bachleda P. Skin cancer incidence in renal transplant recipients—a single center study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010;154(3):257-260.
3. Zwald FO, Brown M. Skin cancer in solid organ transplant recipients: advances in therapy and management: part I. epidemiology of skin cancer in solid organ transplant recipients. J Am Acad Dermatol. 2011;65(2):253-261.
====================================================================
That is an excellent approach, but SCC is not a possibility here. I like your evidence to support your arguments.
Ajay
Sincerely, Prof Sharma
What is your differential diagnosis?
This is a well-defined dark blue skin lesion – mostly not raised
Differential diagnosis would be:
– Benign blue nevus.
– Benign melanocytic lesion.
– Dysplastic nevus.
– Malignant melanoma.
– Pigmented spindle cell tumor.
– Atypical fibroxanthoma.
Council this patient regarding kidney transplantation?
I’ll tell him that this lesion should be seen by a dermatologist to identify it, as this lesion is suspicious and if it is a melanoma, and in early stage with Breslow thickness < 1mm will be cured fully and pears a long disease free survival.
If this is a benign lesion we would proceed with transplantation but he must be in regular follow up after transplant with the dermatologist, as he recommends.
If this is a melanoma, he should be screened for distant metastasis and treated by an oncologist. And the stage of the disease would help in when to do the transplantation, as shown in table below.
What is your workup strategy?
After a detailed history including family history, travel history, sexual history and alcohol history, a thorough clinical examination including mucous membrane examination.
Full blood chemistry and CBC, ESR , viral serology including HIV, HSV-8, HSV-6, Hepatitis B and C profile, EBV and CMV.
Will ask for excisional biopsy and CT whole body with contrast and may be PET Scan, this to be discussed with oncologist for screening of visceral involvement.
Such a case needs multidisciplinary team work( dermatologist, infectious disease, oncologist and surgeon).
References:
– Al-Adra DP, Hammel L, Roberts J, Woodle ES, Levine D, Mandelbrot D, Verna E, Locke J, D’Cunha J, Farr M, Sawinski D, Agarwal PK, Plichta J, Pruthi S, Farr D, Carvajal R, Walker J, Zwald F, Habermann T, Gertz M, Bierman P, Dizon DS, Langstraat C, Al-Qaoud T, Eggener S, Richgels JP, Chang GJ, Geltzeiler C, Sapisochin G, Ricciardi R, Krupnick AS, Kennedy C, Mohindra N, Foley DP, Watt KD. Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement. Am J Transplant. 2021 Feb;21(2):460-474. doi: 10.1111/ajt.16318. Epub 2020 Oct 23. PMID: 32969590; PMCID: PMC8576374.
UpToDate- kidney transplantation in adults: Evaluation of the potential kidney transplant recipient
That is an excellent approach. I like your evidence to support your arguments.
Ajay
-Hyperpigmentation
–acquired perforating dermatosis
-Malignant skin lesion
-hematoma
If the lesion is malignant:
Active malignancy—excluding nonmelanoma skin cancers—precludes transplantation.
We and most clinical recommendations recommend a two-to-five-year recurrence-free period for most cancer survivors.
This is to minimize the risk of recurrence due to the enhanced development of micrometastases by immunosuppressive medications. There is, however, a marked variability in the likelihood of recurrence according to tumor type that determines the recommendations for patients with pre-existing tumors. Discussion with a multidisciplinary team, including an oncologist, is recommended.
The suggested cancer-free interval prior to transplantation should be individualized based on patient and tumor characteristics.
In organ transplant patients, long-term immunosuppressive medication to maintain host tolerance increases the risk of cancer. cSCCs and BCCs are the most prevalent skin cancers. These people may acquire skin cancer because of immunosuppressive intensity and duration, ethnicity, sun exposure history, and geography.
Take a thorough history from the patient, including the length of the lesion, whether it is painful, and any other lesions similar to this one in the body.
U-S doppler on the lower limb vessels.
Reference :
I like your approach
Differential diagnosis of this lesion are;
Calciphylaxis
Vasculitis, warfarin associated skin necrosis, skin malignancy,
Treatment should be adequate dialysis, measurement of calcium, phosphate, iPTH, and treat accordingly, stop calcium based drug, treatment of pain and infection,
May consider transplant if work up is normal and there is no absolute contraindication to transplant.
Calciphylaxis Scott G. Westphal; Troy Plumb.
Any other diagnosis?
acquire perforating dermatosis, hematoma, gangrene
Differential diagnosis;
Counsel this patient regarding kidney transplantation
Patient education about risk of carcinoma in post renal transplant and counseling regarding wait time till definite diagnosis.
Workup strategy
I like your approach
What is your differential diagnosis?
Council this patient regarding kidney transplantation?
What is your workup strategy?
1- Dermatology consultation and assessment for the need of excision biopsy in the current case, and setting a definite diagnosis
2- Patient should receive treatment according to the diagnosis of the lesion
3- Counseling the patient about screening, wait time and the use of sunscreen
4- Post-transplant screening should be done by the patient every month and by expert dermatologist every year.
5- Wait time before transplantation (3)
6- Patient should void sun exposure especially in the mid-day and the use of sun screen with high protection (5 stars 50+ SPF) is recommended especially in the early period after transplantation (using of triple therapy)
7- Reassuring the patient since the patient will receive minimal immunosuppression in the form of basiliximab induction and maintenance triple therapy including CNI, MMF, and corticosteroids for the first 3-6 months then we can switch to dual therapy including MMF and steroids. So we will stop CNI which is associated with higher incidence of skin cancer (4), and keep MMF which is associated with lower incidence of skin cancer when compared to azathioprine.
REFERANCES
1. Park CK, Fung K, Austin PC, et al. Incidence and Risk Factors of Keratinocyte Carcinoma After First Solid Organ Transplant in Ontario, Canada. JAMA Dermatol 2019; 155:1041.
2. Chockalingam R, Downing C, Tyring SK. Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients. J Clin Med 2015; 4:1229.
3. Zwald F, Leitenberger J, Zeitouni N, et al. Recommendations for Solid Organ Transplantation for Transplant Candidates With a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma: A Consensus Opinion From the International Transplant Skin Cancer Collaborative (ITSCC). Am J Transplant 2016; 16:407.
Kuschal C, Thoms KM, Boeckmann L, et al. Cyclosporin A inhibits nucleotide excision repair via downregulation of the xeroderma pigmentosum group A and G proteins, which is mediated by calcineurin inhibition. Exp Dermatol 2011; 20:795
Thankyou for an exellent answer.
•My DD?
•Melanoma is the main DD Then , calciphylaxis , organized hematoma , necrotic ulcer, …..
•Calciphylaxis, = calcific uremic arteriolopathy (CUA) or “Grey Scale”, is a rare syndrome characterized by painful skin lesions.
•Melanoma w 2.6% SIR post transplant
•In the Oxford transplant population studied melanomas occurred at approximately 8 times the rate in the general population.
•Regular Dermatology fu & Early Diagnosis => good outcome
Laing ME, et al. Br J Dermatol. 2006.
•The main factors to consider in organ-transplant candidates with a history of melanoma are :
•tumor stage,
•presence or absence of residual disease,
•time from diagnosis to transplantation.
•Solid organ transplant recipients have a greater risk of melanoma than immunocompetent individuals
•Mortality is also higher in this population, especially in patients with advanced melanoma, as treatment is especially challenging.
•Donor-derived melanoma has a very poor prognosis
C. González-C, et al , 2021
•SOT recipients have a 2- to 8-fold increased risk of developing melanoma compared with members of the general population
•Management and Treatment
•Excision
•IS Reduction
•Convert CNI => Sirolimus
•Chemo-therapy & Immune checkpoint inhibitors (ICIs) should be considered in SOT recipients with advanced non-BRAF-mutant melanoma.
•Dermatologic Follow-up of SOT Recipients=> to ensure that any melanoma that may occur is diagnosed early
•avoid sun exposure
•Strict sun protection(BROAD SPECTRUM)
•Summary :
•Early-stage melanoma, prognosis in SOT recipients is similar to that of the general population.
•Dermatologists have an essential role in post-transplant follow-up
•Much work remains regarding the management of advanced melanoma in SOT recipients, who currently face a worse prognosis than immunocompetent patients with metastatic disease.
•Because SOT recipients have been excluded from clinical trials of ICIs, treatment decisions should be reached by a multidisciplinary committee, with the informed consent of the patient and knowing that there is a high risk of acute rejection.
•Further research is also necessary on the role of adjuvant therapy in SOT recipients as it has been demonstrated to improve survival in immunocompetent patients.
C. González-C, et al , 2021
Br J Dermatol, 154 (2006)
Transpl Int, 30 (2017)
JAMA Dermatol, 153 (2017)
Australia. J Am Acad Dermatol (2019)
Transplant Res, 4 (2015)
What will be the wait time in a case of treated melanoma.
will it depend on stage?
residual disease?
time elapsed since clinical cure?
What is your differential diagnosis?
Council this patient regarding kidney transplantation?
What is your workup strategy?
Ofcourse Dermatology will be decisive but this one has no ulcer for ssc
no necrotic ulceration!!