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 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.     

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.     

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.     

Malignant perivascular epithelioid cell tumour of the fibula: a report and a short review of bone perivascular epithelioid cell tumour

Perivascular epithelioid cell tumour (PEComa) is a term applied to a family of mesenchymal tumours composed of varying proportions of spindle and epithelioid cell components associated with HMB-45 expression. PEComa rarely arises in the soft tissue, visceral organs, skin and bone. This report details an instance when a purely epithelioid PEComa arose from the right fibula of a 52-year-old Chinese woman without features of tuberous sclerosis complex. The excision specimen disclosed an epithelioid tumour with a nested pattern associated with areas of nuclear pleomorphism, mitotic activity, necrosis and vascular invasion in addition to HMB-45 expression on immunohistochemistry. To the best of the authors' knowledge, this represents the first case of a histologically malignant PEComa of the bone. A short review of primary bone PEComas and potential problems in diagnosis is presented.     

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.     

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.     

Synchronous uterine carcinosarcoma and contralateral breast cancer after tamoxifen therapy: a case report

Uterine carcinosarcoma (malignant mixed Müllerian tumor, MMMT) is a rare aggressive malignant tumor, which demonstrates both malignant epithelial (carcinoma) and mesenchymal (sarcoma) components. Synchronous uterine carcinosarcoma and contralateral breast cancer in patient received tamoxifen treatment had not been reported. We present a case of uterine carcinosarcoma co-occurrenced with contralateral breast cancer in a 56-year-old nulliparous, obese breast cancer patient, who had been treated with tamoxifen for 5 years. The patient presented with palpable pelvic mass and vaginal bleeding. Histopathological evidence revealed that the tumor was comprised of an admixture of malignant epithelial and mesenchymal components. The epithelial component was endometrioid type adenocarcinoma, while sarcomatous component had heterologous elements including fusiform cell sarcoma and a prominent component of cartilage. The infiltrating ductal carcinoma has been diagnosed on her right breast. The patient died of disease 8 months after diagnosis. Postmenopausal patients, with adjuvant tamoxifen treatment for breast cancer, are at increased risk for the development of uterine carcinosarcoma and less benefit for contralateral breast cancer.     

Sinonasal teratocarcinosarcoma with rhabdoid features

Sinonasal teratocarcinosarcoma (SNTCS) is a very rare tumor developed in the nasal cavity and paranasal sinuses. The rhabdoid phenotype represents an aggressive biological behavior, but the rhabdoid feature has hitherto not been reported in cases of SNTCS. A 46-year-old man complained of a 1-month history of left-sided nasal obstruction. Computed tomography scan and magnetic resonance imaging showed a tumor mass involving the left nasal cavity, ethmoid sinus, and ethmoid bone with extension to the left frontal lobe of the brain. A gross total resection of the mass was performed and postoperative radiation therapy administered. Seven weeks later, several recurring masses were detected in the left frontotemporal lobe of the brain. A gross total resection of the mass was performed and postoperative chemotherapy administered. Histopathologically, the tumor showed benign and malignant epithelial, mesenchymal, neural, and immature elements. In addition, diffuse sheets of rhabdoid cells were immunopositive for vimentin, nestin, neuron-specific enolase, and INI1. Ultrastructurally, rhabdoid cells showed paranuclear aggregates and whorls of intermediate filaments with a 9-10 nm diameter. In conclusion, we report first case of rhabdoid features in SNTCS. The present case showed an advanced stage and early recurrence; the rhabdoid component was probably responsible for this aggressive behavior.     

Malignant melanotic Xp11 neoplasms exhibit a clinicopathologic spectrum and gene expression profiling akin to alveolar soft part sarcoma: a proposal for reclassification

The classification of the distinct group of mesenchymal neoplasms, first described as ‘Xp11 translocation perivascular epithelioid cell tumor (PEComa)’ and for which the term ‘melanotic Xp11 neoplasm’ or ‘Xp11 neoplasm with melanocytic differentiation’ has recently been proposed, remains challenging and controversial. We collected 27 melanotic Xp11 neoplasms, the largest series to date, for a comprehensive evaluation. Fourteen of the cases, together with eight alveolar soft part sarcomas (ASPS), nine conventional PEComas and a control group of seven normal tissues were submitted to RNA sequencing. Follow-up available in 22 patients showed 5-year overall survival and 5-year disease-free survival of 47.6 and 35.7%, respectively, which were similar to ASPS and significantly worse than conventional PEComa. Univariate analysis of location (occurring in the kidney versus not kidney), infiltrative growth pattern, nuclear pleomorphism, mitotic activity ≥2/50 high-power fields (HPF), necrosis and lymphovascular invasion were found to be associated with overall survival and/or disease-free survival. Multivariate analysis identified that location was the only factor found to independently correlate with disease-free survival. More importantly, RNA sequencing-based clustering analysis segregated melanotic Xp11 neoplasm and ASPS from other tumors, including conventional PEComa and Xp11 translocation renal cell carcinoma, and formed a compact cluster representative of the largely similar expression signature. Here we clearly define the true biologic nature of melanotic Xp11 neoplasms which are distinctive malignant mesenchymal tumors, rather than simply PEComa variants with occasionally unpredictable behavior. Meanwhile, melanotic Xp11 neoplasm and ASPS more likely represent phenotypic variants of the same entity, which is distinct from conventional PEComa and Xp11 translocation renal cell carcinoma. Based on these important findings, melanotic Xp11 neoplasm might be reclassified into a distinctive entity together with ASPS, independent from PEComa, in future revisions of the current WHO categories of tumors of soft tissue and bone for the improved reclassification. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

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 gastrointestinal neuroectodermal tumor: Cytologic,histologic, immunohistochemical,and molecular pitfalls

Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare malignant primary gastrointestinal mesenchymal tumor which can be diagnosed via fine-needle aspiration (FNA) cytology. In the context of FNA, the diagnosis requires a cell block and the use of significant resources including immunohistochemical stains and molecular testing. The differential diagnosis of GNET includes clear cell sarcoma (CCS), gastrointestinal stromal tumor (GIST), gastric schwannoma, metastatic melanoma, malignant perivascular epithelioid cell tumor (PEComa) and granular cell tumor, among others. Here we describe a case which was initially diagnosed as malignant granular cell tumor by FNA which was later revised to GNET following the finding of an EWSR1-ATF1 fusion gene rearrangement.     

Carcinosarcoma of the urinary bladder--an aggressive tumor with diverse histogenesis. A clinicopathologic study of 4 cases and review of the literature

OBJECTIVE: Carcinosarcomas of urinary bladder are rare malignant neoplasms. Seventy-eight cases have been previously described. The histologic composition of these tumors is variable, but diagnosis requires the presence of both epithelial and mesenchymal malignant components. We report 4 additional cases, with an emphasis on unusual histologic features. METHODS: Histologic and immunohistochemical examinations were performed on bladder tumors from 4 patients. Clinicopathologic features of previously reported and current cases were reviewed and summarized. RESULTS: Four patients (3 men, 1 woman) age 54 to 77 years were found to have polypoid masses in the urinary bladder. In all cases, histologic examination showed biphasic neoplasms with distinct mesenchymal and epithelial components. The morphologic and immunohistochemical characteristics of the tumors varied. One of the cases was remarkable for the presence of liposarcoma, malignant peripheral nerve sheath tumor, and micropapillary urothelial carcinoma. Two of the patients died 2 years after diagnosis, which is consistent with the previously reported aggressive nature of urinary bladder carcinosarcomas. CONCLUSIONS: Carcinosarcomas of the urinary bladder are rare, aggressive malignant neoplasms. To our knowledge, a liposarcomatous component has been reported in only 1 case previously, and components of micropapillary urothelial carcinoma and malignant peripheral nerve sheath tumor have not been reported previously in carcinosarcomas of the urinary bladder. Because of the aggressive biologic behavior of these tumors, they should be identified promptly and treated appropriately.     

具有血管周上皮样细胞分化的肿瘤15例临床病理分析

目的探讨具有血管周上皮样细胞分化的肿瘤(perivascular epithelioid cell tumor,PEComa)临床病理特征及免疫表型。方法对15例PEComa行EnVision两步法免疫组化及特殊染色,并分析其临床表现、病理学特征和免疫组化特点。结果 15例PEComa中13例为女性,且术后无复发。肿瘤可发生在身体任何部位,以肝脏和肾脏最多见,有包膜,多为实性,可有出血。特征性组织学改变是肿瘤细胞围绕血管生长。PAS染色显示该肿瘤细胞中有糖原物质沉积,弹力纤维染色显示该肿瘤中的血管壁缺乏弹力层。免疫组化显示所有PEComa病例均明显表达HMB-45、Melan-A、SMA,Ki-67阳性率低。结论 PEComa是一组具有恶性潜能的肿瘤,多发于女性,来源于血管周上皮样细胞。大部分肿瘤呈良性过程,生物学分级极低,预后良好;极少部分病例可发生转移,预后不佳。免疫组化检测对其组织来源、生物学行为具有提示意义,并可辅助诊断。     

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.     

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.     

Sinonasal teratocarcinosarcoma: a clinicopathologic and immunohistochemical study of 6 cases

Teratocarcinosarcoma (TCS) is a rare and unusual malignant neoplasm of the sinonasal tract with a heterogenous morphology and an aggressive behavior. Patients are predominantly adults with a male predominance. The aim of this study was to describe clinicopathologic and immunohistochemical features of 6 cases of TCS. The ages ranged from 18 to 67 years (mean, 33 years) with a male-to-female ratio of 5:1. Most tumors were located in the nasal cavity. Nasal obstruction and epistaxis were the common presenting symptoms. Histologically, all tumors exhibited a heterogeneous morphology with varying proportions of benign and malignant epithelial, mesenchymal, and neuroepithelial elements. Adenocarcinoma was the malignant epithelial component in all cases. The mesenchymal elements were composed of benign to malignant spindle cells. Osteosarcomatous areas were seen in 2 cases and rhabdomyosarcoma in 1 case. Rhabdoid differentiation was also seen in 1 case. Immunohistochemical stains CKAE1/AE3 and CK Cam 5.2 were positive in the epithelial elements, vimentin in mesenchymal, and CD56 and neuron-specific enolase in neuroepithelial elements. Follow-up was available in 4 patients and ranged from 21 to 40 months (mean, 31 months). Lung and dura metastasis, respectively, were seen in 1 patient each. However, all 4 patients are alive and free of disease to date. In conclusion, TCS is a rare but highly malignant tumor with aggressive behavior characterized by benign and malignant epithelial, mesenchymal, and neuroepithelial components. Two patients in our series were younger than 20 years. The occurrence of rhabdoid differentiation and osteosarcomatous component seen in our series were rarely described in literature. Recognition of all the components requires adequate sampling, which is crucial for a correct diagnosis.     

Gene expression analysis of human soft tissue leiomyosarcomas

Leiomyosarcoma of the somatic soft tissue is a rare malignant mesenchymal neoplasm that metastasizes to other organs in a subset of cases. Much remains to be learned about the mechanisms underlying the development of aggressive behavior of this tumor. It has been difficult to predict the clinical behavior of leiomyosarcomas using the morphology-based grading system, even though tumor size and histological grade have correlated with biologic behavior in some studies. In this study we analyzed the gene expression patterns of 35 samples of mesenchymal origin, including 11 cases of leiomyosarcomas of different histological grades arising in soft tissue and the retroperitoneum, using the Affymetrix U133a chips, which contain more than 22,000 genes and expression sequence tags (ESTs). We identified a set of genes whose expression was commonly altered in all leiomyosarcoma samples. In addition, we identified specific gene expression patterns in several subsets of the tumor. We used these alterations of gene expression to subclassify the leiomyosarcomas into 3 groups. Interestingly, the grouping of these samples correlated well with tumor differentiation and clinical aggressiveness. The analysis identified 92 genes that distinguish low-grade, well-differentiated leiomyosarcomas from less well-differentiated, high-grade, and metastatic leiomyosarcoma. Thesse alterations of gene expression appear to be correlated with the clinical behavior and histological grade of the tumor. The striking differences in terms of gene expression pattern among leiomyosarcomas of different differentiation status and clinical aggressiveness imply that several genetic abnormalities are responsible for the genesis and progression of this tumor.