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Ovary - nontumor

Normal histology

Reviewer: Mohiedean Ghofrani, M.D. (see Reviewers page)
Revised: 28 December 2011, last major update December 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.


● Ovaries are covered by surface epithelium (OSE), which is a modified mesothelium, also called coelomic or germinal epithelium (Reprod Biol Endocrinol 2006 Aug 21;4:42)
● OSE is one layer of flat to cuboidal mesothelial-type cells, which appear to actively participate in the ovulatory rupture and repair process
● OSE is closely related to müllerian duct lining epithelium
Stroma: comprises bulk of ovarian tissue; resembles fibroblasts in whorls/storiform pattern surrounded by dense reticulin network; contains luteinized stromal cells, decidual cells, smooth muscle, fat, neuroendocrine cells, and endometrial stroma-like cells
Follicles: ~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); prominent cystic follicles present at birth and at puberty
● Post-menopausal ovary has thick walled medullary and hilar vessels, also granulomata and hyaline scars

Stages of follicular development:
● 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 surrounding granulosa cell layer; lacks reticulum; contains Call-Exner bodies (rosette-like formations with central filamentous / eosinophilic material consisting of excess basal lamina), and theca cells (within follicle are luteinized and produce sex hormones, external to follicle are very cellular)
● 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: located in ovarian medulla, rarely within ovarian stroma; located away from the hilum, round to polygonal, epithelial appearing, presumed vestigial remnant of gonad from its "ambisexual" phase
● Produce steroids (predominantly androstenediaone); resemble Leydig cells of testis; may produce masculinizing tumors (hilus 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 cells are seen in the fetal ovary but not in infancy and childhood; they reappear at puberty
Hilar cell hyperplasia: Associated with hCG administration, pregnancy, choriocarcinoma
Rete ovarii: counterpart of rete testis, seen as clefts, tubules, cysts, papillae lined by epithelium, surrounded by spindle cell stroma
Walthard cell nests: usually microscopic cystic/solid structures with urothelial-type epithelium and variable mucin seen in mesovarium, mesosalpinx, and ovarian hilus

Case reports

● 70 year old woman with hilar mesonephric rests associated with nonteratoid prostatic differentiation (Am J Surg Pathol 1999;23:232)

Gross images

Corpus luteum

cystic, with follicular cysts


Various drawings of ovary

Micro images

Hilus cell hyperplasia:
Left-large nodular masses of hilus cells are present, one surrounding the rete ovarii
Right-post-menopausal woman whose hilus cells have bizarre shapes and abundant eosinophilic cytoplasm, some nuclei are enlarged and hyperchromatic

Nodular hilar cell proliferation

Primordial and antral follicles

Primordial follicles #1; #2; tertiary follicle

Ruptured follicle #1; #2

Atretic follicle #1; #2

Serosa; hilus

Corpus luteum - hemorrhagic

Low columnar cells are separated from cortical stroma by basement membrane

Ovarian stroma is composed of spindle cells with scant cytoplasm in a storiform pattern

Luteinized stromal cells have moderate eosinophilic cytoplasm, round nucleus and prominent nucleolus

Adrenocortical rest in mesosalpinx: top image shows fibrous capsule and zonation into glomerulosa, fasciculata and reticularis layers; bottom image shows cells of zona glomerulosa and zona fasciculata with spongy (lipid- rich) cytoplasm

Corpus luteum of menstruation: larger cells are granulosa lutein cells, smaller cells with clear (lipid- rich) cytoplasm are theca lutein cells

Involuting corpus luteum has granulosa lutein cells filled with (lipid) vacuoles and containing pyknotic nuclei

Corpus luteum of pregnancy: left-central hyaline bodies are present; right-foci of calcification in involuting corpus luteum


4 primordial follicles (left), 2 primary follicles (center) and a secondary follicle (right) are present

Secondary follicle: stratified granulosa cells surround the oocyte enveloped by its zona pellucida, theca interna layer is not yet apparent

Graffian follicle: cumulus oophorus, containing the oocyte and its zona pellucida, projects into the antrum

Granulosa cells of proliferating follicle exhibit marked mitotic activity

Follicles - mature:
#1 - Layers from top to bottom are antrum, a layer of granulosa cells with a single Call-Exner body, a layer of luteinized theca interna cells, an ill- defined theca externa, and the ovarian stroma;
#2 - Reticulin stain shows abundant reticulin in theca interna layer but no reticulin in granulosa layer;
#3 - Theca externa has numerous mitotic figures

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

Mesothelial hyperplasia (left to right):
#1-Present between outer surface of an ovarian serous borderline tumor (left) and vascular adhesion (right)
#2-Mesothelial cells have abundant pale eosinophilic cytoplasm, small focus of calcification is evident
#3-Numerous small tubular structures and cords of mesothelial cells are growing in a parallel array


Surface epithelial stromal proliferation

Vacuolar change within surface epithelial inclusion glands

Artifact-granulosa cells in blood vessel lumina

Infarcted appendix epiploica attached to ovarian surface, with focal calcification

Pregnancy-related changes:
Granulosa cell proliferation:
An atretic follicle is filled with a proliferation of granulosa cells growing in a pattern resembling a microfollicular granulosa cell tumor
The granulosa cell layer of a cystic atretic follicle is replaced by solid tubules resembling a Sertoli cell tumor. the tubules are surrounded by a layer of theca lutein cells

Ectopic decidua:
One cell is vacuolated, somewhat resembling a signet- ring cell
Large nodules were present on the ovarian and peritoneal surfaces, the cells have abundant eosinophilic cytoplasm and central, pale, round nuclei

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

Virtual slides

Normal ovary - infant


Corpus luteum; corpus albicans

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

End of Ovary - nontumor > Normal histology

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