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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.

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

Gross images
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Corpus luteum

cystic, with follicular cysts

Drawings
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Various drawings of ovary

Micro images
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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

Follicles:

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

Miscellaneous:

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

Miscellaneous:
   
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

Virtual slides
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Normal ovary - infant

Videos
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Corpus luteum; corpus albicans

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

Negative stains
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● CD10

End of Ovary - nontumor > Normal histology

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