The ulcer that deceived: Squamous cell carcinoma masquerading as a primary chancre

Dear Editor,

A 44-year-old married male presented to the dermatology outpatient department with a solitary ulcer on the inner aspect of the prepuce, persisting for 1 month. The lesion was nontender and associated with mild serous discharge. The patient reported no systemic symptoms such as fever or weight loss and had no significant medical history or previous sexually transmitted infections. He was heterosexual, admitted to occasional unprotected sexual activity, but denied recent exposure to high-risk partners, including men who have sex with men. His partner also had no history suggestive of a sexually transmitted infection.

On clinical examination, he was uncircumcised, with well-maintained penile hygiene. A single, well-demarcated ulcer measuring 2 cm in diameter was observed on the inner aspect of the prepuce. The ulcer exhibited indurated edges and a clean base, with no significant purulent discharge [Figure 1]. There was no inguinal lymphadenopathy, and systemic examination was unremarkable. The initial clinical impression suggested a primary syphilitic chancre.

Figure 1.

A solitary painless ulcer with an indurated edge and clean base over the prepuce

Serologic tests, including rapid plasma reagin and Treponema pallidum hemagglutination assay, were negative. Screening for other sexually transmitted infections, including HIV, was nonreactive. Bacterial culture of the ulcer exudate showed no growth, and viral polymerase chain reaction for herpes simplex virus was also negative. A crush smear was performed to rule out granuloma inguinale. Given the atypical presentation and negative findings for sexually transmitted diseases (STDs), a biopsy of the lesion was performed to rule out malignancy.

Histopathological examination revealed nests and islands of atypical squamous epithelial cells infiltrating the stroma, consistent with well-differentiated squamous cell carcinoma (SCC) [Figure 2]. Further evaluation, including inguinal ultrasound and contrast-enhanced computed tomography of the abdomen and pelvis, showed no evidence of metastasis. The patient was referred to an oncologist and underwent circumcision. Postoperative recovery was uneventful, and the patient was counseled regarding follow-up for recurrence or metastasis.

Figure 2.

(a) Histopathology of the ulcer showed well-defined irregular epidermal hyperplasia with elongated rete ridges invading into the dermis and well-differentiated squamoid epithelium. There is marked acanthosis with hyperkeratosis, hypogranulosis, parakeratosis, and dyskeratotic cells. (b) In a few regions, there is mild-to-moderate atypia, with subtle nuclear hyperchromatism and mitotic figures in the basal layer. Prominent inflammatory cell infiltrate is present around the lesion consisting predominantly of lymphocytes admixed with histiocytes

Discussion

Penile neoplasms are rare, constituting <2% of cancers worldwide. Among these, penile SCC (PSCC) accounts for approximately 95% of cases, while other malignancies, such as sarcomas, basal cell carcinomas, and melanomas, are less common.[1] The incidence of PSCC varies geographically, with India reporting the highest rates in Asia, at 1.6 cases per 100,000 individuals.[2] Penile cancer typically affects men aged 50–70, though it is sometimes seen in younger patients. Younger individuals generally present with less severe disease, while invasive lesions are more common in older age groups.[3]

The pathogenesis of PSCC is multifactorial, with risk factors including poor hygiene, lack of circumcision, human papillomavirus (HPV) infection, chronic inflammation, tobacco use, lichen sclerosus, phimosis, balanitis, history of STDs (particularly HIV), penile intraepithelial neoplasia, genital warts, ultraviolet light exposure, immune dysfunction, and chronic mechanical irritation.[3,4]

PSCC predominantly arises on the mucosal surfaces of the penis. Studies indicate that tumors most often involve the glans (35%–48%) or inner prepuce (13%–21%), with only a small percentage (2%) occurring on the keratinized penile shaft. Lesions are typically painless and, when associated with phimosis, may present with purulent discharge beneath the foreskin.[4,5]

PSCC exhibits five principal growth patterns. The most common is superficial spreading, often seen in non-HPV-related SCC, involving the glans, foreskin, and sulcus. Other patterns include verruciform lesions, such as verrucous, warty, and cuniculatum carcinomas, as well as pseudo-hyperplastic multicentric growths and mixed patterns. Ulcerative lesions on the glans or prepuce necessitate histopathological confirmation, as the differential diagnosis includes penile tuberculosis, chronic trauma, donovanosis, primary syphilitic chancre, and PSCC.[1,3,4,5]

Cases of primary syphilis mimicking penile malignancy have been reported.[6] Our case is noteworthy for the patient’s relatively young age, brief history of the ulcer, and the lesion’s striking resemblance to a classical syphilitic chancre – a condition often described as one of medicine’s greatest imitators.

Aggressive treatment for PSCC can impact psychosocial well-being, emphasizing the need for penile-preserving procedures. Circumcision is effective for lesions confined to the foreskin, while lymph node involvement necessitates further intervention. Topical agents, such as 5-fluorouracil or imiquimod, are effective for in situ carcinoma or superficial lesions, while surgical options such as wide local excision, glansectomy, and Mohs micrographic surgery are reserved for early-stage invasive disease.[1,3,4,5]

Conclusion

This case underscores the importance of vigilance when diagnosing painless penile ulcers, as PSCC can closely mimic benign conditions such as syphilis. Comprehensive evaluation, including biopsy, is crucial for early detection and effective management, ensuring improved outcomes and preserving quality of life.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.