**3. Histopathology of ovarian cancer**

Ovarian tumours have different histologic features and patterns due to the different tissues found within the ovary. With increased histologic examinations over the years, the classification of ovarian tumours has evolved, which is mostly based on the presumed tissue of origin, and includes common epithelial tumours, lipoid cell tumours, gonadoblastoma, sex cord-stromal tumours, germ cell tumours, soft tissue tumours not specific to the ovary, metastatic tumours and unclassified tumours [10]. The malignant variants of the common epithelial tumours and germ cell tumours will be discussed briefly.

## **3.1 Common epithelial Tumours**

Most benign and malignant ovarian tumours belong to this group and are derived from the common celomic epithelium on the surface of the ovary, which is also derived from the split lateral mesoderm and which also infolds to form the Mullerian duct. The Mullerian duct forms the endocervix, uterine corpus and uterine tube, thus explaining the different epithelial patterns (serous, mucinous, clear cell and endometrioid) in this group of tumours. Each of these patterns includes a completely benign (partly cystic, regular lining cells often covering stromal projections and with glandlike spaces) type and an adenocarcinoma (with invasive features that are either well differentiated with gland-like spaces or poorly differentiated sheets). Between these two patterns is an intermediate pattern termed carcinoma of low malignant potential that exhibits cellular stratification with variable mitotic activity and clear atypia but without stromal invasion [10].

Histologic diagnosis of an ovarian tumour should be done on the primary tumour, not on the histologic pattern of metastasis because not all peritoneal lesions are metastases even when there is a confirmed primary ovarian carcinoma [11].

One of the problems associated with adenocarcinoma of low malignant potential and sometimes with low-grade adenocarcinoma is the evaluation of glandular structures in lymph nodes to determine if such are metastases or simple benign glandular inclusions. It is also vital to ascertain the significance of glandular inclusions in lymph nodes after surgical removal because the epithelium in benign inclusion is tubal with cilia, shows a simple papillary pattern and has peripheral gland-like spaces that may extend around lymphoid follicles and sometimes extends into a follicle, but without stromal response, while adenocarcinoma usually invades a follicle and often shows a desmoplastic response. Mitoses are rarely seen in benign inclusions but present in adenocarcinoma [10].

Invasion of stroma by cribriform-like tumour composed of strands of infiltrating malignant cells is a feature of mucinous adenocarcinoma. Mucinous tumours might

either be of the endocervical or intestinal type, the former is characterized by cells with basal nuclei and the latter is characterized by goblet cells, sometimes argentaffin cells and rarely Paneth cells [10].

Clear cell carcinoma of the ovary usually arises from the ovarian surface epithelium, and sometimes from endometriosis and is said to represent a separate clinicopathologic entity. This carcinoma has been reported to exist in three architectural patterns viz.: solid, papillary and tubulocystic [12, 13]. Clear cell tumours are generally considered malignant due to failure to recognize benign or borderline types. Recent studies have found benign, borderline and micro-invasive tumours, with borderline tumours having 1–3 layers of clear, eosinophilic or hobnail cells, while the micro-invasive tumours showed evidence of focal stromal reaction with rare mitoses [14].

Endometrioid adenocarcinoma however is less common than the mucinous or serous type and has a histologic pattern similar to that of carcinoma of the endometrium that ranges from a well-differentiated glandular pattern to poorly differentiated adenocarcinoma with very few glands.

## **3.2 Malignant germ cell tumours**

These are derived from the primitive germ cells found between the junction of the hindgut and yolk sac. They later migrate through the mesentery to the posterior wall of the embryo, just beneath the celomic epithelium. In the process of their migration, some germ cells become arrested or extend beyond their usual position to form extragonadal germ cell tumours that are histologically similar to those in the ovary. Most types of germ cell tumours occur in pure form, with few occurring in mixed form. Thus, multiple sections must be examined to make a definitive diagnosis.

Malignant germ tumours include dysgerminoma, endodermal sinus tumour, immature teratoma and mixed germ cell tumour. Dysgerminoma is similar to seminoma of the testis and is derived from undifferentiated germ cells, and consists of strands, sheets, and groups of cells that are large and uniform in size with a central nucleus and varying mitotic activity. Lymphoid follicles with germinal centres are sometimes present with some showing granulomatous reaction [10].

Endodermal sinus tumours exhibit a central vascular strand with thin walls covered by a single layer of epithelial-like cells of hobnail pattern. Another common feature seen is a meshwork pattern with round hyaline globules that reacts to a-fetoprotein (AFP) in addition to other multiple pattern such as glandular, alveolar, hepatoid and myxomatous [10].

Teratomas are considered to arise from a single germ cell following the first meiotic division, with each of the three germ cell layers represented and consisting of both mature and immature elements. The histologic grade of immature teratomas is based on the presence of neuroepithelial components, the quantity of the neuroepithelial component and the degree of immaturity. Mature teratomas on the other hand are either cystic, constituting 99% or solid accounting for the remaining 1%. Solid mature teratoma usually constitutes tissues from all three cell layers with a well-differentiated glial component. The benign cystic teratoma that shows squamous epithelial involvement, and mesodermal and endodermal differentiation is usually benign, only a minute percentage undergo malignant progression to form squamous cell carcinoma [10, 15].

Mixed germ cell tumours include gonadoblastoma which is usually benign but sometimes associated with endodermal sinus tumour, embryonal carcinoma, choriocarcinoma or dysgerminoma.
