Ovary-nontumor Printer Friendly Version

Ovary-nontumor - Printer Friendly Version

Last revised 7 February 2009

Last major update February 2009

Table of Contents

Primary references, embryology, normal anatomy, normal histology

Gonadal dysgenesis: general, pure, mixed, female pseudohermaphroditism, testicular feminization, true hermaphroditism, Turner’s syndrome

Inflammatory disorders: abscess, autoimmune oophoritis, eosinophilic perifolliculitis, giant cell arteritis, gonorrhea, granulomatous inflammation, microsporidia, pelvic inflammatory disease

Non-neoplastic cysts/other: DD of small cystic follicles, calcification, cholelithiasis, corpus luteum cyst, developmental cyst, ectopic decidual reaction, endometriosis, endosalpingiosis, epidermoid cyst, follicular cyst, germinal inclusion cyst, heterotopic ovarian splenoma, hyperreactio luteinalis, hyperthecosis, hypothyroidism, large solitary luteinized follicular cyst of pregnancy and puerperium, massive edema, ovarian pregnancy, polycystic ovary disease, postoperative carbon pigment granuloma, pregnancy luteoma, rete ovarii cyst, splenic gonadal fusion, stromal hyperplasia, supernumerary ovaries, torsion, uterus-like mass

Primary references - Ovary chapter

AJCC Cancer Staging Manual (6th Ed)

American Journal of Clinical Pathology, January 1975 to February 2009

American Journal of Surgical Pathology, March 1977 to February 2009

Archives of Pathology and Laboratory Medicine [always free full text and no registration], January 1976 to January 2009

Biomed Central [always free full text and no registration], 27 May 1999 to 3 February 2009

Human Pathology, December 1971 to February 2009

Modern Pathology [free full text and no registration after 1 year], March 1988 to February 2009

Rosai, J: Ackerman’s Surgical Pathology (9th Ed), Mosby, 2004

Scully: Tumors of the Ovary, Maldeveloped Gonads, Fallopian Tube, and Broad Ligament (AFIP Atlas of Tumor Pathology, Series 3, Vol 23); 1999

Tavassoli: Tumours of the Breast and Female Genital Organs (WHO, 2003)

Websites: PathoPic

Journal search terms: each disease entity listed - last searched January 2009

Please refer to these primary references for more detailed discussions and photographs

Embryology of Ovary - Ovary chapter

First, germ cells migrate from yolk sac to posterior body wall at level of T10 to enter Genital Ridge

Then germ cells differentiate into oogonia, then primary oocytes, then arrest until puberty

Then ovary descends to pelvis along gubernaculum (attached inferiorly to inguinal region); gubernaculum becomes part of uterine wall at entry of fallopian tube, and persists in adults as ovarian and round ligaments

Future ovarian surface epithelium (OSE) forms part of coelomic epithelium, the mesoderm derived epithelial lining of intraembryonic coelom; overlies presumptive gonadal area and gives rise to gonadal blastema

At 10 weeks to 5 months, OSE becomes multistratified and papillary on well defined basement membrane, but reverts to single layer by term

OSE is negative for CA125, unlike other coelomic derivatives

Gonadal development is influenced by both male and female promoting signals (Mol Endocrinol 2008;22:1)

Normal anatomy - Ovary chapter

Paired ovoids close to lateral pelvic wall, behind broad ligament, anterior to rectum

Connected to broad ligament by mesovarium (double fold of peritoneum), to uterine cornu by utero-ovarian ligament, to lateral pelvic side wall by infundibulopelvic (suspensory) ligament

Premenopausal ovaries are each 4 cm long and weigh 5-8 g
Neonates often have cysts, which spontaneous resolve (J Pediatr Endocrinol Metab 2007;20:397)

Lymphatic drainage to para-aortic, internal iliac, external iliac, common iliac, sacral, obturator, pelvic, retroperitoneal, inguinal nodes image (AFIP)

Function first described by Reinier de Graaf (Arch Pathol Lab Med 2000;124:1115)

Ovulation: induces cyclic rupture and regenerative repair of the ovarian coelomic epithelium

References: Wikipedia

Normal histology- Ovary chapter

Covered by surface epithelium (modified mesothelium, also called coelomic or germinal epithelium, Reprod Biol Endocrinol 2006 Aug 21;4:42), which is one layer of flat to cuboidal mesothelial-type cells, which appear to actively participate in ovulatory rupture and repair process; are closely related to mullerian duct lining epithelium

Follicles: primordial, maturing (primary, secondary, tertiary, graafian), atretic; corpora lutea, corpora albicantia; 400K primordial follicles containing primary oocytes are present at birth in ovarian stroma (100K at gestational age 15 weeks, 680K at 8 months, Fertil Steril 2007;88:675); follicular decay appears to advance with increasing age (Hum Reprod 2008;23:699)

primordial follicle: travels from yolk sac endoderm to ovary, develops into oogonia and oocytes, arrests at prophase of mitosis; neo-oogenesis may occur in adults (Endocrine 2005;26:301)

maturing follicle: oocyte with granulosa layer; lacks reticulum; contains Call-Exner bodies (rosette-like formations with central filamentous / eosinophilic material consisting of excess basal lamina), theca cells (within follicle are luteinized and produce sex hormones; external to follicle are very cellular); immunoreactive for vimentin, keratin, desmoplakin

Corpus luteum: 2 cm, round, yellow, lobulated structure with cystic center; has luteinized granulosa and theca cells; in pregnancy is larger, bright yellow with prominent central cavity, hyaline droplets and calcification

Corpus albicans: remnant of corpus luteum

Hilus (hilar) cells: in ovarian medulla, round to polygonal, epithelial appearing, presumed vestigial remnant of gonad from its "ambisexual" phase; produce steroids; resemble Leydig cells of testis; may produce masculinizing tumors (hilar cell tumors); closely associated with large hilar veins and lymphatics and may protrude within their lumina; also associated with nerves; may contain Reinke’s crystalloids, lipid, lipochrome pigment; resemble steroid cells by EM with microtubular smooth endoplasmic reticulum, mitochondria with tubular cristae

Hilar cell hyperplasia: associated with hCG administration, pregnancy, choriocarcinoma

Hilar mesonephric rests: case report of association with nonteratoid prostatic differentiation in 70 year old woman (Am J Surg Pathol 1999;23:232)

Rete ovarii: counterpart of rete testis; clefts, tubules, cysts, papillae lined by epithelium, surrounded by spindle cell stroma

Stroma: in whorls/storiform pattern, resembles fibroblasts, surrounded by dense reticulin network; stroma contains luteinized stromal cells, decidual cells, smooth muscle, fat, neuroendocrine cells, endometrial stroma-like cells

Walthard cell nests: urothelial-type epithelium, variable mucin, cystic/solid, in mesovarium, mesosalpinx, ovarian hilus

Ovary at birth and puberty: prominent cystic follicles present

Post-menopausal ovary: thick walled medullary and hilar vessels, also granulomas and hyaline scars

hilus cells - darkly staining hilus cells are adjacent to a small nerve fiber (top); rounded hyaline bodies are present at the top, Reinke crystals are seen below with 2 parallel strands of a nerve

mesothelial hyperplasia - present between outer surface of an ovarian serous borderline tumor (left) and vascular adhesion (right)); mesothelial cells have abundant pale eosinophilic cytoplasm, small focus of calcification is evident; numerous small tubular structures and cords of mesothelial cells are growing in a parallel array

miscellaneous - surface epithelial stromal proliferation; vacuolar change within surface epithelial inclusion glands; artifact-granulosa cells in blood vessel lumen #1; #2; infarcted appendix epiploica attached to ovarian surface, with focal calcification

post-menopausal - atrophic ovary has scant cortical stroma, most of medulla is filled by corpora albicantia; cortical granuloma consists of loose cluster of spindle cells, epithelioid cells and lymphocytes

rete ovarii - network of branching tubules in cellular stroma, which may resemble ovarian stroma; polypoid projections with fibrous cores occupy the lumen of a cystically dilated portion; epithelium varies from flat to cuboidal to columnar

surface epithelial inclusion glands - arise from invaginations of surface epithelium into cortical stroma; lined predominantly by columnar cells

Walthard nest - composed of transitional cells that abut the ovarian stroma

Positive stains: keratin, EMA, calretinin (granulosa and theca cells), actin/desmin (stroma cells), CD56, WT1, ER-beta, PR, Ber-EP4, CA-125, vimentin, desmoplakin

Negative stains: CD10

Gonadal dysgenesis

Gonadal dysgenesis-general - Ovary chapter

A disorder of sex development, defined as a congenital condition with atypical development of chromosomal, gonadal or anatomic sex

Disorders of sex development are either female pseudohermaphroditism (46XX with 2 ovaries), male pseudohermaphroditism (46XY with two testes), true hermaphroditism (ovotestis present) or gonadal dysgenesis (either pure with normal 46XX or 46XY chromosomes and bilateral streak gonads, or mixed with streak gonad)

Pure (complete) gonadal dysgenesis - Ovary chapter

Either 46XX or 46XY

Pure gonadal dysgenesis - 46XX - Ovary chapter

Phenotypic female, 46XX, but no functional ovaries are present to induce puberty (may have streak ovaries)

May be familial (Am J Med Sci 1980;280:157)

Occasionally due to mutation in FSH receptor (Cell 1995;82:959)

Perrault syndrome: with sensorineural deafness

Laboratory: low serum estrogen and progesterone (since no functional ovaries), high serum FSH and LH

Treatment: estrogen and progesterone therapy

Pure gonadal dysgenesis - 46XY - Ovary chapter

Also called Swyer syndrome

Phenotypic female, hypoplastic (streak) gonads without germ cells,

Causes: mutation in SRY, the sex-determining region of the Y chromosome in 10-15%

Presents with primary amenorrhea (delayed puberty), since no functional gonads are present to induce puberty

May develop pubic hair through androgens produced from adrenal gland

Absence of Mullerian inhibiting factor (various causes) leads to absence of testosterone, which causes Wolffian duct regression and failure of male internal reproductive tracts to develop; absence of Mullerian inhibiting factor also allows Mullerian ducts to differentiate into oviducts and uterus

High risk of gonadoblastoma or germ cell tumor from gonads (Zhonghua Fu Chan Ke Za Zhi 2008;43:442); dysgerminoma may develop by age 10 years (BJOG 2008;115:737)

Laboratory: low serum estrogen and progesterone, high serum FSH and LH

Case reports: successful pregnancy using donor oocytes and oocyte transfer (Fertil Steril 2008;90:2015.e1)

Treatment: early excision of gonads (J Gynecol Obstet Biol Reprod (Paris) 2008 Jan 31 [Epub ahead of print]), estrogen and progesterone therapy

References: OMIM 306100, Gene Reviews

Mixed gonadal dysgenesis - Ovary chapter

A type of asymmetrical gonadal dysgenesis (usually testis plus streak gonad) due to chromosomal abnormality

Often mosaicism: 45X / 46XY, 45X / 46XX or 45X / 47XXY; may also have 46XX but missing part of one X chromosome

Patients with 45X mosaicism are often considered to have a variant of Turner’s syndrome

Phenotype may be ambiguous, male, female or intersex

Either (a) testis plus contralateral streak gonad, (b) testis and contralateral gonadal agenesis, (c) hypoplastic gonads with tubules in one gonad or (d) streak gonad with contralateral tumor

Usually also bilateral fallopian tubes, chromatin negative Barr bodies; occasionally vas deferens

Streak testis: streak tissue identified at periphery of differentiated testis

Streak gonad: ovarian-type stroma without differentiated gonadal structures

External genitalia: female with clitoromegaly, male with hypospadias or normal male

Phenotypic females may develop virilization at puberty, often complete; no breast development except with tumors

High risk for gonadoblastoma (30%) if Y chromosome material is present, which may obliterate testicular elements and cause incorrect diagnosis

Higher risk for other medical problems, including deficient immunoglobulin levels, aberrant bony development of inner ear structures, cardiovascular and renal anomalies

Laboratory: elevated FSH

Case reports: short stature in phenotypic male with 45X / 46XY mosaicism (Nat Clin Pract Endocrinol Metab 2008;4:524)

Treatment: excise gonads early to prevent tumors

Micro: prepubertal patients show normal immature testis; at/after puberty, tubules exhibit mild hypospermatogenesis to total sclerosis; streak gonad has ovarian stroma without primordial ovarian follicles; streak ovary is streak gonad with primordial follicles and primitive sex cord-like structures with or without germ cellcomponents within the ovarian-type stroma, mimicking gonadoblastoma, granulosa cell tumor or Sertoli cell tumors

Molecular: FISH may be helpful (Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2008;25:570); no mutations of SRY (Eur J Obstet Gynecol Reprod Biol 2004;115:55)

DD: true hermaphroditism (ovary has numerous primordial follicles containing primary oocytes, nature of internal or external genitalia is not relevant, Mod Path 2002;15:1013)

Female pseudohermaphroditism - Ovary chapter

Female genotype (46XX), female internal phenotype (two ovaries) with variable virilization

Two types: associated with congenital adrenal hyperplasia or not

Female pseudohermaphroditism associated with congenital adrenal hyperplasia - Ovary chapter

46XX, Barr bodies are chromatin positive, autosomal recessive

Ovary with female ducts, variable virilized external genitalia, amenorrhea at puberty with virilization, markedly elevated 17 ketosteroids

Usually due to 21-hydroxylase or 11beta-hydroxylase deficiency; also other rare mutations (Arq Bras Endocrinol Metabol 2005;49:126), partial 17alpha-hydroxylase/17,20-lyase deficiency (Gynecol Endocrinol 2008;24:362)

Female pseudohermaphroditism of nonadrenal cause - Ovary chapter

46XX, Barr bodies are chromatin positive

Ovary with female ducts and variable virilized external genitalia; normal puberty

May be due to maternal exposure to progestins or androgens

17-keratosteroids and estrogen levels are normal

Case reports: with luteoma of pregnancy (Hum Reprod 2002;17:821)

References: eMedicine

Testicular feminization - Ovary chapter

Most common type of male pseudohermaphroditism

Also called androgen insensitivity syndrome

Male genotype (46XY), female phenotype due to end order defect (androgen insensitivity)

Patients present with amenorrhea or sterility; vagina but no uterus; also bilateral cryptorchid testes with nodular masses of immature tubules resembling Sertoli-Leydig tumor

9% develop tumors in cryptorchid testis, which should be removed after puberty

Case reports: 36 year old with abdominal seminoma (J Obstet Gynaecol Res 2004;30:109)

References: Wikipedia, eMedicine

True hermaphroditism - Ovary chapter

Rare; ovarian and testicular tissue in same patient; either bilateral or unilateral ovatestes OR testis opposite ovary

All have uterus, most have fallopian tubes, some have vas deferens

Usually ambiguous genitalia (J Pediatr Endocrinol Metab 2001;14:421)

At puberty, 80% have gynecomastia, 50% menstruate

80% have chromatin positive Barr bodies

60% are 46XX only in blood cells with Y chromosome present in most of rest of cells

Hormonal levels are normal

Important to assign gender early since (a) usually no other developmental anomalies and (b) will have normal sexual and reproductive lives if remove gonad inappropriate for gender assignment

May be associated with transexualism (Urologiia 2008;2:14)

Case reports: due to tetragametic chimerism (fertilization of two ova by two sperm, followed by the fusion of the zygotes and the development of an organism with intermingled cell lines, Urology 2009;73:293), 16 year old phenotypic male with gynecomastia and pubertal arrest (Horm Res 2007;68:261)

Treatment: conservative gonadal surgery with long term followup (J Urol 2007;177:726)

Micro: ovary usually normal (prepubertal ovary has primordial follicles with primary oocytes with a few primary or antral follicles); prepubertal testis has immature seminiferous tubules lined by immature Sertoli cells and primitive germ cells, usually without spermatogonia

DD: mixed gonadal dysgenesis (ovarian tissue, if present, lacks primordial follicles; internal/external genitalia are not relevant for distinguishing these two conditions)

Turner’s syndrome - Ovary chapter

Also called Ullrich-Turner syndrome

1/2500 live female births; increased frequency in abortuses or women with short stature

Have female ducts and external genitalia, but usually no pubertal development, 50% of chromosomes lack Barr bodies (the inactivated X chromosome)

Patients are 45X (also called 45X0) in some or all cells

Associated with nongonadal neoplasms including atypical polypoid adenomyoma of uterus, endometrial adenocarcinoma, leukemia and soft tissue tumors; also other medical disorders

Laboratory: markedly elevated serum FSH, reduced serum estrogen

Case reports: mother and daughter with nonmosaic Turner's syndrome (Fertil Steril 2004;82:923)

Treatment: growth hormone (to increase stature), estrogens; also search for hidden Y chromosome mosaicism (J Pediatr Endocrinol Metab 2006;19:1113); followup medical care for various conditions in adulthood (Endocr Rev 2002;23:120)

Micro: streak gonad with fibrous tissue resembling ovarian stroma

References: Wikipedia

Inflammatory disorders

Abscess - Ovary chapter

Nonspecific inflammation is usually due to tubal and endometrial involvement

Gross: large, loculated cyst with pus or secretion

Micro: cyst wall often contains ovarian stroma

Autoimmune oophoritis - Ovary chapter

Causes 10% of premature ovarian failure, defined as amenorrhea before age 40 years with elevated serum gonadotropins

Associated with Addison’s disease and hypothyroidism (Endocr Rev 1997;18:107)

In teenagers, associated with autoimmune polyendocrine syndrome type I or II (Wikipedia, Ann N Y Acad Sci 2008;1135:118)

Diagnosis: ovarian failure plus serum adrenal cortical or steroid cell antibodies (StCA), or serum antibodies to adrenal and ovarian steroidogenic enzymes; higher serum levels of total inhibin and inhibin B than other ovarian failure cases (J Clin Endocrinol Metab 2008;93:1263)

Laboratory: low estradiol, high FSH, normal/high inhibin A and B

Treatment: hormone replacement therapy; steroids are not standard treatment

Gross: cystic ovaries

Micro: lymphocytes and plasma cells infiltrate developing follicles and corpora lutea but not primordial follicles; preservation of granulosa cells

References: Fertil Steril 2005;84:958, Johns Hopkins

Eosinophilic perifolliculitis - Ovary chapter

May cause autoimmune oophoritis

Case reports: 45 year old woman with ovarian cyst (J Reprod Med 2006;51:141), two middle aged women with cystic ovaries (Int J Gynecol Pathol 1993;12:360)

Gross: cystic ovaries

Micro: eosinophils, lymphocytes, macrophages and plasma cells

Giant cell arteritis - Ovary chapter

Part of generalized condition or isolated; usually elderly women

Common presentation is elderly woman with apparent ovarian or breast tumor and constitutional symptoms and elevated sedimentation rate (Medicine (Baltimore) 2000;79:349)

References: Am J Surg Pathol 1986;10:696

Gonorrhea - Ovary chapter

Begins in Bartholin’s or other vestibular or periurethral glands; spreads to cervix, fallopian tubes, ovaries

A type of pelvic inflammatory disease (see below)

Micro: acute suppurative reaction, tubo-ovarian abscess

Granulomatous inflammation - Ovary chapter

Causes: actinomyces (associated with IUDs, Am J Clin Pathol 1977;68:622), Crohn’s disease (extension from bowel), Enterobius vermicularis, foreign materials (talc or starch, keratin from ruptured teratoma), post-surgical (including carbon, Hum Pathol 1996;27:1008), schistosomiasis, tuberculosis (hematogenous spread to ovary, also involves fallopian tube and uterus, Arch Gynecol Obstet 2008;278:359), xanthogranulomatous oophoritis (solid mass in long standing cases of inflammation with foamy macrophages, Indian J Pathol Microbiol 2003;46:80); rarely sarcoidosis

Case reports: due to microfibrillar collagen hemostat (Avitene) used to control bleeding (Arch Pathol Lab Med 1995;119:1161), due to malakoplakia (Obstet Gynecol 1987;69:537)

Micro: central suppuration and surrounding giant cells in Crohn’s disease; tuberculosis

Microsporidia - Ovary chapter

Case reports: disseminated microsporidiosis due to Encephalitozoon cuniculi involving ovary of Italian woman with AIDS (Mod Path 2002;15:577)

Pelvic inflammatory disease (PID) - Ovary chapter

Also called tubo-ovarian abscess

Pelvic pain, adnexal tenderness, fever, vaginal discharge

Due to gonorrhea, chlamydia, enteric bacteria or puerperal infections (from end of third stage of labor until uterus completely involutes at 3-6 weeks); usually polymicrobial

Usually begins in endometrium and is associated with tubal involvement, tubo-ovarian abscess or cyst

Complications are infertility, peritonitis, bacteremia or intestinal obstruction due to adhesions

References: eMedicine, Wikipedia

Non-neoplastic cysts / other

DD of small, cystic follicles - Ovary chapter

Cystadenoma / cystadenocarcinoma, cystic corpus luteum, cystic granulosa cell tumor, endometriosis, epidermoid tumor, rete ovarii cyst, surface inclusion cyst

Calcification - Ovary chapter

Usually more important to radiologists than pathologists

Often in normal ovaries by ultrasound, but may be associated with neoplasms (Radiology 1996;198:415)

Most calcifications are found in stroma (Mod Pathol 2003;16:219)

Asymptomatic children may present with calcified abdominal mass (Radiology 1981;141:83)

Case reports: 50 year old with bilateral, multifocal ovarian stromal calcification (Arch Pathol Lab Med 1992;116:204), ossification adjacent to endometriosis (Clin Exp Obstet Gynecol 2007;34:113), heavily calcified hemangioma (Br J Radiol 2008;81:e269)

Cholelithiasis - Ovary chapter

Gallstones may be lost during laparoscopic cholecystectomy and adhere to ovary

Case reports: surgery 2-3 years previous (Arch Pathol Lab Med 2001;125:579, Arch Pathol Lab Med 1997;121:155), surgery > 7 years previous (J Reprod Med 2007;52:968)

Corpus luteum cyst - Ovary chapter

Usually occurs during reproductive years, at end of menstrual cycle or during pregnancy

Note: normal corpus luteum is cystic

Case reports: ruptured corpus luteum cyst of pregnancy causing massive hemoperitoneum (J Pediatr Adolesc Gynecol 2007;20:97), spontaneous rupture of hemorrhagic corpus luteum cyst torsion (Kaohsiung J Med Sci 2003;19:75)

Gross: single, usually 2-6 cm, convoluted yellow lining; fluid may be bloody

Micro: inner lining of connective tissue, outer layer of large luteinized granulosa cells; pregnant patients have hyaline bodies and calcific foci within granulosa cells; when rupture, may be difficult to distinguish from endometriosis or ruptured ectopic pregnancy

Developmental cyst - Ovary chapter

From mesonephric (wolffian) or paramesonephric (mullerian) remnants

Common in ovarian hilus

Case reports: with serous borderline tumor (Histopathology 1983;7:601)

Mesonephric (wolffian) origin: cuboidal, nonciliated epithelium, on well developed basement membrane; has smooth muscle coat

Paramesonephric (mullerian) origin: resembling fallopian tube; taller, often ciliated epithelium with larger nuclei, inconspicuous basement membrane; has smooth muscle coat

Ectopic decidual reaction - Ovary chapter

Definition: response of stromal cells to high levels (systemic or local) of estrogen or progesterone from functioning corpus luteum

May occur as early as week 9 of gestation

Found in almost all ovaries at term (Am J Anat 1978;152:7)

May be associated with trophoblastic disease, pelvic radiation, other causes of increased estrogen / progesterone

Gross: tan nodules on ovarian surface, may be hemorrhagic

Micro: decidua usually within superficial cortical stroma or adhesions; resembles decidua elsewhere; some cells may resemble signet ring cells due to cytoplasmic vacuoles (Mod Pathol 2005;18 Suppl 2:S113)

Negative stains: keratin

Endometriosis - Ovary chapter

Ovary is most common site

Defined as endometrial glands and stroma outside the uterus

Usually associated with infertility (although mechanism is unclear, Fertil Steril 2008;90:247), remains active during reproductive years

Pain, occasionally massive ascites or perforation

Associated with clear cell or endometrioid carcinoma (Singapore Med J 1997;38:289), particularly if atypia (Hum Pathol 1988;19:1080)

Rarely presents as polypoid endometriosis which is usually also associated with nonpolypoid endometriosis, no atypia and no hypercellularity (Am J Surg Pathol 2004;28:285)

Case reports: with ovarian ossification (Clin Exp Obstet Gynecol 2007;34:113)

Gross: small, raised blue spots on ovarian surface with fibrous adhesions; chocolate cysts are due to repeated hemorrhage; rarely have granulomatous nodules attached to peritoneum or free within peritoneal cavity (Am J Surg Pathol 1988;12:390)

Micro: need 2 of 3 features of endometrial glands, endometrial stroma or hemorrhage; stromal cells have naked nuclei, are surrounded by reticulin and spiral arterioles; smooth muscle stroma is common; repeated hemorrhage may destroy stromal tissue; specimen may be composed of necrotic pseudoxanthomatous nodules; may see endometrial glandular atypia (atypical endometriosis), hyperplasia, carcinoma (endometrioid most common); rarely Liesegang rings (acellular, ringlike structures that may form near inflamed or necrotic tissue, Int J Gynecol Pathol 1998;17:358), stromal elastosis

Molecular: Trisomy 1 and 7 and monosomy 9 and 17 are more common in ovarian versus nonovarian endometriosis (Mod Pathol 2006;19:1615)

Positive stains: CD10 (highlights endometrial cells, Arch Pathol Lab Med 2003;127:1003)

Endosalpingiosis - Ovary chapter

Arises from secondary mullerian system (pelvic and lower abdominal mesothelium)

Associated with ovarian serous tumors, usually borderline

May be difficult to distinguish from implants

Case reports: cystic mass involving ovary and full thickness of uterine fundus (Ultrasound Obstet Gynecol 2008;32:106), with psammoma bodies (J Reprod Med 1991;36:675)

Micro: benign glands and tubules lined by tubal type cells; calcifications or psammoma bodies are common (Mod Pathol 2003;16:219); smooth contours; variable papillae beneath the peritoneal surface

DD: noninvasive or invasive ovarian implants

Epidermoid cyst - Ovary chapter

Also called epidermoid inclusion cyst

Very rare; often an incidental finding (Am J Obstet Gynecol 1976;124:523)

May be associated with monodermoid teratoma or Walthard nests

No skin adnexae or other tissues (or would be a mature cystic teratoma)

May be associated with squamous cell carcinoma (Clin Exp Obstet Gynecol 2005;32:265)

Case reports: with ovarian endometrioid carcinoma (Zentralbl Gynakol 2002;124:443)

Micro: smooth inner lining of stratified squamous epithelium with no evidence of hair or a Rokitansky tubercle (Int J Gynecol Pathol 1996;15:69); also focally cystic nests within cyst wall containing mucin and keratin debris (Am J Clin Pathol 1980;73:272)

Follicular cyst - Ovary chapter

Ovarian follicle matures during proliferative phase of menstrual cycle, then LH surge causes release of mature oocyte at mid-cycle, then follicle transforms to a corpus luteum; if no fertilization, corpus luteum typically atrophies

If no LH surge or no ovulation, follicle grows and becomes a cyst, which usually disappears within 2-3 menstrual cysts but may persist

Follicular cyst is common in reproductive years, usually asymptomatic or forms an adnexal mass

Pedicle may twist and cause hemorrhagic infarction

Associated with precocious puberty in children; also endometrial hyperplasia and metrorrhagia (cyst fluid may contain estrogens)

Case reports: associated with tamoxifen (Gynecol Obstet Invest 1993;35:62)

Treatment: excision if symptomatic, LHRH agonists, watchful waiting (Arch Pediatr 1994;1:903)

Gross: up to 10 cm, glistening membrane, thin walled, unilocular or multilocular, clear serous fluid, no solid component

Micro: outer layer of theca interna cells, usually luteinized, may be surrounded by reticulum; variable inner layer of granulosa cells, luteinized after puberty

Cytology: may be highly cellular with granulosa cells, resembling granulosa cell tumor (Acta Cytol 2003;47:1059); may have atypical cells (Diagn Cytopathol 1991;7:48)

References: eMedicine

Germinal inclusion cyst - Ovary chapter

Definition: invaginations of surface epithelium with loss of connection from surface

Also called inclusion cyst, serous inclusion cyst

Common in older women; small, multiple, no clinical significance

Probably not a risk factor for ovarian cancer (Am J Epidemiol 1993;138:90)

May be related to ovulation (Gynecol Oncol 2005;96:496)

Micro: cuboidal, columnar or flat epithelium; tubal metaplasia common; psammoma bodies occasionally seen

Heterotopic ovarian splenoma - Ovary chapter

Definition: form of heterotopic splenic hamartoma consisting of red pulp tissue without associated white pulp in otherwise normal ovary

Very rare

Case reports: Arch Pathol Lab Med 2001;125:1483

Micro: interanastomosing vascular channels of splenic sinusoidal red pulp; sinuses lined by cuboidal to flattened cells with ovoid and grooved bland-looking nuclei

Positive stains: von Willebrand factor, CD8 (splenic lining cells)

EM: Weibel-Palade bodies, lysosomes

Hyperreactio luteinalis - Ovary chapter

Definition: ovarian enlargement due to multiple luteinized follicle cysts secondary to hCG stimulation OR hypersensitivity to hCG

Rare; associated with hydatidiform mole, choriocarcinoma, fetal hydrops due to Rh sensitization, multiple gestations

Rarely seen in uncomplicated single pregnancy; only rarely recurs (J Clin Pathol 2005;58:439)

Usually no symptoms, may have pain from hemorrhage; rarely ascites

Virilization in 15% of mothers but not female infants in cases without gestational trophoblastic disease

Case reports: associated with HELLP syndrome (Fertil Steril 2008;90:2008 e13), with hirsutism (Gynecol Endocrinol 2007;23:248), with marked virilization and hyperglycemia (Am J Perinatol 2006;23:85)

Treatment: cysts involute within 6 months; operate only to remove infarcted tissue or to control hemorrhage

Gross: multiple, bilateral, thin-walled cysts, filled with clear or hemorrhagic fluid

Micro: follicular cysts with luteinization of theca interna or granulosa cells, edema of theca layer and stroma

References: Arch Pathol Lab Med 1989;113:921

Hyperthecosis - Ovary chapter

Definition: hyperplastic stroma with clusters of luteinized stromal cells

Similar symptoms to polycystic ovarian syndrome but higher testosterone levels and no/fewer cysts

Typically patients are obese with striking virilization and insulin resistance; either pre- or post-menopausal

Luteinized stromal cells produce androgens

Case reports: associated with endometrial adenocarcinoma and pseudosarcomatous changes in endometrial stroma (Am J Surg Pathol 1984;939), due to adrenal tumor (Arq Bras Endocrinol Metabol 2008;52:1184)

Treatment: possibly excision, leuprolide if poor surgical candidate (Obstet Gynecol 2002;99:893)

Gross: uniform enlargement of both ovaries; solid, yellow-white cut surface; may have superficial cysts

Micro: scattered nests of luteinized theca cells in ovarian stroma

Hypothyroidism and ovarian cysts - Ovary chapter

Van Wyk and Grumbach syndrome: juvenile hypothyroidism, precocious puberty and ovarian enlargement - regresses with thyroid medication (Pediatr Radiol 2008;38:538)

Case reports: 9 year old girl, 22 year old woman with multiple ovarian cysts and hypothyroidism (Gynecol Endocrinol 2008;24:586)

Large solitary luteinized follicular cyst of pregnancy and puerperium - Ovary chapter

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Definition: rare solitary follicular cyst that occurs during pregnancy and puerperium, may be related to hCG

Palpable adnexal mass or seen at C-section

No clinical endocrine disturbance

Treatment: conservative, may need to excise if symptomatic (Obstet Gynecol 2005;105:1218)

Gross: large, solitary, unilocular cyst, resembles follicular cyst, but markedly larger (mean 25 cm)

Micro: cyst lined by 1 or more layers of luteinized cells with clear to pink cytoplasm, no theca/granulosa distinction; focal nuclear atypia (enlarged, pleomorphic and hyperchromatic nuclei) is probably degenerative; also nests of luteinized cells within fibrous tissue of cyst wall (Pathol Res Pract 2006;202:471)

References: Am J Surg Pathol 1980;4:431, Arch Pathol Lab Med 1986;110:928

Massive edema of ovary - Ovary chapter

Definition: tumor like enlargement of ovary due to edema fluid

First described in 1969 (Obstet Gynecol 1969;34:564)

Pain, abdominal mass, menstrual irregularities, virilization, precocious puberty, Meig’s syndrome (with ascites and pleural effusion, eMedicine)

May be due to partial torsion of mesovarium leading to interference of venous / lymphatic drainage

Usually young women; right sided involvement is more common

Gross: marked ovarian enlargement, watery cut surface, no necrosis

Micro: marked edema of stroma surrounding follicles and clusters of luteinized cells; stroma around vessels and in superficial cortical zone is normal; variable stromal luteinization

DD: fibroma (circumscribed, tumor cells replace ovarian architecture), Krukenberg tumor (usually bilateral, signet ring cells present)

References: Am J Surg Pathol 1979;3:11, Arch Pathol Lab Med 1979;103:42

Ovarian pregnancy - Ovary chapter

1-3% of ectopic pregnancies; often conceptus dies or involutes spontaneously

Resembles tubal pregnancy due to similar symptoms (abdominal pain, amenorrhea, abnormal vaginal bleeding) and risk factors (pelvic inflammatory disease, prior pelvic surgery, IUD [Eur J Obstet Gynecol Reprod Biol 2004;114:92], use of progesterone only minipill)

Due to retention of ovum in ovarian operculum and continued entrapment within ruptured ovarian follicle; sperm fertilizes entrapped ovum, and implantation occurs within ovary

Difficult to diagnose clinically or even intraoperatively

Patients have excellent prognosis for future fertility; recurrence is virtually nonexistent

Spiegelberg criteria: (1) intact ipsilateral tube, clearly separate from the ovary; (2) gestational sac within or replacing the ovary; (3) sac connected to the uterus by the ovarian ligament; and (4) histologically proven ovarian tissue located in the sac wall (Arch Gynaekol 1878;13:73)

Case reports: 23 year old woman (Indian J Pathol Microbiol 2008;51:37), 31 year old woman (Arch Pathol Lab Med 2003;127:1635), patient with intact IUD (Arch Pathol Lab Med 1981;105:112)

Treatment: methotrexate, wedge resection if unsuccessful (MedGenMed 2006;8:35)

Gross: enlarged gray-tan ovaries; may clinically resemble tumor (Ann Afr Med 2007;6:36)

Micro: evidence of pregnancy (chorionic villi, trophoblastic tissue), ovarian tissue in wall of gestational sac

Polycystic ovary disease (PCO) - Ovary chapter

Formerly called Stein-Leventhal syndrome

Affects 5-10% of women in US; most common cause of anovulatory infertility

Two different diagnostic criteria:

NIH: androgen excess, oligoovulation and exclusion of other entities that cause polycystic ovaries

ESHRE/ASRM in Rotterdam: 2 of 3 present - (a) oligoovulation or anovulation, (b) excess androgen activity, (c) polycystic ovaries present (by ultrasound) but no other endocrine disorders

Occurs during teenage and childbearing years

Associated with endometrial hyperplasia, well differentiated adenocarcinoma; also acne, obesity, hirsutism, insulin resistance and diabetes

Endometrium may show metaplastic changes resembling adenoacanthoma or adenocarcinoma (Am J Surg Pathol 1982;6:223)

Treatment (for infertility): clomiphene citrate or FSH, weight loss; also “ovarian drilling”-puncture of small follicles with electrocautery (Hum Reprod 2002;17:2851); formerly did wedge resections

Gross: large ovaries (2x normal), numerous subcortical cysts (“cysts” may be immature follicles)

Micro: multiple cystic follicles covered by a dense fibrous capsule; luteinization of the theca interna (hyperthecosis), few corpora lutea or corpora albicantia since anovulatory, atretic follicles simulate corporate albicantia

References: Wikipedia, eMedicine #1; #2

Postoperative carbon pigment granuloma - Ovary chapter

At sites of prior laser or fulguration surgery (Hum Pathol 1996;27:1008)

Pregnancy luteoma - Ovary chapter

Definition: single or multiple nodules of luteinized cells with abundant eosinophilic cytoplasm, detected during pregnancy

Rare (100 cases described), probably hyperplasia due to hCG, not neoplasia

80% in multiparous women, 80% in blacks

Usually an incidental finding at cesarean section or post-partum tubal ligation

25% are associated with virilization in latter half of pregnancy, 2/3 of female infants of virilized mothers are virilized (note: usually placenta aromatizes androgens to estrogens); testosterone levels are 70x normal, elevated even in non-virilized patients

Case reports: with rupture and bleeding (Singapore Med J 2008;49:e78), with female pseudohermaphroditism (Hum Reprod 2002;17:821)

Treatment: none - tumors are benign and regress weeks after delivery (infarct like necrosis leads to scar)

Gross: soft, fleshy, circumscribed, yellow/orange nodules, hemorrhagic, may be very large; 1/3 bilateral, 1/2 multiple, may see separate corpus luteum

Micro: sharply circumscribed, rounded masses of polygonal cells with abundant pink cytoplasm containing little lipid (theca-lutein cells), round nuclei, variably prominent nucleoli, mild nuclear atypia; 2-3 MF/10 HPF, scant stroma; may have colloid filled spaces

Positive stains: alpha-inhibin, cytokeratin, vimentin, CD99

EM: smooth ER, dispersed Golgi, tubular cristae in mitochondria (associated with steroid hormone producing cells)

DD: large solitary luteinized follicular cyst of pregnancy and puerperium, hyperreactio luteinalis, corpus luteum of pregnancy (central cavity, convoluted border, cells have hyaline or calcified bodies); also granulosa tumor, thecoma, steroid cell tumor (not usually in pregnant women, usually unilateral, more non-luteinized foci, more lipid, more nuclear atypia), melanoma (pigment present, S100+, HMB45+, alpha-inhibin negative)

Rete ovarii cyst - Ovary chapter

Also called adenoma of rete ovarii

Rare; mean age 59 years

Case reports: 11 year old girl (J Pediatr Surg 2005;40:e17),

Gross: mean 9 cm, usually hilar

Micro: tubulopapillary proliferations of columnar cells with clear cytoplasm; stroma has extensive polygonal, Leydig-like cells associated with simple endometrial hyperplasia; rete and hilar mesonephric remnants found in vicinity of the lesion

Positive stains: CAM 5.2, vimentin, EMA, progesterone receptor

References: Int J Gynecol Pathol 1988;7:330, Hum Pathol 1997;28:1428

Splenic-gonadal fusion - Ovary chapter

Definition: congenital anomaly due to fusion of splenic and gonadal anlage during embryonic development

Extremely rare (90 cases)

More common in males; often associated with skeletal anomalies or cryptorchidism

Either continuous or discontinuous

Continuous: cord-like structure connects the spleen and the gonadal-mesonephric structures

Discontinuous: no such connection exists

Case reports: adult woman-continuous (Pathol Int 1995;45:871), adult woman-discontinuous (Hum Pathol 1989;20:486)

Stromal hyperplasia - Ovary chapter

Definition: tumor like proliferation of ovarian stroma, without luteinization

Less frequently estrogenic or androgenic than stromal hyperthecosis

Patients may be obese, have hypertension or abnormal glucose tolerance

Gross: ill defined white-yellow nodules in ovary; may lead to enlarged ovary

Micro: medullary or occasionally cortical clusters of densely cellular ovarian stroma with scant collagen; may entirely replace ovarian architecture; no luteinized stromal cells; no mitotic figures

DD: stromal hyperthecosis (luteinized cells), low grade endometrial stromal sarcoma (spiral arterioles and mitotic figures present)

Supernumerary ovaries - Ovary chapter

Also called ectopic ovary, accessory ovary

Very rare, usually < 1 cm

Supernumerary: occurs widely situated from normal ovary, formed from a separate anlage

Accessory: due to splitting of embryonic gonad, usually attached to the normal gonad

May actually be ovarian implant or due to torsion

Case reports: stillborn (Arch Pathol Lab Med 1991;115:233), in labia of 5 month old (J Belge Radiol 1998;81:288), in omentum with dermoid cyst (Arch Gynecol Obstet 1995;256:111), intrarenal supernumerary ovary with completely duplicated pelvis and ureter (Int Urogynecol J Pelvic Floor Dysfunct 2007;18:1243), on broad ligament (J Reprod Med 2000;45:435), on sigmoid colon (J Obstet Gynaecol Res 2006;32:613), cases with fibroma and endometriosis (Pathol Res Pract 2001;197:847), ovarian remnant at laparoscopic port site (J Minim Invasive Gynecol 2008;15:505), ovary possibly placed in inguinal canal at prior surgery (Fertil Steril 2006;85:1822e9),

Torsion - Ovary chapter

Definition: partial or complete rotation of ovarian vascular pedicle, causing obstruction to venous outflow and arterial inflow

Rare; associated with cysts, neoplasms and in vitro fertilization; in children, ovary is often normal (Arch Pediatr Adolesc Med 2005;159:532)

Presents with abdominal pain, patients need emergency ultrasound and laparoscopy (J Pediatr Adolesc Gynecol 2008;21:201)

Case reports: normal ovary in third trimester (J Med Case Reports 2008 Dec 8;2:378)

Treatment: unwinding (J Obstet Gynaecol Res 2008;34:683); even necrotic appearing ovaries can often be saved (Clin Obstet Gynecol 2006;49:459)

References: eMedicine #1; #2

Uterus like mass of ovary - Ovary chapter

Case reports: 18 year old (Arch Pathol Lab Med 1985;109:361), 31 year old with endometriosis (Arch Pathol Lab Med 1981;105:508), three women in India ages 38-43 years with breast cancer (Am J Surg Pathol 1998;22:333); resembling adenomyoma (Arch Pathol Lab Med 2005;129:1041)

May be due to endomyometriosis-like metaplasia or congenital malformation of urogenital system (Int J Gynecol Pathol 2005;24:382)

Gross: resembles uterus, no anatomic abnormalities

Micro: resembles uterus but residual ovarian stroma

End of Ovary-nontumor chapter

See also Ovary-tumor chapter

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