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OVARIAN TUMORS- III Dr Aksharaditya Shukla Resident, Department Of Pathology MGM Medical College & M.Y. Hospital, Indore

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OVARIAN TUMORS-III

Dr Aksharaditya ShuklaResident, Department Of Pathology

MGM Medical College & M.Y. Hospital, Indore

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Dr Aksharaditya Shukla

Ovarian tumours

Tumour of the ovary are common form of neoplasia in women

Accounts for 3% of all cancers in females80% are benignMore common in older white women of

northern European ancestry90% of malignancies are carcinoma, 80%

have spread beyond the ovary at diagnosis.

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Risk factors for carcinoma

NulliparityFamily historyChildhood gonadal dysgenesisClomipheneHereditary non polyposis colon cancerBRCA1 and BRCA2 mutationsCA-125 present in 80% of serous and

endometrioid tumoursCytogenetics-gain of 12 & 8loss of chr X,22 18,17,14,13,12 & 8 ,benign/borderline tumor exhibit trisomy12

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Classification of ovarian tumours

Novak's classification (1967) has advantage of being simple but has certain obvious drawbacks, since it depends primarily on two fundamental factors; benign or malignant and solid or cystic.

Thus the borderline tumors, solid tumors with cystic degeneration and predominantly cystic tumors with solid areas fall into grey zone.

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In 1971, the cancer committee of International Federation of Gynecology and Obstetrics (FIGO) proposed a histological classification of common primary epithelial ovarian tumors. Although this classification covered only epithelial tumors, it was a step in the direction of uniformity in classification and it also included the group of tumors of "low potential malignancy".

A significant stride in the direction of a histogenesis-based classification system was made in 1973 with the publication of the World Health Organization (WHO) Classification of Ovarian Tumors. This classification system was updated in 1999 and recently in 2003.

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WHO classification of ovarian tumours

1. SURFACE EPITHELIAL TUMOURS2. GERM CELL TUMOURS3. SEX CORD STROMAL TUMOURS 4. GERM CELL SEX CORD STROMAL TUMOURS 5. TUMOUR OF THE RETE OVARII 6. MISCELLANEOUS TUMOURS 7. TUMOUR LIKE CONDITIONS8. LYMPHOID AND HEMATOPOETIC TUMOURS9. SECONDARY TUMOURS

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Granulosa stromal cell tumours

Sertoli stromal cell tumoursSex cord stromal tumours of mixed or

unclassified cell types Steroid cell tumours

SEX CORD STROMAL TUMOURS

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Sertoli stromal cell tumors

Sertoli leydig cell tumour group (androblastoma).

a) well differentiated b) intermediate differentiation

c) poorly differentiated (sarcomatoid)

d) retiform

2. Sertoli cell tumour.3. Stromal leydig cell

tumour

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Sertoli leydig cell tumor

Young patients (average 25 years)

50% shows signs of androgen excess i.e defeminisation

(breast atrophy, loss of subcutaneous Fat)

Later masculinisation appears

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Sertoli leydig cell tumor

Mixture of variable proportions of cells morphologically resembling male sertoli and leydig cells.

0.1% of ovarian neoplasms.

Grossly predominantly solid.

Variegated appearance of cut surface of ovarian Sertoli–Leydig cell tumor.

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Microscopic pattern

Well differentiated

(meyer’s type I)

Tubules lined by sertoli like cells seperated by variable number of leydig like cells

Well-differentiated (Meyer’s type I) Sertoli–Leydig cell tumor.

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Microscopic patterns of SLCT

Intermediate(meyer’s type II)

Formation of cords, sheets sertoli like cells seperated by spindle stromal cells

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Microscopic patterns of SLCT

Poorly differentiared

(meyer’s type III)

Composed of masses of spindle shaped cells arranged in “sacomatoid” pattern

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Special Stains and Immunohistochemistry of SLCT

Testosterone and estradiol both in sertoli and leydig cells

Areas of sertoli cell differentiation are Keratin+

Gonadal stromal components- inhibin+

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Sex Cord Tumor with Annular Tubules (Sex cord stromal tumours of mixed or unclassified cell types )

A distinctive variant of sex cord stromal-tumor with features of Sertoli and granulosa cell differentiation, divided in two subsets including those associated with Peutz-Jeghers syndrome and those without such association

33% associated with Peutz–Jeghers syndrome

Symptoms suggestive of hyperestrinism in ≈50%

Gross Pathology

If associated with Peutz–Jeghers syndrome typically:

- multifocal - bilateral - small (or even

microscopic) - calcified - benign * If unassociated with

Peutz–Jeghers syndrome: - unilateral - often large - ≈22% of cases

clinically malignant

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Sex cord tumor with annular

tubules

Combines: - features

suggestive of granulosa

cell tumor - pattern of

growth reminiscent sertoli cells Simple and

complex annular tubules containing eosinophilic hyaline bodies, often calcified.

- morphologic hallmark

Sex cord tumor with annular tubules. The patient had Peutz–Jeghers syndrome

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Steroid cell tumor (Sertoli stromal cell tumors)

Syn. Lipid, lipoid cell tumor

Heterogeneous group of tumors composed entirely of cells with morphologic features indicative of steroid hormone secretion.

Any age

Most associated with a virilizing syndrome (defeminization and amenorrhea)

Sometimes: - Cushing's syndrome -associated with

endometrioid carcinoma

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Gross Pathology

Usually unilateral Composed of yellow

or yellowish brown nodules separated by fibrous trabeculae

Malignant tumors tend to:

- be larger (≥06cm in

diameter) - have foci of

necrosis and hemorrhage

Cut surface of ovarian lipid cell tumor.

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Steroid cell tumor

Masses of large rounded or polyhedral cells

Composed entirely of cells with features indicative of steroid hormone secretion:

cytoplasm: + abundant + eosinophilic + may be vacuolated + often positive for

fat stains

Malignant tumors tend to exhibit:

- nuclear atypia - mitotic activity

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Special Stains and Immunohistochemistry

* Immunohistochemically: - reactivity for: + vimentin in 75% + keratin in 50% + actin in ≈33%8

consistent reactivity for: - inhibin - A103 - Mart-1

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GERM CELL SEX CORD STROMAL TUMOURS

a) Gonadoblastoma

b) Mixed germ cell sex cord stromal tumour

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Gonadoblastoma

Tumor composed of a combination of germ cells and sex-cord cells that arises almost exclusively in dysgenetic gonads.

Usually sexually abnormal:

commonly gonadal dysgenesis and carrying Y chromosome, i.e.:

- XY gonadal dysgenesis - XO–XY mosaicism - but not XX gonadal dysgenesis1 estimated 25% risk of neoplasia in these dysgenetic

gonads

Also documented in: * phenotypically and chromosomally normal females, even

during pregnancy * ataxia–telangiectasia

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Gross Pathology

Usually small

Often impossible to determine nature of gonad bearing tumor:

- sometimes identified as: + a streak(many become

apparent only on microscopic examination)

+ cryptorchid testis

Never a normal ovary

* ≈36% bilateral Streak gonad microscopically

shown to contain gonadoblastoma. The tumor was barely apparent grossly.

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Gonadoblastoma

Admixture of: primitive germ cells:

resembling those of dysgerminoma

sex cord–stromal cells: resembling

morphologically and immunohistochemically immature Sertoli and granulosa cells

Commonly: hyalinization:

when abundant may be obvious on plain abdominal radiograph

calcification

Ovarian gonadoblastoma. Note the sharply outlined tumor nests and the heavy calcification

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Special Stains and Immunohistochemistry

Hyaline material reacts strongly with anti-laminin antibodies,

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Metastatic tumors

Malignant secondary tumors involving ovaries originated in other organs.

* ≈7% of lesions presenting as primary ovarian tumors are metastatic

* >50% bilateral * Most common sources: - stomach - large bowel - appendix - breast - uterus (corpus and

cervix) - lung - skin (melanoma)

Metastases From Breast Carcinoma * Immunoreactive for GCDFP-15: - important in differential

diagnosis with primary ovarian carcinoma, which is generally negative

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Metastases From Adenocarcinoma of Large Bowel

Large bowel adenocarcinoma metastatic to ovary

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Krukenberg Tumors Usually: * >40 years of age * bilateral * metastatic origin

Usual primary sources: * stomach: - diffuse gastric carcinoma (linitis plastica) used to be

most common* large bowel, Appendix, Breast

May be: * retroperitoneal lymph node metastases * peritoneal implants

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Gross Pathology

Krukenberg Tumor

Moderate solid multinodular enlargement of the ovaries.

Typical gross appearance of Krukenberg tumors of ovary. The involvement is bilateral and the tumors are characterized by a multinodular outer appearance

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Krukenberg Tumor

* Diffuse infiltration by signet ring cells

- signet ring cells.

* Tumor emboli >50% of cases

Krukenberg tumor of ovary. Presence of intracellular

mucin

Krukenberg tumor of ovary. Microscopic appearance. Numerous signet ring cells are present in a highly fibrous stroma, either individually or in small nests

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Features favoring primary ovarian tumor:

* expansile (pushing) pattern of invasion

* complex papillary architecture

* size over 10cm

* smooth external surface

* benign- and borderline-appearing foci

Ovarian metastases tend to be:

* cystic

* well differentiated

* mucin-producing

* associated with necrosis and hemorrhage

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References

ROSAI AND ACKERMAN`S SURGICAL PATHOLOGY

DIAGNOSTIC SURGICAL PATHOLOGY- STERNBERG

PATHOLOGIC BASIS OF DISEASE– ROBBINS AND COTRAN

ANDERSON`S PATHOLOGY

CURRAN`S ATLAS OF PATHOLOGY

WWW.WEBPATH.COM

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Dr Aksharaditya Shukla

Thanks Presented By: Dr Aksharaditya Shukla

Resident, Department Of PatholgyMGM Medical College & M.Y. Hospital, Indore