Diagnosis and Discussion

Diagnosis

Pulmonary epithelioid hemangioendothelioma.

Discussion

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor which can occur anywhere in the body with the most common sites being liver, bone, and lung. Pulmonary EHE (PEH) can affect both sexes at all ages; however, it preferentially occurs in females with a median age of onset of 36-years-old. Approximately 50-70% of patients with PEH are asymptomatic while others often present with nonspecific symptoms, such as chest pain, cough, dyspnea on exertion, or hemoptysis. The majority of patients with PEH often have incidental slow growing pulmonary nodules bilaterally that range anywhere from a few millimeters to a few centimeters in size, with most of the nodules being less than 1 cm. Regardless of the size of the pulmonary nodules, approximately 20% of the patients with PEH have concurrent EHE in other anatomic sites such as liver, bone, or skin.

The diagnosis of PEH is often achieved by the characteristic histology of the tumor, which is distinct from its soft tissue counterpart. Grossly, PEH often presents as multiple gray-white, firm, and well-demarcated nodules with a chondroid appearance. Microscopically, PEH has the characteristic alveolar filling pattern and is made up of various sized nests with a central eosinophilic hyalinized stroma. The neoplastic cells are variable in size and are either individually embedded in the center of stroma or aggregate at the periphery of the nests. The tumor cells exhibit well-defined cell borders and have round nuclei with open chromatin and ample eosinophilic cytoplasm. Some intracytoplasmic vacuoles can be seen in occasional tumor cells.

Similar to other vascular tumors PEH will express endothelial markers including FLI-1, CD31, CD34, and ERG. However, the recently identified chromosomal translocations can be used to distinguish PEH from other vascular neoplasms that share the same IHC features. Recent studies have identified that approximately 90% of the PEH cases have the characteristic chromosomal translocation, t(1;3)(p36;q25), resulting in WWTR1-CAMTA1 fusion gene. A second chromosomal translocation, t(X;11)(p11.2;q22.1), resulting in YAP1-TFE3 fusion gene was also identified in a subset of PEH patients who were found to be negative for the WWTR1-CAMTA1 fusion. Interestingly, both chromosomal translocations are not mutually exclusive and can coexist in PEH. Nuclear expression of CAMTA1 by immunohistochemistry is seen in approximately 90% of EHE, is a very sensitive and specific marker for EHE, and is helpful to differentiate this tumor from other vascular tumors.

Due to the rarity of PEH, there is no definitive treatment available. Surgical resection for limited nodules or symptomatic relief is often the treatment of choice, if feasible. Other treatment modalities include radiotherapy and chemotherapy for patients who are not good surgical candidates. The overall prognosis of PEH is unpredictable.

References

Lau K, et al., Clinical Patterns and Outcome in Epithelioid Hemangioendothelioma With or Without Pulmonary Involvement: Insights From an Internet Registry in the Study of a Rare Cancer. Chest. 2011;140:1312-1318.

Einsfelder B., et al. Epitheloides Hämangioendotheliom der Lunge (IVBAT). Der Pathologe. 2006;27:106-115.

Doyle LA, et al. Nuclear expression of CAMTA1 distinguishes epithelioid hemangioendothelioma from histologic mimics. Am J Surg Pathol. 2016;40:94-102.

Antonescu CR, et al. Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. Genes, Chromosomes and Cancer. 2013;52:775-784.

Lee SJ, et al. Epithelioid hemangioendotheliomas with TFE3 gene translocations are compossible with CAMTA1 gene rearrangements. Oncotarget. 2016;7:7480-7488.

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