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PA28.{2,6} | Penile Carcinoma & Male Genital Morphology — SDL Guide (Part 4)

Morphology Practical Walk-Through: Nodular Hyperplasia of Prostate (BPH)

GROSS recognition of BPH:
- Enlarged prostate gland (normal ~20 g; BPH can reach 60–100+ g)
- Nodular enlargement predominantly in the periurethral/transition zone
- Cut surface: well-defined nodules of variable size, cream-white, firm to rubbery
- Central nodules compress the urethra into a slit-like lumen (crescent or slit shape)
- No necrosis, no capsule invasion
- Peripheral zone appears compressed and thinned (pushed outward)

MICROSCOPIC recognition of BPH:
- Nodular proliferation of three components in variable proportions:
1. Glandular component: large, cystically dilated glands lined by two cell layers — inner tall columnar secretory cells and outer flattened basal cells. Gland lumina contain inspissated secretions (corpora amylacea — concentrically laminated calcified bodies, blue-gray on H&E)
2. Fibromuscular stroma: proliferating smooth muscle and fibrous tissue between glands
3. Papillary infoldings of the glandular epithelium into the lumen
- Two-cell layer preservation (columnar + basal) is a key feature distinguishing BPH from carcinoma (which LACKS the basal cell layer)

IHC for basal cells: High-molecular-weight cytokeratin (HMWCK/34βE12) and p63 highlight the basal layer in BPH; this layer is ABSENT in adenocarcinoma.

Sagittal educational illustration of benign prostatic hyperplasia showing transition zone nodules compressing the urethra with peripheral zone and surgical capsule labeled. — **Panel A:** Sagittal cut surface of BPH prostate showing transition zone nodules, slit-like compressed urethra, peripheral zone, and surgical capsule.. **Panel B:** Simplified sagittal orientation inset showing bladder, prostatic urethra, transition zone, peripheral zone, and relationship of nodular enlargement to urethral compression..

Histology diagram of BPH showing cystically dilated prostatic glands with corpora amylacea, two-cell epithelial lining, and fibromuscular stroma. — **Panel A:** Low-power H&E view showing nodular glandular proliferation, large cystically dilated glands, gland lumina, corpora amylacea, and intervening fibromuscular stroma.. **Panel B:** Magnified gland wall showing the two-cell epithelial lining with inner tall columnar secretory cells and outer flattened basal cells bordering the gland lumen.. **Panel C:** Simplified recognition schematic highlighting nodular glandular proliferation, corpora amylacea within lumina, and fibromuscular stroma between glands..

Morphology Practical Walk-Through: Prostatic Adenocarcinoma & Gleason Grading

GROSS recognition of prostatic adenocarcinoma:
- Tumor often not grossly visible, especially in early stages
- Arises in the peripheral zone in ~70% of cases — firm, yellow-white, indurated area on cut surface (NB: the peripheral zone is posterolateral — palpable as a hard nodule on DRE)
- In advanced cases: ill-defined, gritty, gray-white mass in peripheral zone
- Capsule invasion (extraprostatic extension) and seminal vesicle invasion are gross features in locally advanced disease
- On radical prostatectomy specimen: routine inked margins, multisection sampling

MICROSCOPIC recognition — the Gleason grading system:

Gleason grading is based on the glandular architecture of the tumor (not cytology). There are 5 patterns:

Gleason Pattern	Architecture	Description
1	Well-formed, closely packed, round uniform glands	(Rarely assigned today)
2	Well-formed glands, loose arrangement, minimal stromal separation
3	Individual, well-formed but variable-sized glands, infiltrating stroma	Most common; glands still well-defined
4	Poorly formed, fused, or cribriform glands; or glomeruloid pattern	Significant; drives Grade Group 2–4
5	No glandular differentiation; sheets, cords, single cells; necrosis	Highest grade

Gleason score = Primary pattern + Secondary pattern (most common + second most common pattern)
- Score 6 (3+3) = Grade Group 1 — Favorable
- Score 7 (3+4 or 4+3) = Grade Group 2 or 3
- Score 8 = Grade Group 4
- Score 9–10 = Grade Group 5 — Unfavorable

Key microscopic features of adenocarcinoma vs BPH:
- Absent basal cell layer (no HMWCK/p63 staining) — cardinal feature
- Small, irregular infiltrating glands in desmoplastic stroma
- Prominent nucleoli (large, pink — 'owl-eye' nucleoli, ≥1.6 µm)
- Perineural invasion — tumor cells wrapping around nerve bundles in the stroma (pathognomonic)
- Intraluminal crystalloids (hard, angular eosinophilic deposits)
- Luminal blue mucin (amorphous basophilic material)

A four-quadrant H&E-style histology diagram compares Gleason grades 3, 4 fused or cribriform, 5 solid sheets, and 4 glomeruloid prostate adenocarcinoma patterns. — **Panel A:** Gleason grade 3 with infiltrating individual well-formed glands separated by stroma.. **Panel B:** Gleason grade 4 with fused glands, cribriform architecture, and loss of separate gland formation.. **Panel C:** Gleason grade 5 with solid sheets, cords, nests, and no gland formation.. **Panel D:** Gleason grade 4 glomeruloid pattern with dilated glands containing attached intraluminal epithelial tufts..

Annotated H&E-style histology diagram showing Gleason 3+4 prostatic adenocarcinoma with infiltrating small glands, absent basal cells, prominent nucleoli, perineural invasion, and benign gland comparison. — **Panel A:** Overview H&E 400x field showing infiltrating small malignant glands, adjacent benign glands, fibromuscular stroma, and a nerve bundle involved by tumor.. **Panel B:** Close-up of malignant glands showing absent basal layer and irregular crowded epithelial cells.. **Panel C:** High-power cellular detail showing enlarged nuclei with prominent nucleolus, including an owl-eye nucleolus.. **Panel D:** Perineural invasion by tumor glands around a nerve bundle, with adjacent benign gland showing preserved basal cell layer and secretory cell layer..

CLINICAL PEARL

Three 'absent/present' rules for the prostatic adenocarcinoma practical:
1. Absent basal cell layer (HMWCK/p63 negative) — must be absent for carcinoma diagnosis
2. Present perineural invasion — if you see tumor cells around a nerve, it is almost certainly adenocarcinoma
3. Present prominent nucleoli (owl-eye) — in small glands invading stroma, this is carcinoma until proven otherwise
BHP has ALL THREE REVERSED: present basal layer, no perineural invasion, no prominent nucleoli.

Morphology Summary Table — Male Genital Tract Practical Recognition

Use this table as your final revision checklist before the practical:

Disease	Gross Hallmark	Microscopic Hallmark	Key Marker
Seminoma	Homogeneous cream-white, lobulated	Large cells, clear cytoplasm, prominent nucleoli, lymphocytic stroma	PLAP+, OCT3/4+, CD117+
Embryonal carcinoma	Variegated, hemorrhagic	Anaplastic epithelial sheets/glands, CD30+	CD30+, OCT3/4+
Yolk sac tumor	Gray-white, mucoid	Schiller-Duval bodies, microcystic	AFP+, serum AFP↑
Choriocarcinoma	Hemorrhagic, necrotic	Cytotrophoblasts + syncytiotrophoblasts	β-hCG+
Mature teratoma	Cystic, cartilage, hair	Tissues from all 3 germ layers	—
BPH	Nodular, periurethral, slit-like urethra	Large glands, two-cell layer, corpora amylacea, fibromuscular nodules	HMWCK+ (basal)
Prostatic adenocarcinoma	Peripheral zone, firm, yellow-white	Small infiltrating glands, no basal layer, prominent nucleoli, perineural invasion	AMACR(P504S)+, PSA+
Condyloma acuminatum	Cauliflower papillary	Koilocytes, fibrovascular cores, no dysplasia	HPV 6/11
PeIN (Bowen/EQ/BP)	Plaque (keratotic/red)	Full-thickness dysplasia, intact BM	HPV 16/18
Penile SCC	Ulcer with rolled margins	Invasive nests, keratin pearls, desmoplasia	SCC, p16+ (if HPV)

AMACR (alpha-methylacyl-CoA racemase / P504S) is the most clinically useful IHC stain for prostatic adenocarcinoma — positive in carcinoma, negative in BPH and normal glands.

Three side-by-side histology panels compare H&E, HMWCK/34βE12, and AMACR/P504S staining patterns in benign prostatic glands and prostatic adenocarcinoma. — **Panel A:** H&E field showing benign prostatic glands with two-cell layers beside small crowded carcinoma glands in fibromuscular stroma.. **Panel B:** HMWCK/34βE12 IHC showing brown basal cell staining around benign glands and absent basal staining in carcinoma glands.. **Panel C:** AMACR/P504S IHC showing granular brown cytoplasmic positivity in carcinoma glands with negative benign glands..

SELF-CHECK

In a pathology practical, a slide shows an enlarged testis with a homogeneous cream-white cut surface divided by fibrous septa. Histology shows sheets of large cells with clear glycogen-rich cytoplasm, prominent central nucleoli, and a dense lymphocytic infiltrate in the fibrous stroma. What is the diagnosis and which immunohistochemical marker is positive?

A. Embryonal carcinoma — CD30 positive

B. Seminoma — PLAP and CD117 positive

C. Yolk sac tumor — AFP positive

D. Mature teratoma — HMWCK positive

Reveal Answer

Answer: B. Seminoma — PLAP and CD117 positive

Seminoma is characterized by a homogeneous cream-white gross appearance, sheets of large clear polygonal cells with prominent nucleoli, and diagnostic lymphocytic infiltrate in fibrous septa. PLAP (placental alkaline phosphatase), OCT3/4, CD117 (c-Kit), and D2-40 are positive. CD30 marks embryonal carcinoma. AFP marks yolk sac tumor. The 'fried-egg' clear cell appearance with lymphocytic stroma is the most tested histological pattern in practical exams.