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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT  
Year : 2016  |  Volume : 27  |  Issue : 2  |  Page : 377-380
Occurrence of double primary malignancies in an African renal transplant recipient


1 Department of Nephrology, Madras Medical Mission, Chennai, Tamil Nadu, India
2 Department of Urology, Madras Medical Mission, Chennai, Tamil Nadu, India
3 Department of Renal Pathology, Madras Medical Mission, Chennai, Tamil Nadu, India
4 Department of Surgery, Madras Medical Mission, Chennai, Tamil Nadu, India

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Date of Web Publication11-Mar-2016
 

   Abstract 

A 63-year-old African male with end stage renal disease who received a renal transplantation from his daughter after successful treatment of hepatitis C virus, type 1 genotype developed metastatic Kaposi's sarcoma and subsequently adenocarcinoma of the prostate. He was successfully treated with chemotherapy and reduction of immunosuppression and switch over to rapamycin.

How to cite this article:
Mohan P, Yuvaraj A, Abraham G, Kurien A, Abraham A, Mathew M, Saravanan S, Nair S. Occurrence of double primary malignancies in an African renal transplant recipient. Saudi J Kidney Dis Transpl 2016;27:377-80

How to cite this URL:
Mohan P, Yuvaraj A, Abraham G, Kurien A, Abraham A, Mathew M, Saravanan S, Nair S. Occurrence of double primary malignancies in an African renal transplant recipient. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2019 Nov 22];27:377-80. Available from: http://www.sjkdt.org/text.asp?2016/27/2/377/178566

   Introduction Top


Immune suppression after organ transplantation is associated with a markedly increased risk of nonmelanoma skin cancer and a few virus-associated cancers. [1] The overall increase in risk is 3-5-fold over age-matched controls in the general population. [2] The risk increase is not equivalent for all types of malignancies. [3] Among the neoplasms which are markedly increased are skin cancer, cancers of the oral cavity, non-Hodgkin's lymphoma, Hodgkin's disease, Kaposi's sarcoma (KS), cervical carcinoma, anogenital cancers, renal cell carcinoma, and hepato-cellular carcinoma (HCC). [3],[4]

In this case report, we present a rare occurrence of two primary malignancies in a previously hepatitis C positive, renal transplant recipient.


   Case Report Top


A 63-year-old Tanzanian physician with hypertension and obstructive uropathy leading to end stage renal disease, who was on maintenance HD, three times/week, since February 2009, presented to us for renal transplantation in July 2009. His past history was significant for transurethral resection of prostate (TURP) for benign prostatic hypertrophy in 2007. He quit alcohol four years ago and was not a smoker. He had a history of blood transfusion and was detected to be hepatitis C positive, genotype I, with a viral load of 52,9000 IU/mL. He was treated with peg-interferon 135 μg for 24 weeks. He had live-related transplantation from his daughter, aged 25 years, when he had sustained viral remission (SVR). His pretransplantation PRA was 25%, human leukocyte antigen (HLA) typing showed one mismatch in the A locus. Immediate posttransplantation period was uneventful with good urine output and graft function. He was inducted with a single dose of 20 mg basiliximab. On discharge, his investigations showed hemoglobin (Hb) 96 g/L (9.6 g/dL), blood urea nitrogen 17.136 mmol/L (48 mg/dL), serum creatinine 97.24 μmol/L (1.1 mg/dL), serum PSA 6.8 μg/L (6.8 ng/mL), and body weight was 85.2 kg. The trough level of cyclosporine was monitored and dosage was adjusted accordingly and he was discharged with the following immunosuppressants: microemulsion form of cyclosporine A 300-0-250 mg, prednisolone 25 mg OD, and mycophenolate mofetil 1 g BD. He developed new onset diabetes after transplant which was controlled with diet. He returned for review six months later in September 2010, complaining of multiple hyper-pigmented raised lesions on his hands and feet and enlarged left supraclavicular group of lymph nodes. Investigation showed blood urea nitrogen 18.207 mmol/L (51 mg/dL), serum creatinine 114.92 μmol/L (1.3 mg/dL), Hb 111 g/L (11.1 g/dL), white blood cell (WBC) 6 × 10 9 /L (6000 cells/ mm 3 , platelet 110 × 10 9 /L (110,000/mm 3, urinalysis showed-protein 2+, red blood cell (RBC) 8-10/high power field (HPF), WBC 15-20/HPF, and urine culture was unremarkable. His weight had increased to 96 kg. He was on the same dosage of immunosuppressive drugs. Biopsy of the lymph node was consistent with visceral KS [Figure 1].
Figure 1: Showing cervical lymph node with Kaposi's sarcoma with dispersed spindle cells with slit-like spaces lined by endothelial cells, extravasated red blood cells, formation of new blood vessels with endothelial lining and mitotic figures.

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Computed tomography chest showed mediastinal lymphadenopathy, but bronchial washings were negative for malignant cells. Viral studies showed that human herpes virus-8 (HHV-8) was positive, vascular endothelial growth factor (VEGF) receptor was negative, hepatitis C virus (HCV) viral load was undetectable, and he was initiated on intravenous pegylated liposomal doxorubicin 60 mg once a month for six months, and mycophenolate mofetil was discontinued. He was switched over to rapamycin 8 mg OD. Dosage of cyclosporine was reduced to 25-0-25 mg and prednisolone to 5 mg OD.

He returned a year later in September 2011, with dysuria and lower urinary tract symptoms and serum PSA was 15.6 μg/L (15.6 ng/mL), urinalysis showed trace albumin, and microscopy showed WBCs 10-12/HPF, RBC 4-5/HPF, and urine culture was negative. Blood urea nitrogen was 10.71 mmol/L (30 mg/dL), serum creatinine was 106.08 μmol/L (1.2 mg/dL), and HCV was undetectable. His immunosuppressive drugs were microemulsion form of cyclosporine A 25 mg BD, prednisolone 5 mg OD, and rapamycin 8 mg OD. A 13 core trans-rectal ultrasound (TRUS) biopsy showed adenocarcinoma of the prostate, gleason score of 3 + 5, with no evidence of metastasis [Figure 2].
Figure 2: A 13 core transrectal ultrasound biopsy showed adenocarcinoma of the prostate, gleason score of 3 + 5, with no evidence of metastasis, (a) Gleason pattern 3 – showing neoplastic prostatic glands of varying sizes lined by single layer of epithelial cells with wide stromal separation; (b) Gleason pattern 5 – showing neoplastic cells arranged in sheets, cords, and as single cells.

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A bone scan and other imaging showed no evidence of metastasis. He was started on androgen deprivation therapy with intramuscular luteinizing hormone-releasing hormone analog leuprolide 22.5 mg, once in three months and anti-androgen tablet bicalutamide 50 mg OD. The dosages of his immunosuppressive medications were reduced to micro-emulsion cyclosporine A to 25 mg on alternate days, prednisolone 5 mg thrice a week and rapamycin 7 mg once a day. His urinary symptoms became better and currently has good graft function.


   Discussion Top


Renal transplantation recipients are approximately three times more likely to develop cancers than the general population. The reported cumulative incidence of any cancer was 13%, 33%, and 47% after 10, 20, and 30 years, respectively. [5] Cancers may result from oncogenic viral infections, [1] variety of nonviral tumor antigens, and ingestion of calcineurin inhibitors. [6],[7]

The increased risk for occurrence of KS is 500 times and the average time to development after transplantation is 5-21 months. [6] As in our patient, KS is seen as an endemic disease in African and Mediterranean populations, and as an epidemic disease associated with human herpes virus-HHV 8 reactivation. [4] Control of infection in healthy individuals appears to be mediated via an antiviral T-cell response to viral lytic proteins. The mechanism through which KS develops is unclear, although recent evidence suggests that development involves initial latent HHV-8 infection of endothelial cells and subsequent conversion to spindle cells, increased secretion of VEGF, upregulation of its receptor fetal liver kinase 1/kinase domain receptor, along with other paracrine events play a pivotal role in the development of the final tumor. [6] As our patient had metastatic disease, the reduction of immunosuppressive drugs combined with switch over to mTOR inhibitor, rapamycin and chemotherapy ameliorated the disease process. The anti-angiogenic properties of rapamycin has been proven in arresting the growth of KS. [8],[9]

Adenocarcinoma of the prostate can remain dormant without producing symptoms. However, our patient had a TURP in 2008 and the specimen showed no evidence of malignancy. The occurrence of recurrent urinary tract infections and doubling of serum PSA in September 2011, led to further investigations requiring a 13 core TRUS biopsy, which showed adenocarcinoma of the prostate with a gleason score 3 + 5, which required therapy. There is 2-5-fold increased risk of prostate cancer in renal transplant recipients with early occurrence and dissemination, especially when a calcineurin inhibitor and azathioprine were used as immunosuppressive therapy. [10],[11] Although HCV, genotype 1, was appropriately treated and he attained SVR, the development of two malignancies in an African national with no evidence of other infections is a rare occurrence. No specific associations for the occurrence of these two malignancies have been reported previously.

Management of two primary malignancies in a posttransplant patient is difficult, and involves reduction of immunosuppression at the cost of stable graft function, and the decision has to be weighed carefully. As the daughter with minimal HLA mismatch was the donor and patient's graft function remained good and stable, he was managed with significant reduction of immunosuppression and switching over to rapamycin. He is presently doing well until September 2012.

Double primary malignancy in a renal transplant is rare. Though there have been a few cases of multiple primary malignancies in a renal transplant recipient, [12] management is based largely on case studies, and involves reduction of immunosuppresion and treatment of the primary malignancy.

 
   References Top

1.
Vajdic CM, McDonald SP, McCredie MR, et al. Cancer incidence before and after kidney transplantation. JAMA 2006;296:2823-31.  Back to cited text no. 1
    
2.
Dantal J, Pohanka E. Malignancies in renal transplantation: An unmet medical need. Nephrol Dial Transplant 2007;22 Suppl 1:i4-10.  Back to cited text no. 2
    
3.
Morath C, Mueller M, Goldschmidt H, Schwenger V, Opelz G, Zeier M. Malignancy in renal transplantation. J Am Soc Nephrol 2004;15: 1582-8.  Back to cited text no. 3
    
4.
Yildirim Y, Ozyilkan O, Emiroglu R, Demirhan B, Karakayali H, Haberal M. Early diagnosis of cancer in renal transplant patients: A single center experience. Asian Pac J Cancer Prev 2006;7:336-9.  Back to cited text no. 4
    
5.
Wisgerhof HC, van der Geest LG, de Fijter JW, et al. Incidence of cancer in kidney-transplant recipients: A long-term cohort study in a single center. Cancer Epidemiol 2011;35:105-11.  Back to cited text no. 5
    
6.
Campistol JM, Schena PF. Kaposi's sarcoma in renal transplant recipients-the impact of proliferation signal inhibitors. Nephrol Dial Transplant 2007;22 Suppl 1:i17-22.  Back to cited text no. 6
    
7.
Hojo M, Morimoto T, Maluccio M, et al. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature 1999;397: 530-4.  Back to cited text no. 7
    
8.
Guba M, von Breitenbuch P, Steinbauer M, et al. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: Involvement of vascular endothelial growth factor. Nat Med 2002;8:128-35.  Back to cited text no. 8
    
9.
Hussein MM, Mooij JM, Roujouleh HM. Regression of post-transplant Kaposi sarcoma after discontinuing cyclosporin and giving mycophenolate mofetil instead. Nephrol Dial Transplant 2000;15:1103-4.  Back to cited text no. 9
[PUBMED]    
10.
Birkeland SA, Storm HH, Lamm LU, et al. Cancer risk after renal transplantation in the Nordic countries, 1964-1986. Int J Cancer 1995; 60:183-9.  Back to cited text no. 10
    
11.
Kleinclauss F, Gigante M, Neuzillet Y, et al. Prostate cancer in renal transplant recipients. Nephrol Dial Transplant 2008;23:2374-80.  Back to cited text no. 11
[PUBMED]    
12.
Gómez E, Portal CG, Seco MA, AlvarezGrande J. Multiple solid malignancies in a renal transplant patient. Nephrol Dial Transplant 1999;14:803-4.  Back to cited text no. 12
    

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Correspondence Address:
Georgi Abraham
Department of Nephrology, Madras Medical Mission, Chennai, Tamil Nadu
India
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DOI: 10.4103/1319-2442.178566

PMID: 26997394

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    Abstract
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