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| Year : 2007 | Volume
: 18
| Issue : 4 | Page : 617-620 |
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| Successful Treatment of Post-Renal Transplant Gastric and Pulmonary Kaposi's sarcoma with Conversion to Rapamycin Treatment |
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Slim Charfi1, Salwa Krichen-Makni1, Soumaya Yaich2, Hafedh Makni3, Abdelmajid Khabir1, Ali Amouri4, Khaled Charfeddine2, Jamil Hachicha2, Tahya Sellami-Boudawara1
1 Department of Pathology, University Hospital of SFAX, Tunisia
2 Department of Nephrology, University Hospital of SFAX, Tunisia
3 Department of Immunology, University Hospital of SFAX, Tunisia
4 Department of Gastroenterology, University Hospital of SFAX, Tunisia
Click here for correspondence address and email
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 Abstract | | |
The incidence of Kaposi's sarcoma (KS) is higher in organ transplant recipients. The lesions are mainly cutaneous and isolated visceral involvement is rare. We herewith report a 38-year-old male patient, who underwent a cadaveric donor renal transplantation for chronic interstitial nephropathy. His immunosuppression protocol consisted of corticosteroids, tacrolimus and mycophenolate mofetil. Twenty-five months later, he presented with diarrhea and epigastric pain. An upper gastrointestinal endoscopy revealed an ulcer in the body of the stomach. Histological examination coupled with immunohistochemistry was suggestive of KS. Detailed examination did not show any skin lesions. Computed tomography of the chest revealed multiple bilateral lung micronodules. The patient tested positive for anti-Herpes Human Virus (HHV8) antibodies. Tacrolimus and mycophenolate mofetil were withdrawn and rapamycin was introduced. This resulted in a regression of both stomach and pulmonary KS. One-year later, the patient developed an episode of acute rejection, which was successfully treated with bolus steroids. Our case suggests that rapamycin-based immunosuppression offers a promising approach to the management of post-transplant KS, particularly with visceral involvement. Keywords: Immunosuppression, Kaposi′s sarcoma, Kidney transplantation, Rapamycin
How to cite this article:
Charfi S, Krichen-Makni S, Yaich S, Makni H, Khabir A, Amouri A, Charfeddine K, Hachicha J, Sellami-Boudawara T. Successful Treatment of Post-Renal Transplant Gastric and Pulmonary Kaposi's sarcoma with Conversion to Rapamycin Treatment. Saudi J Kidney Dis Transpl 2007;18:617-20 |
How to cite this URL:
Charfi S, Krichen-Makni S, Yaich S, Makni H, Khabir A, Amouri A, Charfeddine K, Hachicha J, Sellami-Boudawara T. Successful Treatment of Post-Renal Transplant Gastric and Pulmonary Kaposi's sarcoma with Conversion to Rapamycin Treatment. Saudi J Kidney Dis Transpl [serial online] 2007 [cited 2022 Aug 13];18:617-20. Available from: https://www.sjkdt.org/text.asp?2007/18/4/617/36523 |
| Introduction | |  |
Increased incidence of malignancies is a well-known complication among organ transplant recipients and constitute a major cause of morbidity and mortality. Several studies have indicated that skin cancer, lymphoproliferative diseases and Kaposi's sarcoma (KS) are the most common neoplasms occurring in renal transplant recipients. In KS, the lesions are mainly cutaneous and isolated visceral involvement is rare. [1] In this report, we present a 38-year-old man who underwent a cadaveric donor renal transplantation for chronic interstitial nephropathy who presented with KS with visceral involvement and without any cutaneous lesions.
| Case Report | | |
We report on a 38-year-old male patient who had chronic renal failure secondary to chronic interstitial nephropathy and had received dialysis for 14-months. The patient underwent a cadaveric donor renal transplanttation. In the post-operative period, he had delayed graft function due to acute tubular necrosis. Additionally, he developed infection with the cytomegalovirus (CMV), which occurred 36 days after transplantation; he was successfully treated with ganciclovir. The allograft function stabilized with the serum creatinine being about 180 µmol/L. The initial immunosuppressive treatment consisted of anti-thymocyte globulin (ATG), tacrolimus, mycophenolate mofetil (MMF) and corticosteroids. Twenty-five months following transplantation, the patient presented with epigastric pain, not responding to treatment with proton pump inhibitors, with recent weight loss of about four kg; an upper gastrointestinal endoscopy showed a bleeding ulcer in the body of stomach associated with multiple purpuric lesions [Figure - 1]. Histological study of the biopsy taken from the ulcer showed proliferation of spindle cells and blood vessels in association with increased cellular density and moderate nuclear atypia [Figure - 2]. Perl's staining showed the presence of hemosiderin deposits. On immunohistochemistry, the tumor cells were positive for vimentine, vascular spaces were positive for CD34 and smooth muscle was positive for actin. A diagnosis of gastric KS was made. Detailed clinical examination did not reveal any cutaneous lesions of KS or, lymph node enlargement. The patient tested positive for anti-Herpes Human Virus (HHV8) antibodies with IgG levels of 64 IU/ml; the PCR for HHV8 was negative. Computed tomography of the chest and abdomen revealed a multiple micronodules in both lungs [Figure - 3] with hepatosplenomegaly. Endoscopy of the lower gastrointestinal tract as well as biopsy and scintigraphy of the bones, were normal.
The treatment consisted of modifying the immunosuppression with replacement of tacrolimus with rapamycin, an initial 50% reduction in the dose, followed by complete cessation of MMF, combined with two doses of monoclonal anti-CD20 antibody. This resulted in a regression of the clinical symptoms, a weight gain of six kg with total disappearance of the gastric lesion on endoscopy which was performed six months later. Also, repeat computed tomography of the chest was normal. During subsequent follow-up, oneyear later, we found an alteration of the graft function (increase of serum creatinine from 180 to 240 µmol/L); allograft biopsy revealed acute cellular rejection [Figure - 4], which was successfully treated with steroid boluses.
| Discussion | | |
The prevalence of KS varies depending on geography and ethnic variations; this tumor is more prevalent (1.5 to 4%) among patients of Arabic, Jewish or Mediterranean ancestry. [2] The mean age of the affected patients was 38 to 47 years (range 23 to 65 years). The mean time interval between transplantation and diagnosis of KS was 23.45 months (range, 6 to 102 months).[1],[3] A major determinant of KS is infection with HHV8, which is a KSassociated herpes virus (KSHV). However, it is still unclear whether iatrogenic KS is due to the reactivation of HHV8/KSHV as a result of immunosuppression or to the transfer of HHV8/KSHV infected progenitor cells through the renal allograft.[2],[4] Quinibi et al. report a high proportion of HHV8/KSHV seropositivity in renal transplant patients with KS (92% of cases) compared to renal transplant patients without KS (28%) and normal healthy controls. [4] A genetic predisposition related to human leukocyte antigen (HLA) system has also been reported. HLA-DR5 antigen is a particular predisposing marker. This antigen was seen in 32% of post transplant patients with KS. [2] Calcineurin inhibitors such as cyclosporine and tacrolimus have been associated with a further rise in the incidence of cancer probably by increasing the production of growth factors such as transforming growth factor β (TGF β), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), all of which enhance angiogenesis, tumor growth and metastasis. [5] The localization of KS is mainly cutaneous (60%); concomitant visceral and cutaneous or lymph node involvement are less frequent. Isolated visceral involvement, described in our patient, is rare.[1],[3]
The diagnosis of KS is based on pathologic examination. Microscopic features reveal intersecting fascicles of spindle cells with only mild atypia and numerous slit-like spaces containing red cells with frequent extravasation of erythrocytes and deposits of hemosiderin, surrounding the vascular spaces. On immunohistochemistry, the lining cells of clearly developed vascular structures are usually positive for vascular markers, while the spindle cells consistently show positive reaction for CD34 and less commonly, for CD31; however, they are negative for factor VIII.[6]
Once diagnosed, treatment of KS is primarily in the form of a reduction in dose or, total cessation of the immunosuppression.[1],[3] A complete remission was reported in 83 to 100% of the patients; most of them without visceral involvement.[1],[3] This strategy carries a risk of irreversible rejection of the graft and a possible return to dialysis.[1],[3] Systemic chemotherapy and radiotherapy are secondline options for treatment of this neoplasm. [1] Recently, many studies have shown that conversion of the immunosuppression to rapamycin constitutes a therapeutic alternative for treatment of KS, without causing allograft dysfunction.[7],[8],[9] Rapamycin is a macrolide with antifungal and immunosuppressant activities. Experimentally, rapamycin inhibits metastatic tumor growth and angiogenesis and has shown anti-angiogenic activities related to a decrease in production of VEGF as well as inhibiting response of vascular endothelial cells to stimulation by VEGF. [10] Stallone et al. [7] reported 19 cases of posttransplant cutaneous KS, who were successfully treated with conversion to rapamycin. [7] Similar results have been reported by Gutierrez-Dalmau et al on seven cases. [9] Zmoranski et al. reported on two cases of concomitant visceral and cutaneous posttransplant KS that regressed after conversion to rapamycin. [8]
In our patient, an episode of acute rejection was observed one-year after conversion to rapamycin; it was probably related to low sirolimus blood levels. Gutierrez-Dalmau et al. [9] have suggested maintaining a rapamycin level between 8 and 15 mg/ml during the first six months after the conversion.
In conclusion, our case study suggests that rapamycin-based immunosuppression enhances the possibility of KS regression, especially with visceral involvement. Maintaining adequate blood levels of rapamycin is recommended to avoid acute rejection.
| References | | |
| 1. | Zavos G, Bokos J, Papacondtantinou J, et al. Study of « de Novo » malignancies among Greek renal transplant recipients. Transplant Proc 2003;35:1399-403.  |
| 2. | Frances C. Kaposi's sarcoma after renal transplantation. Nephrol Dial Transplant 1998;13:2768-73. |
| 3. | Duman S, Toz H, Asci G, et al. Successful treatment of post-transplant Kaposi's sarcoma by reduction of immunosuppression. Nephrol Dial Transplant 2002;17:892-6. |
| 4. | Qunibi W, Al-Furayh O, Almeshari K, et al. Serologic association of human herpesvirus eight with posttransplant Kaposi's sarcoma in Saudi Arabia. Transplantation 1998;65: 583-5. [PUBMED] [FULLTEXT] |
| 5. | Hojo M, Morimoto T, Maluccio M, et al. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature 1999;397:530-4. [PUBMED] [FULLTEXT] |
| 6. | Lamovec J, Knuutila S. Kaposi sarcoma. In: Fletcher CD, Krishnan Unni K, Mertens F, eds. World health organisation classification of tumours pathology and genetics. Tumours of soft tissue and bone. Lyon: IARC Press; 2004; :170-2. |
| 7. | Stallone G, Schena A, Infante B. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med 2005;352:1317-23. |
| 8. | Zmonarski SC, Boratynska M, Rabczynski J, Kazimierczak K, Klinger M. Regression of Kaposi's sarcoma in renal graft recipients after conversion to sirolimus treatment. Transplant Proc 2005;37:964-6. |
| 9. | Gutierrez-Dalmau A, Sanchez-Fructuoso A, Sanz-Guajardo A, et al. Efficacy of conversion to sirolimus in post transplantation Kaposi's sarcoma. Transplant Proc 2005;37: 3836-8. |
| 10. | Guba M, von Breitenbuch P, Steinbauer M, et al. Rapamycin inhibits primary and metastatic growth by angiogenesis involvement of vascular endothelial growth factor. Nat Med 2002;8:128-35. [PUBMED] [FULLTEXT] |
Correspondence Address:
Slim Charfi
Department of Pathology, University Hospital Habib Bourguiba, 3029 SFAX
Tunisia
 Source of Support: None, Conflict of Interest: None  | Check |
PMID: 17951954 
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4] |
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