Circinate erythematous penile plaque.

Case

A 63-year-old-male male presented with a 1.5-year asymptomatic recalcitrant penile lesion that was initially diagnosed as candida balanitis and unsuccessfully treated with antifungal creams. He denied any systemic symptoms, and a review of systems was unremarkable. He admitted having a monogamous heterosexual relationship and denied any previous sexually transmitted infections, recent changes in medications, or a history of malignancy. Physical examination demonstrated a well-demarcated circinate erythematous velvety plaque on the penile corona with extension into the ureteral meatus (Fig 1). Inguinal lymph node examination was negative. A shave biopsy revealed atypical keratinocytes throughout the epidermis (Fig 2, A and B). The lesion was positive for cytokeratin 5/6 and p63 immunostains (Fig 3, A and B).

Fig 1

Fig 2

Fig 3

Question 1: What is the diagnosis?

Behçet disease

Erosive lichen planus

Extramammary Paget disease

Erythroplasia of Queyrat

Zoon’s balanitis

Answer:

Behçet disease – Incorrect. Behçet disease is a multisystem inflammatory syndrome defined by recurrent mucosal ulcerations of the mouth and genitalia, ocular anomalies, and cutaneous lesions. Clinically, oral ulcers develop a yellow pseudeomembrane surrounded by erythema, while the anogenital aphthae can be painful and have irregular margins. Histologic characteristics demonstrate an angiocentric neutrophilic infiltrate with vasculitic features.

Erosive lichen planus – Incorrect. Erosive lichen planus can be a clinical mimicker of squamous cell carcinoma in situ (SCCIS); however, the histopathology would discriminate between them. Key histology findings include interface dermatitis with a band-like lymphocytic infiltrate, granular layer accentuation, saw-toothed rete ridges, Civatte bodies, pigment incontinence, and subepidermal clefting.

Extramammary Paget disease – Incorrect. Extramammary Paget disease (EMPD) is a rare neoplastic condition that can be either primary or secondary in nature due to an underlying contiguous or noncontiguous adenocarcinoma or visceral malignancy. Histology demonstrates pagetoid cells (large vacuolated cells with abundant cytoplasm) that display variable immunohistochemical staining patterns depending on whether or not the tumor is primary or secondary. Primary EMPD would be negative for stains such as p63 and cytokeratin 5/6 which were positive in this case.

Erythroplasia of Queyrat – Correct. Erythroplasia of Queyrat is a clinical form of a high-grade penile intraepithelial neoplasia or SCCIS that presents as a velvety erythematous plaque on the glabrous skin of the penis or perianal region. Histology exhibits atypical keratinocytes with hyperchromatic nuclei that would stain positive for both cytokeratin 5/6 and p63, confirming squamous differentiation.

Zoon’s balanitis – Incorrect. Zoon’s balanitis is a reactive condition typically seen in older uncircumcised males. Although this disease may be considered in the clinical differential, the hallmark histopathologic features distinguish this entity: diamond-shaped basal keratinocytes, spongiosis, and plasma cells of varying density.

Question 2: Which of the following would be considered the most efficacious treatment modality?

Reassurance & zinc oxide

Class I topical steroids

Photodynamic therapy

Apremilast

Mohs micrographic surgery

Answer:

Reassurance & zinc oxide – Incorrect. Management for balanitis would include addressing any aggravating risk factors like poor hygiene, warmth, or friction. A twice daily application of bland emollient, like zinc oxide, would minimize friction and improve barrier function but would not medically address SCCIS.

Class I topical steroids – Incorrect. Certain inflammatory conditions, such as lichen sclerosus and erosive lichen planus of the genitalia, would warrant treatment with ultrapotent topical steroids; however, this topical therapy would be ineffective for the treatment of penile SCCIS.

Photodynamic therapy – Incorrect. There are limited case reports demonstrating clinical efficacy for penile SCCIS with photodynamic therapy albeit without urethral involvement. With extension into the urethra, this therapeutic modality would not be able to confirm margin clearance and may portend to unsatisfactory cure rates.

Apremilast – Incorrect. Apremilast is approved for the treatment of psoriatic arthritis, plaque psoriasis, and Behçet disease. While penile psoriasis and Behçet disease may be considered in the clinical differential of this case, this medication would be ineffective in the treatment of penile SCCIS.

Mohs micrographic surgery – Correct. There are multiple modalities delineated in the literature for the treatment of erythroplasia of Queyrat including topical chemotherapy, radiation, surgical excision (partial or total penectomy), and Mohs micrographic surgery. With maximal tissue preservation, Mohs micrographic surgery is a first-line treatment for the SCCIS with urethral involvement as other therapies are associated with low clearance rates, frequent recurrences, and poor surgical cosmesis.,

Question 3: What is the most likely predisposing etiologic association with this condition?

HLA-B51

Human papillomavirus, type 16

Genitourinary malignancy

Sulfonamides

Treponema pallidum subsp. pallidum

Answer:

HLA-B51 – Incorrect. Behçet disease is strongly associated with the HLA-B51 allele, accounting for more than 80% of cases in the Asian population. This immunogenetic allele is not associated with penile squamous cell carcinoma.

Human papillomavirus, type 16 – Correct. There are several identifiable risk factors for penile squamous cell carcinoma including the following: human papillomavirus, lack of circumcision, poor hygiene, immunosuppression, and psoralen and ultraviolet A treatment of penile psoriasis. High-risk human papillomavirus, mainly type 16, is associated in up to 40% of penile squamous cell carcinomas.

Genitourinary malignancy – Incorrect. EMPD is an intraepithelial malignancy that can be primary or secondary to an underlying visceral carcinoma such as a genitourinary malignancy. Patients diagnosed with EMPD in the penoscrotal region should be evaluated for an occult neoplasm of the bladder, urethra, and prostate.

Sulfonamides – Incorrect. Given the nummular configuration and location of the primary lesion, consideration may be given to a diagnosis of fixed drug eruption. Sulfonamides are 1 of the most common antibiotics associated with this fixed drug eruption; however, the patient denied any recent changes in medications and the histopathology did not support this diagnosis.

Treponema pallidum subsp. pallidum – Incorrect. A solitary, painless, chancre located on the genitalia should raise concern for venereal diseases particularly syphilis caused by Treponema pallidum subsp. pallidum. While this is a cause of infectious genital ulcers, this species does not have any etiologic relationship with penile SCCIS.

Conflict of interest

None disclosed.