Epithelial

ovarian tumors

WHO classification of ovarian epithelial ( epithelial – stromal ) tumors .

1- Serous tumors

2- Mucinous tumors

3- Endometrioid tumors

4- Clear cell tumors

5- Brenner tumors

6- Seromucinous tumors

7- Undifferentiated tumors

8- Unclassified tumors ?

Ovarian tumors

1- Surface epithelial tumors .

2- Sex cord – stromal tumors .

3- Germ cell tumors .

4- Miscellaneous tumors .

Ovarian cancer represents about 30% of all cancers of the female genital organs .

Two factors consistently associated with a reduced risk of the disease are high parity and the use of OCP .

Dietary factors , western life style , obesity , high socioeconomic status .

- Unfortunately there is no early warning symptoms and specific diagnostic tests to allow early detection .

- Approximately 70% of patients present when this cancer is in an advanced stage .

- Sonography is the imaging method of choice to assess

an ovarian lesion and to determine the presence of solid

and cystic elements .

- The distinction between benign , borderline and

malignant tumors is generally not possible by US , CT

or MRI .

Ovarian cancers spread mainly by local extension ,

intraabdominal dissemination , lymphatic vessels and

blood vessels .

Surface epithelial tumors account for

approximately two – thirds of all ovarian neoplasm and 90% of all ovarian cancers

Mostly derived from the ovarian surface

epithelium which develops from the coelomic

epithelium ( Mesothelium ) that covers the embryonic gonads

Three major precursors :

- Surface epithelium ( Dysplastic epithelium ) .

- Surface epithelial inclusions ( inclusion cysts ) .

- Endometriosis .

- Epithelial tumors can have endophytic or exophytic

nature ( or both ) based on its main source .

- They can be cystic or solid or mixture of both

They often reveal two or even three cell types .

- When one or more additional cell types account for less

than 10% of the neoplasm , it is classified on the basis of

predominant cellular element , otherwise , it is designated a form of mixed epithelial tumors

All the epithelial tumors are subdivided to three

groups according to the degree of proliferation

and nuclear features :

1- Benign .

2- Malignant .

3- Borderline

Borderline tumors are intermediate between

clearly benign and obviously malignant ( in

their histologic features and clinical behavior ) .

WHO : Borderline tumor

FIGO : Tumors of low malignant potential .

CAP : Atypical proliferative tumors

- Tumors in this category are characterized by a degree of

proliferation greater than seen in benign tumors but an

absence of destructive stromal invasion .

- Borderline tumors may be associated with peritoneal implants ( invasive , non – invasive )

- Ovarian epithelial tumors divided into two broad

groups ( Type I , Type II ) , based on their

clinicopathologic features and characteristic molecular

genetic changes .

- Type I and II refer to tumorigenic pathways and are not histopathologic diagnostic terms

Type I tumors ( 25% )

- Low – grade .

- Relatively indolent tumors .

- Arise from well – characterized precursor lesions ( Borderline

tumors , endometriosis ) .

- Usually present as large stage I neoplasms .

- Often harbor somatic mutations KRAS , BRAF , PTEN ,

Type II tumors ( 75% )

- Aggressive , High grade .

- 75% shows P53 mutation .

- Most type II tumors are high grade serous carcinomas

Serous

tumors

Benign

- Serous cystadenoma

- Serous adenofiroma , cystadenofibroma .

- Serous surface papilloma

Borderline

- Serous borderline tumor ( Atypical proliferative serous

tumor ) .

- Serous borderline tumor , Micropapillary variant ( Non –invasive low – grade serous carcinoma )

Malignant

- low – grade serous adenocarcinoma

- High – grade serous adenocarcinoma

- Serous tumors account for 20% - 50% of all

ovarian tumors .

- 70% are benign , 5-10% are borderline , 20-25% are malignant

- The typical serous cystadenoma is a thin –

walled unilocular cyst , filled by watery fluid .

- The cyst may contain polypoid projections

which are firm or soft .

- Benign serous tumors are bilateral in 10% of cases

- Borderline serous tumors usually show large

cystic lesion with large polypoid projections .

- They are bilateral in 25-35% of cases

- Serous carcinoma may be predominantly

cystic and papillary , entirely solid and firm or

both cystic and solid .

- Serous carcinoma are bilateral in about 75% of cases

- Microscopically benign serous cysts are lined by

columnar ciliated epithelial cells similar to that of fallopian

tube .

- Serous borderline tumors show polypoid projections and

papilla , lined by atypical epithelial cells with stratification and nuclear atypia

- Serous carcinoma shoes obvious ovarian

stromal invasion with following microscopic

features , papillary structures , small nests and

large sheets of tumor cells , glands with slit –

like lumens , infiltrating single cells and psammoma bodies

Serous carcinoma is the most common type of ovarian

cancer ( 68% ) .

Mutation is P53 gene are present in the most cases .

High grade serous carcinoma is the type of ovarian

cancer most associated with mutations in the BRCA

genes .

Low grade serous carcinoma is uncommon ,

characterized by BRAF or KRAS mutations .

Most of the poorly – differentiated as well

as undifferentiated carcinomas of ovary are indeed High – grade serous carcinoma

Serous carcinoma should be distinguished from

the other types of carcinomas and specially Metastatic carcinoma

Women with breast cancer are at increased risk

of ovarian carcinoma , indeed when a patient

with breast cancer has an adnexal cancer , it is

more likely to be primary in ovary than metastatic

Mucinou

tumors

- Mucinous tumors account for about 15% of all

ovarian tumors .

- 85% are benign

- 6-10% are borderline .

- Remainder malignat

- Mucinous tumors tend to be larger than other ovarian

neoplasms

- Mucinous cystadenoma is usually thin – walled and

multilocular , and filled by mucinous fluid .

- Borderline and malignant tumors are solid – cystic , contain

papilla that may be solid or firm .

- Because benign , borderline and invasive components are

frequently admixed it is important to sample mucinous tumor

thoroughly .

- Mucinous tumors may be associated with Brenner tumor or dermoid cyst

- Microscopically : The mucinous cysts are lined by single

layer of endocervical – like epithelium or less often by

intestinal like epithelial cells ( goblet rich ) .

- In borderline tumors there are significant epithelial

stratification , budding , bridging , nuclear atypia .

- Intestinal type borderline tumors are more common ( 85 –90% ) than the endocervical type

- 30% of borderline mucinous tumors ( the

endocervical type ) are accompanied by

endometriosis .

- Borderline tumors have an excellent prognosis

despite of peritoneal or lymph nodes metastasis ( Especically endocervical type )

- Mucinous carcinomas vary considerably in

their microscopic appearance . Cysts , glands ,

solid mases , clusters and individual cells may be present in various combination

Pseudomyxomatous peritonei is a

progressive condition mostly seen in

patients with Borderline ovarian mucinous

tumors .

Differential DX :

- Endometrioid adenocarcinoma .

- Metastatic adenocarcinoma .

Clinical and operative findings as well as patient history

are more helpful diagnostic clues than the microseopicfeatures of the tumor

Endometrioid

tumor

- They are less than 5% of all ovarian tumors .

- Endometrioid carcinoma account for up to 15% of all

ovarian cancers .

- 5-10% are related to endometriosis .

- Borderline endometrioid tumors are very rare .

- Endometrioid benign ( and borderline ) tumors are

predominantly solid . Carcinoma may be solid or cystic .

- Up to one – third of ovarian endometrioid carcinomas are

accompanied by carcinoma of uterine corpus , which

usually closely resembles ovarian tumors on microscopic inspection and is most often an independent primary tumor

Microscopically , Endometrioid tumors are characterized

by tubular glands simulating to different extents those of

proliferative , secretory , hyperplastic or adenocarcinomatous epithelium

Differential DX :

- Poorly – differentiated serous carcinoma ( WT – 1 ) .

- Intestinal Metastatic carcinoma . ( CK7 , CK20 , CEA , ER ,

PR , CA – 125 ) .

- Sex cord – stromal tumors ( CK7 , EMA , α – inhibin ) .

- MMMT

- Yolk sac tumor ( AFP , EMA )

Malignant Mixed

Mullerian Tumors

( MMMT )

- Highly malignant tumors contain epithelial

and mesenchymal elements , develop in post

menopausal women , spread beyond the ovary in more than half of the cases

- The epithelial component is usually high grade

( Serous , endometrioid , less often mucinous ,

squamous , clear cell ) .

- The mesenchymal component may be

homologous ( Fibrosarcoma , leiomyoma ,

stromal sarcoma ) or heterologous (

Rhabdomyosarcoma , chondrosarcoma , osteosarcoma )

Differential DX :

- Immature teratoma .

- Sertoli leydig cell tumor

Clear cell

tumors

- Benign and borderline clear cell tumors are very uncommon .

- Clear cell carcinoma account for more than 5% of all ovarian

cancers , most frequently between the ages of 40 to 70 .

Clear cell carcinomas are predominantly cystic , an unilocular

cyst containing one or more solid nodules protruding into the

lumen .

- It is the ovarian tumor that is most often associated with

ovarian and pelvic endometriosis .

- They are rarely bilateral

Clear cell carcinoma is strongly associated with

endometriosis . Paraneoplastic syndromes ,

Hypercalcemia , DVT , pulmonary emboli .

Clear cell carcinoma appears overrepresented among

women with the Lynch syndrome .

The most important differential diagnosis :

1- Dysgerminoma

2- Yolk sac tumor .

3- Metastatic RCC .

4- Metastatic intestinal adenocarcinoma

Transitional cell

tumors

1- Brenner tumor ( 2 to 3% of all ovarian

tumors ) .

2- Proliferative Brenner tumor ( Borderline ) .

3- Malignant Brenner tumor .

4- Transitional cell carcinoma

Undifferentiated carcinoma

- A high – grade lesion , half are bilateral and spread

beyond the pelvic at the time of diagnosis .

- The mass is predominantly solid with areas of

hemorrhage , necrosis and cyst formation .

- The clinical features of most undifferentiated carcinoma resemble those of high – grade serous carcinomas