Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) Immunohistochemistry Can Be a Useful Ancillary Tool to Identify Perivascular Epithelioid Cell Tumor.

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors that express smooth muscle and melanocytic makers. Diagnosis of PEComas can be challenging due to focal or lost expression of traditional immunohistochemical markers, limited availability of molecular testing, and morphological overlap with much more common smooth muscle tumors. This study evaluates the use of glycoprotein nonmetastatic melanoma protein B (GPNMB) immunohistochemical staining as a surrogate marker for TSC1/2/MTOR alteration or TFE3 rearrangement to differentiate PEComas from other mesenchymal tumors. Cathepsin K was also assessed for comparison. A total of 399 tumors, including PEComas, alveolar soft part sarcomas, and other histologic PEComa mimics, were analyzed using GPNMB and cathepsin K immunohistochemistry. GPNMB expression was seen in all PEComas and alveolar soft part sarcomas with the majority showing diffuse and moderate-to-strong labeling, whereas other sarcomas were negative or showed focal labeling. When a cutoff of diffuse and at least moderate staining was used, GPNMB demonstrated 95% sensitivity and 97% specificity in distinguishing PEComas from leiomyosarcoma, well-differentiated/dedifferentiated liposarcomas, and undifferentiated pleomorphic sarcomas. Cathepsin K with a cutoff of any labeling had lower sensitivity (78%) and similar specificity (94%) to GPNMB. This study highlights GPNMB as a highly sensitive marker for PEComas and suggests its potential use as an ancillary tool within a panel of markers for accurate classification of these tumors.

Systematic analysis of perivascular epithelioid cell neoplasms in the female reproductive tract: a comprehensive review.

Perivascular epithelioid cell neoplasms (PEComas) are rare mesenchymal lesions, with gynecological PEComas accounting for just over a quarter of cases. Limited reports exist on gynecological PEComa, primarily treated with surgery; adjuvant therapy is considered in high-risk cases. This systematic review aims to summarize the origin and clinical, pathological and molecular characteristics of uterine PEComa, focusing on treatment options for gynecological PEComa. A comprehensive PubMed review of gynecological PEComa reports was conducted. A detailed examination of the literature ensured a thorough understanding. Gynecological PEComa diagnosis relies on histology and immunology. Despite therapy controversies, surgery remains the mainstay. Adjuvant therapy efficacy in high-risk cases is uncertain. mTOR inhibitors are the first line; alternative treatments, including angiogenesis and aromatase inhibitors, should be considered.

A retrospective clinical analysis of 11 cases of PEComa from different sites.

PURPOSE: The objective of this paper is to offer a thorough examination of the clinical presentations, etiology, and treatment strategies associated with perivascular epithelioid cell tumors (PEComas). METHODS: This retrospective study examined the comprehensive archival data of PEComa cases diagnosed at Beijing Hospital from 2015 to 2023. The pathology slides of all patients were thoroughly reassessed by two experienced pathologists. A thorough retrospective analysis was undertaken, incorporating clinicopathological data including gender, age at diagnosis, initial clinical manifestations, signs, disease onset site, tumor markers, imaging findings, therapeutic modalities, pathological features, immunohistochemical profiles, treatment responses, and prognostic indicators. Patients were evaluated for disease severity according to established pathological classification criteria and were followed up until the designated analysis cut-off date. In instances where patients were unable to be monitored on-site, they were contacted via telephone for postoperative follow-up inquiries. RESULTS: This study included 11 patients with ages ranging from 17 to 66 years old, presenting with the disease in multiple anatomical sites, including the retroperitoneum (2/11), liver (4/11), kidney (4/11), lung (1/11), and broad ligament of the uterus (1/11). Most patients presented with non-specific clinical symptoms and were subsequently diagnosed with space-occupying lesions upon physical examination. The tumor demonstrated progressive growth and enlargement, which could result in compression of neighboring organs. Preoperative imaging alone is insufficient for a definitive diagnosis of PEComa, but MRI can provide an initial evaluation of the tumor's potential malignancy. Molecular marker testing specific to PEComa, such as HMB-45 (90.0%), SMA (81.8%), Melan-A (90.9%), vimentin (90.9%), and Desmin (36.3%), was conducted on all patients. No adjuvant therapies were administered postoperatively. Upon analysis, no instances of relapse at the primary site or the development of new tumors at other sites were observed. Regular imaging reviews of three patients with malignant PEComa post-surgery showed no evidence of recurrence. CONCLUSIONS: The clinical presentation, tumor biomarkers, and imaging characteristics of PEComa lack specificity, necessitating dependence on pathology and immunohistochemistry for precise diagnosis. The mainstay of treatment consists of surgical resection, with patients typically experiencing a favorable prognosis.

Gynecologic perivascular epithelioid cell tumors (PEComas): a review of recent evidence.

Gynecologic perivascular epithelioid cell (PEC) tumors, or 'PEComas,' represent a rare and intriguing subset of tumors within the female reproductive tract. This systematic literature review aims to provide an updated understanding of gynecologic PEComas based on available literature and data. Although PEComa is rare, there are varied tumor-site presentations across gynecologic organs, with uterine PEComas being the most prevalent. There is scarce high-quality literature regarding gynecologic PEComa, and studies on malignant PEComa underscore the challenges in diagnosis. Among the diverse mutations, mTOR alterations are the most prominent. Survival analysis reveals a high rate of local recurrence and metastatic disease, which commonly affects the lungs. Treatment strategies are limited, however mTOR inhibitors have pivotal role when indicated and chemotherapy may also be used. with some cases demonstrating promising responses. The paucity of data underscores the need for multicentric studies, an international registry for PEComas, and standardized reporting in case series to enhance clinical and pathological data.

Primary Liver Perivascular Epithelioid Cell Tumor (PEComa): Case Report and Literature Review.

A primary liver perivascular epithelioid cell tumor (PEComa) is an extremely rare entity. In this article, we present a case report with a review of the literature on the patients diagnosed with primary liver PEComa and an elaboration of diagnostic and treatment modalities. A systematic literature search was conducted using the terms "perivascular epithelioid cell tumor", "PEComa", "liver", and "hepatic". All articles describing patients diagnosed with primary liver PEComa were included. We identified a total of 224 patients of primary liver PEComa from 75 articles and a case from the present study with a significant preponderance of females (ratio 4:1) and with a mean age of 45.3 ± 12.1 years. Most of the patients (114 out of 224, 50.9%) were asymptomatic. A total of 183 (81.3%) patients underwent surgical hepatic resection at the time of diagnosis, while 19 (8.4%) underwent surveillance. Recurrence and metastases were detected in seven (3.1%) and six (2.7%) patients, respectively. In conclusion, surgical resection remains the cornerstone of therapy; however, the presence of nonspecific imaging features makes it difficult to reach a definite diagnosis preoperatively. Therefore, a multidisciplinary approach should be the gold standard in selecting the treatment modality.

Soft Tissue Perivascular Epithelioid Cell Tumors.

Perivascular epithelioid cell tumors (PEComas) are a heterogenous group of mesenchymal neoplasms with a mixed myomelanocytic immunophenotype. PEComa-family tumors include angiomyolipoma, lymphangioleiomyomatosis, and a large category of rare neoplasms throughout the body that are now classified under the umbrella term "PEComa." This review focuses on recent advances in the clinicopathological and molecular features of PEComas, with an emphasis on PEComas that originate in soft tissue.

Clinicopathological features of two ultra-rare cases of malignant perivascular epithelioid cell tumors (PEComas) involving the uterus with recent updates.

Malignant perivascular epithelioid tumors (PEComas) involving the uterus are uncommon. Herein, we present the clinicopathological features of two such cases, including their diagnostic implications with recent updates. A 62-year-old lady presented with vaginal bleeding. Ultrasonogram revealed a heterogeneous uterine mass. She underwent an endometrial biopsy and total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO), which revealed a 3.2 cm-sized proliferative tumor in the fundus. A 45-year-old lady presented with recurrent abdominal pain. She underwent cytoreductive surgery twice with adjuvant chemotherapy for multiple tumors and TAH-BSO for a uterine tumor, 2 years before. Microscopic examination of both tumors revealed markedly atypical, polygonal-shaped/epithelioid tumor cells containing eosinophilic cytoplasm and arranged in a nesting pattern with intervening thin-walled blood vessels, mitotic figures (≥ 6/10 high power fields (hpfs)), and tumor necrosis. Tumor infiltration was more than half the myometrial thickness in the first tumor and pelvic nodal metastasis. The second tumor revealed rhabdoid-like and vacuolated cells along with "spider-like" giant cells. Immunohistochemically, both the tumors were positive for HMB45 and desmin, while negative for epithelial markers. Additionally, the second tumor was positive for smooth muscle actin (SMA) and TFE3. Both patients developed tumor recurrences. In view of multiple tumor deposits, the second patient was induced with a mammalian target of rapamycin (m-TOR) inhibitor (everolimus) but unfortunately died of the disease. Malignant PEComas involving the uterus are ultra-rare, aggressive tumors. An index of suspicion, based on certain histomorphological features, supported by immunohistochemical expression of myomelanocytic markers is necessary for a correct diagnosis. Certain PEComas display TFE3 positivity. A correct diagnosis has significant implications, including an aggressive clinical course and the possibility of targeted therapy, especially in recurrences or metastasis.

Hepatic perivascular epithelioid cell tumors: The importance of preoperative diagnosis.

Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors (PEComas) because PEComas are mainly benign tumors and may not require surgical intervention. By analyzing the causes, properties and clinical manifestations of PEComas, we summarize the challenges and solutions in the diagnosis of PEComas.

Hepatic perivascular epithelioid cell tumors: Benign, malignant, and uncertain malignant potential.

In 2013, the World Health Organization defined perivascular epithelioid cell tumor (PEComa) as "a mesenchymal tumor which shows a local association with vessel walls and usually expresses melanocyte and smooth muscle markers." This generic definition seems to better fit the PEComa family, which includes angiomyolipoma, clear cell sugar tumor of the lung, lymphangioleiomyomatosis, and a group of histologically and immunophenotypically similar tumors that include primary extrapulmonary sugar tumor and clear cell myomelanocytic tumor. Clear cell tumors with this immunophenotypic pattern have also had their malignant variants described. When localizing to the liver, preoperative radiological diagnosis has proven to be very difficult, and most patients have been diagnosed with hepatocellular carcinoma, focal nodular hyperplasia, hemangioma, or hepatic adenoma based on imaging findings. Examples of a malignant variant of the liver have been described. Finally, reports of malignant variants of these lesions have increased in recent years. Therefore, we support the use of the Folpe criteria, which in 2005 established the criteria for categorizing a PEComa as benign, malignant, or of uncertain malignant potential. Although they are not considered ideal, they currently seem to be the best approach and could be used for the categorization of liver tumors.

Hepatic and perihepatic PEComas: A study describing a series of five rare cases.

BACKGROUND: Perivascular epithelioid cell tumors (PEComas) encompass a group of rare mesenchymal neoplasms, with dual melanocytic and muscular differentiation. Hepatic PEComas are rare and difficult to diagnose, and their behavior is still unclear. MATERIALS AND METHODS: Herein, we report a total of five cases of hepatic and perihepatic PEComas over a period of the last 5 years from our and collaborating center's archive. A detailed histological evaluation was done. A comprehensive panel of immunohistochemical stains was used and fluorescence in-situ hybridization analysis was performed for the TFE3 gene using break-apart probes. RESULT: All these patients were women, with an average age of presentation of 44 years. The lesions were in the right hepatic lobe: three cases, the left hepatic lobe: one case, and gastrohepatic ligament: one case. The preoperative clinicoradiological diagnoses were hepatocellular carcinoma (HCC), focal nodular hyperplasia, hemangioma, metastasis, and gastrointestinal stromal tumor, respectively. Surgical excision was performed in four cases with no further adjuvant therapy. Histopathological examination and subsequent immunophenotyping revealed a diagnosis of PEComa. Fluorescence in-situ hybridization analysis was performed for TFE3 gene rearrangement in four cases. CONCLUSIONS: This series highlights the fact that accurate histological diagnosis of hepatic or perihepatic PEComas is important to prevent unnecessary aggressive treatment, unlike primary hepatocellular carcinomas or hepatoid/epithelioid metastatic tumors.

Challenges in Diagnosing Metastatic Uterine PEComa: Insights from Two Case Studies.

BACKGROUND Perivascular epithelioid cell tumor (PEComa) is usually a benign perivascular tumor that expresses both melanocytic and myogenic cell markers. We report 2 cases of advanced malignant uterine perivascular epithelioid cell tumor (PEComa) in a 74-year-old woman and a 50-year-old woman undergoing surgery in our center. CASE REPORT Case 1: A 74-year-old woman presented with a painful and massive abdominal mass. The imaging revealed a 19-cm necrotic mass close to the mesentery, a suspicious lesion in the uterus, and a probable liver metastasis. The pathological diagnosis was quite difficult with mixed features of leiomyosarcoma and PEComa with an uncommon immunohistochemistry staining pattern. Therefore, we gave a diagnosis of sarcoma with PEComa-like features. Case 2: A 50-year-old woman with metrorrhagia and abdominal pain. Imaging revealed a 7-cm mass in the uterus and suspicious metastatic lesions in the lung and the liver. The immunohistochemistry pattern was typical, with a strong positivity of Human Melanoma Black-45 (HMB-45) and focal positivity of H-Caldesmon. The patient benefited from targeted adjuvant therapy (MTOR inhibitor-based), with 8-month a follow-up showing no recurrence for this Grade IV PEComa mutated for TP53, ATRX, and TSC1. CONCLUSIONS We have report 2 cases of metastatic PEComa with different clinicopathological features. An overlap remains between characteristics of PEComas and smooth-muscle tumors. At present, there are no known pathognomonic findings or specific diagnostic markers.

Unusual PEComa With PRCC :: TFE3 Fusion Mimicking Sinonasal Tract Melanoma.

BACKGROUND: We report a nasal cavity unusual perivascular epithelioid cell tumor (PEComa) mimicking mucosal melanoma. METHODS: Immunohistochemistry was performed using BenchMark Ultra and panel of antibodies. The Ion Torrent platform and Ion AmpliSeq cancer hotspot panel were utilized for DNA genotyping. Target-specific RNA libraries for the detection of fusion transcripts were constructed using Archer Universal RNA Reagent Kit v2 and Archer FusionPlex Solid Tumor panel and sequenced on the MiSeqDx instrument. RESULTS: The tumor, diagnosed in 46-year-old female, was composed of spindle cells, and lacked pigmentation. Immunohistochemically, it showed a patchy HMB-45 positivity. Other melanocytic markers (S100 protein, Melan-A, SOX10) were negative. The tumor cells were weakly positive for KIT (CD117) while negative for smooth muscle actin, pancytokeratin cocktail (AE1/AE3), and synaptophysin. Diagnosis of primary sinonasal tract mucosal melanoma was favored. Additional molecular studies detected PRCC :: TFE3 fusion as the sole genetic change, and suggested the diagnosis of unusual PEComa. Previously, TFE3 fusions were reported in a subset of PEComas but not in melanomas, while PRCC involvement has only been documented once in an ocular PEComa. Immunohistochemistry revealed strong nuclear TFE3 expression concordant with the molecular findings. CONCLUSIONS: This report emphasis the importance of molecular testing in the differential diagnosis between PEComa and melanoma, especially when the tumor arises in a site typical of melanoma but showing an unusual morphology and immunophenotype. The detection of TFE3 fusion transcripts suggested the diagnosis of SNT PEComa, although it cannot be excluded that this and similar tumors represent a distinct diagnostic category.

Angioleiomioma oral: relato de um caso e revisão dos achados atuais / Oral angioleiomyoma: case report and a review of current findings

Resumo O angioleiomioma é uma neoplasia benigna que, a partir da nova classificação da OMS (2013) para os tumores de tecidos moles, deixou de ser considerado um tumor de origem muscular lisa, passando a ser considerado um tumor de origem perivascular. Raramente os angioleiomiomas ocorrem na cavidade oral. A lesão é tratada cirurgicamente, com prognóstico considerado favorável. Este trabalho revisa os casos de angioleiomioma oral relatados na literatura nos últimos 5 anos e descreve esse tumor em um homem de 44 anos que apresentou um nódulo assintomático localizado em lábio superior, com evolução de 6 meses. As hipóteses diagnósticas foram de adenoma pleomórfico e adenoma canalicular. A lesão foi submetida à biópsia e análise histopatológica e imuno-histoquímica (S100, CD34, α-SMA, H-caldesmon e desmina) confirmaram o diagnóstico de angioleiomioma. Destacamos a imuno-histoquímica como um importante método auxiliar no diagnóstico diferencial do angioleiomioma com outras lesões e, principalmente, com o miopericitoma.

Abstract Angioleiomyoma is a benign neoplasm that was considered a tumor of smooth-muscle origin until the most recent (2013) WHO classification of soft tissue tumors, in which it was reclassified as a tumor of perivascular origin. Angioleiomyomas rarely occur in the oral cavity. These lesions are treated surgically with good prognosis. This article presents a review of reports of oral angioleiomyoma in the literature from the last 5 years and describes the case of a 44-year-old man who presented with an asymptomatic nodule in the upper lip that had developed over a 6-month period. Diagnostic hypotheses of pleomorphic adenoma or canalicular adenoma were raised. Biopsy of the lesion, histopathological and immunohistochemical analysis (S100, CD34, H-caldesmon, and desmin) confirmed a diagnosis of angioleiomyoma. It is noteworthy that immunohistochemistry is an important auxiliary method for differential diagnosis of angioleiomyoma from other tumors, particularly myopericytoma.