Penile Epithelioid Hemangioendothelioma in a Child

ABSTRACT

An 8-year-old boy initially thought to have a penile arteriovenous malformation was later diagnosed with a rare vascular sarcoma, epithelioid hemangioendothelioma (EHE). Despite challenges in diagnosis, he underwent supraselective angioembolization and partial penectomy for oncological clearance. EHE, a low-grade malignancy, requires prompt identification and treatment due to potential systemic involvement.

INTRODUCTION

Penile tumors are uncommon in the pediatric population, with only a handful of reported cases in the literature. Epithelioid hemangioendothelioma (EHE)is a vascular sarcoma, i.e., exceedingly rare in children. Due to its low incidence and the paucity of standard management guidelines, the diagnosis and treatment of EHE is challenging. The literature has several reports of penile EHE in adults, misdiagnosed as other painful penile lesions, leading to delays in initiating appropriate treatment.[1] We present the case of an 8-year-old boy who was erroneously diagnosed with penile arteriovenous malformation (AVM) but later detected to have EHE of the penile shaft.

CASE REPORT

An 8-year-old boy presented with complaints of firmness and tenderness of the penile shaft for 2 years. On suspicion of high-flow priapism secondary to an AVM, he underwent supraselective embolization of arterial feeders from the branches of the right internal and external pudendal arteries. Two months after a favorable early response, a rapidly enlarging exophytic mass appeared over the glans penis, causing obstructive lower urinary tract symptoms.

The patient then presented to our center with a mass replacing the entire glans and extending up to the proximal one-third of the shaft of the penis [Figure 1a]. After a suprapubic cystostomy, to relieve symptoms, a magnetic resonance imaging of the pelvis and external genitalia showed diffuse enlargement of the distal two-thirds of the corpora spongiosum, with multiple small vascular channels compressing the urethra while sparing the corpora cavernosa [Figure 2a]. On digital subtraction angiography, penile arterial feeders to the lesion were identified mainly from the right internal pudendal artery with no evidence of a nidus or venous lakes to suggest an AVM [Figure 2b and c]. The feeders were selectively embolized with polyvinyl alcohol particles and coils, and the tumor was debulked after 72 h.

Figure 1.

(a) Penile epithelioid hemangioendothelioma involving the glans penis and distal two-third of the shaft of the penis. (b) Resected specimen of penile epithelioid hemangioendothelioma postmodified partial penectomy. (c) Mid-penile neomeatus postmodified partial penectomy in a case of penile epithelioid hemangioendothelioma

Figure 2.

(a) T2-weighted sagittal MRI showing penile epithelioid hemangioendothelioma involving the glans penis and the corpus spongiosum of distal and mid-penile shaft. (b) Selective right internal pudendal artery angiogram showing abnormal hypervascular tumor blush. Note made of coils placed during earlier embolization. (c) Postembolization, complete disappearance of tumor blush. (d) Hematoxylin and eosin stain in a case of penile epithelioid hemangioendothelioma showing oval to epithelioid cells with coarse chromatin and moderate cytoplasm, arranged in cords, sheets, and short fascicles in a mildly myxoid stroma

Histopathological examination finally clinched the diagnosis of EHE. The tumor was highly cellular, with oval to epithelioid cells, arranged in cords, diffuse sheets, and short fascicles, with focal perivascular arrangement in a mildly myxoid stroma. The cells had coarse chromatin, low mitosis, and a moderate amount of cytoplasm, with some cells showing vacuolation. The tumor cells were positive for FLI1, CD31, and vimentin, and negative for STAT6 and SMA [Figure 2d].

A whole-body [18F]-fluorodeoxyglucose-positron emission tomography-computed tomography (CT) showed a 2.8 cm × 1.4 cm, SUVmax 7.8, residual soft-tissue lesion involving the shaft of the penis, with no evidence of any distant metastases.

The patient then underwent a modified partial penectomy, with excision of the glans, the involved corpus spongiosum, and the anterior urethra up to the mid-penile shaft while preserving the entire length of the corpus cavernosum. The neomeatus was created at the mid-penile junction with a residual penile length of 5 cm [Figure 1b and c]. The patient had an uneventful postoperative recovery and is planned for a reconstructive urethroplasty on follow-up.

DISCUSSION

Weiss and Enzingern first described EHE as a borderline variant of vascular tumors with features in between a completely benign hemangioma and a malignant angiosarcoma.[2] The 2018 International Society for the Study of Vascular Anomalies Classification recently recategorized EHE from borderline to a malignant type of vascular tumor. The prevalence of EHE is <1/10,00,000 and peaks in the fourth to fifth decade. The most available information on its natural history, diagnosis, and management is based on adult literature.[3,4] Clinically and radiologically, it can be challenging to distinguish from other soft tissue and vascular lesions. Around 50% of cases demonstrate origin from a blood vessel on radio imaging. Twenty to 50% of patients have metastatic disease at presentation, commonly involving the liver, lungs, and bone.[3]

Penile EHE can mimic Peyronie’s disease and priapism, causing a delay in diagnosis. It can also present with local mass systemic symptoms such as fever and weight loss. Penile EHE can be differentiated from high-flow priapism by the absence of a bruit and an inability to aspirate corporal blood from the lesion.

The diagnosis of EHE is primarily histopathological, characterized by epithelioid cells arranged in cords, nests, or strands. The cells have a glassy, eosinophilic cytoplasm with cytoplasmic vacuoles. They show low mitotic activity and mild nuclear atypia. The cells express markers of endothelial differentiation, such as CD31, CD34, ERG, and FLI-1. Recent molecular studies have identified t(1;3)(p36.3;q25) translocation in over 90% of EHE, leading to the formation of the WWTR1-CAMTA1 fusion gene. Another subset carries a t(X; 11)(p11;q22) translocation, leading to a YAP1-TFE3 fusion.[3] Tumors larger than 3 cm and with >3 mitotic figures/50 high-power fields have a worse prognosis.

The management of EHE is based on its local and metastatic spread. Surgical excision, based on the principles of sarcoma surgery, is the modality of choice for treating unifocal EHE. The aim of resection is to achieve R0 margins, including the vessel of origin, leaving a cuff of normal tissue all around the tumor. Small penile lesions have been managed successfully with local R0 excision alone, whereas larger tumors require partial or total penectomy, with or without reconstruction.[1] Preoperative angioembolization has not been reported for penile EHE, although it has been utilized to aid surgical excision of other penile vascular tumors in children, with no reported adverse effects. In an angiocentric tumor like EHE, supraselective embolization of the feeder will reduce the inflow to the tumor alone, reducing the potential blood loss during the resection while preserving the blood supply to the healthy tissue.

Since EHE is relatively radiosensitive, adjuvant radiotherapy (RT) at a dose of 60 Gy in 30 fractions can complement surgery in case of R1 resections.[3] Management of metastatic or unresectable disease is more challenging. In locally inoperable cases, definitive RT up to 60 Gy in conventional fractionation is recommended. Metastatic disease warrants multimodality treatment. Conventional chemotherapy for sarcomas has limited activity, with the best results observed using doxorubicin. Promising results have been seen with newer agents such as interferon, thalidomide, multityrosine kinase inhibitors, and mechanistic target of rapamycin inhibitors. Systemic chemotherapy can be combined with locoregional therapies such as RT, isolated limb perfusion, and transarterial chemoembolization.

The risk of local recurrence of EHE following complete surgical resection is 10%–15%.[3] In a retrospective case series of 24 pediatric patients with EHE, 63% of patients had progressive disease with a mean time to progression of 18.4 months.[5] In adults, 15% mortality has been reported in patients with systemic spread. The European Society for Medical Oncology consensus on EHE recommends a follow-up with a magnetic resonance imaging of the primary tumor site and a whole-body CT scan every 6 months for the first 4–5 years and yearly scans thereafter.[3]

To conclude, penile EHE is exceedingly rare in children, necessitating prompt diagnosis and treatment. EHE should be considered a differential in children presenting with a vascular soft-tissue penile mass or a Peyronie’s disease or a priapism-like picture; however, the diagnosis can only be confirmed on histopathology. Nonmetastatic disease should be managed within the ambit of the principles of sarcoma management. Reconstruction of the residual phallus is essential to maintain the quality of life for these boys.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that his name and initials will not be published and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.