Pseudomyogenic hemangioendothelioma (PHE) is a rare neoplasm that typically presents as nodules on the extremities. Genital involvement is rare. We present the case of a young man with a localized PHE on the penis.

A 23-year-old male presented for consultation regarding sexually transmitted diseases. He reported an asymptomatic ulcer on his penis with a 2-week duration. He had no history of sexually transmitted infections (STIs). Over the previous three months, he had engaged in sexual activity with two female partners.

On physical examination, a round ulcer with raised edges at the inner foreskin was evident (Fig. 1). No urethral discharge or lymphadenopathy was observed. An empirical dose of benzathine penicillin G (2.4 million units intramuscularly) was administered. An STIs screening was performed.

Fig. 1.

Circular ulcer with raised edge at the inner foreskin.

One week later, the patient reported no improvement. PCR testing of the ulcer was negative for Treponema pallidum, Haemophilus ducreyi, Chlamydia trachomatis serovars L1, L2, and L3, as well as herpes simplex virus types 1 and 2. Serologic testing for syphilis, hepatitis, and HIV was negative.

A biopsy revealed a multinodular, poorly defined dermal lesion. It consisted of epithelioid and spindle-shaped cells with abundant eosinophilic cytoplasm, moderate nuclear atypia with prominent nucleoli, and isolated mitotic figures. There was a prominent infiltrate of neutrophils, numerous vascular structures with interspersed prominent endothelial (tack) cells, and areas of central fibrosis. The adjacent epidermis exhibited focal parakeratosis, mild spongiosis, and associated focal lymphocytic exocytosis (Fig. 2). PAS, Grocott, Gram, and Ziehl-Neelsen (BK) stains showed no microorganisms.

Fig. 2.

Light microscopy – (A) Hematoxylin & eosin (Hematoxylin & eosin, ×20) image of the ulcerated dermal lesion with multinodular architecture and poorly defined borders. (B) (Hematoxylin & eosin, ×40) Prominent polymorphonuclear infiltrate; vascular structures with interspersed prominent endothelial (tack) cells, and areas of central fibrosis. (C‒D) (Hematoxylin & eosin, ×100, ×200) Higher power section of atypical spindle and epithelioid cells, some of them with dense eosinophilic cytoplasm and eccentric nuclei, resembling rhabdomyoblasts.

Immunohistochemistry was negative for herpes viruses 1, 2, and 8, cytomegalovirus, and Treponema. CKAE1/AE3 showed weak, diffuse positivity, while SOX10 and CD45 were negative. Moderate, diffuse positivity for ERG and CD31 and strong, diffuse positivity for FOSB (Fig. 3), with weak positivity for smooth muscle actin and retained SMARCA4 expression. Stains for p40, D2-40, CD34, desmin, and H-caldesmon were negative. CD3, CD20, and CD30 highlighted sparse accompanying inflammatory cells (Table 1). Next-generation sequencing revealed an ACTB–FOSB gene fusion.

Fig. 3.

Imunnohistochemistry -The tumor cells showed weak and diffuse positivity for Cytokeratin AE1/AE3 (A, ×100), moderate and diffuse positivity for ERG (B, ×100), and strong and diffuse positivity for FOSB (C, ×100).

Diagnosis of PHE was reached. The lesion was excised with clear margins after two rounds of Mohs surgery.

PHE is a locally aggressive endothelial neoplasm1,2 that predominantly presents as nodules on the lower extremities. Extension into the underlying bone is relatively frequent.

Genital involvement is rare. Eight cases have been documented (Table 2).2–7 It usually presents as non-ulcerated, asymptomatic nodules. In males, the predominant location is the glans penis; in females, the labia majora.3 The ulcerated and non-nodular presentation is exceptional and can mimic more common entities such as squamous cell carcinoma, cutaneous sarcomas, STIs, or traumatic ulcers. This atypical clinical form can delay diagnosis or lead to initial diagnostic errors, given that the ulcerated appearance is not usually associated with low-grade vascular tumors.

Histopathologically, genital PHE is similar to cases reported in other locations. At low magnification, the tumor appears as a poorly circumscribed dermal and hypodermal proliferation. At higher magnification, it shows numerous cells with abundant eosinophilic cytoplasm, reminiscent of rhabdomyoblasts. In some areas, vascular lumina are infiltrated by tumor cells. The infiltrative nature of the tumor may extend into muscle, fat, and occasionally bone, with sporadic intracytoplasmic vacuoles and rare lumina.8

Immunohistochemically, PHE shows dual expression of endothelial markers (ERG, FLI1) and cytokeratins (most commonly AE1/AE3), aiding in differentiation from other vascular and soft tissue tumors. Focal expression of smooth muscle actin is present in up to one-third of cases. Nuclear positivity for FOSB is a consistent and distinctive feature. Retained INI1 (SMARCB1) expression also helps distinguish PHE from morphologically similar entities, mainly conventional and proximal type epithelioid sarcoma.9

Molecularly, recurrent FOSB gene fusions are a hallmark of PHE, contributing to its pathogenesis and providing diagnostic and potentially therapeutic targets. Translocations involving chromosomes 7 and 19 are common and may play a role in tumor development.9

Surgery remains the mainstay of treatment.10 PHE may exhibit local aggressiveness and a high recurrence rate if not completely excised, but distant metastases are rare.

A high index of suspicion is essential in young patients presenting with persistent genital nodular lesions of several weeks’ or months’ duration, particularly when serologic testing for STIs is negative and empirical antimicrobial treatment is ineffective. In such cases, a biopsy should be performed to rule out neoplasms.