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Testicular Tumors - Complete MUHS Exam Notes (2nd MBBS Pathology)

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3. CLASSIFY TESTICULAR TUMORS ⭐

WHO 2022 Classification of Testicular Tumors

• Seminoma

• Embryonal carcinoma
• Yolk sac tumor (postpubertal type)
• Choriocarcinoma
• Teratoma (postpubertal type)
• Teratoma with somatic-type malignancy

• Spermatocytic tumor
• Teratoma (prepubertal type)
• Yolk sac tumor (prepubertal type)
• Mixed teratoma and yolk sac tumor (prepubertal type)

• Leydig cell tumor
• Sertoli cell tumor
• Granulosa cell tumor (adult and juvenile types)
• Mixed and unclassified sex cord-stromal tumors

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5. TESTICULAR GERM CELL TUMORS - DETAILED (EXAM ANSWER)

Enumerate

Pathogenesis of GCTs

1. Primordial germ cell undergoes acquired genetic/epigenetic modification in utero (due to cryptorchidism, KIT/BAK germline variants, pesticides, nonsteroidal estrogens)
2. This leads to arrested differentiation
3. KIT mutation + other growth stimulating events → Germ Cell Neoplasia In Situ (GCNIS)
4. At puberty: isochromosome 12p + hormonal effects → Invasive GCT

• Cryptorchidism (10% of GCTs)
• Klinefelter syndrome (50x risk for mediastinal GCTs)
• Family history (8-10x risk in brothers)
• Testicular dysgenesis syndrome

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2. SEMINOMA ⭐⭐⭐⭐⭐

Introduction

• Most common GCT (~50% of all GCTs)
• Peak age: 4th decade (30-40 years)
• Identical tumor in ovary = Dysgerminoma; in CNS = Germinoma
• Most radiosensitive of all GCTs
• Best prognosis among GCTs

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GROSS FEATURES

Exam tip: The absence of hemorrhage and necrosis on cut surface is a classic distinguishing feature of seminoma compared to embryonal carcinoma.

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MICROSCOPIC FEATURES (Classical Seminoma Morphology)

• Sheets of uniform cells divided into poorly demarcated lobules
• Lobules separated by delicate fibrous septa
• Septa contain lymphocytic infiltrate (T-lymphocytes)
• Ill-defined granulomas may be present (host response)

• Round to polyhedral cells
• Distinct cell membrane
• Clear/watery cytoplasm (contains glycogen)
• Large, central nucleus with one or two prominent nucleoli
• Cells uniform in size (no significant pleomorphism)

• Positive: KIT (CD117), OCT3/4, podoplanin (D2-40)
• Negative: cytokeratin (helps distinguish from embryonal carcinoma)
• ~15% have syncytiotrophoblasts → elevated serum hCG (but not as high as choriocarcinoma)

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LABELLED DIAGRAM OF SEMINOMA (Schematic)

SEMINOMA - MICROSCOPIC (Schematic Diagram)

┌─────────────────────────────────────────┐
│   FIBROUS SEPTUM with LYMPHOCYTES       │
│         │         │                     │
│    ╔════╧═════════╧════╗                │
│    ║  LOBULE           ║                │
│    ║  ┌──────────────┐ ║                │
│    ║  │ ○ ○ ○ ○ ○    │ ║ ← Uniform     │
│    ║  │ ○ ○ ○ ○ ○    │ ║   tumor cells │
│    ║  │ ○ ○ ○ ○ ○    │ ║               │
│    ║  └──────────────┘ ║                │
│    ╚════════════════════╝                │
│                                         │
│  SINGLE CELL DETAIL:                   │
│   ┌────────────────────┐               │
│   │  Round cell        │               │
│   │  ┌──────────┐      │               │
│   │  │ Nucleus  │◄─── Large, central  │
│   │  │ ●●Nucleol│      nucleus         │
│   │  └──────────┘      │               │
│   │  Clear cytoplasm   │               │
│   │  (glycogen)        │               │
│   │  Distinct membrane │               │
│   └────────────────────┘               │
└─────────────────────────────────────────┘

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MODES OF SPREAD OF SEMINOMA

• First: Retroperitoneal para-aortic lymph nodes
• Then: Mediastinal lymph nodes
• Then: Supraclavicular lymph nodes (especially left-sided - Virchow's node)
• Note: Seminomas typically spread via lymphatics FIRST

• Occurs later in course compared to NSGCTs
• Sites: Lungs (most common), liver, brain, bone

Exam Mnemonics:

• "Seminoma = Slow, Lymphatics first, Later hematogenous"
• Lymph node drainage of testis: Para-aortic (NOT inguinal - testis drains to para-aortic because of its embryological origin from the abdomen)

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1 & 4. TERATOMA - DEFINITION, CLASSIFICATION, GROSS, MICROSCOPIC, EXTRAGONADAL SITES

Definition

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Classification of Teratoma

1. Mature teratoma - all elements well-differentiated (adult tissue types)
2. Immature teratoma - contains embryonic/fetal elements (especially immature neural tissue)
3. Teratoma with malignant transformation - somatic malignancy arising (squamous cell carcinoma, adenocarcinoma, sarcoma) - chemoresistant

• Mature cystic teratoma (Dermoid cyst) - most common benign ovarian tumor
• Immature teratoma (malignant)
• Monodermal teratoma (Struma ovarii, Carcinoid)

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GROSS FEATURES of Testicular Teratoma

Contrast with seminoma: teratoma has a heterogeneous cut surface whereas seminoma is homogeneous

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MICROSCOPIC FEATURES of Teratoma

• Collections of differentiated cells or organoid structures from multiple germ layers:
  • Ectoderm: Neural tissue, squamous epithelium, skin adnexae (hair follicles, sebaceous glands)
  • Mesoderm: Muscle bundles (smooth/skeletal), cartilage islands, connective tissue
  • Endoderm: Bronchial epithelium, intestinal wall, thyroid-like structures, glandular elements
• Elements embedded in fibrous or myxoid stroma
• Disorganized arrangement (unlike normal tissue)
• May be mature or immature

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EXTRAGONADAL SITES OF TERATOMA

Exam tip: Sacrococcygeal teratoma is the most common solid tumor of the newborn. Klinefelter syndrome has 50x increased risk for mediastinal GCTs specifically.

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SERUM TUMOR MARKERS (Very Important for Exams)

Key point: Pure seminoma does NOT elevate AFP. If AFP is elevated in a "seminoma," it contains non-seminomatous elements (mixed GCT).

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MODES OF SPREAD - GENERAL (ALL GCTs)

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KEY CONCEPTS SUMMARY (Quick Revision)

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