Neoadjuvant sirolimus for a large hepatic perivascular epithelioid cell tumor (PEComa)

World Journal of Surgical Oncology

Umberto Cillo²  Enrico Gringeri²  Vittorina Zagonel¹  Maria Cristina Montesco³  Umberto Basso¹  Marco Maruzzo¹  Francesca Bergamo¹ 

[1] Medical Oncology 1 Unit, ISTITUTO ONCOLOGICO VENETO IOV– IRCCS, Via Gattamelata 64, 35128 Padova, Italy;Hepatobiliary Surgery and Liver Transplantation Unit, University of Padova, Padova, Italy;Sarcoma and Melanoma Pathology Unit, ISTITUTO ONCOLOGICO VENETO IOV–IRCCS, Padova, Italy

关键词: sirolimus;    soft tissue sarcoma;    neoadjuvant;    PEComa;    Perivascular epithelioid cell;   

Others  :  820312
DOI  :  10.1186/1477-7819-12-46

 received in 2013-08-12, accepted in 2014-02-19,  发布年份 2014

【 摘 要 】

Perivascular epithelioid cell tumors (PEComas) are rare soft-tissue tumors with an extremely heterogeneous clinical behavior. They may arise in different organs and may behave indolently or sometimes metastasize with different grades of biological aggressiveness. We report the case of a young woman with a primary inoperable PEComa of the liver with malignant histological features. Since the mTOR pathway is often altered in PEComas and responses have been reported with mTOR-inhibitors such as sirolimus or temsirolimus, we decided to start a neoadjuvant treatment with sirolimus. The patient tolerated the treatment fairly well and after 8 months a favorable tumor shrinkage was obtained. The patient then stopped sirolimus and 2 weeks later underwent partial liver resection, with complete clinical recovery and normal liver function. The histological report confirmed a malignant PEComa with vascular invasion and negative margins. Then 6 additional months of post-operative sirolimus treatment were administered, followed by regular radiological follow-up. For patients with a large and histologically aggressive PEComa, we think that neoadjuvant treatment with mTOR-inhibitor sirolimus may be considered to facilitate surgery and allow early control of a potentially metastatic disease. For selected high-risk patients, the option of adjuvant treatment may be discussed.

【 授权许可】

   
2014 Bergamo et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Maruzzo M, Rastrelli M, Lumachi F, Zagonel V, Basso U: Adjuvant and neoadjuvant chemotherapy for soft tissue sarcomas. Curr Med Chem 2013, 20(5):613-620.
• [2]Zamboni G, Pea M, Martignoni G, Zancanaro C, Faccioli G, Gilioli E, Pederzoli P, Bonetti F: Clear cell ‘sugar’tumor of the pancreas. A novel member of the family of lesions characterized by the presence of perivascular epithelioid cells. Am J Surg Pathol 1996, 20(6):722-730.
• [3]Folpe AL: Neoplasms with perivascular epithelioid cell differentiation (PEComas). In Pathology and Genetics of Tumours of Soft Tissue and Bone. Edited by Fletcher CDM, Unni KK, Epstein J, Mertens F. Lyon: IARC Press; 2002:221-222. [WHO Classification of Tumours.]
• [4]Folpe AL, Kwiatkowski DJ: Perivascular epithelioid cell neoplasms: pathology and pathogenesis. Hum Pathol 2010, 41(1):1-15.
• [5]Wagner AJ, Malinowska-Kolodziej I, Morgan JA, Qin W, Fletcher CD, Vena N, Ligon AH, Antonescu CR, Ramaiya NH, Demetri GD, Kwiatkowski DJ, Maki RG: Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumors: targeting the pathogenic activation of mTORC1 in tumors. J Clin Oncol 2010, 28(5):835-840.
• [6]Folpe AL, Mentzel T, Lehr HA, Fisher C, Balzer BL, Weiss SW: Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol 2005, 29:1558-1575.
• [7]BisslerJJ MCFX, Young LR, Elwing JM, Chuck G, Leonard JM, Schmithorst VJ, Laor T, Brody AS, Bean J, Salisbury S, Franz DN: Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med 2008, 358(2):140-151.
• [8]Hofbauer GF, Marcollo-Pini A, Corsenca A, Kistler AD, French LE, Wüthrich RP, Serra AL: The mTOR inhibitor rapamycin significantly improves facial angiofibroma lesions in a patient with tuberous sclerosis. Br J Dermatol 2008, 159(2):473-475.
• [9]Italiano A, Delcambre C, Hostein I, Cazeau AL, Marty M, Avril A, Coindre JM, Bui B: Treatment with the mTOR inhibitor temsirolimus in patients with malignant PEComa. Ann Oncol 2010, 21(5):1135-1137.
• [10]Yudoh K, Kanamori M, Ohmori K, Yasuda T, Aoki M, Kimura T: Concentration of vascular endothelial growth factor in the tumour tissue as a prognostic factor of soft tissue sarcomas. Br J Cancer 2001, 84(12):1610-1615.
• [11]van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S, Lindhout D, van den Ouweland A, Halley D, Young J, Burley M, Jeremiah S, Woodward K, Nahmias J, Fox M, Ekong R, Osborne J, Wolfe J, Povey S, Snell RG, Cheadle JP, Jones AC, Tachataki M, Ravine D, Sampson JR, Reeve MP, Richardson P, Wilmer F, Munro C, Hawkins TL, et al.: Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 1997, 277(5327):805-808.
• [12]Bonetti F, Martignoni G, Colato C, Manfrin E, Gambacorta M, Faleri M, Bacchi C, Sin VC, Wong NL, Coady M, Chan JK: Abdominopelvic sarcoma of perivascular epithelioid cells. Report of four cases in young women, one with tuberous sclerosis. Mod Pathol 2001, 14(6):563-568.
• [13]Smolarek TA, Wessner LL, McCormack FX, Mylet JC, Menon AG, Henske EP: Evidence that lymphangiomyomatosis is caused by TSC2 mutations: chromosome 16p13 loss of heterozygosity in angiomyolipomas and lymph nodes from women with lymphangiomyomatosis. Am J Hum Genet 1998, 62(4):810-815.
• [14]Kenerson H, Folpe AL, Takayama TK, Yeung RS: Activation of the mTOR pathway in sporadic angiomyolipomas and other perivascular epithelioid cell neoplasms. Hum Pathol 2007, 38(9):1361-1371.
• [15]Pan CC, Chung MY, Ng KF, Liu CY, Wang JS, Chai CY, Huang SH, Chen PC, Ho DM: Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa with angiomyolipoma. J Pathol 2008, 214(3):387-393.