Cervix
Last revised 25 July 2008
Last major update February 2006
Copyright © 2003-2008, PathologyOutlines.com, Inc.
Reviewed by Dr. Branko Perunovic (see Reviewers Page)
See also Cervix-cytology, Uterus
Cervix: embryology, normal anatomy, normal histology, metaplasia
Inflammation: inflammation-general, actinomycosis, amebiasis, bacterial vaginosis, Candida/fungi, Chagas’ disease, chlamydia, chronic cervicitis, CMV, Enterobius, granuloma inguinale, granulomas, herpes, pseudolymphoma, Schistosomiasis, syphilis, Trichomonas, tuberculosis, vasculitis, Wuchereria
Benign/non-neoplastic lesions: adenomyoma, adenosis, Arias-Stella reaction, atrophy, atypical polypoid adenomyoma, blue nevus, cervical pregnancy, decidual nodule, decidual reaction, diffuse laminar endocervical glandular hyperplasia, ectopic tissue/heterotopia, endocervical polyp, endometrial polyp, endometriosis, endosalpingiosis, florid deep glands, glial polyp, hemangioma, inflammatory pseudotumor, inverted urothelial papilloma, leiomyoma, lipoleiomyoma, lobular endocervical hyperplasia, melanosis, mesonephric papilloma, mesonephric rests, mesonephric hyperplasia, microglandular hyperplasia, myofibroblastoma, Nabothian cysts, necrobiotic granulomas, neurofibroma, pagetoid dyskeratosis, papillary adenofibroma, papillary endocervicitis, placental site nodule, post-operative spindle cell nodule, pseudosarcomatous fibroepithelial stromal polyps, pyogenic granuloma, rhabdomyoma, squamous papilloma, traumatic neuroma, tunnel clusters
Premalignant/preinvasive lesions: HPV, condyloma, atypical squamous lesion, SIL-general, LSIL/CIN I, HSIL/CIN II, HSIL/CINIII, SIL variants, endocervical glandular atypia/dysplasia, adenocarcinoma in situ, radiation atypia, stratified mucin producing intraepithelial lesions
Carcinoma: WHO classification, squamous cell and variants, microinvasive squamous cell, adenocarcinoma and variants, microinvasive adenocarcinoma, adenoid basal, adenoid cystic, adenosquamous, basaloid squamous cell, carcinoid, clear cell, endometrioid, epithelioid trophoblastic tumor, glassy cell, large cell neuroendocrine, lymphoepithelioma-like, mesonephric adenocarcinoma, metastases to cervix, minimal deviation adenocarcinoma, mixed, serous papillary adenocarcinoma, small cell, spindle cell, urothelial, verrucous, villoglandular papillary adenocarcinoma, warty
Sarcoma/lymphoma/other: adenosarcoma, aggressive angiomyxoma, alveolar soft parts sarcoma, Ewing’s sarcoma/PNET, granulocytic sarcoma, leiomyosarcoma, lymphoma, malignant mixed mullerian tumor, melanoma, other (case reports), plasmacytoma, rhabdomyosarcoma, stromal sarcoma, teratoma, Wilm’s tumor, yolk sac tumor
Miscellaneous: procedures, grossing, staging of cervical carcinoma, features to report
Go to Cervix-cytology
AJCC Cancer Staging Manual (6th Ed)
American Journal of Clinical Pathology (AJCP), August 1975 to February 2006
American Journal of Surgical Pathology (AJSP), March 1977 to January 2006
Archives of Pathology and Laboratory Medicine (Archives), June 1976 to January 2006
Human Pathology (Hum Path), May 1974 to January 2006
Modern Pathology (Mod Path), March 1988 to January 2006
Kurman: Tumors of the Cervix, Vagina, and Vulva (AFIP, 3rd Series, Vol 4)
Rosai, J: Ackerman’s Surgical Pathology (9th Ed); Mosby, 2004
Sternberg,
S: Diagnostic Surgical Pathology (4th Ed); Lippincott Williams & Wilkins,
2004
Website: Histopathology and cytopathology
of the Uterine Cervix – Digital Atlas
Journal search terms: cervix, cervicovaginal
Please refer to these primary references for more detailed discussions and photographs
Mesoderm derived mullerian ducts fuse at day 54 post-conception and form uterovaginal canal, lined by mullerian columnar epithelium
Uterovaginal canal joins endoderm lined urogenital sinus at mullerian tubercle, which becomes vaginal orifice at hymenal ring
Epithelium stratifies at caudal uterovaginal canal to become squamous; epithelium proliferates to become almost purely squamous in vagina by day 77
Endocervical glands and vaginal fornices appear between days 91 and 105
Cervix responds to estrogenic stimulation by marked growth
Lower 1/2 to 1/3 of uterus, cylindrical, connects uterus to vagina via endocervical canal
Consists of portio vaginalis (portion that protrudes into vagina) and supravaginal portion
2.5 to 3.0 cm long and 2.0 to 2.5 cm in diameter
Anteriorly abuts on bladder; posteriorly is covered by peritoneum that forms lining of cul-de-sac
Endocervix: relates to endocervical canal
Ectocervix (exocervix): vaginal portion of cervix
External os: opening of endocervical canal to ectocervix
Fornix: reflection of vaginal wall that surrounds ectocervix
Internal os: indistinct upper limit of endocervical canal
Transformation zone: see also under histology; usually appears red due to rich capillary network and is called cervical erosion, although ectropion is a better term
Cardinal ligaments: fibromuscular bands that fan out from lower uterine segment and cervix to lateral pelvic walls and provide main support for cervix
Uterosacral ligaments: connective tissue surrounding cervix and vagina that extends towards vertebrae
Lymphatics: cervix is drained by parametrial, cardinal and uterosacral ligament routes
Drawings: local anatomy; microanatomy; saggital section of local anatomy #1; #2; uterus, cervix and vagina #1; #2; vasculature
Gross: nulliparous cervix; endocervical canal
References: ASCCP
Most of cervix is composed of fibromuscular tissue
Epithelium is either squamous or columnar
Endocervix: lined by columnar epithelium that secretes mucus; epithelium has complex infoldings that resemble glands or clefts on cross section; mucosa rests on inconspicuous layer of reserve cells
Ectocervix (exocervix): covered by nonkeratinizing, stratified squamous epithelium, either native or metaplastic; has basal, midzone and superficial layers; after menopause is atrophic with mainly basal and parabasal cells with high N/C ratio that resembles dysplasia; prepubertal girls have similar appearing epithelium
Stem cells are in suprabasal layer
Squamocolumnar junction: where squamous and glandular epithelium meets; usually in exocervix; nearby reserve cells are involved in squamous metaplasia, dysplasia and carcinoma
Transformation zone: also called ectropion, between original squamocolumnar junction and border of metaplastic squamous epithelium; epidermalization and squamous differentiation of reserve cells transform this area to squamous epithelium; site of squamous cell carcinomas and dysplasia
Note: endocrine cells and melanocytes are seen occasionally in cervix; multinucleated giant cells may be a normal finding, often accompanied by edema (Archives 1985;109:200)
Basal cells (reserve cells): cuboidal to low columnar with scant cytoplasm and round/oval nuclei; acquire eosinophilic cytoplasm as they mature; positive for low molecular weight keratin and estrogen receptor; negative for high molecular weight keratin and involucrin
Suprabasal cells: have variable amount of glycogen, detectable with Lugol/Schiller’s test (application of iodine) or microscopically by PAS stain; positive for high molecular weight keratin and involucrin
Glandular epithelium: positive for estrogen receptor
Menarche: ovaries produce estrogen, which stimulates glycogen update by cervical and vaginal mucosa, which promotes growth of endogenous vaginal microorganisms, which produce acid and drop in vaginal pH; basal/reserve cells respond by proliferating, causing squamous and columnar metaplasia; squamous epithelium overgrows columnar epithelium, obstructing crypt openings and forming Nabothian cysts; also produces acute and chronic inflammatory infiltrate
Drawings: location of glandular and squamous epithelium
Gross images: squamocolumnar junction
){kind=link}
Micro images: ectocervix (H&E, stains, EM); normal nonkeratinizing squamous epithelium #1; #2; #3; #4
){kind=link}
transformation zone #1-various images; #2; #3
endocervix (H&E, stains, EM); endocervix #1; #2; #3; #4; #5; infoldings resemble glands; endocervical canal (whole mount)
){kind=link}
cervical myometrium #1; #2; myometrium and adventitia; prepubertal squamous epithelium shows only basal and parabasal cells with no maturation
Virtual slides: normal cervix
Cytology: see Cervix-cytology
References: ASCCP
Defined as change in differentiation pathway to which the stem cell progeny commit
Not neoplastic
Micro images: osseous and cartilaginous metaplasia
DD: metaplastic growth pattern, which may be neoplastic
Atypical oxyphilic metaplasia of cervix
Very rare
Incidental finding with benign behavior
Mean age 48 years, range 41 to 62 years
Case reports: 37 year old woman (Cesk Patol 2000;36:60)
Micro: large, cuboidal or polygonal epithelial cells with dense eosinophilic, focally vacuolated cytoplasm; variable nuclear atypia in endocervical glands due to enlarged, hyperchromatic or multinucleated / multilobated nuclei; rarely apical snouts; no mitotic figures, no stratification
References: Int J Gynecol Pathol 1997;16:99
Epidermoid metaplasia of cervix
Very rare
Associated with uterine prolapse, prolonged irritation or synthetic steroids (Obstet Gynecol 1974;44:53)
Case reports: 44 year old woman with ectocervical lesion (Archives 2004;128:1052)
Micro: epidermis, sebaceous glands and hair follicles
Micro images: (1) with sebaceous glands; (2) figure 1: cervix covered by keratinized squamous epithelium with prominent granular cell layer; 2: stroma has mature sebaceous glands; 3: sebaceous cells are surrounded by epithelial cells
DD: mature teratoma
Immature squamous metaplasia of cervix
Micro: resembles squamous metaplasia but without cytoplasmic glycogen; mild reactive changes include mild variation in nuclear size and hyperchromasia; often surface maturation; when acutely inflamed may resemble SIL, but cells are not crowded or disorganized, nuclei are round and uniform and not hyperchromatic, background cells have prominent nucleoli (reactive changes); often overlying mucinous epithelium
Cytology: see Cervix-cytology
Micro images: immature squamous metaplasia; with mild atypia
Intestinal metaplasia of cervix
Rare, may have mucin extravasation into stroma
Case reports: with HSIL (Histopathology 1985;9:551), with florid endocervical glandular hyperplasia (Gynecol Oncol 1999;74:504), with cervical dysplasia and leiomyosarcoma (Rev Chil Obstet Ginecol 1993;58:481), with villous adenoma and adjacent adenocarcinoma (Int J Gynecol Pathol 1986;5:163)
Micro: goblet cells, occasionally Paneth cells
Squamous metaplasia of cervix
See also immature squamous metaplasia above
Replacement of endocervical epithelium by subcolumnar reserve cells, which differentiate into immature and then mature squamous epithelium (see also normal histology above)
Common response to chronic irritation in nonsquamous tissue; present in almost every cervix
Centered on transformation zone
May also arise from ingrowth of squamous epithelium from ectocervix (squamous epithelialization)
Not a premalignant condition by itself
Keratosis: appearance of granular and horny epithelial layers, often associated with prolapsed uteri (see pagetoid dyskeratosis below)
Micro: squamous epithelium overlies endocervical glands, may replace glands; metaplastic cells may be immature, intermediate or mature; resembles epithelium normally lining ectocervix with flat architecture; may have cytologic atypia
Cytology: see Cervix-cytology
Micro images: various images #1; #2; early metaplasia; involving clefts; with cytoplasmic vacuoles
Tuboendometrial metaplasia of cervix
Common (1/3 of women); in upper portion of endocervical canal, often in deep glands
Often seen after cervical cone biopsy; may represent response to injury
Micro: tubal metaplasia - endocervix contains ciliated cells (clear cytoplasm, abundant apical cilia and large, oval, variably hyperchromatic nuclei), secretory cells (nonciliated with dark eosinophilic or basophilic cytoplasm, apical cytoplasmic protrusions but no mucin vacuoles, basal nuclei); and intercalated cells (also called peg cells, scant cytoplasm, thin and long nuclei), as found in normal fallopian tube; glands are regular; minimal mitotic activity, rare crowding or atypia; also associated with endometrial type cells; usually near squamocolumnar junction, usually no inflammation
May have cystic glands and periglandular stromal alterations suggestive of premalignant conditions, or deep glands with periglandular edema suggestive of well differentiated adenocarcinoma, but cells are ciliated with bland cytology, no mitotic figures, no definite desmoplastic stroma (AJCP 1995;103:618)
Cytology: see Cervix-cytology
Micro images: tubal metaplasia #1; #2; #3; #4; #5 (bcl2+)
Positive stains: CEA (not helpful in differential diagnosis below)
DD: endometrioid adenocarcinoma (invasive growth pattern, marked nuclear atypia, increased Ki-67 staining), adenocarcinoma in situ (lesion at squamocolumnar junction involving superficial but not deep glands; cells do not resemble fallopian tube or endometrium; have coarse nuclei, abundant mitotic figures)
References: Archives 1993;117:734, Mod Path 2000;13:261
Urothelial metaplasia of cervix
Also called transitional cell metaplasia
An incidental microscopic finding of exocervical squamous epithelium associated with atrophic changes in the elderly
May represent basal cell hyperplasia or atrophy associated with androgen exposure
Case reports: with ectopic prostatic tissue in 23 year old woman with adrenogenital syndrome (Int J Gynecol Pathol 2004;23:182)
Micro: hyperplastic epithelium without maturation composed of urothelial type cells with tapered ends, spindled nuclei with longitudinal nuclear grooves and perinuclear halos, but minimal nuclear atypia, low N/C ratios and rare/no mitotic activity
Cytology: see Cervix-cytology
Micro images: urothelial metaplasia #1; #2; #3; #4 (serotonin+); transitional metaplasia and atrophy after androgen treatment #1; #2
Positive stains: CK13, CK17, CK18; basal cells-calcitonin, serotonin
Negative stains: CK20 (same as normal urothelium)
DD: HSIL (high N/C ratio, cellular disorganization and pleomorphism, high mitotic rate)
References: AJSP 1997;21:510, Mod Path 2000;13:252
Inflammation of cervix
Inflammation of cervix-general
At menarche, the ovaries produce estrogen, leading to glycogen uptake by cervix and vaginal squamous mucosa; shedding cells promote the growth of vaginal aerobes and anaerobes, leading to a reduced (acidic) vaginal pH, which causes metaplastic transformation of transformation zone mucosa from columnar to squamous in exposed endocervix; squamous epithelium overgrows columnar epithelium, obstructing crypt openings and forming Nabothian cysts; also produces acute and chronic inflammatory infiltrate
Micro images: reactive (inflammatory) atypia #1 (various images-mainly ectocervix); #2-endocervix; #3-transformation zone
Actinomycetes normally reside in the female genital tract, so presence does not indicate disease (Am J Obstet Gynecol 1999;180:265)
Associated with IUDs with colonization rate of 11%, increases with duration of use (J Reprod Med 1994;39:585, IPPF Med Bull 1983;17:1)
Less common than pseudoactinomycotic radiate granules that form around microorganisms or biologically inert substances
Micro: tangled clumps of gram positive filamentous organisms, often with acute angle branching, sometimes showing irregular wooly appearance; swollen filaments may be seen with clubs at periphery; often cotton ball-like acute inflammatory response
Cytology: see Cervix-cytology
May simulate or accompany carcinoma (Am J Trop Med Hyg 1992;46:759, Int J Gynaecol Obstet 1987;25:249, Archives 1985;109:1121)
Gross: polypoid and ulcerated mass; may engraft on pre-existing carcinoma
Micro images: various images (not cervix), figures 1-5; clusters of trophozoites (liver)
See Cervix-cytology
See Cervix-cytology
Case reports: HIV+ patient (Hum Path 2000;31:120)
Cytology: See Cervix-cytology
Chlamydia trachomatis of cervix
Most common sexually transmitted disease (STD) in Western world; 4 million new cases annually in US
Affects cervix, uterus, adnexae; not vulva/vagina
Chlamydia trachomatis is an obligate intracellular parasites with elementary bodies (infectious but incapable of cell division) and reticulate bodies (multiply within cytoplasm, but not infectious until they transfer back into elementary bodies)
Causes infertility
Diagnose based on culture, PCR of urine or enzyme immunoassay on cervical / urethral swab (Archives 2000;124:840)
Nucleic acid amplification of urine has similar sensitivity as samples from cervix or urethra (Ann Intern Med 2005;142:914)
Does NOT cause dysplasia
Micro: lymphoid germinal centers (follicular cervicitis-sensitive but not specific for chlamydia), plasma cells, reactive epithelial atypia
Cytology: see Cervix-cytology
Positive stains: immunocytochemistry can detect organisms
Found in almost all women (see normal histology above)
Depending on etiology, may cause endometritis, salpingitis, pelvic inflammatory disease (PID) or chorioamnionitis
Organisms of concern are gonococci, Chlamydia, Mycoplasma, HSV
Micro: affects squamocolumnar junction and endocervix; produces intercellular edema (spongiosis), submucosal edema, mononuclear inflammation, fibrosis
Micro images: chronic cervicitis; various images; ectocervicitis; endocervicitis
Cytology: See Cervix-cytology
Patients are usually NOT immunocompromised (J Clin Pathol 2004;57:691)
Viral shedding common in HIV+ women (Med Virol 1999;59:469)
Micro: large, basophilic intranuclear inclusions or intracytoplasmic eosinophilic inclusions in occasional endocervical glandular epithelial cells; inclusions also in endothelial and stromal cells but not squamous cells; associated with fibrin thrombi, dense acute inflammatory infiltrate, lymphoid follicles, vacuoles in glandular cells, reactive changes in glandular epithelial cells
Micro images: intracytoplasmic inclusions #1 (endocervical cells); #2 (endothelial cells); CMV+ glands and stroma; associated acute inflammatory infiltrate; intracytoplasmic vacuoles within endocervical glandular cells; fibrin thrombi within small vessels; not cervix - lung #1 (Giemsa stain); #2; kidney; pancreas; brain
Cytology: See Cervix-cytology
Cytology: See Cervix-cytology
Also called donovanosis
Due to gram negative rod, Calymmatobacterium granulomatis, which has characteristic bipolar staining
Sexually transmitted disease which affects genital skin and mucosa and causes inguinal lymphadenopathy; rarely becomes disseminated
May occur in children of infected mothers via birth canal (AJCP 1997;108:510)
May mimic carcinoma (Genitourin Med 1990;66:380)
Micro images: Donovan bodies
Cytology: See Cervix-cytology
Rare
Usually foreign body-type; also diffuse
Associated with prior biopsy or surgery (AJCP 2002;117:771)
Only rarely associated with sarcoidosis or systemic conditions
Ceroid (with early lipofuscin) granulomas may be related to endometriosis
Case reports: ceroid granulomas (Int J Gynecol Pathol 2002;21:191, Histopathology 1992;21:282), due to pinworms (J Trop Med Hyg 1981;84:215)
Micro images: (1) xanthogranuloma (ceroid granuloma); (2) A: PAS+; B: Perls’ iron stain+; C: Ziehl-Neelsen (acid fast)+; D: Schmorl’s reagent (melanin)+
Cytology: See Cervix-cytology
References: ceroid granulomas (J Clin Pathol 1995;48:1057)