This presentation details the histopathological features of a rare soft tissue tumor in a 20-year-old male, initially presenting as a thigh nodule. The tumor exhibits large cells with abundant, dense, eosinophilic, somewhat "squamoid" cytoplasm, resembling epithelioid sarcoma or poorly differentiated carcinoma. A key diagnostic clue highlighted is the presence of scattered neutrophils amidst spindled to epithelioid cells with pale, open nuclear chromatin. The entity discussed is Pseudomyogenic Hemangioendothelioma (PMHE), also known as Epithelioid Sarcoma-like Hemangioendothelioma. Crucially, PMHE is characterized immunohistochemically by being diffuse positive for Pan-Cytokeratin, negative for CD34, strong positive for Ulex Europaeus Agglutinin-1 (ERG), and often positive for CD31, while retaining INI1 nuclear expression (distinguishing it from epithelioid sarcoma which typically loses INI1). Despite its confusing nomenclature and immunophenotype suggesting a vascular origin (due to ERG/CD31 positivity), the tumor lacks definitive vascular structures. Molecularly, PMHE is supported by the presence of FOSB gene fusions (e.g., FOSB-SERPINE1 or FOSB-ACTB). Clinically, PMHE is notable for its high rate of multifocality (around 60%), often regional within an extremity, and generally indolent behavior, despite having features that can mimic aggressive metastases.
Case Study: Pseudomyogenic Hemangioendothelioma (PMHE)
0:00:11 Case Presentation: A 20-year-old male presented with a thigh nodule/multinodular proliferation growing in the deep dermis and subcutis.
0:00:42 Morphological Features: Lesions consist of large cells with abundant, dense, eosinophilic cytoplasm, sometimes appearing somewhat "squamoid," alongside spindled cells with pale nuclear chromatin.
0:02:06 Key Diagnostic Clue: Scattered neutrophils are observed between the tumor cells in about half of cases, serving as a helpful clue for diagnosis.
0:02:22 Immunohistochemical Profile: Classically strongly positive for Pan-Cytokeratin, negative for CD34, strongly positive for Ulex Europaeus Agglutinin-1 (ERG), and often positive for CD31. It is negative for Desmin (ruling out rhabdomyosarcoma).
0:02:51 Diagnosis: Pseudomyogenic Hemangioendothelioma (PMHE), also known as Epithelioid Sarcoma-like Hemangioendothelioma.
0:03:41 Distinguishing from Epithelioid Sarcoma (ES): PMHE is positive for INI1 (retains expression), whereas most ES cases show loss of INI1.
0:04:01 ERG Positivity: ERG is a sensitive vascular marker but is not specific; it can also be positive in AML and prostate cancer.
0:05:35 Nomenclature Confusion: Despite the "Hemangioendothelioma" name and positive vascular markers (ERG, CD31), the tumor lacks clear vascular lumens, requiring reliance on IHC and molecular data.
0:06:24 Molecular Support: Recent studies support its endothelial lineage due to frequent FOSB gene fusions (e.g., FOSB-SERPINE1 or FOSB-ACTB).
0:07:37 Clinical Behavior (Multifocality): PMHE is often multifocal (around 60% of cases), frequently regional within one extremity (arm or leg), thought to represent regional metastases.
0:08:10 Tissue Involvement: Commonly involves skin (75%), muscle (50%), and occasionally bone (20%).
0:08:52 Prognosis: Behavior is generally indolent; morphologic features do not predict metastasis, which is rare, though lung metastasis has been reported.
0:09:22 Differentiation: PMHE is molecularly and morphologically unrelated to other entities sometimes grouped with it (e.g., Kaposi Sarcoma, other endotheliomas).