The work-up of a suspicious penile lesion: history and physical (including the inguinal nodes); laboratory (serum calcium, HPV status); imaging (of the primary if large/invasive, and for metastasis if indicated); and biopsy.
History & Physical Exam
- Delay in seeking care is common, and pain is uncommon.
- Penile lesion — note size, location, fixation, and corporeal involvement. Lesions are most often on the glans (48%) and foreskin (21%). Physical exam alone misclassifies the pathologic T stage in 26% of cases.
- Inguinal area — careful palpation is essential. Per EAU, palpably enlarged nodes are highly indicative of metastasis; record the number of nodes on each side and whether they are fixed or mobile (additional imaging does not change management here).
Laboratory
- Serum calcium — hypercalcemia can occur without osseous metastasis, from PTH-related substances produced by the tumour.
- HPV status — mandatory to determine in all patients diagnosed with penile cancer.
Imaging
- Primary tumour — no imaging for small glanular lesions; for larger or invasive-appearing lesions, ultrasound assesses corporal infiltration. Penile Doppler US has higher staging accuracy than MRI for corporal infiltration; MRI with an artificially induced erection can detect corporal invasion but is unpleasant; CT has poor soft-tissue resolution and is not useful for the primary.
- Regional nodes — physical exam of the groin is the clinical gold standard in non-obese patients. CT/MRI is reserved for obese patients or those with prior inguinal surgery (unreliable exam), and pelvic CT/PET assesses pelvic nodes; ultrasound helps when habitus or lymphedema limits the exam.
- Distant — CT of chest/abdomen/pelvis, bone scan, or CT/PET.
Biopsy & Grading
Biopsy before treatment to confirm the diagnosis and assess depth of invasion, vascular invasion, and histologic grade. SCC is graded 1–4 (Broders); low-grade (1–2) lesions are the majority (70–80%) at diagnosis. Risk factors for nodal metastasis: high grade, depth of invasion (pT stage), sarcomatoid histology, perineural invasion, and vascular invasion.
Differential Diagnosis
Condyloma acuminatum (HPV warts), verrucous carcinoma (Buschke-Löwenstein tumour), lichen sclerosus, STI lesions (chancre, chancroid, herpes, lymphogranuloma venereum, granuloma inguinale), and tuberculosis.
Self-Test
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What two laboratory tests are obtained in penile cancer, and why? Serum calcium (paraneoplastic hypercalcemia from PTH-related substances, even without bone metastasis) and HPV status (mandatory at diagnosis).
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What is the best imaging for assessing corporal infiltration of the primary? Penile Doppler ultrasound — higher staging accuracy than MRI; CT is not useful for the primary.
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What five pathologic features predict nodal metastasis? High grade, depth of invasion (pT stage), sarcomatoid histology, perineural invasion, and vascular invasion.