Perivascular epithelioid cell tumor (PEComa) of soft tissue: case report with ultrastructural study

A perivascular epithelioid cell tumor (PEComa) arising in the abdominal wall of a 44-year-old female is described. The lesion was a well-circumscribed but unencapsulated, rubbery, subcutaneous mass measuring 3.5 x 3.5 x 3.0 cm which was removed by simple excision. It was characterized by a nest- or sheet-like arrangement of round to polygonal cells with round nuclei and abundant clear to slightly eosinophilic cytoplasm containing glycogen. There was mild to moderate nuclear pleomorphism with mitotic activity of 6 per 10 high power fields. A short fascicular proliferation of the tumor cells was observed focally. The stroma contained abundant small vascular channels with hyalinization. Immunohistochemically, the tumor cells were strongly positive for vimentin, epithelial membrane antigen, alpha-smooth muscle actin, and HMB45. Ultrastructural examination showed poorly differentiated mesenchymal tumor cells without premelanosomes. There was local recurrence 6 years after excision. Pathologists and clinicians should be aware of the existence of PEComa in soft tissue and should differentiate it from other similar lesions.     

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.     

Sclerosing TSC1 mutated renal cell carcinoma: An unusual pattern mimicking MITF family translocation renal cell carcinoma

The tuberous sclerosis genes and MTOR are increasingly being found to have important roles in novel subtypes of renal cancer, particularly emerging entities eosinophilic solid and cystic renal cell carcinoma (RCC) and high‐grade oncocytic renal tumor (HOT)/RCC with eosinophilic and vacuolated cytoplasm. We report a unique renal neoplasm in a 66‐year‐old woman that initially mimicked MITF family translocation RCC due to mixed clear and eosinophilic cells, extensive stromal hyalinization, and psammoma bodies, yet which was negative for TFE3 and TFEB fluorescence in situ hybridization and a next generation sequencing (NGS) gene fusion assay. Cytoplasmic stippling triggered consideration of TSC‐associated neoplasms, and a targeted NGS assay revealed a variant in exon 21 of TSC1 resulting in c.2626G>T p.(Glu876*) truncating mutation. This report adds to the morphologic spectrum of TSC‐related renal neoplasms, including prominent stromal hyalinization as a potentially deceptive pattern. Due to the overlap in cytoplasmic stippling between eosinophilic solid and cystic RCC and HOT/RCC with eosinophilic and vacuolated cytoplasm, it is debatable which category this example would best fit. Further understanding of these entities and other renal neoplasms with alterations in the TSC genes will elucidate whether they should be considered a family of tumors.     

Perivascular epithelioid cell tumor (PEComa) of the liver: a case report and review of the literature

Perivascular epithelioid cell tumor (PEComa) is rare entity and has been described only recently. By immunohistochemistry and genetics it belongs to the family of tumours which comprises angiomyolipoma, clear cell "sugar" tumor of lung, lymphangioleiomyomatosis and clear cell myomelanotic tumor of ligamentum falciforme/teres hepatis. We describe an unusual case of hepatic PEComa arising in a 55-year-old woman with previous history of glioblastoma. Histologically the tumor grew in expansive way, and was composed of clear and eosinophilic epithelioid cels, without vascular or lipomatous component characteristic of angiomyolipoma. There was mild nuclear pleomorphism, sporadic mitotic activity and haemorrhage without necrosis. On immunohistochemistry, the tumor was HMB-45+50, Melan-A and smooth muscle actin positive. Tyrosinase, S-100 protein, cytokeratin coctail, EMA, vimentin, muscle specific actin, CD10, TTF-1, hepatocyte, desmin and cyclin D1 were negative. Sporadic nuclear p53 positivity was seen. The main differential diagnosis of hepatic PEComa includes clear cell variant of liver cell adenoma and hepatocellular carcinoma, metastases of various clear cell carcinomas and metastasis of malignant melanoma. In respect of uncertain biologic potential of PEComa, long term follow up is indicated.     

Comparative genomic hybridization study of perivascular epithelioid cell tumor: molecular genetic evidence of perivascular epithelioid cell tumor as a distinctive neoplasm

Perivascular epithelioid cell tumor (PEComa) is a neoplasm composed chiefly of HMB-45-positive epithelioid cells with clear to granular cytoplasm and a perivascular distribution. Such tumors have been reported in different organs under a variety of designations. The cytogenetic features of these neoplasms have not been well studied. We collected 9 tumors (5 of kidney, 1 of prostate, 1 of urinary bladder, 1 of the pelvic cavity soft tissue, and 1 of uterus) from 8 patients, including one patient with tuberous sclerosis complex. The paraffin blocks of tumor tissue were submitted for comparative genomic hybridization analyses. Gross chromosomal aberrances were observed in all cases. The frequent imbalances were losses on chromosome 19 (8 cases), 16p (6 cases), 17p (6 cases), 1p (5 cases), and 18p (4 cases) and gains on chromosome X (6 cases), 12q (6 cases), 3q (5 cases), 5 (4 cases), and 2q (4 cases). The frequent deletion of 16p in which TSC2 gene is located indicates the oncogenetic relationship of PEComas with angiomyolipoma as a TSC2-linked neoplasm. From a molecular genetic perspective, the recurrent chromosomal alterations in both renal and extrarenal tumors further support the concept of PEComa as a distinctive tumor entity regardless of anatomic location.     

Primary hepatic clear cell myomelanocytic tumor. Case report and review of the literature

A case of hepatic clear cell myomelanocytic tumor in a 31-year-old woman presenting clinically with abdominal pain is reported. Histopathologic examination showed a lesion characterized by a population of large epithelioid cells with clear or eosinophilic granular cytoplasm, rich in glycogen. Immunohistochemically, the tumor cells were positive for HMB-45, Melan-A and muscle-specific actin, but negative for epithelial markers, desmin, S-100 protein, and neuroendocrine markers. Ultrastructurally, the tumor cells had abundant glycogen, well-developed rough endoplasmic reticulum, microtubules and aberrant melanosomes. Clinical and pathologic features with a brief review of the relevant literature for hepatic CCMMT as a variant of perivascular epithelioid cell tumor (PEComa) are discussed.     

Digestive PEComas: a solution when the diagnosis fails to "fit"

We report two cases of digestive/intra-abdominal PEComa. The first lesion developed in the caecum of a 36-year-old woman, the second in the pararectal region of a 35-year-old woman. The first tumor was formed from spindle cells arranged in fascicles, the second contained predominantly epithelioid cells with prominent nucleoli. Immunohistochemically, tumor cells expressed smooth muscle actin and melanocyte markers (HMB45), S-100 protein and CD117 were negative. Based on the morphologic aspect and, above all, on the immunohistochemical study the diagnosis of PEComa was retained for both lesions. In the gastrointestinal tract, the principal differential diagnoses of PEComas are gastrointestinal stromal tumors, particularly the round cell/epithelioid subtype, and metastases of carcinoma and melanoma. Other differential diagnoses include rhabdomyosarcoma, paraganglioma, leiomyosarcoma, and clear cell sarcoma.     

Malignant perivascular epithelioid cell tumor involving the prostate

Perivascular epithelioid cell tumor (PEComa) is a neoplasm chiefly composed of HMB-45-positive epithelioid cells with clear-to-granular cytoplasm and a perivascular distribution. We describe such a tumor involving the prostate and seminal vesicle in a 46-year-old man. The tumor had characteristic histologic features of PEComa. Immunohistochemically, the tumor cells were positive for HMB-45 but negative for epithelial markers, Melan-A, and S100 protein. The tumor behaved in a malignant fashion, and the patient died of the disease 4 years after diagnosis.     

Epithelioid angiomyolipoma: a morphologically distinct variant that mimics a variety of intra-abdominal neoplasms

This review examines the histopathologic, immunohistochemical, ultrastructural, and molecular biologic features of epithelioid angiomyolipoma (EAML), with an emphasis on the differential diagnosis of intra-abdominal EAML. Epithelioid angiomyolipoma is an uncommon mesenchymal tumor with malignant potential, frequently associated with tuberous sclerosis complex. Histologically, EAML is characterized by sheets or nests of large polygonal epithelioid cells with abundant eosinophilic or occasionally clear cytoplasm, often with prominent nucleoli, and EAML may include multinucleated and markedly pleomorphic forms. As these tumors share a distinctive perivascular epithelioid cell phenotype, they belong to the PEComa tumor family. Nearly all EAMLs show immunoreactivity for both melanocytic and myoid markers. Ultrastructurally, EAMLs show evidence of melanogenesis by the presence of premelanosomes. Epithelioid angiomyolipoma can pose significant diagnostic challenges as it mimics morphologically a variety of neoplasms including renal cell carcinoma, renal oncocytoma, adrenal cortical neoplasm, epithelioid smooth muscle tumor, epithelioid peripheral nerve sheath tumor, epithelioid gastrointestinal stromal tumor, epithelioid melanoma, hepatoblastoma, and hepatocellular carcinoma. The variation in immunophenotype in these tumors requires a prudent use of immunohistochemistry, which may occasionally need complementation by electron microscopy to establish the correct diagnosis.     

Diffuse intra-abdominal clear cell myomelanocytic tumor: report of an unusual presentation of "PEComatosis" simulating peritoneal mesothelioma

We report a case of diffuse myomelanocytic tumor of the peritoneum that simulates, clinically and instrumentally, a malignant mesothelioma. The patient was a 70-year-old woman with a history of ancient hysterectomy for fibroids, who presented with abdominal discomfort. Exploratory laparotomy revealed diffuse encasing of the peritonealized organs by a thin, fleshy, gray-white tissue rind. Scattered tumor masses were present as well. A dominant lesion measuring 6 cm in larger size was resected from the pelvis. Histological examination revealed a tumor composed of epithelioid and spindle cells, exhibiting either a clear or slightly eosinophilic cytoplasm and a mild to moderate nuclear pleomorphism. Focal areas of necrosis could be documented. Immunohistochemically, tumor cells were positive for HMB45, melan-A, and smooth muscle actin, but negative for other antibodies, including epithelial markers, desmin, and S100 protein. We believe that this case represents an example of myomelanocytic tumor of uncertain biologic potential, a member of the recently devised perivascular epithelioid cell tumors (PEComa), with an unusual presentation simulating a diffuse mesothelial neoplasm. The origin of this particular lesion is briefly discussed in light of the recent literature published on the subject.     

Fine needle aspiration cytology of clear cell "sugar" tumor (PEComa) of the lung: report of a case

PEComa (clear cell "sugar" tumor) of the lung is a rare benign tumor of the lung probably arising from the perivascular epithelioid cells (PECs). We report a case of pulmonary PEComa arising from the periphery of the right lobe of a 64-year-old male. To our knowledge, this is the second case in the English literature diagnosed by fine needle aspiration biopsy. In this case report, the clinical, cytologic and immunohistochemical features clear cell "sugar" tumor of the lung are discussed and compared with the previously published literature. The differential diagnosis and methods for distinguishing the various clear cells lesions in the lung are discussed.     

Primary perivascular epithelioid cell tumor in the rectum: A case report and review of the literature

Perivascular epithelioid cell tumor (PEComa) is a rare collection of tumors arising in a wide array of anatomic locations. It is characterized by the presence of a peculiar population of myomelanocytic marker-positive perivascular epithelioid cells, and is commonly detected in the uterus. The colorectal area is an uncommon site for primary PEComa. In this study, we describe a 17-year-old patient presenting with a rectal polyp. Histologically, the tumor consisted of sheets of round to polygonal epithelioid cells with clear and granular cytoplasm, and a prominent capillary network. Some of the tumor cells were positive for Fontana-Masson staining. Immunohistochemically, the tumor cells were positive for HMB-45, and were negative for cytokeratin, vimentin, S-100 protein, actin, desmin, EMA, CD34, and c-kit. After finding melanosomes or premelanosomes at the ultrastructural level, the diagnosis of PEComa was made. Although PEComa arising within the intestinal tract is unusual and clinically unexpected, PEComa should be considered in the differential diagnosis of rectal polypoid lesions.     

Perivascular epithelioid cell tumor in the duodenum: challenge in differential diagnosis

Defined as a family of scarce mesenchymal neoplasm which distinctively co-express melanocytic markers and muscle markers, perivascular epithelioid cell tumors (PEComas) have been reported almost everybody site. Perivascular epithelioid cell tumors-not otherwise specified (PEComas-NOS) arising in the gastrointestinal (GI) tract are still restricted into sporadic case reports. Herein we present a case of GI PEComas-NOS which occurs in the duodenum of a 27-year-old male. Our initial diagnosis tended to gastrointestinal stromal tumor or smooth muscle tumor till the correct diagnosis of perivascular epithelioid cell tumor (PEComa) was established by postoperative pathological examination. We also make a literature review of GI PEComas-NOS and highlight the challenge it brings to the differential diagnosis.     

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.     

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.     

Late pulmonary metastasis in uterine PEComa

Perivascular epithelioid cell tumours (PEComas) other than angiomyolipoma, clear cell "sugar" tumour of the lung, and lymphangioleiomyomatosis are very rare mesenchymal tumours. The uterus seems to be the most prevalent site of involvement, but only 13 cases of uterine PEComa have been described. Three of these cases exhibited local aggressive behaviour and only one showed metastasis. Because of the extremely small number of cases, PEComas are considered tumours of uncertain malignant potential. This report describes a 68 year old woman, who presented with multiple pulmonary lesions seven years after the initial diagnosis of well differentiated endometrial stromal sarcoma. Histological and immunohistochemical analysis of the pulmonary lesions, in addition to re-evaluation of the primary uterine tumour, led to the final diagnosis of metastatic uterine PEComa. The findings indicate that any PEComa might have malignant potential. Spreading of this tumour to other organs might become evident even several years after primary manifestation.     

肾脏上皮样色素性透明细胞肿瘤病理形态观察

目的 探讨上皮样色素性透明细胞肾脏肿瘤形态学特点,加强对该肿瘤的认识,减少误诊.方法 回顾性分析2000余例肾脏肿瘤,符合上皮样色素性透明细胞肿瘤3例,通过HE、免疫组织化学EnVision法观察3例肿瘤形态学特点,对其中1例行超微结构观察,同时复习相关文献.结果 女性2例,男性1例,2例形态学表现为透明细胞癌样,1例见透明细胞和嗜酸性细胞构成乳头结构.免疫组织化学上皮标记及S-100蛋白均为阴性,HMB45均为阳性,2例Melan A阳性.电镜末见黑色素小体结构.结论 色素性透明细胞上皮样肿瘤是非常罕见的肾脏肿瘤,病理学特征兼有肾细胞癌、上皮样血管平滑肌脂肪瘤与黑色素瘤等肿瘤特征,免疫组织化学有利于鉴别诊断.其可能是上皮样血管平滑肌脂肪瘤的一种亚型.     

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.     

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.