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.     

Perivascular epithelioid cell tumor of the pancreas: case report and literature review

Neoplasms with perivascular epithelioid cell differentiation (PEComas) of the pancreas are rare, and only 22 cases have been reported globally. Therefore, clinician and pathologist knowledge of this tumor’s biologic behavior and molecular genetics has been limited. A 40-year-old female patient presented with a space-occupying mass in the pancreas found by abdominal B-mode ultrasonography upon physical examination. Laparoscopic resection of the pancreatic body and tail was performed, and a cystic-solid tumor of about 2 × 2 cm was identified. PEComa is a type of mesenchymal tumor with uncertain biologic behavior, more frequently found in females. PEComa features a unique histomorphology and immunophenotype. We summarize the characteristics and research progress of the pancreatic PEComa, which will be convenient for physicians and pathologists to fully understand the disease to avoid misdiagnosis and to provide a reference for treatment and prognosis.     

Primary perivascular epithelioid cell tumor of the bladder

The perivascular epithelioid cell family of tumors includes angiomyolipoma, clear cell “sugar” tumor of the lung, lymphangioleiomyomatosis, and clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres. Less frequently, perivascular epithelioid cell tumors arise in various other locations throughout the body including soft tissue, bone, and visceral organs. We report a case of a 23-year-old man who presented with 2-month history of frequent micturition and odynuria. Based on clinical examination, ultrasound computed tomography imaging, surgical operation, and histopathologic studies, a definitive diagnosis was made. Further characteristic images and pathology of this disease are discussed.     

Perivascular epithelioid cell tumor of the rib

We present a rare case of perivascular epithelioid cell tumor (PEComa) in the right 6th rib of a 28-year-old man. A plain computed tomography scan showed a round osteolytic lesion in the right 6th rib. The resected tissue contained a globular-shaped, soft tumor. Histologically, the tumor was rich in vasculature and exclusively composed of perivascular epithelioid cells with clear cytoplasm. Immunohistochemically, the tumor expressed diffusely a melanocyte marker, human melanoma black-45, and focally a myogenic marker, alpha-smooth muscle actin, but not an epithelial marker, AE1/AE3. Fontana-Masson-positive melanin pigments were present and c-kit receptor tyrosine kinase (CD117), involved in the development of melanocytes but not myogenic cells, was expressed in tumor cells. These findings indicate that the tumor is PEComa with some differentiation into melanocytes. Notably, owing to the unique location of the occurrence, the tumor occupied bone marrow tissues of the rib, resulting that the tumor has the potential for hematogenous metastasis. In spite of the lack of cells with severe atypia, necrosis, and numerous mitoses, tumor cells invaded into surrounding tissues and overexpressed cyclin D1. To the best of our knowledge, this is the first case report of PEComa arising from the rib with the signs of malignant potential.     

Perivascular epithelioid cell tumor of the uterine cervix identified on a conventional cervical smear

Perivascular epithelioid cell tumors (PEComas) most frequently involve the uterus, particularly the uterine corpus and very occasionally the cervix. One case of PEComa identified using a conventional cervical smear has previously been documented. Herein, we present the second such case. The patient was a 51‐year‐old woman with abnormal genital tract bleeding. Samples collected for conventional cervical smears were submitted for cytopathological examination, which revealed discohesive monotonous tumor cells showing epithelioid morphology, ample cytoplasm that was pale to weakly eosinophilic, and mildly enlarged nuclei. The cytopathological features were well correlated with histopathological findings. Upon immunohistochemistry, the tumor cells were positive for both melanocytic and smooth muscle markers. Based on these findings, PEComa was diagnosed. Subsequently, a total hysterectomy with bilateral salpingo‐oophorectomy was performed, revealing that the tumor (28 × 22 × 12 mm) was located at the superficial part of the endocervix. We propose that the cytopathological findings described herein can guide the diagnosis of PEComa, even though this tumor is rare. Diagn. Cytopathol. 2015;43:1011–1016. © 2015 Wiley Periodicals, Inc.     

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.     

Perivascular epithelioid cell tumour (PEComa) of the soft tissue

AIMS: PEComa is a rare tumour developing from perivascular epithelioid cells (PEC) and is characterised by positive immunoreactivity for HMB45. Since PEComas are tumours having both a spindle cell component and an epithelioid and giant cell component, as seen in many sarcomas, as well as having a wide distribution in various organs and soft tissue, we reviewed cases originally diagnosed as sarcomas of the soft tissue in our institution and screened them by immunostaining for HMB45. METHODS: Consecutive soft tissue sarcomas (31 tumours) retrieved from the Surgical Pathology file at our institution for a period of 3 years were submitted for immunostaining for HMB45. Cases with positive HMB45 immunostaining were submitted for further immunostaining for MART1, CD68, S100 protein, cytokeratin AE1/3, EMA, vimentin, MSA and CD117. RESULTS: Of 31 sarcomas, three tumours in the group of 11 malignant fibrous histiocytomas (MFH) and unclassified sarcomas showed positive immunoreactivity for HMB45 and MART1 in 1-25% of tumour cells. The three tumours were located in the lower extremities and measured 8, 11 and 12 cm in diameter. Patient gender male:female was 2:1 and ages were 46, 56 and 60 years. Microscopically, the tumours were composed of a variable proportion of spindled cells, multinucleated cells and epithelioid cells disposed in diffuse sheets or nests. Mitotic figures and necrosis were frequent. The immunoreactivity was diffuse for CD68, focal for AE3 and EMA, negative or focal for MSA and CD117, and negative for S100 and AE1. All three patients developed lymph node or distant metastases and died of the disease within 1-2 years. CONCLUSIONS: PEComa re-screened from the group of high grade sarcomas without definite differentiation range from pleomorphic to monomorphic cytohistopathological features. Immunostaining for HMB45 of unclassified sarcomas is useful for the classification of these tumours. They occur preferentially in the lower extremities and have a high malignant potential when associated with large size, tumoural necrosis and high mitotic activity.     

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 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.     

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.     

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.     

Monotypic epithelioid angiomyolipoma of the liver

AIMS: Monotypic epithelioid angiomyolipoma is a recently recognized renal tumour, which is composed purely of epithelioid cells coexpressing markers of both smooth muscle differentiation and melanogenesis (HMB45). We report here the first case of monotypic epithelioid angiomyolipoma arising in the liver. CASE DETAILS: A 30-year-old woman without tuberous sclerosis complex (TSC) was incidentally found to have a hepatic mass by ultrasonography. Grossly, the resected tumour showed a nodule-in-nodule appearance, with large areas of haemorrhagic necrosis. Microscopically, the tumour was composed of pleomorphic epithelioid cells with clear, eosinophilic cytoplasm. Neither adipocytes nor abnormal vessels were recognized in the tumour. Immunohistochemically, the tumour cells were strongly positive for HMB45 and S100 protein, focally positive for desmin, vimentin and smooth muscle actin, and negative for epithelial markers (cytokeratins, EMA). Ultrastructural analysis showed numerous dense granules with some striated ones resembling melanosomes, myofilaments and pinocytic vesicles in the cytoplasm. Molecular analysis showed no allelic loss of the TSC2 region or 12 other chromosomal regions. The patient is free of disease over 1 year after the operation. CONCLUSION: We consider that this hepatic tumour is closely related to angiomyolipoma, and a counterpart of renal monotypic epithelioid angiomyolipoma.     

Ultrasound‐guided fine needle aspiration cytology in the diagnosis of hepatic and pancreatic perivascular epithelioid cell tumors: A case series

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors that can affect any part of the body. They can be sporadic or arise in the setting of tuberous sclerosis (TSC). In this article, we report a series of three hepatic and two pancreatic PEComas diagnosed preoperatively with ultrasound‐guided fine needle aspiration (FNA). All patients were female (age range 28‐70), had no personal history of TSC and presented with a single, localized painless mass. Rapid on‐site evaluation (ROSE) of cytologic samples was performed for all cases to evaluate for cellular content and adequacy of specimens. Direct smears and cell block preparations revealed a proliferation of medium to large polygonal epithelioid cells, with abundant eosinophilic and vacuolated cytoplasm, arranged in sheets and nests. On immunohistochemistry (IHC), neoplastic cells showed co‐expression of melanocytic and smooth muscle markers and a diagnosis of PEComa was rendered. PEComas of the pancreas and liver are rare neoplasms, but should always be considered when examining “clear cell” neoplasms, especially in young female patients. If good quality cytologic samples are obtained by FNA, a correct diagnosis can be achieved with the help of IHC. This is of particular importance in order to plan adequate surgical strategy and to avoid overtreatment.     

4例胃肠道血管周上皮样细胞肿瘤临床病理学分析

目的 探讨胃肠道血管周上皮样细胞肿瘤(perivasculaRepithelioid cell tumor,PEComa)的临床及病理学特点.方法 回顾性复习4例胃肠道原发血管周上皮样细胞肿瘤的病理切片及临床资料,选取典型蜡块做相关的免疫组化染色,抗体包括黑色素相关抗原HMB45、melan-A、肌源性标记抗原SMA、desmin,以及vimentin、CgA、CK、S-100、CD117、CD34.结果 4例PEComas中男性3例,女性1例,年龄分别为36、38、42及45岁.其中2例位于升结肠,1例位于降结肠,1例位于乙状结肠.肿瘤大小4.5～10 cm,境界清楚,切面灰白色,质地均匀,局部可见出血.镜检:肿瘤细胞呈上皮样排列,细胞质丰富,透亮或嗜酸性颗粒状,细胞核空泡状,有明显的核仁,间质富于毛细血管、血窦以及厚壁血管.细胞异型性小,个别病例局部可见轻～中度异型性,分裂象0～3个/10 HPF.免疫组化结果 :肿瘤弥漫表达HMB45(4/4),弥漫或片状表达vimentin(4/4)、SMA(4/4)以及desmin(3/4).CgA、Syn、CK、S-100、CD117、CD10及CD34均阴性.4例患者行局部肠管及肿瘤切除,术后随访8、15、32及36个月均无复发和肿瘤转移.结论 胃肠道PEComa少见,为低度恶性潜能肿瘤,形态类似于软组织和其他部位的同类肿瘤,手术切除为首选治疗.     

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.     

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.     

子宫血管周上皮样细胞肿瘤临床病理观察

目的研究子宫血管周上皮样细胞肿瘤的病理学特征、诊断、鉴别诊断和生物学行为。方法对5例子宫血管周上皮样细胞肿瘤进行常规组织学和免疫组织化学（SP法）染色和观察,对患者进行随访,并复习相关文献。结果光镜下5例肿瘤均由透明或嗜酸细胞巢或宽窄不等的细胞索组成,间质有丰富的小血管和程度不等的透明变。免疫组织化学染色示5例瘤细胞均黑色素细胞标记阳性和程度不等的结蛋白和平滑肌肌动蛋白（SMA）阳性,CK和CD10阴性。5例患者现均存活。结论子宫血管周上皮样细胞肿瘤具有较特征性的组织病理及免疫组织化学特点,HMB45阳性对诊断有重要作用。该肿瘤分良性、恶性潜能不能确定和恶性三类,应与透明细胞癌和上皮样平滑肌肿瘤区别。