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Classic Mediterranean Kaposi’s Sarcoma Regression With Sirolimus Treatment

Classic Mediterranean Kaposi’s Sarcoma Regression With Sirolimus Treatment Replacement of mycophenolate mofetil, cyclosporine, or tacrolimus by sirolimus results in regression of Kaposi's sarcoma (KS) in organ transplant recipients.1-3 In these patients, clearance from KS might result either from reduced immunosuppression or from the direct antiangiogenic effects of sirolimus. Report of a Case Herein we describe a 62-year-old man with disseminated Mediterranean KS that regressed almost completely during sirolimus therapy at a blood concentration of 6 ng/mL. The heterosexual, immunocompetent patient tested negative for both human immunodeficiency virus 1 and human immunodeficiency virus 2. However, he had 17 disseminated KS lesions that continuously erupted after excision of 2 single KS lesions that tested positive for human herpesvirus 8 and the D2-40 antibody (which is raised against M2A, an oncofetal antigen, and has been used as a marker for lymphatic endothelium). Owing to the large number of KS lesions and a history of depression, treatment with established therapies such as excision, cryotherapy, radiotherapy, intralesional or systemic chemotherapy, or interferon alfa was problematic. Eight weeks after initiation of sirolimus therapy, all KS lesions showed complete clinical, histologic (Figure), and immunohistochemical regression with the exception of a partial regression of the largest lesion on the lateral aspect of the front of the left foot. No adverse effects had occurred. Therapy was discontinued and after 6 months, no KS lesions had recurred. Figure. View LargeDownload Regression of classic Kaposi's sarcoma in a 62-year-old immunocompetent man without human immunodeficiency virus receiving sirolimus monotherapy (hematoxylin-eosin, original magnification ×100 for both histologic views). A, Pretreatment clinical and histologic views. B, Clinical and histologic views after 2 months of sirolimus therapy at a blood concentration of 6 ng/mL. Comment Sirolimus is a member of the calcineurin inhibitor family that, in contrast to cyclosporine or tacrolimus, exerts strong antiangiogenic effects. It binds to the mammalian target of rapamycin (commonly called mTOR),4 which severely inhibits the response of endothelium to vascular endothelial growth factor.5 The previously observed regression of KS in transplant recipients1,2 might be explained either by reduced strength of immunosuppression or the antiangiogenic effects of sirolimus. Since the present patient had no prior immunosuppressive therapy, regression of disseminated KS lesions can only be explained by the antiangiogenic effects of sirolimus. This indicates that sirolimus may be beneficial not only for iatrogenic but also for classic KS. Correspondence: Dr Guenova, Department of Dermatology, Eberhard Karl University, Liebermeisterstrasse 25, D-72076 Tuebingen, Germany (emmanuella.guenova@med.uni-tuebingen.de). Financial Disclosure: None reported. References 1. Boeckle EBoesmueller CWiesmayr S et al. Kaposi sarcoma in solid organ transplant recipients: a single center report. Transplant Proc 2005;37 (4) 1905- 1909PubMedGoogle ScholarCrossref 2. Stallone GSchena AInfante B et al. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med 2005;352 (13) 1317- 1323PubMedGoogle ScholarCrossref 3. Weenink JJGroeneveld JOde Fijter CW Sirolimus monotherapy for Kaposi's sarcoma in an HIV-negative patient. Lancet Oncol 2006;7 (10) 875- 876PubMedGoogle ScholarCrossref 4. Sodhi AChaisuparat RHu J et al. The TSC2/mTOR pathway drives endothelial cell transformation induced by the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor. Cancer Cell 2006;10 (2) 133- 143PubMedGoogle ScholarCrossref 5. Guba Mvon Breitenbuch PSteinbauer M et al. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med 2002;8 (2) 128- 135PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

Classic Mediterranean Kaposi’s Sarcoma Regression With Sirolimus Treatment

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References (5)

Publisher
American Medical Association
Copyright
Copyright © 2008 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archderm.144.5.692
Publisher site
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Abstract

Replacement of mycophenolate mofetil, cyclosporine, or tacrolimus by sirolimus results in regression of Kaposi's sarcoma (KS) in organ transplant recipients.1-3 In these patients, clearance from KS might result either from reduced immunosuppression or from the direct antiangiogenic effects of sirolimus. Report of a Case Herein we describe a 62-year-old man with disseminated Mediterranean KS that regressed almost completely during sirolimus therapy at a blood concentration of 6 ng/mL. The heterosexual, immunocompetent patient tested negative for both human immunodeficiency virus 1 and human immunodeficiency virus 2. However, he had 17 disseminated KS lesions that continuously erupted after excision of 2 single KS lesions that tested positive for human herpesvirus 8 and the D2-40 antibody (which is raised against M2A, an oncofetal antigen, and has been used as a marker for lymphatic endothelium). Owing to the large number of KS lesions and a history of depression, treatment with established therapies such as excision, cryotherapy, radiotherapy, intralesional or systemic chemotherapy, or interferon alfa was problematic. Eight weeks after initiation of sirolimus therapy, all KS lesions showed complete clinical, histologic (Figure), and immunohistochemical regression with the exception of a partial regression of the largest lesion on the lateral aspect of the front of the left foot. No adverse effects had occurred. Therapy was discontinued and after 6 months, no KS lesions had recurred. Figure. View LargeDownload Regression of classic Kaposi's sarcoma in a 62-year-old immunocompetent man without human immunodeficiency virus receiving sirolimus monotherapy (hematoxylin-eosin, original magnification ×100 for both histologic views). A, Pretreatment clinical and histologic views. B, Clinical and histologic views after 2 months of sirolimus therapy at a blood concentration of 6 ng/mL. Comment Sirolimus is a member of the calcineurin inhibitor family that, in contrast to cyclosporine or tacrolimus, exerts strong antiangiogenic effects. It binds to the mammalian target of rapamycin (commonly called mTOR),4 which severely inhibits the response of endothelium to vascular endothelial growth factor.5 The previously observed regression of KS in transplant recipients1,2 might be explained either by reduced strength of immunosuppression or the antiangiogenic effects of sirolimus. Since the present patient had no prior immunosuppressive therapy, regression of disseminated KS lesions can only be explained by the antiangiogenic effects of sirolimus. This indicates that sirolimus may be beneficial not only for iatrogenic but also for classic KS. Correspondence: Dr Guenova, Department of Dermatology, Eberhard Karl University, Liebermeisterstrasse 25, D-72076 Tuebingen, Germany (emmanuella.guenova@med.uni-tuebingen.de). Financial Disclosure: None reported. References 1. Boeckle EBoesmueller CWiesmayr S et al. Kaposi sarcoma in solid organ transplant recipients: a single center report. Transplant Proc 2005;37 (4) 1905- 1909PubMedGoogle ScholarCrossref 2. Stallone GSchena AInfante B et al. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med 2005;352 (13) 1317- 1323PubMedGoogle ScholarCrossref 3. Weenink JJGroeneveld JOde Fijter CW Sirolimus monotherapy for Kaposi's sarcoma in an HIV-negative patient. Lancet Oncol 2006;7 (10) 875- 876PubMedGoogle ScholarCrossref 4. Sodhi AChaisuparat RHu J et al. The TSC2/mTOR pathway drives endothelial cell transformation induced by the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor. Cancer Cell 2006;10 (2) 133- 143PubMedGoogle ScholarCrossref 5. Guba Mvon Breitenbuch PSteinbauer M et al. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med 2002;8 (2) 128- 135PubMedGoogle ScholarCrossref

Journal

Archives of Dermatology – American Medical Association

Published: May 1, 2008

Keywords: rapamycin,kaposi sarcoma

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