PECs, first described by Bonetti et al [2
], do not have a normal anatomic homologue. PECs are characterized by co-expression of melanocytic and muscle markers, epithelioid to spindle shapes with ample clear to eosinophilic cytoplasm, and at least in some cases, arrangement around blood vessels [3
]. The term "PEComa"(perivascular epithelioid cell tumor) was introduced in 1996 by Zamboni et al [4
], as synonym for tumors composed primarily by PECs. In the WHO soft tissue volume, PEComas are defined as "mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells" [5
], including entities such as AML, LAM, and CCST of the lung. In recent years, more tumors are being reported and categorized as members of the PEComa family, including monotypic epithelioid AML, extrapulmonary CCST, and clear-cell myomelanocytic tumor (CCMMT) of the falciform ligament/ligamentum teres.
PEComas may arise from multiple anatomical sites, including the kidney, lung, pancreas, liver, uterus, breast, ligament teres, falciform ligament, orbit, skin and soft tissue, with the uterus and retroperitoneum appearing to be the most frequent sites of origin. The first case of uterus PEC tumor was reported by Pea et al [6
]. PEComas share a common morphophenotypic feature: diffuse, nested and/or fascicular proliferation of spindled and epithelioid cells, tumor cells with clear to eosinophilic cytoplasm, centrally located nuclei, and immunoreactivities to both the melanogenic-related markers and to a lesser extent, muscular markers. Folpe et al [7
] reported CD117 reactivity in about 5% of PEComas. Ultrastructurally, structures interpreted as melanosomes and premelanosomes have been demonstrated in PEComa of the uterus [8
]. Vang and Kempson [9
] divided uterine PEComas into A and B types. Type A tumors show a tongue-like growth pattern and are composed of cells with clear to eosinophilic pale granular cytoplasm, diffuse HMB-45 expression, and focal smooth muscle reactivity. Type B tumors are composed of epithelioid cells with less prominent clear cell features, with only a few of being HMB-45 positive; in addition, cells of type B tumor demonstrate an extensive muscle marker expression and a lesser degree of tongue-like growth pattern.
Uterine PEComa lacks characteristic clinical and imaging changes; the diagnosis mainly relies on pathological approach, and should be differentiated from the following tumors: (1) Epithelioid smooth muscle tumor(ESMT)- the ESMT cells are round, polygonal and spindle-shaped; the spindle-shaped cells had cigarette-like nuclei with rounded ends; there was typical smooth muscle transition; they are usually HMB45 negative, without characteristic capillarity network of bloodvessels. PEComa is supplied by rich blood vessels, and the tumor cells surrounded the blood vessels, forming into patches and nests; they are often HMB45 positive. It has also been reported that a small number of ESMT cells could be HMB45 positive, but Melan-A negative; therefore double positive for SMA and Melan-A indicate a higher probability of PEComa. (2) Endometrial stromal sarcoma(ESS)-the tumor cells are spindle-shaped with less cytoplasm and negative for HMB45; PEComa cells are large and round or polygonal in shape, with rich eosinophilc cytoplasm, and are HMB45 positive. Some PEComa patients also have lymphangioleiomyomatosis and tuberous sclerosis, which has not reported in ESS patients. (3) Uterine clear cell carcinoma (UCC)-the tumor is composed of cells with clear cytoplasm and a hobnail morphology, which forming into solid, ductal or papillary shapes, negative for HMB45 and positive for CK. (4) Metastatic renal clear cell carcinoma (MRCcc)-the cytoplasm is clear and polygonal shaped; the round tumor cells arranged into nest, alveolar, ductal, or papillary shapes, but with no perivessel structure; the tumor is HMB45 negative, and CK, EMA positive. (5) Paraganglioma-it should be differentiated with PEComa when the cytoplasm is clear. Paraganglioma cells are arranged in streaks, glands, or nests, with flat supporting cells lining around, and with distinct organoid and pseudorosette structure; besides, they are HMB45 negative, and NSE, Syn, CgA and NF positive; the supporting cells are positive for S-100 protein.
PEComas have been reported as predominantly benign. Greene [10
] believed that uterine PEComas were tumors with uncertain malignant potentials. Folpe et al [7
] reported PEComas in 26 patients with soft tissue and gynaecologic origin, and classified the tumors as "benign", "of uncertain malignant potential" and "malignant"; they also observed a significant association between tumor size > 5 cm, infiltrative growth pattern, high nuclear grade, necrosis and mitotic activity > 1/50 HPF with aggressive behavior of PEComas. The 2002 WHO soft tissue and bone book [5
] states that PEComas have the following features: infiltrative growth, marked hypercellularity, nuclear enlargement, hyperchromasia, high mitotic activity, atypical mitotic figures, and coagulative necrosis, and therefore PEComas should be regarded as malignant. However, by now we have failed to understand the real behavior of these ubiquitous tumors, because some tumors with "benign" appearance have aggressive behavior and others with "malignant" appearance have indolent course. Late recurrences of the tumor have been reported, including one with lung metastasis 7 years after the primary tumor had been described [11
Due to the multicentricity of the lesions, we favor the designation of PEComatosis proposed by Fadare et al [12
]. PEComatosis is very rare. Table summarizes the clinical properties of all the five PEComatosis cases reported in the English literature. All the 5 cases were women aged 39-70 years old (a mean of 54 years old). Most cases involved the uterus, cervix and the genital system, and were complicated with TSC. Our case was a 46 years old woman involving the uterus, cervix, broad ligament and pelvic cavity, but without evidence of TSC.
Reported Cases of PEComatosis in the English Language Literature (5 Cases)
Whether the multiple foci of PEComas are truly multicentric or whether they originate from a single primary site remains to be further investigated. To the best of our knowledge, the present case is the first PEComatosis in China. Treatment of PEComas is challenging since chemotherapy and radiotherapy seem not effective, and surgery is currently the most important treatment of these tumors.