Case study: A penile lesion led to one of the rarest cancer diagnoses
Vital Signs
Male
47 years old
Presents with a 4-month history of an enlarging lesion on the glans penis
Initial symptom of pruritus, followed by severe pain
Bilateral inguinal lymphadenopathy present
A changing penile lesion warrants the same diagnostic urgency as a suspicious lesion elsewhere on the skin. Embarrassment, concealed anatomy, and the rarity of penile melanoma often delay biopsy until regional disease is present.
A 2026 Cureus case report describes a 47-year-old man with a progressively enlarging lesion involving the glans penis.[] Pruritus was the first symptom. Severe local pain and bilateral inguinal lymphadenopathy followed.
An incisional biopsy confirmed malignant melanoma. The tumor had a Breslow thickness of 12 mm, Clark level V invasion, a high mitotic index (21 mitoses/mm²), and lymphovascular and perineural invasion. Imaging studies demonstrated regional lymph node involvement and disseminated visceral disease. Despite surgery and systemic treatment, the patient died approximately 12 months after diagnosis.
Primary penile melanoma accounts for less than 2% of all penile tumors and less than 0.1% of all melanomas, according to a 2026 case report article.[] Most lesions arise on the glans, foreskin, urethral meatus, coronal sulcus, or penile shaft.
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A dark lesion is the classic presentation, but color alone is an unreliable gatekeeper for biopsy. Reported lesions include brown, blue, black, and amelanotic growths.[]
Related: Why penis amputation rates are increasing globallyMelanie Palm, MD, board-certified dermatologist and cosmetic surgeon at Art of Skin MD, says, “Any new or changing lesion on the penis deserves attention, particularly one that is asymmetric, has irregular or poorly defined borders, contains multiple colors, or is enlarging. I would also be concerned about a lesion that becomes raised or firm, develops a nodule, bleeds, ulcerates, crusts or fails to heal.”
Absence of symptoms is not a reassuring sign either. “Persistent itching, pain or discharge can occur, but melanoma may be completely asymptomatic, so the absence of discomfort is not reassuring,” Dr Palm adds.
Elaine Kunzler, MD, assistant professor of dermatology at Case Western Reserve University, agrees that examination should precede assumptions about morphology. “It can be difficult to distinguish benign from malignant penile lesions, and melanocytic lesions on the penis are notoriously atypical. In dermatology, we consider the penis a ‘special site,’ as atypia is common in this area,” Dr. Kunzler says.
Differentials to keep in mind
The differential includes genital melanosis, atypical genital nevi, seborrheic keratoses, and pigmented squamous cell carcinoma, according to Drs. Palm and Kunzler. Penile sarcoma, distal urethral urothelial carcinoma, and metastatic melanoma are additional histopathologic considerations.[] Dr. Palm notes that genital melanoma may be flat, minimally pigmented, or “deceptively uniform,” so symmetry or uniform pigmentation should not provide false reassurance.
“There can be significant overlap with other benign and malignant lesions, which is why visual inspection alone is not enough to reliably distinguish these conditions,” Dr. Palm explains. “Melanoma tends to raise greater concern when there is irregular pigment, but both cancers can be ulcerated, nodular, or amelanotic. Ultimately, the diagnosis has to be made under the microscope.”
Why diagnosis is delayed
“This exam can be uncomfortable for anyone. I oftentimes find that my patients are not expecting to have their genitals examined during skin cancer screening appointments,” Dr. Kunzler says. “Additionally, patients may not regularly examine their external genitals; some areas may be impossible to see even with use of a handheld mirror. Thus, they may be unaware that they have a concerning lesion.”
Melanoma over a UV-protected site
The assumption that melanoma occurs only on sun-exposed skin also contributes to delay.
We oftentimes think of melanomas and squamous cell carcinomas only occurring in body sites with high sun exposure—not the genitals. Therefore, patients may not think to ask about a new or changing genital lesion.
—Elaine Kunzler, MD, assistant professor of dermatology at Case Western Reserve University
Penile mucosal melanoma is not considered UV-driven. Its genomic profile also differs from that of cutaneous melanoma, with BRAF V600E mutations occurring less frequently and KIT alterations enriched in some mucosal and anogenital melanoma cohorts.[][]
Related: Beer is replacing tanning oil — TikTok trend gives new meaning to the term 'beer belly'Getting the biopsy right
Although dermoscopy supports lesion assessment, histopathology establishes the diagnosis.
When anatomically feasible, literature supports that a complete excisional biopsy with narrow margins offers the best specimen for assessing Breslow thickness and ulceration.[]
Dr. Kunzler shares her clinical perspective: “As a dermatopathologist and dermatologist, I am grateful to be able to correlate the histopathologic features with what I find on the clinical exam. … Pathology by way of biopsy is required to make the diagnosis.”
“The biopsy approach depends on the size of the lesion. If the lesion is small enough to sample entirely, a dermatologist may remove it via a shave or punch biopsy,” she explains.
Scouting biopsy in selected cases
“We try our best in dermatology to avoid transecting a lesion as the entire depth is required to appropriately stage a melanoma, which can affect treatment and prognosis. If the lesion is too broad or in a cosmetically or functionally sensitive body site, a partial biopsy to represent the most worrisome part of the lesion, or multiple "scouting" biopsies, may be performed,” Dr. Kunzler says. “It is a balance between wanting to minimize scar and functional sequelae and obtaining adequate tissue to make an accurate diagnosis.”
“If a lesion is large and ulcerated, we oftentimes try to sample the border of the ulcer where there is still intact epidermis to increase our diagnostic yield. A nodular lesion would raise concern for increased depth; therefore, the biopsy may extend deeper until there is no residual pigment left at the biopsy site,” Dr. Kunzler adds.
Histopathologic assessment is supported by melanocytic markers such as SOX-10, S100, Melan-A, and HMB-45.[]
PRAME (Preferentially Expressed Antigen in Melanoma) can also assist in distinguishing melanoma from a benign melanocytic nevus, in conjunction with morphology and immunohistochemistry results.[]
Following diagnosis, penile MRI is also useful to assess local extension. CT or PET-CT is used for systemic staging.[]
Why timing matters
A population analysis cited in the 2026 Frontiers in Oncology case report article found a 10-year cancer-specific mortality as high as 38.4% for penile melanoma, compared with 16.6% for matched penile squamous cell carcinoma.[]
The patient case report shows what is at stake. The patient’s history was only 4 months old, but by the time of diagnosis, it involved the entire glans and proved to be a 12 mm-thick pT4b stage melanoma with adjacent structural invasion, bilateral inguinal lymphadenopathy, and extensive visceral metastases, which proved to be fatal.[]
As Dr. Palm explains, “That combination of a hidden location, few early symptoms, and an unfamiliar presentation can allow diagnosis to be delayed until the lesion has become larger or more advanced.”
For all physicians, the clinical takeaway should be that a persistent or evolving penile lesion warrants examination and a low threshold for adequately deep biopsy, regardless of symptoms.