Ovarian Cysts and Benign Overay Neoplasms: Causes

Pathogenesis (disease development)

The pathogenesis of most benign (benign) neoplasms of the ovary is unknown. Some exceptions are:

• Functional cysts (retention cysts):
  • Endometriosis cysts (chocolate cysts,tar cysts): the pathogenesis is unclear. There are currently several theories:
    • Immunological theory – this theory describes a possible immunodeficiency of affected women.
    • Metaplasia theory – this theory assumes that metaplasia (cell changes) are stimulated by irritation of the epithelium
    • Transplantation theory – this assumes that during menstruation endometrial tissue retrograde (backwards) via the tubes (fallopian tubes) into the abdominal cavity.
  • Corpus luteum cysts are caused by hormonal changes after ovulation (luteinization of the Graaf follicle after ovulation).
  • Follicular cysts occur during cycle irregularities (failed ovulation/ovulation).
  • Thecalutein cysts (granulosa theca lutein cyst, lutein cyst) arise due to high HCG levels (human chorionic gonadotropin levels).
  • PCO syndrome (polycystic ovaries, polycystic ovary syndrome, Stein-Leventhal syndrome, polycystic ovary syndrome, polycystic ovary syndrome, sclerocystic ovary syndrome): Pathogenetically, there is a disturbance of the regulatory circuit between the pituitary gland (pituitary gland) and ovary (ovary), the cause of which is unknown.

Etiology (causes)

Biographical causes

• Corpus luteum cyst: Because a cyclic event is necessary for its formation, it develops during sexual maturity.
• Endometriosis cysts (chocolate cysts, tar cysts): since a cyclic event is necessary for the formation, they develop during sexual maturity.
• Follicular cysts: Since a cyclical event is necessary for the formation, they develop during sexual maturity, especially in times of hormonal change (puberty, menopause).
• Germinal epithelial cysts: arise during menopause as invaginations of the covering epithelium.
• Luteoma gravidarum (pregnancy luteoma): development is pregnancy-dependent.
• PCO syndrome (polycystic ovaries, polycystic ovary syndrome, Stein-Leventhal syndrome, polycystic ovary syndrome, polycystic ovary syndrome, sclerocystic ovary syndrome): Genetic burden from parents, grandparents is suspected, as a familial cluster is observed.
• Thecalutein cysts (granulosa theca lutein cyst, lutein cyst): they develop as a result of high human chorionic gonadotropin concentrations at the time of sexual maturity, in case of childbearing problems or in multiples.

Epithelial tumors (tumors from surface epithelial cells,tumors of the covering epithelium with all levels of differentiation of the Müller-Gang epithelium, tumors from derivatives of the paramesonephric celomic epithelium).

• Adenomatoid tumors: they probably arise from cells of the mesothelium (mesenchyme-derived polygonal squamous epithelium of the serous skins (pleura/chest, pericardium/heart sac, peritoneum/belly)). They grow to 1-5 cm in size. They are often incidental findings.
• Brenner tumors (* extremely rare): arise from fibrous ground tissue with epithelial islands of urothelial character, often occur in women > 50 years, unilaterally, and can produce estrogens. Because they are usually very small (< 2 cm), they are often incidental findings.
• Endometrioid tumors* : They arise from endometrial-like tissue (endometrium = uterine lining) as kystadenoma, adenofibroma and kystadenofibroma. They account for about 10% of epithelial ovarian tumors.
• Kystadenomas: These are unicompartmental or multicompartmental cystic neoplasms with varying histologic structure.
  • Kystadenofibromas are rarely occurring tumors that are structured like a serous kystadenoma and sometimes contain fibromatous white connective tissue sections.
  • Surface papillomas* are rarely occurring tumors that are structured like a serous kystadenoma and bear papillary structures on the surface and often a cystadenofibroma-like core in central portions. They are usually medium-sized, bilateral, and associated with ascites (abdominal fluid). Peritoneal (“affecting the peritoneum” settlements are possible.
  • Mucinous kystadenomas* (about 15% of all ovarian tumors) are composed of a single row of mucinous cylinder epithelium and are smooth on the surface; internally, they may have wart-like papillary growths. They are usually unilocular and unicompartmented, rarely multilocular. The cyst contents, which consist of a mucilaginous, thin or viscous, gelatinous substance, are called pseudomucin. If a cyst ruptures spontaneously or during surgery, viable, mucus-forming epithelial cells settle in the abdomen, resulting in what is known as a bilious cyst (pseudomyxoma peritonei). Although it is a benign tumor, this leads over many years to cachexia (morbid, severe emaciation) and death of the patient.
  • Serous kystadenomas* (about 30-35% of all ovarian tumors) consist of a single-row cylindrical epithelium and are smooth on the surface. The inner surface may be smooth or have papillary structures. They occur in single or multiple chambers, filled with serous, protein-rich fluid, often bilaterally, and may be very large. Occasionally, they fill the entire abdominal cavity. They are predominantly observed in the second half of sexual maturity.

Germ cell tumors (about 25% of all ovarian tumors): most of these tumor types occur in early sexual maturity (up to 20 years of age). They arise from scattered embryonic tissue containing portions of all three germ layers. Monodermal forms are the exceptions.

• Gonadoblastomas* (germinomas; gonads = gonads) are rare tumors. They usually occur bilaterally, in both women and men. They arise in women with impaired gonadal development (gonadal dysgenesis) and almost exclusively in dysgenic gonads of patients with a Y chromosome in the chromosome set. (Females with gonadal dysgnesia often do not have two X chromosomes, but only one or, instead of the second X chromosome, one Y chromosome.) These patients are usually phenotypically female and genotypically male, with hypoplastic internal genitalia (intersex patients). The tumors consist of germ cell derivatives, Sertoli and/or granulosa cells. They may form androgens or estrogens or be hormone inactive. The risk of tumor formation is > 30%. For this reason, complete removal of both ovaries before puberty is often recommended.
• Teratoma adultum: It is the most common form of germ cell tumors (about 15% of all ovarian tumors). The tissue is differentiated. Solid and cystic tumors occur:
  • Dermoid cyst = cystic form (about 10-25% of all benign ovarian tumors): 8-15% are bilateral. Of the three cotyledons, ectodermal tissues predominate, followed by mesodermal and entodermal. The cyst contents are doughy, oily and contain hair, sebum, bone, teeth, cartilage, nails and others.
  • Solid form: it is rare. Only about 10% of all solid teratomas are of mature, or benign, tissue. Of the three cotyledons, the glial and mesodermal components predominate
  • Struma ovarii (monodermal form): this tumor type includes about 3% of mature teratomas. Most are hormone inactive, and some may present with the clinical signs of hyperthyroidism (hyperthyroidism).
  • Carcinoid (monodermal form): carcinoids are very rare tumors, some cystic, some solid. The predilection period is perimenopause or menopause (age peak 65 years). According to the secretion of serotonin, especially in larger tumors, symptoms of the so-called carcinoid syndrome may develop in > 30%: Flushing, flushing, dizziness, visual disturbances, gastrointestinal pain, asthma attacks.

Lipid cell tumor* (adrenal remnant tumor, hypernephroid tumor) (scattered adrenal cortical tissue): these are rare, usually small, tumors of scattered adrenal cortical germs occasionally found in the ovarian hilum. They are histologically similar to the adrenal cortex. Virilization (masculinization), occasionally a Cushing’s syndrome-like picture, occurs in about 10%. Stromal tumors of the germinal cord (germinal cord stromal tumors, tumors of the endocrine-differentiated gonadal mesenchyme (sex cord)).

• Androblastoma (arrhenoblastoma, Sertoli-Leydig cell tumor) (predominantly androgen-forming)* : Tumors are rare (0.2% of all ovarian tumors), usually unilateral, small, and coarse. They occur predominantly in younger women. In 40-60% they are androgen-forming (amenorrhea/absence of menstruation (> 3 months), virilization).
• Fibroma (ovarian fibroma): 4-5% of all ovarian tumors are fibromas. They occur in all age groups, but are clustered after the age of 50. They are usually unilateral, dermal tumors, occasionally with cystic degeneration. Mixed forms with thecomas include thekofibroma (fibroma xanthomatodes). About 40% of the mostly larger (> 7-10 cm) ovarian fibromas are associated with ascites. If there is also a pleural effusion (about 1%), this combination is called Meigs syndrome.
• Granulosa cell tumor (estrogen-forming)* : They account for 1-2% of all ovarian tumors and 70% of all estrogen-producing tumors. In children (juvenile type about 5%) they are associated with pubertas praecox, in adults (adult type, in 2/3 after menopause/menopause) with glandular-cystic endometrial hyperplasia (a particular form of abnormal increase in volume of the endometrium). The solid-cystic tumors reach a mean size of 12 cm and are > 95% unilateral.
• Gynandroblastoma (estrogen- or androgen-forming)* : It is a very rare tumor that contains granulosa and/or theca cells and Sertoli-Leydig cells.
• Hilus cell tumor (mostly androgen-forming)* : It is a very rare, usually unilateral, well encapsulated small tumor usually in the ovarian hilus area. It contains intermediate Leydig’s cells, corresponding to those found in the testis, with the typical so-called Reinke crystals (histologically proving). The tumor is predominantly benign and usually forms androgens with clinical signs of virilization.
• Luteoma gravidarum (pregnancy luteoma) (progesterone and or androgen-forming): they are very rare ovarian tumors occurring during pregnancy, made of theca and granulosa cells, 6-10 cm (-20cm) in size. 30-50% occur bilaterally. After gravidity they regress spontaneously. In the case of androgen formation, depending on the amount of androgens, there may be virilization symptoms in the mother and female fetuses.
• Theca cell tumor (thecom) (estrogen-forming)* : They account for only 0.5-1% of all ovarian tumors and occur preferentially in older women. They are usually unilateral, dermal tumors with intense yellow color. Most often they form estrogens (endometrial hyperplasia / increase in volume of the endometrium), rarely androgens (virilization / masculinization).

Tumor-like diseases

• Tumor-like, but not neoplastic, predominantly cystic changes, i.e., true ovarian cysts = functional cysts or retention cysts arise
  • By passive stretching of existing cavities
  • By fluid secretion or bleeding from follicles (follicular, corpus luteum, thecalutein cyst, corpus albicans (cysts)),
  • By invaginations of the covering epithelium (germinal epithelial cysts), from heterotopic epithelium (endometriosis cysts).

  Caused by gonadotropins (sex hormones that stimulate the gonads), endogenous local ovarian hormones and exogenous hormone therapy. Regular and irregular cystic, solid and cystic-solid tumor-like structures may develop. They may show growth and regression processes.

• Corpus luteum cysts:
  • Corpus luteum menstruationis: It develops from the remains of the ruptured Graaf follicle and produces estrogens and progesterone. Hemorrhage gives rise to the corpus rubrum (corpus haemorrhagicum), which after a short time turns yellow due to progesterone production. A small corpus luteum is solid. A larger one contains a cystic cavity. After the absence of pregnancy, the corpus luteum spontaneously regresses. In the case of cysts, this may take months. The final state is called the corpus albicans.
  • Corpus luteum graviditatis: If pregnancy occurs, the corpus luteum enlarges due to HCG (human chorionic gonadotropin) mediated hormone formation, which lasts until about the tenth week of pregnancy. After that, the regression takes place.
  • Corpus albicans: After loss of function, the corpus luteum is scarred and remains visible in the ovary as a whitish discoloration.
• Endometriosis cysts (chocolate cysts, tar cysts) arise in the context of endometriosis by deposition of endometrium (endometrium) in the ovary. There, the endometrium undergoes hormonal cyclical changes. In the first half of the cycle, the mucosa grows and is shed at the end of the cycle. The rejected mucosa collects in a blood-filled cyst in the ovary.
• Follicular cysts: they develop from an unruptured Graaf follicle containing the oocyte, which continues to produce fluid. The cysts are usually only 2-3 cm in size, but can be as large as 15 cm. They spontaneously regress after 6-8-12 weeks.
• Germinal epithelial cysts: they develop at menopause as multiple bark cysts several millimeters in size, lined with covering epithelium, without clinical manifestations. .
• PCO syndrome (polycystic ovaries, polycystic ovary syndrome, Stein-Leventhal syndrome, polycystic ovary syndrome, polycystic ovary syndrome, sclerocystic ovary syndrome): This is a disorder of the hypothalamic-pituitary-ovarian regulatory circuit, the exact origin and cause of which is unclear. It possibly results from decreased activity of aromatases in the granulosa cells of the ovary. The disease usually manifests between the ages of 20 and 30. Frequency: about 5-10% of women of childbearing age. The cyst walls contain theca cells that produce androgens. The resulting hyperandrogenemia leads to virilization/masculinization, cycle disorders (oligomenorrhea/interval between bleeding is > 35 days and ≤ 90 days, i.e. bleeding occurs too infrequently, amenorrhea/absence of menstruation (> 90 days), anovulation/absence of ovulation), obesity and often infertility. The sonographic image shows bead chain-like polycystic structures in both ovaries. The ovarian capsule (tunica albuginea) is fibrously thickened.
• Thecalutein cysts (granulosa theca lutein cyst, lutein cyst): thecalutein cysts develop in ovarian hyperstimulation, multiple pregnancies, bladder mole and chorionic epithelioma due to high HCG (human chorionic gonadotropin) concentrations. They can become very large, usually occur bilaterally and regress very quickly after the HCG level drops.

Optional malignant tumors are marked with an * .