Ovary pathology

Question 1

General facts about ovarian tumors

Answer 1

• Ovarian cancers less common than those of uterus and breast but produce more deaths because of late detection
• 4th most common cancer after lung, breast and colon
• In general, pregnancy and oral contraceptives reduce the risk of ovarian cancer

Question 2

Pathologic lesions of ovary

Answer 2

Cysts

• Follicular
• Corpus Luteaum (C.L)
• Chocolate
• PCOD

Tumors

• Metastasis
• Epithelial
• Stromal
• Germ cell Cystic
• Solid

Question 3

Answer 3

Cysts of the ovary aka Simple cysts:

• solid cysts
• Usually < 1.5cms, sometimes large (4 to 5 cm)
• Lining may atrophy due to pressure
• follicular cyst: failure of follicle to rupture during ovulation-> dilation; lined by layers of cuboidal granulosa rimmed by ovarian tissue
• corpus luteal cyst: hemorrhagic from corpus luteum (yellow; image below; Pathoma)
• chocolate cysts: RBC w hemosiderin due to endometriosis;
• Induce fibrosis, adhesions, pain
• Consist of normal looking endometrial glands + stroma + RBC + hemosiderin
• May extend along pelvic ligaments
• Need to be distinguished from corpus luteum cysts
• Usually associated with infertility
• assoc w infertility

Etiopath:

• functional cyst: hormonal secreting
• non-functional: no secretion; chocolate cyst

Sx:

• asx & benign (usually)
• endometrial hyperplasia
• pain

Investigations

• US & CT

Question 4

Answer 4

PCOD

• cysts more towards outside
• Ovaries are 2x larger
• Ovaries - large, thick capsule, multiple unruptured follicles as cysts- lined by granulosa cells and hypertrophied theca interna cells
• Thick, hypertrophied stroma
• Persistent anovulation, no CL
• enlarged ovaries w thick capsule and hypertrophied stroma
• Multiple unruptured follicles as cysts (lined by granulosa cells and hypertrophied theca interna cells)

Etiopath:

• Young women, post menarche, persistant anovulation
• Oligomenorrhea, secondary amenorrhea, hirsutism, obesity (40%), infertility
• ↑ androgen (hirsuitism 50%, rarely virulization)
• High levels of LH
• Low levels of FSH
• Hyperinsulinemia due to peripheral resistance to insulin
• Excess androgens secreted by ovary and adrenals (?under the influence of abnormal pituitary axis)
• Androgens converted in to estrogen by adipose tissue
• Excess estrogens inhibit release of FSH by pituitary and stimulate the release of GnRH by hypothalamus
• GnRH acts on pituitary to release LH
• LH elevated, FSH levels fall, LH:FSH ratio
• elevated (greater than 3)
• Persistently elevated LH stimulates theca cells in ovary to produce excess androgens
• Cycle continues unabated

Hormonal effects & sx

Excess estrogen–
– endometrial hyperplasia

– stimulates adipose cells in body-obesity

Excess androgens–

– hirsutism, virilization, obesity

– androgens processed through adipose tissue and liver excess leading to estrogens

Dx

• hormonal assay, transvaginal ultrasound

Rx: chlomiphene - induce ovulation

• *C&C**
• endometrial carcinoma due to incr estrogen levels
• diabetes, hypertension, dyslipidemia, cardiovascular diseases, non-alcoholic fatty liver disease

Question 5

Tumors of the Ovary

Answer 5

• 4th commonest cause of cancer in women, 6% of all cancer in women
• 80% benign (20-45 years), 20% malign (40-65 years)), often bilateral more in nulliparous, family history, oral contraceptives reduce risk
• Problem is late detection,
• Rarely functional
• Marker: CA 125 useful for:
  
  • useful in screening asymptomatic postmenopausal women for ovarian malignancy
  • Greater value in monitoring response to therapy

Question 6

Ovarian tumour gross features

Answer 6

• Cystic - generally benign
• Benign: Solid - homogenous, cystic, unilocular, no papillae, smooth
• Malignant: Solid variegated - , solid, multilocular, nodular,papillae
• Spread:
  
  • Peritoneum - ascites, omental pancakes
  • LN - iliac, paraaortic
  • Blood - lungs

Question 7

Surface epithelial tumors

Answer 7

Classification based on differentiation

• Serous: Towards fallopian tube - columnar cells with cilia -
• Mucinous: Towards endocervix - tall mucin secreting cell -
• Endometrioid: Towards endometrium - nonciliated - columnar cell
• Brenner’s tumor: Towards transitional epithileum - transitional cells

Pathoma Note: surface epithelium of ovary aka coelomic epithelium

Sx

• Similar clinical features in most
• Abdominal pain, swelling, tumor mass or compression
• Gastro intestinal symptoms, dysuria, increased frequency urine, pelvic pressure
• Resection of benign tumors leads to cure

C&C

• Malignant: progressive weakness, weight loss, cachexia
• Seedling into peritoneum - massive ascites
• Tumor implants grow on the surface of other structures (not invade)
• Regional lymph nodes can be involved
• Metastasis to liver, lung, GIT, 50% to opposite ovary

Question 8

Serous cystadenomas, borderline, cystadenocarcinoma

Answer 8

Gross

• Lined by single layer of tall columnar ciliated cells
• Cysts filled with serous fluid
• uniloculated typically
• unilateral typically
• Benign - 20-50 years, over 50 years - malignant
• 20% of benign are bilateral, 2/3 of malignant are bilateral
• 10-15 cm diameter, lining smooth and glistening

Microscopic

• Papillae and polyps are seen in benign but are more numerous in malignant
• Psammoma bodies are seen in both benign and malignant
• Solid nodules indicate serosal penetration and hence are evidence of malignancy
• Serous tumors can reach very large sizes and may fill the abdomen
• recognize malignancy by solid nodules, more papillae and more polyps
• Borderline: multi layering, moderate mitosis, nuclear atypia BUT no stromal invasion
• Malignant: multi layering, nuclear atypia and Stromal invasion
• 10 year survival - borderline - 75% malignant - 10-20%
• Variant - cystadenofibroma - abundant fibrous tissue under epithelium, usually benign

Etiopath:

• Nulliparity, family history, and heritable mutations may play a role
• BRCA1 and p53

Question 9

Answer 9

Mucinous tumors

• Multiloculated cyst w septa in bw, sticky gelatinous material rich in glycoproteins
• Papillae, polyps and psammoma bodies are not a feature of mucinous tumors
• Benign tumors tend to have few locules
• Look for multiloculation and solid nodules to suspect malignancy
• commonly unilateral

Microscopic

• tall columnar & non-ciliated
• Malignant: atypia, BM invasion, invasion into stroma (all stroma on figure), stroma producing mucin

Etiopath:

• K-RAS & smoking

C&C

• small percentage complicated by pseudomyxoma pertionei (next card)
• Occasionally mixed with dermoid cyst or Brenner’s tumor
• 10 year survival - 70% for Borderline and 35% for carcinoma-so it is better than that of serous carcinomas

Question 10

Pseudomyxoma peritonei

Answer 10

• 2 - 5% of borderline and malignant mucinous tumors complicated by Pseudomyxoma peritonei
• Peritoneal cavity filled with mucoid material, matted tumor implants all over the abdomen on serosal surfaces -> “Jelly Belly”
• (It is also a complication of mucocele of the appendix due to carcinoma of appendix).
• Can also be a complication of mucocele of the appendix
• Mucocele of appendix can be caused by either carcinoma or a fecolith blocking the lumen
• Only the mucocele due to carcinoma can lead to pseudomyxoma peritonei

Question 11

Endometroid tumours

Answer 11

• Mostly behave as carcinomas
• 20%ofallovariancarcinomas,15-30% associated with concomitant endometrial carcinoma (not metastasis)
• Gross: solid and cystic, small, papillae, velvety surface
• Micro: resemble endometrial carcinoma - not normal endometrium (as seen in endometriosis)
• 40% bilateral, 5 year survival 4-50%
• Variant - clear cell carcinoma

Question 12

Answer 12

Brenner’s tumour

Gross

• solid mass, unilateral, pale yellow
• dense fibrous tissue

Microscopic

• nodules of epithelium not resembling that ovary called “nest cells”
• coffee bean shaped nuclei indicating transitional epithelial cells
• dense stroma w cells inside
• Transitional epithelial cells - like urinary bladder(may come from urogenital remnants)
• Plus - dense fibrous tissue • Small multiple nodules (not
• cysts)
• Clinically silent
• Usually benign - Occasionally malignant

C&C

• infertility

Question 13

Germ cell tumours

Answer 13

• 95% are benign cystic teratomas
• 5% - in children and young adults - malignant
• Teratoma,dysgerminoma,endodermal sinus tumor and choriocarcinoma (nongestational)

Question 14

Answer 14

Mature teratoma aka dermoid cyst

• Young women in active reproductive years
• Skin, adnexa, sebaceous - cheesy material
• hair, teeth, bone cartilage, thyroid, etc
• predominant ectodermal differentiation
• 90% unilateral,10% bilateral mostly right sided
• Usually associated with sterility reason not clear
• Unilocular, wrinkled opaque epidermal lining
• 1% malignant - squamous cell carcinoma

C&C

• infertility
• torsion
• 1% malignant transformation -> squamous cell carcinoma
• presence of neuroepithelial cells indicates malignancy
• Rapid growth
• May be mixed with chorio carcinoma, endodermal sinus tumor, embryonal carcinoma

Question 15

Immature teratoma (Malignant teratoma)

Answer 15

Wide variety of embryonic immature tissue

Usually seen in young women (18 years)

Bulky, solid, hemorrhage, necrosis

Micro:

• immature cartilage, glands, bone, muscle, nerves, etc
• Presence of neuroepithelium/neuroectoderm generally suggests malignancy
• Rapid growth
• May be mixed with chorio carcinoma, endodermal sinus tumor, embryonal carcinoma

Question 16

Answer 16

Monodermal or specialised teratomas

• Struma ovarii: hyperthyroidism
• Carcinoid tumor: carcinoid syndrome
• Strumal carcinoid: combined

Etiopath: unknown

C&C: malignancy (rare)

Question 17

Endodermal sinus tumor (Yolk sac tumor)

Answer 17

• Children and young women
• Malignant behavior
• serum AFP elevated and alpha I antitrypsin
• Cystic spaces, papillary projections
• Schiller Duval bodies:
  
  • layers of epithelial cells around blood vessels
  • resemble glomeruli
• Cytoplasmic pink inclusion:

Question 18

Answer 18

Dysgerminoma

Gross
- no necrosis or hemorrhage; characteristic of dysgerminoma, seminoma, medullary carcinoma

Microscopic

• large cell
• clear cytoplasm
• large nucleus w prominent nucleolous
• Unilateral solid tumor
• Homogenous gray-pink, soft fleshy tumor
• Large uniform round cells, clear cytoplasm, central regular nuclei, no stroma
• Infiltration by lymphocytes
• 2% of all ovarian cancers, 75% in II and III decades
• Similar in appearance to seminoma testis and medullary carcinoma breast

Dx: elevated LDH (Pathoma)

Question 19

Answer 19

Ovarian choriocarcinoma

• multinucleated giant cells
• synctial trophoblasts -> surrounding and takes over villi (no villi) -> produce HCG
• cytotrophoblasts
• high mitotic activity
• presence of hemorrhage
• resembles normal placental tissue
• *Etiology**
• not monoclonal
• nongestational refers to without pregnancy
• gestational related to pregnancies and moles
• quick metastasis
• *Investigations:**
• high HCG in blood and urine (higher than pregnancy) -> nausea, vomiting, vaginal bleed
• alpha-HCG similar to TSH
• *Clinical presentation:**
• nausea, vomiting, vaginal bleed

Dx

• Raised chorionic gonadotrophin (CGT syn to HCG) in blood and urine

C&C

• Highly fatal; More malignant than uterine choriocarcinoma
• Similar to placental choriocarcinoma
• Early and widespread metastasis
• Hemorrhage, necrosis, pleomorphism, giant cells, multi nucleation
• resistant to therapy
• primary may regress leaving only secondaries

Question 20

Sex cord stromal tumors

Answer 20

• Granulosa + Theca cell tumors • May produce ovarian steroids -
• feminizing features
• Embryonal sex cords - may differentiate into masculine — >
• Sertoli Leydig cell tumors or androblastomas

Question 21

Answer 21

Granulosa theca cell tumors (GTCT)

• sex cord tumour
• proliferation of G & T cells
• Rosette around Call-Exner bodies (eosinophilic filled w fluid from Granulosa cells) but may not be present in all GTCT
• variegated cells
• GRANULOSA + THECA with or without leutinisation, Call-Exner bodies
• Estrogen - precocious puberty, endometrial hyperplasia, carcinoma
• 5-25% of granulosa cell tumors can be malignant NOT theca cell tumors
• 2/3rd are postmenopausal

Etiology:
- 2/3 postmenopausal

Sx (Pathoma): varies w age

• heavy menstrual bleeding
• post-menopausal bleeding

Investigations:
- inhibin secreted by Granulosa cells

Question 22

Answer 22

Fibrothecoma

• Large polygonal cells and spindle cells resembling fibrocytes (bottom layer right image) and thecal cells (top layer right image)
• Lipid droplets
• Similar in appearance to thecomas
• Curious association with ascites (40%) and pleural effusion/hydrothorax on right side (Meig’s syndrome)
• Occasionally associated with basal cell nevus syndrome

Question 23

Sertoli Leydig cell tumor (Androblastoma)

Answer 23

• Recapitulate the cells of testis
  
  • Sertoli cells form tubules (Pathoma)
  • Leydig cells contain characteristic Reinke crystals (Pathoma)
• Usually benign
• II to III decade

Sx:

• Defeminization - atrophy of breasts, amenorrhea, sterility, loss of hair
• Masculinization - hirsutism, male distribution of hair, hypertrophy of clitoris, voice changes

Question 24

Gonadoblastoma

Answer 24

• Germ cell tumor + sex cord tumor

Question 25

Answer 25

KRUKENBERG TUMOURS **Gross:** solid, shiny tumours **Microscopic** - signet ring cells - mucin stained w PAS Etiopath: - most common in young women - most likely seeding from ab cavity; can be hematogenous

Question 26

Clinical scenarios: ovarian tumors with hormones

Answer 26

* Estrogen excess - granulosa theca(look for carcinomas of breast and uterus) * Estrogen and androgen excess- PCOD(not a tumor) * Androgen excess - Sertoli Leydig * CGT excess- Chorion carcinoma * Thyroxine- Struma Ovarii-dermoid cyst * 5HT- carcinoid syndrome-dermoid cyst

Question 27

Clinical scenarios- solid ovarian tumors

Answer 27

* Small- Brenner, Granulosa, Endometroid * Large-(hemorrhage,necrosis) malignant teratoma * Bilateral- Metastasis