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2nd MBBS Pathology - MUHS Exam Notes

Source: Robbins & Kumar Basic Pathology + Robbins, Cotran & Kumar Pathologic Basis of Disease

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Q1. FIBROID UTERUS (Uterine Leiomyoma)

Definition

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Pathogenesis / Etiology (Exam Points)

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Classification by Location (FIGO System)

                    UTERINE CAVITY
            ┌─────────────────────────────┐
            │  ┌──────────────────────┐   │
Submucosal──►  │   Intramural         │   ◄── Subserosal
(Type 0,1,2)│  │   (within wall)      │   │   (under serosa)
            │  └──────────────────────┘   │
            └─────────────────────────────┘
                    ▼
            Parasitic (pedunculated subserosal
            attached to adjacent organs)

• Type 0 - Intracavitary (pedunculated submucosal, entirely within cavity)
• Type 1 - <50% diameter within myometrium (submucosal)
• Type 2 - ≥50% diameter within myometrium (submucosal)
• Type 3 - Abuts endometrium, no intracavitary component (intramural)
• Type 4-6 - Intramural
• Type 7 - Subserosal (pedunculated)
• Type 8 - Other (cervical, parasitic)

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GROSS PATHOLOGY (High-yield exam point)

GROSS FEATURES OF LEIOMYOMA
─────────────────────────────────────────────
• Single or multiple (most often multiple)
• Sharply circumscribed / well demarcated
• Firm, rubbery consistency
• Gray-white to pinkish-white color
• Cut surface: WHORLED / TRABECULATED appearance ★
• Variable size: few mm to very large (can fill pelvis)
• Pseudocapsule present (can be shelled out)
• Locations: intramural > submucosal > subserosal
─────────────────────────────────────────────

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MICROSCOPIC (HISTOPATHOLOGY) (Exam diagram point)

HISTOLOGY OF LEIOMYOMA
────────────────────────────────────────────────────
• Bundles/fascicles of smooth muscle cells
• Cells: elongated spindle-shaped with:
   - Abundant eosinophilic cytoplasm
   - Cigar-shaped (blunt-ended) nuclei ★
   - No/rare mitoses (<5 per 10 HPF)
   - No nuclear atypia
• Cells arranged in INTERLACING FASCICLES ★
• Connective tissue stroma between bundles
• Foci of FIBROSIS, CALCIFICATION may be present
• Well-defined border from surrounding myometrium
────────────────────────────────────────────────────

         ┌─────────────────────────────────────┐
         │  Smooth muscle cells in fascicles   │
         │  ═══════════════════════════════    │
         │  ───────────────────────────────    │
         │  ═══════════════════════════════    │
         │  (interlacing pattern seen)          │
         │  ○  Cigar-shaped nuclei             │
         │  Fibrous stroma between bundles     │
         └─────────────────────────────────────┘
         Well-circumscribed, pseudocapsule

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COMPLICATIONS (★ Very Important for MUHS)

COMPLICATIONS OF UTERINE FIBROIDS
─────────────────────────────────────────────────
MENSTRUAL:
  • Menorrhagia (most common symptom) ★
  • Metrorrhagia, dysmenorrhea
  
REPRODUCTIVE:
  • Infertility (distortion of cavity)
  • Recurrent abortions
  • Malpresentation in pregnancy
  • Obstructed labour
  • Red degeneration in pregnancy (pain)
  
PRESSURE EFFECTS:
  • Urinary frequency/retention (bladder compression)
  • Constipation (rectal compression)
  • Hydronephrosis (ureteric compression)
  • Venous thrombosis (large tumors)
  
TORSION: Pedunculated fibroid can twist → acute abdomen
  
MALIGNANT TRANSFORMATION:
  • Leiomyosarcoma - EXTREMELY RARE (<0.5%) ★
  (Not from leiomyoma → arises de novo in postmenopausal)
─────────────────────────────────────────────────

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Q2. GERM CELL TUMORS OF OVARY

Definition

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Classification (Must-Know for MUHS)

GERM CELL TUMORS OF OVARY
│
├── A. TUMORS OF GERM CELLS THEMSELVES
│   ├── 1. Dysgerminoma ★ (most common malignant GCT)
│   └── 2. Gonadoblastoma
│
├── B. TUMORS SHOWING EMBRYONIC DIFFERENTIATION
│   └── Teratoma
│       ├── Mature (Benign) Teratoma / Dermoid Cyst ★
│       ├── Immature (Malignant) Teratoma
│       └── Monodermal Teratoma (Struma ovarii, Carcinoid)
│
└── C. TUMORS SHOWING EXTRA-EMBRYONIC DIFFERENTIATION
    ├── Yolk Sac Tumor (Endodermal Sinus Tumor) ★
    ├── Choriocarcinoma (Primary ovarian)
    └── Embryonal Carcinoma

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DYSGERMINOMA (High-yield MUHS topic)

Definition

Epidemiology (Exam points)

Molecular / Genetics (★ Exam)

• Expresses stem cell markers: OCT3, OCT4, NANOG (pluripotency markers)
• Associated with isochromosome 12p (i12p) - same as testicular seminoma
• KIT receptor tyrosine kinase expressed; 30-50% have activating KIT mutations ★
• 30% have amplification of KIT

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GROSS PATHOLOGY of Dysgerminoma

GROSS FEATURES
───────────────────────────────────────────
• Unilateral in 80-90% ★
• Large tumors - may fill the abdomen
• Solid tumor ★ (NOT cystic)
• Cut surface: Yellow-white to GRAY-PINK ★
• Soft, FLESHY consistency ★
• May have areas of necrosis in large tumors
• Smooth, lobulated external surface
───────────────────────────────────────────

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MICROSCOPIC (HISTOPATHOLOGY) of Dysgerminoma

HISTOLOGY OF DYSGERMINOMA
────────────────────────────────────────────────────
• Large VESICULAR cells (polyhedral/round) ★
• Clear cytoplasm ★
• Well-defined cell boundaries
• Centrally placed REGULAR NUCLEI ★
• Prominent nucleoli
• Cells arranged in SHEETS or CORDS ★
• Separated by SCANT FIBROUS STROMA
• Stroma infiltrated by LYMPHOCYTES ★ (key feature!)
• Non-caseating granulomas may be present
• Occasional syncytiotrophoblastic giant cells (hCG +ve)
────────────────────────────────────────────────────

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Prognosis of Dysgerminoma

• All dysgerminomas are malignant but behavior is variable
• Only ~1/3 are aggressive
• Unilateral tumor without capsular breach: >90% 10-year PFS after salpingo-oophorectomy
• Highly radiosensitive and chemosensitive ★
• Even metastatic disease can often be cured

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Q3. TERATOMA

Definition

Key concept: Teratomas contain tissues NOT normally found at the site of origin - they can contain teeth, hair, cartilage, neural tissue, thyroid, etc.

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Classification of Teratoma (Most Important)

TERATOMA CLASSIFICATION
│
├── 1. MATURE (BENIGN) TERATOMA ★★
│   ├── Mature Cystic Teratoma (Dermoid Cyst) - MOST COMMON
│   └── Mature Solid Teratoma (rare)
│
├── 2. IMMATURE (MALIGNANT) TERATOMA ★
│   └── Graded I, II, III based on amount of immature neuroepithelium
│
└── 3. MONODERMAL (HIGHLY SPECIALIZED) TERATOMA ★
    ├── Struma Ovarii (composed entirely of thyroid tissue)
    └── Carcinoid Tumor (from intestinal tissue in teratoma)
    └── Strumal Carcinoid (rare combination)

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A. MATURE (BENIGN) TERATOMA (Dermoid Cyst) (Most common GCT of ovary)

Gross Pathology (Exam Diagram)

GROSS - MATURE CYSTIC TERATOMA (DERMOID CYST)
──────────────────────────────────────────────────
• Most common ovarian GCT
• Usually UNILOCULAR CYST ★
• Bilateral in 10-15% of cases ★
• Contains HAIR and SEBACEOUS material ★
• Cut surface:
   - Cyst wall lined by opaque, GRAY-WHITE, WRINKLED epidermis
   - PROTRUDING HAIR SHAFTS ★
   - TOOTH structures and CALCIFICATION visible grossly ★
   - Sebaceous (greasy/cheesy) material fills cyst
• Rokitansky's protuberance (dermoid plug) - solid nodule on cyst wall
──────────────────────────────────────────────────

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Microscopic Pathology of Mature Teratoma (Exam Diagram)

HISTOLOGY - MATURE CYSTIC TERATOMA
──────────────────────────────────────────────────────
CYST WALL: Lined by STRATIFIED SQUAMOUS EPITHELIUM ★
SKIN ADNEXA (ECTODERM):
  • Sebaceous glands ★
  • Hair follicles / hair shafts ★
  • Sweat glands
  
OTHER GERM LAYER ELEMENTS:
  MESODERM: Cartilage, bone, smooth muscle, fat
  ENDODERM: Bronchial epithelium, GI epithelium, thyroid tissue

• NEURAL TISSUE may be present
• NO mitotic activity, NO atypia in mature teratoma
──────────────────────────────────────────────────────

Genetics of Mature Teratoma

• Karyotype: 46, XX in almost all cases
• Arise from ovum after first meiotic division (majority)
• Remainder arise before first meiotic division

Malignant Transformation

• Occurs in ~1% of dermoid cysts (mainly in postmenopausal women)
• Most common: Squamous cell carcinoma ★
• Others: Thyroid carcinoma, melanoma

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B. IMMATURE (MALIGNANT) TERATOMA

Gross Pathology

GROSS - IMMATURE TERATOMA
───────────────────────────────────────────
• BULKY tumor
• SMOOTH external surface
• SOLID on sectioning ★
• May contain hair, sebaceous material, cartilage
• Areas of NECROSIS and HEMORRHAGE ★
• May have calcification
───────────────────────────────────────────

Microscopic Pathology

HISTOLOGY - IMMATURE TERATOMA
───────────────────────────────────────────────────────
• Tissues resemble EMBRYONAL and IMMATURE FETAL tissue ★
• Key: IMMATURE NEUROEPITHELIUM in varying amounts ★
  (resembles developing neural tube/rosettes)
• Immature cartilage, bone, muscle
• Graded I-III based on amount of immature neuroepithelium
• Grade I (<1 low-power field), Grade II (1-3 LPF), Grade III (>3 LPF)
• Mitotic figures present
───────────────────────────────────────────────────────

Prognosis

• Age: Mean 18 years (prepubertal adolescents)
• Stage I, Grade 1: Excellent prognosis
• Higher grade: Chemotherapy required
• Recurrences mainly in first 2 years

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C. MONODERMAL (SPECIALIZED) TERATOMA (★ Exam - Functional Tumors)

Exam point: Primary ovarian carcinoid can cause carcinoid syndrome WITHOUT hepatic metastases because ovarian veins connect directly to systemic circulation. ★

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EXTRAGONADAL SITES OF TERATOMA (★ Important - Frequently asked)

EXTRAGONADAL SITES OF TERATOMA
(In order of frequency)
──────────────────────────────────────────────────────────
SITE                    NOTES
──────────────────────────────────────────────────────────
1. SACROCOCCYGEAL ★★   • Most common extragonadal site
                        • Most common tumor of newborns
                        • More common in females (4:1)
                        • Can be benign or malignant
                        
2. ANTERIOR MEDIASTINUM • 2nd most common
                        • Young adults
                        • Can compress mediastinal structures
                        
3. RETROPERITONEUM      • 3rd most common extragonadal site
                        • Often large at diagnosis
                        
4. PINEAL GLAND         • Intracranial (most common intracranial GCT)
                        • Parinaud syndrome (upward gaze palsy)
                        
5. NECK (CERVICAL)      • Neonates; may cause airway obstruction
                        
6. ORBIT                • Rare
                        
7. LIVER, STOMACH       • Very rare
──────────────────────────────────────────────────────────

• During embryogenesis, primordial germ cells migrate from yolk sac along the midline to gonadal ridges
• If germ cells are misplaced along this migratory pathway → form extragonadal teratomas

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COMPARISON TABLE - Mature vs Immature Teratoma (MUHS Exam)

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DYSGERMINOMA vs SEMINOMA (Comparison - MUHS)

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TUMOR MARKERS SUMMARY (MUHS Short-Answer Tip)

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KEY EXAM POINTS - QUICK RECAP

• Most common = menorrhagia (★)
• Whorled cut surface (★)
• Estrogen dependent, shrinks after menopause (★)
• Degenerations: Hyaline (most common), Red (in pregnancy) (★)
• Malignant change = extremely rare

• = Ovarian counterpart of testicular seminoma (★)
• Solid, fleshy, gray-pink tumor
• Large clear cells + lymphocytic stroma (★)
• OCT3/4, NANOG, KIT, i(12p) (★)
• Highly chemo/radiosensitive (★)

• Mature cystic = dermoid cyst = most common ovarian GCT (★)
• Contains hair, teeth, skin adnexa
• 1% malignant change → SCC most common (★)
• Immature = graded by immature neuroepithelium (★)
• Struma ovarii → hyperthyroidism; Carcinoid → carcinoid syndrome (★)
• Extragonadal: Sacrococcygeal (most common) > Mediastinum > Retroperitoneum (★)

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