ovary slide share 2

OVARIAN TUMORS-II

Dr Aksharaditya ShuklaResident, Department Of Pathology

MGM Medical College & M.Y. Hospital, Indore

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.


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


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.


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.


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


GERM CELL TUMOURS

Origin- germ cells (totipotent) which migrate to ovary from yolk sac .

Frequency-15-20%

Age group- children & young adults

~95% are benign.

The younger the patient, more chances of malignancy


Dysgerminoma

Dysgerminoma is the most common malignant germ cell neoplasia of the ovary, and is similar to seminoma which is the testicular counterpart

<1% of all ovarian tumors ≈5% of malignant ovarian

tumors Usually young <30 years

of age. ≈5% arise in abnormal

gonads: a) pure or mixed

gonadal dysgenesis (from

a gonadoblastoma), b) testicular

feminization (androgen insensitivity) syndrome

More common on right. Bilateral in 15% of cases. Metastases commonly

in:

* contralateral ovary * retroperitoneal nodes * peritoneal cavity: (associated with

decreased survival rate).

Exceptionally associated with hypercalcemia

Extremely radiosenstive.


DYSGERMINOMA

Often: large: may be >1000g encapsulated Smooth, often convoluted surface

Cut surface solid gray

Cut surface of ovarian dysgerminoma. The multinodular solid quality and the tan color are characteristic features.

Foci of hemorrhage and necrosis: not as common or

prominent as in other malignant germ cell tumors.

Typical lobulated outer aspect of ovarian dysgerminoma


Dysgerminoma Diffuse insular or trabecular pattern.

Tumor cells: uniform

* nuclei: Central large

nucleoli: - one or more - prominent * cytoplasm: -abundant - clear to finely - contains: + glycogen + sometimes fine droplets of fat * cell membrane prominent

fibrous strands infiltrated by lymphocytes (most T-cell type5)

May be: * focal necrosis * hyaline changes in vessels * germinal centers * granulomatous foci


Special Stains and Immunohistochemistryof dysgerminoma

Tumor cells reactive for: -PLAP -CD117 (c-KIT)

Often keratin (erratically and focally)

Sometimes -GFAP -Desmin


Yolk Sac Tumor

Malignant germ cell tumor of the ovary developed as a result of differentiation of primitive malignant germ cell elements in the direction of yolk sac or vitelline structures.

Usually children and young adults:

* Median age 19 years * ≈25% prepubertal at diagnosis

Vaginal bleeding in 1%

Serum AFP level invariably elevatedChorionic gonadotropin levels normal.Highly aggressive, and associated with other germ cell

tumour


Yolk Sac Tumor

Average diameter 15cm

External surface: * smooth * glistening

Cut surface: * variegated * partially cystic * often large foci of

hemorrhage and necrosis

Component of benign cystic teratoma in ≈15% of cases

Gross appearance of yolk sac tumor. The cut surface is remarkably heterogeneous due to extensive hemorrhage, necrosis, and cystic degeneration


YOLK SAC TUMOR

Many histologic variants occur, including the reticular, endodermal sinus (papillary), polyvesicular–vitelline, hepatoid, and glandular patterns.

The endodermal sinus pattern is the second most common pattern(after reticular).

This pattern features

characteristic Schiller–Duvall bodies (rounded papillae containing a single central vessel and lined by columnar tumor cells) .


YOLK SAC TUMOR

PAS-positive hyaline droplets

* intracytoplasmic and extracellular * nearly always present

High-power view of ovarian yolk sac tumor. Numerous hyaline globules are seen in the cytoplasm of the tumor cells lining the papillae


Yolk Sac Tumor

Some show differentiation toward hepatic, intestinal, and parietal yolk sac structures

Yolk sac tumor with endometrioid features


Special Stains and Immunohistochemistry

Yolk sac tumor: stains positive for : pankeratin negative for : keratin 7: (in contrast with endometrioid and clear cell ovarian ca) stains positive for -WT-1: ( in contrast with serous ovarian carcinoma)

Hyaline droplets: - usually stain for α-fetoprotein - may also contain: - α1-antitrypsin - basement membrane components: #type IV collagen # laminin


Embryonal carcinoma

Rare and the least differentiated of the ovarian germ cell tumors.

Considered to be homologous to the embryonal carcinoma of adult testis.

Young age group (median age 15 years): 47% prepubertal at diagnosis, 43% of whom present

with precocious pubertyVaginal bleeding in 33%Amenorrhea in 7%Hirsutism in 7%Serum α-fetoprotein levels often elevatedChorionic gonadotropin levels invariably high:

results in consistently positive pregnancy tests


Embryonal carcinoma

Median diameter 17cm.

External surface: smooth and

glistening.

Cut surface: predominantly

solid and variegated.

extensive areas of necrosis and hemorrhage.

Gross appearance of embryonal carcinoma of ovary.


Embryonal carcinoma

Similar appearance to embryonal carcinoma of adult testis.

Solid sheets and nests of large primitive cells: occasionally

forming papillae and abortive glandular structures.

Frequently

syncytiotrophoblast-like tumor cells scattered among smaller cells

Microscopic appearance of embryonal carcinoma of ovary


Special Stains and Immunohistochemistry of embryonal carcinoma

Syncytiotrophoblast-like tumor cells immunoreactive for hCG.

CD30 and cytokeratin


Choriocarcinoma

Malignant tumor of the ovary with trophoblastic differentiation composed of syncytiotrophoblast, cytotrophoblast and intermediate trophoblast.

Exceedingly rare.

May be associated with mature cystic teratoma of contralateral ovary.


Choricarcinoma

Typical admixture of syncytial and cytotrophoblastic elements in a necrotic and hemorrhagic background

Choriocarcinoma arising in a dermoid cyst



Usually immunohistochemical reactivity for hCG.

Keratin 7 said to represent a marker for subset of trophoblastic cells.

LK26 (a folate-binding protein): - consistently expressed


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


Thanks Presented By: Dr Aksharaditya Shukla

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


OVARIAN TUMOURS II

Moderator: Dr Poonam Nanwani

Asst. Prof. Department Of PathologyMGM Medical College & M.Y. Hospital, Indore


Immature Malignant TeratomaMalignant ovarian

germinal tumor composed of mixture of immature embryonal and mature adult tissue derived from all three germ layers.

Usually children and adolescents.

May be: * solid throughout * solid with multiple minute cysts * predominantly cystic

Gross appearance of ovarian immature teratoma


Immature teratoma

Mixture of embryonal and adult tissues derived from all three germ layers:

* any type of tissue * main component usually

neuroepithelial * mesodermal elements also

common * sometimes predominantly

composed of endodermal derivatives, including

-esophagus - liver -intestinal structures

This is immature teratoma containing immature neuroepithelium forming rosettes

immature teratoma containing immature neuroepithelium forming rosettes.


Grading system for immature teratoma (Norris et al)

Grade Ia. Abundance of mature

tissuesb. Loose mesenchymal tissue

with occasional mitosesc. Immature cartilaged. Tooth anlage

Grade IIa) Fewer mature tissuesb) Rare foci of neuroepithelium

with common mitoses not exceeding three low-magnification (×10) fields in any one slide

Grade IIIa) Few or no mature tissuesb) Numerous neuroepithelial

elements merging with a cellular stroma occupying four or more low-magnification fields



Glial fibrillary acidic protein (GFAP): - helpful in identification of mature and immature glial tissue - also detectable in chondrocytes * Long-chain polysialic acid moiety of neural cell

adhesion molecule: - another marker of immature and mature

neural tissue


Mature Cystic Teratoma

Cystic germ cell tumors composed of multiple mature elements derived from ectoderm, mesoderm and endoderm.

Almost 20% of all ovarian neoplasms:

Most common ovarian tumor in childhood

88% unilateral

usually benign

Symptoms:

* relate to mass * occasionally: - hemolytic anemia - virilization * May coexist with: - mucinous cystadenoma - Brenner tumor - * Usually benign


Usually multiloculated Cystic content:

greasy largely composed of:

keratin sebum hairs

commonly teeth (tend to be in well-

defined nipple-like structure covered with hair (Rokitansky's protuberance)

Admixture of sebum and hair within the cavity of an ovarian mature cystic teratoma


Mature cystic teratoma

#Cystic cavities lined by mature epidermis

Extremely common: * skin appendages * neural (particularly

glial) tissue

Also: * cartilage * respiratory tissue * gastrointestinal tract

tissue (- may be peptic ulcer

formation)

Mature cystic teratoma of ovary: gastric mucosa of pyloric type


Germ cell tumors (continued)

Monodermal teratoma

a) Thyroid tumour group Struma ovarii –benign or

malignant

b) Carcinoid group -insular -trabecular -mucinous -strumal carcinoid

c) Neuroectodermal tumour group

-ependymoma -primitive neuroectodermal

tumour-glioblastoma multiforme

-medulloblastoma

d) Carcinoma

e) Melanocytic group

f) Sarcoma group

g) Sebaceous tumour group


Struma Ovarii

Ovarian teratoma composed exclusively or predominantly of thyroid tissue

May show any of the pathologic changes seen in a normally placed gland, including:

diffuse or nodular hyperplasia: - may lead to hyperthyroidism - thyroiditis -carcinoma: ( sometimes resulting in metastases)

Thyroid nature fully documented with biologic and immunohistochemical studies for thyroid hormones


Struma Ovarii

Color and consistency of thyroid tissue, but often cystic


Struma Ovarii

Dominant growth of thyroid tissue in a teratoma, sometimes to exclusion of other components

Struma ovarii. The thyroid tissue, which has a microscopically unremarkable appearance, is sharply delimited from the ovarian stroma


Carcinoid Tumor (monodedrmal teratoma)

Primary well differentiated neuroendocrine tumor of the ovary.

Carcinoid syndrome: * more likely the larger tumor ( > 7 cm)

Sometimes severe constipation: * presumably due to secretion of peptide YY


carcinoid

Usually unilateral Mean diameter 10

cm External surface: * smooth or

bosselated * predominantly

solid * firm * tan to yellow

Cut surface of carcinoid tumor of ovary showing typical solid appearance and white to yellowish color

Cut surface of carcinoid tumor of ovary showing typical solid appearance and white to yellowish color


Carcinoid (monodermal teratoma)

insular pattern of growth similar to in appendix and small bowel

-trabecular appearance

similar to in rectum - mucinous (goblet

cell) appearance similar to those seen primarily in appendix

Primary ovarian carcinoid tumor with a trabecular pattern of growth


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 CONDITION8. LYMPHOID AND HEMATOPOETIC

TUMOURS9. SECONDARY TUMOURS.

SEX CORD STROMAL TUMOURS


Granulosa stromal cell tumours

Sertoli stromal cell tumours

Sex cord stromal tumours of mixed or unclassified cell types.

Steroid cell tumours

SEX CORD STROMAL TUMOURS


Granulosa stromal cell tumours (SEX CORD STROMAL TUMOURS)

Granulosa cell tumour group

a) Adult granulosa cell tumour.

b) Juvenile granulosa cell

tumour.

Thecoma fibroma group

a) Thecoma (typical or lutenised)

b) Fibromac) Cellular fibroma

d) Fibrosarcomae) Sclerosing stromal tumours f) Signet ring stromal

tumourg) Stromal tumour with

minor sex cord elementsh) Unclassified


Granulosa Cell Tumor group(sex cord stromal tumor)

Differentiation towards follicular granulosa cells that can occur in adults (adult granulosa cell tumor) and in younger patients (juvenile granulosa cell tumor).

Two distinct types: * adult * juvenile


Adult Granulosa Cell Tumor

Usually childbearing age.

- 75% have hyperestrinism, which may result in: +isosexual precocious puberty +metrorrhagia in adults, including postmenopausal women

Elevated serum inhibin and follicle regulatory proteins.


AGCT

The tumors are usually large (>10 cm) and unilateral.

The cut surface is soft and yellow-tan with cysts and hemorrhage.

encapsulated smooth, lobulated outline Cut surface: -predominantly solid May be: cystic:

-filled with straw-colored or mucoid fluid

-sometimes so prominent

as to simulat appearance

of a cystadenoma

Granulosa cell tumor with solid cut surface.


AGCT

Different histologic patterns occur, including microfollicular, macrofollicular, “watered-silk,” gyriform, and diffuse.

However, all are composed of round to oval granulosa cells that have little cytoplasm and round to angular nuclei with longitudinal nuclear grooves (coffee bean appearance)

There is minimal cytologic atypia

Mitotic rate is low.


Coffee-bean( longitudnally grooved) nuclei in adult type of ovarian granulosa cell tumor


The microfollicular and diffuse variants often contain characteristic Call–Exner bodies consisting of a very small collection of eosinophilic material lined by well-differentiated granulosa cells.


Juvenile Granulosa Cell Tumor

More aggressive than adult

More likely to produce distant metastases

≈80% during first two decades of life * Usually presents with isosexual

precocity * Occasionally associated with: - enchondromatosis (Ollier's disease) - Maffucci's syndrome


Juvenile Granulosa Cell Tumor

Typical morphologic features include:

diffuse or macrofollicular patterns

of growth (former predominating)

- eosinophilic mucin-positive intrafollicular secretion. - larger tumor cells with extensive luteinization - paucity of nuclear grooves - nuclear atypia - variable but often high

mitotic activity.

On high power the tumor cells lack the coffee-bean nuclei seen in the adult type

The follicle-like spaces seen on low-power examination are a common feature of this neoplasm.


Special Stains and Immunohistochemistry granulosa cell tumors

Adult Granulosa Cell Tumor

* Immunohistochemically: - steroid production: + by both theca and granulosa

cells with predominance of: # estradiol in granulosa cell

# progesterone in luteinized theca

cells - vimentin - desmoplakin (desmosomal plaque

protein) - inhibin (also JGCT) follicle regulatory proteins - CD99 keratin: + 33–50% of cases + typical dot-like distribution + mainly CK8 and CK18

types25,26 smooth muscle actin: + nearly all cases S-100 protein: + ≈50% of cases

Strong immunoreactivity for inhibin in granulosa cell tumor.


Thecoma

Postmenopausal women.

Symptoms of hyperestrogenism.

Most are unilateral and can measure up to 10 cm in diameter.

Immunohistochemically, the tumor is positive for

inhibin expression. Oil Red O fat stains (which require fresh tissue) highlight the intracellular lipid.


Thecoma

Cut surface of thecoma showing a predominance of yellow areas alternating

with whitish foci

Usually unilateral

Variable size

Well-defined capsule

Firm consistency

Cut surface: * largely or entirely

solid * may be cysts

Yellow color


THECOMA

Fascicles of spindle cells with:

centrally placed nuclei moderate amount of pale cytoplasm.

Only mild atypia and rare mitoses

Intervening tissue may show:

-considerable collagen deposition.

- focal hyaline plaque formation.

Degree of cellularity varies considerably

Some in young women are heavily calcified

Bland microscopic appearance of thecoma, with some variability in cellularity.



Oil red O: (require fresh tissue) - abundant intracytoplasmic neutral fat

Positive for inhibin expression

Silver stains: Estradiol usually limited to a small number of

tumor cell


FIBROMA

The most common type of sex-cord stromal tumor developing from specialized ovarian stroma.

CommonUsually unilateralAlmost invariably after puberty Fibromas are not hormonally functionalaverage of 5 cm in diameterSometimes in young women with basal cell nevus

(Gorlin's) syndrome.BenignMay be ascites:

especially if large sometimes with right-sided pleural effusion (Meigs'

syndrome)(disappears on removal of tumor).


Gross Pathology

Solid Lobulated Firm Uniformly white Usually no adhesions Average diameter 6cm May be myxoid

changes, sometimes resulting in cystic degeneration

Cut surface of ovarian fibroma.

Outer aspect of ovarian fibroma


FIBROMA

Spindle stromal cells: - closely packed - arranged in 'feather-

stitched' or storiform pattern - no atypia and few

mitoses May be: - hyaline bands - edema If in basal cell nevus

(Gorlin's) syndrome: - calcified - usually bilateral - often multinodular

Cellular fibroma. The tumor is hypercellular, but

pleomorphism and mitotic activity are minimal


Immunohistochemistry of Fibromas

diffusely positive for vimentin


Small Cell Carcinoma

Poorly differentiated tumors, composed mostly of small cells, and subclassified into hypercalcemic and pulmonary type

Two types: * hypercalcemic: -most common * pulmonary

Hypercalcemic-type Small Cell Carcinoma

Young females (average age 23 years)

Nearly always bilateral

Occasionally familial

Hypercalcemia: - 67% of cases - disappears following

removal * High-grade

malignancy


Gross Pathology


Large and solid

Areas of necrosis and hemorrhage



Diffuse proliferation of small, closely packed cells of carcinomatous appearance with:

- scant cytoplasm - small nuclei May be: - clusters of larger and more

pleomorphic cells, some resembling luteinized

cells: + if a large number

referred to as large variant of small cell carcinoma - cytoplasmic hyaline globules - islands - cords - mucinous glands - follicle-like structures + important clue to

diagnosis

Small cell carcinoma, hypercalcemic type. The presence of follicle-like formations is an important diagnostic feature


Pulmonary-type Small Cell Carcinoma

Resembles homonymous lung tumor.

May be pure or associated with endometrioid carcinoma or other patterns.

Ultrastructurally: - neurosecretory-

type granule


Thanks Presented By: Dr Aksharaditya Shukla

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

ovary slide share 2

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