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Diagnosis and Discussion: Case 1169

Final Diagnosis

Features most suggestive of PEComa

Discussion

Perivascular epithelioid cell tumors (PEComas) are a family of rare mesenchymal tumors composed of perivascular epithelioid cells, which have distinctive cytomorphologic and immunohistochemical characteristics (1). These tumors show a wide anatomical distribution, marked female predominance, and a wide age range at presentation with a median age of approximately 46 (2). The current PEComa WHO definition describes an entire spectrum of previously described neoplasms including epithelioid angiomyolipomas, pulmonary lymphangioleiomyomatosis, clear cell myomelanocytic tumors, and sugar tumors of the lung. PEComas usually show a nested architecture with a perivascular arrangement around large blood vessels and epithelioid cells that have abundant granular to clear cytoplasm and round nuclei with small but distinct nucleoli; in addition, a small subset of sclerosing PEComas show extensive stromal hyalinization (3-4). These tumors are all characterized by the coexpression of smooth muscle immunohistochemical markers such as smooth muscle actin, desmin, and h-caldesmon and melanocytic markers such as HMB45, melan-A, and MITF (5-6) The most common genetic alterations identified in PEComas are TSC1 and TSC2 inactivating mutations which are linked to mTOR pathway activation, and a subset of PEComas harbor TFE3 rearrangements (7-8).

Most PEComas tend to follow an indolent clinical course with recurrences and metastases rarely reported. Features that are associated with a malignant clinical course are marked nuclear atypia, the presence of mitoses and necrosis, and infiltrative margins (2,6).  In addition, tumor size greater than or equal to 5 cm and the presence of mitoses (1/50 HPF) are associated with a higher risk of recurrence following surgical resection (9).

Subsequent molecular testing on the fine needle aspiration cell block material identified TSC2 mutations p.R786_splice and p.A1617_splice as well as an SF3b1 mutation p.R625H. The patient underwent a subsequent resection of the right hepatic lobe segment 7 mass, and the final surgical pathology specimen was reported as PEComa, epithelioid angiomyolipoma variant, and the specimen had close but negative margins. The patient tolerated the surgery well and her postoperative course was uneventful.

References

  1. Wangsiricharoen S, Larman TC, Wakely PE Jr, Siddiqui MT, Ali SZ. Cytopathology of extra-renal perivascular epithelioid cell tumor (PEComa): a series of 7 cases and review of the literature. J Am Soc Cytopathol. 2021 Mar-Apr;10(2):175-186. doi: 10.1016/j.jasc.2020.09.006. Epub 2020 Sep 22. PMID: 33162379.
  2. 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 Dec;29(12):1558-75. doi: 10.1097/01.pas.0000173232.22117.37. PMID: 16327428.
  3. Doyle LA, Hornick JL, Fletcher CD. PEComa of the gastrointestinal tract: clinicopathologic study of 35 cases with evaluation of prognostic parameters. Am J Surg Pathol. 2013 Dec;37(12):1769-82. doi: 10.1097/PAS.0b013e31829caab3. PMID: 24061520.
  4. Hornick JL, Fletcher CD. Sclerosing PEComa: clinicopathologic analysis of a distinctive variant with a predilection for the retroperitoneum. Am J Surg Pathol.
  5. Folpe AL, Kwiatkowski DJ. Perivascular epithelioid cell neoplasms: pathology and pathogenesis. Hum Pathol. 2010 Jan;41(1):1-15. doi: 10.1016/j.humpath.2009.05.011. Epub 2009 Jul 15. PMID: 19604538.2008 Apr;32(4):493-501. doi: 10.1097/PAS.0b013e318161dc34. PMID: 18223480.
  6. Bennett JA, Braga AC, Pinto A, Van de Vijver K, Cornejo K, Pesci A, Zhang L, Morales-Oyarvide V, Kiyokawa T, Zannoni GF, Carlson J, Slavik T, Tornos C, Antonescu CR, Oliva E. Uterine PEComas: A Morphologic, Immunohistochemical, and Molecular Analysis of 32 Tumors. Am J Surg Pathol. 2018 Oct;42(10):1370-1383. doi: 10.1097/PAS.0000000000001119. PMID: 30001237; PMCID: PMC6133752.
  7. Akumalla S, Madison R, Lin DI, Schrock AB, Yakirevich E, Rosenzweig M, Balar AV, Frampton GM, Edgerly C, Erlich RL, Miller VA, Ganesan S, Ross JS, Ali SM. Characterization of Clinical Cases of Malignant PEComa via Comprehensive Genomic Profiling of DNA and RNA. Oncology. 2020;98(12):905-912. doi: 10.1159/000510241. Epub 2020 Sep 23. PMID: 32966992.
  8. Argani P, Aulmann S, Illei PB, Netto GJ, Ro J, Cho HY, Dogan S, Ladanyi M, Martignoni G, Goldblum JR, Weiss SW. A distinctive subset of PEComas harbors TFE3 gene fusions. Am J Surg Pathol. 2010 Oct;34(10):1395-406. doi: 10.1097/PAS.0b013e3181f17ac0. PMID: 20871214.
  9. Bleeker JS, Quevedo JF, Folpe AL. "Malignant" perivascular epithelioid cell neoplasm: risk stratification and treatment strategies. Sarcoma. 2012;2012:541626. doi: 10.1155/2012/541626. Epub 2012 Apr 26. PMID: 22619565; PMCID: PMC3350998.