Pathology of Ovarian Tumors – Quick Review

The latest TNM and FIGO staging for Ovarian Cancer has been discussed earlier here. Here, we will discuss pathology of ovarian tumors in short and in a way thats easy to grasp.ovarian neoplasm

WHO Classification of Ovarian Tumors

Cells of originSurface coelomic epitheliumGerm cellsSex cord, stromal cellsMetastatic
Proportion (%) of ovarian tumors65-7015-205-105
Proportion (%) of malignant ovarian tumors903-52-35
Affected age group>20 years0-25 and >25 yearsAll agesAdults
Predisposing factorsHereditary breast ovarian cancer syndrome i.e. BRCA1 (17q) and BRCA2 (13q) mutations

 

Hereditary nonpolyposis colon cancer (HNPCC) i.e. DNA mismatch repair genes (MLH1, MSH2, MSH6) mutations

 

Site specific ovarian cancer syndrome

 

Increased number of ovulation cycles: Nulliparity, Early menarche, Late menopause

 

Pelvic irradiation

 

Viral infection (mumps, rubella)

 

Dietary (high fat, low fiber)

 

Racial (White, Jewish)

 

Asbestos and Talc exposure

Genetic causes

 

Constitutional chromosomal abnormalities

 

Dysgenetic gonads

Peutz-Jegher’s syndrome

 

Cushing’s syndrome

 

Meig’s syndrome (Ovarian fibroma + Ascites + Hydrothorax usuallt right sided)

 

Gorlin syndrome

Histologic subtypesSerous

Mucinous

Endometroid

Clear cell

Brenner

Teratoma

Dysgerminoma

Endoderma sinus (yolk sac) tumor

Choriocarcinoma

Embryonal carcinoma

Polyembryoma

Thecoma

Fibroma

Granulosa cell tumor

Sertoli-Leydig cell tumor

Hilus cell (Pure leydig cell) tumor

Small cell carcinoma

Mullerian primaries: Uterus, fallopian tube, contralateral ovary, pelvic peritoneum

 

Non-mullerian primaries (Krukenberg tumor): Breast and GIT (colon, stomach, biliary tract, pancreas)

Gonadoblastoma (composed of germ cells and sex cord-stromal derivatives)
Tumor markersCA-125: Non-mucinous

 

CEA, CA19-9: Mucinous

 

Activin: Undifferentiated

AFP and alpha-1-antitrypsin: Endoderma sinus (yolk sac) tumor

 

hCG: Choriocarcinoma

 

LDH and Neuron-specific enolase: Dysgerminoma

 

AFP + hCG: Embryonal cell carcinoma, Polyembryoma

 

None: Immature teratoma

Androgen: Sertoli-Leydig cell tumor

 

Inhibin and Estradiol: Granulosa cell tumor

 

 

Pathology of Subtypes of Ovarian Tumors

Type and SubtypeProportion (%)Benign/MalignantUni- or Bi-lateralCharacteristic pathologic features
Epithelial
Serous50%60% benign

25% malignant

 

40% of all malignant ovarian tumors and 20% of all benign ovarian tumors

Bilaterality: 20% in benign, 30% in borderline and 66% in malignant.Ciliated columnar serous epithelium; +/- papilla; +/- psammoma bodies; tend to be unilocular
Mucinous25%80% benign

5-10% malignant

 

10% of all malignant tumors.

10-20% are bilateralNon-ciliated tall columnar epithelium with apical mucin; tend to be larger and multilocular; pseudomyxoma peritonei
Endometrioid10%Majority are malignant

 

8-15% of all malignant tumors.

Bilaterality in 25-40%Non-ciliated columnar epithelium similar to endocervical glands; Synchronous endometrial carcinoma or hyperplasia in 1/3rd cases
Clear cell5%MalignantBilaterality in 12-40%Clear cells resembling clear cell renal carcinoma (mesonephros); hobnail cells; Endometriosis in 25%; worse prognosis, poor platinum response
Brenner2.5%Mostly benignUsually unilateral

 

Can be associated with another epithelial ovarian neoplasm of ipsilateral or contralateral ovary in 30%

Transitional cells resembling urothelium; Nest of cells; Tend to multilocular
Germ cell (GCT)
Dysgerminoma35-50%Commonest Malignant GCT10-15% bilateralOvarian counterpart of seminoma; large cells arranged in alveoli with clear cytoplasm; intense infiltration of lymphocytes and plasma cells in fibrous septa; extremely radiosensitive
Endodermal sinus (yolk sac) tumor20%2nd commonest Malignant GCTUsually unilateralSchiller-Duval bodies (glomeruloid bodies)
Embryonal carcinomaRareMalignantUsually unilateralPrimitive embryonal elements
PolyembryomaRareMalignantEmbryoid bodies; least radiosensitive GCT
ChoriocarcinomaPure choriocarcinomas are extremely rare (often found in combination with other GCT)MalignantUsually unilateralGestational or non-gestational (metastatic from uterine choriocarcinoma); trophoblasts; isosexual precocious puberty is common
TeratomaImmature account for 20% of malignant GCTMature/Dermoid cyst and Struma ovarii – Benign

 

Immature and carcinoid – Malignant

2-5% immature teratoma are bilateralMature/Dermoid cyst (46, XX)  – germ cells arrested in 1st meiotic division: Rokitansky protuberance, Unilocular cyst lined by stratified squamous epithelium with underlying sebaceous glands, hair shafts, skin adnexa (ectodermal) +/- cartilage, bone, thyroid, etc.

 

Monodermal: thyroid tissue (struma ovarii); intestinal epithelium (ovarian carcinoid)

 

Immature: Fetal tissues derived from 3 germ layers

Mixed GCT10-15%Dependent upon cell types presentDysgerminoma is the commonest tissue element
Sex cord stromal tumor
Thecoma1% of all ovarian tumorsBenignBilaterality is rarePostmenopausal; Spindle-shaped cells with Oil-red O positive estrogen vacuoles; Endometrial hyperplasia (functional ovarina tumor)
Fibroma4% of all ovarian tumorsBenign Bilaterality is rareSpindle-shaped cells; Oil-red O negative; Non-functional; Meig’s syndrome
Sertoli-Leydig cell tumor (Androblastoma); hilus cell tumors are pure leydig cell tumors0.5% of all ovarian tumorsPotentially malignantUsually unilateral (90%); Bilaterality is rareTesticular cells – sertoli and leydig cells (reinke crystalloids typical of leydig cells); functional (androgens >>estrogen); may stain inhibin positive
Granulosa cell tumor2% of all ovarian tumors (commonest ovarian stromal tumor)5% of all ovarian malignanciesUsually unilateral (bilateral only in 2%, i.e. rare)Inhibin positive; Call-Exner bodies (like rosette), functional (estrogen >>androgen); tend to rupture (acute abdomen)
Metastatic
Krukenberg tumor5-10% of all ovarian tumors30-40% of all ovarian metastasesCommonly bilateralsignet ring appearance; intact capsule; retrograde lymphatic spread (most common gastric cancer followed by colorectal carcinoma)

Benign Vs Malignant Ovarian Tumors in general

FeaturesBenignMalignant
Clinical               
LateralityUnilateralBilateral
MobilityMobileFixed
FeelCysticSolid/Variegated
SurfaceSmoothIrregular
AscitesAbsentPresent
GrowthSlowRapid
Patient’s ageYoungerOlder
Nodular Pouch od DouglasAbsentPresent
Laparatomy
AscitesAbsentPresent – often hemorrhagic
Exophytic growth on surfaceAbsentPresent
AdhesionsAbsentPresent
Cut-sectionCysticSolid and hemorrhagic
Peritoneal nodulesAbsentPresent
Ultrasonography
Solidity and sizeCystic; <8 cm; calcification and teethCystic with solid component >50%; 8 cm; multilocular; bilateral; ascites; peritoneal masses/omental caking; lymph node involvement
Color Doppler evaluationRegular vascular branching and flowNeovascularization, low resistance flow with pulsatility index <1.

Patterns of Spread of Ovarian Tumor

1. Surrounding pelvic tissues: Directly

  • Fallopian tubes
  • Uterus
  • Contralateral adnexa
  • Rectum, urinary bladder and pelvic sidewall

2. Dissemination beyond pelvis: 3 modes –

a. Intraperitoneal (commonest): Tumors are shed into peritoneal cavity and follow the normal routes of peritoneal circulation.

  • Greater omentum
  • Right subphrenic region (in supine position)
  • Pouch of Douglas (in upright position)

b. Lymphatic:

  • Follow ovarian veins (mainly): to the left para-aortic and the right paracaval lymph nodes at the level of the renal hilum and are the most common sites for metastatic adenopathy.
  • Lymphatics of the broad ligament: drain into the pelvic lymph nodes, external iliac, hypogastric, and obturator chain.
  • Round ligaments: Spread to the superficial and deep inguinal nodes

c. Hematogenous (rare): Choriocarcinoma, embryonal carcinoma

  • Commonest: to liver
  • 2nd commonest: to lungs
  • Others: Brain, bone, kidney, adrenal glands, spleen

Risk of Malignancy Index (RMI)

FeatureRMI 1 ScoreRMI 2 Score (more sensitive)
Ultrasound features:

  • multilocular cyst
  • solid areas
  • bilateral lesions
  • scites
  • intra-abdominal metastases
0= none
1= one abnormality
3= two or more abnormalities

 

0= none
1= one abnormality
4= two or more abnormalities

 

Premenopausal11
Postmenopausal34
CA125U/mlU/ml
RMI score = ultrasound score x menopausal score x CA125 level in U/ml.

Score over 200 = high risk of malignancy

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