Ovary
Last revised 22 July 2008
Last major update December 2003
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Primary references, normal anatomy, normal histology
Gonadal dysgenesis: general, mixed, female pseudohermaphroditism, true hermaphroditism, Turner’s syndrome
Inflammatory disorders: 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 cysts, developmental cysts, ectopic decidual reaction, endometriosis, endosalpingiosis, epidermoid inclusion cyst, follicular cysts, germinal inclusion cysts, heterotopic ovarian splenoma, hydatids of Morgani, hyperreactio luteinalis, hyperthecosis, large solitary luteinized follicular cyst of pregnancy and puerperium, massive edema, ovarian pregnancy, polycystic ovary disease, postoperative carbon pigment granuloma, pregnancy luteoma, rete ovarii cysts, splenic gonadal fusion, stromal hyperplasia, supernumerary ovaries, torsion, uterus-like mass
Neoplasms: ovarian tumors-general
Surface epithelial tumors: general
Serous tumors: general, cystadenoma, borderline, microinvasive, carcinoma, micropapillary, psammomacarcinoma, surface, ovarian implants
Mucinous tumors: general, mural nodules, cystadenoma, adenofibroma, primary retroperitoneal mucinous cystadenoma, borderline, microinvasive, carcinoma, mucinous metastases, pseudomyxoma peritonei, peritoneal mucinous carcinomatosis
Endometrioid tumors: general, cystadenoma, adenofibroma, borderline, carcinoma
Brenner tumors: general, benign, borderline, malignant
Other surface epithelial tumors: clear cell carcinoma, urothelial carcinoma, mixed epithelial-papillary
Germ cell tumors: general, carcinoid tumors, choriocarcinoma, dysgerminoma, embryonal carcinoma, polyembryoma, struma ovarii, teratoma-mature, teratoma-immature, yolk sac tumor
Sex cord stromal tumors: general, fibroma, gonadoblastoma, granulosa cell-adult, juvenile, gynandroblastoma, Leydig cell, lipid cell, myxoma, sclerosing stromal, Sertoli cell, Sertoli-Leydig, sex cord tumor with annular tubules, steroid cell tumor NOS, thecoma, tumor of adrenogenital syndrome, unclassified
Other: female adnexal tumor of wolffian origin, small cell carcinoma-hypercalcemic type, pulmonary type
Other tumors (not specific to ovary): adenoid cystic/basaloid carcinoma, adenoma of rete ovarii, angiosarcoma, benign papillary mesothelioma, endometrial stromal sarcoma, fibromatosis, fibrosarcoma, granulocytic sarcoma, hemangioma, infantile hemangioendothelioma, leiomyoma, leiomyosarcoma, lymphoma, malignant mixed mullerian tumor, mesothelioma, metastases to ovary, mullerian adenosarcoma, myofibroblastoma, nephroblastoma, neuroendocrine carcinoma, osteoclast-like giant cell tumor, osteosarcoma, PNET, rhabdomyosarcoma, squamous cell carcinoma, undifferentiated carcinoma
Other: staging, features to report
AJCC Cancer Staging Manual (6th Ed)
American Journal of Clinical Pathology (AJCP), Jan 1975 to Aug 2002 (no photos)
American Journal of Surgical Pathology (AJSP), Mar 1977 to Dec 2003
Archives of Pathology and Laboratory Medicine (Archives), Jan 1976 to Dec 2003
Human Pathology, Dec 1971 to Oct 2003
Modern Pathology, March 1988 to Oct 2003
Rosai, J: Ackerman’s Surgical Pathology (8th Ed); Mosby-Year Book, Inc., 1996
Please refer to these primary references for more detailed discussions and photographs
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 weight 5-8 g
Lymphatic drainage to para-aortic, internal iliac, external iliac, common iliac, sacral, obturator, pelvis, retroperitoneal, inguinal nodes
Function first described by Reinier de Graaf, Archives 2000;124:1115
Gross images: drawing
Covered by surface epithelium (modified mesothelium, also called coelomic or germinal epithelium), closely related to mullerian duct lining epithelium
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
Follicles: primordial, maturing (primary, secondary, tertiary, graafian), atretic; corpora lutea, corpora albicantia; 400,000 primordial follicles containing primary oocytes are present at birth in ovarian stroma
Primordial follicle: travels from yolk sac endoderm to ovary, develops into oogonia and oocytes, arrests at prophase of mitosis
Maturing follicle: oocyte with granulosa layer; lacks reticulum, immunoreactive for vimentin, keratin, desmoplakin; contains Call-Exner bodies (rosette-like formations with central filamentous / eosinophilic material consisting of excess basal lamina), theca cells (within follicle, luteinized cells that produce sex hormones; external to follicle)
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
Hilus cells: in ovarian medulla, round to polygonal, epithelial appearing, around vessels, 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
Rete ovarii: counterpart of rete testis; clefts, tubules, cysts, papillae lined by epithelium, surrounded by spindle cell stroma
Walthard cell nests: urothelial-type epithelium, variable mucin, cystic/solid, in mesovarium, mesosalpinx, ovarian hilus
Note: prominent cystic follicles are present at birth and puberty; postmenopausal ovary usually has thick walled vessels, granulomas, hyaline scars
Hilar mesonephric rests: case report of association with nonteratoid prostatic differentiation in 70 year old woman, AJSP 1999;23:232
Hilar cell hyperplasia: associated with hCG administration, pregnancy, choriocarcinoma
Gross images: corpus luteum #1, #2
Micro images: drawing, corpora albicans; corpus luteum #1, #2
Virtual slides: normal ovary-infant
Positive stains: calretinin (granulosa and theca cells), actin/desmin (stroma cells)
Negative stains: CD10
Gonadal dysgenesis
Ambiguous genitalia, persistent mullerian duct structures and wolffian duct derivatives, abnormally developed gonads, karyotypes with Y, potential for neoplastic transformation of gonads (gonadoblastoma)
Note: some don’t separate types of gonadal dysgenesis
A type of asymmetrical gonadal dysgenesis (one side is more developed than the other)
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
Streak testis: streak tissue identified at periphery of differentiated testis
Streak gonad: ovarian-type stroma without differentiated gonadal structures
Mullerian structures present since no/minimal anti-Mullerian hormone produced
Usually bilateral fallopian tubes; occasionally vas deferens
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
Chromatin negative Barr bodies
Karyotypes: 45 X0/46 XY, 46 XY, 45 X0/47 XXY most common
Elevated FSH
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
Treatment: prevent tumors by removing gonads early
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-cordlike structures with or without germ cell components within the ovarian-type stroma, mimicking gonadoblastoma, granulosa cell tumor or Sertoli cell tumors
Micro images: mixed gonadal dysgenesis #1, #2
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
Two types: associated with congenital adrenal hyperplasia or not
Female pseudohermaphroditism associated with congenital adrenal hyperplasia
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
Female pseudohermaphroditism of nonadrenal cause
46 XX, 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
Rare; ovarian and testicular tissue in same patient; either bilateral or unilateral ovatestes OR testis opposite ovary
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
All have uterus, most have fallopian tubes, some have vas deferens
Patients have ambiguous genitalia, but most favor male
At puberty, 80% have gynecomastia, 50% menstruate
80% have chromatin positive Barr bodies
60% are 46 XX only in blood cells with Y chromosome present in most of rest of cells
Hormonal levels are normal
? if patients are prone to tumors
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
Micro images: ovatestis
DD: mixed gonadal dysgenesis (ovarian tissue, if present, lacks primordial follicles; internal/external genitalia are not relevant for distinguishing these two conditions)
1/7000 newborns, increased frequency in abortuses or women with short statute
No pubertal development, 50% of chromosomes have chromatin negative Barr bodies
Patients are 45 XO in some or all cells; have female ducts and external genitalia
Associated with nongonadal neoplasms including atypical polypoid adenomyoma of uterus, endometrial adenocarcinoma, leukemia, soft tissue tumors
Associated with markedly elevated FSH, reduced estrogen levels
Not associated with gonadal tumors, although case report with mixed germ cell tumor and gonadoblastoma, Archives 1994;118:1135
Micro: streak gonad with fibrous tissue resembling ovarian stroma
Lymphocytes and plasma cells infiltrate developing follicles and corpora lutea but not primordial follicles
Causes primary ovarian failure
Associated with Addison’s disease and hypothyroidism, AJCP 1984;81:105
Eosinophils around follicles
Part of generalized condition or isolated; usually elderly women
References: AJSP 1986;10:696
Begins in Bartholin’s or other vestibular or periurethral glands, spreads to cervix, tubes, ovaries
Micro: acute suppurative reaction, tubo-ovarian abscess
Causes: tuberculosis (hematogenous spread to ovary, also involves fallopian tube and uterus), actinomyces (associated with IUDs, AJCP 1977;68:622), schistosomiasis, Enterobius vermicularis, Crohn’s disease (extension from bowel), foreign materials (talc, keratin from ruptured teratoma), post-surgical, xanthogranulomatous oophoritis (solid mass in long standing cases of inflammation with foamy macrophages), rarely sarcoidosis
Case report due to microfibrillar collagen hemostat (Avitene) used to control bleeding, Archives 1995;119:1161
Case report of disseminated microsporidiosis due to Encephalitozoon cuniculi, involving ovary of Italian woman with AIDS, Mod Path 2002;15:577
Micro images: gram stain
Pelvic inflammatory disease (PID)
Pelvic pain, adnexal tenderness, fever, vaginal discharge
Due to gonorrhea, chlamydia, enteric bacteria, 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, intestinal obstruction due to adhesions,
Other bacteria have less exudates, but infection extends throughout wall to serosa; may cause bacteremia
Cystic corpus luteum, endometriosis, epidermoid tumor, cystadenoma / cystadenocarcinoma, rete ovarii cyst, cystic granulosa cell tumor, surface inclusion cyst
Case report of bilateral, multifocal ovarian stromal calcification in 50 year old woman, Archives 1992;116:204
Gallstones may be lost during laparoscopic cholecystectomy and adhere to ovary
Case reports: surgery 2 years previous (Archives 2001;125:579), 2.5 years previous (Archives 1997;121:155)
Gross images: gallstone adherent to ovary
Usually occur during reproductive years
Note: normal corpus luteum is also cystic
Gross: convoluted yellow lining, single, usually 2-6 cm; at end of menstrual cycle or during pregnancy; fluid may be bloody
Micro: inner lining of connective tissue, outer layer of large luteinized granulosa cells, with pregnancy have hyaline bodies and calcific foci within granulosa cells; when rupture, may be difficult to distinguish from endometriosis or ruptured ectopic pregnancy
From mesonephric and paramesonephric remnants
Common in ovarian hilus
Mesonephric origin: cuboidal, nonciliated epithelium, on well developed basement membrane
Paramesonephric origin: taller, often ciliated epithelium with larger nuclei, inconspicuous basement membrane
Occurs during pregnancy or in absence of current/recent pregnancy
Usually due to functioning corpus luteum that has undergone destruction
Ovary most common site
Defined as endometrial glands and stroma outside the uterus
Usually associated with infertility, remains active during reproductive years
Pain, occasionally massive ascites or perforation
Atypical endometriosis associated with clear cell or endometrioid carcinoma, Hum Path 1988;19:1080
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 (AJSP 1988;12:390)
Gross images: endometriosis; intraoperative image #1, #2 with adhesions
Micro: need 2 of 3 (glands, stroma, hemorrhage); stromal cells have naked nuclei, are surrounded by reticulin and spiral arterioles; smooth muscle stroma is common; repeated hemorrhage may destroy stromal tissue; may be composed of necrotic pseudoxanthomatous nodules; may see endometrial glandular atypia (atypical endometriosis), hyperplasia, carcinoma (endometrioid most common)
Micro images: H&E and CD10
Virtual slides: endometriotic cyst
Positive stains: CD10 (highlights endometrial cells, Archives 2003;127:1003)
Arises from secondary mullerian system (pelvic and lower abdominal mesothelium)
Associated with ovarian serous tumors, usually borderline
May be difficult to distinguish from implants
Micro: glands and tubules with variable psammoma bodies and papillae beneath the peritoneal surface; lined by tubal type cells
DD: noninvasive or invasive ovarian implants
May be associated with monodermoid teratoma or Walthard nests
Very rare
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)
May be related to abnormal release of FSH/LH
Usually regress within 2 months; high dose estrogen/progesterone accelerates regression
See also hyperreactio luteinalis below
Gross: up to 10 cm, glistening membrane, thin walled, unilocular or multilocular, clear serous fluid
Gross images: follicular cyst
Micro: outer layer of theca interna cells, usually luteinized, may be surrounded by reticulum; optional inner layer of granulosa cells, luteinized after puberty
Micro images: theca lutein cyst
Common in older women; small, multiple, no clinical significance
Invaginations of surface epithelium with loss of connection from surface
Micro: cuboidal, columnar, flat epithelium; tubal metaplasia common; psammoma bodies occasionally seen
Case report, Archives 2001;125:1483
Form of heterotopic splenic hamartoma consisting of red pulp tissue without associated white pulp in otherwise normal ovary
Micro: interanastomosing vascular channels of splenic sinusoidal red pulp; sinuses lined by cuboidal to flattened cells with ovoid and grooved bland-looking nuclei
Micro images: splenic hamartoma
Positive stains: von Willebrand antigen, CD8 (splenic lining cells)
EM: Weibel-Palade bodies, lysosomes
EM images: Weibel-Palade body
Pedunculated cysts at fimbriated end of fallopian tube of paramesonephric origin
Rare; ovarian enlargement due to multiple luteinized follicle cysts secondary to hCG stimulation (may have normal hCG) OR hypersensitivity to hCG
Associated with hydatidiform moles, choriocarcinoma, fetal hydrops due to Rh sensitization, multiple gestations
Rarely seen in uncomplicated single pregnancy
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
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: Archives 1989;113:921
Case report associated with endometrial adenocarcinoma and pseudosarcomatous changes in endometrial stroma, AJSP 1984;939
Hyperthecosis assumed to have progesterone-like effect
Large solitary luteinized follicular cyst of pregnancy and puerperium
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
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 is probably degenerative
References: AJSP 1980;4:431, Archives 1986;110:928
Tumor like condition in young women
Pain, abdominal mass, menstrual irregularities, virilization, precocious puberty, Meig’s syndrome
May be due to partial torsion of mesovarium leading to interference of venous / lymphatic drainage
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
References: AJSP 1979;3:11, Archives 1979;103:42
1-3% of ectopic pregnancies; often conceptus dies or involutes spontaneously
Symptoms (abdominal pain, amenorrhea, abnormal vaginal bleeding) and risk factors (pelvic inflammatory disease, prior pelvic surgery, IUD, treatment with progesterone-only minipill) are similar to tubal pregnancies
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 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
Case reports: 31 year old woman (Archives 2003;127:1635), patient with intact IUD, (Archives 1981;105:112)
Gross/micro images: hemorrhagic cavity
Polycystic ovary disease (PCO)
Multiple cystic follicles with luteinization of the theca interna, covered by a dense fibrous capsule
Associated with endometrial hyperplasia, well differentiated adenocarcinoma
If idiopathic, have “masculine” response to LHRH agonist nafarelin, suggesting abnormal regulation of ovarian enzymes; known causes are congenital adrenal hyperplasia, ovarian neoplasms, primary hyperthyroidism
Endometrium may show metaplastic changes resembling adenoacanthoma or adenocarcinoma, AJSP 1982;6:513
Treatment: cortisol, clomiphene citrate; formerly did wedge resections
Stein-Leventhal syndrome: polycystic ovaries and oligomenorrhea / sterility; persistent anovulation, obesity (40%), hirsutism (50%), rarely virilism
Gross: large ovaries (2x normal), numerous subcortical cysts
Micro: