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PA28.{2,6} | Penile Carcinoma & Male Genital Morphology — SDL Guide (Part 3)

Spread, Staging, and Prognosis of Penile SCC

Routes of spread:

1. Direct extension — tumor extends along the penile shaft; deep invasion into corpus spongiosum then cavernosum; late extension to scrotum, perineum, or pubic symphysis.

2. Lymphatic spread — the most important route clinically:
- First station: superficial inguinal nodes (palpable in inguinal region)
- Second station: deep inguinal nodes (Cloquet node — the most cephalad deep inguinal node at the femoral ring; its status on FNA/biopsy determines further pelvic dissection)
- Third station: iliac (pelvic) nodes
- Cross-drainage: bilateral spread from midline tumors

3. Haematogenous spread — late; liver, lung, bone.

TNM staging summary (simplified):

Stage	Features	5-year OS
T1a N0	LP only, low grade, no LVI	~90%
T2 N0	Into corpus spongiosum/cavernosum	~70%
Any T, N1	1 inguinal node metastasis	~50%
Any T, N2-3	Multiple/bilateral nodes	<30%
M1	Distant metastasis	<10%

Prognostic factors: Node status > depth > grade. Inguinal lymph node dissection (ILND) improves survival in node-positive patients.

Diagram showing lymphatic spread from a penile primary site to superficial inguinal nodes, then deep inguinal nodes including Cloquet node, and finally pelvic iliac nodes. — **Panel A:** Penis primary site, lymphatic vessels, superficial inguinal nodes as first station, deep inguinal nodes, Cloquet node, external iliac nodes, internal iliac nodes, pelvic iliac nodes, femoral vessels, directional arrows indicating spread sequence. **Inset:** Spread sequence: Penis primary site to superficial inguinal nodes to deep inguinal nodes including Cloquet node to pelvic iliac nodes.

SELF-CHECK

A 55-year-old uncircumcised man has a 1.5 cm ulcerative lesion on the glans with rolled margins. Biopsy shows irregular nests of squamous cells with keratin pearls invading into the lamina propria, with stromal desmoplasia. HPV 16 is detected by ISH. Which histological feature is most characteristic of well-differentiated SCC?

A. Koilocytes with perinuclear halos

B. Full-thickness epithelial dysplasia with intact basement membrane

C. Concentric whorls of squamoid cells with central laminated keratin (keratin pearls)

D. Fibrovascular cores within papillary fronds

Reveal Answer

Answer: C. Concentric whorls of squamoid cells with central laminated keratin (keratin pearls)

Keratin (squamous/epithelial) pearls — concentric whorls of squamoid cells with central laminated keratin — are the hallmark of well-differentiated keratinizing SCC. Koilocytes are the cytopathic effect of HPV in condyloma (benign). Full-thickness dysplasia with intact basement membrane = PeIN (in-situ, no invasion). Fibrovascular cores in papillary fronds = condyloma acuminatum.

SELF-CHECK

A pathology practical slide shows a bright red, velvety, moist plaque from the glans penis of a 62-year-old. Microscopically there is full-thickness squamous dysplasia with loss of normal maturation, abnormal mitoses, and no surface hyperkeratosis. The basement membrane is intact. What is the diagnosis?

A. Condyloma acuminatum

B. Bowen disease

C. Erythroplasia of Queyrat

D. Invasive squamous cell carcinoma

Reveal Answer

Answer: C. Erythroplasia of Queyrat

Erythroplasia of Queyrat is PeIN occurring on the glans/inner prepuce (mucosal surface). The mucosal location explains the absence of hyperkeratosis (no stratum corneum on mucosa). The red, velvety appearance is classic. Bowen disease occurs on keratinized shaft skin and shows hyperkeratosis. The intact basement membrane rules out invasive SCC.

Morphology Practical Walk-Through: Seminoma

This block begins the systematic morphology identification review. Use it as a recognition guide.

GROSS recognition of seminoma:
- Enlarged testis (may be 3–5× normal size)
- Cut surface: homogeneous, lobulated, cream-white to tan mass with a characteristic 'fish-flesh' appearance
- Soft to firm consistency
- No cystic spaces, no hemorrhage, no necrosis (these features suggest NSGCT)
- Fibrous septa dividing tumor into lobules may be visible
- Tunica albuginea usually intact (late breech)

MICROSCOPIC recognition of seminoma:
- Large cells arranged in sheets and nests separated by fibrous septa
- Individual cells: large, polygonal, with clear/pale cytoplasm (rich in glycogen — PAS-positive) and prominent central nucleoli
- Nuclei: round, vesicular, with 1–2 prominent nucleoli ('fried-egg' appearance)
- Lymphocytic infiltrate in the fibrous stroma (T-lymphocytes) — diagnostic feature
- Granulomatous reaction in ~20% (mimics TB on gross!)
- ITGCN (intratubular germ cell neoplasia) in adjacent seminiferous tubules

IHC markers (for viva): PLAP+, OCT3/4+, D2-40+, CD117(c-Kit)+; CD30−, AFP−, β-hCG− (a few syncytiotrophoblasts may cause faint β-hCG)

Diagram of an orchidectomy specimen with seminoma showing a homogeneous cream-white lobulated tumor, fibrous septa, tunica albuginea, and compressed residual normal testis at the periphery. — **Panel A:** Orchidectomy specimen cut surface showing homogeneous cream-white seminoma, fibrous septa, tunica albuginea, and compressed residual normal testis at the periphery. **Panel B:** Magnified tumor cut surface showing pale lobulated tumor and thin fibrous septa. **Panel C:** Comparison inset showing expanding seminoma compressing residual normal testis beneath the tunica albuginea.

Two-panel H&E histology diagram of seminoma showing sheets of clear polygonal tumor cells separated by fibrous septa with lymphocytes and a high-power inset of fried-egg appearing cells. — **Panel A:** Seminoma at 200x showing sheets of large polygonal cells with clear cytoplasm, prominent nucleoli, fibrous septa, and dense lymphocytic infiltrate.. **Panel B:** High-power 400x inset showing individual seminoma cells with fried-egg appearance, central nucleus, prominent nucleolus, clear cytoplasm, and distinct cell borders..

Morphology Practical Walk-Through: Non-Seminomatous GCT (NSGCT)

GROSS recognition of NSGCT (e.g., mixed GCT, embryonal carcinoma, teratoma):
- Enlarged testis with variegated cut surface — the key distinguishing feature from seminoma
- Areas of hemorrhage (dark red-brown), necrosis (yellow-white), cystic spaces (teratoma), and solid tan-gray areas
- Non-homogeneous, heterogeneous appearance — 'mixed' macroscopic picture
- Cartilage or bone may be palpable in mature teratoma

Individual component histology:

Embryonal carcinoma:
- Sheets, glands, tubules of large, anaplastic epithelial cells with indistinct cell borders
- Marked nuclear pleomorphism, prominent nucleoli, many mitoses and apoptoses
- Necrosis common
- IHC: CD30+, OCT3/4+, AFP− (usually)

Yolk sac tumor (endodermal sinus tumor):
- Schiller-Duval bodies — diagnostic: glomeruloid structures with central capillary surrounded by tumor cells in a loose stroma (resembles glomerulus)
- AFP strongly positive (serum AFP elevated)
- Microcystic/reticular pattern common

Choriocarcinoma:
- Biphasic pattern: cytotrophoblasts (mononucleate, pale) + syncytiotrophoblasts (multinucleate, dark, produces β-hCG)
- Extensive hemorrhage and necrosis
- Worst prognosis of GCTs

Mature teratoma: Well-differentiated tissues from all three germ layers — skin (with sebaceous glands), cartilage, intestinal epithelium, neural tissue

Side-by-side gross pathology diagram comparing variegated hemorrhagic cystic NSGCT with homogeneous cream-white seminoma cut surface. — **Panel A:** NSGCT / mixed germ cell tumor cut surface showing hemorrhage, necrosis, cystic space, and solid tumor.. **Panel B:** Seminoma cut surface showing homogeneous cream-white tumor for contrast.. **Bottom strip:** Gross rule: seminoma is homogeneous cream-white; NSGCT is variegated, hemorrhagic, cystic, and often necrotic..

Histology diagram of yolk sac tumor showing a Schiller-Duval body with a central vessel surrounded by tumor cells in loose myxoid stroma. — **Panel A:** Yolk sac tumor H&E field at 200x showing Schiller-Duval body, central vessel, surrounding tumor cells, and myxoid stroma.. **Panel B:** Magnified schematic of a classic Schiller-Duval body showing glomeruloid central vessel, tumor cell cuff, sinus-like space, and pale myxoid stroma..

CLINICAL PEARL

The 'variegated gross' rule for testicular GCTs: Homogeneous cream-white cut surface = Seminoma. Variegated, hemorrhagic, cystic cut surface = NSGCT. This single gross observation guides the first clinical decision — because seminomas are exquisitely radiosensitive while NSGCTs require BEP chemotherapy. Get this distinction right in the practical and you will impress the examiner.