| Topic | Summary | Key quantitative details | Key sources |
|---|---|---|---|
| Disease name / synonyms | **Perivascular epithelioid cell neoplasm/tumor (PEComa/PEComa family)**; rare mesenchymal neoplasm composed of distinctive perivascular epithelioid cells with dual melanocytic and smooth-muscle differentiation. WHO-style definition quoted as: “a mesenchymal tumor which shows a local association with vessel walls and usually expresses melanocyte and smooth muscle markers.” (pqac-00000004, pqac-00000000) | Malignant PEComa estimated annual incidence **~<1 per 1,000,000**. (pqac-00000000, pqac-00000001) | Amante 2024, *World J Gastroenterol*, doi:10.3748/wjg.v30.i18.2374, https://doi.org/10.3748/wjg.v30.i18.2374; Wagner 2021, *J Clin Oncol*, doi:10.1200/JCO.21.01728, https://doi.org/10.1200/JCO.21.01728 |
| Defining pathology | Histology typically shows epithelioid to spindle cells with clear-to-eosinophilic cytoplasm arranged around vessels; abundant vasculature; radial/clustered perivascular growth. Diagnosis is pathology-led and often difficult on imaging alone. (pqac-00000004, pqac-00000006) | Hepatic PEComa imaging correctly diagnosed only **19.4% (7/36)** in one 2024 series. (pqac-00000006) | Dong 2024, *World J Oncol*, doi:10.14740/wjon1794, https://doi.org/10.14740/wjon1794; Ji 2024, *Front Oncol*, doi:10.3389/fonc.2024.1416254, https://doi.org/10.3389/fonc.2024.1416254 |
| Core IHC markers | Most useful diagnostic phenotype: melanocytic markers **HMB45**, **Melan-A**, often **MiTF**; myoid markers **SMA**, **desmin**, ± caldesmon/actin. HMB45 is commonly the most sensitive routine marker. TFE3 IHC may suggest the rearranged subset but requires molecular confirmation. (pqac-00000004, pqac-00000003, pqac-00000007) | Hepatic PEComa positivity: **HMB45 97.2% (35/36)**, **Melan-A 97.1% (34/35)**, **SMA 88.5% (23/26)**. Cutaneous review: **MiTF 100%**, **HMB45 94%**, **NKIC3 94%** among reported cutaneous cases. (pqac-00000006, pqac-00000007) | Ji 2024, *Front Oncol*, doi:10.3389/fonc.2024.1416254, https://doi.org/10.3389/fonc.2024.1416254; Cohen 2022, *Dermatol Online J*, doi:10.5070/d328157058, https://doi.org/10.5070/d328157058 |
| Molecular subtype 1: mTOR-pathway PEComa | Canonical subtype driven by **TSC1/TSC2 loss-of-function** and sometimes **MTOR** alterations, disrupting the hamartin–tuberin complex and releasing **mTORC1** signaling via RHEB; downstream activation includes phosphorylation of **p70S6K/S6**. This is the principal biologic rationale for mTOR inhibitors. (pqac-00000000, pqac-00000003, pqac-00000006) | Renal PEComa review reports roughly **~70% TSC2** and **~20% TSC1** mutations; bladder series found **mTOR-pathway mutations 53%**, including **TSC1/2 35%**, **MTOR 6%**, and **TSC/MTOR co-mutations 12%**. (pqac-00000006) | Dong 2024, *World J Oncol*, doi:10.14740/wjon1794, https://doi.org/10.14740/wjon1794; Wagner 2021, *J Clin Oncol*, doi:10.1200/JCO.21.01728, https://doi.org/10.1200/JCO.21.01728 |
| Molecular subtype 2: TFE3-rearranged PEComa | Distinct subset with **TFE3 gene fusions** (e.g., **SFPQ–TFE3**, **ASPSCR1–TFE3**); often shows strong TFE3 expression and may be biologically different from classic TSC-mutant PEComa. Molecular confirmation by **FISH or RNA-seq** is recommended when suspected. (pqac-00000003, pqac-00000004) | Bladder PEComa series: **TFE3 fusions 47% (8/17)**; in that series metastatic disease occurred in **5 TFE3-rearranged** vs **2 TSC/MTOR-mutated** tumors. TFE3 overexpression in advanced PEComa correlated with higher death risk **HR 11.8, P=0.04**. (pqac-00000001) | Testa 2023, *Cancer Res Commun*, doi:10.1158/2767-9764.CRC-23-0139, https://doi.org/10.1158/2767-9764.CRC-23-0139 |
| Epidemiology / demographics | PEComas occur across many organs, especially **kidney, uterus, lung, retroperitoneum, gastrointestinal tract, liver**; there is a clear **female predominance**, and uterine/gynecologic presentations are especially common. TFE3-rearranged tumors may present at younger ages than TSC-driven tumors. (pqac-00000000, pqac-00000003, pqac-00000006) | Female predominance outside sex-specific organs reported as **1.6- to 5-fold**. Hepatic series: **29 women / 7 men**, median age **47.8 y**. (pqac-00000006) | Dong 2024, *World J Oncol*, doi:10.14740/wjon1794, https://doi.org/10.14740/wjon1794; Ji 2024, *Front Oncol*, doi:10.3389/fonc.2024.1416254, https://doi.org/10.3389/fonc.2024.1416254 |
| Risk stratification (Folpe-type) | Commonly used malignant-risk features: **size >5 cm**, **infiltrative growth**, **high nuclear grade/cellularity**, **mitotic activity >1/50 HPF**, **necrosis**, and **vascular invasion**; tumors with **≥2 worrisome features** are generally considered malignant/high risk in practice. (pqac-00000002, pqac-00000004) | Framework is qualitative rather than universally validated; still widely used due to rarity and lack of better models. (pqac-00000004) | Amante 2024, *World J Gastroenterol*, doi:10.3748/wjg.v30.i18.2374, https://doi.org/10.3748/wjg.v30.i18.2374 |
| Standard local treatment | **Surgical resection** is the cornerstone for localized disease; ablation/embolization may be used in selected organ-specific settings when surgery is not feasible. (pqac-00000002, pqac-00000006) | Hepatic PEComa management in one series: **resection 67.7% (24/36)**, **radiofrequency ablation 16.7% (6/36)**, **TACE 2.7% (1/36)**, **sirolimus-chemotherapy 8.3% (3/36)**. (pqac-00000006) | Ji 2024, *Front Oncol*, doi:10.3389/fonc.2024.1416254, https://doi.org/10.3389/fonc.2024.1416254 |
| Key systemic therapy evidence: AMPECT primary report | **nab-Sirolimus (albumin-bound sirolimus; FYARRO)** is the first prospective, registration-trial–supported therapy for advanced malignant PEComa. (pqac-00000000) | In AMPECT, **31 efficacy-evaluable / 34 treated** patients: **ORR 39% (12/31; 95% CI 22–58)** with **1 CR + 11 PR**; **stable disease 52%**, **progressive disease 10%**; **67%** of responses occurred by **week 6**; **median PFS 10.6 mo**; **median OS 40.8 mo**; **median DOR not reached** at primary analysis after median **2.5 y** response follow-up. (pqac-00000000) | Wagner 2021, *J Clin Oncol*, doi:10.1200/JCO.21.01728, https://doi.org/10.1200/JCO.21.01728 |
| AMPECT long-term update / biomarker effect | Long-term follow-up confirmed durable benefit and strengthened the predictive value of **TSC2** alteration for response. Table 2/Figure 1 in the 2024 JCO update summarize efficacy visually/tabularly. (pqac-00000008, pqac-00000009) | Final update: **confirmed ORR 38.7% (95% CI 21.8–57.8)**; **mDOR 39.7 mo**; **median PFS 10.6 mo**; **median OS 53.1 mo**. Biomarker analysis in primary report: **8/9 (89%)** with **TSC2 mutation** responded vs **2/16 (13%)** without **TSC2** mutation (**P<.001**). Common TRAEs: **stomatitis 82.4%**, **fatigue 61.8%**, **rash 61.8%**; no grade ≥4 TRAEs in update. (pqac-00000000, pqac-00000008) | Wagner 2024, *J Clin Oncol*, doi:10.1200/JCO.23.02266, https://doi.org/10.1200/JCO.23.02266; Wagner 2021, *J Clin Oncol*, doi:10.1200/JCO.21.01728, https://doi.org/10.1200/JCO.21.01728 |
| 2023–2024 practice-oriented updates | Recent reviews emphasize molecularly informed classification, especially separating **mTOR-driven** from **TFE3-rearranged** tumors; they also note that **nab-sirolimus is the only FDA-approved therapy** for advanced malignant PEComa and that TFE3 overexpression may indicate worse prognosis. (pqac-00000001, pqac-00000006) | Single-institution advanced PEComa study (2023, n=29): **median OS 204.9 mo**, **median first-line PFS 92.4 mo**, **combined PFS 15.8 mo**; mTOR inhibitors and chemotherapy had similar OS/PFS in that retrospective dataset, but mTOR inhibitors were favored for lower morbidity. (pqac-00000001) | Testa 2023, *Cancer Res Commun*, doi:10.1158/2767-9764.CRC-23-0139, https://doi.org/10.1158/2767-9764.CRC-23-0139; Dong 2024, *World J Oncol*, doi:10.14740/wjon1794, https://doi.org/10.14740/wjon1794 |


*Table: This table condenses high-yield disease-characteristics evidence for PEComa, spanning diagnostic pathology, molecular subtypes, epidemiology, risk stratification, and the strongest current treatment data. It is designed as a compact reference for knowledge-base population and report drafting.*