Diseases of the Ovaries

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Non-neoplastic cystic lesions in ovaries are extremely common, the majority arising from development of Graafian follicles, others being derived from surface epithelium.
Among the main types are mesothelial-lined inclusion cysts, which are small lesions ranging from microscopic up to 3-4 cm in diameter.
They are lined by cells that are the same as those of the ovarian surface epithelium, and are filled with clear fluid.
Follicular cysts are derived from ovarian follicles and are lined by granulosa cells, with an outer coat of thecal cells. Cysts are, by definition, over 2 cm in diameter.
In some cysts the thecal coat becomes luteinized. Although most cysts are clinically insignificant, some may be a cause of hyperoestrogenism.
Corpus luteum cysts are caused by failure of involution of the corpus luteum. Cysts are typically 2-3 cm in diameter, with a thick, yellow lining of luteinized granulosa cells.
There is continued production of progesterone, resulting in menstrual irregularity. Theca-lutein cysts are usually seen as multiple bilateral cysts, up to 1 cm in diameter, filled with clear fluid. They are caused by high levels of gonadotrophin, which precipitates follicle development (e.g. in hydatidiform mole and drug treatment). Endometriosis may be the cause of cystic ovarian lesions filled with dark brown, iron-containing fluid.

Polycystic ovary syndrome (Stein-Leventhal syndrome) is a common cause of infertility
The polycystic ovary syndrome is an important and common cause of infertility.
Patients are obese, hirsute, and have acne and menstrual abnormalities (amenorrhoea or irregular periods). The ovaries show thickening of the capsule, and multiple follicular cysts with stromal hyperplasia.
The pathogenesis of this syndrome is still uncertain.
Patients have a persistent anovulatory state, high levels of LH and oestrogen, low levels of FSH with high levels of circulating androgen produced by the ovary. There is insulin resistance and hyperinsulinism.
The high oestrogen levels may cause endometrial hyperplasia and increase the risk of development of endometrial carcinoma.
It is not uncommon to see luteinizing hormone-driven ovarian hyperandrogenism, acne, anovulation, oligomenorrhoea, and large, multifollicular ovaries in early to mid-puberty, arising as a self-limited maturational stage in development. However, it is not possible to tell if this is a precursor of polycystic ovary syndrome in a proportion of cases.

Neoplastic diseases of the ovaries
Primary tumours of the ovary may be derived from any of the normal cellular constituents of the ovary. They are divided into those derived from surface epithelium (70%), those from sex-cord and stromal cells (10%), and those from germ cells (20%).
In addition to primary tumours, the ovary is frequently involved in metastatic disease from other sites. Malignant tumours of ovary spread locally and particularly seed to peritoneum, when ascites is an important complication.
Epithelial tumours of the ovary can differentiate into several types
The epithelial tumours of the ovary are derived from the surface epithelium which is, in turn, derived from embryonic coelomic epithelium. Tumours with this origin differentiate into a variety of tissues.
Endocervical differentiation: mucinous ovarian tumours.
Tubal differentiation: serous ovarian tumours.
Endometrial differentiation: endometrioid and clear-cell ovarian tumours.
Transitional differentiation: Brenner tumours.
In histological assessment of epithelial tumours of the ovary, it can be difficult deciding which lesions are benign and which are malignant. In between those tumours that are obviously benign or malignant are some cases in which there are histological features of atypical cells and abnormal tissue architecture, but no evidence of invasion. Such lesions are termed 'tumours of borderline malignant potential'. Most borderline tumours behave in a benign fashion, the remainder behaving as low-grade malignant tumours.
Serous tumours of the ovary contain watery fluid and are often bilateral.
Benign serous tumours of the ovary (70% ) are termed 'serous cystadenomas'. These thin-walled, unilocular cysts contain watery fluid and are bilateral in about 10% of cases. Histologically they are lined by a cuboidal, regular epithelium in which small papillary projections may be seen. A related tumour, termed an adenofibroma, is a benign, sometimes solid and sometimes cystic (cystadenofibroma) tumour, composed of benign serous epithelium and spindle-cell stroma.

Malignant serous tumours of the ovary are termed 'serous cystadenocarcinomas'. These are the most common form of ovarian carcinoma and are bilateral in about half of all cases. Macroscopically, tumours may be cystic, mixed solid and cystic, or largely solid in appearance. Histologically they are composed of cystic cavities lined by columnar and cuboidal cells, with papillary proliferations of cells and solid areas. Cells are pleomorphic and mitoses are seen. Importantly, invasion of the ovarian stroma does occur, confirming the malignant character. These lesions are associated with an overall 20% five-year survival. Borderline serous tumours of the ovary are bilateral in about 30% of cases. Macroscopically, tumours may be cystic, or mixed solid and cystic. Histologically they are composed of cystic cavities lined by columnar and cuboidal cells, with papillary proliferations of cells and solid areas. Cells are pleomorphic and mitoses are seen. However, invasion of the ovarian stroma does not occur, despite the presence of cellular atypia. These lesions are associated with an overall 75% ten-year survival.

Molecular pathology of ovarian carcinoma
Endometrioid tumours of the ovary are usually malignant and often bilateral
Brenner tumours of the ovary contain transitional-type epithelium...
Mucinous tumours of the ovary are usually multilocular and contain gelatinous material
Benign mucinous tumours of the ovary are multilocular cystic lesions that contain glutinous viscid mucoid material. They are bilateral in only 5% of cases. Histologically the cysts are lined by a single layer of columnar, mucin-secreting cells with regular nuclei and no atypical features or mitoses.
Malignant mucinous tumours of the ovary, termed 'mucinous cystadenocarcinomas' are bilateral in 25% of cases. These tumours may occur in young women, and the median age at diagnosis is 35 years. Macroscopically they are multilocular cystic lesions that contain viscid or gelatinous mucoid material. They may grow to a very large size. Solid areas may be seen in the walls of some cysts. Histologically the tumours are composed of columnar, mucin-secreting cells, which show heaping of nuclei, solid areas, pleomorphism and mitoses. Importantly, invasion of ovarian stroma is seen, confirming the malignant nature of the lesion. Overall survival is 34% at ten years. Borderline mucinous tumours of the ovary are bilateral in 10% of cases. Apart from the fact that there is no evidence of invasion of ovarian stroma, they resemble mucinous cystadenocarcinomas macroscopically and histologically. Overall survival is 90% at ten years.
There are several forms of sex-cord stromal tumours of the ovary
About 10% of ovarian tumours are derived from the stromal cells and sex-cord cells of the ovary. As several of this group secrete oestrogen, patients may develop endometrial hyperplasia and a predisposition to endometrial neoplasia.

Fibromas are benign tumours, usually seen in post-menopausal women. They are tough, whorled, white lesions composed of spindle cells and collagen.
Thecomas are solid tumours composed of the spindle cells of the ovarian stroma. These stromal cells are commonly functional, producing oestrogen. The vast majority of lesions are benign.
Some lesions show features of fibroma with focal areas developing features of thecoma (fibrothecoma). This reflects a common origin of both fibroma and thecoma from the spindle cells of the ovarian stroma.
Granulosa-cell tumours are composed of the granulosa cells derived from follicles. Around 75% secrete oestrogen and present with signs of hyper-oestrogenism. There are several forms of sex-cord stromal tumours of the ovary
Macroscopically, tumours are soft and yellow, and can vary in size from a few centimetres to large masses. If confined to the ovary, they are associated with an excellent prognosis. If tumours are large or extend outside the ovary, they are more likely to behave in an aggressive manner, with local recurrence or metastasis.

Sertoli-Leydig cell tumours (androblastomas)} are very uncommon and most are small benign lesions confined to the ovary. They may cause masculinizing effects from secreted hormones. Fibrothecoma of the ovary.
A large, well-circumscribed, spherical tumour with a whorled cut-surface appearance replaces one ovary. The slightly yellow tinge is a reflection of accumulated lipid within the plump spindle cells of the thecoma component. On the left is the cut surface of the attached uterus.
Germ-cell tumours of the ovary may be benign or malignant, histologically resembling those seen in the testis
Germ-cell tumours account for 20% of ovarian neoplasms, occurring from childhood onwards. The classification of these lesions closely follows that for germ-cell tumours of the testis .
Benign cystic teratomas (dermoid cyst of ovary) are the most common ovarian germ-cell tumours, accounting for about 10% of all neoplasms of the ovary, Macroscopically the affected ovary is replaced by a cyst lined by skin with skin appendage structures, particularly hair, Teeth, bone, respiratory tract tissue, mature neural tissue and smooth muscle are other common elements. Lesions can vary in size from 2-3 cm up to masses that are 10-20 cm in diameter. These lesions are benign, but are bilateral in 10% of cases.
A small number of cases develop secondary malignant change in one of the elements of the teratoma, commonly squamous-cell carcinoma of the epidermal component. Solid teratomas are very uncommon and are seen mainly in adolescents.
These large, solid lesions are composed of a variety of tissue components such as squamous epithelium, cartilage, smooth muscle, respiratory mucosa, and neural tissue. In most cases, small areas of primitive embryonal tissue are also seen, or other types of germ-cell tumour are encountered (classifying the lesions as 'malignant immature teratoma' or 'mixed malignant germ-cell tumour with a propensity for metastasis respectively).

In cases in which only mature tissues are seen, there is a good prognosis after removal.
Struma ovarii is composed of mature thyroid tissue. Considered by many to be a teratoma with only one line of maturation, it may cause hyperthyroidism.
Dysgerminomas of the ovary are similar to seminomas of the testis. Affected ovaries are enlarged and replaced by soft ,white tumour with histological appearances like those seen in seminoma.
Yolk-sac tumour is a rare, highly malignant form of germ-cell tumour, usually seen in women under the age of 30 years. Lesions are typically large and necrotic, secreting a fetoprotein detectable in the blood as a tumour marker.
Choriocarcinoma is a rare form of germ-cell tumour composed of trophoblastic cells. It is highly malignant, with a propensity for vascular spread. Tumours secrete HCG, which can be used as a tumour marker.
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