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2. A 36-year-old kidney transplant recipient developed this lesion 14 years after his cadaveric transplantation. Currently, he is on Tacrolimus (trough level 8.3 ng/ml) and MMF 500 mg bd. He has excellent kidney function (S Cr is 113 µmol/L).
- What is your differential diagnosis?
- How do you manage this case?
- Substantiate your answer.
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1. Differential diagnosis
Kaposi sarcoma
Pyogenic granuloma
Melanoma
2. History and examination
Skin biopsy
HHV8 PCR
search for visceral involvement CT abdomen, colonoscopy
Reduction if immunosuppressive drugs
Switch to mTor inhibitors
What is your differential diagnosis?
The provisional diagnosis is Kaposi’s sarcoma
Other differentials may include-
Bacillary angiomatosis
Pyogenic granuloma
How would you manage this case?
Biopsy of the skin lesion can confirm the diagnosis. Involvement of the mucous membranes and internal organs should be assessed.
Tacrolimus trough levels are high. Dose reduction must be done to allow the body’s immune system to clear the viruses (HHV 8) responsible for the disease. Another option is to switch to Sirolimus.
Treatment for sarcoma is liposomal doxorubicin.
This is kaposi sarcoma
this viral related infection
If there is visceral involvement,in addition to mTOR we should give liposomal anthracyclines. Cardiomyopathy should be ruled out before giving Liposomal anthracyclines.
Kaposi sarcoma (biopsy from the lesion )
–In up to 30% of patients with PT-KS, reducing immunosuppressive therapy alone has the potential to lead to complete remission. . If possible, patients should be switched from calcineurin inhibitors to mTOR inhibitors.
Kaposi sarcoma
Treatment withbreduction of immunosuppression and changing tacrlimus to mTOR close monitoring
What is your differential diagnosis?
The present figure most likely showing kaposi sarcoma
Other possible Diagnosis-
Bacillary angiomatosis
Hemangioma
Dermatofibroma
Pyogenic granuloma
Purpura
How do you manage this case?
Biopsy of the lesion is must for diagnosis of kaposi sarcoma.In addition Visceral involvement should be ruled out if symptoms of viscreal involvement is present, by ct scan of abdomen,Ct of chest,endoscopy or bronchopscopy.If it is local KS,we should reduce his immunosuppression and change the tacrolimus to mTOR inhibitor..If there is visceral involvement,in addditon to mTOR we should give liposomal anthacyclines.Cardiomyopathy should be ruled out before giving Liposomal anthacyclines.
The provisional diagnosis is skin malignancy mostly non melanoma skin cancer (Kaposi Sarcoma) occurs by HHV 8 with high tacrolimus level being over immunosuppressed.
Management by switching CNI to mTORi as they help to regain the effector memory and T cell activity. Tailoring immunosuppression according to patient’s status is advised.
Multidisciplinary team is required involving transplant professional, dermatologists and oncologists.
Biopsy from the lesion determines the chemotherapeutic and other treatment options.
Full screening of internal organs is necessary especially to exclude visceral involvement.
Reference
BMJ Open2020;10:e029265. doi:10.1136/bmjopen-2019-029265
The most likely diagnosis for non-melanoma skin cancer (NMSC) is Kaposi sarcoma, which fits the clinical profile (a 14-year-old kidney transplant recipient, a male patient taking Tacrolimus with nadir levels of 8.3, and typical skin lesions).
Human herpes virus type 8 (HHV-8)-related vascular tumors like kaposi sarcoma are 100 times more common in transplant recipients than in the general population, and those taking calcineurin inhibitors are at an increased risk. Lesions are typically observed on the distal extremities, particularly the lower limbs, but they can be widely distributed throughout the body.
How do you handle this situation?
A dermatologist should evaluate the patient. A complete clinical examination, including mucosal examination and abdominal ultrasound (to determine the extent of lesions and visceral involvement), should be performed.
The treatment consists of a biopsy of the lesion to confirm the diagnosis. The biopsy will disclose endothelial fusiform cells and the formation of new blood vessels. Immunohistochemical staining of endothelial cells may reveal HHV-8.
The treatment consists of:
1) Reinforcement of sun protection behavioral interventions
2) Immunosuppression reduction: The patient’s tacrolimus basal level is 8.3 ng/ml, which is high and should be reduced to 4-5 ng/ml.
3) Switching from Tacrolimus to mTOR inhibitors (Sirolimus) for immunosuppression:
The cornerstone of the management of such a patient is a biopsy to diagnose the lesion, followed by immunosuppression transitioning from Tacrolimus to Sirolimus. Essential is a multidisciplinary approach involving a dermatologist and an oncologist.
Immunosuppression modification has been associated with regression of the lesions. Chemotherapeutic agents such as liposomal pegylated doxorubicin, immune response modifier imiquimod, or radiotherapy, if chemotherapeutic agents are contraindicated, would be used to treat nonresponsive lesions.
References:
1) Kaposi Sarcoma after kidney transplantation. Juliette Raedemaeker et al. BMJ case reports, volume 12, issue 5.
This most likely Kaposi sarcoma
Management involve manipulation ote immunosuppression therapy with stopping MMF therapy and reducing tacrolimus tabs or be changed to mTOR tabs
What is your differential diagnosis?
The differential diagnosis is of Kaposi sarcoma as purple lesions are present. Confirmation of the diagnosis is done by a skin biopsy and HHV8 serology or PCR test.
How do you manage this case?
Alteration or management of immunosuppressive drugs. Lowering immunosuppressive drugs or switching to either sirolimus or mTOR inhibitors.
Substantiate your answer.
Campistol JM, Schena FP. Kaposi’s sarcoma in renal transplant recipients–the impact of proliferation signal inhibitors. Nephrol Dial Transplant. 2007;22 Suppl1:i17-22.
Kaposi sarcoma, biliary angiomatosis, AIDS related lymphoma and seborrheic keratosis.
confirm the diagnosis by checking HHV-8 PCR in addition to HIV testing and ct abdomen .skin biopsy.
reduce immunosuppresion (tacrolimus to keep level between 4-6.)
change stop MMF and start mtor inhibitors.
*This man transplanted 14 years ago presented with this purple skin lesions which classic for Kapossi sarcoma
the diagnosis should be confirmed by skin biopsy
* Mangment includes minimise the immunosuppressive medication and change to mTOR inhibitors
Q1: Kaposi sarcoma is the most probable diagnosis. Other differential diagnosis includes bacillary angiomatosis, angiosarcoma, melanoma, or cutaneous lymphoma.
Q2: A skin biopsy and NHV-8 PCR test are necessary to confirm the diagnosis. On the other hand, imaging includes head and neck, abdominopelvic CT scan, gastroscopy, and colonoscopy or bronchoscopy if needed—consultation with different related specialists about the dissemination of the disease. They are changing from CNI to mTOR inhibitors, chemotherapy, or radiotherapy if required. Finally, close up follow-up is considered.
Kaposi sarcoma occur due to HHV-8 especially in immunocompromised, organ transplant and HIV patients.
Histologically, spindle cell vascular lesions in the skin include a differential diagnosis of :
Interstitial granuloma annulare
Spindle cell hemangioma
Acquired tufted angioma
Kaposiform hemangioendothelioma
Cutaneous angiosarcoma
Fibrosarcomatous dermatofibrosarcoma protuberans
Aneurysmal dermatofibroma
Acroangiodermatitis
Spindle cell melanoma
High-grade sarcomas
The differential diagnosis of Kaposi sarcoma on mucocutaneous surfaces includes :
Nevi
Pyogenic granuloma
Bacillary angiomatosis
Hemangioma
Angiosarcoma
Melanoma
Management of Kaposi sarcoma
Sun protection especially from UV rays
Reducing the dose of Tacrolimus decreasing trough level to 4-5 ng/ml or
Shift from Tacrolimus to mTOR inhibitors e.g Sirolimus
The long-term use of immunosuppressive agents for prevention of allograft rejection increases the risk of malignancy approximately 100 times as high as that in the general population.1 The prevalence rate of post-transplant malignancies in total differs between geographical areas; for example, in Europe, that rate is 1.6% and in Australia is 24%, with a mean of 6%. Skin cancers, mostly squamous cell carcinoma (SCC), are the most common tumors among persons have solid organ transplantation.1 But, however, Iranian studies found that the most common malignancy after kidney transplantation was Kaposi Sarcoma (KS) among the Iranian patients.2 KS is a skin tumor of multicentre origin, characterized histologically by endothelium-lined vascular spaces and spindle-shaped cells.3 KS presents as single or multiple lesions on mucosal surfaces, including the skin, lungs, gastrointestinal tract and lymphoid tissues.4 The etiopathogenes of KS is complex and poorly understood, but is almost certainly dependent on human herpes virus type 8 (HHV -8) infection in immunosuppressed, immunogenetically susceptible individuals.5–7 Although the treatment of KS is controversial, it should ideally address these pathogenic issues.8, 9 The current guideline is reduction of immunosuppression as first-line treatment, but these recommendations are based on anecdotal experience or uncontrolled studies.9, 10 Perhaps the most fundamental controversy that has implications for all aspects of the disease surrounds the nature of KS: i.e. whet her it is a true malignancy or reversible hyperplasia.11, 12
References
1.Einollahi B, Noorbala MM, Lessan Pezeshki M, et al. Incidence of post renal transplantation malignancies: a report of two centers in Tehran, Iran. Transplant Proc. 2001;33:2812.
2. Nafar M, Einollahi B, Hemati K, Gholi FP, Firouzan A. Development of malignancy following living donor kidney transplantation. Transplant Proc. 2005;37:3065–7.
3. Tan HH, Goh CL. Viral infections affecting the skin in organ transplant recipients: epidemiology and current management strategies. Am J Clin Dermatol. 2006;7:13–29.
4. Mendez JC, Paya CV. Kaposi’s sarcoma and transplantation. Herpes. 2000;7:18–23.
5. Moosa MR, Treurnicht FK, van Rensberg EJ, Schneider JW, Jordaan HF, Engelbrecht S. Detection and subtyping of human herpesvirus-8 in renal transplant patients before and after remission of Kaposi’s sarcoma. Transplantation. 1998;66:214–18.
6. Penn I. Kaposi’s sarcoma in transplant recipients. Transplantation. 1997;64:669–73.
7. Giraldo G, Beth E, Buonaguro FM. Kaposi’s sarcoma: a natural model of interrelationships between viruses, immunologic responses, genetics, and oncogenesis. Antibiot Chemother. 1983;32:1–11
Ultrasound abdomen and pelvis is mandatory to exclude visceral involvement
What is your differential diagnosis?
On top of my differential diagnosis is Kaposi Sarcoma and that is because the history of immunosupression and cutanous mainfestation showen in the picture. Other differnetial diagnosis includes Angiosarcoma, malignant melanoma, bacillary angiomatosis and cutaneous Lymphoma.
How do you manage this case?
Management of any case starts with detalied and focused medical history and physical examination. Then establishing the diagnosis with skin biopsy for histopathology and immunohistochemistry, HHV 8 and HIV PCR testing. In case of Kaposi Sarcoma, we need to assess for visceral dissemintation which associated with poor prognosis using whole body CT Scan, gastroscopy, colonoscopy and bronchoscopy. MDT including dermatology, oncology, nephrology and GI of visceral dissemination will help in establishing treatment plan. Transplant wise we need to switch the patient to Sirolimus and stop CNI with close follow-up to assess for regression and if no response to consider chemotherapy / radiotherapy after discussion with oncology in MDT. Lastly and most important is to include the patient with counselling and involving him in the plan of management.
Assalam o Alaikum
1. What is your differential diagnosis?
Differentials:
· Kaposi sarcoma
· Bacillary angiomatosis
· Cutaneous Lymphoma
Keeping in view the history of immunosuppression use I would keep Kaposi sarcoma as my diagnosis. Although classically present in first 2 years post transplant it can occur later on as well.
2. How do you manage this case?
o History and examination
§ Detailed history and examination for systemic involvement. Special emphasis on mucocutaneous surfaces and lymphadenopathy.
o Confirm the diagnosis
§ Deep skin biopsy for histopathology and immunohistochemistry for LANA-1
§ HHV 8 PCR
§ HIV
§ Stool for occult blood (if positive then endoscopic imaging)
o Counseling:
§ Breaking the news gently
§ Reassure the patient
§ Inform in detail regarding current status and management plan
o Multidisciplinary care
§ Oncology (radiation and medical)
§ Dermatology
§ Nephrology
§ Gastroenterology (in case of GI involvement)
o Treatment:
§ Switch from CNI to mTOR therapy after evaluating the history and risk of rejection
§ No proven role for stopping or switching antimetabolite for KS unlike other post-transplant malignancies
§ Radiotherapy +/- chemotherapy if indicated for systemic disease after MDT
§ Close follow up for assessing resolution of lesions
REFERENCES:
1. Raeisi D, Payandeh M, Madani SH, Zare ME, Kansestani AN, Hashemian AH. Kaposi’s Sarcoma after Kidney Transplantation: a 21-Years Experience. Int J Hematol Oncol Stem Cell Res. 2013;7(4):29-33. PMID: 24505540; PMCID: PMC3915423.
2. Bishop BN, Lynch DT. Kaposi Sarcoma. [Updated 2022 Jun 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534839/
3. Schneider JW, Dittmer DP. Diagnosis and Treatment of Kaposi Sarcoma. Am J Clin Dermatol. 2017 Aug;18(4):529-539. doi: 10.1007/s40257-017-0270-4. PMID: 28324233; PMCID: PMC5509489.
What is your differential diagnosis?
How do you manage this case?
a) Investigation
b) Treatment
References
1) D/ D:
Kaposi sarcoma
Bacillary angiomatosis
Angiosarcoma
Naevus
2) Mx:
History:
H/O exposure( HIV)
MSM
Exam:
Extent of lesion
Investigations:
Biopsy and histopathology of lesion
HH8 Serology, HIV serology
Bronchoscopy, Endoscopy, colonoscopy (If
need)
Treatment:
To reduce MMF
To shift mTor(Sirolimus) from Tacrolimus
References:
1. Blumenfeld W, et al. “Differential diagnosis of Kaposi’s Sarcoma”. Arch Pathol Lab Med. 1985 (109): 123–127.
2. Mikulska M, Balletto E, Mularoni A. Human herpesvirus 8 and Kaposi sarcoma: how should we screen and manage the transplant recipient? Curr Opin Infect Dis. 2021 Dec 1;34(6):646-653.
What is your differential diagnosis?
Kaposi sarcoma
Naevus
Histiocytoma
Cryptococcosis
Histoplasmosis
Leishmaniasis
Pneumocystis lesions
Dermatophytosis
Angioma
Bacillary angiomatosis
Pyogenic granuloma
Melanoma
How do you manage this case?
* History and physical examination
*Investigation routine and skin biopsy
*The doses of immunosuppressive agents were reduced, with changed drugs to sirolimus, or the agents were withdrawn upon diagnosis of KS. The method of reduction of immunosuppression and decision on which the agent to be reduced or withdrawn were dependent on the individual patient’s health condition
*Kaposi sarcoma is not curable, but it can often be treatable for many years.
*High active antiretroviral therapy (HAART).
*Local lesions can often be treated with local measures such as radiation therapy or cryosurgery.
*Weak evidence suggests that antiretroviral therapy in combination with chemotherapy is more effective than either of those two therapies.
*Topical Beta-blockers.
*In general, surgery is not recommended, as Kaposi sarcoma can appear in wound edges. In general, more widespread disease, or disease affecting internal organs, is treated with systemic therapy with interferon alpha,
*liposomal anthracyclines
1)Einollahi B, Noorbala MM, Lessan Pezeshki M, et al. Incidence of post renal transplantation malignancies: a report of two centers in Tehran, Iran. Transplant
Tehran, Iran. Transplant Proc. 2001;33:2812.
2)Sand M, Sand D, Thrandorf C, Paech V, Altmeyer P, Bechara FG (June 2010). “Cutaneous lesions of the nose”. Head & Face Medicine. 6: 7. doi:10.1186/1746-160X-6-7. PMC 2903548. PMID 2052532
What is your differential diagnosis?
Kaposi Sarcoma
How do you manage this case?
Switch calcineurin inhibitors to mTOR inhibitors specially Sirolimus.
What is the differential diagnosis ?
Diagnosis by biopsy of skin lesion
with HHV8 serology and Viral load by PCR
HIV serology and viral load (PCR), CD4 cell count – as association of HIV / AIDS are very high.
Nutritional status cum pre-chemotherapy work up – CBC, LFT, Calcium
treatment –
Kaposi sarcoma usually regresses after withdrawal or reduction of immunosuppressive agents. So my plane is –
What is your differential diagnosis?
1. Malignant Melanoma
2. Bacillary angiomatosis
3. Squamous cell carcinoma
4. Dermatofibroma
How do you manage this case?
Treatment –
Kaposi sarcoma usually regresses after withdrawal or reduction of immunosuppressive agents. So my plane is –
Substantiate your answer –
1. Shepherd FA, Maher E, Cardella C, Cole E, Greig P, Wade JA, Levy G. Treatment of Kaposi’s sarcoma after solid organ transplantation. Journal of clinical oncology. 1997 Jun;15(6):2371-7.
2. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Kaposi Sarcoma Version 1.2023-Dec 20,2022.
3. Einollahi, B., 2007. Kaposi sarcoma after kidney transplantation. Iran J Kidney Dis, 1(1), pp.2-11.
What is the differential diagnosis :
How do you manage this case :
By Taking Good History of B symptoms (fever, weight loss,night sweats), Shortness of breath and cough, abdominal pain and Diarrhea
Physical Examination,
Brown rounded lesions on trunk and other parts of body
Assessment of all mucous membranes and lymadenopathy
Investigations,
Confirmation by Skin Biopsy of Human Herpes Virus 8 and PCR of HHV-8
CECT chest and Abdomen to look for extent of disease
Treatment :
Reduction of immunosuppresion and conversion of tac to Sirolimus
Most of the times that;ll cure the disease in few months
Symptomatic management of other issues
Poor prognosis in case of visceral and mucosal involvement
Substantiate your answer :
malignancy. Transplantation. 2009;87(2):157-163. doi:10.1097/TP.0b013e318193886e
There are multiple rounded and some irregular shaped discrete dark brown patches or plaques on the body. From history & such type of pictorial findings my differential diagnosis are-
a. Kaposi sarcoma
b. Bacillary angiomatosis
c.Angiosarcoma
History-
-GIT sympyoms : Abdominal pain, vomiting, bloody diarrhoea, obstructive symptom.
-Pulmonary symptoms : Dry cough, haemoptysis, dyspnoea
-Fever
-Weight loss
Physical examination-
-Such type of lesion in other part of body, oral cavity
-Lymphadenopathy
– Proctoscopy
Investigations–
A)To confirm diagnosis
-Biopsy of lesion & histopathological examination(angioptoliferative histologic features)
-Immunohistochemistry of the biopsy slide to detect HHV-8.
-PCR for HHV-8
B)Other investigations to confirm visceral involvemrnt-
-Endoscopy of upper GIT & biopsy
– CT scan of chest
– Bronchoscopy & biopsy
-FNAC from lymph node
-USG of whole abdomen( hepatomegaly)
Treatment
Dissemination is common if not treated rapidly & adequately.
– Conversion to sirolimus based, CNI free therapy has been shown to produce remission of kaposi’s syndrome in renal transplant recipient.
-After 3 months of withdrawl of CNI skin lesion disappear and biopsy become negative after 6 month.
Prognosis- poor prognosis in case of visceral involvement.
References–
1. NCCN Clinical Practice Guidelines in Oncology(NCCN Guideline Kaposi Sarcoma Version1.2023-December20,2022
2. Duma S, Toz H, Asci G, Alper S, Ozkahya M, Unal I et al. Successful treatment of post-transplant Kaposi’s Sarcoma by reduction of immunosuppression, Nephrol Dial Transplant(2002)17: 892-896
3.Rosai J, A riddle within a puzzle In : Gott Lieb G, Acuerman AB, eds, Kaposi’s Sarcoma: a Text and Atlas. Lea and Febiger, philadlphia, 1988; 255-269
clinically looks like Kaposi Sarcoma – especially in the background of 14years post transplant
other clinical differential diagnosis could be Bacillary angiomatosis,
Angiosarcoma
Diagnosis by biopsy of skin lesion
with HHV8 serology and Viral load by PCR
HIV serology and viral load (PCR), CD4 cell count – as association of HIV / AIDS are very high.
Nutritional status cum pre-chemotherapy work up – CBC, LFT, Calcium
Staging of the disease with CECT chest and abdomen
Additional invasive tests like Brochoscopy (if hemoptysis, breathing problem), upper GI endoscopy and colonoscopy (if GI bleed, anemia or pain abdomen) may be required.
Management of this index case shall require
Stopping MMF and Switching Tacrolimus to Sirolimus (Sirolimus + Prednisone)
— most of the times the skin lesions would regress by 3-6 months
2. may require additional chemotherapy in case of extensive visceral involvement, no response to reduction of immunosupression or recurrence of the KS.
3.Evaluation (history of sexual promiscuity / drug abuse) and Treatment of HIV / AIDS — with ART regimen containing (Dolutagravir + Abacavir + Lamivudin)
improve nutrition
treatment of associated ailments like tuberculosis, GI intolerance, GI bleed, breathing problems etc.
4.Frequent monitoring for rejection and proteinuria (may need ACE inhibitor / AR blocker)
Retrospective review of 7 caucasian renal transplant recipients affected by KS.
All 7patients were under CNI treatment at the onset of KS limited to the skin, without regression despite minimized immunosuppression. After conversion to SRL, 6patients showed regression of KS lesions, with only hyperpigmented atrophic cutaneous lesions remaining after a mean time of 8.1 months (2-18 months). The seventh patient has completed 9 months follow-up with a near complete regression of KS lesions.
2.Josep M Campistol 1, Francesco P Schena. Nephrol Dial Transplant 2007 May;22 Suppl 1:i17-22. Kaposi’s sarcoma in renal transplant recipients–the impact of proliferation signal inhibitors.Lower incidence of post-transplant malignancies in renal transplant recipients receiving PSI-based immunosuppression compared with those receiving CNIs are evident. Conversion from CNIs to PSIs has been shown to lead to the regression of Kaposi’s sarcoma in renal transplant recipients and is now part of accepted standard care for this tumour in this setting.
3.Schena, Francesco P, Pascoe, Michael D, Alberu, Josefina et al. the Sirolimus CONVERT Trial Study Group. Transplantation 87(2):p 233-242, January 27, 2009.
Conversion From Calcineurin Inhibitors to Sirolimus Maintenance Therapy in Renal Allograft Recipients: 24-Month Efficacy and Safety Results From the CONVERT Trial.
Reduced rate of overall malignancies in Sirolimus group at 12-24 months.
Case details:
36-year-old male with ESRD of unspecified cause who received a cadaveric renal transplant aged 22 (14 years ago)
Current immunosuppression strategy: Tacrolimus (target trough levels presumed 5-9 ng/ml) and MMF 500mg BD
Excellent kidney function with serum creatinine 113 µmol/L
Presenting with multiple pigmented lesions across his torso (>30 discrete lesions). The lesions appear to be predominantly macular although there are also some maculopapular lesions. The cutaneous lesions are well-defined with circular/oval shape and dark brown pigmentation. There is no evidence of any bleeding or ulceration of the lesions. The patient appears slim but not cachectic as far as can be ascertained from this isolated image.
What is the differential diagnosis?
The colour, texture and number of lesions would point towards a diagnosis of Kaposi’s sarcoma, which, although rare, has a significantly higher incidence in transplant recipients compared to the general population (200 times higher)
The differential diagnosis would include:
– Malignant melanoma (based on colour, less likely with number of lesions)
– Angiosarcoma
– Bacillary angiomatosis
– Benign haemangiomas
How would you manage this patient’s case?
In order to establish the diagnosis and confirm the extent of disease the following would be required:
a) History and clinical examination
A focussed history from the patient may elicit details that will affect the further work-up, for example any symptoms arousing suspicion of disseminated disease requiring more extensive investigations such as bronchoscopy or gastro-intestinal endoscopy.
Salient points in the history/examination would include:
· Establishing where the patient comes from geographically as the prevalence of HHV-8 differs in different populations
· Questions regarding sexual history or high-risk behaviours: HHV-8 has higher prevalence in men who have sex with men (MSM). In this case, where Kaposi’s sarcoma is occurring 14 years post-transplant rather than in the highest risk timeframe in the 2 years after transplant, it is important to consider risk factors for a new diagnosis of HIV although in all post-transplant Kaposi’s sarcoma HIV serology should be part of the mandatory work-up investigations
· Any evidence of mucosal, lymph node or other organ involvement
b) Blood tests
HIV serology should be performed routinely. Standard blood tests including full blood count, renal and liver function tests and protein electrophoresis should be performed
c) Skin biopsy of lesion
A biopsy for histology is absolutely essential to make the diagnosis of Kaposi’s sarcoma. A monoclonal antibody against HHV-8 latent nuclear antigen (LANA) is used to identify the presence of HHV8 within lesions
Once a diagnosis of KS had been established, the following tests would be performed to help stage the disease. Although there is no formal classification of stages for iatrogenic Kaposi’s sarcoma (only for AIDS-associated KS) it is helpful in terms of treatment and prognosis to know whether this is 1. Localised non-aggressive disease, 2. Locally aggressive disease or 3. Disseminated Kaposi’s sarcoma
d) Further blood tests:
HHV-8 viraemia and CD4 count
e) Radiological imaging
Whole body CT to detect any evidence of disseminated disease
Treating this patient once a diagnosis of Kaposi’s sarcoma has been established
It should be mentioned that the treatment goal for KS is to control the disease/symptoms: complete cure is not feasible as HHV-8 cannot be eradicated
In patients with post-transplant (iatrogenic) subtype of KS the mainstay of treatment is to reduce their immunosuppression to the lowest level tolerated and switch calcineurin inhibitors (CNI) to a mammalian target of rapamycin (mTOR) inhibitor.
For the patient in this case his tacrolimus should be switched to sirolimus and the MMF should be stopped.
The patient should then be under frequent follow-up (minimum monthly) to monitor closely for any signs of allograft rejection in the context of immunosuppression reduction and also establish Kaposi sarcoma response to the treatment initiated. If there is severe/disseminated disease and inadequate response to the above reduction in immunosuppression then chemotherapy may need to be considered.
References
Lebbe C, Garbe C, Stratigos AJ, Harwood C, Peris K, Marmol VD, Malvehy J, Zalaudek I, Hoeller C, Dummer R, Forsea AM, Kandolf-Sekulovic L, Olah J, Arenberger P, Bylaite-Bucinskiene M, Vieira R, Middleton M, Levy A, Eggermont AM, Battistella M, Spano JP, Grob JJ, Pages C; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organisation for Research and Treatment of Cancer (EORTC). Diagnosis and treatment of Kaposi’s sarcoma: European consensus-based interdisciplinary guideline (EDF/EADO/EORTC). Eur J Cancer. 2019 Jun;114:117-127. doi: 10.1016/j.ejca.2018.12.036. Epub 2019 May 1. Available at: https://pubmed.ncbi.nlm.nih.gov/31096150/
Mikulska M, Balletto E, Mularoni A. Human herpesvirus 8 and Kaposi sarcoma: how should we screen and manage the transplant recipient? Curr Opin Infect Dis. 2021 Dec 1;34(6):646-653. Available at: https://pubmed.ncbi.nlm.nih.gov/34693921/
1.What is your differential diagnosis?
My first ddx in the light of the patient’s
medical hx is Kaposi Sarcoma
or more precisely:latrogenic (transplant(related
kaposi sarcoma
other ddx
The differential diagnosis of Kaposi sarcoma on mucocutaneous surfaces includes:
1.Nevi
2.Pyogenic granuloma
3.Bacillary angiomatosis
4.Hemangioma
5.Angiosarcoma
6.Melanoma.
7.dermatofibroma
8.purupra
Histologically, spindle cell vascular lesions in
the skin include a differential diagnosis of:
1.Interstitial granuloma annulare
2.Spindle cell hemangioma
3.Acquired tufted angioma
4.Kaposiform hemangioendothelioma
5.Cutaneous angiosarcoma
6.Fibrosarcomatous dermatofibrosarcoma
protuberans
7.Aneurysmal dermatofibroma
8.Acroangiodermatitis
9.Spindle cell melanoma
10.High-grade sarcomas(1)
2.How do you manage this case?
managent of this patient requires first
confirmation of my clinical dx because:
Although KS can be strongly suspected in an
appropriate clinical setting, recent studies
confirmed the limited predictive value of clinical
diagnosis of KS and Histopathological confirmationi.e.skin biopsy of the clinical dx of KS remains the gold standard(2)
and also we need to test for HHV8 viral load
and serology
HIV viral load
we also need to search for visceral involovemnt
which is usually seen in transplant and AIDS
related Kaposi sarcoma. so we need
enodscopy/colonoscopy and bronchospoy.
Regarding treatment:Iatrogenic or post-transplantation Kaposi sarcoma commonly responds to reduction or discontinuation of immunosuppression. In one study, tapering of immunosuppressive therapy alone led to complete or partial KS regression in 9 of 20 patients(3)
Switching the chemical immune suppressive regimen from cyclosporine A/FK506 to mammalian target of rapamycin (mTOR) inhibitors such as rapamycin/sirolimus/everolimus often leads to KS regression(4,5)
3.Substantiate your answer.
1.Bishop BN, Lynch DT. Kaposi Sarcoma.
[Updated 2022 Jun 1 1]. In: StatPearls [Internet]
Treasure lsland (FL): StatPearls Publishing:
2022 Jan-.
2.Schneider JW, Dittmer DP. Diagnosis and
Treatment of Kaposi Sarcoma. Am J Clin
Dermatol. 2017 Aug;18(4):529-539. doi:
10.1007/S40257-017-0270-4. PMID: 28324233;
PMCID: PMC5509489
3.Barete S, Calvez V, Mouquet C, et al. Clinical Features and Contribution of Virological Findings to the Management of Kaposi Sarcoma in Organ-Allograft Recipients. Arch Dermatol. 2000;136(12):1452–1458. doi:10.1001/archderm.136.12.1452
4.Stallone G, Schena A, Infante B, Di Paolo S, Loverre A, Maggio G, et al. Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. N Engl J Med. 2005 Mar 31;352(13):1317–23.
5.Nichols LA, Adang LA, Kedes DH. Rapamycin blocks production of KSHV/HHV8: insights into the anti-tumor activity of an immunosuppressant drug. PLoS One. 2011 Jan 14;6(1):e14535.
On the top of the differential is kaposi sarcoma
other differentials : bacillary angiomatosis, Angiosarcoma, Malignant melanoma
physical examination of skin, mouth , rectum and lymph nodes.
Systemic therapeutic management of post-transplant Kaposi sarcoma (KS) is mainly based on 3 axes: reduction of immunosuppression, conversion to mammalian target of rapamycin (mTOR) inhibitors and/or chemotherapy such as Pegylated Liposomal doxorubicin in cases of disseminated Kaposi Sarcoma resistant to switching medications .
References:
1) Kaposi Sarcoma after kidney transplantation. Juliette Raedemaeker et al. BMJ case reports, volume 12, issue 5
2) Management of Kaposi sarcoma after solid organ transplantation: A European retrospective study Julie Delyon, Clementine Rabate, Sylvie Euvrard, Catherine A. Harwood, Charlotte Proby, A.Tülin Güleç, Deniz Seçkin, Veronique del Marmol, Jan Nico Bouwes-Bavinck, Carla Ferrándiz-Pulido, et al.
3) https://www.hopkinsmedicine.org/health/conditions-and-diseases/sarcoma/kaposi-sarcoma
Most likely KAPOSI sarcoma
differential diagnoses are bacillary angiomatosis, Angiosarcoma, Malignant melanoma, Benign lymphangioendothelioma
WORK UP
Biopsy with (HHV-8) DNA sequences PCR immunohistochemistry for (LANA-1)
CT abdomen and pelvis
bronchoscopy
HIV serology
TREATMENT
controlling the disease whilst maintaining graft function is still a challenge
Reduction of immunosuppression(IS) is an effective therapeutic option but is limited by the risk of graft rejection. In KS, remission after a decrease of IS alone ranged from 30% to 50% in the retrospective series
Therapy for post-transplant KS has changed over the past two decades. In 2005, conversion to mTORi was shown to have a therapeutic effect: conversion from calcineurin inhibitors (CNI) and/or purine antagonists to sirolimus induced responses in 72-100% of patients
However, relapse and the apparent absence of remission in patients with visceral KS were
reported in a significant proportion of patients treated with sirolimus ,
regarding this case stoppage of MMF is appropriate with Tacrolimus switch to an mTOR
if no improvement radiation and chemotherapy may be started
1. Stallone G, Schena A, Infante B, et al. Sirolimus for Kaposi’s sarcoma in renal-342
transplant recipients. N Engl J Med. 2005;352(13):1317-1323.343
doi:10.1056/NEJMoa042831344
17
2. Lebbé C, Euvrard S, Barrou B, et al. Sirolimus conversion for patients with345
posttransplant Kaposi’s sarcoma. Am J Transplant Off J Am Soc Transplant Am Soc346
Transpl Surg. 2006;6(9):2164-2168. doi:10.1111/j.1600-6143.2006.01412.x347
3. Monaco AP. The role of mTOR inhibitors in the management of posttransplant348
malignancy. Transplantation. 2009;87(2):157-163. doi:10.1097/TP.0b013e318193886e
1. Kaposi’s sarcoma( most likely), D/D is SCC, BCC, Malignant Melanoma.
2. Skin biopsy for confirmation, do HHV-8 PCR, HIV testing, search for visceral involvement.
Rx: Reduce dose of TAC & switch to Sirolimus, consultation taken from oncologist & dermatologist.
–What is your differential diagnosis?
Kaposi sarcoma
Squamous cell carcinoma
Basal cell carcinoma
–How do you manage this case?
-Work up for this lesion:
send HHV8 PCR, virology, CMV, EBV, skin biopsy, CBC.
treatment:
The best treatment is to shift from CNI to sirolimus.
–Substantiate your answer.
MN, Uldrick TS, Yarchoan R. Kaposi sarcoma-associated herpesvirus-associated malignancies: epidemiology, pathogenesis, and advances in treatment. Semin Oncol. 2015;42(2):223-46.
Classic Kaposi sarcoma: Clinical features, staging, diagnosis, and treatment
AIDS-related Kaposi sarcoma: Staging and treatment
Malignancy after solid organ transplantation
1-What is your differential diagnosis?
-Kaposi sarcoma (most likely)
-Haemangioma with bruises
-Angiosarcoma
-Squamous cell carcinoma
-Basal cell carcinoma
Risk factors for Kaposi Sarcoma:
-The intensity and duration of immunosuppression
-The presence of HHV8 -HIV
-Male gender -Non-White patients
-Mediterranean origin Jewish, Arabic, Caribbean, or African descent parallels HHV-8 seroprevalence
-Lung transplant recipients were at increased risk of KS.
2-How do you manage this case?
A-Work up for this lesion required;
-CBC, Virology, Serology of HHV-8-PCR, HIV,CMV,EBV,
-Skin Biopsy of skin lesion.
B-Searching for visceral affection;
-So pan CT with contrast is indicated in all cases of KS.
-Upper and Lower GIT Endoscopy
-Bronchoscopy
C-Dermatology consultation; and Biopsy from the lesion is mandatory for confirmation of the diagnosis.
D-Treatment;
-Reduction of immunosuppression is associated with regression IN 17% of cases of KS,
-FK level in the current patient is (8.3) which is above the target in a patient with renal transplant for 14 years, so tacrolimus dose can be reduced maintain trough between 3-5 ng/l.
-The ideal treatment is to shift from CNI to sirolimus if not contraindicated with is associated with complete resolution within 3-6 months of conversion,
-In the current case sirolimus can be used due to stable graft function (S Cr is 113 µmol/L)
-So in the current case if the biopsy confirmed Kaposi sarcoma, I will stop antimetabolite and reduce tacrolimus dose to keep a target between 3-5ng/ml.
-If no resolution after reduction of immunosuppression, Chemotherapy may be offered to patients with diffuse and symptomatic disease .
3-Substantiate your answer.
1-Schwartz RA. Kaposi’s sarcoma: an update. J Surg Oncol. 2004 Sep 1;87(3):146-51. doi: 10.1002/jso.20090. PMID: 15334644.
2-American cancer society cancer.org | 1.800.227.2345.
3-Aseni P, Vertemati M, Minola E, et al. Kaposi’s sarcoma in liver transplant recipients: morphological and c Francès C. Kaposi’s sarcoma after renal transplantation. Nephrol Dial Transplant 1998; 13:27681.
*Kaposi’s sarcoma
* Substitute Tacrolimus with Serolimus
– Mostly a case of Kaposi sarcoma in post-kidney transplant.
– DD: SCC, BSC, melanoma, dermatofibroma, hemangioma& Bacillary angiomatosis.
Management:
– Dermatology consultation for histological diagnosis by skin biopsy & options of treatment (surgical excision , chemotherapy & radiotherapy ) with oncology involmenet.
– Reduction of immunosuppression:
1- hold MMF
2- decrease dose of tacrolimus, targeting trough level 2-4
3- add mTORi (sirolimus or everolimus)
– Work up for organ involvement ( CT & endoscopes)
– Preventive measures: use of sunscreen & avoid prolonged sun exposure, especially in sun peak hours.
-Lesions are dark purple , some raised some not , patient is immunosuppressed with very high Tac level , may be for long time , so Kaposi sarcoma should be the 1st to exclude .
-Other differential diagnosis include :
Iatrogenic lesions (immunosuppression)
Infections (Bacterial, viral, fungal, protozoal)
Precancerous lesions (actinic keratosis, warts)
Malignancy (lymphoma, melanoma, angiosarcoma , Merkel cell carcinoma (MCC))
Management should entail :
-Dermatological consultation , biopsy and pathological analysis.
-Decreasing tac levels , and shifting to mTORi if diagnosis of Kaposi is confirmed , due to the certican anticancerous effects .
-Blood pressure and blood sugar monitoring , proteinuria and lipid profile regular check.
-Psychological reassurance
-Exclusion of current infections ( CMV , EBV )
References:
1-Dreno B (2003) Skin cancers after transplantation. Nephrol Dial Transplant 18: 1052-1058.
2-Hengge UR, Ruzicka T, Tyring SK, Stuschke M, Roggendorf M, et al. (2002) Update on Kaposi’s sarcoma and other HHV8 associated diseases.
3-Francès C (1998) Kaposi’s sarcoma after renal transplantation.
4-Penn I, First MR (1999) Merkel’s cell carcinoma in organ recipients: report of 41 cases.
5-Koljonen V, Kukko H, Tukiainen E, Böhling T, Sankila R, et al. (2009) Incidence of Merkel cell carcinoma in renal transplant recipients.
6-Kibe Y, Kishimoto S, Katoh N, Yasuno H, Yasumura T, et al. (1997) Angiosarcoma of the scalp associated with renal transplantation.
7-Lai KN, Lai FM, King WW, Li PK, Siu D, et al. (1995) Dermatofibrosarcoma protuberans in a renal transplant patient.
What is your differential diagnosis?The spot diagnosis of these skin lesions points to Kaposi Sarcoma as the first differential diagnosis.Other DD possibilities include:
Bacillary angiomatosis, Hemangioma, Purpura, pyogenic granuloma, dermatofibroma, hematoma, Fibrous histiocytoma, interstitial granuloma annulare, angiosarcoma.
How do you manage this case?
Multidisciplinary team is required including dermatologist, oncologist and nephrologist.
The risk of death from disseminated malignancy should be outweighed against the risk of rejection.
Skin biopsy: Kaposi Sarcoma histopathology reveals spindle cell proliferation with prominent vascular spaces and extravasated RBCs, confirm HHV8 in the biopsy.
Check virology for HIV, HHV8.
Organs involvement:
Chest X-ray: non-specific findings. Bronchoscopy.
CT-chest, abdomen and pelvis.
GIT Endoscopy.
Thallium/Gallium scan helps differentiate KS (takes thallium) from infection (takes gallium).
Treatment:
Suns-protection (avoid exposure, protective clothing, sun-protective creams)
Modify immunosuppression:
Switch Tacrolimus to m-TOR inhibitors (CONVERT trial and TUMORAP trial).
Reduce MMF dose.
Keep steroids.
Chemotherapy: indications for treatment with Liposomal doxorubicin:
Mucosal and visceral involvement, diffuse symptomatic lesions on multiple body parts, extensive nodular disease, bulky disease in a localized area, moderate to severe associated lymphoedema.
Pamidronate can be used instead of chemotherapy
Local therapy: surgical resection, radiotherapy, cryotherapy, laser treatment or topical creams like retinoic acid, silver nitrate and rapamycin.
Radiotherapy.
If HHV8+ve, treat with ganciclovir, or foscarnet or cidofovir.
Substantiate your answer.
Renal transplant recipients should have regular self-skin examination and annual dermatologist skin examination for early detection of suspicious skin lesions.
Reduction of immunosuppression and switching CNIs to m-TOR inhibitors help treatment of cutaneous malignancy.
5% of malignancy post organ transplantation is attributed to Kaposi Sarcoma.
Organ transplant recipients are at 50-500-fold risk of developing KS in comparison to general population.
Description of KS skin lesions: non-painful, non-itchy macules, papules or nodules purple-red-bluish in color, they can ulcerate and bleed.
Lesions usually start on lower limbs, they mostly remain localized but can spread to visceral mucosa of the trachea, lungs and GIT.
KS can be divided into 5 types with variable course and prognosis:
1-Sporadic classic KS.
2-KS in iatrogenic immunosuppression.
3-Endemic African KS.
4-Epidemic HIV associated KS.
5-KS in men having sex with men (MSM) without HIV infection.
Reference
Bhutani M, Polizzotto Delyon J, Rabate C, Euvrard S, Harwood CA, Proby C, Güleç AT, et al. Management of Kaposi sarcoma after solid organ transplantation: A European retrospective study. J Am Acad Dermatol. 2019;81(2):448-55.
Delyon J, Rabate C, Euvrard S, et al. Skin Care in Organ Transplant Patients Europe (SCOPE) group. Management of Kaposi sarcoma after solid organ transplantation: A European retrospective study. J Am Acad Dermatol. 2019 Aug;81(2):448-455.
MN, Uldrick TS, Yarchoan R. Kaposi sarcoma-associated herpesvirus-associated malignancies: epidemiology, pathogenesis, and advances in treatment. Semin Oncol. 2015;42(2):223-46.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Kaposi Sarcoma Version 1.2023 — December 20, 2022.
Raeisi D, Payandeh M, Madani SH, Zare ME, Kansestani AN, Hashemian AH. Kaposi’s Sarcoma after Kidney Transplantation: a 21-Years Experience. International journal of hematology-oncology and stem cell research. 2013;7(4):29-33. PubMed PMID: 24505540. Pubmed Central PMCID: PMC3915423. Epub 2014/02/08. eng.
Stallone G, Schena A, Infante B, Di Paolo S, Loverre A, Maggio G, et al. Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. The New England journal of medicine. 2005 Mar 31;352(13):1317-23. PubMed PMID: 15800227. Epub 2005/04/01. eng.
Uptodate:
Classic Kaposi sarcoma: Clinical features, staging, diagnosis, and treatment
AIDS-related Kaposi sarcoma: Staging and treatment
Malignancy after solid organ transplantation
Kaposi’s sarcoma
would shift tacrolimus to serolimus
The Differential diagnosis in this case is mostly like Kaposi’s sarcoma…..The most likely lesion involving multiple purple papular plaques with areas over the trunk with few areas of ulceration….This is consistent with the time line of transplant after 14 years……
Spindle cell like inclusion in the skin biopsy in the clinical background of renal transplant is usually Kaposi’s sarcoma…the other differential diagnosis are bacillary angiomatosis, Angiosarcoma, Malignant melanoma, Benign lymphangioendothelioma….
Confirming the diagnosis involves skin biopsy and doing the serology testing for HHV 8….Team work for the diagnosis and management includes dermatologist and hematologist consultation with oncologist consultation…We should screen for other symptoms of involvement in kaposi sarcoma in GI and CNS…
The management of this case involves the reduction of immunosuppression…The patients must be stopped on MMF…Tacrolimus must be tapered to a lower trough level..I would add sirolimus or everolimus as mTOR inhibitors are cell cycle regulators and they help in cell proliferation regulation….Skin involvement of Kaposis sarcoma is treated by local excision, liquid nitrogen and injection of vincristine, but this is valid for local lesions…Small superficial lesions maybe excised…The Radiation therapy maybe given for localized lesions…Extensive systemic Kaposi’s sarcoma like these will need radiation and chemotherapy with Vinblastine, doxorubicin, etoposide, Gemcitabine and interferon alpha…
References:
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.
LIKELY TO BE KAPOSI SARCOMA WHCH IS COMMON AFTER PROLONGED IMMUNOSUPRESSION
THESE LESIONS CAN BE MULTIPLE WITH VISCERAL INVOLVEMENT
DIFFERENTIAL DIAGNOSIS CAN BE
BASAL CELL CA
SCC
MELANOMA
MERKEL CELL CA
MANAGEMENT-
KS IS ASSOCIATED WITH HHV8, AND GENERALLY RESPOND TO REDUCTION OF IMMUNOSPUPRESSION VERY WELL UNLESS IT HAS VISCERAL LESION WHEN CHEMOTHARPY IS WARRANTED
The mainstay of treatment is reduction opn immunosippression tac/cylcosporin and steroid , as steroid reduction is equally important but garft preservation need to be monitered
Sirolimus works in dual fashion like preserve the graft function by immunisuppression and anti tumor activity based on VEGF pathways
within 6 month most of the lesions are resolved
Kaposi Sarcoma After Kidney Transplantation
Behzad Einollahi
IJKD 2007;1:2-11
http://www.ijkd.org
What is your differential diagnosis?
· Mostly these multiple papules and plaques may suggest an Extensive form of Kaposi sarcoma, this type is Iatrogenic (immunosuppression related), and relatively common in patients on immunosuppressive drugs, especially post solid organ transplant.
· Patients with organ transplants have a 50- to 500-fold increased risk to develop Kaposi Sarcoma compared to the normal population
· Another differential diagnosis may include bacillary angiomatosis and other infections, angiosarcoma, and benign vascular lesions, such as hemangiomas.
· A biopsy is required to establish the diagnosis. Also, PCR can be performed on the skin lesions to detect amplified human herpes virus 8 (HHV-8) DNA sequences, and immunohistochemical staining of biopsy specimens can also be performed to detect the presence of HHV-8 latency-associated nuclear antigen (LANA-1) within the spindle cells, to confirm the diagnosis.
· If visceral KS involvement is suspected, a whole-body computed tomography (CT: thorax, abdomen/pelvis) should be performed.
· Also, esophageal-gastro-duodenoscopy, colonoscopy, and bronchoscopy may also be done.
How do you manage this case?
· The type and degree of immunosuppression play an important role in the development of posttransplant KS.
· Patients treated with calcineurin inhibitor-based immunosuppressive therapies are at particularly high risk of developing aggressive KS.
· Reducing the intensity of immunosuppression or switching immunosuppressants to mTOR inhibitors, such as sirolimus or everolimus, are cornerstones of treatment.
· Regression of KS has been reported after switching from calcineurin inhibitors to sirolimus by restoring effector and memory T-cell immune activity against HHV-8
· If no response to a change in immunosuppression, KS is treated similarly to classic KS.
· We should exclude visceral involvement, extensive lymph node involvement, or progressive mucocutaneous involvement, as this indicates systemic chemotherapy such as Doxorubicine
· The use of interferon alfa is not recommended because its use is associated with a higher risk of rejection
1) https://onlinelibrary.wiley.com/doi/full/10.1111/ddg.14788#:~:text=Guidelines%20for%20the,03%20June%202022
2) https://www.uptodate.com/contents/classic-kaposi-sarcoma-clinical-features-staging-diagnosis-and-treatment?
Kaposi sarcoma (KS)
KS is an angioproliferative cutaneous cancer caused by human herpesvirus 8.
KS may respond to reduction or discontinuation of the immunosuppressive regimen, and this should be the first therapeutic manoeuvre. Among patients listed in the Cincinnati registry, for example, reduction in immunosuppressive therapy was associated with the disappearance of KS in 17 and 16 percent of patients with mucocutaneous disease and visceral involvement, respectively.
In addition, the substitution of sirolimus for cyclosporine in a total of 17 kidney transplant recipients has been associated with complete regression of KS.
Given these results, converting to sirolimus from a calcineurin inhibitor in this setting may be reasonable if there are no contraindications for this strategy.
1. Raedemaeker J, Marot L, Camboni A, et al. Kaposi sarcoma after kidney transplantation. BMJ Case Reports CP 2019;12:e229681.
2. Malignancy after solid organ transplantation. UpToDate. Accessed on 1/2/23
3. Campistol JM, Schena FP. Kaposi’s sarcoma in renal transplant recipients–the impact of proliferation signal inhibitors. Nephrol Dial Transplant. 2007 May;22 Suppl 1:i17-22. doi: 10.1093/ndt/gfm089. PMID: 17456614.
Differential Diagnosis
Histologically, spindle cell vascular lesions in the skin include a differential diagnosis of
The differential diagnosis of Kaposi sarcoma on mucocutaneous surfaces includes:-
It is caused by infection with human herpesvirus-8, which in healthy individuals causes no symptoms. However, in patients with weakened immune systems, such as in HIV and organ transplant patients, the virus can proliferate leading to KS.
Kidney transplant recipients are at higher risk of Kaposi sarcoma because of immunosuppression and human herpes virus type 8 reactivation.
KS is an angioproliferative cutaneous cancer caused by human herpesvirus 8. Skin lesions are typical and make the diagnosis. These are purple- red-bluish lesions presenting as non-painful, non-itchy, macules, papules, plaques or nodules. Due to their vascular aetiology, they can ulcerate and bleed. The incidence of KS is higher in trans- plant patients than in non-immunosuppressed populations. In kidney transplant recipients, the intensity and duration of immunosuppression, and the presence of HHV8 serology pretransplantation increase the risk of developing KS, which occurs 13 months after transplantation (range few weeks to 18 years).
Mucosal dissemination or visceral involve- ment has usually a poor prognosis.
Management
History and exam
Key diagnostic factors
age >50 years
male sex
geographic location: central Africa or the Mediterranean
HIV infection
weight loss
abdominal pain
gastrointestinal (GI) bleeding
diarrhea
Risk factors
male sex
HIV infection
immunosuppressive therapy
human herpesvirus-8 (HHV-8, also known as Kaposi sarcoma-associated herpesvirus [KSHV]) infection
1st investigations to order
HIV test
skin/mucosal biopsy
lymph node biopsy
fecal occult blood
Biopsy is required for definitive diagnosis. In addition to observing typical histologic features on standard microscopy, polymerase chain reaction can be performed on the skin lesions to detect amplified human herpes virus 8 (HHV-8) DNA sequences, and immunohistochemical staining of biopsy specimens can also be performed to detect the presence of HHV-8 latency-associated nuclear antigen (LANA-1) within the spindle cells, thus confirming the diagnosis.
Investigations to consider
CT scan
MRI
bronchoscopy
gastrointestinal (GI) endoscopy
human herpesvirus-8 (HHV-8) viremia and serology
-Dissemination is common if not treated rapidly and adequately.
– A late diagnosis with visceral involvement has a poor prognosis.
Treatment
Systemic therapeutic management of post-transplant Kaposi sarcoma (KS) is mainly based on 3 axes:
1-reduction of immunosuppression
2-conversion to mammalian target of rapamycin (mTOR) inhibitors
3-chemotherapy, or a combination of these.
Tapering down the immunosuppressive regimen remains the cornerstone of KS management.
In localized skin KS, the switch from CNI- to sirolimus-based immunosuppressive regimens is the first option, In addition, we also consider surgical excision, and to a lesser extent, electro-chemotherapy, for limited cutaneous PT-KS lesions, refractory to the changes of immunosuppressive regimen.
using single-agent liposomal anthracycline infusions (20 mg/m2),94 in association with modifications of immunosuppression, as front-line therapy for disseminated aggressive PT-KS.
reserving chemotherapy as salvage treatment for refractory or relapsing diseases, despite the reduction of the immunosuppressive levels.
in patients presenting with aggressive disseminated PT-KS, associated with either high HHV8 viremia or hematologic abnormalities and systemic inflammatory symptoms, we usually suggest to promptly start an antiviral course (possibly with cidofovir or foscarnet), at least with the aim to resolve HPS or refractory thrombocytopenia (III).
Radiotherapy has largely been abandoned because of persistently associated local side effects (eg, edema, ulcerative lesions; III).
Reference
1-panel JulieDelyonMD, PhDa Management of Kaposi sarcoma after solid organtransplantation: A European retrospective study, Journal of the American Academy of Dermatology, Volume 81, Issue 2, August 2019, Pages 448-455
2-Juliette Raedemaeker, Liliane Marot, Alessandra Camboni, Nada Kanaan, ges in… Kaposi sarcoma after kidney transplantation, Raedemaeker J, et al. BMJ Case Rep 2019;12:e229681. doi:10.1136/bcr-2019-229681.
3-David Aboulafia, MD
Attending Hematologist and Oncologist, Virginia Mason Clinical Professor of Medicine,Division of Hematology and Oncology, University of Washington, Seattle WA, BMJ Best Practice
4-Riva G, Luppi M, Barozzi P, Forghieri F, Potenza L. How I treat HHV8/KSHV-related diseases in posttransplant patients. Blood. 2012;120(20):4150-9.
What is your differential diagnosis?
This patient presents with multiple skin lesions on the trunk in the form of dark brown macules.
He is on long time immunosuppression for 14 years with CNI, the differential diagnosis includes
Kaposi sarcoma
Cutaneous squamous cell carcinoma (cSCC)
basal cell carcinoma (BCC)
melanoma
Skin cancers account for almost 40% of malignancies in organ transplant recipients and develop in more than 50 % of White organ transplant recipients and in approximately 6 percent of non-White patients .
In the latter group, approximately two-thirds of the skin cancers occur on partially sun-exposed or sun-protected areas (eg, genitals).
This picture mostly shows Kaposi sarcoma
KS is seen in solid-organ transplant recipients, with a prevalence of between 0.5% and 5% depending on the patient’s country of origin.
A French study showed that the prevalence of KS was significantly higher in liver transplant recipients (1.24%) than in kidney (0.45%) and heart transplant (0.41%) recipients
The incidence of KS in transplant recipients is 500 times that in the general population.
It is associated with immunosuppressive therapy particularly CNI
Recent study has shown that HHV-8 reactivates in transplant patients who were seropositive prior to transplantation, and that a significant number of seronegative patients seroconvert to HHV-8 following transplantation.
KS may present with single or multiple skin lesions as well as mucosal, lymphatic, and visceral involvement.
The course of the disease may be aggressive or indolent, with slow progression of the disease characterized by increasing numbers of cutaneous and mucosal lesions and by darkening of pre-existing lesions.
Identification of early lesions may require a higher index of suspicion, and biopsies should be done on any suspicious looking lesion.
How do you manage this case?
Management strategy in organ transplant recipients is to reduce immunosuppression. It has been well documented that KS in kidney transplant recipients shows remission when immunosuppressive treatment is reduced or withdrawn and switch to mTor if no proteinuria and there is stable graft function
The choice of treatment for KS will also depend on the extent and location of the lesions: solitary lesions may be excised or subjected to ionizing radiation,while superficial and flat lesions may be treated with cryotherapy.
Other established therapies for KS include interferon and chemotherapy with cytotoxic drugs including paclitaxel, vincristine, vinblastine, adriamycin, and bleomycin.
Liposomal-encapsulated doxorubicin and daunorubicin are treatment strategies targeted at lowering undesired adverse effects. These treatments are generally considered when the n burden is higher.
Hiok-Hee Tan & Chee-Leok Goh.Viral Infections Affecting the Skin in Organ Transplant Recipients,Epidemiology and Current Management Strategies.American Journal of Clinical Dermatology volume 7, pages13–29 .2006.
Thomas Stasko, MDAllison M Hanlon, MD.Epidemiology and risk factors for skin cancer in solid organ transplant recipients.2023 UpToDate.
1- What is your differnial diagnosis
a- Kaposi sarcoma
Bacillary angimatosis
b- hemosidoretic hemangioma
c- fibrous histiocytoma
d- interstitial granuloma annulare
e- A-V malformation
f- Pyogenic granuloma
Due to history of kiney transplantation and IS therapy ,so this lesion is mostly Kaposi sarcoma . Kaposi sarcoma is a vascular tumer related to HHV-8 infection ,Its uncommon in general population and more common in immunecompremised patients mainly organ transplant recipients and AIDs .in organ transplantation related Kaposi sarcoma the main treatment strategy is to lower IS doses , shift from CNI to m TOR as m TOR use was associated with Kaposi rarcoma remission.
2- How to manage this case ?
First we need to establish the diagnosis of kaposi sarcoma , its type and spread through
a- Skin biopsy
b- Immune histochemestry using monoclonal Ab against latent HHV-8 protien to DD Kaposi sarcoma from other angioproliferative tumers.
c- Screening CT ( chest ,pelvi abd ) for any lymph adenopathy or visceral invasion.
Treatment plan depends on type and extend of Kaposi sarcoma and involve
a- Switch from CNI to m Tor
b- Decrease the dose of IS
c- For localized lesion :
– Radiotherapy
– Intra lesion injection of vinblastine or bleamycin
– Topical gel as aletretinoin
– Surgery and cryotherapy
d- For visceral spreed
– Systemic therapy with anti proliferative drugs as taxanes and liposomal anthracyclins.
e- Monitoring of graft function to detect early rejection
Ref
1- M.R. Moosa, Kaposi’s sarcoma in kidney transplant recipients: a 23-year experience, QJM: An International Journal of Medicine, Volume 98, Issue 3, March 2005, Pages 205–214, https://doi.org/10.1093/qjmed/hci028
2- Gheith, Osama & Bakr, Adel & Wafa, Ehab & Fouda, Ashraf & El-Agroudy, Amgad & Refaie, Ayman & Donia, Ahmed & Sabry, Alaa & Sobh, Mohamed & Shokeir, Ahmed & Ghoneim, Mohamed. (2007). Sirolimus for visceral and cutaneous Kaposi’s sarcoma in a renal-transplant recipient. Clinical and experimental nephrology. 11. 251-4. 10.1007/s10157-007-0470-y.
Differential .what is differential diagnosis?
– kaposi sarcoma.
– squamous cell carcinoma.
– basal cell carcinoma,
– bacillary angionatosis.
-angiosaroma.
– benign vascular lesion (hemangioma)
Management.
Switch of calcinurins inhibitors to sirolimens or evrolims which proved to have role to decrease proliferation
– patient eduction for sun protection and .skin examination, daily use of skin protection measures and avoid sun exposure with vitamin d3 supplementation
-Chemo prevention.
– surveillance post-transplant”- prior to transplant and if there any past history of skin cancer, lymph nodes should be examined..
Chemotherapy:-
– pacitaxel for the initial disease progression as subsequent therapy .
– vincristine. Or vinblastine either alone or with combination of bleomycin..
References:
Krown SE, Moser CB, MacPhail P, et al. Treatment of advanced AIDS-associated Kaposi sarcoma in resource-limited settings: a three-arm, open-label, randomised, non-inferiority trial. Lancet 2020; 395:1195.Cianfrocca M, Lee S, Von Roenn J, et al. Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcoma: evidence of symptom palliation from chemotherapy. Cancer 2010; 116:3969.
What is your differential diagnosis?
D/d
1.Kaposi sarcoma.
2.Fungal infection
3.Bacillary angiomatosis
4.Haemangioma
5.Dermatitis
most likely Kaposi Sarcoma
How do you manage this case?
To confirm diagnosis, we need skin biopsy.
MDT with dermatologist, transplant team and oncologist
1st line of treatment is.
Immunosuppression reduction reducing tacrolimus dose to trough level of 3-5, holding the MMF, if MTOR is feasible (access, cost, availability) switching CNI to the MTOR inhibitor sirolimus/everolimus
Needs evaluate for visceral involvement of GIT tract and other part of body.
If no response or disseminated disease needs radio and chemotherapy (like vincristine or doxorubicin.)
To prevent recurrence or development of new lesion, avoidance of sun exposure and use of sunscreen may help.
Substantiate your answer.
References
1.Josep M. Campistol, Francesco P. Schena, Kaposi’s sarcoma in renal transplant recipients—the impact of proliferation signal inhibitors, Nephrology Dialysis Transplantation, Volume 22, Issue suppl_1, May 2007, Pages i17–i22, https://doi.org/10.1093/ndt/gfm089
2.Uptodate last reviewed Dec 2022: Classic Kaposi sarcoma: Clinical features, staging, diagnosis, and treatment (accessed 27 Jan 23)
3.KDIGO guidelines 2020
What requirements are needed to replace CNI with mTORi?
Thank you sir for your questions.
Patients factor.
We need to see urine for protein as mtor increses the proteinuria
We need to see if he had dyslipidemia
He dont have any resiratory symptoms as it may cause interstitial pneumonia
There is no active wounds
His blood pressure and blood sugar are well controlled.
Reference.
Diekmann, F., Campistol, J.M. Practical considerations for the use of mTOR inhibitors. Transplant Res 4 (Suppl 1), 13–17 (2015). https://doi.org/10.1186/s13737-015-0029-5
Social factor
The drug is easily available and we can monitor the level easily
Affordability as the drug and drug level cost more than tacrolimus
Clinical examination to check for other lesions in other sites [oral mucosa], associated lymph node enlargement and other organ involvement
A dermatologist consultation is neccesary: a biopsy of the lesion will be taken. Histology of the biopsy sample is to be done, along with immunohistochemical staining for Human Herpes Virus type 8.
Treatment involves a change in the immunosuppresion therapy, ensuring that Sirolimus is included, or a discontinuation of the immunosuppression.
3. The diagnosis of Kaposi Sarcoma in this case is made on the premise of the classical lesions presentation of Kaposi sarcoma: skin lesions that are located mostly on the trunk and limb; purplish/dark blue macules and plaques.
The incidence of Kaposi Sarcoma is much higher in patients who have received a transplant and are on immunosuppression, than in non immunouppressed patients.Other factors that predispose these set of patients to this increased risk include the intensity and duration of immunosuppression, and the presence of Human Herpes-Virus type 8 [detected by serology] before the transplant. In transplant recipients Kaposi Sarcoma presentetaion is often limited to the skin. There have however been cases of visceral Kaposi Sarcoma.
References
Differential diagnosis:
Kaposi sarcoma: most likely. extensive purplish papules or plaques in renal transplant on immunosuppressive medications.
– less likely:
. pityriasis versicolor: immunocompromised, affects mainly, face, trunk and proximal upper limb; usually pale macules, no papules,
– allergic or infective dermatitis
-Hemagioma ,pyogenic granuloma bacillary angiomatosis
-Management:
skin biopsy, dermatologist consultation..
Primary treatment includes:
– Immunosuppression reduction, holding MMF, switching CNI to the MTOR inhibitor sirolimus.
-Staging: Evaluation for visceral involvement of GIT tract.
– Oncology consultation if no improvement.
– Prevention of recurrence or new lesion, avoidance of sun exposure and use of sunscreen.
References
Post renal-transplant malignancy surveillance, Clinical Medicine 2020 Vol 20, No 2: 142–5
Kaposi sarcoma after kidney transplantation Juliette Raedemaeker, Liliane Marot, Alessandra Camboni, Nada Kanaan
· What is your differential diagnosis?
The most likely Kaposi sarcoma multiple purplish skin lesions are typical
Other deferential diagnosis are bacillary angiomatosis ,pyogenic granuloma ,disseminated melanoma.
· How do you manage this case?
-Start by good history and proper clinical examination looking for mucus membrane involvement any lymph node enlargement plus complete systemic examination .
-Skin biopsy and histopathology
-Imaging including CXR .CT chest or abdomen when indicated also endoscopy and bronchoscopy in suspected mucus membrane involvement .
– Reduction or discontinuation of immunosuppression caused complete remission in all patients without surgical intervention, chemotherapy or radiotherapy .In this patient if proved Kaposi sarcoma we need to discontinue antiprolpiferative MMF and replace tacrolimus with mTOR inhibitors like sirolimus as the sirolimus inhibits the progression of dermal Kaposi’s sarcoma in kidney-transplant recipients while providing effective (1) (2)(3)
-General measures of prevention (use of sunscreen, hats, avoidance of exposure to ultraviolet radiation during sun peak hours) (4)
Reference:
1- Nephrology Dialysis Transplantation, Volume 17, Issue 5, May 2002, Pages 892–896, https://doi.org/10.1093/ndt/17.5.89
2- N Engl J Med 2005; 352:1317-1323 . DOI: 10.1056/NEJMoa042831
3.-KDGO guidelines 2020
4- Clinical Medicine 2020 Vol 20, No 2: 142–5
This patient’s lesions are typical for Kaposi sarcoma, but the definite diagnosis is made by biopsy. HHV-8 seropositivity is a risk factor for developing Kaposi sarcoma in immunocompromised patients. In such case, we need to shift the Tacrolimus to mTOR inhibitors, everolimus &sirolimus. They are known to decrease the risk of skin cancers. In resistant cases, chemotherapy is the choice
With excellent renal function after 13 years, shifting from tacrolimus seems acceptable
Hosseini-Moghaddam SM, Soleimanirahbar A, Mazzulli T, Rotstein C, Husain S. Post renal transplantation Kaposi’s sarcoma: a review of its epidemiology, pathogenesis, diagnosis, clinical aspects, and therapy. Transpl Infect Dis. 2012 Aug;14(4):338-45. doi: 10.1111/j.1399-3062.2011.00714.x. Epub 2012 Feb 9. PMID: 22316356.
What is your differential diagnosis?
Brown, pink, red maculopapular, nodular and plaque-like lesions, most likely Kaposi sarcoma. Other differential diagnoses:
1. Haematoma
2. Purpura
3. Haemangioma
4. Dermatofibroma
5. Pyogenic granuloma
How do you manage this case?
MD approach
Full history and examination
Evaluate for oral mucosa, lymph nodes, and visceral organs (GIT and pulmonary)
One year incidence after transplantation is 46%
Diagnosed by histopathology
Reduction of immunosuppressive drugs and switching CNIs to mTORi are the mainly approach of treatment. Conversion to mTORi in patients with KS causes regression of lesions through effects on VEGF signaling
Serologic studies support that infection with HHV-8 is nearly universal in patients with KS
Local and systemic therapies may be used in the management of KS
Patient should be counseled on the use of sunscreens, sun protective clothing, and the warning signs of cutaneous malignancy with supplementation of vitamin D. frequent follow-up and self examination
Substantiate your answer.
References
1. Josep M. Campistol, Francesco P. Schena, Kaposi’s sarcoma in renal transplant recipients—the impact of proliferation signal inhibitors, Nephrology Dialysis Transplantation, Volume 22, Issue suppl_1, May 2007, Pages i17–i22.
2. Dariyush et al. Kaposis Sarcoma after Kidney Transplantation: a 21 Years Experience. International Journal of Haematology-Oncology and Stem Cell Research.
UpTodate
What is your differential diagnosis?
Mutiple purple papular plaques at the trunk of different sizes and shapes with some of them shows areas of ulceration for differential diagnosis
How do you manage this case?
History and clinical examination, skin biopsy to confirm diagnosis and determine staging, visceral involvment. Holistic approach with MDT discussion, dermatology, transplant team, local protocol and discuss with the patient options of management and risk stratifications:
Substantiate your answer.
DD
1. Kaposi sarcoma
2. Hemosiderotic hemangioma
3. Bacillary angiomatosis
4. Angiomatoid histiocytoma
How to manage. History and clinical examination looking to detect the extension of the disease followed by
1. Skin biopsy for diagnosis of Kaposi
2. Imaging to detect any visceral involvements
3. May need endoscopies or bronchoscopy for detection of other mucous membranes involvements.
After that
1. If only skin shift to sirolomus and prednisone regimen.
2. Close follow up for response includingbvskin rebiopsy and screening for any visceral and other epithelial invovemnt guided by clinical situation.
If with extensive involvement patient need chemotherapy in addition to changing tacrolimus to sirolimus.
Why you are interested in investigating for visceral involvement?
There is multiple violecous discoloiration all over the trunk. The most likely diagnosis is Kaposi sarcoma. The differential is multiple hematoma , chicken pox or psoriasis guttae but they are remote possibilities.
This patient had a high trough level of tacrolimus, so the first step would be reduction of TAC.
Reduction of immunosuppression resulted in complete remission of KS in 28% of patients from Saudi Arabia, and 61% of Italian patients. Duman et al., report on complete remission after reduction of immunosuppressive drugs in all patients , with a graft loss rate of 20% in Turkey.
Shifting tacrolimus into sirolimus is a better option as cutaneous KS lesions disappeared in all patients three months from the initiation of sirolimus therapy. Another option would be total discontinued of immunosuppression drugs if the above measures fail. The risk of death from dissemination of malignancy should be weighed against the risk of graft rejection.(1) A number of small studies have recently demonstrated that conversion to proliferation signal inhibitors (PSIs),ie m TOR I, along with the concomitant withdrawal of CNIs leads to a rapid resolution of both cutaneous and visceral Kaposi’s lesions. PSIs inhibit tumour angiogenesis through impaired vascular endothelium growth factor production, a key element in the development of the tumour. Previously unpublished data on renal transplant recipients from a number of European and Australian centres have been pooled to provide further insight into the use of PSIs in the management of post-transplant KS. Both members of the PSI class, everolimus and sirolimus, along with CNI withdrawal lead to regression of KS lesions in 11 out of 12 patients. Conversion to PSIs was generally well tolerated with stable renal function maintained in most patients and no episodes of acute rejection recorded. (2)
New antiviral agents have recently been introduced as a therapeutic option in patients with KS but they still need further studies. (1) letermovir has been approved for clinical use in stem cell transplant recipients. Nelfinavir, an HIV protease inhibitor, histone deacetylase (HADAC) inhibitors like sodium butyrate (NaB/SB), 12-O-tetradecanoylphorbol-13-acetate (TPA), and trichostatin (TSA), with the DNA methyltransferase inhibitor 5-Azacytidine (5-AZaC) or with some African autochthonous plant extracts, bortezomib, inhibitors of cellular tyrosine kinases, five compounds (dasatinib, ponatinib, bosutinib, gefitinib, and nilotinib), lenalidomide, an immunomodulatory drug, with arsenic trioxide showed promising results (3)
Ref:
1- Raeisi D, Payandeh M, Madani SH, Zare ME, Kansestani AN, Hashemian AH. Kaposi’s Sarcoma after Kidney Transplantation: a 21-Years Experience. Int J Hematol Oncol Stem Cell Res. 2013;7(4):29-33. PMID: 24505540; PMCID: PMC3915423.
2- Campistol JM, Schena FP. Kaposi’s sarcoma in renal transplant recipients–the impact of proliferation signal inhibitors. Nephrol Dial Transplant. 2007 May;22 Suppl 1:i17-22. doi: 10.1093/ndt/gfm089. PMID: 17456614
3- Naimo, E.; Zischke, J.; Schulz, T.F. Recent Advances in Developing Treatments of Kaposi’s Sarcoma Herpesvirus-Related Diseases. Viruses 2021, 13, 1797. https://doi.org/10.3390/v13091797
Thank you DR Hinda Hassan
You referred to many of the new antiviral and wondered about the role of these medications in Kaposi sarcoma post kidney transplantation not in the context of HIV?
The most probable diagnosis is kaposi sarcoma .
Differential diagnosis include:
SCC
BCC
Pyogenic granuloma
Fibrous histiocytoma
bacillary angiomatosis
Dermatofibroma
Kaposi sarcoma is a malignant,rare tumor originated from endothelial lymphatic vessels.
It can affect the skin and mm. And can disseminate to involve the visceral organs like the GIT liver and lung.
It caused by human herpes virus type 8.
High intensity and duration of IS is the main risk factor .
It occurs in 5% of recipient of kidney transplant and there is 500 fold rise in the risk of KS as compared to general population.
The management plan include:
Proper history
Full examination of the skin and mm by inspection and palpating the abdomen and lymph nodes.
Investigation start by deep skin biopsy for confirmation and staging.
HIV exclusion
Full body scan (CT scan of chest / abdomen/pelvis).
If indicated esophagogastro-duodenoscopy, colonoscopy, and bronchoscopy may be performed.
Consider reduction or stopping immunosuppressant medication like CNIs and MMF. Or switch to mTOR I like sirolimus or everolimus.
If no response or disseminated disease start chemotherapy like vincristine or doxorubicin.
Avoid sun exposure and use of sunscreen and 5-FLU.
Multidisciplinary team must be involved with individualization for every case with regard to termination of treatment and follow up.
Thank you Dr Asmaa Khudhur
Why are you interested in bronchoscopy and OGD in these cases?
Looking for visceral involvement and metastasis.
What is your differential diagnosis?
Based on the history and the nature of the lesions, it’s strongly suggestive of Kaposi sarcoma,
Differential diagnoses are:
1- Pyogenic granuloma.
2- bacillary angiomatosis.
3- Necrotizing sialometaplasia.
4- Granulomatous inflammatory conditions (such as coccidioidomycosis, paracoccidioidomycosis,
How do you manage this case?
Appropriate management increases patient survival. There is no uniform schema of KS treatment in renal transplant recipients. Immunosuppression should be reduced to the lowest adequate levels that preserve allograft function, involving discontinuing CNIs and switching to mTOR inhibitors (1)
Since this is a common cause of death, an examination to rule out gastrointestinal or pulmonary involvement should be conducted. A patient’s life is at danger more from either of these than from losing a kidney transplant if either is present (2)
1- Zavos G, Moris D, Vernadalds S, Bokos J, Lionaki S, Mamarelis G, et al. Incidence and management of Kaposi sarcoma in renal transplant recipients: the Greek experience. Transplant Proc. 2014;46(9):3199-202.
2- A. Harwood, D. Osoba, S. Hofstader, et al. (1979). Kaposi’s sarcoma in recipients of renal transplants. , 67(5), 0–765.doi:10.1016/0002-9343(79)90731-9
Well done Dr Saiwan Haias
what are the common causes of death in Kaposi sarcoma?
Who is at risk to develop Kaposi sarcoma?
1- What are the common causes of death in Kaposi sarcoma?
· Traditional Kaposi sarcoma (KS) patients typically die from the disease rather than from it.
· Although Kaposi sarcoma restricted to the skin is also prevalent, patients with AIDS-related Kaposi sarcoma frequently have widespread visceral Kaposi sarcoma.
· They typically pass away from gastrointestinal Kaposi sarcoma with bleeding or related opportunistic infections.
· Additionally, Kaposi sarcoma may be fatal because to gut perforation, cardiac tamponade, severe lung obstruction, or, in extremely rare cases, brain metastases.
· In the original Kaposi description, fever, diarrhea, and hemoptysis were associated with death, which often occurred within 3 years. (1)
2- Who is at risk to develop Kaposi sarcoma?
Risk factors associated with the development of Kaposi sarcoma posttransplantation include
· -Geographical origin of the patient,
· -HSV-8 infection before and after transplantation,
· -The immunosuppressive regimen used,
But the importance of each factor remains to be determined. (2)
References:
1. Medscape
2. Mendez JC, Paya CV. Kaposi’s Sarcoma and Transplantation. Herpes. 2000 Feb; 7 (1):18-23
1- What is your differential diagnosis?
2- The most likely diagnosis is Kaposi sarcoma. Extensive purplish, blue papules or plaques in kidney transplant recipient on immunosuppressive medications.
3- Other differential diagnoses: less likely.
a. 1-Fungal infection, pityriasis versicolor: can occur in immunocompromised patient, affects mainly trunk, face and proximal upper limb. But usually pale macules, no papules,
b. Dermatitis, allergic or infective
c. Haemagioma
d. Pyogenic granuloma
e. Bacillary angiomatosis
To confirm diagnosis we need skin biopsy, dermatologist involvement.
Primary treatment is:
1- Immunosuppression reduction, holding the anti inflammatory MMF, switching CNI to the MTOR inhibitor sirolimus or reducing tacrolimus dose to trough level of 3-5, if there is contra indication or unavailability of sirolimus.
2- Evaluate for visceral involvement of GIT tract and other part of body.
3- Oncology consultation for second line options if no improvement.
4- To prevent recurrence or development of new lesion, avoidance of sun exposure and use of sunscreen may help.
References
1- KDIGO guidelines 2020
2- Post renal-transplant malignancy surveillance, Clinical Medicine 2020 Vol 20, No 2: 142–5
3- Kaposi sarcoma after kidney transplantation Juliette Raedemaeker, Liliane Marot, Alessandra Camboni, Nada Kanaan
Well done.
Thank you Dr Muntasir Mohammed
Why evaluate for visceral involvement of GIT?
Do you think MMF anti-inflammatory?
Diagnosis
Kaposi sarcoma
Differential Diagnosis
fibrous histiocytoma
pyogenic granuloma
bacillary angiomatosis
because of long standing immunosuppression Kaposi sarcoma is the likely diagnosis. induced by HHV-8. it is primarily skin lesion can affect internal organs ad lymphatic system.
Managment plan
multidisciplinary approach would be required like dermatologist, oncologist, infectious control internist.
Reducing the intensity and type of immunosuppressive therapy.
stopping CNI and switching over to mTOR inhibitor (Sirolimus) would be the treatment of choice.
avoidance of sun exposure and usage of sun blocking cream
topical use of 5 fluorouracil has also shown promising results.
for extensive disease and visceral involvement use of systemic chemotherapy with the help of oncologist would be required.
Ref;
Kaposi Sarcoma after kidney transplantation. Juliette Raedemaeker et al. BMJ case reports, volume 12, issue 5.
Riva G, Luppi M, Barozzi P, Forghieri F, Potenza L. How I treat HHV8/KSHV-related diseases in posttransplant patients. Blood. 2012;120(20):4150-9.
Thankyou.
Diagnosis
Kaposi sarcoma
Differential diagnosis
bacillary angiomatosis
pyogenic granuloma
dermatofibroma
Management
Switch from tacrolimus to sirolumus or reduce the dose of tacrolimus and add sirolimus
Consultation to dermatologist
Substantiate your answer
Sirolimus inhibit the growth of KS tumor cells by down regulating VEGF, Flk-1/KDR and phosphorylated Akt which are commonly upregulated in Kaposi sarcoma. Sirolimus also inhibit tumor growth generally due to its action on the growth cycle via the mTOR pathway.
Thankyou.
References.!
What is your differential diagnosis?▪︎This picture shows multiple spots on the skin of the trunk.These lesions are dark red and brown in colour.
▪︎ This picture is suggestive of Kaposi Sarcoma.
◇Differential diagnosis:
1. Melanoma.
2. Pyogenic granuloma.
3. Fibrous Histiocytoma.
4. Bacillary angiomatosis.
5. Angiosarcoma.
• How do you manage this case? Substantiate your answer
▪︎ Proper medical history to learn about illnesses, operations, sexual activity, and other possible exposures to Kaposi sarcoma–associated herpesvirus (KSHV).
▪︎ If there are other symptoms and about any skin tumors that is noticed.
▪︎Complete physical examination: examine the skin and the mouth to look for KS lesions. Sometimes KS lesions develop inside the rectum, so rectal examination is important, check the stool for occult blood, since KS in the intestines can cause bleeding.
▪︎Skin bopsy: to confirm the lesions
▪︎We can consult a dermatologist.
▪︎ PCR for HHV8 and HIV.
▪︎Chest x-ray.
▪︎CT scan, might be needed to tell for sure if it is KS or some other condition. ▪︎Bronchoscopy, if there is shortness of breath or coughing up blood, or if the chest x-ray or CT scan shows something abnormal.
▪︎GIT Endoscopy ( upper and colonscopy). ▪︎Systemic therapeutic management of post-transplant Kaposi sarcoma (KS) is mainly based on 3 axes: reduction of immunosuppression, conversion to mammalian target of rapamycin (mTOR) inhibitors, chemotherapy, or a combination of these [1].
______________________
Reference:
[1] Julie Delyon et al. Management of Kaposi sarcoma after solid organ transplantation: A European retrospective study. J Am Acad Dermatol. 2019.
What is your differential diagnosis?
Kaposi sarcoma is the most likely diagnosis, considering the pattern of lesions and the history of organ transplant for more than 14 years.
Other differentials are:
Bacillary angiomatosis.
Acro-angio-dermatitis.
Angio-sarcoma.
Seborrheic keratosis.
Melanoma.
Pyogenic granuloma.
Benign lymphangioendothelioma.
SLE.
How do you manage this case?
· Team work-up for diagnosis and management; including dermatologist, hematologist and oncologist.
· Screening for HHV-8 and skin biopsy.
· Looking for other systems involvement; GIT respiratory and LNs.
· Tapering down the immunosuppressive regimen remains the cornerstone of KS management(1).
· Iatrogenic Kaposi sarcoma treatment must balance a reduction in immune suppression or withdrawal of steroid treatment with transplant rejection and treatment of the sarcoma(2).
· Decreasing the intensity or switching immunosuppressive agents to an mTOR inhibitor is the cornerstone of treatment(3).
· Skin involvement of Kaposi sarcoma is treated by local excision, liquid nitrogen, and injection of vincristine(4).
· Radiation therapy: For solitary lesions or lesions of limited extent.
· Surgical excision may be of benefit in some patients with small superficial lesions.
· Treatment options for widespread skin disease include radiation therapy and Chemotherapy(vinblastine, doxorubicin, etoposide, taxanes, gemcitabine, and recombinant interferon alfa)(5).
References
1. Delyon J, Rabate C, Euvrard S, Harwood CA, Proby C, Güleç AT, Seçkin D, Del Marmol V, Bouwes-Bavinck JN, Ferrándiz-Pulido C, Ocampo MA, Barete S, Legendre C, Francès C, Porcher R, Lebbe C; Skin Care in Organ Transplant Patients Europe (SCOPE) group. Management of Kaposi sarcoma after solid organ transplantation: A European retrospective study. J Am Acad Dermatol. 2019 Aug;81(2):448-455. doi: 10.1016/j.jaad.2019.03.028. Epub 2019 Mar 19. PMID: 30902727.
2. Schneider JW, Dittmer DP. Diagnosis and Treatment of Kaposi Sarcoma. Am J Clin Dermatol. 2017 Aug;18(4):529-539.
3. Al-Adra D, Al-Qaoud T, Fowler K, Wong G. De Novo Malignancies after Kidney Transplantation. Clin J Am Soc Nephrol. 2022 Mar;17(3):434-443. doi: 10.2215/CJN.14570920. Epub 2021 Mar 29. PMID: 33782034; PMCID: PMC8975024.
4. Kaplan LD. Human herpesvirus-8: Kaposi sarcoma, multicentric Castleman disease, and primary effusion lymphoma. Hematology Am Soc Hematol Educ Program. 2013;2013:103-8.
5. Régnier-Rosencher E, Guillot B, Dupin N: Treatments for classic Kaposi sarcoma: a systematic review of the literature. J Am Acad Dermatol 68 (2): 313-31, 2013.
Thankyou.
·What is your differential diagnosis?
This is a widespread cutaneous Kaposi sarcoma.
Patch, plaque, or nodular lesions are the typical cutaneous manifestations of conventional KS, and each subtype has a unique histomorphology.
Classic KS, AIDS-associated (epidemic) KS, African (endemic) KS, and transplant-associated (iatrogenic) KS are the four main clinico-pathological types.
Less common variants, notably lymphangioma-like KS and anaplastic KS, can be mistaken for other neoplasms.
The risk of developing KS, which occurs 13 months after transplantation (range: few weeks to 18 years), is increased in kidney transplant recipients by the strength and duration of immunosuppression as well as the existence of HHV8 serology pretransplantation.
===============================
How do you manage this case?
===============================
References
1.Reubina Wadee Wayne Grayson, Cutaneous Kaposi sarcoma and its mimics, Diagnostic HistopathologyVolume 28, Issue 1, January 2022, Pages 38-52
2. Raedemaeker J, Marot L, Camboni A, et al. Kaposi sarcoma after kidney transplantation. BMJ Case Rep 2019;12:e229681. doi:10.1136/bcr-2019- 229681
What is your differential diagnosis?
Kaposi sarcoma
Bacillary angiomatosis
Purpura
Squamous cell carcinoma
Basal cell carcinoma
How do you manage this case?
Proper history taking and clinical examination
Confirm diagnosis by skin biopsy
Assess Mets and visceral involvement by pan CT scan
Management:
Reduce immunosuppressive medications ( Tac level less than 5), stop MMF
Shift to mTOR inhibitors as Sirolimus
If no response, chemotherapy is indicated
Reference
Dantal J, Soulillou JP. Immunosuppressive drugs and the risk of cancer after organ transplantation. N Engl J Med 2005; 352:1371.clinical description. Liver Transpl 2001; 7:816.
Shepherd FA, Maher E, Cardella C, Cole E, Greig P, Wade JA, et al,Treatment of Kaposi’s sarcoma after solid organ transplantation. J Clin Oncol. 1997;15(6):2371-7.
Thank you.
What is your differential diagnosis?
This clinical features is more likely of Kaposi Sarcoma.
Other differential diagnosis are:
Bacillary Angiomatosis
Hematoma
Hemangioma
Dermatofibroma
Pyogenic granuloma
Purpura
How do you manage this case?
-Dermatological consultation and lesion biopsy.
-Post-transplantation Kaposi sarcoma commonly responds to reduction or discontinuation of immunosuppression. In one study, tapering of immunosuppressive therapy alone led to complete or partial KS regression in 9 of 20 patients. (1) However, this approach may not always be feasible and can place patients at risk for graft rejection.
-Detail medical history, a complete inspection including the visible mucous membranes as well as palpation of the lymph nodes and the abdomen with recording of all lesions and symptoms are part of the (initial) examination .
-All KS patients without known HIV infection should be offered HIV testing at initial KS diagnosis.
– Further investigation should be individualized based on disease dissemination, symptoms, course, and KS subtype.
– In the case of (suspected) visceral KS involvement, a whole-body computed tomography (CT: thorax, abdomen/pelvis) should be performed. If necessary, esophagogastro-duodenoscopy, colonoscopy, and bronchoscopy may also be performed.
-Switching from calcineurin inhibitors ( tacrolimus) to a mammalian target of rapamycin (mTOR) inhibitor, specifically sirolimus.
– Chemotherapy is commonly reserved for limited disease refractory to local therapy or in patients with disseminated disease.(2)
-Monitor graft function.
References:
1.Barete S, Calvez V, Mouquet C, Barrou B, Kreis H, Dantal J, et al. Clinical features and contribution of virological findings to the management of Kaposi sarcoma in organ-allograft recipients. Arch Dermatol. 2000 Dec. 136 (12):1452-8. [QxMD MEDLINE Link].
2.Stefan Esser, Helmut Schöfer et al. S1 Guidelines for the Kaposi Sarcoma.JDDG. 03 June 2022 https://doi.org/10.1111/ddg.14788
Thankyou , are there precautions to be noticed during switch to mTORs.
The lesions are typical of Kaposi sarcoma
History and examination to look for mucosal, lymph node and visceral involvement
Skin biopsy (IHC)
HHV8 PCR
CT TAB +/- OGD, colonoscopy, bronchoscopy to look for visceral involvement
Reduction of immunosuppression (stop/reduce antiproliferative), switch CNI to mTORI, if no response consider chemotherapy
Monitor graft function
The lesion showed large violaceous macules/ nodules affecting skin of anterior chest and abdomen with symmetrical distribution
DDx
regarding the available history of immunosuppression this is most probable Iatrogenic KS . Iatrogenic KS may develop under long-term immunosuppression and may regress after discontinuation, reduction, or conversion of immunosuppressive therapy. Kaposi’s sarcoma occurred in more than 5 % of organ transplant patients who subsequently developed malignancy [16]. The risk of developing KS is increased 50- to 500-fold in organ transplant patients compared to the normal population
management: showed be through MDT
from nephrology side
1- focused history taking to trace for visceral involvement through system review especially pulmonary and gastrointestinal symptoms review . additionally history of any infectious disease is worthy enough
2- clinical examination of mucous membrane for any lesion . Additionally abdominal exam for any swelling or tenderness
3- work up as deep biopsy ,serology + pcr for hhv 8 and whole body CT scan in case of positive clinical history taking and examination ( visceral involvement)
4- explaining to the patient answering his concerns giving information about the management plan , importance of follow up , and prognosis
5- reducing the CNi; aim trough level of tacrlimus less than 5 ng/ml as 1st step explaining that it could be replaced by mTOR if there is no improvement
6- Oncology involvement and follow up as systemic or local chemotherapy/ radiotherapy is indicated
7- Giving advice regarding the drug interaction with the selected systemic chemotherapy if any and the immunosuppressive regimen
Ref”
1- Esser, S., Schöfer, H., Hoffmann, C., Claßen, J et al . (2022), S1 Guidelines for the Kaposi Sarcoma. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 20: 892-904.
Well done.
The most likely diagnosis is Kaposi sarcoma as the patient on long standing immunosuppression.
Kaposi sarcoma is a cutaneous malignancy of blood or lymphatic endothelial origin, mainly caused by HHV8. It can be presented as single or multiple lesions. For definite diagnosis skin biopsy is mandatory in addition to HHV8 test.
After diagnosis the treatment should include:
Early treatment is important because dissemination is common with subsequent visceral involvement and poor prognosis.
References:
This is most probably a case of Kaposi sarcoma.
Differential diagnosis of the skin lesion:
1. Bacillary angiomatosis
2. squamous cell carcinoma,
3. basal cell carcinoma
4. Angiosarcomas
How do you manage this case?
I need to confirm the diagnosis by Dermatology consultation and skin biopsy.
Grading and search for metastasis and visceral involvement using pan CT OR PET scan
Treatment:
1. Reduction of immunosuppression starting with a decrease of tacrolimus dose targeting trough between 3-5 ng/l.
2. Shift from CNI to sirolimus in stable graft function with proteinuria below 800mg/24h()
3. If no resolution chemotherapy like doxorubicin vinblastine or vincristine (with or without bleomycin).
REFERENCES
1. Fenig E, Brenner B, Rakowsky E, et al. Classic Kaposi sarcoma: experience at Rabin Medical Center in Israel. Am J Clin Oncol 1998; 21:498.
2. Dantal J, Soulillou JP. Immunosuppressive drugs and the risk of cancer after organ transplantation. N Engl J Med 2005; 352:1371.clinical description. Liver Transpl 2001; 7:816.
Thankyou.
This index case is a kidney transplant recipient 14 years ago with excellent graft function, he is maintained on Tacrolimus and MMF.
The picture show multiple brownish maculo-papular skin lesions of different size all over his body.
Differential diagnosis of the skin lesion include non-melanoma skin cancer (NMSC) including Kaposi sarcoma(KS). Other causes include:
· Bacillary angiomatosis
· Acroangiodermatitis
· AV malformation
· Angiosarcoma
· Pyogenic granuloma
· Fibrous histiocytoma
· Interstitial granuloma annulare.
In view of the transplantation history and the immunosuppression received during that time, Kaposi sarcoma is the most probable diagnosis.
Kaposi’s sarcoma (KS) is a rare, malignant, multi-locular vascular disease originating from lymphatic endothelial cells.
It is induced by human herpesvirus-8 (HHV-8)/Kaposi’s sarcoma-associated herpes virus (KSHV).
It can primarily affect the skin and mucous membranes, but also the lymphatic system and internal organs such as the gastrointestinal tract, lungs or liver
Any age may be affected and it is more common in males.
Five subtypes of KS with variable course and prognosis, which occur more frequently in specific populations, are distinguished:
KS occurred in more than 5 % of organ transplant patients who subsequently developed malignancy. The risk of developing KS is increased 50- 500-fold in organ transplant patients compared to the normal population.
It occurs 13 months following transplantation (range few weeks to 18 years).
In kidney transplant recipients, the intensity and duration of immunosuppression, and the presence of HHV8 serology pre-transplantation increase the risk of developing KS.
The skin lesions are typical and make the diagnosis. These are purple-red-bluish lesions presenting as non-painful, non-itchy, macules, papules, plaques or nodules. Due to their vascular etiology, they can ulcerate and bleed.
Lesions usually begin on the lower limbs, with multifocal and asymptomatic development. KS may remain localized to the skin, but dissemination to visceral mucosa of the trachea, lungs and gastrointestinal tract is common in immunosuppressed patients.
Management:
· Multidiscipline approach including the dermatologist, oncologist and the infectious disease..
· Investigations, staging, and management of the various KS subtypes should be individualized based on symptoms, course, and involvement.
· At least one deep biopsy should always be performed to histologically confirm the clinical KS diagnosis before initiating specific therapy.
· All KS patients without known HIV infection should be offered HIV testing at initial KS diagnosis.
– A full medical history, examining the mucous membranes, lymph nodes and the abdomen is required. In suspected visceral involvement, a whole-body computed tomography (CT: thorax, abdomen/pelvis) should be performed. If necessary, esophagogastro-duodenoscopy, colonoscopy, and bronchoscopy may also be performed.
· Patients treated with CNI immunosuppressive therapies (trough level was > 8 despite having the transplant 14 years back, maintain trough between 3-5 ng/l after that time.) are at particularly high risk of developing aggressive KS. Reducing the intensity of immunosuppression or switching immunosuppression to mTOR inhibitors(if no contraindications), such as Sirolimus or Everolimus, are cornerstones of treatment. Regression of KS has been reported after switching from calcineurin inhibitors to Sirolimus by restoring effector and memory T-cell immune activity against HHV-8.aAdditionally, Avoid sun exposure and topical5 fluro-uracil can be also applied.
· Transplant patients with KS who do not respond to a change in immunosuppression, KS is treated similarly to classic KS.
· Systemic chemotherapy should be considered in patients with visceral involvement, extensive lymph node involvement, or progressive muco-cutaneous involvement. pegylated, liposomal Doxorubicin is most commonly used.
· Termination of KS therapy must be determined individually and should consider patient preferences. Follow-up should be based on the individual extent of KS and disease progression rate.
References:
1. Blumenfeld W, et al. “Differential diagnosis of Kaposi’s Sarcoma”. Arch Pathol Lab Med. 1985 (109): 123–127.
2. Wadee R and Grayson W. Cutaneous Kaposi sarcoma and its mimics. Diagnostic Histopathology.2022;28(1) : 38-52.3. Esser S et al. Guidelines for the Kaposi Sarcoma.JDDG.2022;20(6): 892-904.4. Raedemaeker J et al. Kaposi sarcoma after kidney transplantation. . BMJ, Case Rep. 2019;12:e229681.
Thankyou this is an exellent review.
The differentials are,
Kaposi sarcoma,
squamous cell carcinoma,
basal cell carcinoma,
Bacillary angiomatosis, and
Angiosarcomas.
Initially the lesion biopsy to confirm the diagnosis.
To assess for metastasis of the disease.
Serological test for HHV8 DNA quantitative test, if positive treat with antiviral agents.
If metastasize to other organ, look for its secondary consequences.
Reduction of immunosuppression, better to stop MMF.
Switch calcineurin inhibitors to mTOR inhibitors.
If distant spread and not responding to immunosuppression modification than need to start chemotherapy like CHOP regime has very good response.
1.Shepherd FA, Maher E, Cardella C, Cole E, Greig P, Wade JA, et al,Treatment of Kaposi’s sarcoma after solid organ transplantation. J Clin Oncol. 1997;15(6):2371-7.
2.NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Kaposi Sarcoma Version 1.2023-Dec 20,2022.
3.https://www.uptodate.com/contents/prevention-and-management-of-skin-cancer-in-solid-organ-transplant-recipients?search=how%20to%20treat%20kaposi%20sarcoma%20post%20renal%20transplantation&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=3.
I like that you have supported your arguments by uploading scientific evidence.
Ajay
Differential diagnoses include bacillary angiomiomatosis, hemosiderotic angioma, fibrous histeocytoma,interstitial granuloma annulare, arteriovenous malformation and pyogenic granuloma.
Kaposi Sarcoma is cutaneous purplish confluent plaques with no ulceration, bleeding or edema. Its not rarely encountered post kidney transplantation with incidence reached to 5 % in some ethnic groups.
Its principally related to over immune suppression with particular use of calcineurin inhibitors CNi. triggered by the infection with human herpesvirus 8 HH8 virus.
Its an angiogenic proliferative tumor stimulated through vascular endothelium growth factor production. Tumor is non hypermetabolic lesion by positron emission tomography PET. Immunohistochemistry staining revealed HH8 on endothelial cells. It is usually featuring multiple skin lesions which might consequently spread to visceral organs.
Management:
Minimization of immunosuppression is the key in the treatment of Kaposi Sarcoma, involves withholding Mycophenolate mofetil and switching CNi (Tacrolimus and Cyclosporin) to proliferation signal inhibitors PSIs Sirolimus and Everolimus.
In some cases of disseminated Kaposi Sarcoma resistant to switching medications, Pegylated Liposomal doxorubicin PLD might be added.
5 -years survival rate of localized cancer is 81%, regional cancer 63% and spread cancer 40%.
References:
1) Kaposi Sarcoma after kidney transplantation. Juliette Raedemaeker et al. BMJ case reports, volume 12, issue 5.
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Ajay
Diagnosis and Differential diagnosis:
Kaposi Sarcoma
Bacillary angiomatosis
Melanoma
Angiosarcomas
Haemangiomas
Management:
1. Detailed physical examination, examining the whole skin for similar lesions, mucosal surfaces, and lymph nodes.
2. Biopsy of skin lesion.
3. HHV-8 DNA PCR
4. Extracutaneous manifestations:
CBC.
If respiratory symptoms such as cough, dyspnea, hemoptysis, fever then Chest X-ray, CT chest, bronchoscopy.
GIT evaluation: Stool for occult blood, Ultrasound abdomen, Endoscopy.
FNAC for lymph node biopsy in case of lymphadenopathy.
5. Reduction of immunosuppression and monitoring for rejection.
Withdrawal of MMF/AZA, reduction in dose of TAC.
Switch to mTOR inhibitors
Oncology consult.
Chemotherapy
Thankyou.
Kidney transplant recipient presents 14 years later with nodules and papules that are purple to black in colouration and mainly on the trunk. The diagnosis is kaposi sarcoma with differential diagnosis of pyogenic granuloma and bacillary angiomatosis.
How to manage this case starts with history looking for any respiratory or gastrointestinal symptoms since kaposis sarcoma involves the skin and the mucous membrane. Full physical exam including the buccal cavity, rectal exam and palpating for any lymph nodes follows.
Next to confirm the diagnosis via a biopsy of the lesions and findings of spindle cells proliferation will be confirmatory. Further tests to rule out any visceral involvement via complete blood count, a chest X-ray and probable bronchoscopy, and endoscopy or colonoscopy if there and intestinal symptoms. A HIV PCR should also be done to rule out other conditions associated with kaposi sarcoma.
Reduction of the immunosuppression would be the next step since it’s associated with over immunosuppression. If there is no resolution of symptoms then the CNI can be switched to MTOR inhibitor. Other treatment options includes cryotherapy, vinblastine and paclitaxel.
Thank you.
Kaposi Sarcoma
Bacillary angiomatosis
SCC
BCC
Switching of calcineurin inhibitos to sirolimas.
Patients treated with calcineurine inhibitors are at high risk for kaposi sarcoma. Decreasing the intensity or switching immunosuppressive agents to an mTOR inhibitor is the cornerstone of treatment.
Short and precise reply. I wish you could have supported your arguments by uploading scientific evidence with more details.
Ajay
Diagnosis:
Multiple, discrete, oval, round, and few irregular shaped, dark brownish patches, plaques, or nodules on the chest in this immunosuppressed post-transplant patient are highly suggestive of kaposi’s sarcoma.
Differential diagnosis may include:
Diagnostic Algorithm:
Step 1: Physical Examination
Examination of oral cavity, rectum, entire skin and lymph nodes to look for presence of similar or other lesions and lymphadenopathy
Step 2: Confirmation of diagnosis(1)
Step 3: Finding associated HHV 8 antigenemia (seropositivity)
Step 4: Look for extracutaneous manifestations (2).
Kaposi’s sarcoma has been described less frequently in the adrenal glands , pancreas, heart, testis, bone marrow, bones, and skeletal muscles.
IHC confirmation in biopsy slides is necessary for ascertaining the diagnosis.
Treatment algorithm:
Step 1: Reduction of immunosuppression
In this particular case, withdrawal of MMF and reducing tacrolimus dose to half
Step 2: If no or partial response or relapse to above in 4 to 6 weeks
Step 3: If still no response or relapse
Step 4: If still refractory (6)
Associated steps:(6)
Monitoring of response:(1)
References:
It is very well structured. I like that you have supported your arguments by uploading scientific evidence.
Ajay
Thank you,Sir
This transplant patient has macula nodular purple to black rashes, mainly trunkal
These pictures look like Kaposi sarcoma.
Main DD includes:
Melanoma
Angiosarcoma
Pyogenic granuloma
Fibrous histiocytoma
This case needs to be discussed in MDT and he will need to have a skin biopsy first.
need to send PCR for HHV8 and HIV
need full assessment as he may have visceral involvement for that he may need to do US,and CT chest and abdomen
In such case we need to reduce the IS medication and CNI will be shifted to mTOR
will over all reduction in IS medications
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Ajay
Management of this case:
Multiple purple and dark brown nodules and macules on the trunk in the above image are suggestive of Kaposi sarcoma, the likely diagnosis.
Other possible differentials include Melanoma, Pyogenic granuloma, fibrous histiocytoma, Bacillary angiomatosis, and Angiosarcoma.
Approach to this case should start with the confirmation of the diagnosis. Included in the multidisciplinary team should be a dermatologist, oncologist, and transplant specialist. Risk factors for Sarcoma kapoci should be reviewed. After a thorough history and physical examination, a skin biopsy from the lesion will be performed to confirm the diagnosis, followed by polymerase chain reaction (PCR) testing for HHV8 and HIV. For distant metastases, imaging will include X-rays and CT scans of the chest and abdomen, followed by invasive tests such as endoscopy and bronchoscopy.
The initial step will be to minimize immunosuppression before converting from Tacrolimus to sirolimus and monitoring response. Typically, response to the treatment modification happens between three to six months. If initial treatment option failed, other therapeutic options such as chemotherapy and radiotherapy can be considered. Surgical excision in association with cryotherapy may be also effective.
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Ajay
1. The index case has been transplanted 14 years ago and has been on immunosupression therapy for long duration with higher trough level than the target at this duration so over immunosupression mostly precipitated malignancy.
– the cutaneous lesions are dark elevated papules scattered over the chest and the trunk mostly Kaposi sarcoma.
* Differential diagnosis:
Bacillary angiomatosis (bacterial infection treated by antibiotics).Hemosiderotic hemangioma.Fibrous histiocytoma.interstitial granuloma annulare,Arteriovenous malformations,Pyogenic granuloma.Multiple skin melanomas.Management of the case:it needs multidisciplinary team.confirmation of diagnosis by skin biopsy is essential.Detection of viral particles (HSV type 8) in involved lesions.Exclusion of visceral involvement by CT with contrast and mucosal involvement by colonoscopy and bronchoscopy which are essential for management.Treatment mainly depends on minimization of IS therapy and shift from CNI to sirolimus that can cause regression. Of the lesions within 3_6 months.Use of topical 5FU.Systemic chemotherapy as cyclophosphamide and vinblastine are beneficial in case of invasive disease.
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Ajay
The likely diagnosis in the above picture shows multiple purplish ,dark brown nodules and macules on the trunk which are suggestive of Kaposi sarcoma. Other differentials which can be considered include • Melanoma, Pyogenic granuloma , fibrous histiocytoma ,Bacillary angiomatosis and Angiosarcoma.
How do you manage this case? Substantiate your answer
MDT should be involved including dermatologist, oncologist and transplant physician.After taking detailed history and doing physical examination,skin biopsy will be done to confirm the diagnosis followed by PCR for HHV8 and HIV. Imaging including X-ray and CT scan Chest and Abdomen followed by invasive tests like Endoscopy and Bronchoscopy will be done for distant metastasis.
Treatment –First thing will be to reduce the immunosuppression and then switching Tacrolimus to sirolimus and observe for response. Generally response occurs in 3-6 months. If there is no response ,then chemotherapy ( like vincristine , vinblastine, bleomycin, and liposomal doxorubicin )and radiotherapy ,surgical excision with or without cryotherapy can be considered.
REFERENCES:
1- Campistol JM, Racusen L, Polinsky MS, et al. Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial. Transplantation. 2009 Jan 27;87(2):233-42.
2- Delyon J, Rabate C, Euvrard S, et al. Skin Care in Organ Transplant Patients Europe (SCOPE) group. Management of Kaposi sarcoma after solid organ transplantation: A European retrospective study. J Am Acad Dermatol. 2019 Aug;81(2):448-455.
It is very well structured. I like that you have supported your arguments by uploading scientific evidence.
Ajay
1-Kaposi sarcoma
is an antiproliferative disorder that requires infection with the human herpesvirus 8 (HHV-8)iatrogenic type associated with immunosuppression
risk factors age more than 50 and use of cyclosporine
presentation locally or disseminated type such as in this case.
visceral involvement is common and regresses with modification of immunosuppression or may be aggressive
Other differentials include: which caused by Bartonella gram-negative bacillus and treated by antibiotics therapy
1- bacillary angiomatosis
2-angiosarcoma
diagnosis confirm by skin biopsy and PCR and immunohistology for HHV8 confirm the diagnosis.
CT chest, endoscopy, and bronchoscopy to role out mucosal involvement.
treatment of Kaposi sarcoma there are a variety of local and systemic tumor-directed therapy options, the choice of which depends on the extent, location, and place of the disease
indication of systemic therapy:
1- systemic visceral or mucosal involvement
2-diffuse symptomatic lesion on multiple body parts.
3- extensive nodular disease or diffuse involvement of a large part of the extremity
4-bulky disease in a localized area.
5- moderate to severe associated lymphoedema.
chemotherapy such as doxorubicin.
pamidronate is an alternative option to chemotherapy
local disease
surgical, radiotherapy, cryotherapy, laser therapy, and intralesional
Topical therapy: retinoic acid,imiquimod, Timolol, topical silver nitrate, and
rapamycin.
switch the TAC to mTORi
mTOR leads to disease regression
CNI is a risk factor for malignancy and reduction of immunosuppression stop the viral replication.
reference UpToDate
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Ajay
My provisional diagnosis is Kaposi’s sarcoma and differential diagnosis are-
· SCC
· BCC
· Bacillary angiomatosis
· Hemosiderotic hemangioma
· Fibrous histiocytoma
· Interstitial granuloma annulare
Management:
A multidisciplinary approach is needed with nephrologist, dermatologist and oncologist to treat this case .
Most probably this is a case of Kaposi’s sarcoma in kidney transplant recipient and treatment includes-
· Reduction of immunosuppression is the first step
· Switching immunosuppressive therapy to mTOR inhibitors eg. Sirolimus instead of tacrolimus
· Adjuvent chemotherapy or radiotherapy when necessary
Substantiation of answer:
The incidence of Kaposi’s sarcoma in kidney recipient is increased and the majority of patients having skin involvement only. Recurrence is frequent and associated with the increase of immunosuppression with CNI. Kaposi’s sarcoma in kidney transplanted patients are associated with persistent infection with human herpes virus 8.
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Ajay
What is your differential diagnosis?
————————————————–
1-Kaposi sarcoma .
2- Bacillary angiomatosis.
3- Hemosiderotic hemangioma.
4- Fibrous histiocytoma.
5- interstitial granuloma annulare .
6- Arteriovenous malformations .
7- pyogenic granuloma.
How do you manage this case?
————————————————————–
A multidisciplinary approach, with nephrologists, dermatologists and oncologists, is required for the treatment of this case .
Management of Kaposi’s sarcoma in kidney transplant patients includes ;
1-immunosuppression reduction as a first step.
2-Switching immunosuppressive therapy to sirolimus or other mTOR inhibitors is another option.
3- In patients without good response,chemotherapy or radiotherapy are additional options.
Substantiate your answer.
———————————————-
The incidence of Kaposi’s sarcoma in kidney transplanted patients is increased, but in the majority of patients, the disease involves only the skin . The visceral involvement carries a poor prognosis. Recurrence is frequent and associated with the increase of immunosuppression.
The risk factors for development of Kaposi’s sarcoma in kidney transplanted patients includes ;
1-Patients with persistent infections with oncogenic viruses, such as human herpes virus 8.
2- Patients with black skin, even in European series .
Kaposi’s sarcoma is diagnosed by skin biopsy and immunohistochemistry. CT scan and endoscopy to rule out visceral involvement .
Reference;
1-Zavos G, Moris D, Vernadakis S et al.. Incidence and management of Kaposi sarcoma in renal transplant recipients: the Greek experience. Transplant Proc 2014;46:3199–202. 10.1016/j.transproceed.2014.09.165 [PubMed] [CrossRef] [Google Scholar].
2-Lebbé C, Euvrard S, Barrou B et al.. Sirolimus conversion for patients with posttransplant Kaposi’s sarcoma. Am J Transplant 2006;6:2164–8. 10.1111/j.1600-6143.2006.01412.x [PubMed] [CrossRef] [Google Scholar] .
That is a wonderful reply. It is very well structured. I like that you have supported your arguments by uploading scientific evidence.
Ajay
2. A 36-year-old kidney transplant recipient developed this lesion 14 years after his cadaveric transplantation. Currently, he is on Tacrolimus (trough level 8.3 ng/ml) and MMF 500 mg bd. He has excellent kidney function (S Cr is 113 µmol/L).
• What is your differential diagnosis?
– Kaposi sarcoma (KS)
– Bacillary angiomatosis
– Hemosiderotic hemangioma
– Fibrous histiocytoma
– Arteriovenous malformations
– Pyogenic granuloma
– Interstitial granuloma annulare
• How do you manage this case?
– Perform a skin biopsy plus immunohistochemistry to confirm the diagnosis of KS.
– Examine for mucosal involvement and screen for visceral involvement – abdominopelvic and chest CT scans, endoscopy, bronchoscopy
– Sun-protection
– In the early stages of disease – reduction of immunosuppressive therapy to the lowest levels which preserve kidney function and a switch of CNI (Tacrolimus) to mTORi (Everolimus/ Sirolimus) may result in resolution of the disease.
– In extensive disease – liposomal anthracyclines are considered as 1st line therapy.
– Chemotherapy and local radiotherapy – helps improve the lesions
– Remission can be confirmed histologically by doing a repeat biopsy
– Ganciclovir, foscarnet and cidofovir – if HHV seropositive
• Substantiate your answer. (1-3)
– Reduction of immunosuppression enables the immune system reduce viral replication resulting in clinical remission of the disease
– CNIs are associated with increased risk for malignancies.
– mTORi have antitumor effects hence inhibit the progression of KS while providing effective immunosuppression
– mTORi are well tolerated and most patients maintain stable kidney function with no episodes of acute rejection
References
1. Stallone G, Schena A, Infante B, Di Paolo S, Loverre A, Maggio G, et al. Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. The New England journal of medicine. 2005 Mar 31;352(13):1317-23. PubMed PMID: 15800227. Epub 2005/04/01. eng.
2. Campistol JM, Schena FP. Kaposi’s sarcoma in renal transplant recipients–the impact of proliferation signal inhibitors. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association – European Renal Association. 2007 May;22 Suppl 1:i17-22. PubMed PMID: 17456614. Epub 2007/04/26. eng.
3. Raeisi D, Payandeh M, Madani SH, Zare ME, Kansestani AN, Hashemian AH. Kaposi’s Sarcoma after Kidney Transplantation: a 21-Years Experience. International journal of hematology-oncology and stem cell research. 2013;7(4):29-33. PubMed PMID: 24505540. Pubmed Central PMCID: PMC3915423. Epub 2014/02/08. eng.
That is a wonderful reply. It is very well structured. I like that you have supported your arguments by uploading scientific evidence.
Ajay
Thank you Prof.
What is your differential diagnosis?
Diffuse cutaneous brown blotches/ spots most likely kaposi sarcoma
DDx
How do you manage this case?
Dermatology and oncology consult and regular follow up
history and physical examination
Investigation including routine labs CBC,KFT,LFT,….
Diagnosis is supported by pathology and by the presence of HHV-8 DNA sequences in involved tissue
Chest and abdomen CT scan >>> visceral involvement and used for staging
Treatment consists of radiation and chemotherapy.
Conversion from cyclosporine to sirolimus has been shown to be effective treatment for cases of Kaposi sarcoma.
Reference
Orphanet kaposi sarcoma
Uptodate
Handbook of Kidney Transplantation 6 th edition
Short and precise reply. I wish you could have supported your arguments by uploading scientific evidence with more details.
Ajay
1-Differential diagnosis?
Cutaneous Malignancy in Organ Transplant Recipients
Kaposi’s sarcoma
SCC
Basal cell carcinoma (BCC)
Precancerous actinic keratosis
Merkel cell carcinoma (MCC). RARE
primary neuroendocrine carcinoma RARE
VIRAL INFECTION (HIV )+ Kaposi’s sarcoma
DRUG ERUPTION
**Switching from calcineurin inhibitors to sirolimus
**Biopsy of any lesions that persist following medical therapy is recommended.
** For actinic keratosis, cryotherapy or curettage of individual lesions is the treatment of choice.
topical 5-fluorouracil daily or under Unna boot occlusion (chemowrap),diclofenac or imiquimod.Ingenol mebutate (Picato)
Photodynamic therapy with a topical photosensitizer more effective and cosmetically acceptable than 5-fluorouracil cream.
**. Patients with aggressive lesions may require adjuvant radiotherapy or chemotherapy.
**Kaposi’s sarcoma Treatment includes discontinuation of immunosuppressive therapy or changing the treatment regimen to include sirolimus. Imiquimod, interferon alpha and chemotherapy
**primary MCC is surgical excision with sentinel lymph node biopsy followed by adjuvant chemotherapy or radiotherapy.
** All OTRs should be advised to avoid sun exposure, to protect exposed areas with sunscreen or clothing and regularly receive full mucocutaneous skin examinations. If possible, patients should be seen prior to transplantation for identification and management of any pre-existing lesions. Surveillance intervals of OTRs in dermatology clinics should be based on overall risk
REFERENCE
1. Alberu J, Pascoe MD, Campistol JM, et al. Lower malignancy rates in renal allograft recipients converted to sirolimus-based, calcineurin inhibitor-free immunotherapy: 24-month results from the CONVERT trial. Transplantation. 2011;92(3):303-310.
2. Salgo R, Gossmann J, Schöfer H, et al. Switch to a sirolimus-based immunosuppression in long-term renal transplant recipients: reduced rate of (pre-)malignancies and nonmelanoma skin cancer in a prospective, randomized, assessor-blinded, controlled clinical trial. Am J Transplant. 2010;10(6):1385-1393.
3. van den Reek JM, van Lümig PP, Janssen M, et al. Increased incidence of squamous cell carcinoma of the skin after long-term treatment with azathioprine in patients with auto-immune inflammatory rheumatic diseases. J Eur Acad Dermatol Venereol. 2014;28(1):27-33.
4. Campbell SB, Walker R, Tai SS, Jiang Q, Russ GR. Randomized controlled trial of sirolimus for renal transplant recipients at high risk for nonmelanoma skin cancer. Am J Transplant. 2012;12(5):1146-1156.
5. Euvrard S, Morelon E, Rostaing L, et al. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med. 2012;367(4):329-339.
6. Colegio OR, Hanlon A, Olasz EB, Carucci JA. Sirolimus reduces cutaneous squamous cell carcinomas in transplantation recipients. J Clin Oncol. 2013;31(26):3297-3298.
7. Bahner JD, Bordeaux JS. Non-melanoma skin cancers: photodynamic therapy, cryotherapy, 5-fluorouracil, imiquimod, diclofenac, or what? Facts and controversies. Clin Dermatol. 2013;31(6):792-798.
8. Prinz Vavricka BM, Hofbauer GF, Dummer R, French LE, Kempf W. Topical treatment of cutaneous Kaposi sarcoma with imiquimod 5% in renal-transplant recipients: a clinicopathological observation. Clin Exp Dermatol. 2012;37(6):620-625.
– Mostly a case of post renal transplant Kaposi sarcoma
Differential diagnosis
Bacillary angiomatosis,
hemosiderotic hemangioma,
fibrous histiocytoma,
Interstitial granuloma annulare
pyogenic granuloma.
-Management
A multidisciplinary team is needed involving oncologist and dermatologist along with the transplantation team as death risk due to dissemination of malignancy should be weighed against the risk of graft rejection.
For the treatment plan
· The chronic use of immunosuppressive agents is associated with the long-term risk of malignancies as Kaposi’s sarcoma in renal transplant recipients meanwhile no specific medications were significantly associated with KS risk.
Dose reduction or cessation of immunosuppressives is the main treatment of KS in renal transplant patients, therefore switching Tacrolimus to mammalian target of rapamycin inhibitors as Sirolimus and decreasing MMF dose is an option with monitoring of graft function
· local radiotherapy or chemotherapy can improve the lesions .
· If HHV is seropositive, ganciclovir can be given .
· Behavioural education for avoidance of sun exposure and wearing protective clothing and using sun protective creams and utensils will be needed to avoid UV light
Reference
-Ercan Z et al. Kaposi’s sarcoma in the early post-transplant period in a kidney transplant recipient. Nefrologia 2013;33(6 ):751-868
– Raeisi D, Payandeh M, Madani SH, Zare ME, Kansestani AN, Hashemian AH. Kaposi’s Sarcoma after Kidney Transplantation: a 21-Years Experience. Int J Hematol Oncol Stem Cell Res. 2013;7(4):29-33.
Yes, this picture is typical of Kaposi.
Where else would you look for lesions?
Ajay
The lesions can appear on the legs, feet or face ,genital area, mouth or lymph nodes. In severe Kaposi’s sarcoma, lesions may develop in the digestive tract and lungs.
Transplant associated KS.
RISKS;
Male.
High tac levels 14 yrs post transplant.
DDX;
Bacillary angiomatosis.
Hemangioma.
Purpura.
Pyogenic granuloma
Dermatofibroma
Hematoma.
2.MANAGEMENT;
a. Multi displinary approach – Dermatologist, Oncologist, and Nephrologist
b, Make a diagnosis;
c. Supportive – Sun protection.
– Definitive – Modify immunosuppresion;
-In consultation with an oncologist – Initiate chemo -Liposomal doxorubicin,/daunorubicin, Radiotherapy
4.Ganciclovir if HHV8 + VE
SUBSTANTIATE ANSWER;
REFERENCES;
1.Prof Halawa Lecture.
2.Schwartz et al.Kaposi Sarcoma ;An update j.Surg,ONC 2004,Sep 1;87(3) 146-51
3.Berman et al ;Skin cancer in solid transplant organ recipients ;A review for non dermatologists ; Mayo clin pro.2022 DEC 9970;12;2355-2368
4.Hand book pf kidney transplants 6th edition.
5.Francesco P et al ;Conversion from Cacineurin Inhibitors to Sirolimus Maintanance therapy in renal allograft recipients ;24 month efficacy and Safety results from CONVERT Trial.Transplantation.2009 jan 27;87(2);233-42
Yes, this picture is typical of Kaposi.
Where else would you look for lesions?
Ajay
Mucous membranes – Palate, conjunctiva, gingiva.
Lymph nodes – may present with lymphadenopathy
Resp system- might present with pleural effusion or show non specific findings on imaging- interstitial infiltrates, hilar lymphadenopathy or pulmonary nodules.
GI tract -Lesions might be found on endoscopy.
Skin cancer (kaposi sarcoma)
Spindle cell sarcasms
skin melonoma
Patient need serology test for HIV and HHV-8 and HPV DNA test
Skin biopsy
chest X ray to role out lung lesions and upper, lower endoscopy to role out digestive kapsi sarcoma
Evaluation by dermatologist and Oncologist.
treated by pegylated liposomal doxorubicin (PLD), cessation or reduce dose of MMF and a switch from tacrolimus to sirolimus
recipient with Transplant kidney are more exposure to skin cancer and should be counseling patients regarding risk of calcinurine inhibitors for developing skin cancer and many studies shows role of mTOR inhibitors (sirolimus) in treatment of skin cancer in transplanted kidney and sunscreen for skin protection.
Reference:
Jessica Katz, Edwin Choy,et.al; Kaposi Sarcoma: medscape Updated: Feb 15, 2022
Short and precise reply.
Ajay
What is your differential diagnosis?
Kaposi’s sarcoma is my main diagnosis. Disseminated erythematous brownish lesions with skin impregnation (there may also be visceral).
Would perform a biopsy for differential diagnosis of other cutaneous and lymphoproliferative neoplasms
How do you manage this case?
I would suspend the calcineurin inhibitor (tacrolimus) by sirolimus if there is no contraindication to this drug. Sun protection is necessary!
Reducing MMF must be discussed. Since the patient does not show signs of rejection or changes in renal function, the dose of MMF would be reduced (HSV 8 reactivation)
Substantiate your answer.
Patients using calcineurin inhibitors are at increased risk for neoplasms, especially in the first five years. Kaposi’s sarcoma increases the risk by more than 17 times when compared to the general population, probably by two mechanisms, the first being the decrease in interferon activity induced by this drug and the decrease in viral response increases the risk of reactivation of the latent virus, in this case, Herpes Virus 8.
mTor inhibitors act through another axis without interfering with interferon activity, keeping this immune response intact. Additionally, these agents have an associated antineoplastic effect, including being able to treat Kaposi’s sarcoma directly.
That is a wonderful reply. It is very well structured. However, I wish you could have supported your arguments by uploading scientific evidence.
Ajay
The index patient is a 36-year-old male kidney transplant recipient (cadaveric donor – 14 years back), with excellent graft function, and is on Tacrolimus and MMF.
He presents with multiple brownish-black maculopapular lesions of varying size over his body.
The differential diagnosis with such skin lesions would include non melanoma skin cancer (NMSC) – Kaposi Sarcoma, peripheral vascular disease, infections like bacillary angiomatosis, blue rubber bleb nevus syndrome, pyogenic granuloma (lobular capillary hemangioma), tufted angioma, melanocytic nevi, melanoma, cavernous hemangioma, angiokeratoma, Stewart–Treves syndrome, carcinoma cutis (especially renal cell carcinoma), nodal myofibromatoma, spindle cell hemangioendothelioma, arteriovenous malformations, and severe statis dermatitis (1).
The most probable diagnosis in view of the clinical picture (14 year of kidney transplant, male patient, on Tacrolimus with trough levels of 8.3, and typical skin lesions) is non melanoma skin cancer (NMSC) – Kaposi Sarcoma (2,3).
Kaposi Sarcoma, a vascular tumor, caused by human herpes vius-8 (HHV-8) is 100 times more common in transplant recipients than in the general population, with increased risk in those on calcineurin inhibitors (2). The lesions are usually seen on distal extremities, especially lower limbs, but can be extensively spread over whole body.
The patient should be evaluated by a dermatologist. Complete clinical examination, including mucosal examination and ultrasound abdomen should be done (to assess the extent of lesions – for visceral involvement).
The management includes confirmation of diagnosis by a biopsy from the lesion (1). The biopsy will reveal endothelial fusiform cells and neovessel formation (4). Immunohistochemical staining may show HHV-8 on endothelial cells (4).
The treatment includes (1,5):
1) Re-enforcement of behavioural interventions for sun-protection.
2) Reduction of immunosuppression: The tacrolimus trough level in the patient is 8.3 ng/ml, which is high and should be reduced to 4-5 ng/ml.
3) Switching of immunosuppression from Tacrolimus to mTOR inhibitors (Sirolimus):
The cornerstone to manage such patient is diagnosing the lesion by a biopsy, and then treatment by switching the immunosuppression from Tacrolimus to Sirolimus. Multidisciplinary approach with involvement of dermatologist and oncologist is essential.
Alteration in immunosuppression has been shown to be associated with regression of the lesions (6). If the lesions do not respond, then treatment would involve use of chemotherapeutic agents like liposomal pegylated doxorubicin, immune response modifier imiquimod, or radiotherapy, in case chemotherapeutic agents are contraindicated (3,7).
References:
1. Schwartz RA. Kaposi’s sarcoma: an update. J Surg Oncol. 2004 Sep 1;87(3):146-51. doi: 10.1002/jso.20090. PMID: 15334644.
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. doi: 10.2215/CJN.14570920. Epub 2021 Mar 29. PMID: 33782034; PMCID: PMC8975024.
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.
4. Raedemaeker J, Marot L, Camboni A, Kanaan N. Kaposi sarcoma after kidney transplantation. BMJ Case Rep. 2019 May 5;12(5):e229681. doi: 10.1136/bcr-2019-229681. PMID: 31061183; PMCID: PMC6506100.
5. Sunil M, Reid E, Lechowicz MJ. Update on HHV-8-Associated Malignancies. Curr Infect Dis Rep. 2010 Mar;12(2):147-54. doi: 10.1007/s11908-010-0092-5. Epub 2010 Mar 26. PMID: 20461118; PMCID: PMC2860558.
6. Delyon J, Rabate C, Euvrard S, Harwood CA, Proby C, Güleç AT, Seçkin D, Del Marmol V, Bouwes-Bavinck JN, Ferrándiz-Pulido C, Ocampo MA, Barete S, Legendre C, Francès C, Porcher R, Lebbe C; Skin Care in Organ Transplant Patients Europe (SCOPE) group. Management of Kaposi sarcoma after solid organ transplantation: A European retrospective study. J Am Acad Dermatol. 2019 Aug;81(2):448-455. doi: 10.1016/j.jaad.2019.03.028. Epub 2019 Mar 19. PMID: 30902727.
7. Di Lorenzo G. Update on classic Kaposi sarcoma therapy: new look at an old disease. Crit Rev Oncol Hematol. 2008 Dec;68(3):242-9. doi: 10.1016/j.critrevonc.2008.06.007. Epub 2008 Jul 25. PMID: 18657433.
That is a wonderful reply. It is very well structured. I like that you have supported your arguments by uploading scientific evidence.
Ajay
1- Most probably Kaposi sarcoma:
hyper-pigmented macules and nodules (purple and dark red)
in a renal transplant patients with longstanding immunosuppression
2- Melanoma
3- Angiosarcoma
4- bacillary angiomatosis
5- hemosideric hemangioma
6- fibrous histocytoma
7-pyogenic granuloma
diagnosis is confirmed by biopsy
1- modification of the immunosuppression:
2- radiotherapy as being multiple lesions
3- chemotherapy
3- antiviral treatment (gancyclovir) if seropositive for human herps virus 8
Yes, this picture is typical of Kaposi.
Where else would you look for lesions?
We expect you to provide evidence to support your arguments.
Ajay
Lebbé C, Legendre C, Francès C. Kaposi sarcoma in transplantation. Transplantation Reviews. 2008 Oct 1;22(4):252-61.
Differential diagnosis:
· Kaposi sarcoma
· Bacillary angiomatosis
· Hemosiderotic hemangioma
· Fibrous histiocytoma
· Pyogenic granuloma
.
The skin is the common site for post transplant malignancy accounting 40%.
This patient has multiple hyper pigmented cutaneous nodules diagnosis as case of Kaposi sarcoma .
Kaposi sarcoma is a disease of the endothelial cell of blood vessels and lymphatic system .
KS is a common long term complication post kidney transplant .
Treatment :
Ø MODIFIED IMMUNOSUPRSSANT MEDICATION
1.Start PSI (Proliferation Signal Inhibitor ) sirolimus
2-Stop CNI (Calcinuerin inhibitor )
3- Minimized AZAl MMF Maintain steroid
4-Monitor disease if no response high dose of PSI
Ø Radiotherapy
Ø Chemotherapy .
Ø Ganciclovir in case of HHV seropositive .
References :
handbook of kidney transplant 6th edition
Yes, this picture is typical of Kaposi.
Where else would you look for lesions?
We expect you to provide evidence to support your arguments.
Ajay
The picture showed multiple skin lesions involving the trunk ; the lesions looked purplish, reddish blue, or dark brown macules and nodules on the skin.
In the setting of kidney transplantation and long term exposure to immunosuppressive therapy (14 years, high level of Tac ) skin cancer should be suspected. The lesions are typical for extensive cutaneous Kaposi Sarcoma.
-KS is an angio-proliferative cutaneous cancer caused by HHV 8
-The incidence is higher in transplant patients, the SIR is 17 in transplant population
-Generally, occurred 13 months after transplantation (range few weeks to 18 years)
-Dissemination to visceral mucosa of the trachea, lungs and gastrointestinal tract is common in immunosuppressed patient, develops in 25 to 30 percent of renal transplant recipients and 50 percent of heart or liver transplant recipients
-Mucosal dissemination or visceral involvement has usually a poor prognosis
Risk factors:
· The intensity and duration of immunosuppression,
· The presence of HHV8
· Male
· Non-White patients; Mediterranean origin Jewish, Arabic, Caribbean, or African descent parallels HHV-8 seroprevalence
· lung transplant recipients were at increased risk of KS.
· HIV
Differential diagnosis:
· Bacillary angiomatosis
· Angiosarcoma.
· Melanoma.
· Fibrous histiocytoma
· interstitial granuloma annular
How do you manage this case?
· Dermatology opinion
· Skin biopsy to confirm the diagnosis.
· Send for HHV8 and HIV
· Screen for dissemination and visceral involvement CT, endoscopy, bronchoscopy.
· Reduce immunosuppression level which is likely to result in partial or complete regression of the lesions
· If no response to switch from Tacrolimus to Sirolimus based IS.
-Several studies showed remission of the lesions after conversion from CNI to Sirolimus.
-CONVERT trial evaluated the efficacy and safety of converting maintenance renal transplant recipients from CNIs to sirolimus (SRL).
-The result of the study showed at 2 years, SRL conversion was associated with excellent patient and graft survival, no difference in biopsy confirmed acute rejection, increased urinary protein excretion, and a lower incidence of malignancy compared with CNI continuation.
Superior renal function was observed among patients who remained on SRL through 12 to 24 months, particularly in the subgroup of patients with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11.
· Oncologist opinion in case of persistent lesion or life threatening disease for chemotherapy (vincristine
or vinblastine, bleomycin, and doxorubicin (singly or in various combinations)
· Radiation oncologist involvement; Radiotherapy
· Isolated lesions can be excised surgically or treated with cryotherapy.
· The clinical usefulness of antiviral drugs (foscarnet, ganciclovir, cidofovir, and adefovir) that have in vitro activity against HHV-8 has not yet been adequately documented.
Substantiate your answer.
· Collet et al AJT 2010; 10: 1889–1896
· Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med. 2003 Apr 24;348(17):1681-91. doi: 10.1056/NEJMra022137. PMID: 12711744.
· Raedemaeker J, Marot L, Camboni A, et al Kaposi sarcoma after kidney transplantation BMJ Case Reports CP 2019;12:e229681
· Zmonarski SC, Boratyńska M, Rabczyński J, Kazimierczak K, Klinger M. Regression of Kaposi’s sarcoma in renal graft recipients after conversion to sirolimus treatment. Transplant Proc. 2005 Mar;37(2):964-6. doi: 10.1016/j.transproceed.2004.12.172. PMID: 15848592.
· Schena FP, Pascoe MD, Alberu J, del Carmen Rial M, Oberbauer R, Brennan DC, Campistol JM, Racusen L, Polinsky MS, Goldberg-Alberts R, Li H, Scarola J, Neylan JF; Sirolimus CONVERT Trial Study Group. Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial. Transplantation. 2009 Jan 27;87(2):233-42. doi: 10.1097/TP.0b013e3181927a41. PMID: 19155978.
That is an excellent reply: well debated and well supported by evidence.
It can affect skin, buccal cavity or internal organs. Immunosuppression allows the HHV-8 virus to multiply to high levels in the blood, increasing the chance of it causing Kaposi’s sarcoma.
Differential diagnosis: Kaposi sarcoma diagnosis can be proved easily with skin biopsy.
The incidence of Kaposi sarcoma in recipients of transplants exceeds 100 times that of the general population.
There are 4 main types of Kaposi’s sarcoma, and each type is treated in a different way:
1-HIV-related Kaposi’s sarcoma and can be treated with use of antiretroviral therapy.
2-Classic Kaposi’s sarcoma: It affects people with a genetic vulnerability to the HHV-8 virus. It’s most common in older men with a Mediterranean or Jewish background.
3-Transplant Kaposi’s sarcoma
4-Endemic or African Kaposi’s sarcoma.
How do you manage this case?
Patients treated with CNIs are at high risk for Kaposi sarcoma. Decreasing the intensity or switching immunosuppressive agents to an mTOR inhibitor is the cornerstone of treatment. In the current scenario with stable renal graft function we can switch to mTOR inhibitors provided that ,there is no significant proteinuria. Regression of Kaposi sarcoma has been reported after switching from calcineurin inhibitors to sirolimus by restoring effector and memory T-cell immune activity against human herpesvirus 8
References:
Sunil M, Reid E, Lechowicz MJ: Update on HHV-8-associated malignancies. Curr Infect Dis Rep 12: 147–154, 2010
Yes, this picture is typical of Kaposi.
Where else would you look for lesions?
Ajay
Buccal cavity and may be in internal organ,lungs,gut
1- other skin malignancies like BCC and SCC ,melanoma
2-Interstitial granuloma granulare
3-AV malformations
4- fibrous histiocytoma
Risk factors:
1-white patients
2- Duration of immunosuppressive therapy
3- Sun exposure
4- ethnicity and geographic location e.g Australian
5- HHV virus 8
Management :
Diagnosis : biopsy
exclude systemic affection
Treatment:
switch tacrolimus tos sirolimus as according to CONVERT trial switching from CNI to sirolimus has less incidence of malignancy
and as per the TUMORAPA study patients who developed skin cancer who received sirolimus instead of CNI has 44% reduction in recurrence
Yes, this picture is typical of Kaposi.
Where else would you look for lesions?
We expect you to provide evidence to support your arguments.
Ajay
What is your differential diagnosis?
There are nodular lesions which are hyperpigmented and distributed on trunk in the current picture. As the patient is on immune suppression , I suspect it is Kaposi Sarcoma.
The differential diagnosis include:
· Bacillary angiomatosis
· Hemosiderotic hemangioma
· Fibrous histiocytoma
· Interstitial granuloma annulare
· Arteriovenous malformations
· Pyogenic granuloma.
How do you manage this case?
A skin biopsy can confirm the diagnosis
Presence of HHV virus-8
Assessment should be done to rule out systemic involvement by Kaposi sarcoma.
It is important to rule out underlying HIV infection. Assessment should be done after consent
Management
A dermatology consultation should be sought
Modification of immune suppression. e.g Converting Tacrolimus to Sirolimus.
Oncology review and consideration of chemo radiotherapy.
Avoid mid day sun exposure
Topical 5 FU
Self examination and regular follow up.
References
Hand book of kidney transplant 6th edition
Lecture by Prof Halawa on malignancies post renal transplant
Campistol JM, Schena FP. Kaposi’s sarcoma in renal transplant recipients–the impact of proliferation signal inhibitors. Nephrol Dial Transplant. 2007 May;22 Suppl 1:i17-22.
Yes, this picture is typical of Kaposi.
Where else would you look for lesions?
Ajay
Dear Prof, Apart from skin i will look into oral cavity as oral mucosa can be involved
A 36-year-old kidney transplant recipient developed this lesion 14 years after his cadaveric transplantation. Currently, he is on Tacrolimus (trough level 8.3 ng/ml) and MMF 500 mg bd. He has excellent kidney function (S Cr is 113 µmol/L).
What is your differential diagnosis?
Skin lesion looks as purplish, reddish or dark brown macules, it is mainly extensive form of cutaneous Kaposi sarcoma (iatrogenic type) and due to immunosuppression in post kidney transplant.
Screening for HHV8 .
We should exclude any systematic affection by Kaposi lesion.
Gold standard for diagnosis is skin biopsy.
Differential diagnosis:
-Bacillary angiomatosis.
-Angiosarcoma.
-Benign vascular lesions, such as hemangiomas.
How do you manage this case?
-Dermatological consultation.
-The most important point in treatment is modulation of immunosuppressive therapy as shifting CNI to mTORis, here we will shift tacrolimus to sirolimus .
-Oncologist consultation (chemotherapy specially with extensive form).
-Radiotherapy ad other local strategies.
References:
1-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.
2-Johari Y, Nicholson ML. Complete resolution of oral Kaposi’s sarcoma achieved by changing immunosuppression: a case report. Ann R Coll Surg Engl. 2010;92(5):W45-W46. doi:10.1308/147870810X12699662980475.
3-Pranteda G, Feliziani G, Grimaldi M, et al. Sirolimus and regression of Kaposi’s sarcoma in immunosuppressed transplant patient. J Eur Acad Dermatol Venereol. 2008;22(8):1022-1023. doi:10.1111/j.1468-3083.2007.02536.x.
4-Campistol JM, Schena FP. Kaposi’s sarcoma in renal transplant recipients–the impact of proliferation signal inhibitors. Nephrol Dial Transplant. 2007;22 Suppl 1:i17-i22. doi:10.1093/ndt/gfm089.
Yes, this picture is typical of Kaposi.
Where else would you look for lesions?
Ajay
We should exclude any systematic Kaposi sarcoma (internal organ Kaposi such as GIT, Respiratory system).
1.Modification of the immune-suppression by converting tacrolimus to mTORi e.g.
sirolimus
2.Radiotherapy
3.Chemotherapy
References
Yes, this picture is typical of Kaposi.
Where else would you look for lesions?
Ajay
Yes, prof as mentioned above; There is a possibility of disseminated disease and therefore through examination is needed to exclude visceral involvement such as a lung, GIT, other mucus membranes.
Kidney recipient with long-term use of immunosuppressive agents (14 Y )
has multiple raised red patches and
purplish spots affect the upper part of the body mostly consist with skin cancer ( KS )
We have to screen patient for underlying cause as infection with ( human herpesviru 8 or HIV) .
Treatment :
▪︎Reduction of immunosuppression ( our patient has high trough level tacrolimus )
▪︎Switching to a different immunosuppressive as MTORs
▪︎Lesions improved when patients received additional local radiotherapy or chemotherapy.
▪︎In the patients with HHV seropositive, ganciclovir were prescribed.
Hi Dr Huda,
Yes, this picture is typical of Kaposi.
Where else would you look for lesions?
Ajay
Thank you prof Ajay
KS presents as single or multiple lesions on mucosal surfaces, including the skin, lungs, gastrointestinal tract and lymphoid tissues
Dear All
I’m not impressed with most of the answers. I wished to see a clear diagnosis for a typical picture of a well-known condition affecting immunosuppressed patients.
cutaneous Kaposi sarcoma is the most likely diagnosis in this scenario considering the typical multiple skin lesions with some nodules and plagues with a typical history of long duration and intensity of CNI exposure (13 years )as he was on tacrolimus-based IS with a higher trough level for the period of TX, skin malignancy one of the common malignancies after transplantation up to 40%, many risk factors associated with increased risk of skin cancer including white race, male sex, sun exposure, some oncologic viral infection like HPV, type of IS like CNI, Azathioprine exposure time and intensity, history of previous skin lesions need to be addressed., examination for lymph nodes involvements.
Kaposi sarcoma is rare skin cancer in the general population but after solid organ transplant including kidney transplantation is 100 times high rate due to Cyclosporine, and tacrolimus use and is more found in central Europe, Africa, and the Mediterranean region(3), however, the main treatment is to stop tacrolimus and shifted to m TOR inhibitors like everolimus or sirolimus, screen for HPV infection and the key managing and inhibition of such tumors by given proper education and awareness about the risk factors for skin cancers before the transplant like avoid sun exposure, use of sunblock, self-examination, and regular follow-up, any suspicious skin lesions should be referred to a dermatologist for formal skin biopsy, especially in such multiple skin lesions and screen for HPV infection, HIV viral screen, also skin M-mode high-resolution US and doppler can help in the diagnosis of cutaneous Kaposi sarcoma with the typical characteristic structural and vascular lesion (2).
the best treatment option is to stop CNI and shift to M tor inhibitors which can help in regression of the pre-existing skin lesions (1,3).
References
1. handbook of kidney transplant 6th edition
2. Carrascosa R, Alfageme F, Roustán G, Suarez MD. Skin Ultrasound in Kaposi Sarcoma. Actas Dermosifiliogr. 2016 May;107(4):e19-22.
3.De Novo Malignancies after Kidney Transplantation David Al-Adra,1 Talal Al-Qaoud,1 Kevin Fowler , and Germaine Wong3,4,
Yes, this picture is typical of Kaposi.
Where else would you look for lesions?
Ajay
we should look for visceral involvement
The most likley diagnosis is a kaposi sarcoma due to HIV infection in immunocompromised patient .
The lesions in this patient consist with kaposi sarcoma.
There are 4 type of kaposi sarcoma:
1-Calssic .
2-Endemic .
3-HIV related .
4-Iatrogenic .
Clinically, non-AIDS KS mostly presents itself as multiple bilateral cutaneous lesions of the lower limb.
Unlike KS in AIDS patients, non-AIDS associated KS is a rather localized process which rarely involves lymph nodes or organs.
It is mostly seen in elderly males from Mediterranean or Eastern European countries and in most cases responsive on local or systemic therapeutic strategies.
So based on that i think this an HIV related Kaposi sarcoma .
Othe Differential diagnosis :
For defenetive diagnosis,a skin biobsy should be done .
Histological picture shows networks of spindle shaped cells and vascular spaces surrounded by an endothelial cell layer.
DNA for HH8.
Test for HIV infection .
If HIV come positive then treat with anti retroviral therapy .
If not then the treatment are the following :
1- Decrease sun exposure: mid- day and use of sun protection more than 50% .
2-Topical 5 flu.
3_ Switch to MTOR sirolimos approch.
4-Surgical .
5-oncologic consultantation .
Refference:
1-Iscovich J, Boffetta P, Franceschi S, Azizi E, Sarid R. Classic kaposi sarcoma: epidemiology and risk factors. Cancer. 2000;88:500–517. [PubMed] [Google Scholar].
2-Sehgal SN. Sirolimus: its discovery, biological properties, and mechanism of action. Transplant Proc. 2003;35:7S–14S. [PubMed] [Google Scholar].
Yes, this picture is typical of Kaposi.
Where else would you look for lesions?
Ajay
What is your differential diagnosis?
Brownish raised lesions all over the body of variable sizes in a kidney transplant recipient 13 yrs ago, the DDx :
Infectious causes- HIV , disseminated herpes, bacillary angiomatosis.
Malignancies- Lymphoma, Kaposi sarcoma, melanoma, unlikely basal cell, or squamous cell carcinoma.
How do you manage this case?
First I would ask for CBC, ESR, LDH , full chemistry and a blood film, then consult both dermatologist and oncologist and will review his viral serology in the medical chart, and do a thorough clinical examination including mucous membranes, and organomegaly.
Then will do a skin biopsy-
Lymphoma can present with such an angioprolifreative skin lesions (B-cell lymphoma-sezary syndrome) can be caused by EBV.( the most likely diagnosis >36 months post transplant).
Melanoma
Kaposi sarcoma as it is cutaneous angioproliferative lesions caused by HSV-8, rarely disseminated usually occurs in the first two years post transplant
Will discuss the screening for metastatic disease by oncologist.
After getting the diagnosis the first thing to do is to stop CNI and MMF, consider starting on m-TOR inhibitors to control the disease, and I insist the patient to follow the oncologist work up and management.
Substantiate your answer.(references):
– 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.
– Stenz NA, Stampf S, Arnold AW, Cozzio A, Dickenmann M, Gaide O, Harms M, Hunger RE, Laffitte E, Mühlstädt M, Nägeli M, Hofbauer GFL; and the Swiss Transplant Cohort Study. Skin Cancer Development in Solid Organ Transplant Recipients in Switzerland (Swiss Transplant Cohort Study). Dermatology. 2021;237(6):970-980. doi: 10.1159/000510685. Epub 2020 Nov 23. PMID: 33227788; PMCID: PMC8619732.
Dr Hasan,
I like you reply. It would be good to type headings or questions (as headings) in italics or bold.
Ajay
Differential diagnosis:
Managment;
7 .Topical cream;
i. 5-florouracil, topical chemotherapy.
ii. Imiquimod, topical immunomodulator.
iii. Retinoids.
iv, Diclofenac cream,anti-inflammatoryy.
8 .Photodynamic therapy
9 .Curettage and Electrodiscection
10 .Surgical excision.
11.Mohs micrographicc surgery.
12.Immunosuppressant modulation.
13.Sirolimus treatment as part of immunosuppressant protocol.
References:
Werner Kempf 1, Kirsten D Mertz, Günther F L Hofbauer, Marianne Tinguely
2.Yanik EL, Clarke CA, Snyder JJ, et al. Variation in cancer incidence among patients with esrd during kidney function and nonfunction intervals. J Am Soc Nephrol 2016;27:1495.
3.Trappe R, Oertel S, Leblond V, et al. Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell posttransplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial. Lancet Oncol 2012;13:196.
Hi Dr Kamal,
I like your differential diagnoses (DD) but the above is not enough? Can you write the text of your thought process and approach.
What is the most likely diagnosis among all those DDs?
SCC does not look like what is shown in this picture.
AJay
The top differential is, Non-melanoma skin cancer , followed by basal and squamous cell carcinoma according to the studies
Such a multitude of simultaneous lesions would not be a feature of SCC and BCC. This picture is typical of Kaposi.
Where else would you look for lesions?
Ajay
History :
====================================================================
What is your differential diagnosis?
Differential diagnosis
1- Topic 5 FU
2- Reduction of immunosuppression
3- Consider Sirolimus.
4- avoid sun.
====================================================================
Reference:-
1. Einollahi B, Noorbala MM, Lessan Pezeshki M, et al. Incidence of post renal transplantation malignancies: a report of two centers in Tehran, Iran. Transplant Proc. 2001;33:2812
2.Tan HH, Goh CL. Viral infections affecting the skin in organ transplant recipients: epidemiology and current management strategies. Am J Clin Dermatol. 2006;7:13–29
3-Management of Kaposi sarcoma after solid organ
transplantation: A European retrospective study 2021
4- Chang Y, Cesarman E, Pessin MS, Lee F, Culpeper J, Knowles DM. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 1994;266:1865-9.
Many thanks for a good reply, Dr Wadi.
Ajay
Thank you verey much Prof.Sharma
Please continue with your contribution for everyone’s learning, dear dr Wadi.
Sincerely, Prof Sharma
Multiple skin lesions distributed over the chest and abdomen, brownish-violet, raised, and irregular pattern. The lesion looks like skin cancer due to the cumulative effects of immunosuppressants. Most likely Kaposi sarcoma (confirmation requires a biopsy and the presence of HHV-8 DNA in the involved tissue). HHV-8 is associated with Kaposi sarcoma, which occurs a median of 30 months after transplantation.
The differential diagnosis may include bacillary angiomatosis, hemosiderotic hemangioma, fibrous histiocytoma, interstitial granuloma annulare, and pyogenic granuloma.
-Shifting the patient from CNI to sirolimus
-Radiation and chemotherapy in resistant cases
Several retrospective and prospective studies have shown that switching from calcineurin inhibitors like cyclosporine and tacrolimus to a mTOR inhibitor like sirolimus is helpful. Even though we don’t fully understand how it works, sirolimus is thought to kill KS tumor cells directly by stopping vascular endothelial growth factor, Flk-1/KDR, and phosphorylated Akt, all of which are often overactive in Kaposi sarcoma. As with other types of KS, chemotherapy is usually only used for limited disease that doesn’t respond to local treatment or for patients with a disease that has spread to other parts of the body.
Reference :
I wish you could consider other differentials.
Differential diagnosis are.
Extensive Kaposi sarcoma, granuloma interstial or pyogenic, histocytoma, drug eruption reaction, autoimmune dermatitis, allergic eczema, post chicken pox scar.
Treatment. Reduce immunosuppression, switch CNIs to mTOR.
Anti-viral therapy if viral serology positive.
Avoid sun exposure, need to use silk or cotton cloths, use of sun protection cream of lotion with maximum SPF.
Expert reviewer(s): Pr Nicolas DUPIN – Last update: May 2019
I wish you could support your arguments with evidence.
Differential diagnosis;
Kaposi sarcoma
Pyogenic infection
Angiosarcoma
drug eruption
How do you manage this case?
Hi Dr Ullah,
I like you differential diagnoses (DD) but the above list is not enough? Can you write text of your thought process and approach.
What is the most likely diagnosis among all those DDs?
Pyogenic granuloma does not look like this.
I wish you could support your arguments with evidence.
Ajay
My differential diagnosis?
Extensive cutaneous Kaposi sarcoma is the Main D.D w Hi incidence post kidney tx. 13 to 21 Months
the other DD Drug Eruption , Pyogenic Infection , Dermato-fibroma , cutaneous angiosarcoma , ……
Managment :
C. Lebbé , et al AJT, 2006.
Dantal J, N Engl J Med 2005
Jessica K, 2022
I like your diagnosis. However, more details of your thought process would be better to write in this reply.
This is a case of disseminated non melanoma skin cancer most probably Kaposi sarcoma
Kaposi sarcoma is a common complication of renal transplantation related to immunosuppression, males are commonly affected than females (male to female ration 3:1), the median age at presentation is 43 years (1,2) , commonly presented 1-3 years after transplantation, usually in the areas of distribution of HHV-8 including those from mediterranean, Arabic, African, Jewish and Caribbean descent [3].
How do you manage this case? Substantiate your answer.
A- Dermatology consultation, and biopsy from the lesion is mandatory for confirmation of the diagnosis
B- Searching for visceral affection is important
C- Treatment
REFERANCES
1. Iscovich J, Boffetta P, Winkelmann R, et al. Classic Kaposi’s sarcoma in Jews living in Israel, 1961-1989: a population-based incidence study. AIDS 1998; 12:2067.
2. Fenig E, Brenner B, Rakowsky E, et al. Classic Kaposi sarcoma: experience at Rabin Medical Center in Israel. Am J Clin Oncol 1998; 21:498.
3. Moosa MR. Racial and ethnic variations in incidence and pattern of malignancies after kidney transplantation. Medicine (Baltimore) 2005; 84:12.
4. Aseni P, Vertemati M, Minola E, et al. Kaposi’s sarcoma in liver transplant recipients: morphological and c Francès C. Kaposi’s sarcoma after renal transplantation. Nephrol Dial Transplant 1998; 13:2768.
5. Dantal J, Soulillou JP. Immunosuppressive drugs and the risk of cancer after organ transplantation. N Engl J Med 2005; 352:1371.linical description. Liver Transpl 2001; 7:816.
excellent
Kaposi sarcoma.
Bacillary angiomatosis .
Pyogenic granuloma..
Dermatofibroma.
Cutaneous angiosarcoma.
Melanoma.
post-transplantation Kaposi sarcoma commonly responds to reduction or discontinuation
of immunosuppression.
switching from calcineurin inhibitors (eg, cyclosporine, tacrolimus) to a mammalian target
of rapamycin (mTOR) inhibitor, specifically sirolimus (1)
Chemotherapy is usually required in cases of extensive or symptomatic visceral KS..
References:
2-C. Lebbé, S. Euvrard, B. Barrou, C. Pouteil-Noble, J. L. Garnier, D. Glotz, C.
Legendre, C. Francès. Sirolimus Conversion for Patients with Posttransplant Kaposi’s
Sarcoma. American Journal of transplant.19 June 2006.
I agree, Dr Sobair.
1- this picture of kaposi sarcoma can be differentiated from the following:
1- bacillary angiomatosis
2-hemosiderotic hemangioma
3- fibrous histiocytoma
4- interstitial granuloma annulare
5-arteriovenous malformations
6-pyogenic granuloma
2- management of kaposi sarcoma
Jessica Katz. Kaposi Sarcoma Differential Diagnoses. Medscape. 2022.
Hi Dr Riham,
I like your diagnosis. However, more details of your thought process would be better to write in this reply.
What is your differential diagnosis?
· Kaposi sarcoma.
· multiple melanomas.
· fixed drug eruption due to possible recent drug exposure.
How do you manage this case?
· checking PCR for HHV-8
· changing Tacrolimus to sirolimus.
· Dermatologist opinion for possible skin biopsy for a definite diagnosis.
· Oncologist opinion for possible chemo and/or radiotherapy.
Will you take a biopsy first?
yes sir.
the patient may need chemotherapy. therefore, a definite diagnosis should be available.