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PA28.{2,6} | Penile Carcinoma & Male Genital Morphology — SDL Guide

Learning Objectives

Describe the pathogenesis, risk factors, and HPV-related pathways in penile carcinoma (PA28.2)
Distinguish the premalignant lesions of the penis — Bowen disease, erythroplasia of Queyrat, and bowenoid papulosis — by site, HPV type, and malignant potential (PA28.2)
Describe the gross types (papillary vs flat/ulcerative) and microscopic features of invasive penile squamous cell carcinoma, including spread and staging (PA28.2)
Identify on gross and microscopic images: seminoma, mixed/non-seminomatous germ cell tumor, nodular hyperplasia of prostate, prostatic adenocarcinoma (Gleason grading), condyloma acuminatum, and penile SCC — as required for the morphology practical (PA28.6)
Apply the Gleason grading system to describe prostatic adenocarcinoma patterns and understand the Gleason score (PA28.6)
Explain the distinguishing histological features that allow pattern recognition in the male genital tract for exam-based image identification (PA28.6)

INSTRUCTIONS

This is the morphology consolidation SDL for the Male Genital Tract cluster. It is written primarily for the practical examination — you must be able to look at a gross specimen or a microscopic slide and NAME the disease. Read each block, study the image markers carefully, and ask yourself: 'If I see this in the practical, what do I say?' The micro_quiz questions are typical spotting-type viva questions. Complete SDL1 (Testicular Tumors) and SDL2 (Prostate Pathology) before this session.

References

Robbins & Cotran Pathologic Basis of Disease, 10th ed., Ch. 21 (textbook)
Harsh Mohan Textbook of Pathology, 7th ed., Ch. 24 (textbook)
WHO Classification of Tumours of the Urinary System and Male Genital Organs, 5th ed. (textbook)

Version 2.0 | NMC CBUC 2024

CLINICAL SCENARIO

A 58-year-old man from rural Rajasthan presents with a 3-month history of a painless, slowly enlarging ulcer on the glans of his penis. He has never been circumcised. He mentions he had difficulty retracting his foreskin for years. On examination, there is a 2 cm indurated, crater-like ulcer with raised, everted margins on the glans and adjacent prepuce, with firm, non-tender left inguinal lymph nodes. His wife asks: 'Doctor, is this cancer? Is it because of something he did?' — How will you answer her? And before you answer a single clinical question, you need to know exactly what this lesion looks like under the microscope, what predisposed him, and how it spreads. That is what this SDL teaches.

WHY THIS MATTERS

Penile carcinoma and male genital tract morphology appear in the Year-2 Pathology practical exam in two formats: (1) Spot diagnosis — you are shown a gross specimen or histology slide and asked to name the disease; (2) Short questions about pathogenesis and distinguishing features. PA28.2 and PA28.6 together cover the entire male genital tract. This SDL is your morphology consolidation: penile pathology in depth, followed by a systematic review of what to look for in testicular tumors, prostate lesions, and penile lesions — all framed as practical exam recognition. This is the most image-dense SDL in the cluster intentionally. Think of each image marker as a flashcard you will see in the practical hall.

RECALL

Before reading further, recall from SDL1 and SDL2:

Testicular tumors — seminoma vs non-seminomatous germ cell tumor (NSGCT); tumor markers AFP, β-hCG, LDH; the concept of ITGCN (intratubular germ cell neoplasia unclassified) as the in-situ precursor.

Prostate — the anatomical zones (peripheral, central, transition); BPH arises in the transition zone; prostatic adenocarcinoma arises predominantly in the peripheral zone; PSA as serum marker.

HPV biology — HPV is a double-stranded DNA virus; low-risk types (6, 11) → condylomas (warts); high-risk types (16, 18) → dysplasia and carcinoma via E6 (inactivates p53) and E7 (inactivates Rb).

If any of these are hazy, re-read the relevant SDL before continuing.

Penile Anatomy and the Staging Context

Understanding penile pathology requires a brief anatomical framework. The penis is composed of two corpora cavernosa (paired, dorsal, erectile) and one corpus spongiosum (ventral, surrounding the urethra). The distal expansion of the corpus spongiosum forms the glans penis, covered by the prepuce (foreskin).

The epithelium covering the glans and inner prepuce is non-keratinized stratified squamous epithelium — identical in character to mucosal surfaces. The outer skin of the penile shaft is keratinized squamous epithelium.

Why anatomy matters for staging: TNM staging of penile carcinoma is largely determined by depth of invasion:
- T1a: lamina propria only, no lymphovascular invasion (LVI), grade 1–2
- T1b: lamina propria with LVI, or grade 3
- T2: corpus spongiosum or cavernosum
- T3: urethra
- T4: adjacent structures (scrotum, prostate)

Lymphatic spread follows the inguinal nodes (superficial → deep inguinal → pelvic). Inguinal node status is the single most important prognostic factor.

Medical diagram showing penile shaft cross-section, distal glans and prepuce anatomy, and epithelial-to-deep tissue layers relevant to staging depth. — **Panel A:** Penile shaft cross-section showing corpora cavernosa, corpus spongiosum, urethra, tunica albuginea, Buck fascia, dartos fascia, skin, and keratinized squamous epithelium.. **Panel B:** Distal penis cutaway showing glans penis, corona, prepuce, outer keratinized preputial epithelium, inner non-keratinized mucosal epithelium, urethral meatus, fossa navicularis, corpus spongiosum, and distal corpora cavernosa.. **Panel C:** Staging-depth inset showing epithelium, basement membrane, lamina propria, corpus spongiosum, tunica albuginea, corpus cavernosum, urethra, and arrows distinguishing superficial epithelial lesion from invasive spread..

Condyloma Acuminatum — HPV 6/11 (Benign)

Condyloma acuminatum (plural: condylomata acuminata) — commonly called genital warts — is caused by HPV types 6 and 11 (low-risk types). It is the most common STI-related penile lesion.

Gross appearance: Soft, moist, papillary or cauliflower-like excrescences (projections) on the glans, prepuce, or penile shaft. May be single or multiple. Color varies from skin-colored to pink-red. They do NOT ulcerate unless secondarily infected.

Microscopic features — the hallmark is koilocytosis:
- Koilocytes: squamous cells with perinuclear cytoplasmic halos and dark, wrinkled (raisinoid) nuclei — this is the cytopathic effect of HPV replication
- Papillary architecture with fibrovascular cores (acanthosis + papillomatosis)
- Surface hyperkeratosis (thickened keratin layer) and parakeratosis
- NO dysplasia (no atypia in deeper layers, no abnormal mitoses)
- Basement membrane intact — no invasion

Malignant potential: Negligible for HPV 6/11 condylomas. However, a giant condyloma (Buschke-Löwenstein tumor) is a locally destructive but non-metastasizing variant.

Medical illustration of condyloma acuminatum showing papillary cauliflower-like lesions on the glans penis with labeled papillary fronds, adjacent normal glans skin, and a histology correlate. — **Panel A:** Gross view of glans penis showing multiple soft papillary/cauliflower condyloma acuminatum lesions, individual papillary fronds, lesion cluster, and adjacent normal glans skin.. **Panel B:** Magnified lesion detail showing branching papillary fronds, rounded cauliflower-like tips, soft mucosal surface, and base of lesion.. **Panel C:** Histology correlate showing papillary fronds, fibrovascular cores, acanthotic squamous epithelium, superficial koilocytes, and intact basement membrane..

Histology diagram of condyloma acuminatum showing papillary fronds with fibrovascular cores, acanthosis, superficial koilocytes, and an intact basement membrane with a magnified koilocyte inset. — **Panel A:** Low-power H&E view showing papillary fronds, fibrovascular cores, acanthosis, superficial koilocytes, and intact basement membrane.. **Panel B:** High-power inset showing a koilocyte with perinuclear halo and raisinoid hyperchromatic nucleus.. **Panel C:** Schematic papillary frond showing superficial koilocytotic epithelium, acanthotic squamous epithelium, intact basement membrane, central fibrovascular core, and capillaries..

Premalignant Penile Lesions — The HPV 16/18 Trio

Three lesions are traditionally grouped as penile intraepithelial neoplasia (PeIN) — all carry high malignant potential, all are linked to HPV 16/18, and all show full-thickness or near-full-thickness squamous dysplasia without invasion. They differ primarily in anatomical location and clinical presentation:

Feature	Bowen Disease	Erythroplasia of Queyrat	Bowenoid Papulosis
Location	Penile shaft skin	Glans / inner prepuce	Shaft skin (or glans)
Gross	Solitary, thickened, hyperkeratotic, grayish-white plaque	Bright red, velvety, moist plaque	Multiple (1–10 mm) red-brown papules
HPV	16/18	16/18	16/18
Histology	PeIN — full-thickness dysplasia with hyperkeratosis	PeIN — full-thickness dysplasia, NO hyperkeratosis (mucosa)	PeIN — but often self-limited in young adults
Malignant risk	~10% → invasive SCC	~10–30% → invasive SCC	LOW in immunocompetent young adults; higher in immunosuppressed
Patient age	Older men	Older men	Younger men (often multiple sex partners)

Key histological feature common to all three: Full-thickness dysplasia — large atypical keratinocytes with hyperchromatism, abnormal mitoses (including tripolar/bizarre forms), loss of normal maturation from base to surface, and dyskeratotic cells. The basement membrane is intact (in-situ lesion).

Exam tip: The most tested distinction is location — Bowen on skin (keratinized, so hyperkeratosis on top), erythroplasia on glans/mucosa (red and moist because no keratin). Histologically identical otherwise.

Side-by-side gross comparison of Bowen disease on penile shaft skin as a gray hyperkeratotic plaque and erythroplasia of Queyrat on the glans as a bright red velvety moist plaque. — **Panel A:** Bowen disease; penile shaft skin; hyperkeratotic grayish plaque; rough scaly thickened surface callout. **Panel B:** Erythroplasia of Queyrat; glans penis; bright red velvety moist plaque; smooth moist velvety surface callout.

Educational H&E-style diagram of penile intraepithelial neoplasia showing full-thickness squamous dysplasia with dyskeratotic cells, abnormal mitosis, superficial keratin, and an intact basement membrane. — **Panel A:** H&E 200x histology showing full-thickness dysplasia, atypical cells at all levels, loss of maturation, abnormal mitotic figure, dyskeratotic cell, superficial keratin, intact basement membrane, and lamina propria.. **Panel B:** Normal squamous epithelial maturation pattern with basal proliferative layer, progressive maturation, superficial keratin, and basement membrane.. **Panel C:** Schematic penile intraepithelial neoplasia showing atypia through the full epithelial thickness with basement membrane preserved.. **Panel D:** Diagnostic comparison of in situ lesion with intact basement membrane versus invasive carcinoma with basement membrane breach and stromal invasion..

CLINICAL PEARL

HPV risk stratification in penile lesions — one rule to remember: HPV 6/11 → Condyloma (NO cancer risk). HPV 16/18 → PeIN / SCC (HIGH cancer risk). The same HPV types drive cervical carcinoma. Quadrivalent HPV vaccine (Gardasil) covers 6, 11, 16, 18 — preventing condyloma AND squamous cell carcinoma of both cervix and penis.