PEComas are soft tissue neoplasms arising from perivascular epithelioid cells, a distinctive cell type with smooth muscle and melanocytic differentiation markers. The precise cellular origin of perivascular epithelioid cells remains an area of investigation. Most PEComas occur sporadically without a clear hereditary predisposition. A subset is associated with tuberous sclerosis complex, a genetic condition — this association is most established for angiomyolipoma and LAM subtypes. However, PEComa as a disease class does not follow a recognized inheritance pattern, and no specific causative genes are catalogued for the broader PEComa family in current datasets. The risk factors for sporadic PEComa are not well defined.

Diagnosis of PEComa relies on histopathological examination of tumor tissue. These tumors characteristically co-express smooth muscle markers (such as actin and desmin) and melanocytic markers (such as HMB-45 and Melan-A) on immunohistochemistry, a combination that is diagnostically distinctive. Imaging studies including computed tomography and magnetic resonance imaging are used to characterize tumor anatomy and extent. Radiological features vary by subtype — angiomyolipoma, for example, may show characteristic fat attenuation on CT. Distinguishing benign from malignant PEComa requires careful pathological assessment of tumor size, mitotic activity, necrosis, and vascular invasion.

Surgical resection is a primary treatment approach for localized PEComa when feasible. For malignant or unresectable PEComa, systemic therapy is indicated. Fyarro (sirolimus protein-bound particles for injectable suspension, albumin-bound) has received FDA approval for the treatment of locally advanced unresectable or metastatic PEComa. This mTOR pathway inhibitor represents the first and currently only targeted therapy with regulatory approval specifically for PEComa. Other mTOR inhibitors are used in related contexts, particularly in tuberous sclerosis-associated subtypes. Clinical trials are evaluating additional systemic agents including checkpoint inhibitors and novel combination approaches.

Prognosis in PEComa is highly variable and dependent on subtype, tumor size, histological grade, and the presence of malignant features. Benign PEComas, including most small angiomyolipomas, follow an indolent course with low risk of recurrence following resection. Malignant PEComas — characterized by large size, high mitotic rate, necrosis, and infiltrative growth — carry a substantially worse prognosis and may recur or metastasize. The prognosis for locally advanced or metastatic disease has been challenging to define due to the rarity and heterogeneity of this tumor family, but active treatment options including approved targeted therapy have expanded the management landscape.

PEComa research is characterized predominantly by case reports and case series given the rarity of these tumors, with 84 case reports and 15 review articles among recent publications. Ongoing clinical trials are evaluating novel immunotherapy approaches including checkpoint inhibitors and combination regimens in rare soft tissue tumors broadly, as well as PEComa-specific cohorts. Biomarker research is also active, including investigation of molecular features that may predict response to mTOR inhibition or other targeted agents. The rarity and histological heterogeneity of PEComa present challenges for conducting large prospective trials, making multi-institutional collaboration and registry studies particularly important for advancing knowledge in this field.