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4. A 43-year-old CKD 5 patient who was on HD for 2 years secondary to unknown aetiology presented to you in the transplant clinic 1 year after his transplantation with this lesion on the right side of his neck (see below). He is currently on tacrolimus-based immunosuppression with excellent kidney function.
- What is your differential diagnosis?
- Briefly outline his management
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Differential diagnosis
Basal cell carcinoma
Squamous cell carcinoma
Management
History and examination
Tissue biopsy
Treatment
Reduction of immunosuppressive drugs . switch the Tac to mTor inhibitors
Surgical excision if possible
If is not possible, as non surgical ones give topical therapy as fluorouracil
Prevention
Avoid sun exposure
Regular self examination
Sirolimus has many studies that it can decrease the progression of skin cancers
DD :BCC ,SCC
most common skin cancers after transplant
can be diagnosed with biopsy
protective measures like :avoiding mid-day sun exposure, using sunscreen with at least 50 SPF and five stars against UVA, protective cloths like silk, using protective hat and sunglasses
Treatment is according to the size and if there is distant metastasis or not
Transplant recipients have a significantly higher risk of developing non-melanoma skin cancers compared with the general population and squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the most common post-transplant malignancies.
The skin cancers in transplant patients also tend to be more aggressive, with higher morbidity and mortality.
Preventive strategies play an important role in transplant recipients given their increased frequency of developing both premalignant and malignant skin lesions. Sun protection and regular skin cancer screening are critical.
In addition, chemoprophylaxis with systemic retinoids, nicotinamide and capecitabine can significantly reduce the development of new skin cancers.
Topical 5-fluorouracil, imiquimod, photodynamic therapy and cyclooxygenase inhibitors have all been investigated in transplant patients for the treatment of field cancerisation. Adjusting the immunosuppressive regimen is also an important adjuvant therapeutic strategy for managing skin cancers in transplant recipients and requires integrated multidisciplinary care with the entire transplant team.
https://pubmed.ncbi.nlm.nih.gov/31500949/
This lesion could be basal cell carcinoma then squamous cell carcinoma, these are the most common diagnoses. Confirmation by biopsy from the lesion is mandatory to offer the best treatment policy according to staging and differentiation as well.
The management ought to involve a multidisciplinary team including dermatologists, oncologists and transplant specialists. Tailoring of immunosuppression is mandatory with better switching to mTORi.
Excision of the lesion may be needed. Excluding metastasis is also required.
Behavioural and pharmaceutical attitude regarding sun exposure ought to be educated to our patients. Routine self-skin examination and screening is a must.
What is your differential diagnosis?
Basal cell carcinoma
SCC
Briefly outline his management
Biopsy of the Lesion to confirm the diagnosis.Surgical excision of the lesion or Mohs surgery.Cryosurgery for who are not candidate for surgery or who refused and opt for Cryosurgery.Although in recent review cryosurgery found to be equally good as surgery.Reduction of immunosuppresion and conversion of tacrolimus to mTOR inhibitors.Avoidance of sun exposure
What is your differential diagnosis?
Management plan:
· Approach including dermatologist, oncologist and nephrologist.
· history taking and physical examination including LNs.
· Laboratory investigations: FBC, U&E, Ca, urate , LDH and TAC trough level
· skin biopsy and histopathology for definitive diagnosis
· Check for any distant metastasis with CT head, chest, abdomen and pelvis or PET scan
· Management of the patient:
General measures:
· Proper education about the increased incidence of skin malignancy after transplantation.
· Reduce exposure to UV sun rays, use sun screen ( high SPF 50+ to protect against UV rays – A & B) and protective clothes.
· Regular self-examination, annual dermatology review
· Switch to MTOR inhibitors as they have been found to have a decreased incidence of skin cancer compared to CNIs.
· Definitive treatment(according to cancer type- Liaise with the dermatologist and oncologist):
· BCC: Surgical excision, Topical therapy with Imiquimod cream or 5FU, or photodynamic therapy depending on stage of the tumor.
· For SCC depending on stage:
– excision for single low risk malignancies
– Topical 5FU,Retinoid therapy for multiple skin malignancies
– Surgical excision, Topical 5FU,Imiquimod 5% creams or Cryotherapy, for in situ lesion
References:
1. Choon Chiat Oh, Haur Yueh Lee, Bien Keem Tan, Pryseley Nkouibert Assam,Terence Yi Shern Kee, Shiu Ming Pang. Dermatological conditions seen in renal transplant recipients in a Singapore tertiary hospital. Singapore Med J. 2018 Oct; 59(10): 519–52
2. 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.
● Differential Diagnosis
SSC
BCC
Acanthokeratosis
● Management
☆ Consulting Dermatologist
☆ Excisional biopsy for the lesion
☆ Reduction the immunotherapy
☆ Switching to m-TORi if non melanoma that have anti proliferative and anti tumor effects
☆ Radiotherapy or chemotherapy in specific cases
● I will advise this patient regarding the sun :
☆ Avoiding sun exposure especially mid day ( 10 am and 4 pm)
☆ Sun protection factors with SPF>50 and 5 stars
☆ Advice with Silk or cotton clothes
☆ Using hats and sunglasses
1-Differential diagnosis include:
cutaneous squamous cell carcinoma
basal cell carcinoma
Kaposi sarcoma
malignant melanoma,
2- Management include:
full investigations to confirm the exact diagnosis including biopsy and to define metastasis.
Manipulation of immunosuppressive drugs and adding mTORi
The lesion reddish, raised above the skin in the sun exposed area, in patient under immunosuppression include:
– Squamous cell carcinoma which is the most common cutaneous malignancy in solid organ transplant recipients, risk of SCC is about 250 times more than general population
-Basal cell carcinoma
– Kaposi sarcoma has 100 times higher incidence in transplant recipients than general population, it is seen commonly in patients Africa Mediterranean areas and Central Europe.
-Excisional biopsy is the most important diagnostic tool to confirm diagnosis
-treatment according to biopsy result
-Preventive measures to decrease exposure to sun UV rays as, protective clothes, avoid direct sun exposure especially in mid-day time, sun screen with high SPF.
-Reduction of immunosuppression.
Stopping of CNI and the use of mTOR inhibitors is supported by literature for Kaposi sarcoma only.
-Another option to maintain graft function and to lower the effect of immunosuppression on cancer progression is the use of mTOR inhibitors, without withdrawal of other immunosuppressive drugs.
mTOR inhibitors was also shown to have a synergistic effect with anti-neoplastic agents
– For in situ SCC management with topical fluorouracil and imiquimod cream, with the use of photodynamic treatment, and surgical removal and curettage showed good outcomes.
For biopsy proven SCC in recipients, micro-graphic surgery, with negative margins is the most definitive treatment method, cure rates are up to of 95%–100%.
references
Al-Adra, David1; Al-Qaoud, Talal1; Fowler, Kevin2; Wong, Germaine3,4,5. De Novo Malignancies after Kidney Transplantation. CJASN 17(3):p 434-443, March 2022.
Differential diagnoses are for the different types of skin cancer.
Decrease the dose of immunosuppressants
I would arrange a biopsy to perform histopathology for diagnosis. Depending on the diagnosis, I would assess the need for imaging tests for staging.
What is your differential diagnosis?
The differential diagnosis is basal cell carcinoma, Merkel cell carcinoma, squamous cell carcinoma
Briefly outline his management
Reducing the Tacrolimus or switching to mTOR inhibitors
Scenario 4:
Q1: Differential diagnosis:
1. Bcc (Basal cell carcinoma)
2. Squamous cell carcinoma (SCC)
3. Amelanocytic melanoma
Q2: Management includes:
1. Extensive examination of the skin to rule out other sites’ involvement
2. Excisional biopsy
3. Switching from CNI to mTOR inhibitors and using MMF as an antimetabolite
4. Topical 5-FU
5. Sun protection: by sun screening with SPF of more than 50 and a 5-star rating.
– wearing a hat and sun-protective clothes
– avoiding mid-day sun
6. Monthly self-examination of skin and annually by a dermatologist
7. For another diagnosis, radiation or even system therapy may be considered.
· What is your differential diagnosis?
DD includes: SCC, BCC, skin infection, actinic keratosis, allergic reaction, melanoma, dermatofibroma
· Briefly outline his management:
1- Referral to dermatologist fr proper assessment and possible skin biopsy.
2- He will need MDT that involves dermatologist, oncologist, nephrologist and transplant follow up.
3- Proper history and examination especially for more lesions and lymph nodes and rule out metastasis by proper imaging scans like CT-Chest, abdomen and pelvis, neck and spine.
4- Reduction of immune-suppression. CNI may be switched to m-TOR inhibitors.
5- Management will differ according to histopathology results and will be decided by dermatologist and oncologist.
Education and advice regarding sun-protection.
SCC
BCC
Acanthokeratosis
Thorough history and physical examination of the skin and LN
encourage self skin examination
surveillance skin examination
avoid sun exposure
encourage sun block use
exisional biopsy for the lesion
switch CNIS to mTOR inhibitors
Topical treatment
surgical removal if indicated
radiotherapy .
What is your differential diagnosis?
· Squamous cell carcinoma.
· Basal Cell Carcinoma
· Keratoacanthoma.
Briefly outline his management:
· Counseling for sun protection and self-examination. Surveillance visits for skin examination by dermatologist alongwith self-examination as a routine.
· Dermatology consult for dermoscopy and excision biopsy with wide margins.
· Systemic retinoids, oral nicotinamide, oral capecitabine have all proven efficacy in reducing risk of development of skin cancer post-transplant.
· Switching CNI to mTOR as patient has stable renal functions and risk of dermatological malignancies is higher with CNIs. Antimetabolite drug though not mentioned, if patient is on Azathioprine it should be switched to MPA. With these changes in immunosuppressive therapy risk of graft dysfunction should be considered and a close eye should be kept on renal profile.
· Multidisciplinary management once proven to be malignant lesion, wide excision biopsy by Mohs surgery is standard of treatment. Radiotherapy can be offered to those patients who are not suitable for surgical procedures. In case of extensive or malignant lesions chemotherapeutic options can be considered as well.
REFERENCES:
1. Oh CC, Lee HY, Tan BK, Assam PN, Kee TYS, Pang SM. Dermatological conditions seen in renal transplant recipients in a Singapore tertiary hospital. Singapore Med J. 2018 Oct;59(10):519-523. doi: 10.11622/smedj.2018126. PMID: 30386860; PMCID: PMC6199188.
2. Knoll GA, Kokolo MB, Mallick R, et al. Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data [published correction appears in BMJ. 2014;349:g7543]. BMJ. 2014;349:g6679. Published 2014 Nov 24. doi:10.1136/bmj.g6679
3. Bottomley MJ, Massey PR, Thuraisingham R, Doyle A, Rao S, Bibee KP, Bouwes Bavinck JN, Jambusaria-Pahlajani A, Harwood CA. Interventions After First Post-Transplant Cutaneous Squamous Cell Carcinoma: A Proposed Decision Framework. Transpl Int. 2022 Nov 22;35:10880. doi: 10.3389/ti.2022.10880. PMID: 36484063; PMCID: PMC9722441.
DD:
.Squamous cell carcinoma
. .Keratoacanthoma
Diagnosis:
Complete history& examination and tissue biopsy.
Treatment:
– Immunosuppression reduction
-Switching of CNI to mTOR inhibitors and surgical removal.
-Topical therapies ;imiquimod or topical fluorouracil, and photodynamic therapy for non surgical cases.
Prevention:
– sun protective clothes, hats and sun blocks.
-Regular self- examination of skin.
-Annual visits for dermatology monitoring
Differential diagnosis:
Management:
Diagnosis:
Need complete history and examination
Need to Obtain tissue biopsy.
Treatment:
Preventive measures:
This lesion can be Basal cell carcinoma or Sqaumous cell carcinoma; we need to excise and send to pathology. after excicon , It will be helpful to shift Tacrolimus to mTor inhibitor (everolimus or sirolimus)
Differential diagnosis of skin lesion are-
a) Squamous cell carcinoma
b) Basal cell carcinoma
c) Amelanotic melanoma
d) Cutaneous lymphoma
– History taking & physical examination
– Skin biopsy & histopathological examination
– Baseline investigations
– Search for metastases- CT scan of chest, abdomen & pelvis
Treatment-
– Surgical excision & topical 5 FU
– Reduction of immunosuppression ( CNI free sirolimus based therapy).
– Counselling patient regarding:
a) Avoid sun: Avoid intense sun exposure & avoid sun exposure for an hour or two on either side of mid day.
b) Sun protective clothing : Long sleave silk clothing, sunglass, cotton cricket hat is better.
c) Regular use of high factor sun block
d) Regular self examination.
Basal cell carcinoma , Squamous cell carcinoma , Keratoacanthoma
1- Multidisciplinary team should be involved including : Nephrologist , drematologist and oncologist
2 – biopsy for definite diagnosis
3 – Reduction of immunosupressive and change CNI with mTOR inhibitor ( anti malignant effect )
4- Avoid mid day sun and advice to use sun block in addition to use silk or cotton clothes
5- surgical excision or topical 5 FU according to oncology protocol
6- regular counselling and self examination .
Reference
1) Prof. Ahmed Halawa lecture on Post-Transplant malignancies
This patient has a skin lesion on the side of the neck after 1 year of transplantation…The patient has normal graft function and he is on CNI based immunosuppression…
The differential diagnosis include Basal cell carcinoma, squamous cell carcinoma and malignant melanoma and actinic keratosis….
the patient needs a skin biopsy of the lesion….he also needs basic metabolic workup and a regional; examination to detect lymphadenopathy and a PET CT scan to detect the spread of the disease
Squamous cell carcinoma is more common in renal transplant patient as compared to BCC…. Management includes wide local excision ..Topical agents like imiquimod and retinoids maybe used on the skin if there is BCC. .Local radiotherapy maybe needed for bigger lesions…
The patient maybe changed to sirolimus or everolimus as the rate of new onset skin malignancy and solid organ malignancy is very less as compared to CNI based regimen as evidenced by several meta analysis…
the patient should be advised about the exposure to the sun…. He should avoid mid day sun exposure and 2 hours before and later to noon… the patient should self examine himself for skin lesions which are new and get medical attention immediately…The patient should wear sunscreen with SPF of atleast 50 and 5 star rating to prevent UVA exposure…
1. What is your differential diagnosis?
BCC – nodular variant is most common BCC Shiny, Pink / erythematous, Pearly /Translucent, Early Papule / Nodule, with Telangiectatic Vessels Within The Lesion; Multiple Similar Papule in surrounding; on Sun Exposed Area (neck).
SCC – is most common skin cancer post-Transplant (1.8-4 times more than BCC)
Amelanotic Melanoma – early lesion with erythematous / pinkish border
2. Briefly outline his management
Diagnosis:
Dermatologist consultation – thorough examination of Skin for any other lesion and Lypmh nodes involvement
Excision Biopsy, with wide free margin – is curative; wound closure by flap cover by a plastic surgeon
IHC of biopsy specimen
Tacrolimus and MMF level
Treatment:
5 Fluorouracil or 5% Imiquimod cream local application
-Multidisciplinary Tumour Board Consultation: further treatment with modified Radical Neck dissection / Radiation / Chemotherapy depending on Lymph node involvement
– discuss with patient party the details problems, treatment options with pros and cons and immunosuppression change with side effects / rejection etc
Reduce Immunosuppression –
Stop MMF / Azathioprine (sensitizes UV ray induced damage)
Switching CNI to mTOR inhibitors
Proteinuria and Increased risk of Rejection – needs frequent monitoring
Patient education regarding skin cancer and counseling (3)
Surveillance for recurrent lesions – regular self-examination
3-6monthly skin examination by Dermatologist
How do you advise the patient regarding the sun?
Sun protection behaviour;
Avoid sun exposure (outdoor activity) – especially 2hrs before to 3hrs after midday 10am – 3pm)
Apply broad spectrum sunscreen with SPF >50, 5star UVA rating – ½ hour before going out (even on cloudy day, as reflected UV rays can come to land); reapply every 2hr during out door stay.
• Use photoprotective clothing (silk) – cover neck also, cotton hats, sunglasses
References:
Prof. Ahmed Halawa lecture on Post-Transplant malignancies
Stoff B, Salisbury C, Parker D, O’Reilly Zwald F.Dermatopathology of skin cancer in solid organ transplant recipients. Transplant Rev 2010;24(4):172–189.
Euvrard S, Morelon E, Rostaing L, et al. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med 2012; 367:329
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.
The index case is a post transplant patient with a skin lesion in the side of the neck…The lesion is well demarcated with elevated nature of papules and erythematous in nature… The patient has normal renal functions and is on tacrolimus based regimen for transplantation….
The differential diagnosis for the skin lesions are squamous cell carcinoma, basal cell carcinoma, amelanotic melanoma…. Other lesions like viral warts or keratoacantoma have characteristics descriptions and will not fit into the definitions
Patient needs a routine workup for LDH, CBC, Liver function test, Whole body PET scan is needed to detect can spread after the malignant nature is proven.. Patient needs skin biopsy of the lesion to confirm the diagnosis…..
If the biopsy is suggestive of BCC, I will wait for evaluation of metastasis as it is a locally spreading tumor If there is SCC, we have to evaluate for distant metastasis….Infact SCC is more common than BCC in transplant patient
Patient needs wide skin excision of the tumor.Patient needs to be switched on to mTOR inhibitors from CNI as mTOR inhibitors have anti proliferative properties….I will continue MMF and steroids for local skin tumors … If there is extensive spread of the skin lesion, multifocal lesions I will reduce my immunosuppression even further…
The patient needs to counselled about sun exposure and skin self examination…Weekly skin examination for new lesions should be encouraged… Skin protection from sun is almost impossible as sunlight gets reflected from the earth, water surface and will reach us…The mid day sun exposure should be avoided as it has the least atmosphere to penetrate and reach the skin… avoidance of mid day sun exposure 2 hours before and after the peak noon is encouraged… they should be counselled about wear sunscreen with SPF of atleast 50 for UVB and 5 star rating for UVA….
LIKELY TO BE NMSC
BCC
SCC
MERKEL CELL CA
MULTIDISCIPLINARY TEAM
BIOPSY OF LESION
ASSES IF ANY OTHER LESION SEEN
CHECK H/O PRIOR SKIN CANCER
ADVICE REGARDING SUN
SUN EXPOSURE ALONG WITH IS IS THE REASON FOR SKIN CANCER
PROTECTIV CLOTHING
SUN CREAM USE
AVOID MID DAY SUN
PATIENT EDUCATION
SELF EXAMINATION
ROLE OF MTOR
CNI HAS TO BE REDUCED
MTOR HAS ANTI-TUMOR PROPERTIES ALONG WITH IS
SIROLIMUS IS THE DRUG OF CHOICE AFTER REDUCING DOSE OF TACROLIMUS AND WAITING FOR SKIN LESION TO RESOLVE AS THSI MAY SUFFICE IN EARLY CASES
What is your differential diagnosis?
Basal cell carcinoma (most likely)
Squamous cell carcinoma
Keratoacanthoma
Amelanotic melanoma
Briefly outline his management
Diagnosis
Complete history and examination
To Obtain tissue biopsy.
Treatment
Reduction of immunosuppression
Switching CNI to mTOR inhibitors
Surgical excision
For Nonsurgical candidates’ Topical therapies (imiquimod or topical fluorouracil), C&E, and photodynamic therapy (PDT).
Preventive measures
Sun avoidance, sun protective clothes and sun blocks.
Regular self-skin examination
Annual review by physician or dermatology.
Squamous cell carcinoma, Basal cell carcinoma, Kaposi sarcoma
Skin cancers are the most common de novo post-transplant tumors in the adult transplant population and occur with increasing frequency with time.
SCC more common than BCC in renal transplant patient
avoid sun exposure use sun block even with Cloude weather.
excision of lesion.
reduction of immunosuppression with good graft function follow-up.
change AZA to mTOR, AZA increase risk of skin cancer in renal transplant patient.
Reference:
https://www.uptodate.com/contents/prevention-and-management-of-skin-cancer-in-solid-organ-transplant-recipients?search=skin%20cancer%20transplant&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H2295760:~:text=Prevention%20and%20management%20of%20skin%20cancer%20in%20solid%20organ%20transplant%20recipients
The lesion is raised, in the sun exposed area, with capillaries on the surface. Possible cause in immunocompromised patient include:
1- Basal cell carcinoma
2- Squamous cell carcinoma
3- Kaposi sarcoma
4- Skin warts
Taking detailed history and examination, to have full insight of the extent of the disease, degree of immunosuppression, and risk factor for skin cancers, like sun exposure.
Excisional biopsy
Dermatology and oncology involvement.
According to biopsy result will be the specific treatment. Which includes:
Excision with wide free area.
Reduction of immunosuppression.
Consideration of MTOR inhibitors.
For prevention of recurrence the use of sunscreen, hats, avoidance of exposure to
ultraviolet radiation during sun peak hours, should be employed by all patients.
References :
Post renal-transplant malignancy surveillance Clinical Medicine 20 22001 V7o Vl o2l0 1, 7N, oN 2o : 61:4 124–25–8
Basal cell carcinoma (BCC)
Squamous cell carcinoma (SCC)
Squamous cell carcinoma is the most common cutaneous malignancy in solid organ transplant recipients, so biopsy should be done to confirm the diagnosis and decide the proper management.
Biopsy
As transplant recipients at high risk for skin cancer, any suspicious lesion should be biopsied, with excisional biopsy.
PREVENTION
· Patient education concerning sun protection and skin self-examination
· Choice and modulation of immunosuppressive therapy
· Chemoprevention
· Post-transplantation surveillance
Choice and modulation of immunosuppressive regimen
· Regimens including mammalian target of rapamycin (mTOR) inhibitors such as sirolimus and everolimus rather than calcineurin inhibitors may reduce the risk for skin cancer and prolong the time to onset
· The benefit was most pronounced in patients who converted from an established immunosuppressive regimen to sirolimus.
· Mycophenolate mofetil versus azathioprine. A few studies have shown that mycophenolate mofetil and mycophenolic acid are associated with a lower incidence of skin cancer in solid organ transplant recipients compared with azathioprine
Reduction of immunosuppressive therapy.
· On the basis of the information from multiple RCTs and observational studies, we conclude that sirolimus use in kidney transplant recipients is associated with lower cancer risk, but this protective effect is largely limited to NMSC. Reduced NMSC incidence may be a result of the antiproliferative properties of sirolimus, or simply the removal of cyclosporine from the immunosuppressant regimen.
Chemoprevention for SCC: considered for patients who develop multiple (more than five) SCCs per year, aggressive SCCs, or accelerated development of SCCs
· Acitretin — Systemic retinoids such as acitretin, isotretinoin, have been used for the prevention or reduction of nonmelanoma skin cancers
· Capecitabine — may reduce the development of new cutaneous SCCs in solid organ transplant recipients.
· Basal cell carcinoma (BCC), melanoma, and Merkel cell carcinoma are managed similarly in organ transplant recipients and immunocompetent patients.
· There are no definitive guidelines regarding alteration in immunosuppressive regimens in patients with BCC, melanoma, or Merkel cell carcinoma. The risks and benefits of reduction in immunosuppression should be considered carefully.
1)https://www.uptodate.com/contents/prevention-and-management-of-skin-cancer-in-solid-organ-transplant-recipients?search=skin%20cancer%20transplant&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H2295760:~:text=Prevention%20and%20management%20of%20skin%20cancer%20in%20solid%20organ%20transplant%20recipients
2)https://www.uptodate.com/contents/epidemiology-and-risk-factors-for-skin-cancer-in-solid-organ-transplant-recipients?search=skin%20cancer%20transplant&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2#:~:text=Epidemiology%20and%20risk%20factors%20for%20skin%20cancer%20in%20solid%20organ%20transplant%20recipients
3)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567030/#:~:text=Sirolimus%20effects%20on,A%20Engels1
What is your differential diagnosis?
Briefly outline his management
depending on the casue
If scc……
excise
change CNI to mTOR
close follow up
general measures for prevention of skin
Differential diagnosis
Management
1.Thorough history and examination.
2.Skin biopsy to confirm diagnosis.
3.Other investigations such as imaging will be determined by presence of additional l symptoms and extent of disease.
4.Change tacrolimus to sirolimus and follow up closely to monitor for rejection.
What is your differential diagnosis?
BCC
SCC
Amelanotic melanoma
Briefly outline his management
Biopsy of the lesion with free margins is mandatory for diagnosis and treatment. An immunohistochemical study should be performed.
Guide the patient to avoid sun exposure, especially at times of higher concentrations of UV rays. Sunscreen 50+ and UV protective clothing are required.
Switching from a calcineurin inhibitor to an mTOR inhibitor to decrease tumor proliferation and block its inflammatory and metabolic cascade
What is your differential diagnosis?
Briefly outline his management
How do you advise the patient regarding the sun?
References:
Prof. Ahmed Halawa lecture, Post-transplantation lymphoproliferative disorders: Current concepts and future therapeutic approaches
Stoff B, Salisbury C, Parker D, O’Reilly Zwald F (2010) Dermatopathology of skin cancer in solid organ transplant recipients. Transplant Rev 24(4):172–189.
– What is your differential diagnosis?
– SCC
– BSC
– Amelanotic melanoma
– Keratoacanthoma
– Briefly outline his management
– Dermatology consultation for biopsy, staging & management options, and surgical excision.
– Reduction of immunosuppression (reduce or hold antiproliferative, reduce CNI, or shift to sirolimus)
– Patient education for preventive measures with avoidance of prolonged sun exposure especially in peak hours, using sun protective clothing, use of sunblock & self-examination of skin.
I would put BCC as the first diagnosis. I would appreciate if you could upload evidence to support your arguments.
What is your differential diagnosis?
Diagnosis: Nodular basal cell carcinoma(BCC)
Characteristic features include:
Shiny, Pink, Pearly Or Translucent, Flesh-coloured Early Papule/Nodule
-Telangiectatic Vessels Within The Lesion
-Presence On Sun Exposed Area (neck)
-Surrounding Similar Papule Or Flat Smaller Lesions Suggestive Of Multiple Lesions
-Most Common BCC Variant
Differential diagnosis
Squamous cell carcinoma
A melanocytic melanoma
Management: Must Include Multidisciplinary Tumour Board Consultation:
Step 1: Physical Examination
Thorough skin and lymph node examination
Step 2: Biopsy confirmation of diagnosis
Step 3: Risk stratification
After biopsy confirmation of BCC, there is a high risk of recurrence due to the following features:
Occurrence on neck
Immunosuppressed
Multiple lesions
Step 4: Modification of immunosuppression (3):
Switching CNI to mTOR inhibitors
Switching to MMF if on azathioprine
Step 5: Topical therapy (in view of multiple lesions)
5% Imiquimod or 5 Fluorouracil
Step 6: If still unresponsive
Radiation therapy: with increased risk of non-melanoma skin cancer(NMSC) in irradiated skin after treatment must be explained
Step 7: Systemic therapy(experimental evidence in solid organ transplantation)
Hedgehog pathway inhibitors or immune checkpoint inhibitor: higher chance of rejection with therapy should be explained
Patient education regarding skin cancer and counseling (3)
Sun protection with high SPF sunscreen-preferentially SPF 50 or above and 5+ star UVA rating (even if it is cloudy)
•Use of physical UV light barriers, such as photoprotective clothing, hats, sunglasses
•Avoidance of exposure to UV light by limiting outdoor activity during peak daylight (10 AM to 4 PM)
•Abstinence from tanning or artificial UV sources
•Education on the ABCDE rule for skin cancer identification: asymmetry, border, color, diameter, elevation/evolving
How do you advise the patient regarding the sun?
Almost impossible.
Avoid the Mid-day Sun, as mid-day, the sun is directly above you, and the amount of atmosphere it needs to penetrate to get to you is less so more gets through.
Avoid sun exposure for an hour or two on either side of mid-day.
Sun Protection Factor
• SPF range from as low as 2 to as high as 100. SPF is not an amount of protection, but it indicates how long it will take for UVB (not UVA) to burn your skin when using sunscreen, compared to how long it would take to burn without the product.
• A sunscreen with an SPF of 15 will take 15 times longer to BURN than without the sunscreen.
– Even on a cloudy day, UVR will get through to the earth’s surface.
– Sunlight is tricky – it will reflect off water, sand and other structures and can get to you even in the shade.
•Monthly self-examination of skin
Annual skin examination by a dermatologist or primary care physician experienced with skin cancer
Follow-up:
Explaining role of systemic chemoprevention, It requires continuous administration for chemoprevention
–Oral acitretin :10mg to 30mg daily(dose should be titrated)
–Nicotinamide: 500mg BD
Ensuring patient following all skin care educatio
Clinical pearls :
-Cutaneous Malignancies Are The Most Common Cancers After Kidney
Transplant.
– Incidence Depends Upon Degree Of Immune Suppression, type Of Transplant And 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.
References:
Prof. Ahmed Halawa lecture, Post-transplantation lymphoproliferative disorders: Current concepts and future therapeutic approaches
Stoff B, Salisbury C, Parker D, O’Reilly Zwald F (2010) Dermatopathology of skin cancer in solid organ transplant recipients. Transplant Rev 24(4):172–189.
Euvrard S, Morelon E, Rostaing L, et al. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med 2012; 367:329
Schwartz RA. Kaposi’s sarcoma: an update. J Surg Oncol. 2004 Sep 1;87(3):146-51. doi:
10.1002/jso.20090. PMID: 15334644.
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.
Berman H, Shimshak S, Reimer D, Brigham T, Hedges MS, Degesys C, Tolaymat L. Skin Cancer in Solid Organ Transplant Recipients: A Review for the Nondermatologist. Mayo Clin Proc. 2022 Dec;97(12):2355-2368. doi: 10.1016/j.mayocp.2022.07.004. Epub 2022 Nov 3. PMID: 36334939.
Upto Date
That is a very well structured reply. I like BCC as the first diagnosis. I appreciate your evidence to support your arguments.
· What is your differential diagnosis?
. My differentials are,
. Basal cell carcinoma,
. Cutaneous squamous cell carcinoma,
. Non melanoma skin cancer,
· Briefly outline his management;
· A good history,
· Thorough examination,
· Imaging of whole body with contrast like CT with contrast.
· Excisional biopsy with histological examination, electrodissection and
curettage.
· After confirmation will need,
· Opinion from dermatologist, oncologist, surgeon,
· Reduction of immunosuppression,
· Switch to mTORi,
· Cryotherapy.
· Immunomodulation Topical Imiquimod.
· Avoid sun exposure,
· Sun screen up-to 50%,
· Depends on extent may need radiotherapy.
· Chemotherapy like systemic retinoid, Nicotinamide, capecitabine.
. Rerferences;
1. Choon Chiat Oh, Haur Yueh Lee, Bien Keem Tan, Pryseley Nkouibert Assam,Terence Yi Shern Kee, Shiu Ming Pang.Dermatological conditions seen in renal transplant recipients in a Singapore tertiary hospital. Singapore Med J. 2018 Oct; 59(10): 519–523.
2. https://europepmc.org/article/med/22830463.
3.https://www.uptodate.com/contents/search?search=Prevention%20and%20management%20of%20skin%20cancer%20in%20solid%20organ%20transplant%20recipients&sp=0&searchType=PLAIN_TEXT&source=USER_INPUT&searchControl=TOP_PULLDOWN&searchOffset=1&autoComplete=false&language=&max=0&index=&autoCompleteTerm=&rawSentence=
Differential Diagnosis
Basal cell carcinoma
Cutaneous Squamous cell carcinoma
Kertoacanthoma???
Amelanotic melanoma???
Management
Management would require a multidisciplinary approach.
A skin biopsy should be done to confirm the diagnosis
Review of meds is mandatory
CNI s should be stopped
mTor inhibitors should be part of therapy
Avoidance of sun exposure and sun blocks should be used
Definitive treatment should be devised by multi disciplinary team
I note that. Can you upload some evidence please
I like BCC as the first diagnosis. I would appreciate if you could upload evidence to support your arguments. Typing ‘Update……..’ is not enough.
Nodular Basal cell carcinoma (BCC) most likely
squamous cell carcinoma (SCC)
keratoacanthomas
Melanoma
MDT including nephrologist,dermatologist ,oncologist and surgeon.
>>>Choice and modulation of immunosuppressive therapy The choice of the immunosuppressive regimen may influence the risk of post-transplant skin cancer. Regimens including mammalian target of rapamycin (mTOR) inhibitors such as sirolimus and everolimus rather than calcineurin inhibitors may reduce the risk for skin cancer and prolong the time to onset . mTOR inhibitors — Compared with calcineurin inhibitor-based regimens, immunosuppression with the mTOR inhibitors may reduce the risk for malignancies, including nonmelanoma skin cancer, in organ transplant recipients.
Reference
uptodate Prevention and management of skin cancer in solid organ transplant recipients
That is a well structured reply
tha you prof
I like BCC as the first diagnosis. I would appreciate if you could upload evidence to support your arguments. Typing ‘Update……..’ is not enough.
Differential Diagnosis:
· Squamous cell carcinoma
· Basal cell carcinoma
· Kertoacanthoma
· Amelanotic melanoma
Management;
· Multi-discipline approach with focus on patient education to report any lesion developing post organ transplant.
· Physical Exam
· Biopsy of the suspected lesion
In case of NMSC
· Sun protection/ sun block cream
· Reduction of immunosuppression
· CNI switch to mTOR if no other contraindications.
· Excision of lesion if not responding to above measurements and to lock for tumor spread like nodal involvements.
· Preventive strategies
I would put BCC as the first diagnosis. I would appreciate if you could upload evidence to support your arguments.
Melanoma and non melanoma skin cancer
Basal cell cancer
squamous cell cancer
Kaposi sarcoma
History and examination
Serology of IMN, CMV, EBV
Evaluation by dermatologist for biopsy and histology for typing and staging
Counselling regarding sun exposure and use sunscreen with SPF more than 50%. wearing sun protective materials to avoid ultraviolet ray
shift tacrolimus to sirolimus
I note that. Can you upload some evidence please
I would put BCC as the first diagnosis. I would appreciate if you could upload evidence to support your arguments.
What is your differential diagnosis?
Small maculopapular area with irregular outline with crustation in the middle for DD
Most common lesions given the Hx: SCC , BCC will be on top of the list
Briefly outline his management
Full examination and wide Moh excision
Consider reduction of immunusupression / switch to mTOR
avoid sun exposure and use sun cream with high SPF
Patient education about self examination
I note that. Can you upload some evidence please
I would put BCC as the first diagnosis. I would appreciate if you could upload evidence to support your arguments.
Thank you prof. I got all the information form that amazing review article in the journal club, I even presented it last week to my colleaues in the weekly teaching 🙂
Al-Adra, David1; Al-Qaoud, Talal1; Fowler, Kevin2; Wong, Germaine3,4,5. De Novo Malignancies after Kidney Transplantation. CJASN 17(3):p 434-443, March 2022. | DOI: 10.2215/CJN.14570920
Differential diagnosis:
Management outlines:
2.Recipient, behavioural and attitude for sun protection:
3.Self examination.
4.Annual screening and dermatologist visit.
5.Immunomodulators:
6.Convert to mTORi regiment; many trials show patient converting to mTORi therapy show that , there was reduce incidence of NMSC by aboout 49%, other study show significant improvement of skin dysplasia after conversion to mTOR-i.
7.CNI reduction dose.
References:
Euvrard S, Morelon E, Rostaing L, et al. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med 2012;367:329–39. 2 Harwood CA, Mesher D, McGregor JM, et al. A surveillance model for skin cancer in organ transplant recipients: a 22-year prospective study in an ethnically diverse population. Am J Transplant 2013;13:119–29. 3 Ramsay HM, Fryer AA, Hawley CM, et al. Non-Melanoma skin cancer risk in the Queensland renal transplant population. Br J Dermatol 2002;147:950–6. 4 Ulrich C, Kanitakis J, Stockfleth E, et al. Skin cancer in organ transplant recipients–where do we stand today? Am J Transplant 2008;8:2192–8. 5 Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med 2003;348:1681–91. 6 Berg D, Otley CC. Skin cancer in organ transplant recipients: epidemiology, pathogenesis, and management. J Am Acad Dermatol
I would put BCC as the first diagnosis. I appreciate the evidence to support your arguments.
. What is your differential diagnosis?
-Basal cell carcinoma
-Squamous Cell Carcinoma(cSCC)
– keratoacanthoma
Briefly outline his management:
–Detail history and clinical examination.
-Dermatology consultation and excisional or deep incisional biopsy for histopathology and according to the result put plan of management.
-Reduce the immunosuppression and switch tacrolimus to mTOR (sirolimus) with the close monitoring of graft function.
-Advice the patient to avoid direct exposure to the sun and used protective sunscreen and clothes.
I note that. Can you upload some evidence please
I like your superbly structured analysis. I would appreciate if you could upload evidence to support your arguments.
Thanks All
How do you advise the patient regarding the sun?
What is the role of mTOR in the management of this case?
Many thanks Prof.Halawa
How do you advise the patient regarding the sun?
.Almost impossible.
• Even on a cloudy day, UVR will get through to the earth’s surface.
• Sunlight is tricky – it will reflect off water, sand and other structures and can get to you even in the shade.
Avoid the Mid-day Sun
• At mid-day, the sun is directly above you, and the amount of atmosphere it needs to penetrate to get to you is less so more gets through.
• Avoid sun exposure for an hour or two on either side of mid-day.
Sun Protection Factor
• SPF range from as low as 2 to as high as 100.
• SPF is not an amount of protection, but it indicates how long it will take for UVB (not UVA) to burn your skin when using sunscreen, compared to how long it would
take to burn without the product.
• A sunscreen with an SPF of 15 will take 15 times longer to BURN than without the sunscreen.
What is the role of mTOR in the management of this case?
Post-transplant Malignancy By Prof.Ahmed Halawa ,Consultant Transplant Surgeon.Sheffield Teaching Hospitals – UK
Programme Director of the Fellowship in Clinical Transplantation – WKA
MTOR promotes basal cell carcinoma growth through atypical
PKC Rachel Y. Chow1 | Taylor M. Levee1 | Gurleen Kaur1 | Daniel P. Cedeno1 | Linda T. Doan2 | Scott X. At 30 November 2020
I do not agree with you completely that it is ‘almost impossible’ to advise regarding preventive measures.
>>>> Patients who received SRL-based, calcineurin inhibitor–free therapy after CsA withdrawal at month 3 had a reduced incidence of both skin and nonskin malignancies at 5 yr after renal transplantation compared with those who received SRL therapy combined with CsA. Longer follow-up and additional trials are needed to confirm these promising results.
>>> Independent analysis of BCC and SCC indicated that SRLbased, CNI-free immunosuppression after CsA withdrawal had a favorable impact on the mean annualized rate for both of these events, with a pronounced effect in delaying the median time to first occurrence of a BCC.
reference
Sirolimus Therapy after Early Cyclosporine Withdrawal Reduces the Risk for Cancer in Adult Renal Transplantation
advice to avoid sun exposure even not to go in non-sunny days
wear protective clothes
and use protective sunscreen cream
mTor has antitumor and antiproliferative effect
Thank you, prof Halawa.
The patient will be advised as follows:
The mTOR inhibition is an antiproliferative immunosuppressive and it has been shown to reduce the incidence of post-transplant malignancy
References
The pt should be advised to whenever possible avoid sun exposure, minimize midday sun exposure, Use appropriate attire possible silk clothing and Hats when going into the sun and make use of SPF 50 when exposed to the sun.
MTOR inhibitors are antiproliferative and decrease malignancy occurance post transplant.They down regulate expression of tumor HIF and block cell cycle at G1 thus preventing proliferation of cancer cells.
REF;
Prof Halawa lecture on Post Transplant Malignancy.
Zhilin Zou et al; MTOR signaling pathway and MTOR inhibitor in cancer ;progress and challenges.
Sun protectives advise.
Role of mTOR inhibitors
References
I- Advise regarding sun:
1- Avoid sun exposure:
Avoid mid-day sun: 1-2 hour on either side of mid-day (from 10Am-3 Pm)
2- Sun protection factor:
a- Cream:
Ideal sun screen: should be SPF>50 and 5 stars
b- Clothes:
Silk is the best (finest wave)
Nylon is poor
Cotton is better
II- in this case, reduction of immunotherapy and shift to m-TOR inhibitors is recommended if proved to be non-melanoma skin cancer.
1. How would advise the patient regarding the sun?
Educate the patient on preventative measures i.e., wear sunscreen SPF50+ with 5 stars, avoid sun exposure between 11am and 4pm, wear sun protective clothing, hat, sunglasses (1)
2. Role of mTORi in the management of this case
mTORi e.g., sirolimus and everolimus unlike CNIs have been shown to reduce the risk of skin cancer as well as prolong the time to onset. mTORi have anti-tumor and anti-proliferative effects (2)
References
1. Dreno B. Skin cancers after transplantation. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association – European Renal Association. 2003 Jun;18(6):1052-8. PubMed PMID: 12748333. Epub 2003/05/16. eng.
2. Euvrard S, Morelon E, Rostaing L, Goffin E, Brocard A, Tromme I, et al. Sirolimus and secondary skin-cancer prevention in kidney transplantation. The New England journal of medicine. 2012 Jul 26;367(4):329-39. PubMed PMID: 22830463. Epub 2012/07/27. eng.
Sun protection is very important in this regard. Avoidance of mid day sun, wear sun protecting cloths, hats, use of higher SPF sun screen.
mTOR has got anti proliferative property.
Reference: Lecture
-Sun protective procedures and avoidence of UV irradiation is needed
-mTOR has antioncogenic effects
cancers depending on activation of the oncoprotein Akt also require subsequent activation of mTORC1 to drive tumor genesis,many cancer promoting lesions activate the mTORC1 pathway and this complex is sensitive to rapamycin and its analogues.
Rapamycin and its analogues act by forming an inhibitory complex with their intracellular receptor, the immunophilin FK506-binding protein which binds a region in the C terminus of mTORC1 termed FKB12-rapamycin binding, thereby inhibiting mTORC1 activity.
Sirolimus was associated with a 54% reduction in the incidence of NMSCs, a protective effect however limited to conversion trials in which sirolimus was an alternative to cyclosporine
Reference
de Fijter, Johan W. MD, PhD. Cancer and mTOR Inhibitors in Transplant Recipients. Transplantation 101(1):p 45-55, January 2017.
Thank you, Prof.,Ahmad halawa
use sun block even with Cloude weather.
mTOR has antitumor and antiproliferative effect.
How do you advise the patient regarding the sun?
Sun protection with avoiding sun exposure at peak hours,
High SPF (50) sun block, and sun protection.
Clothes including hats and silk material
What is the role of mTOR in the management of this case?
Patients who received SRL-based, calcineurin inhibitor–free therapy after CsA withdrawal at month 3 had a reduced incidence of both skin and nonskin malignancies at 5 yr after renal transplantation compared with those who received SRL therapy combined with CsA. but they are with adverse effect (peripheral oedema and papulopustular acne-like reactions, proteinuria, dyslipidemia, interstitial pneumonia, leucopenia) and lot of patients discontinued the drug due to adverse effect.
Need to check urine for proteinuria, blood pressure and good glycemic control, lipid profile.
Reference
Skin cancer in transplant recipientsAuthor: Dr Mathew Ludgate MBChB, Dept of Dermatology Greenlane Hospital, Auckland, New Zealand, 2005.
Sirolimus Therapy after Early Cyclosporine Withdrawal Reduces the Risk for Cancer in Adult Renal Transplantation
Thanks prof. Halawa
How do you advise the patient regarding the sun?
Avoid intense sun exposure & avoid sun exposure for an hour or two on either side of mid day.
Sun protective clothing : Long sleave silk clothing, sunglass, cotton cricket hat is better.
What is the role of mTOR in the management of this case?
mTOR inhibitor reduce cell growth & proliferation
Advise the patient regarding the sun:
Role of mTOR in the management of this case:
Patients who received SRL-based, calcineurin inhibitor–free therapy after CsA withdrawal at month 3 had a reduced incidence of both skin and nonskin malignancies at 5 year after renal transplantation compared with those who received SRL therapy combined with CsA. but they are with adverse effect.
Peripheral oedema and papulopustular acne-like reactions, proteinuria, dyslipidaemia, interstitial pneumonia, leukopenia) and lot of patients discontinued the drug due to adverse effect.
Need to check urine for proteinuria, blood pressure and good glycaemic control, lipid profile.
Reference:
Sirolimus Therapy after Early Cyclosporine Withdrawal Reduces the Risk for Cancer in Adult Renal Transplantation
Skin cancer in transplant recipientsAuthor: Dr Mathew Ludgate MBChB, Dept of Dermatology Greenlane Hospital, Auckland, New Zealand, 2005.
How do you advise the patient regarding the sun?
Although high quality data is still lacking in this regard, it is widely accepted that reducing sun exposure reduces the risk and incidence of skin lesions in post-transplant patients. It remains a cornerstone and cost effective method to reduce morbidity and mortality. Repeated counseling and poor compliance remains a big issue.
What is the role of mTOR in the management of this case?
mTORi are known to reduce incidence of post-transplant malignancies as well as reduce the malignant potential and spread of many malignancies including skin cancers.
References:
1. Thet, Z., Lam, A.Ky., Ng, SK. et al. An integrated skin cancer education program in renal transplant recipients and patients with glomerular disease. BMC Nephrol 23, 361 (2022). https://doi.org/10.1186/s12882-022-02997-z
2. Geissler EK. Skin cancer in solid organ transplant recipients: are mTOR inhibitors a game changer?. Transplant Res. 2015;4:1. Published 2015 Jan 14. doi:10.1186/s13737-014-0022-4
Sun protection is provided by avoiding mid-day sun exposure, using sunscreen with at least 50 SPF and five stars against UVA, protective cloths like silk, using protective hat and sunglasses.
Drugs classified as m TORi are anti- proliferative and may reduce skin cancers.
1-
●I should advise him to avoid the mid day sun
● In addition to using sunscreen of SPF 50+ five stars
●protective clothes
● self examination
2- MTOR has an anti proliferative effect, several studies reported its role in reducing the risk of SCC.
professor ahmad halawa lecture 2023
What is your differential diagnosis?
——————————————————————————-
1-basal cell carcinoma .
2-Squmaus cell carcinoma .
3- keratoacanthoma
Briefly outline his management;
——————————————————-
1-Multidisciplinary approach to care;
This cases should evaluated and managed at MDT meeting including dermatology and transplant teams .
2-Diagnosis and staging ;
1-Obtain a complete history and perform a physical examination, paying specific attention to sites of prior skin cancers and palpating the regional nodal basin for high-risk skin cancers.
2-Obtain tissue biopsy.
Although the diagnosis of BCC can often be made by the experienced clinician based upon the clinical and dermoscopic examination, a skin biopsy is essential to confirm the diagnosis and provide additional information on the risk for tumor recurrence following treatment.
3-Treatment ;
1- Reduction of immunosuppression with monitoring of renal function +/- switching CNI to mTORi.
2-Surgical candidates ;
For primary, nodular or superficial, low-risk BCCs, we suggest surgical excision .
3-Nonsurgical candidates;
Therapeutic options for patients with low-risk BCC who are not surgical candidates or who prefer to avoid surgery include topical therapies (imiquimod or topical fluorouracil), C&E, and photodynamic therapy (PDT). The choice depends on the clinician’s experience and the patient’s characteristics and preferences.
4-Incompletely excised basal cell carcinoma ;
For the management of incompletely excised, low-risk BCCs located on the trunk or extremities, standard surgical re-excision or Mohs surgery is an appropriate option.
4-Follow-up;
————————————————-
Following treatment, close follow-up is required to detect both local recurrences and new skin cancers and to assess the post-treatment course. Most dermatologists recommend re-evaluation every six months for the first year following treatment and then annually.
Patient education about the importance of preventive measures including sun avoidance, sun protective clothes and sun blocks. Regular self-examination and reporting any new lesions. Annual review by dermatology.
Reference;
————————————————
1-ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Timothy K Chartier, MD (deceased), who contributed to an earlier version of this topic review. Topic 5338 Version 38.0 .
2- https://onlinelibrary.wiley.com › doi › pdf This review provides prognostic guidance to transplant physicians evaluating transplantation candidates who have skin cancer .
I note that.
I like your superbly structured analysis and approach as you have used headings and sub-headings to make it easy to read. I appreciate the evidence to support your arguments.
1- DD
SCC
BCC
Amelanotic melanoma
keratoacanthoma
II- Management:
1- Reduction of immunotherapy
2- Sirolimus based immunotherapy in non-melanoma lesions
3- further management according to the pathology type
4- patient education regarding prophylactic measure for skin malignancies:
Well done
Any suspicious lesion in a transplant patient should be taken seriously and a biopsy should be considered. The biopsy of this lesion confirmed BCC. Remember there are many types of BCC. THIS IS A NODULAR BCC. Other types are superficial spreading, pigmented and sclerosing types.
Thank you very much
Differential diagnosis:
Management:
Well done
Any suspicious lesion in a transplant patient should be taken seriously and a biopsy should be considered. The biopsy of this lesion confirmed BCC. Remember there are many types of BCC. THIS IS A NODULAR BCC. Other types are superficial spreading, pigmented and sclerosing types.
What is your differential diagnosis?
This is a skin lesion with raised edge and hyperemic, carries the possibility of skin cancer. The likely differential for this lesion are:
· BCC.
· SCC.
· Actinic Keratosis.
· Amelanotic melanoma.
Briefly outline his management(1)
· MDT; including transplant nephrologist, pathologist, plastic surgeon, dermatologist and oncologist.
· Detailed history and relevant clinical examination.
· CBC, LFT, RFT, blood sugar.
· Skin biopsy, staging and ruling out metastasis(U/S scan, CXR and CT examination of the suspected sites).
· Surgical excision with safety margin.
· Reduction of immunosuppression.
· Shifting TAC to sirolimus and if on AZA, to be replaced with MMF.
· Advice regarding post-transplant behavioral intervention to minimize the risk of recurrence:
a) Protective sunscreen and clothes.
b) Avoiding direct sunlight at the peak hours.
c) Doing routine self-examination of the skin for early detection of skin lesions or recurrence.
References
1. 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.
Well done
Any suspicious lesion in a transplant patient should be taken seriously and a biopsy should be considered. The biopsy of this lesion confirmed BCC. Remember there are many types of BCC. THIS IS A NODULAR BCC. Other types are superficial spreading, pigmented and sclerosing types.
The above image shows well-defined shiny vascularized pearly papule with rolled borders which is suggestive of basal cell carcinoma ,however other differentials should also be considered.
Cutaneous squamous cell carcinoma
Keratinocyte carcinoma,
Actinic keratoma
Amelanotic melanoma
MDT should be involved including dermatologist,oncologist,surgical specialist,transplant physician and psychologist.Skin biopsy of the lesion should be done first followed by counselling of the patient to avoid sun exposed areas,apply sunscreens whenever going outside with specific treatment according to the size location ,grade af tumor and performance status of the patient..Reduction of immunosuppression and switching of CNIs to mTORi is must.Options are surgical and medical options.Radiotherapy can be conaidered when surgery can’t be done.Low risk BCC can be managed with cryosurgery.Topical therapy and Immune Response Modifiers(Imiquimod 5% Cream)can be used.
REFERENCES:
1-James LJ, Saglimbene V, Wong G, Tong A, Luu LDW, Craig J, Howard K, Howell M. Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trials. BMJ Open. 2020 May 17;10(5):
2-Choon Chiat Oh, Haur Yueh Lee, Bien Keem Tan, Pryseley Nkouibert Assam,Terence Yi Shern Kee, Shiu Ming Pang.Dermatological conditions seen in renal transplant recipients in a Singapore tertiary hospital. Singapore Med J. 2018 Oct; 59(10): 519–523
3-Lecture of Prof Halawa
Well done
Any suspicious lesion in a transplant patient should be taken seriously and a biopsy should be considered. The biopsy of this lesion confirmed BCC. Remember there are many types of BCC. THIS IS A NODULAR BCC. Other types are superficial spreading, pigmented and sclerosing types.
4. A 43-year-old CKD 5 patient who was on HD for 2 years secondary to unknown aetiology presented to you in the transplant clinic 1 year after his transplantation with this lesion on the right side of his neck (see below). He is currently on tacrolimus-based immunosuppression with excellent kidney function.
What is your differential diagnosis?
– Squamous cell carcinoma (SCC) – most predominant, associated with aggressive behaviour (1)
– Basal cell carcinoma (BCC)
– Melanoma
– Actinic keratoses
– Kaposi sarcoma
Briefly outline his management
– Detailed history – assess for risk factors e.g., pre-transplant skin cancer, UV radiation, HPV infection, genetic factors, duration and level of immunosuppression (2)
– Thorough physical examination – check for lymphadenopathy and any other abnormal masses
– Baseline investigations: – CBC, kidney function test, liver function test
– Definitive diagnosis can be confirmed using biopsy and histopathological analysis
– CT Chest to check for spread/ distant metastases
– Treatment of HPV infection if present (3)
– Multidisciplinary approach – involve an oncologist, dermatologist
– Aim of treatment is to: – (2)
o restore the efficiency of the immune system by modulation of immunosuppression – allows the immune system to fight the cancer cells
o remove the tumor by surgery or radiotherapy
– Appropriate immunosuppressive drug reduction is beneficial in cases of SCC with increased risk of local recurrence or metastases i.e., multiple tumors, tumors >2cm in size, tumor infiltration of 3-4mm, low-differentiated lesions, lesions on the forehead, lips, ears (2)
– Modulation of immunosuppressive drugs i.e., switch the patient to an mTORI
o mTORi e.g., sirolimus and everolimus rather than CNI have been shown to reduce the risk of skin cancer as well as prolong the time to onset (4).
o Mycophenolic analogues have been associated a lower incidence of skin cancer compared to azathioprine (5).
o Reduction of immunosuppressive drugs in patients who develop recurrent disease, metastatic disease or patients with numerous lesions. The intensity and duration of immunosuppression promotes development of skin malignancies (6). Balance the risks and benefits associated with reduction in immunosuppressive therapy.
– Chemoprevention e.g., systemic retinoids (Aciretin, Isotretinoin), Capecitabine, Nicotinamide for patients with aggressive SCC or multiple cases of SCC
– Surgery alone may be sufficient in patients without high-risk factors
– Surgical excision or Mohs microscopic surgery – used in the treatment of most skin cancers in transplant patients
– Radiotherapy for patients unable to tolerate surgery and as adjunctive therapy for lesions that cannot be excised completely.
– Electrodessiccation and curettage for small tumors on the trunk if present
– To prevent transformation into squamous cell carcinomas, actinic keratoses and warty lesions need to be treated aggressively. Treatment options include: – cryosurgery, electodessication and curettage of thicker lesions, topical 5-fluorouracil, topical imiquimod, photodynamic therapy
– Educate patient on preventative measures i.e., be sun-smart – wear sunscreen SPF30+, avoid sun exposure between 11am and 4pm, wear sun protective clothing, hat, sunglasses (3)
– Encourage patient to perform the regular skin checks i.e., monthly skin self-examination and report any new lesions to doctor. This will ensure early detection and treatment of cancerous and pre-cancerous skin lesions (3)
References
1. Ramsay HM, Fryer AA, Reece S, Smith AG, Harden PN. Clinical risk factors associated with nonmelanoma skin cancer in renal transplant recipients. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2000 Jul;36(1):167-76. PubMed PMID: 10873887. Epub 2000/06/30. eng.
2. Berg D, Otley CC. Skin cancer in organ transplant recipients: Epidemiology, pathogenesis, and management. Journal of the American Academy of Dermatology. 2002 Jul;47(1):1-17; quiz 8-20. PubMed PMID: 12077575. Epub 2002/06/22. eng.
3. Dreno B. Skin cancers after transplantation. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association – European Renal Association. 2003 Jun;18(6):1052-8. PubMed PMID: 12748333. Epub 2003/05/16. eng.
4. Euvrard S, Morelon E, Rostaing L, Goffin E, Brocard A, Tromme I, et al. Sirolimus and secondary skin-cancer prevention in kidney transplantation. The New England journal of medicine. 2012 Jul 26;367(4):329-39. PubMed PMID: 22830463. Epub 2012/07/27. eng.
5. Coghill AE, Johnson LG, Berg D, Resler AJ, Leca N, Madeleine MM. Immunosuppressive Medications and Squamous Cell Skin Carcinoma: Nested Case-Control Study Within the Skin Cancer after Organ Transplant (SCOT) Cohort. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2016 Feb;16(2):565-73. PubMed PMID: 26824445. Pubmed Central PMCID: PMC5500236. Epub 2016/01/30. eng.
6. Moloney FJ, Kelly PO, Kay EW, Conlon P, Murphy GM. Maintenance versus reduction of immunosuppression in renal transplant recipients with aggressive squamous cell carcinoma. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al]. 2004 Apr;30(4 Pt 2):674-8. PubMed PMID: 15061854. Epub 2004/04/06. eng.
Well done
Any suspicious lesion in a transplant patient should be taken seriously and a biopsy should be considered. The biopsy of this lesion confirmed BCC. Remember there are many types of BCC. THIS IS A NODULAR BCC. Other types are superficial spreading, pigmented and sclerosing types.
Well noted Prof. Thank you.
Skin lesion such as this in immune compromised patient can be basal cell carcinoma or Sq cell Ca (SCCs).
Excision biopsy is essential and accordingly therapy can be decided.
SCCs
Lesion classification — In immunocompetent patients, a combination of clinical and histopathologic features is used to classify individual SCCs as low risk or high risk for aggressive clinical behavior. These classifications are used to guide the approach to treatment.
Treatment — Based upon multiple population-based studies indicating an increased likelihood for aggressive disease in organ transplant recipients, invasive SCCs in this group of patients are generally considered high-risk lesions. Thus, procedures that provide pathologic confirmation of complete tumor removal, such as Mohs surgery or conventional surgical excision with margin control, are the preferred treatments for invasive SCCs in these patients to prevent local recurrence and disease spread.
Lesions classified as high-risk SCC by AJCC criteria or alternative staging systems may require additional workup (eg, computed tomography or magnetic resonance imaging, sentinel lymph node biopsy) and/or adjunctive therapy.
Basal cell carcinoma — Basal cell carcinoma (BCC) is not associated with the same level of morbidity and mortality as SCC in organ transplant recipients. The management of BCC in this population resembles management in the immunocompetent patients.
Imiquimod is a topical immunostimulatory agent that is sometimes used for the treatment of superficial BCC. The use of imiquimod for limited periods on small areas (60 to 100 cm2) appears to be safe in organ transplant recipients.
Reference:
Prevention and management of skin cancer in solid organ transplant recipients. UpToDate
Well done
Any suspicious lesion in a transplant patient should be taken seriously and a biopsy should be considered. The biopsy of this lesion confirmed BCC. Remember there are many types of BCC. THIS IS A NODULAR BCC. Other types are superficial spreading, pigmented and sclerosing types.
Differential diagnosis:
-Skin lesions in immunocompromised patient can be skin cancers including squamous cell carcinoma or basal cell carcinoma (non melanoma skin cancers).
Other differential diagnosis can be:
The Proposed mechanisms through which immunosuppression may contribute to the development of skin cancer include:
-Reduced immune surveillance, that causing survival and proliferation of atypical cells.
-Direct carcinogenic effects of immunosuppressive agents, such as Azathioprine and CNIs.
-Proliferation of oncogenic viruses in the setting of immunosuppression. Epstein-Barr virus (EBV), human papillomavirus (HPV), Kaposi sarcoma herpes virus (KSHV), human T cell lymphotropic virus type 1 (HTLV-1), and Merkel cell polyomavirus (MCV) are the main viruses associated with the development of cancer in immunosuppressed patients.
Management:
-Diagnosis with excisional biopsy
-Treatment depends on site, size and extension
-Surgical removal if limited superficial lesion.
-For patients with squamous cell carcinoma, there is now trial-based evidence to suggest conversion to an mTOR inhibitor may reduce the risk of cancer in the longer term.
-Immunotherapy
-careful Reduction of immunosuppression to avoid acute rejections.
-Regular surveillance.
Well done
Any suspicious lesion in a transplant patient should be taken seriously and a biopsy should be considered. The biopsy of this lesion confirmed BCC. Remember there are many types of BCC. THIS IS A NODULAR BCC. Other types are superficial spreading, pigmented and sclerosing types.
Thankyou
What is your differential diagnosis?
Small lesion in sun exposed area, nodular with capillaries in its surface post kidney transplant which might be :
Squamous cell carcinoma.
Basal cell carcinoma.
Actinic keratosis.
Hypertrophic lupus erythematosus, lichen planus.
Briefly outline his management.
Definitive diagnosis is made by shave, punch or excisional biopsies and management plan will be decided as regards.
1-Multidisciplinary team (dermatologist , transplant nephrologist, oncologist, social worker, dietitian, clinical psychologist, and others).
2-Excisional biopsy for final diagnosis.
3-Reduction of immunosuppression is the main line of treatment.
4-Shifting of tacrolimus to MTOR inhibitors .
5-Preventive measure to avoid recurrence such as skin self-examination, sun block and others.
References:
1- Handbook of Kidney Transplantation, Gabriel M. Danovitch, MD.
2- Epidemiology and risk factors for skin cancer in solid organ transplant recipients UP TO DATE 2022.
If you mean Discoid Lupus it is usually in the face ,and un usual to occur de novo in a post TX case.
Such patient we neeed first of all having skin biopsy then decied what type of skin cancer he has
then his managment will be multidiciplinary approach including the dermatologist ,oncologist and nephrologist
Generally will start by general CBC.CMP,LFT,US ABDOMEN TO SEE. if he has any viseral organ involvement .
Managment of the patient:
first of all need to raise the awareness of the patient about the possible skin malignenecy after RTX
the importance to have sun screen with high SPF 50+ to protect against UV rays – A & B
For SCC depending on stage, excision for single low risk malignancies, Topical 5FU,Retinoid therapy for multiple skin malignancies and Cryotherapy, Surgical excision, Topical 5FU,Imiquimod 5% creams for insitu lesion
references
uptodate
Well done.
DIFFERENTIAL DIAGNOSIS.
Skin cancer, SCC or BCC,SCC is more common post transplant in comparison to BCC in reference to the general population ratio of 8;1 has been noted in some literature.
KS
Amelanotic melanoma.
Actinic keratosis.
Keratoacanthoma.
Merkel cell carcinoma.
MANAGEMENT.
-MDT approach- dermatologist, oncologist and nephrologist.
-Good history taking and physical examination.
-Baseline workups to evaluate the patient; FHG,UECS,LFTS,RBS,TAC levels, Coag profile.
-Biopsy of the lesion for a definitive histological diagnosis.
-Assess any mets -PET scan or Head CT, Thoraco abdominal pelvic CT scan.
-Supportive mgt;
-Definitive management;
1.Switch to MTOR inhibitors as they have been found to have a decreased incidence of skin cancer compared to CNIs.
2.For BCC, Surgical excision, Topicals -Imiquimod cream,5FU or photodynamic therapy depending on stage and in consultation with an oncologist.
3.For SCC depending on stage, excision for single low risk malignancies, Topical 5FU,Retinoid therapy for multiple skin malignancies and Cryotherapy, Surgical excision, Topical 5FU,Imiquimod 5% creams for insitu lesion
.
4.Sytemic therapy i.e Chemo -Carboplatin + paclitaxel can be considered in those with spread in consultation with an oncologist.
REFERENCES.
Prof Halawa lecture on post transplant malignancies.
Very good answer ,thankyou.
Thank you Prof.
–Differential diagnosis
Basal cell carcinoma
Squamous cell carcinoma
Actinic ketratosis
Melanoma
Dermatofibroma
Drug induced lesion
Skin infection
– Management
· An MDT has to be involved ,including dermatologist and an oncologist besides the transplantation team
· The general condition of the patient has to be assessed and excisional biopsy is needed and then for histopathological evaluation also the draining lymph nodes and all body has to be screened for any other lesions
· Pan CT scan to trace any other internal organs affection
· The immunosuppressive medications have to be tailored where CNI can be switched to m TOR.
· Actinic Keratosis s and Squamous cell carcinoma in situ are lesions that can occur within 5 years after transplantation as Actinic keratosis is an early cutaneous carcinogenic lesion that can develop into invasive Squamous cell carcinoma
· If this lesion is a localised one cryosurgery, curettage with electrodesiccation, CO2 laser ablation, and curettage with cryotherapy or surgical excision can be applied.
· If multiple lesions involving other parts of the body ablative skin resurfacing via laser, dermabrasion, chemical peels, topical 5-fluorouracil, topical imiquimod, and photodynamic therapy as well as systemic retinoids can be used
· Screening and education is mandatory including awareness of self examination and follow up regularly, avoidance of sun exposure and UV irradiation with application of regular sun protective creams .
Reference
-Singh M.K. and Brewer J.D. Skin cancer management in organ transplant recipients. Seminars in Cutaneous Medicine and Surgery 2011; 30:35-47.
-Chiat Oh C .et al . Dermatological conditions seen in renal transplant
recipients in a Singapore tertiary hospital .Singapore Med J 2018; 59(10): 519-523
Well done.
1-skin cancer like BCC, SCC
2-infection
3-allargy
4-drug eruption
-dermatology consultation and skin biopsy to confirm diagnosis
-staging and screening by PET CT
-modifications of immunosupression medications either by reduction or by switching to MTOR
-teach patient to do self examination every month and to be examined by dermatologist every 6m
-stick to prophylactic measures like avoid sun exposure and use of sunblock protective measures
Thankyou
1-What is your differential diagnosis?
-Skin Cancers such as SCC or BCC
-Cutaneous T-cell lymphoma.
-Cervical lymphadenopathy due to PTLD
-Drug induced
2-Briefly outline his management
-Complete Physical Examination, check for lymphadenopathy
-Lab. tests including CBC, ESR, RENAL PROFILE , BONE PROFILE,CRP, EBV serology, EBV PCR,
-Radiological tests including CT chest, Abdomen, and brain, bone scan, and possible PET scan.
-Invasive tests such as excision Biopsy for a definitive diagnosis.
-Staging and consult with dermatologist/oncologist.
-Reduction of immunosuppression and it is better for changing CNI to Sirolimus.
-Specific therapy according to the cause.
-Preventive measures: (prevention is better than cure)
-5 FU therapy, Radiotherapy.
Prof.Dr.Ahmed Halawa Lecture (Post Transplant Malignanc)
What is your differential diagnosis?
These include,
Basal cell carcinoma
Squamous cell carcinoma
Melanoma
Dermatofibroma
Keratosis
Fungal infection
Keratinocyte carcinoma.
Briefly outline his management
The case has to be referred to dermatologist. The option will include local excision and biopsy. Further management will depend on biopsy results.
Other options include topical 5 FU
Use of sunscreen
Patient education on avoiding sun exposure , especially mid day.
Self examination
Sun protective clothes
Modification of immune suppression-use of Sirolimus
Reference
Lecture By Prof Halawa
Differential diagnosis:
Ø Basal cell carcinoma
Ø Melanoma
Ø Squamous cell carcinoma
Management :
Biopsy
Surgical excision
Immunosuppressant modulator start sirolimus .
Sun protection and use sun screen
Follow up with dermatological department .
To do further imaging and work up for the patient.
Oncogenic viral screen .
References :
1-Engels EA, Pfeiffer RM, Fraumeni JF Jr, et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA 2011;306:1891–1901.
The above 43 years old man who had kidney transplantation done about a year ago developed a purplish well-demarcated patch around the neck.
Differential diagnosis
The above two skin lesions account for about 90% of the causes of skin cancer in solid organ transplantation.
Others are :
Outline of management
Prevention of skin cancer.
References
1-What is your differential diagnosis?
Infection
fungal infection Mucormycosis, Histoplasmosis, Cryptococcosis,candidiasis
VIRAL EBV -CMV -HPV
BACTERIAL STAPH-STREPTOCOCI
Malignancy basal cell carcinoma -SCC -PTLD -Melanoma-KAPOSI SARCOMA
Inflamattory DERAMATITIS -DRUG ALLERGY
2-Briefly outline his management
A dermatologic consultation
Transplant recipients should be counseled on sun avoidance, the use of sunscreens and sun-protective clothing, and the warning signs of cutaneous malignancy. Patients should be instructed to perform a skin self-examination on a monthly basis.
Chemoprevention with acitretin may be of benefit in patients who develop multiple or aggressive SCCs.
All lesions suspicious for SCC in organ transplant patients should be biopsied and sent for pathologic evaluation.
For SCCs suggest treatment with Mohs surgery due to the high cure rates and tissue-sparing effect of this treatment (Grade 2B). If Mohs surgery is not available, excision with intraoperative frozen sections can be utilized. If neither of these options is feasible, patients can be managed with conventional surgical excision with postoperative margin assessment.
Basal cell carcinoma (BCC), melanoma, and Merkel cell carcinoma are managed similarly in organ transplant recipients and immunocompetent patients.
Modulation of immunosuppression is the primary treatment for Kaposi sarcoma in organ transplant recipients.
*****All patients with Mucormycosis, Histoplasmosis, Cryptococcosis were treated with conventional amphotericin-B at dose 1 mg/kg/day or liposomal amphotericin-B at a dose of 3–5 mg/kg with close observation for side effects for cumulative dose around 3.0 gm and 4.5 gm, respectively. Aspergillus and Phaeohypomycosis were treated with voriconazole and pneumocystis cases were given cotrimoxazole. For Mucormycosis cases, posaconazole was used as maintenance. Simultaneously, the dose of immunosuppressive drugs was reduced in all cases. Mycophenolate and calcineurin inhibitors (CNI’s) were temporarily discontinued. Surgical intervention was done in all cases of mucrmycosis. Graft nephrectomy was done in cases of invasive fungal infection
REFERENCES
What is your differential diagnosis?
In this clinical scenario, one year after his transplant, the patient on tacrolimus based immunosuppression who had excellent graft function presented with a tiny cutaneous lesion on the back of his neck.
Differential diagnoses include squamous cell carcinoma which represents the most common skin cancer after transplantation. Other options include Basel cell Carcinoma, Kaposi sarcoma and amelanotic melanoma.
The patient should be evaluated by an experienced dermatologist for biopsy of the lesion.
Briefly outline his management
After a lesion biopsy confirms a skin cancer diagnosis, the following steps are taken:
– Immunosuppression is reduced or modified
– Substituting mTOR inhibitors for Tacrolimus in immunosuppression, as mTORi are the cornerstone treatment for skin lesions in particular sarcoma kapoci.
– Modifying people’s habits to prevent sunburn and the use of sun protective creams during day hours.
– Surgical removal of the lesion
This patient of transplantation on tacrolimus, with good graft function presented 1 year post-transplantion with a small skin lesion over his neck (sun-exposed region).
The differential diagnosis :
Squamous cell carcinoma – SCC, (most common)
Basel cell Carcinoma
Amelanotic melanoma
early lesion of Kaposi sarcoma
Physical examination for lymphadenoapthy or any other remote lesion
Lab investigation
– CBC :for anemia ,leucopenia and thrombocytopenia
– LDH, uric acid, calcium
– Skin biopsy to confirm the diagnosis
Radiological screening for lymphadenopathy and visceral involvement via CT
(head , neck, chest ,pelvic and abdomen).
Reduction in the doses of Immunosuppression and switching from CNI to m TOR inhibitors
Consult oncologist to be involved in planning management and For patients with distant metastasis consider chemotherapy and radiotherapy .
Other options could be :
o cryosurgery: for localized lesion .
o Topical therapy for superficialn lesions or 5-fluorouracil
Standard excision with postoperative margin around 6 mm, .
o Electrodesication and curettage (ED and C) :for superficial lesions not located lesions on high risk areas.
o Radiation therapy : for SCC with undefined margin
Ref
Carucci J. A .Squamous Cell Carcinoma in Organ Transplant Recipients: Approach to Management . STL Volume 9 Number 4 April 1, 2004
Differential diagnosis
1 year post kidney transplant with a lesion on a sun exposed area likely to be a non-melanoma skin cancer.
Squamous carcinoma would be more likely since it occurs more frequently than basal cell carcinoma in recipients.
Other differentials will be basal cell carcinoma, actinic keratosis, amelanotic melanoma.
Management
Should be in consultation with the dermatology and oncology team.
Should begin with a detailed history and thorough physical exam looking for other lesions and lymphadenopathy.
Wide excision biopsy and histology to confirm the diagnosis.
Imaging to rule out any metastasis- CT chest/abdomen/head
Reduction of the immunosuppression- CNI should be switched with MTOR inhibitors shown to have tumour anti proliferative effect.
Withdrawal of azathioprine if in use since it has carcinogenic synergistic effect.
Squamous cell carcinoma solitary lesion Mohs surgical excision with negative margins would be adequate.
Other treatment options include topical 5FU, imiqumoid and photodynamic therapy.
Patient should also be advised on sun protective behaviour- use of sunscreen, protective clothing and avoidance of the midday sun.
· What is your differential diagnosis?
The index patient is a transplant recipient (on tacrolimus, with excellent graft function) presented 1 year post-transplant with a small papulonodular lesion over his neck (sun-exposed region).
The differential diagnosis in this scenario include (1,2):
1) Skin malignancy (Basal cell carcinoma- BCC, Squamous cell carcinoma – SCC, amelanotic melanoma)
2) Infectious lesion (fungal infections)
· Briefly outline his management
The patient requires a dermatology consultation and histopathological diagnosis by performing a biopsy of the lesion. Oncologist should be involved in widespread/ metastatic disease.
In case of skin cancer, the treatment includes:
1) Reduction in immunosuppression
2) Change of immunosuppression from Tacrolimus to mTOR inhibitors
3) Behavioural intervention with respect to sun-protection measures.
4) Surgical resection of the lesion
5) Diagnosis specific treatment (3):
a. Basal Cell Carcinoma: Curettage, cryosurgery, wide local excision, Mohs micrographic surgery and systemic therapy like vismodegib and sonidegib.
b. Squamous Cell Carcinoma: Mohs surgery and wide local excision, Systemic therapy and radiation therapy in metastatic disease.
References:
1) 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.
2) Caroti L, Zanazzi M, Rogasi P, Fantoni E, Farsetti S, Rosso G, Bertoni E, Salvadori M. Subcutaneous nodules and infectious complications in renal allograft recipients. Transplant Proc. 2010 May;42(4):1146-7. doi: 10.1016/j.transproceed.2010.03.115. PMID: 20534246.
3) Berman H, Shimshak S, Reimer D, Brigham T, Hedges MS, Degesys C, Tolaymat L. Skin Cancer in Solid Organ Transplant Recipients: A Review for the Nondermatologist. Mayo Clin Proc. 2022 Dec;97(12):2355-2368. doi: 10.1016/j.mayocp.2022.07.004. Epub 2022 Nov 3. PMID: 36334939.
What is your differential diagnosis?
The patient is post- KT on Tacrolimus based IS, he has flesh- or pink-colored, pearly papules in sun exposed area.
Differential diagnosis:
-Non-melanoma skin cancers: cSCC and BCC on top of DD.
-Other differential includes:
Briefly outline his management:
– A biopsy should be performed in all patients to confirm the diagnosis and determine the histologic subtype.
– Dermatology and oncology team opinion is essential.
– Thorough examination for other lesions and LN.
– CT looking for metastases.
– The treatment will be guided by the histopathological finding, staging.
– Standard surgical treatments; superficial destructive modalities and surgical techniques including curettage, cryosurgery, wide local excision, and Mohs micrographic surgery are usually effective
– Topical therapy 5-FU,and systemic therapy if there is locally advanced and metastatic disease.
– Reduction of immunosuppression RIS.
– RIS as a strategy to manage Kaposi sarcoma and PTLD is effective and well established.
– In NMSK; No guideline established about what threshold of cancer development that would warrant initiation of reduction of IS, however; may be considered if:
– An expert consensus by the International Transplant Skin Cancer Collaborative and Skin Care for Organ Transplant Patients Europe Reduction of Immunosuppression Task Force has been published. The recommendations based on the number of lesions, the risk for mortality over 3 years and stage of tumor.
– Modification of IS; switch from Tacrolimus to mTORi.
-Trial that compared sirolimus-based versus CNI-based IS in KT recipients with one or multiple cutaneous SCCs:
Sirolimus group maintained a lower SK rate over 5 years, with no difference in rejection or mortality between the two groups.
At five years, the rates of new skin cancers in the sirolimus group were significantly lower than those in the CNI group (22 vs 59 % for SCC, 20 vs 37.5 % for BCC, and 34 vs 66 % for other skin cancers).
The benefit was most marked in patients who converted to a sirolimus-based regimen after the development of the first cutaneous SCC HR 0.20
– Frequent skin examination and surveillance for development of any skin lesion.
– Sun protective methods. Avoid mid-day sun exposure, avoid bed tanning, apply broad spectrum sunscreen, Patients should cover up with long sleeved shirts and pants, wear a hat and sunglasses when outdoors.
References;
Differential diagnosis:
1)Basal cell carcinoma BCC
2)squamous cell carcinoma, certain types.SCC
3) Trichoplastoma.
4) Trichoepithelioma.
Management:
Excisional biopsy result is very important determinant of subsequent therapy. Hence, management of BCC is stratified according to risk of recurrence as detailed below:
1) location on trunk and extremities is associated with lesser risk of recurrence then when its in hands ,feet lips and genitalia.
2) Size of more than 2 Cm is linked to higher recurrence rate.
3) Pathologically , superficial and nodular pattern, well defined borders.
treatment is the excision and Imiquimod which is topical immunostimulatory agent that can be used safely in kidney transplant patient with superficial BCC.
References:
1)Thomas Stasko, MD ,Allison M Hanlon, MD. Prevention and management of skin cancer in solid organ transplant recipients. Uptodate. December 2022.
This is a scaly, erythematous plaque on the neck (a sun exposed area) in a fair skinned individual. The differential diagnosis would be:
Squamous cell carcinoma would be more likely as the incidence is much higher post-transplant as compared to basal cell carcinoma (with some studies quoting ratios of 8:1 respectively)
Merkel cell carcinoma can be a differential but it normal presents as an erythematous nodule on the sun exposed areas
Management
The management involves getting a detailed history and carrying out a comprehensive exam
The duration of the lesion, any associated pain should be taken as part of the history
The exam should involve assessing for any other lesions in the sun exposed areas and assessing for any lymphadenopathy
The dermatologist and oncology team should be involved.
Biopsy should be done as this would give a definitive diagnosis
A CT scan or MRI should be done of the head, neck and chest should be done to check for metastasis
The Tacrolimus should be replaced with an mTOR inhibitor as it has been shown to have anti-tumor effects
The definitive treatment will depend on whether it is carcinoma in situ, localized disease or metastatic disease
The following options are available for single low risk lesions:
Multiple low risk lesions:
Squamous cell carcinoma in situ:
Systemic therapy:
Checkpoint inhibitor immunotherapy: cemiplimab, pembrolizumab
Chemotherapy: carboplatin plus paclitaxel
EGFR inhibitors: cetuximab
Basal cell carcinoma:
It is important to educate our patients during the pre transplant period about the risk of cancers especially skin cancer
They should be advised to avoid prolonged sun exposure, to wear hats and to apply good sunscreen with high SPF against both UVA and UVB
👉 The provided photo shows erythematous skin nodule in sun exposed area , so skin cancer should be suspected and excluded in any transplant recipient withvrelatively long period on dialysis for 2 years prior to tranplantation and due to current immunosupression state.
👉Differential diagnosis includes:
_Basal cell carcinoma.
_squamousbcell carcinoma.
_amelanotic melanoma.
👉 The management depends on definitive diagnosis by skin biopsy.
_ it needs multidisciplinary team involving dermatologist, pathologist , radiologist, nephrologist.
_ Evaluation of organ metastasis by CT chest, abdomen and pelvis.
_ Basic lab as CBC, electrolytes, liver function and close monitoring of graft function.
_ Treatment starts with reduction of immunosupression as shift from CNI to mTORi as sirolimus, stoppage of Azathioprine if used.
_ local therapy as 5_ fluorouracil and local excision with safety margin.
_ use of systemic chemotherapy needs an expert oncologist (in case of distant metasis in case of SCC) as BCC is loaclly malignant disease without distant organ involvement.
_ Close follow up of graft function and urine analysis after reduction of immunosupression due to fear of acute rejection.
_ Follow up protinuria after shift to sirolimus.
_ Avoid sun exposure around midday and use of sun protective clothes and sun screen (SPF 50+, and UVA rays protection 5*).
_ Whole skin examination yearly and by an expert dermatologist every 6 months.
BCC.
Bowen’s disease (SCC in situ).
Nummular dermatitis.
Lichenoid keratosis,
Actinic keratosis,
Early Amelanotic melanoma.
Superficial BCC:
Is the second most common clinical subtype, accounting for up to 15 percent of the
cases.
Well-circumscribed, scaly, pink-to-red macule, patch, thin papule, or thin plaque. It may
demonstrate crust or a thin rolled border consisting of fine translucent small papules.
Areas of spontaneous regression can occur, leaving behind atrophic, hypo pigmented
areas.
Variable amounts of melanin pigment may be present. Superficial BCCs favor the trunk
and extremities, in contrast to the other subtypes, which favor the head and neck.
A biopsy is the only way to definitively diagnose BCC and decide on appropriate
treatment.
BCCs at low risk for recurrence are most commonly managed with electrodessication
and curettage OR surgical excision.
Less frequently used treatments include topical 5-fluorouracil (5-FU) or imiquimod,
cryosurgery, Intralesional injection, and photodynamic therapy for low-risk lesion.
Mohs surgery:
A specialized method of surgical removal, provides the highest cure rate. It is indicated
for lesions at increased risk of recurrence.
SCC in situ:
Are treated with either surgical excision or electrodessication and curettage (ED and C)
The cosmetic results for lesions on the face, nose, lips, and ears are better with surgical
excision, rather than electro surgery.
When surgery and ED&C are not feasible, photodynamic therapy has been shown to be
effective.
Alternatively, 5-FU has been reported to be used. (2)
.
References:
1-Alexander G. Marzuka, Samuel E. Book. Basal Cell Carcinoma: Pathogenesis,
Epidemiology,
Clinical Features, Diagnosis, Histopathology, and Management. Yale J Biol Med. 2015
Jun; 88(2): 167–179.
2-A. Mittal, O. R. Colegio. Skin Cancers in Organ Transplant Recipients. American
Journal of Transplantation. 29 May 2017.
Differntial diagnosis
1- Squamous cell carcinoma
2- Basal cell carcinoma
3- Acnetic keratosis
4- Keratocanthoma
Management
1- Physical examination for lymphadenoapthy or other remote preed of the lesion
2- Lab investigation
– CBC : anemia ,leucopenia and thrombocytopenia
– LDH
– Skin biopsy to confirm the diagnosis
3- Radiological screening for lymphadenopathy and visceral involvement via CT (head , neck, chest ,pelvic and abdomen).
4- Decrease the dose of IS as MMF and switch from CNI to m TOR
5- Consult oncologist to be involved in planning management and For patients with distant metastasis consider chemotherapy and radiotherapy .
6- Other potentiallines :
o cryosurgery: for localized lesion .
o Topical therapy for superficiallesions using imiquimod26 or 5-fluorouracil27
o Mohs micrographic surgery : offers the highest cure rates for SCC ,considered for high risk lesions as larger diameter, high risk location, recurrent lesion, aggressive histopathology and scar carcinoma
o Standard excision with postoperative margin around 6 mm, indicated for high risk lesion that cannot be treated with Moh surgery .
o Electrodesication and curettage (ED and C) :for superficial lesions not located lesions on high risk areas.
o Radiation therapy : for SCC with undefined margin
o
Ref
Carucci J. A .Squamous Cell Carcinoma in Organ Transplant Recipients: Approach to Management . STL Volume 9 Number 4 April 1, 2004
What is your differential diagnosis?
1. SCC
2. BCC
3. Amelanotic melanoma
Briefly outline his management
Full history and clinical examination (complete skin examination and palpation of draining lymph nodes)
MDT and patient counseling
Surgical excision and histopathology for definitive diagnosis
Immunosuppressant: reduction of immunosuppression should be considred carefully and modulation of immunosuppressions (patient already on sirolimus check tacrolimus level, and if on azathioprine stops it). Modulation of immunosuppression is considered for patients with multiple lesions, recurrent lesions, or aggressive or metastatic SCC
Treatment options: radiation, cryotherapy, topical therapy 5-FU, imquimod 5%), and Mohs surgery or conventional surgical excision
Patient education:
Full skin examinations at least once yearly
Sun protection: patients should be counseled on the use of sunscreens, sun protective clothing, and the warning signs of cutaneous malignancy. In a non-randomized controlled study of 120 organ transplant recipients, participants using daily sunscreen developed fewer actinic keratoses and SCCs than subjects with intermittent sunscreen use
Reference: UpTodate
History
====================================================================
What is your differential diagnosis?
Others
====================================================================
Briefly outline his management
Most basal cell carcinomas may be treated by one of the following methods.
The choice of treatment is influenced by:
Physical:
1- Electrodesiccation and curettage is an appropriate choice for low-risk primary nonfibrosing tumors.
2- Consider cryotherapy for low-risk BCC when more effective therapies are contraindicated or impractical.
3–If surgical excision of BCC is not feasible, contraindicated, or not preferred by the patient, radiotherapy is an additional treatment option.
4- Mohs micrographic surgery has the lowest recurrence rate.
5- Radiotherapy requires multiple sessions, and postradiation changes can include dyspigmentation and radiodystrophy.
6- Protection from further skin exposure.
Medical
====================================================================
Reference
Thank you for this excellent answer
Thanks you verey much Prof.Halawa
What is your differential diagnosis?
This is a well-defined vascularized (central telangiectasia) raised skin lesion (nodular) in the neck (sun exposed area) most likely diagnosis is Basal cell carcinoma. Other differential diagnosis are:
Squamous cell carcinoma, intradermal nevus, Fibroepithelioma of Pinkus, Adnexal carcinoma, Sebaceous hyperplasia, and metastatic malignancy.
However, SCC is more common than BCC in solid organ transplantation patients. Sun exposure is the cause in non-melanoma skin cancers.
Briefly outline his management:
Refer the patient to a dermatologist for diagnosis – and do biopsy.
Prevention is better than cure – I would highlight the effect of behavioral and pharmacological measures of sun exposure protection measures, including clothing, sun protective factor and avoid mid-day sun exposure.
The treatment includes:
– Surgery: Complete removal of the tumor, correct any functional impairment caused by tumor, and give the best cosmetic results.
– Radiation: when surgery is contraindicated.
– Cryosurgery: is another treatment option for low risk BCC.
– Topical therapy: 5-FU and Imiquimod 5% cream for superficial/multiple BCC.
– In organ transplant patients: stop MMF and CNI and substitute them with sirolimus (m-TOR inhibitor). With pretreatment quantification of urinary protein and regular monitoring of urinary protein.
References:
(1) McDaniel B, Badri T, Steele RB. Basal Cell Carcinoma. 2022 Sep 19. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 29494046.
(2) James LJ, Saglimbene V, Wong G, Tong A, Luu LDW, Craig J, Howard K, Howell M. Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trials. BMJ Open. 2020 May 17;10(5):e029265. doi: 10.1136/bmjopen-2019-029265. PMID: 32423925; PMCID: PMC7239542.
Thank you for this excellent answer
-What is your differential diagnosis?
-This lesion in a post-transplant paitent is highly suspicious for skin cancer and biopsy is mandatory. Differentials are :
-Briefly outline his management
-`Management will sole depend on the biopsy and therefore this patient should be counsel regarding skin biopsy. Treatment lines for skin cancer are;
-Preventive measures: (prevention is better than cure)
Source: prof Halawa lecture
Thank you for this excellent answer
What is your differential diagnosis?
////////////////////////////////////////////////
Briefly outline his management
References
Thank you for this excellent answer
DDx of skin nodular lesion with ill-defined border, involving sun exposed area post kidney transplantation
– Non melanotic skin cancer BCC or SSC
– Melanoma
– Drug induced
– Systemic infection
– Ptld
Management
History and clinical exam focusing on sun exposure occupation and immunosuppessive regimen associated with regional lymph node exam with other system affection review
Dermatological evaluation ” MDT involvement
Lab : ESR CRP, LDH, Ca, uric acid, serology for HIV HBV HCV EBV
Radiology : CT scan of neck chest abdomen and pelvis
Excision biopsy
Patient education
Avoid prolonged sun exposure
• DO NOT get sunburned
• Use high-factor sun block
• Wear a hat and shirt in sunny weather
• Look for new skin lumps
immunosuppressive modulation
local therapy : 5’Fluorouracil or Imiquimod
Other lines according to the diagnosis and staging
A small lesion in a region that is exposed to the sun, The lesion is nodular and has capillaries on its surface, which may be:
Squamous cell carcinoma.
Basal cell carcinoma.
allergy from insect bites.
full history of the medication and immunosuppressive drugs.
and local examination of lymph nodes.
Interprofessional team (dermatologist, transplant nephrologist, oncologist).
The definitive diagnosis is reached by excisional biopsy. If the skin cancer is confirmed:
The primary goal of therapy is to reduce levels of immunosuppression.
moving away from CNI and toward mTOR inhibitors.
a number of preventive steps, such as self-examination of the skin and using sunblock, to lower the chance of it happening again.
– Kim C, Cheng J, Colegio OR. Cutaneous squamous cell carcinomas in solid organ transplant recipients: emerging strategies for surveillance, staging, and treatment. Seminars in oncology. 2016 Jun;43(3):390-4. PubMed PMID: 27178693. Epub 2016/05/15. eng.
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Diagnosis and Differential diagnosis:
Basal Cell Carcinoma
Squamous cell carcinoma
Melanoma
Management:
1. Complete physical examination, check for lymphadenopathy, Investigations: CBC, ESR, CRP, EBV PCR.
2. Biopsy of lesion,
3. Staging and consult with dermatologist/oncologist.
4. Reduction of immunosuppression: Switching from CNI to mTOR, if patient on AZA then switch AZA to MMF, monitor for rejection.
5. Avoid sun exposure, particularly at mid-day, SPF 50+, UVA 5* sunscreen, self-examination.
6. 5 FU therapy, radiotherapy.
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What is your differential diagnosis?
Briefly outline his management
A- Dermatology consultation for evaluation of the lesion and setting a definite diagnosis through excision biopsy.
B- Assessment of the need for reduction of immunosuppression
Maximum benefit was observed in Kaposi sarcoma, may have benefit in SCC but benefit is not clear in melanoma, BCC and Merkel cell carcinoma. Benefit should be weighed against risk of graft failure
C- Assessment of the need for modification of immunosuppression
In summary
REFERANCES
1- Uptodate
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What is your differential diagnosis?
Briefly outline his management :
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D.D of skin lesion post renal transplant:
1- skin infections; skin nodules may reflect systemic infections
2-skin cancers
3-drug induced
L Caroti, M Zanazzi, P Rogasi, E Fantoni, S Farsetti, G Rosso, E Bertoni, M Salvadori. Subcutaneous nodules and infectious complications in renal allograft recipients. Transplant Proc. 2010 May;42(4):1146-7
Choon Chiat Oh, Haur Yueh Lee, Bien Keem Tan, Pryseley Nkouibert Assam,Terence Yi Shern Kee, Shiu Ming Pang.Dermatological conditions seen in renal transplant recipients in a Singapore tertiary hospital. Singapore Med J. 2018 Oct; 59(10): 519–523.
management:
1- skin biopsy
2- shift from tacrolimus to sirolimus
Thank you for this excellent answer