Perivascular Epithelioid Cell Neoplasm (PEComa) of the Gynecologic Tract

Abstract

Perivascular epithelioid cell tumor (PEComa) belongs to a family of tumors characterized by coexpression of melanocytic and muscle markers. Recent studies have shown that sporadic and tuberous sclerosis complex-associated PEComa may respond to mTOR inhibitors underscoring the importance of recognizing this tumor. However, its occurrence in the gynecologic tract continues to be disputed owing to its common misclassification as other types of uterine sarcoma and its controversial relationship with epithelioid smooth muscle tumors. To more fully characterize PEComa of the female genital tract, 16 cases of gynecologic PEComa were identified (1990 to 2012) and formed the basis of this study. Each case was analyzed for conventional morphologic and immunohistochemical characteristics established for PEComa of extrauterine sites; clinical outcome data were obtained for all cases. The 16 patients were aged 28 to 60 (mean 49; median 50) years, and 1 had a history of tuberous sclerosis complex. Thirteen cases were primary of the uterus, 2 of the adnexa, and 1 of the vagina. Tumor size ranged from 0.3 to 25.0 (mean 8.7) cm. Three patients died of disease, 6 were alive with disease, and 7 were alive without evidence of disease at last follow-up (1 mo to 13 y follow-up; mean 26 mo). All patients with an adverse outcome met established criteria for malignancy as proposed for extrauterine sites (ie, 2 or more features present: size ≥5 cm, high-grade nuclear features, infiltration, necrosis, lymphovascular invasion, or a mitotic rate ≥1/50 high-power fields). Of the melanocytic markers, HMB45 was most commonly expressed (16/16 positive, 100%), followed by microphthalmia transcription factor (11/12 positive, 92%), MelanA (14/16 positive, 88%), and S100 protein (2/10 positive, 20%). Of the smooth muscle markers, desmin was most commonly expressed (15/15 cases, 100%), followed by SMA (14/15 cases, 93%) and h-caldesmon (11/12 cases, 92%). TFE3 immunopositivity was identified in 5 of 13 cases; however, 3 tested cases were negative for a TFE3 rearrangement by fluorescence in situ hybridization. Current criteria for malignancy appear to be valid in the female genital tract, although modified criteria, as described herein, may be more specific. Awareness of the characteristic features of PEComa is important to help distinguish it from epithelioid smooth muscle tumors and other mimics as PEComa may respond to unique chemotherapeutic regimens.

Perivascular epithelioid tumours (PEComas) of the gynaecological tract

“…52 Twelve patients had evidence of tumour metastasis at the time of diagnosis. 20 42 44 54 55 58 60 69 Median survival for those who died of disease was 20 months (table 1).…”

“…78 One patient (11%) recurred locally within 4 months, but had no evidence of disease at 19 months post diagnosis (table 1). 79 Vagina Seven vaginal PEComas have been reported 20 53 67 71 80-82 (table 1). Three patients were aged <18 years.…”

“…[80][81][82] Adnexa Six adnexal PEComas have been reported to date. 20 32 83-85 (table 1). A mixed myomelanocytic immunophenotype was demonstrated in five cases.…”

“…PEComas demonstrate varying levels of nuclear pleomorphism, including multinucleate giant cells (figure 2B) and 'spider cells', analogous to those seen in cardiac rhabdomyoma. 20 Other features include macronucleoli (figures 1C and 2B) and intranuclear pseudoinclusions (figure 1C). 20 While most reported PEComas have been epithelioid, they show a cytological spectrum from purely spindled to purely epithelioid (and combinations of the two).…”

“…20 Other features include macronucleoli (figures 1C and 2B) and intranuclear pseudoinclusions (figure 1C). 20 While most reported PEComas have been epithelioid, they show a cytological spectrum from purely spindled to purely epithelioid (and combinations of the two). Rare features include sex-cord-like features 21 and prolactin secretion.…”