Angiolymphoid hyperplasia with eosinophilia on penis in HIV-positive patient: An unusual presentation

Sir,

A 36-year-old uncircumcised male, known HIV-positive since 3 years, presented with an asymptomatic, solitary, flesh-colored growth on his penis with a history of gradual increase in the size of the lesion over 6 weeks. There was no history of painful erections, deviation of penis on erection, dyspareunia, or any urinary symptoms. The CD4 count, before initiating highly active anti-retroviral treatment (zidovudine, lamivudine, and nevirapine) two years ago, was 198/ mm ³ .

Cutaneous examination revealed a solitary, sub-preputial pink, flesh-colored non-foul-smelling exophytic polypoid eroded indurated growth with moist surface measuring about 1.5 × 1 cm over ventrolateral aspect of penile shaft, [Figure - 1]a which was non-tender, non-friable, did not bleed on manipulation and was covered with scant yellowish slough, without significant inguinal lymphadenopathy. The rest of dermatological and systemic examination was normal. Other differentials considered were donovanosis, hypertrophic genital herpes, and primary chancre.

Figure 1: (a) Single, sub-preputial exophytic polypoid eroded growth measuring 1.5 × 1 cm at first presentation. (b) Lesion measuring 3 cm × 2.5 cm after 12 weeks.

Routine laboratory parameters were normal, and screening tests for sexually transmitted infections including venereal disease research laboratory (VDRL) test were negative. CD4 + T lymphocyte count was 345/mm ³ . On failure to respond to 14 days of oral acyclovir and 21 days of oral erythromycin, incisional biopsy was performed, which revealed extensive mucosal ulceration lined by acute inflammatory infiltrate. [Figure - 2]a Sub-epithelial tissue showed nodulovascular proliferation lined by plump epithelioid endothelial cells with abundant eosinophilic cytoplasm, hyperchromatic nuclei, prominent nucleoli and few lesional cells showed intracytoplasmic vacuoles. [Figure - 2]b The inflammatory infiltrate was rich in eosinophils and lymphocytes with few plasma cells. [Figure - 2]c Pleomorphism was minimal without any cytological atypia, which was consistent with diagnosis of angiolymphoid hyperplasia with eosinophilia (ALHE). There was no peripheral blood eosinophilia.

Figure 2: (a) Ulcerated epithelium. Vascular proliferation with dense infiltrate in sub-epithelial tissue on hematoxylin and eosin stain at 4×. (b) Vascular channels lined by plump endothethelial cells (blue arrow) with intracytoplasmic vacuoles (red arrow) on hematoxylin and eosin stain at 40×. (c) Dense inflammatory infiltrate with predominance of lymphocytes and Eosinophils on hematoxylin and eosin stain at 40×

Due to progressive increase in size of lesion to 3 cm × 2.5 cm over 12 weeks, [Figure - 1]b a complete local excision of the growth with therapeutic circumcision was performed with no recurrence over 14 months of follow-up.

ALHE, first reported in 1969, is an uncommon idiopathic condition with female preponderance, presenting between 3 ^rd to 5 ^th decade of life. ^[1] It is seen most commonly in Asians, followed by whites and rarely in blacks. Approximately 85% of lesions occur near the ear, forehead, or scalp, extremities being the next most common site. It presents as solitary, few or multiple, sometimes grouped, erythematous, violaceous or brown papules, plaques, or nodules, typically being unilateral. ^[1] Most lesions are 0.5-2 cm in diameter and may be eroded or crusted. Lesions may be associated with pruritus or pain, or may pulsate. ^[1] Rare sites of involvement include the hands, shoulders, breasts, penis, oral mucosa and tongue, orbit, eyelids, and lacrimal glands. ^[2] Natural course of ALHE tends to be chronic and non-remitting over months to years. Approximately 20% patients have peripheral blood eosinophilia.

Histology shows a well-defined area of vascular proliferation in the dermis and/or subcutis, with large epithelioid or histocytoid endothelial cells containing abundant cytoplasm, often with vacuoles and an infiltrate of variable numbers of eosinophils and lymphocytes. The stroma is myxoid, with minimal or no fibrosis. ^[1],[3]

Olsen and Helwig found, in 53 cases out of 116, an "an arterial structure" appearing to be associated with venules or "area of endothelial proliferation," which provided evidence that these lesions represent a form of arterio-venous shunt. ^[4]

The pathogenesis of ALHE is unknown but is considered to be a reactive phenomenon, possibly in response to or in association with an underlying vascular malformation. ^[1] There is history of trauma in some cases, and hyperestrogenemia (e.g. pregnancy, oral contraceptive use) may foster lesion growth. ^[1] T-cell monoclonality has been reported in few cases.

A comprehensive review of literature revealed less than 25 cases of ALHE occurring on penis. ^{[5],[6],[7],[8]} In the largest series, Fetsch et al described 19 cases of ALHE occurring on penis. ^[5] D′Offizi et al reported a case of ALHE in an HIV-seroreactive patient at extragenital site. ^[9]

Despite some clinico-pathological overlap, ALHE and Kimura Disease (KD) appear to be distinct entities. Lesions of ALHE are usually smaller, more superficial, more numerous and often symptomatic than those of KD. Histopathologically, lymphoid follicles represent dominant characteristic of KD, whereas large epithelioid endothelial cells are a key feature of ALHE. ^[10]

ALHE should be distinguished from a variety of benign and malignant vascular proliferations, including pyogenic granuloma, epithelioid hemangioendothelioma, angiosarcoma, and Kaposi sarcoma, all of which lack a noticeable eosinophil infiltrate. It should also be differentiated from cutaneous lymphoid hyperplasia, cutaneous B-cell lymphomas, bacillary angiomatosis, and bartonellosis- many of which have distinctive histopathological features.

Intervention is indicated by the number, location, and size of the lesions. Solitary or a few small lesions may benefit from excision or Mohs micrographic surgery. Recurrence at the surgical site has been reported, which fortunately was not noted in our patient. Other treatment modalities used with some success include topical, systemic, and intralesional steroid administration, topical tacrolimus, interferon α-2b therapy, cryotherapy, sclerotherapy, intralesional bleomycin, radiofrequency excision, radiotherapy, and lasers. ^[1]

Thus, ALHE is an uncommon disorder with restricted sites of predilection and its occurrence on penis is extremely rare. To the best of our knowledge, a case of ALHE on penis in an HIV sero-reactive patient is hitherto unreported.