Rapid Communication| Volume 47, ISSUE 6, e31-e40, June 2012

Malignant perivascular epithelioid cell tumor in children: description of a case and review of the literature


      Perivascular epithelioid cell tumors (PEComas) include different morphological entities originating from perivascular epitheliod cells. Their clinical behavior is not predictable, and there are no strict histologic criteria for malignancy, although larger tumors with infiltrative growth, hypercellularity, cellular atypia, atypical mitoses, and necrosis generally have a malignant course. Pediatric PEComas are rare, with less than 40 cases reported, mostly in children older than 5 years. We describe a case of malignant PEComa of the ligamentum teres in a 2-year-old girl, characterized by the occurrence of local relapse after primary treatment with chemotherapy and surgery and poor response to imatinib mesilate and temsirolimus used after further analyses confirmed p70S6K expression involved in the mTOR pathway. The girl was eventually treated with a debulking surgical procedure and is now alive with disease 6 years after diagnosis. Literature data of children affected by PEComas were also analyzed, trying to identify pathologic characteristics that could predict their course and therapeutic options. Histologically, they may be differentiated in 3 prognostic categories: (1) benign, lacking unfavorable morphological markers; (2) with uncertain malignant potential, carrying 1 unfavorable marker; and (3) malignant, with at least 2 unfavorable markers. In the literature, 9% of cases occurred as a second malignancy probably because of genomic instability related to treatment. Their different biology and the potential value of targeted therapies remain to be explored. The indolent evolution in our patient was similar to that reported in some other cases in the literature. In terms of treatment, the present case suggests a minor response to temsirolimus compared with the adult population.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Pediatric Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Zamboni G.
        • Pea M.
        • Martignoni G.
        • et al.
        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: 722-730
        • Benetti F.
        • Pea M.
        • Martignoni G.
        • et al.
        PEC and sugar tumor.
        Am J Surg Pathol. 1992; 16: 307-308
        • Martignoni G.
        • Pea M.
        • Reghellin D.
        • et al.
        PEComas: the past, the present and the future.
        Virchows Arch. 2008; 452: 119-132
        • Hornick J.L.
        • Fletcher C.D.
        PEComa: what do we know so far?.
        Histopathology. 2006; 48: 75-82
        • Martignoni G.
        • Pea M.
        • Reghellin D.
        • et al.
        Perivascular epithelioid cell tumor (PEComa) in the genitourinary tract.
        Adv Anat Pathos. 2007; 14: 36-41
        • Folpe A.L.
        • Goodman Z.D.
        • Ishak K.G.
        • et al.
        Clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres: a novel member of the perivascular epithelioid clear cell family of tumors with a predilection for children and young adults.
        Am J Surg Pathol. 2000; 24: 1239-1246
        • Folpe A.L.
        • McKenney J.K.
        • Li Z.
        • et al.
        Clear cell myomelanocytic tumor of the thigh: report of a unique case.
        Am J Surg Pathol. 2002; 26: 809-812
        • Bonetti F.
        • Martignoni G.
        • Colato C.
        • et al.
        Abdominopelvic sarcoma of perivascular epithelioid cells. Report of four cases in young women, one with tuberous sclerosis.
        Mod Pathol. 2002; 14: 563-568
        • Folpe A.L.
        Neoplasms with perivascular epithelioid cell differentiation (PEComas).
        in: Fletcher C.D.M. Unni K.K. Mertens F. World Health Organization Classification of Tumors. Pathology and Genetic of Tumors of Soft Tissue and Bone. IARC Press, Lyon2002: 221-222
        • Folpe A.L.
        • Mentzel T.
        • Lehr H.A.
        • et al.
        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
        • Rigby H.
        • Yu W.
        • Schmidt M.H.
        • et al.
        Lack of response of a metastatic renal perivascular epithelial cell tumor (PEComa) to successive courses of DTIC based-therapy and imatinib mesylate.
        Pediatr Blood Cancer. 2005; 45: 202-206
        • Allen R.C.
        • Zoghbi H.Y.
        • Moseley A.B.
        • et al.
        Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation.
        Am J Hum Genet. 1992; 51: 1229-1239
        • Pan C.C.
        • Jong Y.J.
        • Chai C.Y.
        • et al.
        Comparative genomic hybridization study of perivascular epithelioid cell tumor: molecular genetic evidence of perivascular epithelioid cell tumor as a distinctive neoplasm.
        Hum Pathol. 2006; 37: 606-612
        • Iyengar P.
        • Deangelis D.D.
        • Greenberg M.
        • et al.
        Perivascular epithelioid cell tumor of the orbit: a case report and review of the literature.
        Pediatr Dev Pathol. 2005; 8: 98-104
        • Ong L.Y.
        • Hwang W.S.
        • Wong A.
        • et al.
        Perivascular epithelioid cell tumour of the vagina in an 8 year old girl.
        J Pediatr Surg. 2007; 42: 564-566
        • Mhanna T.
        • Ranchere-Vince D.
        • Hervieu V.
        • et al.
        Clear cell myomelanocytic tumor (PEComa) of the duodenum in a child with a history of neuroblastoma.
        Arch Pathol Lab Med. 2005; 129: 1484-1486
        • Baek J.H.
        • Chung M.G.
        • Jung D.H.
        • et al.
        Perivascular epithelioid cell tumor (PEComa) in the transverse colon of an adolescent.
        Tumori. 2007; 92: 106-108
        • Prasad M.L.
        • Keating J.P.
        • Teoh H.H.
        • et al.
        Pleomorphic angiomyolipoma of digestive tract: a heretofore unrecognized entity.
        Int Surg Pathol. 2000; 8: 67-72
        • Tazelaar H.D.
        • Batts K.P.
        • Srigley J.R.
        Primary extrapulmonary sugar tumor (PEST): a report of four cases.
        Mod Pathol. 2001; 14: 615-622
        • Govender D.
        • Sabaratnam R.M.
        • Essa A.S.
        Clear cell “sugar” tumor of the breast: another extrapulmonary site and review of the literature.
        Am J Surg Pathol. 2002; 26: 670-675
        • Tanaka Y.
        • IjIri R.
        • Kato Y.
        • et al.
        HMB-45/melan-A and smooth muscle actin-positive clear-cell epithelioid tumor arising in the ligamentum teres hepatis: addition example of clear cell “sugar” tumors.
        Am J Surg Pathol. 2000; 24: 1295-1299
        • Tanaka M.
        • Kato K.
        • Gomi K.
        • et al.
        Perivascular epithelioid cell tumor with SFPQ/PSF-TFE3 gene fusion in a patient with advanced neuroblastoma.
        Am J Surg Pathol. 2009; 33: 1416-1420
        • Furusato E.
        • Cameron D.
        • Newsom R.W.
        • et al.
        Ocular perivascular epithelioid cell tumor: report of 2 cases with distinct clinical presentations.
        Human Pathology. 2010; 41: 768-772
        • De Dominicis G.
        • Boscaino A.
        • Marino Marsilia G.
        • et al.
        Clear cell “sugar” tumor of urethra: a previously undescribed occurrence and review of published data.
        Urology. 2009; 74: 542-543
        • Cho H.Y.
        • Chung D.H.
        • Khurana H.
        • et al.
        The role of TFE3 in PEComa.
        Histopathology. 2008; 53: 236-239
        • Sawyer J.R.
        • Nicholas R.W.
        • Parham D.M.
        A novel t(X;2)(q13;q35) in clear cell sugar tumor of bone.
        Cancer Genetics and Cytogenetics. 2004; 154: 77-80
        • Chen I.Y.
        • Yang S.F.
        • Chen F.M.
        • et al.
        Abdominopelvic perivascular epithelioid cell tumor with overt malignancy: a case report.
        Kaohsiung J Med Sci. 2005; 21: 277-281
        • Righi A.
        • Dimosthenous K.
        • Rosai J.
        PEComa: another member of the MiT tumor family?.
        Int J Surg Pathol. 2008; 16: 16-20
        • Pisharodi U.
        • Craver R.D.
        • Brown R.F.
        • et al.
        Metastatic perivascular epithelioid cell tumor of the colon in a child.
        J Pediatr Gastroenterol. 2008; 46: 598-601
        • Peng J.
        • Yu B.
        • Wang J.
        • et al.
        An unresectable malignant perivascular epithelioid cell tumor resistant to multiple combined chemotherapies. A unique case report.
        J Pediatr Hematol Oncol. 2010; 32: e136-e138
        • Gross E.
        • Vernea F.
        • Weintraub M.
        • et al.
        Perivascular epithelioid cell tumor of the ascending colon mesentery in a child: case report and review of the literature.
        J Ped Surg. 2010; 45: 830-833
        • Kim H.J.
        • Lim S.J.
        • Choi H.
        • et al.
        Malignant clear-cell myomelanocytic tumor of broad ligament—a case report.
        Virchows Arch. 2006; 448: 867-870
        • Ryan P.
        • Nguyen V.H.
        • Gholoum S.
        • et al.
        Polypoid PEComa in the rectum of a 15-year old girl: case report and review of PEComa in the gastrointestinal tract.
        Am J Surg Pathol. 2009; 33: 475-482
        • Jeon J.S.
        • Lee S.M.
        Multimodal treatment using surgery, radiotherapy and chemotherapy in a patient with a perivascular epithelioid cell tumor of the uterus.
        J Pediatr Hematol Oncol. 2005; 27: 681-684
        • Kalyanasundaram K.
        • Parameswaran A.
        • Mani R.
        Perivascular epithelioid tumor of urinary bladder and vagina.
        Ann Diagn Pathology. 2005; 9: 275-278
        • Gronchi A.
        • Diment J.
        • Colecchia M.
        • et al.
        Atypical pleomorphic epithelioid angiomyolioma localized to the pelvis: a case report and a review of the literature.
        Histopathology. 2004; 44: 292-295
        • Martignoni G.
        • Pea M.
        • Gobbo S.
        • et al.
        Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation carcinomas from other renal carcinomas.
        Mod Pathol. 2009; 22: 1016-1022
        • Chilosi M.
        • Pea M.
        • Martignoni G.
        • et al.
        Cathepsin-K expression in pulmonary lymphangioleiomyomatosis.
        Mod Pathol. 2009; 22: 161-166
        • Argani P.
        • Aulmann S.
        • Illei P.B.
        • et al.
        A distinctive subset of PEComas harbors TFE3 gene fusions.
        Am J Surg Pathol. 2010; 34: 1395-1406
        • Fadare O.
        • Parkash V.
        • Yilmaz Y.
        • et al.
        Perivascular epithelioid cell tumor (PEComa) of the uterine cervix associated with intraabdominal “PEComatosis”: a clinicopathological study with comparative genomic hybridization analysis.
        World J Surg Oncol. 2004; 19: 35
        • Pan C.C.
        • Chung M.Y.
        • Ng K.F.
        • et al.
        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: 387-393
        • Mak B.C.
        • Takemaru K.
        • Kenerson H.L.
        • et al.
        The tuberin-hamartin complex negatively regulates beta-catenin signalling activity.
        J Biol Chem. 2003; 278: 5947-5951
        • Kenerson H.
        • Folpe A.L.
        • Takayama T.K.
        • et al.
        Activation of the mTOR pathway in sporadic angiomyolipomas and other epithelioid cell neoplasms.
        Hum Pathol. 2007; 38: 1361-1371
        • Subbiah V.
        • Trent J.C.
        • Kurzrock R.
        Resistance to mammalian target of rapamycin inhibitor therapy in perivascular epithelioid cell tumors.
        J Clin Oncol. 2010; 28: e415
        • Wagner A.J.
        • Malinowska-Kolodziej I.
        • Morgan J.A.
        • et al.
        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; 10: 835-840
        • Argani P.
        • Landanyi M.
        Renal carcinomas associated with Xp11.2 translocations/TFE3 gene fusions.
        in: Eble J. Sauter J. Epstein J. Sesterhenn Pathology and genetics of tumours of the urinary system and male genital organs. Series: WHO Classification of tumours. IARC Press, Lyon2004
        • Argani P.
        • Hawkins A.
        • Griffin C.A.
        • et al.
        A distinctive pediatric renal neoplasm characterized by epithelioid morphology, basement membrane production, focal HMB45 immunoreactivity, and t(6;11)(p21.1;q12) chromosome translocation.
        Am J Pathol. 2001; 158: 2089-2096
        • Argani P.
        • Lui M.Y.
        • Couturier J.
        • et al.
        A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23).
        Oncogene. 2003; 14: 5374-5378
        • Chang I.W.
        • Huang H.Y.
        • Sung M.T.
        Melanotic Xp11 translocation renal cancer: a case with PSF-TFE3 gene fusion and up-regulation of melanogenetic transcript.
        Am J Surg Pathol. 2009; 33: 1894-1901
        • Reeves B.R.
        • Fletcher C.D.
        • Gusterson B.A.
        Translocation t(12;22)(q13;q13) is a nonrandom rearrangement in clear cell sarcoma.
        Cancer Genet Cytogenet. 1992; 64: 101-103
        • Altinok G.
        • Kattar M.M.
        • Mohamed A.
        • et al.
        Pediatric renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions and clinicopathologic associations.
        Pediatr Dev Pathol. 2005; 8: 168-180