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.

Malignant Perivascular epithelioid cell tumour of the uterus without TFE3 gene rearrangement: a case report.

BACKGROUND: Perivascular epithelioid cell tumours (PEComas) are soft tissue tumours. These neoplasms belong to the family of mesenchymal tumours, which include angiomyolipomas, clear-cell sugar tumours of the lung, and PEComas not otherwise specified (NOS). The probability of a perivascular epithelioid cell tumour (PEComa) occurring in the uterus is low, and the incidence, diagnosis, treatment, and outcomes of such tumours are still unclear. CASE PRESENTATION: A 51-year-old woman presented a 4-year history of natural menopause. An intrauterine mass was detected via ultrasound examination; the mass showed a tendency to increase but caused no symptoms. The levels of tumour markers were within the normal range. Pathological analysis of the curettage revealed perivascular epithelioid differentiation of the endometrial tumour. Consequently, a laparoscopic total hysterectomy with bilateral adnexectomy was performed. No distant metastasis was detected via whole-body positron emission computed tomography (PETCT) after the operation. Fluorescence in situ hybridization (FISH) revealed no TFE3 gene rearrangement. Next-generation sequencing of bone and soft tissue revealed negative TSC1/2 and TP53 expression. No recurrence or metastasis was observed during the 18-month follow-up period. CONCLUSION: PEComa of the gynecologic tract is a rare and challenging entity. Diffuse HMB-45 expression, TSC alterations and TFE3 rearrangement are characteristic of uterine PEComas. Surgical resection is the first choice. Genetic testing is helpful for determining the nature of the mass and for choosing targeted therapy. Further research is needed to establish treatment protocols.

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.

Pancreatic PEComa, a not so uncommon neoplasm? Systematic review and therapeutic update. / PEComa pancreático ¿una neoplasia no tan infrecuente? Revisión sistemática y actualización clínico-terapéutica.

Pancreatic PEComas are extremely rare neoplasms with malignant potential, which mostly affect middle-aged women and are characterized by presenting melanocytic and myogenic markers in immunohistochemical analysis. There are no symptoms or pathognomonic imaging tests, so the diagnosis is established with the analysis of the surgical specimen or the FNA obtained with preoperative endoscopic ultrasound. The mean treatment consists on radical excision, adapting the intervention to the location of the tumor. To date, 34 cases have been described; however, more than 80% of them have been reported in the last decade, which suggests that it is a more frequent pathology than expected. A new case of pancreatic PEComa is reported and a systematic review of the literature is carried out according to the PRISMA guidelines with the aim of divulge this pathology, deepening its knowledge and updating its management.

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.

Clinicopathological features of primary malignant perivascular epithelioid cell tumors of ureter: Histologic-radiologic correlation.

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor that is mainly seen in middle-aged women. PEComa originating in the ureter is extremely rare it is unclear whether they display typical clinical and radiographic features seen elsewhere. Herein, we report findings from 2 cases of primary PEComa of the ureter that we classified as malignant. Case 1: A 45-year-old woman was admitted to the hospital with intermittent distension in her waist. After appropriate imaging, the right ureter and right kidney were excised under general anesthesia. The tumor measured 1.4 cm. Microscopically, the tumor displayed infiltrative growth, >2 mitoses per 10 high power fields (HPF), necrosis, and lympho-vascular invasion. Case 2: A 30-year-old woman was admitted to the hospital due to hematuria 20 days duration. The left ureter and left kidney were ultimately excised under general anesthesia. The tumor measured 2 cm. Microscopically, the tumor showed infiltrative growth and >2 mitoses/10 HPF. Our cases were diagnosed as malignant PEComa. No disease recurrence was observed in either of the two patients during the postoperative follow-up period. Malignant primary ureteral PEComa is very rare. The clinical manifestations are not specific, and it is usually misdiagnosed as a malignant neoplasm on imaging. Therefore, its diagnosis requires pathological examination and immunohistochemical analysis of the sampled or resected tumor. Treatment requires a complete surgical resection and regular clinical follow-up.

Vaginal metastasis of renal clear cell carcinoma: a case report emphasizing the role of immunohistochemistry in differential diagnosis in the absence of a clinical history.

We present the case of a 71-year-old patient, with vaginal bleeding, dyspnea, headache, loss of appetite and weakness. Clinical examination revealed a pediculated vaginal mass of 25 mm diameter, of dark-red color and soft spongy consistency, with an ulcerated surface and originating from the anterior wall, which was surgically removed. The morphology was dominanted by large, round to polygonal tumor cells, arranged in a predominantly tubulo-cystic architecture, surrounding numerous blood vessels that dominated the appearance, suggesting a perivascular epithelioid cell tumor (PEComa) or hemangioblastoma but the presence of pleomorphic nuclei, numerous mitoses together with immunohistochemistry helped for a correct diagnosis of vaginal .

Metastatic Adrenal PEComa: Case Report and Short Review of the Literature.

PEComa has become a widely accepted entity, and increased recognition has led to descriptions of this tumor in a wide variety of anatomic sites, including the adrenal gland. PEComa (perivascular epithelioid cell tumor) is a mesenchymal tumor composed of perivascular cells, and the most frequent sites of PEComas are the uterus and retroperitoneum. The incidence is <1 per 1,000,000 people. We report a case of adrenal metastatic PEComa in a 63-year-old man discovered by a spontaneous hematoma of the rectus abdominis. In our case, PEComa of the adrenal gland was a significant diagnostic dilemma as the morphologic and immunophenotypic features of this neoplasm may easily be confused with those of other more commonly encountered lesions.

Malignant perivascular epithelioid cell tumor (PEComa) of the uterus.

BACKGROUND: Perivascular epithelioid cell tumors (PEComas) of the uterus is a rare type of mesenchymal tumors associated with myelomelanocytic differentiation and distinctive histological appearances. So far, the reported cases of uterine PEComas are usually benign. Documented malignant cases with aggressive behavior appear to be less common. CASE PRESENTATION: We report a 37-year-old female who received abdominal hysterectomy for uterine tumor in a local hospital. She was diagnosed with uterine leiomyosarcoma and referred to Hubei Cancer Hospital. Her histological slides were reviewed and immunohistochemical staining for specific markers of epithelial, melanocytic, myoid and some others were analyzed. The pathologic diagnosis was malignant uterine PEComa. Systematic imaging of the patient further revealed an abdominal para-aortic mass. She received pelvic and para-aortic lymph node dissection. Postoperative histology revealed para-aortic lymph nodal metastasis of malignant uterine PEComa. She received 8 cycles of chemotherapy after surgery. The chemotherapy regiment was epirubicin plus ifosfamide The patient is free of recurrence and metastasis 6 years after surgical resection. CONCLUSION: Uterine PEComas are indistinguishable from other uterine tumors such as leiomyoma and leiomyosarcoma before pathologic diagnosis could be made. For patients with malignant uterine PEComas, removal of both primary lesions and metastatic foci, if any, needs to be attempted. Postoperative chemotherapy or radiotherapy should also be considered in patients with distant metastases or positive lymph nodes.

Primary Cutaneous Malignant Perivascular Epithelioid Cell Tumor Mimicking Undifferentiated Pleomorphic Sarcoma: A Report of a Rare Entity.

ABSTRACT: Primary cutaneous malignant perivascular epithelioid cell tumor (PEComa) is a rare and potentially aggressive neoplasm. In this article, we report the case of a 34-year-old man who initially presented with a 3-cm mass involving the skin and soft tissue of the right shoulder that, over 3 months, enlarged to 12 cm. Histologic examination of the mass revealed an infiltrative neoplasm with features resembling an undifferentiated pleomorphic sarcoma, including sheets of pleomorphic cells with abundant atypical mitoses and necrosis. Immunohistochemical evaluation showed features suggestive of PEComa. Next-generation sequencing revealed pathogenic homozygous deletions of TSC2 and TP53 genes and numerous large-scale copy number changes. Taken together, the findings supported malignant PEComa. This case demonstrates only the seventh example of malignant cutaneous PEComa. Although cutaneous PEComa is chiefly a benign mesenchymal neoplasm, in rare cases, it can rapidly transform into a malignant and infiltrative sarcoma, requiring prompt surgical management.

Perirenal perivascular epithelioid cell tumor (PEComa).

A 52-year-old woman, who is a carrier of MLH-1 mutation (HNPCC-type Lynch syndrome) with a history of colon adenocarcinoma, was diagnosed with a 26 mm lobulated contrast-capturing mass located caudally of the pancreas tail, anteromedial of the spleen and medial of the splenic colon angle. She underwent an exploratory laparotomy with resection of the tumor. Initially, this mass was presumed to be metastasis in a patient with a history of colon adenocarcinoma. However, after further histopathological and immunohistochemical examination, the mass appeared to be a rare PEComa. Only a few cases of a PEComa in this retroperitoneal perirenal location have been described.

Cutaneous perivascular epithelioid cell tumor (PEComa): case report and world literature review of clinical and molecular characteristics.

Perivascular epithelioid cell tumor (PEComa) expresses melanocytic and smooth muscle markers. A man with a primary malignant cutaneous (distal left forearm) PEComa is reported. Immunohistochemistry demonstrated MiTF, HMB-45, caldesmon, desmin, and smooth muscle actin, as well as BCL1, CD10, and CD68. Next generation sequencing showed four pathogenic genomic aberrations involving BIRC3, FANCC, TP53, and TSC1 genes. His work-up was negative for metastatic disease; a wide local excision was performed. Including the reported patient, cutaneous PEComa has been described in 65 individuals: primary benign (N=58), primary malignant (N=5), and metastatic malignant (N=2). Cutaneous PEComa typically presented as a painless, slowly growing nodule of <2 centimeters on the lower extremity of a woman in her fifth decade. The neoplasms consisted of epithelioid cells, spindle cells, or both. The most reliable markers were MiTF (100%), HMB45 (94%), and NKIC3 (94%) for melanocytes and smooth muscle actin (43%) and desmin (40%) for smooth muscle. There has been no reported recurrence of a primary cutaneous benign or malignant PEComa after complete excision. Genomic alterations in malignant PEComas frequently involve TSC1 and TSC2 genes (mTOR activators), as well as TFE3 fusions. In November 2021, the FDA approved nab-sirolimus (mTOR inhibitor) for PEComas.

Extremely late-onset pulmonary metastasis from uterine PEComa.

A 79-year-old woman underwent surgical resection of a peripheral, solitary, pulmonary lesion that was diagnosed as malignant PEComa. Her clinical history was positive for uterine leiomyosarcoma, excised 20 years before. Re-evaluation of the primary uterine lesion led to the final diagnosis of lung metastasis from uterine PEComa. While long latency between primary tumour and metastasis is a known and characteristic feature of PEComas, a 20-year interval is unprecedented in the literature.

[Analysis of the diagnosis and treatment of 24 cases of hepatic perivascular epithelioid cell tumor].

Objective: To investigate hepatic perivascular epithelioid cell tumor (PEComa) diagnosis and treatment plan. Methods: 24 cases diagnosed with PEComa clinical manifestations, serum alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), imaging findings, surgical methods, postoperative hospital stay, pathological results and prognosis were analyzed retrospectively from September 2015 to September 2020. Results: Majority of patients were females (79.2%), aged 41.5±11.4 years. Tumors were predominantly located in the right liver (50.0%). 76.7% of the cases were mostly clinically asymptomatic. AFP, CEA and CA199 indices were all negative. CT mostly showed low density tumor in the plain scan phase, enhanced in the enhancement phase, and enhanced and weakened in portal venous and equilibrium phase (66.7%). MRI manifestations of most tumors were hypointense on T1WI and hyperintense on T2WI (72.7%). B-ultrasound mostly showed hyperechoic mass in the tumor area with punctate vascular shadow (52.9%). Postoperative hospital stay was 9.0±2.4 days for laparoscopic surgery patients (n=13), 13.4±6.3 days for traditional laparotomy (hereinafter referred to as laparotomy, n=10), and 3 days for 1 patient with microwave ablation. All postoperative pathological results were positive for HMB45 and Melan-A. Follow-up results: 21 cases survived normally, with no tumor recurrence in the recent physical examination; two cases had tumor recurrence and they died two and three years after surgery, and one case was lost to follow-up. Conclusion: Hepatic PEComa more commonly occurs in middle-aged women, with no specific features for tumor markers and clinical manifestations. Some imaging findings are specific, so its features can be combined as a basis for diagnosis. Postoperative pathological examination results can confirm the diagnosis. Therefore, surgery remains the initial treatment plan. Microwave ablation and laparoscopic surgery are recommended as the preferred option because of shorter hospital stays and less trauma than open surgery.

Gynaecological perivascular epithelioid cell tumour (PEComa): comparative analysis of proposed algorithms for prediction of clinical outcome.

AIMS: Perivascular epithelioid cell tumours (PEComas) are rare mesenchymal tumours that coexpress smooth muscle and melanocytic markers. They have a predilection for gynaecological organs, where they present a unique diagnostic challenge, because of morphological and immunohistochemical overlap with more common smooth muscle and stromal tumours. Limited information regarding the natural history, owing to the rarity of this tumour, makes accurate risk stratification difficult. We aimed to review clinicopathological features of gynaecological PEComa and compare accuracy of five different classification systems for prediction of prognosis. METHODS AND RESULTS: We have described the clinicopathological features of 13 new cases and tested five prognostic algorithms in a total of 67 cases of gynaecological PEComa. Receiver operating characteristic curves were constructed and areas under the curve (AUCs) were calculated to evaluate predictive accuracy. The modified gynaecological-specific algorithm showed high sensitivity and specificity and yielded the highest AUC (0.864). It's earlier version, the gynaecological-specific algorithm, suffered from lower specificity (AUC = 0.843). The post-hoc McNemar test confirmed significant differences between the performances of the modified gynaecological-specific algorithm and the gynaecological-specific algorithm (P = 0.008). The original Folpe algorithm for PEComas of all sites showed low specificity, had a lower AUC (0.591), and was inapplicable in 18% of cases. Its two later versions (the revised Folpe algorithm and the modified Folpe algorithm) also yielded lower AUCs (0.690 and 0.591, respectively). CONCLUSION: We have shown that the modified gynaecological-specific algorithm predicts the clinical outcome of gynaecological PEComa with high accuracy, and have validated its use for prognostic stratification of gynaecological PEComa.

Uterine plexiform tumourlets: multifocal and solitary cases with subsets expressing melanocytic markers.

AIMS: Uterine plexiform tumourlets are traditionally regarded as microscopic epithelioid leiomyomas. They are typically solitary incidental findings, but may be multifocal (plexiform leiomyomatosis). We aim to report novel immunohistochemical and morphological findings, specifically the presence of spindled and epithelioid cell nodules, in these lesions. METHODS AND RESULTS: Three cases of plexiform leiomyomatosis and 16 solitary plexiform tumourlets were included. Two cases of plexiform leiomyomatosis and four solitary plexiform tumourlets demonstrated spindled and epithelioid cell nodules which, in one of the former cases, formed expansile masses up to 15 mm. The nodules demonstrated mild cytological atypia and occasional mitotic activity, and they were associated with a myxoid stroma and a lymphohistiocytic infiltrate which imparted a granulomatous appearance to the microscopic lesions. The plexiform tumourlets (solitary and multifocal) consistently expressed desmin, smooth muscle actin, ER and PR, and they commonly co-expressed melanocytic and perivascular epithelioid cell (PEC) markers HMB45, MiTF and cathepsin K. The spindled and epithelioid cell nodules were generally negative for myoid markers and hormone receptors, but expressed p16, cyclin D1 and TFE3. All lesions tested were negative for cytokeratin, S100, melanA, inhibin, EMA, ALK and BCOR; fluorescence in-situ hybridisation was negative for ALK, TFE3 and BCOR rearrangements in one of the larger spindled and epithelioid cell nodules. CONCLUSIONS: Plexiform tumourlets commonly co-express myoid and melanocytic markers and may represent part of the spectrum of gynaecological PEC-related lesions. Some cases are associated with spindled and epithelioid cell nodules that could potentially mimic other uterine myxoid neoplasms.

Coexistence of Conventional Leiomyoma, Fumarate Hydratase-deficient Atypical Leiomyoma, and Perivascular Epithelioid Cell Tumor in a Uterus: A Case Study.

A 44-yr-old woman with menorrhagia and uterine fibroids underwent total laparoscopic hysterectomy, revealing several submucosal, intramural, and subserosal tan-white nodules in the uterus. Microscopic examination revealed tumors displaying 3 distinct morphologies: 1 tumor with features of conventional leiomyoma; 1 tumor with increased cellularity, staghorn/hemangiopericytoma-like vasculature, and occasional atypical cells with prominent red nucleoli and some perinucleolar halos suggesting a fumarate hydratase (FH)-deficient atypical leiomyoma; and 1 tumor with an admixture of epithelioid and spindled cells with the former arranged around blood vessels suggesting a perivascular epithelioid cell tumor (PEComa). Immunohistochemical studies confirmed these diagnoses by demonstrating loss of FH expression in the atypical leiomyoma and diffuse expression of HMB45 and cathepsin K in the tumor with epithelioid features. Sanger sequencing analysis revealed that the FH-deficient atypical leiomyoma harbored a c.181A>G (p.Lys61Glu) mutation in exon 2 of the FH gene. As this mutation was not present in either the other tumors or peripheral blood, the mutation is somatic and hereditary leiomyomatosis and renal cell cancer syndrome is excluded. This case highlights the importance of thorough examination of uterine mesenchymal tumors with atypical and epithelioid features so that tumors with some potential for recurrence (PEComas) and those that might indicate a hereditary cancer syndrome (FH-deficient atypical leiomyoma) are identified and can trigger appropriate clinical investigation and follow-up.

Primary cutaneous malignant perivascular epithelioid cell tumor: Case of a rare tumor with review of the literature.

Perivascular epithelioid cell tumors (PEComas) are mesenchymal neoplasms with characteristic epithelioid or spindled cytomorphology that typically grow around blood vessels. These tumors are phenotypically and immunohistochemically distinct, expressing markers of both melanocytic and smooth muscle differentiation. Herein, we describe a case of histopathologically malignant cutaneous PEComa without metastatic spread, with review of the pertinent literature. Telescoping punch biopsy demonstrated an epithelioid neoplasm with marked atypia, hypercellularity, and increased mitotic activity. Immunohistochemical stains for HMB-45, NK1-C3, PGP9.5, MiTF, CD10, and CD68 were positive within tumor cells. In addition, there was diffuse expression of caldesmon and focal cytoplasmic staining for smooth muscle actin on the excision specimen. The patient underwent treatment with surgical excision with adjuvant radiation and surveillance computed tomography (CT). The patient remains free of recurrence or metastatic disease after 10 months of follow-up. To our knowledge, this is only the third reported case of a malignant cutaneous PEComa reported in the literature to date.