Pseudomyogenic hemangioendothelioma (PSHE) is a locally aggressive, rarely metastasizing endothelial neoplasm that often presents as multiple discontiguous masses involving different tissue planes in the same general anatomic region. 

PSHE is uncommon and occurs most commonly in the extremities of young adults, with a male predominance. 

PSHE most commonly involves the lower limbs (60% of cases), followed by the upper extremity and trunk (20% each). ¹ It is frequently multifocal, involving multiple tissue planes. Cutaneous involvement is present in 75% of cases, and bone involvement is present in about 20%.¹

PSHE is composed of fascicles of spindle cells with mildly atypical nuclei and eosinophilic cytoplasm that imparts a "myoid" appearance. In 50% of cases, there is a prominent admixed neutrophilic infiltrate, and about half of tumors have admixed rhabdoid cells with brightly eosinophilic cytoplasm.

PSHE shares significant immunohistochemical overlap with epithelioid sarcoma, which is partly why it had been originally termed "epithelioid sarcoma-like hemangioendothelioma".¹ PSHE commonly expresses keratins and ERG, and in half of cases there is CD31 expression. ^1-3 In contrast to epithelioid sarcoma, it does not exhibit loss of INI-1 expression. ^2,4There is nuclear FOSB expression in essentially all cases (Fig. 1), consistent with the presence of the underlying FOSB rearrangements. ^5,6

Figure 1. FOSB immunohistochemistry in pseudomyogenic hemangioendothelioma (PSHE). Immunohistochemistry demonstrates nuclear FOSB positivity in this PSHE of bone, a finding present in nearly all cases of PSHE.

PSHE is locally aggressive and often multicentric; depending on the extent of disease and patient symptoms, radical surgeries, including amputations, might be necessary. Approximately 60% of patients either experience local recurrence or develop additional tumors in the same anatomic region. ² There is, to date, one report of patient developing widely metastatic disease.² Telatinib, a VEGF inhibitor, has been shown to lead to a complete and durable response in a patient with unresectable disease (see below). ⁷

• Recurrent t(7;19)(q22;q13) rearrangement was identified in PSHE, and it was subsequently found to correspond to SERPINE1::FOSB fusion. ^8,9

• More recently, ACTB::FOSB fusion was also reported to be present in about half of cases.^10,11 There are also recent reports of WWTR1::FOSB and CLTC::FOSB fusions. ^12,13

• The characteristic FOSB translocations lead to overexpression of a truncated FOSB protein due to a positive feedback loop that depends on VEGF- and PDGF-receptors. Disruption of this feedback loop via VEGF inhibition has led to a complete and durable response in an isolated case report.⁷