Histology of ovarian and fallopian tube cancer
The malignant epithelial tumors (carcinomas) originate from the surface epithelium and account for about 90% of all ovarian cancers. The remaining 10% originate either from the germ cells or sex cord/stromal cells.
Invasive epithelial ovarian cancer
|Ovarian specimen with serous epithelial cancer. Click to enlarge.
||Photomicrograph of the tumor in the left-hand picture. Click to enlarge.
There are several subtypes of ovarian carcinomas depending on cell type and malignancy grade (1-3). The invasive ovarian carcinomas must be separated from the non-invasive (borderline) tumors, since the treatment and prognosis is different. The serous and mucinous epitheial types are the most common subtypes.
Overview of the different subtypes of ovarian carcinomas and their incidence:
- Serous 55%
- Endometrioid 17%
- Mucinous 13%
- Clear cell 8%
- Mixed 5%
- Undifferentiated type 2%
Borderline ovarian tumors
Borderline tumors are epithelial tumors of low malignant potential also named low malignant potential (LMP-tumors) tumors. These tumors are more frequent in younger women. They are often unilocular and can be smooth or with papillary projections in the lumen. These tumors can easily be misinterpreted as benign.
Borderline tumors differ from benign tumors by proliferation of atypical cells without infiltrating in the underlying stroma.
Contrary to invasive tumors, the atypical cells in borderline tumors are localized on the inside of ovarian cysts and have not penetrated the capsule. They are often limited to the ovary and thus Stage I, although they can spread outside the ovary.
|Cystic ovarian tumor with papillary projections on inner surface. Click to enlarge.
||Photomicrograph from the serous borderline tumor in the left-hand picture. Click to enlarge.
Serous and mucinous are the most common ovarian borderline tumors, other types are unusual (infrequent).
- Clear cell
- Transitional cell type
Non-epithelial ovarian cancer
Germ cell tumors
Germ cells can develop into embryonal or placental tissue and can grow undifferentiated (dysgerminoma) or simulated extraembryonal tissue (yolk sac tumor). Germ cell tumors account only for about 3% of all ovarian cancers and are a heterogenous group of tumors. The majority are benign teratomas. Malignant teratomas are very rare. Correct diagnosis is especially important since most patients with these tumors can be cured with adequate chemotherapy or radiation therapy.
Ovary with yolk sac tumor. Click to enlarge.
Photomicrograph of the yolk sac tumor in the left-hand picture. Click to enlarge.
- Dysgerminoma is the most common type of malignant germ cell tumor. About 5% of these tumors appear in phenotypical women with abnormal gonads, for example 46XY (bilateral streak gonads), 46X/46XY (unilateral streak gonads, contralateral testis) or 46XY (testicular feminization). It is recommended to perform karyotyping when pelvic tumors are detected in premenarchal females.
- Endodermal sinus tumor/yolk sac tumor . These tumors often produce alfa-feto protein (AFP).
- Embryonal carcinoma
- Choriocarcinomas usually originate from trophoblastic tissue. They can also originate from germ cell tumors as a pure tumor or as a component in a mixed.
- Immature teratomas contain tissue developed from an embryo. It is graded according to differentiation and amount of immature tissue. A malignant transformation from a mature teratoma is seldom. The most common type of such malignant transformation is squamous cell carcinoma developed from a mature teratoma.
- Secondary malignant transformation
- Mixed forms
- Mixed tumors are tumors that sometimes contain a mixture of different components in the same tumor.
Sex cord stromal tumors
Sex cord-stromal tumors are a mixed group of hormone-producing tumors. Surgery can often be limited to extirpation of one ovary and thus the woman can still be fertile. Omentectomy and lymph node staging should be considered.
Sex cord-stromal tumors account for only 8% of ovarian tumors. The dominating type of tumor is thecoma/fibroma (benign) followed by granulosa cell tumor (potentially malignant). The other types are very uncommon:
- Granulosa stromal cell tumor
- Granulosa cell tumor (adult and juvenile)
- Thecoma/fibroma (thecoma , fibroma, variants of stromal cell tumors)
- Sertolistromal cell tumor
- Sertoli Leydig cell tumor (androblastoma/arrhenoblastoma)
- Sertoli stromal cell tumors mixed or unclassified type
- Leydig cell tumor
- Unclassifiable tumor
Granulosa stromal cell tumors include granulosa cell tumors and thecomas. Fibrosarcoma can originate from ovarian stroma. These tumors produce estrogen and thus can induce endometrial hyperplasia and endometrial carcinoma. Granulosa cell tumors produce inhibin that can be detected by immunhistochemistry and thus support the microscopic diagnosis.
Sertoli-Leydig cell tumors (also named androblastoma/arrhenoblastoma, Sertoli cell, Sertoli-Leydig cell and Leydig cell tumors are rare tumors that often produce androgen. Gynandroblastoma is an extremly uncommon tumor demonstrating a mixture of ovarian and testicular differentiation often a mixture of granulosa cell elements and Sertoli-Leydig cell elements.
Primary peritoneal carcinoma
A peritoneal carcinoma can not microscopically be separated from serous epithelial ovarian carcinoma. The following criteria must be fulfilled for this diagnosis:
- Both ovary should be of normal size or be enlarged because of a benign process.
- There must be more tumor volume outside the ovaries than on their surfaces.
- Ovarian carcinoma should not be present. Only tumor on the surface without stromal invasion is allowed or maximal cortical growth of 5 x 5 mm.
This diagnosis can only be given when the patient has had primary surgery without chemotherapy, since the above criteria cannot be evaluated for patients who have had chemotherapy.
Fallopian tube carcinoma
Photomicrograph demonstrating a serous papillary carcinoma of the fallopian tube. Click to enlarge.
Carcinomas of the fallopian tubes are microscopically similar to ovarian carcinomas. In order to establish the tumor as tubal in origin, there should limited tumor in the ovary and no similar type of carcinoma in the uterus.
Microscopically, serous carcinoma dominates completely. Less common subtypes are endometrioid, mucinous, clear cell, transitional cell and undifferenitiated carcinomas. The mixed epithelial and mesenchymal such as carcinosarcoma is sometime seen as primary tubal cancers.
DNA ploidy analysis
DNA ploidy analysis determines the amount of DNA in tumor cell nuclei in relation to normal diploid DNA content. DNA index 1 indicates DNA content corresponding to normal diploid nuclei. DNA index 2 corresponds to tetraploid nuclei, and everything in between as abnormal aneuploid nuclei.
DNA ploidy analysis can be performed from formalin-fixed paraffin-embedded material. At Oslo University Hospital, we prefer image analysis instead of flow cytometry for this type of investigation.
DNA ploidy results are useful to evaluate prognosis in stage I ovarian carcinomas.
Examples of DNA distributions: