Most human ovarian tumours are classified into one of several categories based on presumed histogenesis and direction of differentiation.87 The histogenetic classification
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categorizes ovarian neoplasm with regard to their derivation from coelomic epithelium, germ cells and mesenchyme (the stromal and the sex cord).88 Ovarian tumours are divided into three major categories, common epithelial tumours, sex cord stromal tumours and germ cell tumours.87
2.10.1 COMMON/ SURFACE EPITHELIAL TUMOURS
Epithelial tumours are derived from the epithelium that normally lines the outer aspect of the ovary and constitute about two-third of all ovarian neoplasms and an even greater proportion of malignant ovarian neoplasms.87 These tumours have a potential to differentiate in a variety of epithelial directions that simulate the diverse avenues of development of mullerian duct epithelium.87 Common epithelial tumours are divided into five main categories according to the type of cell into which they differentiate: a) serous tumours, whose cells resemble those of the fallopian tube; b) mucinous tumours, whose cells mimic those of the endocervix; c) endometrioid tumours, whose cells are similar to those of the endometrium; d) clear-cell tumours, whose cells resemble those of the endometrium during pregnancy; e) Brenner tumours, whose cells are urothelial in appearance.87
Depending upon the aggressiveness, the surface epithelial tumours are divided into three groups: clearly benign, clearly malignant and borderline or low-grade malignant tumours.4
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Clearly benign tumours are lined by a single layer of well-oriented columnar epithelium.4 Papillary projections when present have the same type of epithelium without stroma invasion.4 Borderline tumours have some morphological features of malignancy, apparent detachment of cellular clusters from their site of origin and essential absence of stroma invasion.4 This group has a much better prognosis stage for stage than their malignant counterpart.89 They exist with relatively benign clinical course and at a younger age.90 Roosing et al. observed that there was an increased risk of developing borderline tumour from benign cystadenoma.91 Clearly malignant tumours have epithelial cells that show features of anaplasia with invasion of the stroma.4
(i) Serous tumours
Serous neoplasms are the most common ovarian neoplasms.88 Together the benign, borderline and malignant type of serous tumours account for 30% of all ovarian neoplasms. About 60% of serous tumours are benign, 15% are borderline and 25%
malignant.4
Serous tumours occur most commonly in the second and fifth decade of life, the malignant one being more common in later life.5 On histological examination the lining epithelium is composed of columnar epithelium with abundant cilia in benign tumours.5 Borderline serous tumours show stratification of the epithelium, cell clusters with moderate features of malignancy that are detached from their site of origin without invasion of the stroma.4 The cells in malignant tumours show features of marked atypia,
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some may be undifferentiated with stroma invasion.76 Areas of haemorrhage and necrosis and psammoma bodies may be seen.76
(ii) Mucinous tumours
Mucinous cystadenomas are less common, accounting for 25% of all ovarian neoplasm and are seen in adult life though, rare before puberty and menopause.5 More than 80%
are benign, 10-15% are borderline and 5-10% are malignant.4 Microscopically, benign mucinous tumours are characterized by a lining of tall columnar epithelial cells with apical mucin and absence of cilia, similar to benign cervical or intestinal epithelia.5
Borderline mucinous tumours are identified using the same criteria for serous tumours.
For mucinous cystadenocarcinoma it may be well differentiated, containing malignant tall columnar mucin producing cells in solid or cribriform pattern and poorly differentiated in which the cells are in irregular sheets, cords with associated stromal invasion.9
(iii) Endometrioid tumours
Endometrioid tumours account for 5-20% of all ovarian neoplasms.4,5 Most endometrioid tumours are malignant.5 They are called endometrioid carcinomas because of their resemblance histologically to uterine endometrial adenocarcinoma.4 It is second to serous adenocarcinoma in frequency and occurs commonly in post menopausal women.9
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On histological examination, glandular pattern bearing strong resemblance to those of endometrial adenocarcinoma are seen.5
(iv) Clear cell tumours
Clear cell tumours are almost always malignant and comprise 5% of ovarian cancers.4 It is characterized by large epithelial cells with abundant clear cytoplasm.5 They are termed mesonephroid carcinoma because of the close histologic resemblance to renal adenocarcinoma.4 Histologically, clear cell carcinoma is characterized by tubules, glands, papillae, cysts and solid sheets of tumour cells.4 The tumour cells are large with clear abundant cytoplasm containing glycogen, and the nuclei protrude into the cytoplasm in a
“hobnail’ fashion.76 Benign and borderline tumours have the appearance of an adenofibroma with abundant stromal component.88
(v) Brenner tumour
Brenner tumour is an uncommon adenofibroma in which the epithelial component consists of nests of transitional cells similar to those lining the urinary bladder and they comprise 2% of all ovarian tumours.4,5 Histologically, there are nests of transitional- type epithelial cells with longitudinal nuclear groove (coffee bean nuclei) lying in abundant fibrous stroma.76 Though Brenner tumours are benign, borderline and malignant types have been reported.5 A case of bilateral proliferating Brenner tumour of the ovary associated with recurrent urothelial carcinoma of the urinary bladder has been reported.92
2.10.2 SEX CORD STROMAL TUMOUR
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Sex cord stromal tumours of the ovaries comprise 6-10% of all ovarian neoplasms.87 They are derived from the sex cord and stromal component of the developing gonads.87 The tumour can originate from granulosa cells, theca cells, sertoli-leydig cells, and the fibroblast that may appear in the stroma of either the male or female gonad.9,87
(i) Granulosa-Theca cell tumours
Granulosa-theca cell tumours comprise about 5% of all ovarian tumours; it comprise pure granulosa cell tumours, pure thecomas, combination of granulosa theca cell tumours and fibroma.4
a) Granulosa cell tumour
Pure granulosa cell tumours may occur at all ages.4 Two distinct types exist, adult and juvenile types.76 The adult granulosa cell tumour is diagnosed during the child bearing years, but it can occur after menopause and before puberty,76 while the juvenile type is diagnosed in nearly 80% of cases during the first two decades of life and is responsible for isosexual precocity.76 These tumours invade locally but may have more aggressive and malignant behaviour.4 Granulosa cell tumour is a prototypical functional ovarian tumour that secretes oestrogen.9
Histologically, granulosa cell display an array of pattern: 1) diffuse (sarcomatoid), 2) insular (islands of cells), 3) trabecular (anastomosing bands of granulosa cells).9 Haphazard orientation of nuclei about a central degenerating space results in a follicular
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pattern known as Call-Exner bodies.9 It also known that all granulosa cell tumour are potentially malignant.5
b) Thecoma
Pure thecoma are rare and almost always benign.4,5 They frequently occur in post menopausal women, and may be found in combination with fibroma of the ovary.4 Histologically, it is composed of fascicles of spindle shaped cells with central nuclei and moderate amount of cytoplasm that contain lipid.9,76 Bands of hyalinized collagen separate nests of theca cells.8 In some cases granulosa-theca cell tumour may occur together.4,5
C) Fibromas
Fibromas are benign tumours that account for 4-7% of all ovarian tumours. They can occur at all ages with peak in the perimenopausal period.9 Microscopically, they are composed of well differentiated spindle cells embedded in variable amount of collagen.9 Sometimes a combination of fibroma and thecoma is present and is called fibrothecoma.4
(ii) Sertoli-leydig cell tumours
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Ovarian sertoli-leydig cell tumours (arrhenoblastoma or androblastoma) are rare mesenchymal neoplasms of low malignant potential that resembles the embryonic testis.9 The peak incidence is in the second and third decades though, they can occur at all ages.5 Histologically, the tumour recapitulate the structure of the testis.4 There are three basic histologic types: a) well differentiated forming well defined tubules; b) intermediate differentiation with biphasic pattern composed of solid pattern and abortive tubules; c) poorly differentiated or sarcomatoid containing spindle cells resembling sarcoma interspersed with scanty leydig cells.4 Other types include: pure sertoli cell tumour, tetratoid androblastoma and retiform type.76
(iii) Steroid cell tumour
Steroid cell tumour of the ovary is also known as lipid cell and lipoid cell tumour. They are composed of cells resembling lutein cells, leydig cells and adrenal cortical cells.9 Where crystalloid of Reinke are found the tumour is called Hilus cell tumour.76 Histologically, they are characterized by masses of large rounded or polyhedral cells with abundant eosinophilic or vacuolated cytoplasm that is positive for fat stains.76 These tumours can occur at all ages and is responsible for endocrine dysfunction such as Cushing’s syndrome.4 Malignant steroid cell tumour tend to be larger, about 7cm in size.76
(iv) Gyandroblastoma
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Gyandroblastoma is a very rare tumour which has a combination of both granulosa-theca cell tumour and Sertoli-Leydig cell tumour.4
(v) Gonadoblastoma
Gonadoblastoma is a rare ovarian tumour seen in women with gonadal dysgenesis and it is thought to be composed of germ cells and sex cord-stroma derivatives.5
2.10.3 GERM CELL TUMOURS
Tumours derived from germ cells constitute a 4th of all ovarian tumours.87 In adult women germ cell tumours are virtually all benign, whereas in children and young adult, they are largely cancerous.9
(i) Teratomas
Teratomas are tumours composed of different types of tissues derived from the three germ cell layers: ectoderm, mesoderm and endoderm.4 Ovarian teratomas are divided into three categories benign, immature or malignant and highly specialized.5 The best known of the highly specialized/ monodermal tumour is struma ovarii and can be found in the wall of 10% of dermoid cyst.87
a)Mature (Benign) Teratomas.
The vast majority of benign teratomas are cystic and are called dermoid cyst in clinical parlance.4,5 Typically they are unilocular cysts that contain hair and cheesy sebaceous material.5 Benign teratomas are bilateral in 10-15% of cases.5 Microscopically, the cyst
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wall is composed of mature epidermis, with skin adnexial structures such as sebaceous gland, hair shaft, neural tissue, cartilage, respiratory tissue, gastrointestinal tissue and thyroid tissue.76
Cytogenetic studies show that teratomas arise from haploid germ cell after the first meiotic division followed by endoreduplication to give rise to diploid female tumour cell (46xx).4,9 Rarely, mature solid teratoma may be found.76 It is composed entirely of benign looking heterogeneous collection of tissues from all the three germ layers.5 Extensive sampling is needed to separate this tumour from grade 1 immature teratoma.76
b) Immature teratomas
These are very rare tumours that account for 0.2% of all ovarian tumours.4 They are different from benign teratomas in that the tumour is composed of tissue that are similar to those of the fetus or embryo than the adult form.5 It occurs commonly in prepubertal adolescents and young women below the age of 20 years.9
Immature teratoma is predominantly solid and lobulated with several small cyst.9 Histologically, the tumour is composed of immature tissue with embryonic appearance that may differentiate towards cartilage, bone, neural structures, glandular structures and all other kinds of structures.4,5 Immature teratoma is graded histologically from grade I -III depending on the degree of immature tissue present.5,10 Survival corresponds to the histological grade.9 Grade I with more mature tissue and confined to the ovary have a
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better prognosis than grade III with metastasis.4,5 Immature neural tissue may be transformed to mature form at metastatic site.4
c) Monodermal or specialized teratomas
These are rare groups of tumours of which struma ovarii and carcinoid tumour are the two most important. Struma ovarii is composed almost entirely of thyroid gland tissue which can be recognized grossly and on histology.4,5
Carcinoid tumour of the ovary arises from argentaffin cells of the intestine in a teratoma.4 In large tumours greater than 7cm, the tumour may be functional, producing 5-hydroxytryptamine and carcinoid syndrome.5
(ii) Dysgerminoma
Dysgerminoma is the ovarian counterpart of testicular seminoma, and is composed of primordial germ cells.9 The neoplastic cells resembles oogonia of the foetal ovary.10,67 Dysgerminoma account for 1-2% of ovarian tumours and half of malignant ovarian germ cell tumour.4,5 They may occur in childhood but 75% of cases are seen in the second and third decades of life.5 Ten percent are bilateral and they are radiosensitive.4 On histologic examination, the dysgerminoma cells are disposed in sheets or cords separated by scant fibrous stroma with infiltration by mature lymphocytes.4
(iii) Endodermal sinus / Yolk sac
The tumour is a rare neoplasm of children and young women (median age 19 years) and is the second most common malignant tumour of germ cell origin.76 It is found in
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combination with other germ cell tumour and is rich in α-fetoprotein and α-1- anti-trypsin.4,5
(iv) Ovarian Choriocarcinoma
Primary ovarian choriocarcinoma usually occurs in young girls under the age of 20 years.4 It is an example of extra embryonic differentiation of malignant germ cells.5 They are histologically similar to the common placenta lesion and are unresponsive to chemotherapy.5
2.10.4 TUMOURS NOT SPECIFIC TO THE OVARY
Ovarian Burkitt lymphoma is rare in adulthood and occurs mostly in African children.93 At the teaching hospital Ibadan, the incidence of Burkitt lymphoma in adults was 3%.94 Another rare tumour of the ovary is ovarian leiomyoma which has been reported by Davor et al.95 The tumour was found to coexist with an endometriotic cyst.
Primary sarcomas of the ovary are also extremely rare and where they occur, there is need to distinguish it from undifferentiated carcinoma, mixed mullerian tumours, sarcomatoid form of sex cord stromal tumours, Krukenberg tumours associated with brisk stromal reaction and cellular fibroma.76 Malignant fibrous histiocytoma of the ovary is extremely rare. A case of a 22 year old female with left adnexial mass that turned out to be inflammatory malignant fibrous histiocytoma has been reported.66
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2.10.5 METASTATIC TUMOUR(S)
Metastatic tumours to the ovary are rare. In a study, only 2 cases were recorded out of a population of 175 patients.25 Metastatic adenocarcinomas to the ovary especially those with mucinous differentiation, mimic primary ovarian adenocarcinomas, a phenomenon known as maturation.9 Ovarian cancer was reported to be bilateral in 25% of cases and this occurred by metastasis from one affected ovary to the other.96 In addition, metastasis had been shown to be a late event in the clonal evolution of neoplastic parenchymal cell.96