Pathology Associates Of Lexington, P.A.
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        Fallopian Tubes and Ovary: [PCOS]
      
Multiple Cysts of Follicular Origin & Polycystic Ovary Syndrome (PCOS)
The normal adult ovary: measures approximately 3-5 cm in length, 1.5-3 cm in width, and 0.5-1.5 cm in thickness (length X width X thickness X 0.523 = approximate volume in cc). Normal ovarian volume in the menstruating females is 5-15 cc, with an approximate mean of 10 cc; however, measurements as high as 22 cc have been reported in normal ovaries. Each weighs between 5-8 g. The volume in cc is roughly equal to the grams in weight. Ova, during physiological enlargement of the follicle toward ovulation, develope a space amongst the granulosa cells which is considered by many as "normal" when less than 2.5cm. There is normally a thin theca cell layer peripheral to the granulosa cell component. In fertility clinics, ultrasound is used to obtain "antral follicle" counts8 which are follicular cysts 2-8 mm in size. So, a clinically significant multicystic or polycystic ovary has (1) more than a couple of cysts of larger size and (2) less oocytes than one would guess an antral follicle count would show.

Polycystic ovary syndrome (PCOS):

This syndrome is discovered deliberately during an infertility or amenorrhea work up. Or polycystic ovaries are incidentally detected during abdominopelvic ultrasound or MRI exams. That polycystic ovaries might herald both the "insulin resistance syndrome" (metabolic syndrome details; syndrome X; MSX; Reaven's syndrome) [definition] and an increased risk of endometrial cancer and cardiovascular disease mean that we should not miss the opportunity to specifically suggest the generic diagnosis. Since the metabolic syndrome causes a proportion of cases of polycystic ovaries, the patient must be diagnoseable as metabolic syndrome to be sure that it is basis of her multicystic ovaries. Otherwise, there must be some other etiology or [L13-14267 28 y/o] just within the range of "average normal". Clinically, aside from central obesity, the skin disorder acanthosis nigricans can also herald this MSX syndrome. Multicystic ovaries might also herald rare things such as prolactinoma.

There are multiple etiologies, and each etiology might also be complicated by the medical condition of insulin resistance which also tends to have some relationship to the liver "fatty liver" condition, NASH.

PCOS is one of the subgroups of disorders comprising the more generic category "sclerocystic ovaries", below. Prior to 1990, NIH Criteria6 of 1992 (1) chronic oligo-anovulation and (2) evidence of androgen excess (hirsutism & acne; male pattern alopecia; elevated testosterone) for which there is no other cause; and the Rotterdam Criteria6 of 2006 add (3) presence of polycystic ovaries...this increased the diagnoses by 50%. Some would add (4) insulin resistance (only about 50% have insulin resistance5) with an average chronic elevation of blood insulin levels which is reflected in elevations of C-peptide. Only a fraction of women with polycystic ovaries have PCOS. Of all women with "insulin resistance", not all have PCOS5. It is the most common endocrine disorder in women and the most common cause of female infertility5!...5-10% of women (about 3.5-5 million reproductive-age women in USA). [PCOS website]

Polycystic ovary syndrome; Stein-Leventhal syndrome (or polycystic ovary disease):  Women with PCOS (POD or PCOD) have normal reproductive organs, otherwise (such as the uterus and fallopian tubes). Their ovaries usually contain about 10 or more small cysts located at the periphery of the ovary. The size of these cysts generally are less than 8 mm and can be detected by ultrasound (string of pearls) examination. These cysts do not appear to grow and usually remain small. They do not require surgical removal. Additionally, these cysts do not represent cancer and are not associated with an in-creased risk of ovarian cancer.

Prevalence of polycystic ovaries in the pathology lab:

The reason we should recognize incidental PCOS ovaries (they were not removed specifically because of PCOS) in general surgical pathology is because of the usually-associated clinical features of androgen excess (with unopposed estrogen increasing risk of endometrial cancer), insulin resistance, obesity, higher risk of diabetes and CHD...some having dyslipidemia and hypertension (qualifying for the "metabolic syndrome"). This is a significant & common, manageable medical disease.

Diagnosis by U/S:

Polycystic ovaries typically exhibit 3 characteristics on sonographic examination: bilateral enlarged ovaries, multiple small cystic follicles ("pearl necklace sign" or "string of pearls"), and increased stromal echogenicity; and, since 20-30% of women have polycystic ovaries at U/S5, not all polycystic cases are PCOS; more as to U/S:

  1. Usually, the ovaries are enlarged symmetrically. The shape changes from ovoid to spherical. Ovarian volume can increase by as much as 6 mL; however, almost 30% of patients with a biochemical and pathologic diagnosis of polycystic ovaries have no increase in ovarian volume by U/S.
  2. The typical polycystic ovary contains numerous cystic follicles at any given time. The follicles are small, sized 0.5-0.8 cm, and no dominant follicle is present. Characteristically, the follicles are peripherally located in the cortex; however, they can occur anywhere in the ovarian parenchyma. The U/S diagnosis of polycystic ovaries should be reserved for patients with at least 5 of these follicles in each ovary.
  3. Typically, the ovaries are hypoechoic in relation to the surrounding pelvic fat and myometrium. Polycystic ovaries often display increased echogenicity; however, as many as one third may remain isoechoic or hypoechoic relative to the myometrium.
The reason for multiple cyst development is not clear. It may be related to the inability of ovulation in PCOS. In comparison to normal ovulation, women with PCOS are usually unable to completely develop a fully mature egg (on their own) due to abnormal pituitary FSH and LH secretion. As a result, the ovulatory process is not completed; and the partially stimulated follicle becomes cystic, followed by degeneration of the egg.
The problems of irregular or absent menstrual bleeding, excess hair growth & maybe acne (evidence of androgen excess, 50% of cases) and infertility are a result of abnormal hormone secretion by the pituitary gland (FSH and LH) and the ovaries (estrogen, androgen...testosterone...and progesterone). Despite irregular ovulation in PCOS, the ovary continues to be stimulated by FSH and LH in an uncoordinated manner, which leads to a constant production of estrogen, excessive amounts of androgen, and very little progesterone.

Pathology: Usually bilateral, smooth surfaced, whitish surfaced ovaries with multiple (5 or more per ovary) 5-8 mm cysts, usually peripheral. Outer cortex often seems fibrotic, collagenized; about 30% of cases have a corpus luteum or two on cut surface; and the multiple cysts are there..."sclerocystic ovaries"[LMC-03-6642]. Ovaries usually, not always, enlarged; medullary stroma with few to no signs of previous ovulation. Most of the cystic follicles are poor in granulosa lining cells & prominent in luteinized theca interna cells. Often have cortical & medullary stromal hyperplasia, sometimes with hyperthecosis. Endometrium varies from a hypoactive or proliferative to cystic hyperplasia to atypical hyperplasia, a low percentage having adenocarcinoma (usually well differentiated).


Entities with numerous small follicular ovarian cysts:

  • Ovarian folliculo-stromal "hyperreactio luteinalis" (HL): multiple theca-lutein cysts and/or thecosis (with or without luteinization) of ovarian stroma which may be luteinized (and may or may not have a yellow color on cut surface) & may cause virilization in mother and/or the newborn (eg., ambiguous genitalia [L07-8857]); seen where high levels of HCG (hydatidiform mole, choriocarcinoma, fetal hydrops, & multiple gestations, and rare single gestation [in PCOS with a dermoid L07-8857]) or in ovaries which are hypersensitive to HCG.
  • Ovarian hyperstimulation syndrome: like HL; but when the woman is being induced to ovulation with FSH followed by HCG or rarely by clomiphene alone.
  • Juvenile hypothyroidism: 75% of these girls have multicystic ovaries.
  • polycystic at onset of puberty: most cases soon revert to normal.
  • Premature infants: may have multicystic ovaries.
  • Congenital deficiency of 17-hydroxylase: patient has absence of sexual maturation and primary amenorrhea.
  • "sclerocystic ovaries" [the basic, generic term] (anything causing chronic oligo-anovulation in the premenopausal women): true PCOS; the metabolic syndrome; adrenal hyperplasias & adenomas & virilizing adrenal tumors; primary hypothalamic-pituitary disorders (especially when prolactin is elevated); and ovarian lesions producing excessive levels of estrogens or androgens (thereby cause virilization and maybe even be basis for androgenetic alopecia, sometimes), such as ovarian stromal hyperplasia [L09-15212] (SH) and stromal hyperthecosis (HT...if much luteinization, cut surface may look yellowish)...SH usually in 6th & 7th decades and noted in 33% of autopsies in that age group. HT in 6th to 9th decades and noted in 33% of autopsies in that age group. Ovaries from normal to enlarged & cut surface of firm white to amber to yellow tissue ([LMC-03-5122; LMC-04-1035]; LMC-04-6303). Stroma may be just thecomatous or may show variable luteinization with clear to foamy cytoplasm. (LMC-03-5221; LMC-03-5811; LMC-03-6092; LMC-03-8735; LMC-04-2460). May see after cessation of long-term oral contraceptive use; may see in instances of periovarian adhesions.

References:

  1. Blaustein's Pathology of the Female Genital Tract, 4th Ed., 1994.
  2. Atlas of Gynecologic and Obstetric Diagnostic Pathology, Janovski NA & Dubrausky V,  1967.
  3. Sternberg (pathology textbook).
  4. NEJM 2005
  5. J. of Clinical Outcomes Management, 12(4):218, April 2005.
  6. Legro RS, "Clinical Crossroads" section, JAMA 297(5):509-519, 7 February 2007.
  7. the eMedicine paper on this condition [HERE].
  8. Antral follicle count, Advanced Fertility Center of Chicago, HERE.

(posted 19 May 2003; latest additions 18 November 2013)

 
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