This presentation details the histopathology of a rare soft tissue tumor from a 20-year-old male, characterized by a multinodular proliferation in the dermis and subcutis. The tumor cells display features that mimic Epithelioid Sarcoma (large cells, abundant eosinophilic cytoplasm) and other entities like Epithelioid Sarcoma, poorly differentiated carcinoma, and Reticulohistiocytoma. A key diagnostic clue highlighted is the presence of scattered neutrophils between spindle-to-epithelioid cells, present in about half of cases. Immunophenotypically, the tumor is typically strongly and diffusely positive for PANCK, negative for CD34, strongly positive for Ulex Europaeus Agglutinin-1 (ERG), and often positive for CD31, while being negative for Desmin, differentiating it from Rhabdomyosarcoma. The tumor is definitively identified as Pseudomyogenic Hemangioendothelioma (PMHE), also known as Epithelioid Sarcoma-like Hemangioendothelioma. The presentation emphasizes that despite its morphological resemblance to Epithelioid Sarcoma (ES), PMHE is molecularly distinct, notably retaining nuclear INI1/SMARCB1 expression (unlike most ES cases which show loss). Molecularly, PMHE often harbors FOSB gene fusions (e.g., FOSB-SERPINE1 or FOSB-ACTB), supporting its vascular origin, even though it lacks overt vascular channels microscopically. Clinically, PMHE is often multifocal (regional involvement in about 60% of cases, thought to represent regional metastasis) across skin, muscle, and bone layers, yet generally follows an indolent course with rare distant metastases.
Key Features and Differential Diagnosis of Pseudomyogenic Hemangioendothelioma (PMHE)
00:00:11 Case Presentation: Review of a 20-year-old male with a multinodular, dermal/subdermal thigh nodule.
00:00:42 Histological Appearance: Cells are large with abundant, dense eosinophilic cytoplasm, sometimes appearing squamoid or epithelioid. Nuclei are large with pale, open chromatin.
00:01:16 Differential Diagnosis: Primary considerations based on morphology include Epithelioid Sarcoma (ES), poorly differentiated carcinoma, and Reticulohistiocytoma. Some authors noted resemblance to Rhabdomyoblasts.
00:02:06 Crucial Diagnostic Clue: Presence of scattered neutrophils between spindle-to-epithelioid cells is noted as a highly helpful clue, present in about half of cases.
00:02:22 Classic Immunophenotype: Diffusely strongly positive for PANCK, negative for CD34, strongly positive for ERG, and often positive for CD31 (but negative for Desmin).
00:02:51 Diagnosis: The tumor is Pseudomyogenic Hemangioendothelioma (PMHE), also called Epithelioid Sarcoma-like Hemangioendothelioma.
00:03:41 Mimicry of ES: The strong, diffuse Keratin positivity and frequent ERG positivity make confusion with Epithelioid Sarcoma easy.
00:04:44 INI1 Status: Unlike Epithelioid Sarcoma, which usually shows loss of INI1/SMARCB1 expression, PMHE retains nuclear INI1 expression.
00:05:35 Vascular Origin Confusion: Despite lacking clear vascular lumens microscopically, the tumor expresses vascular markers (ERG, CD31), leading to its classification as vascular.
00:06:24 Molecular Support: Recent studies suggest PMHE is truly endothelial due to frequent FOSB gene fusions (e.g., FOSB-SERPINE1 or FOSB-ACTB).
00:07:37 Clinical Behavior: PMHE is often multifocal (regional involvement in ~60% of cases, possibly regional metastasis) within an extremity (arm or leg).
00:08:10 Tissue Involvement: Frequently involves skin (~75%), muscle (~50%), and bone (~20%).
00:08:52 Prognosis: Generally indolent behavior with good prognosis, although management of multifocal disease can be problematic; distant metastases are rare.
00:09:22 Unrelated Entities: PMHE is molecularly and morphologically unrelated to Epithelioid Hemangioendothelioma or Kaposi Sarcoma.