PEComas, occasionally associated with the
tuberous sclerosis complex, are defined by the presence of perivascular epithelioid cells that coexpress muscle and melanocytic markers. This family of
tumors includes
angiomyolipoma (AML),
clear cell sugar tumor of the lung (CCST),
lymphangioleiomyomatosis (
LAM), and very rare
tumors in other locations. Because non-AML/non-
LAM PEComas are extremely rare and their natural history and prognostic features undefined, we present our experience with 26
PEComas of soft tissue and the gynecologic tract, the largest series to date. We also performed a detailed review of the literature, with special attention to features predictive of clinical behavior. All
PEComas exclusive of AML and
LAM were retrieved from our consultation files. Immunohistochemistry for pan-
cytokeratin (CK),
S-100 protein, smooth muscle
actins (SMA),
desmin,
vimentin, HMB45,
Melan-A,
microphthalmia transcription factor (MiTF), TFE3, CD117, and CD34 was performed. Clinical follow-up information was obtained. Fisher's exact test was performed. The median patient age was 46 years (range, 15-97 years); there was a marked female predominance (22 females, 4 males). Sites of involvement included the omentum or mesentery (6 cases), uterus (4 cases), pelvic soft tissues (3 cases), abdominal wall (2 cases), uterine cervix (2 cases), and vagina, retroperitoneum, thigh, falciform ligament, scalp, broad ligament, forearm, shoulder, and neck (1 case each). The
tumors ranged from 1.6 to 29 cm in size (median, 7.8 cm).
Tumors were epithelioid (N = 9), spindled (N = 7), or mixed (N = 10). Multinucleated giant cells were present in 18 cases. High nuclear grade was noted in 10 cases, high cellularity in 7 cases,
necrosis in 8 cases, and vascular invasion in 3 cases. Mitotic activity was 0 to 50 mitotic figures (MF)/50 high power fields (HPF) (median, 0 MF/50 HPF) with atypical MF in 6 cases. IHC results were: SMA (20/25),
desmin (8/22), HMB45 (22/24),
Melan-A (13/18), MITF (9/18),
S-100 protein (8/24), CK (3/23),
vimentin (12/14), TFE3 (5/17), c-kit (1/20), and CD34 (0/7). Clinical follow-up (24 of 26 patients, 92%; median, 30 months; range, 10-84 months) showed 3 local recurrences and 5 distant
metastases. At last available clinical follow-up, 2 patients (8%) were dead of disease, 4 patients (17%) were alive with metastatic or unresectable local disease, and 18 patients (75%) were alive with no evidence of disease. No patient in our series had a history of
tuberous sclerosis complex. Recurrence and/or
metastasis was strongly associated
tumor size > median size (8 cm), mitotic activity greater than 1/50 HPF, and
necrosis. We conclude that
PEComas of soft tissue and gynecologic origin may be classified as "benign," "of uncertain malignant potential," or "malignant." Small
PEComas without any worrisome histologic features are most likely benign.
PEComas with nuclear pleomorphism alone ("symplastic") and large
PEComas without other worrisome features have uncertain malignant potential.
PEComas with two or more worrisome histologic features should be considered malignant. Occasional
PEComas express unusual markers, such as
S-100 protein,
desmin, and rarely CK. The role of TFE3 in
PEComas should be further studied.