RARE DISEASE
Perivascular epithelioid cell neoplasm
Perivascular epithelioid cell neoplasm
Perivascular epithelioid cell neoplasm
Synonyms: PEComa, Perivascular epithelioid tumour
Synonyms: PEComa, Perivascular epithelioid tumour
Synonyms: PEComa, Perivascular epithelioid tumour
Drug discovery
2
drugs
With orphan designations
Overview
Perivascular epithelioid cell neoplasms (PEComas) are rare mesenchymal tumors showing myomelanocytic differentiation, characterized by coexpression of melanocytic markers (HMB-45, Melan-A) and smooth muscle markers (actin, desmin) [1][6][12]. These tumors exhibit uncertain malignant potential, with behavior ranging from benign to aggressive/metastatic [3][7][13]. PEComas occur across various anatomic sites and are associated with TSC1/2 mutations or TFE3 gene rearrangements in most cases [6][11][12].
Population
Predominantly affects females (70-80% of cases), with median age at diagnosis of 40-50 years [1][7][12]
Occurs in children/adolescents (median age 15 in pediatric cohorts), often alongside tuberous sclerosis complex (TSC) or Li-Fraumeni syndrome [2][12][15]
Renal angiomyolipoma (AML) and uterine PEComas are common subtypes [4][12][17]
Burden
Incidence estimated at 0.3-1 case per million, with ≤15% exhibiting malignant behavior [7][11][19]
Metastases occur in 6-15% of cases, predominantly to lungs/liver, with median survival <24 months in aggressive subtypes [7][12][13]
Diagnostic challenges due to histologic overlap with carcinomas, sarcomas, and melanomas [6][12][16]
Therapies
Surgical resection with negative margins remains primary treatment for localized disease [3][13][17]
mTOR inhibitors (sirolimus, temsirolimus) show durable responses in advanced/metastatic cases (41-73% response rates) [3][8][11]
Limited efficacy of conventional chemotherapy; emerging options include VEGFR inhibitors (pazopanib) and nab-sirolimus [3][12][16]
Categories: rare neoplastic diseases
Research Papers
404 drug discovery papers about Perivascular epithelioid cell neoplasm, with 1 first-in-class and 16 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
404 drug discovery papers about Perivascular epithelioid cell neoplasm, with 1 first-in-class and 16 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-27 | Epithelioid angiomyolipoma in a horseshoe kidney: a pediatric tuberous sclerosis case report
Abstract Background Epithelioid angiomyolipoma (EAML) is a rare, potentially malignant PEComa-family tumor strongly associated with tuberous sclerosis complex (TSC). Its fat-poor composition and diffusion restriction on MRI render it indistinguishable from renal cell carcinoma (RCC) without tissue sampling. Case presentation A 7-year-old boy with TSC (TSC2 mutation c.2220 + 1 G > T) was found on routine surveillance MRI to have a new left moiety horseshoe kidney mass with interval growth and restricted diffusion on follow-up imaging four months later. Atypical features for classic AML prompted percutaneous image-guided biopsy. Histopathology confirmed EAML; immunohistochemistry showed HMB-45+, SMA+, S-100−, CD10−, and EMA−, with no histologic features of malignancy. The patient was managed with active surveillance; mTOR inhibitor therapy (everolimus) is planned if further growth occurs. Conclusions In a child with TSC, a fat-poor renal mass with interval growth and diffusion restriction should prompt biopsy rather than assumption of classic AML. The ADC map is a critical imaging discriminator, and the characteristic IHC profile is diagnostic. To our knowledge, this is the youngest published case of biopsy-proven EAML in a horseshoe kidney.
2026-07-20 | Clinicopathological characteristics of primary malignant cutaneous perivascular epithelioid cell tumor: case report and literature review.
Primary cutaneous malignant perivascular epithelioid cell tumors (PEComas) are extremely rare. Accurate diagnosis is critical for prognostic evaluation and guiding clinical management. Here, we report a case of a 19-year-old woman with a 1.1 cm exophytic red mass on her left upper limb. Histological examination revealed a dermal tumor composed of clear cells with prominent nucleoli. The tumor cells displayed cytologic atypia, nuclear pleomorphism, multinucleated giant cells, mitoses and invasive growth, with a multinodular distribution within the dermis and vascular invasion. Immunohistochemically, the tumor cells expressed cathepsin K, HMB45, and CD10. Based on morphological and immunohistochemical findings, we classified it as a primary malignant cutaneous PEComa. To date, only eight reported cases have been described as primary malignant cutaneous PEComas. The present case appears to be the youngest patient reported among all malignant PEComas.
2026-07-16 | The many faces of perivascular epithelioid cell tumors: case series illustrating the spectrum of a rare mesenchymal tumor.
Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms composed of distinctive perivascular epithelioid cells that exhibit both melanocytic and smooth muscle differentiation on immunohistochemistry. These tumors can develop in various anatomic locations and display variable biological behavior ranging from benign to aggressive malignant disease. We present a case series of four patients diagnosed with PEComa at different anatomic sites. Histopathological analysis in all cases demonstrated characteristic epithelioid or spindle-shaped morphology, with some cases showing positive staining for melanocytic markers such as HMB-45 and Melan-A, as well as smooth muscle markers. Due to their rarity, definitive management protocols are not yet well established. Surgical resection remains the primary treatment for localized disease, while systemic therapies targeting the mammalian target of rapamycin pathway may be considered for unresectable tumors or metastatic disease. This case series underscores the heterogeneity of PEComas and highlights the importance of multidisciplinary management and long-term follow-up.
2026-07-14 | Sustained Disease Control of High-Risk Metastatic Renal Epithelioid Angiomyolipoma through Multimodal Treatment Including Repeated Thoracic Resection and Systemic Therapy: A Case Report.
Renal epithelioid angiomyolipoma (EAML) is a rare perivascular epithelioid cell tumor with malignant potential. Radiologic distinction from renal cell carcinoma (RCC) may be difficult in fat-poor cases, and standardized treatment strategies for metastatic disease have not been established. A woman in her 30 s presented with a palpable right abdominal mass and anorexia. Contrast-enhanced computed tomography showed an 18-cm heterogeneous right renal mass and a 25-mm liver lesion suspicious for metastasis, without pulmonary metastasis at diagnosis. The pretreatment clinical stage was cT2bN0M1, stage IV. Imaging findings strongly suggested clear cell RCC, and the lesion was managed as presumed metastatic clear cell RCC. The International Metastatic RCC Database Consortium risk category was poor risk. Nivolumab plus cabozantinib was initiated without pretreatment biopsy. At Month 3, the primary tumor showed partial response and the liver lesion remained stable; however, cabozantinib became difficult to continue because of adverse effects, and right nephrectomy was performed in a setting analogous to deferred cytoreductive nephrectomy. Histopathology established renal EAML with pT2b disease, necrosis, mitotic count ≥2, atypical mitoses, severe nuclear atypia, smooth muscle actin negativity, and Ki-67 ≥ 10%, fulfilling six of seven adverse prognostic factors and indicating high-risk disease. Everolimus induced partial response of a new lung metastasis. Subsequent liver and bilateral lung metastases were managed with systemic therapy and staged thoracoscopic resections. Later, isolated subcarinal mediastinal lymph node progression was treated by thoracoscopic resection. The patient remains recurrence-free for 8 months on everolimus. Metastatic renal EAML lacks a standardized treatment strategy. This case suggests that durable disease control may be achievable in selected high-risk patients through individualized multimodal treatment integrating systemic therapy with repeated local treatment for thoracic oligoprogressive lesions.
2026-07-02 | An Evaluation of Radiotherapy and Response in the Management of Perivascular Epithelioid Cell Tumors.
Perivascular epithelioid cell tumours (PEComas) are ultra-rare soft tissue tumours with heterogeneous treatment approaches. While surgery is the standard for localized disease, the role of radiotherapy (RT) remains unclear. This retrospective study aims to evaluate tumour volume response, as well as local outcomes and Overall Survival, in patients with PEComa treated with RT. The cohort included patients diagnosed with PEComa between 2005 and 2023 at a single sarcoma centre. Demographic, clinical, RT, and volumetric tumour data were collected. Response was assessed using RECIST v1.1. In total, 24 lesions in 12 patients were evaluable for analysis, with a median radiological follow-up of 10 months. Of these, 7 lesions were treated with perioperative RT and 17 with palliative RT. Systemic treatments during imaging follow-up were administered in 19/24 lesions. Among 17 lesions treated with palliative intent without surgery, four local failures occurred- all at EQD2 (α/β = 5) <40 Gy- and the estimated 1-year local control rate was 61.9%.Among these 17 lesions, mean tumour volume decreased from 301.5 cm³ (range: 0.9-2251) to 108.3 cm³ (range: 0.1-754) as best response after RT. Seven patients (58.3%) died from their disease, with a median overall survival of 46 months after diagnosis. PEComas appear to be radiosensitive, with substantial tumour volume reduction after RT and a dose-response signal favouring higher EQD2 dose. Nonetheless, overall survival was poor, reflecting the aggressive nature of this disease. This is the largest RT series in PEComa to date and suggests radiosensitivity in this disease.
2026-07-27 | Epithelioid angiomyolipoma in a horseshoe kidney: a pediatric tuberous sclerosis case report
Abstract Background Epithelioid angiomyolipoma (EAML) is a rare, potentially malignant PEComa-family tumor strongly associated with tuberous sclerosis complex (TSC). Its fat-poor composition and diffusion restriction on MRI render it indistinguishable from renal cell carcinoma (RCC) without tissue sampling. Case presentation A 7-year-old boy with TSC (TSC2 mutation c.2220 + 1 G > T) was found on routine surveillance MRI to have a new left moiety horseshoe kidney mass with interval growth and restricted diffusion on follow-up imaging four months later. Atypical features for classic AML prompted percutaneous image-guided biopsy. Histopathology confirmed EAML; immunohistochemistry showed HMB-45+, SMA+, S-100−, CD10−, and EMA−, with no histologic features of malignancy. The patient was managed with active surveillance; mTOR inhibitor therapy (everolimus) is planned if further growth occurs. Conclusions In a child with TSC, a fat-poor renal mass with interval growth and diffusion restriction should prompt biopsy rather than assumption of classic AML. The ADC map is a critical imaging discriminator, and the characteristic IHC profile is diagnostic. To our knowledge, this is the youngest published case of biopsy-proven EAML in a horseshoe kidney.
2026-07-20 | Clinicopathological characteristics of primary malignant cutaneous perivascular epithelioid cell tumor: case report and literature review.
Primary cutaneous malignant perivascular epithelioid cell tumors (PEComas) are extremely rare. Accurate diagnosis is critical for prognostic evaluation and guiding clinical management. Here, we report a case of a 19-year-old woman with a 1.1 cm exophytic red mass on her left upper limb. Histological examination revealed a dermal tumor composed of clear cells with prominent nucleoli. The tumor cells displayed cytologic atypia, nuclear pleomorphism, multinucleated giant cells, mitoses and invasive growth, with a multinodular distribution within the dermis and vascular invasion. Immunohistochemically, the tumor cells expressed cathepsin K, HMB45, and CD10. Based on morphological and immunohistochemical findings, we classified it as a primary malignant cutaneous PEComa. To date, only eight reported cases have been described as primary malignant cutaneous PEComas. The present case appears to be the youngest patient reported among all malignant PEComas.
2026-07-16 | The many faces of perivascular epithelioid cell tumors: case series illustrating the spectrum of a rare mesenchymal tumor.
Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms composed of distinctive perivascular epithelioid cells that exhibit both melanocytic and smooth muscle differentiation on immunohistochemistry. These tumors can develop in various anatomic locations and display variable biological behavior ranging from benign to aggressive malignant disease. We present a case series of four patients diagnosed with PEComa at different anatomic sites. Histopathological analysis in all cases demonstrated characteristic epithelioid or spindle-shaped morphology, with some cases showing positive staining for melanocytic markers such as HMB-45 and Melan-A, as well as smooth muscle markers. Due to their rarity, definitive management protocols are not yet well established. Surgical resection remains the primary treatment for localized disease, while systemic therapies targeting the mammalian target of rapamycin pathway may be considered for unresectable tumors or metastatic disease. This case series underscores the heterogeneity of PEComas and highlights the importance of multidisciplinary management and long-term follow-up.
2026-07-14 | Sustained Disease Control of High-Risk Metastatic Renal Epithelioid Angiomyolipoma through Multimodal Treatment Including Repeated Thoracic Resection and Systemic Therapy: A Case Report.
Renal epithelioid angiomyolipoma (EAML) is a rare perivascular epithelioid cell tumor with malignant potential. Radiologic distinction from renal cell carcinoma (RCC) may be difficult in fat-poor cases, and standardized treatment strategies for metastatic disease have not been established. A woman in her 30 s presented with a palpable right abdominal mass and anorexia. Contrast-enhanced computed tomography showed an 18-cm heterogeneous right renal mass and a 25-mm liver lesion suspicious for metastasis, without pulmonary metastasis at diagnosis. The pretreatment clinical stage was cT2bN0M1, stage IV. Imaging findings strongly suggested clear cell RCC, and the lesion was managed as presumed metastatic clear cell RCC. The International Metastatic RCC Database Consortium risk category was poor risk. Nivolumab plus cabozantinib was initiated without pretreatment biopsy. At Month 3, the primary tumor showed partial response and the liver lesion remained stable; however, cabozantinib became difficult to continue because of adverse effects, and right nephrectomy was performed in a setting analogous to deferred cytoreductive nephrectomy. Histopathology established renal EAML with pT2b disease, necrosis, mitotic count ≥2, atypical mitoses, severe nuclear atypia, smooth muscle actin negativity, and Ki-67 ≥ 10%, fulfilling six of seven adverse prognostic factors and indicating high-risk disease. Everolimus induced partial response of a new lung metastasis. Subsequent liver and bilateral lung metastases were managed with systemic therapy and staged thoracoscopic resections. Later, isolated subcarinal mediastinal lymph node progression was treated by thoracoscopic resection. The patient remains recurrence-free for 8 months on everolimus. Metastatic renal EAML lacks a standardized treatment strategy. This case suggests that durable disease control may be achievable in selected high-risk patients through individualized multimodal treatment integrating systemic therapy with repeated local treatment for thoracic oligoprogressive lesions.
2026-07-02 | An Evaluation of Radiotherapy and Response in the Management of Perivascular Epithelioid Cell Tumors.
Perivascular epithelioid cell tumours (PEComas) are ultra-rare soft tissue tumours with heterogeneous treatment approaches. While surgery is the standard for localized disease, the role of radiotherapy (RT) remains unclear. This retrospective study aims to evaluate tumour volume response, as well as local outcomes and Overall Survival, in patients with PEComa treated with RT. The cohort included patients diagnosed with PEComa between 2005 and 2023 at a single sarcoma centre. Demographic, clinical, RT, and volumetric tumour data were collected. Response was assessed using RECIST v1.1. In total, 24 lesions in 12 patients were evaluable for analysis, with a median radiological follow-up of 10 months. Of these, 7 lesions were treated with perioperative RT and 17 with palliative RT. Systemic treatments during imaging follow-up were administered in 19/24 lesions. Among 17 lesions treated with palliative intent without surgery, four local failures occurred- all at EQD2 (α/β = 5) <40 Gy- and the estimated 1-year local control rate was 61.9%.Among these 17 lesions, mean tumour volume decreased from 301.5 cm³ (range: 0.9-2251) to 108.3 cm³ (range: 0.1-754) as best response after RT. Seven patients (58.3%) died from their disease, with a median overall survival of 46 months after diagnosis. PEComas appear to be radiosensitive, with substantial tumour volume reduction after RT and a dose-response signal favouring higher EQD2 dose. Nonetheless, overall survival was poor, reflecting the aggressive nature of this disease. This is the largest RT series in PEComa to date and suggests radiosensitivity in this disease.
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Drug Discovery Landscape
2 orphan drug designations for Perivascular epithelioid cell neoplasm, including 1 approved therapy.
2 orphan drug designations for Perivascular epithelioid cell neoplasm, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Sirolimus | small molecules | EMA | 2021-07-19 | — | PharmaLex GmbH |
sirolimus protein-bound particles for injectable suspension (albumin-bound) [Fyarro] | small molecules | FDA | 2017-12-21 | 2021-11-22 | Aadi Bioscience, Inc. |
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