C-Kit-positive metastatic malignant pigmented clear-cell epithelioid tumor arising from the kidney in a child without tuberous sclerosis

We report the first pediatric case of malignant pigmented epithelioid clear-cell tumor arising from kidney; the lesion occurred in a 12-year-old girl without tuberous sclerosis. The tumor was widely metastatic to the retroperitoneum and chest, and the patient died of the disease 9 months after diagnosis, despite active chemotherapy. Pigmented epithelioid clear-cell tumor of the kidney is a rare variant of epithelioid angiomyolipoma and a member of the family of perivascular epithelioid cell tumors (PEComas). The tumor demonstrated overlapping features between clear-cell sugar tumor and epithelioid variant of angiomyolipoma. Tumor cells were positive for HMB-45 expression, negative for any evidence of muscular differentiation, and contained melanin pigment and premelanosomes in the cytoplasm. Diffuse C-Kit (CD117) positivity was identified throughout the tumor. This is the first report of C-Kit–positive malignant PEComas.     

Malignant PEComa of the adrenal gland

Perivascular epithelioid cell neoplasms, also known as PEComas, are unique mesenchymal tumors exhibiting perivascular epithelioid cell differentiation, characterized by a mixed myogenic and melanocytic phenotype. PEComas arising in visceral organs outside of the kidney, liver, and lung are rare, and often pose problems in diagnosis. Examples of this neoplasm originating in the adrenal gland are limited. The present report details the clinical and pathologic features of an unusual case of a pure epithelioid PEComa (epithelioid angiomyolipoma) of the adrenal gland exhibiting clinically malignant behavior in the form of pulmonary metastases, a feature not previously described in tumors of this site. The diagnosis was supported by immunohistochemical studies demonstrating expression of myoid and melanocytic antigens. The present case serves to emphasize the potential of PEComa for clinically aggressive behavior and the importance of distinguishing this tumor from other epithelioid neoplasms that are more commonly encountered in the adrenal gland.     

PEComa: what do we know so far?

PEComas (tumours showing perivascular epithelioid cell differentiation) are a family of related mesenchymal neoplasms that include angiomyolipoma, lymphangiomyomatosis, clear cell "sugar" tumour of the lung, and a group of rare, morphologically and immunophenotypically similar lesions arising at a variety of visceral and soft tissue sites. These tumours all share a distinctive cell type, the perivascular epithelioid cell or "PEC' (which has no known normal tissue counterpart). PEComas show a marked female predominance and are composed of nests and sheets of usually epithelioid but occasionally spindled cells with clear to granular eosinophilic cytoplasm and a focal association with blood vessel walls. PEComas appear to arise most commonly at visceral (especially gastrointestinal and uterine), retroperitoneal, and abdominopelvic sites, with a subset occurring in somatic soft tissue and skin. Nearly all PEComas show immunoreactivity for both melanocytic (HMB-45 and/or melan-A) and smooth muscle (actin and/or desmin) markers. A subset of PEComas behave in a malignant fashion. This review examines the members of the PEComa family, with an emphasis on lesions arising outside of the kidney, lung and liver, and discusses preliminary evidence for pathological features that might predict malignant behaviour.     

Malignant perivascular epithelioid tumor of the vagina: Report of a rare case with brief review of literature

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors with immunohistochemical co‐expression of melanocytic and myoid markers. Vaginal PEComas have been described in only nine cases so far. We describe the case of a 65‐year‐old female with a large growth in the left lateral vaginal wall. Biopsy imprint smears showed dispersed tumor cells with anisonucleosis, multinucleation, and bizarre forms, suggestive of a malignant tumor. Histopathology, however, showed perivascular arrangement of clear epithelioid cells, focal necrosis, intracellular brown pigment in few cells, and mitotic activity at 2 to 3 per 50 high power fields. Immunohistochemical positivity for vimentin, HMB‐45, S‐100 protein, desmin, and MyoD1 assisted in rendering a final pathological diagnosis of malignant PEComa of the vagina. Further work‐up revealed metastatic deposits in liver and retroperitoneal lymph nodes. PEComa arising in vagina is an unusual phenomenon with the malignant variant being an extremely rare tumor. Awareness of the characteristic morphology and utilization of a panel of immunohistochemical stains are mandatory to be able to make a precise diagnosis and appropriate prognostication.     

Malignant neoplasm of perivascular epithelioid cells of the liver

Neoplasms of perivascular epithelioid cells (PEComas) have in common the coexpression of muscle and melanocytic immunohistochemical markers. Although this group includes entities with distinct clinical features, such as angiomyolipoma, clear cell sugar tumor of the lung, and lymphangioleiomyomatosis, similar tumors have been documented in an increasing diversity of locations. The term PEComa is now generally used in reference to these lesions that are not angiomyolipomas, clear cell sugar tumors, or lymphangioleiomyomatoses. While most reported PEComas have behaved in a benign fashion, malignant PEComas have occasionally been documented. We present a case of hepatic PEComa with benign histologic features, which nonetheless presented with metastases to multiple sites nearly 9 years later. This case represents the second documented malignant PEComa of the liver, as well as the longest follow-up of a surviving patient with a malignant PEComa, emphasizing both the need for criteria that more accurately predict the behavior of PEComas and the necessity of long-term follow-up of patients with PEComas.     

Malignant perivascular epithelioid cell tumor of the colon: report of a case with molecular analysis

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm, and malignant cases are extremely rare. A case of malignant PEComa arising in the colon is described herein. The patient was a 43-year-old Japanese woman without a history of tuberous sclerosis complex. The tumor occurred in the abdominal cavity attached to the serosal side of the descending colon. Histologically, the tumor consisted of sheets or closely packed nests of epithelioid cells with clear or eosinophilic cytoplasms. The tumor cells were positive for HMB-45 but negative for S-100 protein and cytokeratins by immunohistochemical staining. Ki-67 labeling index was 2.9%. Peritoneal dissemination of tumor occurred at 20 months and the patient died of tumor at 38 months after the initial operation. This was considered to be a case of malignant PEComa, based on the histological and clinical features. Tumor cells showed overexpression of cyclin D1 but lacked the loss of heterozygosity of the TSC1 and TSC2 genes. The result suggests that the overexpression of cyclin D1 may play an important role in the tumorigenesis of PEComa. Because PEComas can behave in an aggressive manner, careful follow up is warranted.     

Malignant uterine perivascular epithelioid cell tumor: histopathologic and immunohistochemical characterization of a rare tumor in a post-menopausal woman

Background: Perivascular epithelioid cell tumors (PEComas) are rare, mesenchymal neoplasms composed of epithelioid cells exhibiting myogenic and melanocytic differentiation. The uterus is an infrequent site of involvement. The most common histopathologic mimics include leiomyosarcoma, endometrial stromal sarcoma, undifferentiated uterine sarcoma, and malignant melanoma. Rendering an accurate histopathologic diagnosis is essential, owing to the prognostic and therapeutic implications. Case: A 65-years-old post-menopausal woman presented with post-menopausal bleeding, abdominal pain, and heaviness for the last four months. Ultrasound abdomen revealed a large uterine mass replacing the endometrial cavity. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Result: Microscopically, a circumscribed tumor with tumor cells arranged in sheets and interlacing fascicles, with interspersed fine capillary network, was seen. The individual tumor cells were epithelioid to spindle with moderate pleomorphism, round nuclei, vesicular chromatin, prominent macronucleoli, and moderate cytoplasm. Mitosis was 2-3/50 HPFs. On immunohistochemistry, tumor cells were positive for HMB-45, Melan-A, and smooth muscle actin and were negative for h-caldesmon, TFE3, S-100, CD10, and pan-cytokeratin. Based on the histopathologic and immunohistochemical features, a final diagnosis of malignant uterine PEComa was rendered. Conclusions: This index report describes the characteristic histopathologic and immunohistochemical features of malignant uterine PEComa and highlights the salient features that distinguish it from other commonly encountered histopathologic mimics.     

Incidental perivascular epithelioid cell tumor in an inguinal hernia sac

Perivascular epithelioid tumors (PEComa) are uncommon mesenchymal neoplasms demonstrating positivity for muscular and melanocytic immuno-markers. Included in this category are angiomyolipoma, lymphangioleiomyomatosis, and clear cell sugar tumors. Lesions which do not fit into these categories are classified as “not otherwise specified”. We present a case of an incidentally discovered PEComa within inguinal hernia sac contents in a 70-year-old woman. It consisted of spindled and epithelioid cells with bland oval nuclei, small nucleoli and clear to light eosinophilic cytoplasm. There was no atypia or mitoses. The lesion was strongly positive for HMB45 and smooth muscle actin. Pelvic soft tissue and peritoneal PEComas are rarely reported in literature and very little is known about their prognosis. We discuss the immunohistochemistry, differential diagnosis, and pathogenesis of PEComas.     

Perivascular epithelioid cell sarcoma (malignant PEComa) of the ileum

Epithelioid angiomyolipoma (AML) is the prototype of a heterogeneous group of lesions characterized by the presence of HMB-45 positive cells with clear cytoplasm, perivascular distribution, and combined myomelanocytic features, so-called perivascular epithelioid cells (PECs). These lesions are being increasingly referred to as PEComas. PEComas have been reported at diverse anatomic sites, but mainly in the abdominopelvic cavity and rarely in parenchymatous organs, skin, and soft tissues. Gastrointestinal (GI) PEComas are exceptionally rare, with less than 10 cases documented so far. Rare examples of PEComas with pleomorphic histology could have been misinterpreted as unusual variants of carcinoma or sarcoma. To make a contribution to the differential diagnosis of difficult-to-classify pleomorphic GI sarcomas, we report on a malignant pleomorphic neoplasm with features of PEComa involving the terminal ileum in a 63-year-old woman. Fourteen months after resection of the primary tumor, a huge abdominopelvic recurrence was successfully resected, but no distant metastases were detected. The differential diagnosis and malignancy criteria of GI PEComas will be discussed.     

Fine‐needle aspiration cytology of epithelioid malignant peripheral nerve sheath tumor: A case report and review of the literature

The epithelioid variant of malignant peripheral nerve sheath tumor (eMPNST) is an extremely rare soft tissue neoplasm comprising less than 5% of all MPNSTs. It is distinguished cytomorphologically from a conventional MPNST by the presence of polymorphous round epithelioid cells arranged in loose clusters with or without spindled tumor cells. These features pose a diagnostic challenge because the differential diagnosis involves a variety of mesenchymal and non‐mesenchymal tumors including epithelioid sarcoma, sclerosing epithelioid fibrosarcoma, malignant rhabdoid tumor, chordoma, metastatic carcinomas, and melanoma. Thus, it may become imperative to perform immunochemical stains on cell blocks of FNA aspirates to arrive at definitive diagnosis. Reports describing the cytologic features of eMPNST are rare. Herein, we report a case of eMPNST with focus on cytomorphologic and cytoimmunochemical features and differential diagnosis. Diagn. Cytopathol. 2016;44:226–231. © 2015 Wiley Periodicals, Inc.     

Extraskeletal myxoid chondrosarcoma arising from the retroperitoneum

A case of extraskeletal myxoid chondrosarcoma is presented. The tumor occurred in the retroperitoneum and systemic metastases were found at autopsy. The primary and metastatic tumors were soft and strikingly myxoid on gross appearance. Microscopic observation revealed undifferentiated malignant tumor having large amounts of myxoid substance and a small amount of well-differentiated chondrosarcoma element in the primary lesions. The authors obtained an immunohistochemical result that the tumor cells showed positivity for alpha-1-antitrypsin and alpha-1-antichymotrypsin. Regarding S-100 protein, the well-differentiated chondrosarcoma element revealed intense positivity, whereas the poorly differentiated myxoid areas were not positive except for a few tumor cells. This is the first case, to our knowledge, of extraskeletal myxoid chondrosarcoma arising from the retroperitoneum, and immunohistologic findings suggest that alpha-1-antitrypsin and alpha-1-antichymotrypsin may be available markers in poorly differentiated chondrosarcomas showing a negative reaction for S-100 protein.     

Perivascular epithelioid cell tumor (PEComa) of the pancreas: Immunoelectron microscopy and review of the literature

A perivascular epithelioid tumor (PEComa) is a rare tumor probably arising from the perivascular epithelioid cells. Only three cases of pancreatic PEComa have been reported in the English-language literature. The present report describes an extremely rare case of pancreatic PEComa. A 47-year-old Japanese woman complained of lower abdominal pain and a well-demarcated solid tumor was found in the pancreatic head. There was no history of tuberous sclerosis complexes. Pylorus-preserving pancreaticoduodenectomy was thus performed. There was a well-demarcated, solid tumor measuring 17 mm in the pancreatic head. The tumor was composed of a diffuse proliferation of epithelioid tumor cells with many blood vessels but no adipose tissue. The tumor cells expressed HMB45 and α-smooth muscle actin. Ultrastructurally, the tumor cells possessed many membrane-bound granules that were positive for HMB45 on immunoelectron microscopy. The results of immunoelectron microscopy show that some PEComas possess not only typical melanosomes or premelanosomes but also aberrant melanosomes.     

Sklerosierendes epitheloides Fibrosarkom

The sclerosing epithelioid fibrosarcoma (SEF), defined as an entity by Meis-Kindblom et al. in 1995 [15] is now considered to be a variant of fibrosing fibrosarcomas. It is a rare tumor with an intermediate malignant potential leading to local recurrences in one third and to metastases in about 40% of the cases. We report six cases of this entity. At the time of diagnosis two patients of our series already showed metastases in the lungs. The tumors were located in the deep soft tissue and measured between 2.5 and 17 cm. The histology is characterized by small epithelioid cells that are arranged individually or in cords and nests and set typically in a hyaline sclerotic matrix. By immunohistochemistry, all cases were vimentin positive, however EMA positive cells are also possible. The differential diagnosis includes metastases of carcinoma, benign and malignant soft tissue tumors. The distinction of SEF from fibromatosis, fibrous histiocytomas, ossifying fibromyxoid tumors, clear cell sarcomas, epithelioid sarcomas, synovial sarcomas and extraskeletal osteosarcomas is discussed.     

Perivascular epithelioid cell tumor of the uterus: a case report

A case of a perivascular epithelioid cell tumor (PEComa) arising in the uterus of a 35-year-old woman is presented. Imaging studies revealed a 5 cm well circumscribed mass in the uterine fundus. The tumor was composed of clear to faintly eosinophilic, epithelioid and spindled cells. Immunohistochemically, most tumour cells were strongly positive for HMB-45, smooth muscle actin and desmine, but negative for epithelial markers, S-100 Protein and neuroendocrine markers. Reevaluation of the patient for signs of tuberous sclerosis complex after the diagnosis gave negative results. At the most recent follow-up 4 months later there was no evidence of recurrence.     

Perivaskuläre Tumoren der Haut und des Weichgewebes

Perivascular neoplasms of skin and soft tissues comprise a group of benign and malignant mesenchymal neoplasms showing a perivascular myogenic differentiation. Whereas glomus tumour including its variants represents a clearly defined clinicopathological entity, the whole concept of haemangiopericytoma has been questioned in the last years, and no clear diagnostic criteria are established at the moment. Myopericytomas and myofibromas represent a morphological spectrum of perivascular spindle-shaped lesions. Infantile myofibroma/infantile myofibromatosis and solitary myofibroma of adults are characterized by a biphasic growth of mature, spindled, myofibroblastic cells and smaller, immature, mesenchymal cells associated with numerous haemangiopericytoma-like vessels. Benign and rare malignant myopericytomas of skin and soft tissues are characterized by a concentric, perivascular growth of plump spindled and round tumour cells staining positively for muscle actin, alpha-smooth muscle actin and more rarely for desmin. PEComas represent an enigmatic family of neoplasms composed of perivascular epithelioid, clear, and spindled tumour cells characterized by a coexpression of melanocytic and myogenic markers.     

Acral myxoinflammatory fibroblastic sarcoma: a report of two cases

Acral myxoinflammatory fibroblastic sarcoma is a rare low-grade malignant soft tissue tumor, usually observed in the extremities of middle-aged adults. We report two cases which occurred in the thumb and knee of middle-aged women. Both tumors showed a multinodular architecture, with cellular areas, occasional foci of hyalinized fibrosis, and hypocellular areas with a myxoid background. Various neoplastic cells were identified including spindled or rounded epithelioid cells and occasional bizarre giant cells, morphologically mimicking Reed-Sternberg cells or ganglion cells. Tumor cells were strongly immunoreactive for vimentin, and variably positive for CD68 and CD34. Both tumors were completely resected and patients were free of disease without any further treatment after a mean follow-up of 14 months.