Dr. Jared Gardner presents a case study focusing on the morphology and diagnosis of Epithelioid Hemangioendothelioma (EHE) involving the lung. EHE is a complicated vascular tumor whose behavior varies significantly by site; in the lungs and liver, it acts more aggressively, while soft tissue/skin lesions carry a better prognosis. Morphologically, EHE is challenging as it presents with epithelioid cells arranged in nests and cords, mimicking carcinoma. In the lung, it exhibits a unique intra-alveolar growth pattern. Key diagnostic features include a dense, hyalinized, and often chondromyxoid stroma, and the presence of "blister cells"—intracytoplasmic vacuoles containing fragments of degenerated red blood cells—which hint at its endothelial origin despite lacking well-formed vascular channels. Diagnosis is confirmed by vascular immunohistochemistry (ERG, CD31, CD34) and molecular testing, primarily identifying the WWTR1/CAMTA1 gene fusion.
Epithelioid Hemangioendothelioma (EHE) Case Study (Lung)
0:03 Introduction & Behavior: Epithelioid Hemangioendothelioma (EHE) is discussed, emphasizing its complicated and site-dependent behavior. In the lung or liver, it behaves more like a malignancy (often slow-growing).
0:40 Morphology Challenge: Although EHE is a vascular tumor, it often looks epithelial (epithelioid cells with round nuclei and abundant cytoplasm) because the cells are arranged in nests, cords, or aggregates, similar to a carcinoma.
1:03 Lung-Specific Pattern: EHE in the lungs is unique because it grows within the alveolar spaces (intra-alveolar growth). Historically, this pattern led to misdiagnosis as an unusual variation of carcinoma (e.g., bronchoalveolar carcinoma).
1:48 Stromal Clues: The tumor is characterized by a dense background stroma, which can appear blue (myxoid), pink (hyalinized sclerotic collagen), or a mixture. This appearance can sometimes look chondroid or cartilage-like.
2:33 Vascular Nature: EHE is endothelial in origin, but it typically does not form the obvious blood vessel channels expected of a vascular tumor.
3:07 Hallmarks – Blister Cells: The microscopic clue to its endothelial nature is the presence of little bubbles or vacuoles in the cytoplasm, sometimes containing fragments of degenerated red blood cells. These are called blister cells and are a hallmark feature.
4:12 Immunohistochemistry (IHC): EHE stains positive with standard vascular markers, including ERG, CD31, and CD34.
4:25 Molecular Diagnosis: The majority of EHE tumors possess a gene fusion involving WWTR1 and CAMTA1. A small subset has an alternative fusion of YAP1 and TFE3.
5:18 Historical Naming: Due to its intra-alveolar growth pattern, the tumor was previously known as IVBAT (Intravascular Bronchoalveolar Tumor) before being formally named Epithelioid Hemangioendothelioma by Sharon Weiss and Franz Enzinger.
Key Takeaway: The combination of epithelioid cells, chondromyxoid stroma, and blister cells, particularly when showing intra-alveolar growth in the lung, is highly indicative of EHE.