Malignant perivascular epithelioid cell tumor of the retroperitoneum

Perivascular epithelioid cell tumors (PEComas) are a rare type of mesenchymal neoplasms characterized by a proliferation of perivascular cells with an epithelioid phenotype and expression of myo-melanocytic markers. The majority of PEComas seem to be benign and usually their prognosis is good. Malignant cases are extremely rare, exhibiting a malignant course with local recurrences and distant metastases. We herein report a case of a malignant PEComa arising in the retroperitoneum. The patient was a 55-year-old woman experiencing abdominal discomfort for approximately one month. Ultrasound and computer tomography (CT) scans of the abdomen revealed a solid mass arising from the retroperitoneum. Microscopically, the tumor was composed of epithelioid cells mixed with spindled cells. The nucleus had significant atypia, and the mitoses were obvious. The focal intravascular tumor embolus was visible. Immunohistochemically, the epithelioid tumor cells were positive for HMB45 and Melan-A, and the spindled tumor celLs were positive for SMA and desmin. Seven months after a surgical resection, an ultrasound revealed liver metastases. In conclusion, the malignant PEComas of the retroperitoneum is a very rare neoplasm with unique morphological and immunohistochemical characteristics. It should be differentiated from other epithelioid cell tumors of the retroperitoneum.     

A huge malignant perivascular epithelioid cell tumor (PEComa) of the uterine cervix and vagina

Perivascular epithelioid cell tumors (PEComas) are a family of rare mesenchymal neoplasms, including angiomyolipoma, clear-cell “sugar” tumor of the lung and extrapulmonary sites, lymphangioleiomyomatosis, clear-cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and clear-cell tumors at various other anatomic sites.     

Malignant pigmented clear cell epithelioid tumor of the kidney: clear cell ("sugar") tumor versus malignant melanoma

A 73-year-old woman presented with an hemorrhagic kidney tumor initially interpreted as a renal cell carcinoma (RCC). A retroperitoneal recurrence infiltrating the duodenal wall was made up of clear cells, some of which contained Fontana-Masson positive pigment, immunopositive for HMB-45, S-100 protein, actin, and vimentin. The same immunohistochemical profile was retrospectively reproduced in the kidney tumor, where melanosomes were also found ultrastructurally. Lipomatous differentiation was not observed. There was no history of malignant melanoma (MM), or stigmata of tuberous sclerosis. The patient died of disease 5 years after the initial diagnosis. This neoplasm can be considered as a malignant, pigmented, clear-cell epithelioid variant of angiomyolipoma, or "sugar" tumor of the kidney, with the peculiarity of having a previously unreported component of pigmented cells visible on light microscopy. This finding raises the possibility that the exceptional cases of MM reported in renal parenchyma may be pigmented variants of epithelioid angiomyolipoma rather than true MM.     

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.     

Triple synchronous neoplasms in one kidney: report of a case and review of the literature

We report the case of a patient with three synchronous but histologically different primary renal tumors that were all in the same kidney. Two tumors were different subtypes of renal cell carcinoma (RCC), and the third was a variant form of angiomyolipoma. The patient was a 62-year-old man who was receiving antihypertensive drugs and came to our hospital for a regular check-up. Ultrasonography performed during the visit revealed a left renal mass, but the patient had no related symptoms. Subsequent computed tomography revealed two round, high-density masses, one in the mid-portion and the other in the lower pole of the left kidney, and multiple cysts in the right kidney and the liver. The mass in the mid-portion measured 3.3 x 3.0 x 2.8 cm, and the mass in the lower pole measured 1.7 x 1.1 x 0.9 cm. A left radical nephrectomy was performed. On gross examination, an additional ovoid nodule (0.6 cm in the greatest dimension) was found in the lower pole. Microscopically, the largest tumor consisted of a broad alveolar arrangement of large round cells with abundant eosinophilic or clear cytoplasm, distinct cell borders, and perinuclear halos, features consistent with chromophobe RCC. The smallest tumor was a conventional (clear-cell) RCC. The third tumor was composed solely of atypical epithelioid cells with prominent nucleoli and yellowish-brown to black pigments. The tumor cells were positive for melanin (Fontana-Masson stain), the melanoma marker HMB45, vimentin, smooth-muscle actin, and the macrophage marker CD68 and were negative for cytokeratin. This tumor was considered a pigmented epithelioid type of angiomyolipoma. The histologic, histochemical, and immunohistochemical features in this case confirmed the presence of three synchronous primary tumors, a chromophobe and a clear-cell type RCC and a pigmented epithelioid angiomyolipoma, all of which were in the same kidney. This case is the first of its type reported in the literature.     

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.     

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 perivascular epithelioid cell tumor of the kidney with rare pulmonary and ileum metastases

Aims: To report one case of malignant perivascular epithelioid cell tumor (PEComa) of the kidney with rare pulmonary and ileum metastases and analyze its clinicopathological features. Methods: We analyzed the clinicopathological features of one case of malignant PEComa of the kidney with pulmonary and ileum metastases. Immunohistochemistry staining was performed. Results: The patient was a 48-year-old man with a renal mass approximately 14 cm × 11 cm × 8 cm in size. Microscopically, the tumor was mainly composed of polygonal epithelioid cells with dense eosinophilic cytoplasm and round nuclei with small nucleoli. Focal tumor cells showed pleomorphism with multinucleated giant cells and prominent nucleoli. The tumor cells nests were surrounded by thick-walled irregular blood vessels. Focal fat cells were found within the tumor. Hemorrhage and coagulative necrosis were also present. The tumor cells were positive for vimentin, HMB45, and Melan-A, and focally positive for SMA and S-100 protein. After 5 years and 5.6 years of nephrectomy, the tumor metastasized to the right lung and ileum, respectively. Conclusion: We first reported one case of malignant PEComa of the kidney with pulmonary and ileum metastases. Metastatic PEComa of the lung and ileum should differentiate from primary carcinoma, metastatic carcinoma, malignant melanoma, and gastrointestinal stromal tumor.     

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.     

Sclerosing variant of perivascular epithelioid cell tumor in the female genital organs

Perivascular epithelioid cell tumor (PEComas), other than angiomyolipoma, clear cell 'sugar' tumor of the lung, and lymphangioleiomyomatosis, is an uncommon mesenchymal neoplasm that arises in the soft tissue and visceral organs. We report herein two cases of sclerosing PEComa; a distinctive variant of PEComa, which is characterized by extensive stromal hyalinization, occurring in the uterus and broad ligament. The patients were 34- and 51-year-old females with no family history of tuberous sclerosis complex. Macroscopically, the tumors had white to gray cut surfaces and were microscopically composed of predominantly spindle- to polygon-shaped cells with clear to slightly eosinophilic cytoplasm and pleomorphic nuclei focally arranged in a perivascular pattern, accompanied by marked stromal hyalinization. These tumor cells were immunohistochemically positive for HMB45 and α-smooth muscle actin. Although this variant of PEComa is very rare, this entity should be considered as a potential primary neoplasm of the female genital organs.     

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.     

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.     

Uterine PEComa with aggressive behavior: A review with an additional case of spontaneous vaginal expulsion

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor originating from perivascular epitheloid cells showing melanocytic and smooth muscle differentiation. The uterus represents the second most common site of origin. A 49 years woman presented to our Hospital for a vaginal spontaneous expulsion of a mass suggestive for malignant mesenchymal tumor. The patient underwent total hysterectomy and bilateral salpingo-oophorectomy and the histopathological report was compliant with a PEComa with aggressive behavior. Medical Literature databases about PEComa were searched. The current literature identified near 90 cases of uterine PEComas and they are categorized as uncertain malignant potential or with aggressive behavior. Primary surgical excision represents the gold-standard treatment. Recently targeted therapy with mTOR inhibitors has been introduced with an important beneficial. In this paper we review the Literature about the uPEComa with aggressive behavior reporting the first case of spontaneous vaginal expulsion.     

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 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.     

CD1a expression in PEComas

According to the World Health Organization classification, neoplasms with perivascular epithelioid cell differentiation (PEComas) are mesenchymal tumors composed of histologically and immunohistochemically distinctive PEC. Generally, nearly all PEComas have immunoreactivity for both melanocytic (HMB-45 and/or melan A) and smooth muscle (actin (SMA) and/or desmin) markers. Recently the authors reported that benign clear cell sugar tumor of the lung, one of the PEComas, expressed CD1a. Therefore the purpose of the present study was to investigate the relationship between PEComas and CD1a expression. Nineteen PEComas were obtained, which included angiomyolipoma of the kidney or liver, lymphangiomyomatosis of the uterus or lung and clear cell sugar tumor of the lung. Eighteen tumors had α-SMA and HMB-45 expression and 16 had melan A expression. In contrast, all 19 tumors had CD1a expression. The present study confirms CD1a expression in many cases of PEComa. These data suggest that CD1a expression can be an additional new marker for PEComas and also supports the distinct and integrated disease entity of PEComas.     

Fine-needle aspiration of epithelioid malignant peripheral nerve sheath tumor (epithelioid malignant schwannoma)

The epithelioid variant of malignant peripheral nerve sheath tumor (MPNST), also known as malignant epithelioid schwannoma, is a relatively rare and recently characterized clinicopathologic entity. The epithelioid variant of MPNST shares many clinical features with conventional MPNST but is characterized by different histologic and cytologic features. These include a distinctive nesting pattern and an abundance of cytoplasm not seen in histology of conventional nerve sheath tumors. Cytologically, the epitheliod variant shows a propensity to cellular discohesiveness and a plasmacytoid or epitheliod appearance that is in contradistinction to the spindled appearance of the usual MPNST. Herein, we report our experience with fine-needle aspiration (FNA) of two epithelioid malignant schwannomas and discuss the FNA cytologic differential diagnosis. Diagn. Cytopathol. 1997;17:200–204. © 1997 Wiley-Liss, Inc.     

Malignant epithelioid angiomyolipoma of the kidney in a patient with tuberous sclerosis: an autopsy case report with p53 gene mutation analysis

We report an autopsy case of malignant epithelioid angiomyolipoma in a 36-year-old male tuberous sclerosis patient. He had been diagnosed to have a bilateral renal tumor 20 years previously. The left kidney had been surgically resected at the age of 34, and the left renal tumor was pathologically diagnosed as classic angiomyolipoma and epithelioid angiomyolipoma. He suddenly died of cardiac arrest, and at autopsy the right kidney weighed 7120 g. The tumor presented with massive necrosis invading the inferior vena cava, but was not hemorrhagic. Microscopic examination revealed tumor cells varying in size with a predominantly solid proliferation pattern and marked atypical large cells with vesicular nuclei and abundant eosinophilic cytoplasm. Mitotic figures were often encountered, and atypical forms were also present. Metastatic lesions were identified in the right lung, liver, diaphragm, and mesentery. Immunohistochemical examination showed epithelioid angiomyolipoma cells that were focally reactive for HMB-45 and showed diffuse positive staining for Melan-A. No mutation was detected in the p53 gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis despite diffuse immunoreactivity for p53. This case was proven to be malignant because of the occurrence of distant metastases, and showed that p53 mutations are not always associated with malignant transformation in epithelioid angiomyolipoma.