Vagina
10 January 2006, links checked 23 February 2006
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Vagina - table of contents
Primary references, normal anatomy, adenosis, cysts, endosalpingiosis, infections, neovagina, urothelial metaplasia
Benign tumors: angiomyofibroblastoma, fibroepithelial polyp, leiomyoma, mullerian papilloma, other non-malignant tumors, polyposis vaginalis, postoperative spindle cell nodule, pseudosarcomatous fibroepithelial stromal polyp, rhabdomyoma, spindle cell epithelioma, squamous papilloma, superficial cervicovaginal myofibroblastoma, tubulovillous adenoma
Malignant tumors: adenocarcinoma NOS, aggressive angiomyxoma, clear cell adenocarcinoma, endometrioid adenocarcinoma, granulocytic sarcoma, leiomyosarcoma, lymphoma, malignant mixed tumor, melanoma, mesonephric adenocarcinoma, metastases, mucinous adenocarcinoma, other malignancies, rhabdomyosarcoma, small cell carcinoma, spindle cell carcinoma, squamous cell carcinoma, urothelial carcinoma, VAIN, verrucous carcinoma, yolk sac tumor
Primary references
AJCC Cancer Staging Manual (6th Ed)
American Journal of Surgical Pathology (AJSP), Mar 1977 to Mar 2003
Archives of Pathology and Laboratory Medicine (Archives), Oct 1975 to Jan 2003
Human Pathology (Hum Path), March 1970 to Feb 2003
Modern Pathology (Mod Path), Jan 1988 to Feb 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
Normal anatomy
Extends from vulva to uterine cervix
Derived from paired mullerian ducts
Layers are mucosa, muscularis, adventitia
Mucosa composed of basal, intermediate and superficial squamous epithelium; responsive to steroid hormones
Lamina propria (subepithelial stroma) composed of elastic fibers, rich venous and lymphatic network, some multinucleated stellate stromal cells
Wolffian (mesonephric) duct aka Gartner’s duct, runs deeply along lateral vaginal walls; single small duct surrounded by cluster of small glands lined by cuboidal epithelium with eosinophilic secretion in lumen
Lymphatic drainage: external iliac nodes (upper anterior wall), deep pelvic, rectal and aortic nodes (posterior vagina), interiliac nodes (lower vagina), also inferior gluteal and femoral nodes.
Gross images: image1
Adenosis
Mullerian type glandular epithelium in vagina, seen in 41% of postpubertal females at autopsy vs. 0% pre-pubertal
May present with excess mucus
Adenosis present in 35% to 90% after in utero exposure to DES, taken by pregnant women until 1971 in USA (100% have adenosis if DES started before gestational week 8, 6% if started week 15 or later)
DES adenosis is similar histologically to non-DES adenosis
Mouse model of DES exposure demonstrates vaginal adenosis and structural changes similar to actual changes observed in women, Hum Path 1982;13:190
Risk of subsequent clear cell adenocarcinoma is increased but very small
Gross: red granular spots or patches that don’t stain with Lugol’s iodide solution
Micro: endocervical-type mucous glands on vaginal surface or in lamina propria, often presenting as cysts or nodules; also tuboendometrial cells and embryonic columnar cells between lamina propria and squamous epithelium; intestinal metaplasia rare; often chronic inflammation and squamous metaplasia (may be extensive and obliterate glandular lumina, may resemble dysplasia / VAIN); microglandular hyperplasia present if patient using oral contraceptives
Positive stains: mucicarmine
Cytology: may be detected in vaginal smears if present on vaginal epithelium
DD: clear cell carcinoma (if microglandular hyperplasia present),
Transverse ridges
Aka cockscomb cervix, rims, collars, hoods, pseudopolyps
In upper vagina or cervix of 25% of women with DES exposure
Micro: fibrous tissue lined by mucinous epithelium or metaplastic squamous epithelium; rarely tubal or endometrial epithelium
DES related VAIN
DES related VAIN I lesions usually regress after therapy or biopsy, but VAIN II/III lesions tend to persist and recur after biopsy or therapy (are often aneuploid)
Non DES-related adenosis
Median age 44 years, range 24 to 88 years
15% symptomatic
Similar microscopic appearance to DES-related adenosis, Hum Path 1986;17:488
Cysts
Vaginitis emphysematosa: rare (<200 cases), vaginal nodules that produce “popping sound”, composed of variably sized cysts with pink, hyaline-like material, foreign body giant cells and chronic inflammatory infiltrate; self-healing, Archives 1987;111:746
Epithelial inclusion cyst: lined by squamous epithelium; may occur post-surgery or trauma
Gartner duct cyst: rare, in lateral vaginal wall, non-mucin secreting
Mullerian/mucous cyst: mucin secreting columnar cells, focal squamous metaplasia
Urothelial cysts: rare, from periurethral and Skene’s glands
Endosalpingiosis
Glands lined by ciliated tubal-type epithelium
Typically affects pelvic and abdominal peritoneum, usually as an incidental microscopic finding, but may be associated with ovarian serous neoplasms
Benign, but may have atypical epithelial changes
Rarely forms a cystic mass (florid cystic endosalpingiosis), Hum Path 2002;33:944
DD: extraovarian serous cystadenoma
Infections
Bacterial vaginosis
Overgrowth of facultative and anaerobic bacterial flora
Micro: often clue cells (squamous cells covered with coccobacilli)
Candida albicans
Common during pregnancy
Human immunodeficiency virus (HIV)
Increased propensity for heterosexual transmission of subtype E in Thailand may be related to vaginal inflammation, leading to accumulation of Langerhans cells and related dendritic cells, which may be HIV reservoir, Mod Path 2001;14:1263
Micro images: image1
Human papillomavirus
Infection may occur in distal vagina
Children or young adults have typical features, may have history of sexual contact
Micro: papillary / verrucous architecture, koilocytotic atypia
Molecular: 77% diagnosed as condyloma were HPV+, usually HPV 6 (67%), HPV 11 (17%), HPV 16 (3%), AJSP 1994;18:728
Lymphogranuloma venereum
May cause vaginal stricture
Trichomonas vaginalis
Common during pregnancy
Neovagina
Aka artificial vagina
Created from isolated segments of sigmoid colon or from peritoneum, for patients with vaginal aplasia or in male to female transsexuals
Patients with sigmoid vaginas but without bowel disease had discharge, slight blood loss and mild diversion colitis
Micro:
sigmoid vaginas - mild diversion colitis with lymphocytic infiltration, variable acute inflammatory infiltrate in lamina propria
peritoneum vaginas - squamous metaplastic epithelium with variable paramesonephric-like glandular elements in mucosa and submucosa resembling mild adenosis
References: Hum Path 1993;24:846, Hum Path 1982;13:1100
Urothelial (transitional) metaplasia
Mean age 68 years (range 50 to 84 years); usually no hormonal therapy; incidental microscopic finding
Micro: hyperplastic epithelium lacking maturation, composed of spindled nuclei with longitudinal nuclear grooves, perinuclear halos, low N/C ratios, rare/no mitotic figures; usually no atypia
DD: VAIN
Reference: AJSP 1997;21:510
Benign tumors
Benign vulvar and vaginal tumor, first described in 1992, AJSP 1992;16:373
Case report of sarcomatous transformation in vulva, AJSP 1997;21:1104
No reported recurrences after excision
Gross: well circumscribed, 0.5 to 12.0 cm
Micro: circumscribed tumor with alternating hypercellular and hypocellular areas, spindle cells and plump stroma cells with eosinophilic cytoplasm that aggregate around small blood vessels; may have binucleated or multinucleated cells; minimal stromal mucin, rare/no red blood cell extravasation, no atypia; rare/no mitotic figures; mast cells common
Positive stains: vimentin, desmin
Negative stains: actin, keratin, S100
EM: well developed rough endoplasmic reticulum, Golgi apparatus, intermediate filaments, pinocytotic vesicles
DD: angiomyxoma (not circumscribed, less cellular, fewer vessels, no hyalinized vessels, stromal mucin, RBC extravasation, infrequent plump stromal cells)
Reference: Mod Path 1996;9:284
Fibroepithelial polyp
Adult women during pregnancy or neonates
Due to hormone induced hyperplasia of loose subepithelial connective tissue or end stage of granulation tissue
Micro: central fibrovascular core covered by normal appearing squamous epithelium; stroma may be edematous, hypocellular; may have atypical stromal cells
Positive stains: desmin, vimentin
Negative stains: actin
DD: botyroid rhabdomyosarcoma (cambium layer, epithelial invasion, rapid growth, cross striations)
Leiomyoma
Most common benign mesenchymal tumor of vagina
Usually affects adults, not children
Mullerian papilloma
Aka mesonephric papilloma, intramural papilloma, but actually mullerian origin
Rare, benign, polypoid lesion of cervix or vagina of young girls to adult women
Micro: superficially located, composed of delicate stalks covered by cuboidal cells; no atypia, minimal mitotic activity
Positive stains: CK7, CA125
Negative stains: CK20, CEA
Other non-malignant tumors
Neurofibromatosis can affect vagina, AJSP 1989;13:873
Polyposis vaginalis of pregnancy
Case report in pregnant 15 year old at Archives 1989;113:1391
Numerous polyps in vagina and cervical portio that disappear post-partum
DD: botyroid rhabdomyosarcoma
Postoperative spindle cell nodule
Pseudosarcomatous vaginal lesion, appears within a few weeks of hysterectomy
Gross: small friable reddish mass in vaginal vault
Micro: granulation tissue, hypercellular spindle-cell proliferation, many typical mitotic figures, extravasated red blood cells, fascicular pattern, no pleomorphism
Positive stains: low molecular weight keratin
DD: leiomyosarcoma, Kaposi’s sarcoma
Pseudosarcomatous fibroepithelial stromal polyps
Resemble fibroepithelial stromal polyps of vagina, vulva and cervix, but with bizarre morphology, frequent mitoses (>10/10 HPF), atypical mitotic figures or hypercellularity
Median age 32 years, range 16-75 years
Often in pregnant patients
May recur locally; no metastases
Positive margin status, which is common, apparently not associated with recurrence
Gross: often multiple lesions, particularly in pregnant women
Positive stains: desmin
DD:
aggressive angiomyxoma: deep, prominent vascular pattern cuffed by myoid bundles
angiomyofibroblastoma: well-circumscribed subserosal nodule, no atypia, stromal cells cluster around vessels, which usually have delicate walls
botyroid embryonal rhabdomyosarcoma: early childhood, submucosal hypercellular zone/cambium layer, rhabdomyoblasts, myoglobin+, myogenin+
cellular angiofibroma: well circumscribed, less polypoid, diffusely vascular with hyalinized walls, no atypical stromal cells, desmin-
leiomyosarcoma: clear boundary of tumor cells with epithelium, smooth muscle differentiation
low grade endometrial stromal sarcoma: vessels resemble spiral arterioles, no central vascular core, thick bands of collagen in starburst pattern, dot like staining of desmin or keratin
MPNST: perivascular accentuation, 50% are S100+, DFSP (CD34+, desmin-, storiform throughout)
Reference: AJSP 2000;24:231
Rhabdomyoma
Presents as polypoid mass in adults
Micro: interweaving and haphazardly oriented bundles of spindle- to strap-shaped cells, some with cross striations; rare mitotic figures, no concentration of neoplastic cells beneath the epithelium; may have huge cells with cytoplasmic vacuolization
DD: rhabdomyosarcoma (children, mitotically active, cambium layer)
Spindle cell epithelioma
Aka benign mixed tumor, but does not appear to derive from myoepithelial cells
Near hymeneal ring
May recur locally
Gross: well-circumscribed, but not encapsulated, not connected to surface epithelium
Micro: small, stromal type spindle cells mixed with squamous cells and mucinous glands; numerous small vessels and localized hyaline globules
Micro images: image1
Positive stains: cytokeratin, vimentin, ER, PgR, CD34, CD99, bcl-2
Negative stains: S100, smooth muscle actin
EM: epithelial differentiation (tonofilaments and desmosomes), no myoepithelial differentiation
References: AJSP 1993;17:509, AJSP 1981;5:413, Archives 2001;125:547
Squamous papilloma
More common in cervix
HPV related
Superficial cervicovaginal myofibroblastoma
Mean age 58 years, range 40 to 74 years
Benign behavior
May be neoplastic proliferation of hormonally responsive mesenchymal cells native to subepithelial stroma of endocervix, vulva and vagina of adult women
Gross: well circumscribed, polypoid or nodular mass, mean 3 cm (range 1 to 6.5 cm) arising in the superficial lamina propria of cervix and vagina
Micro: cellular, composed of bland spindled and stellate mesenchymal cells in collagenous stroma with myxoid and edematous foci; often lacelike pattern in hypocellular area, vague fascicular growth pattern in cellular area; minimal mitotic activity; no atypical mitotic figures
Positive stains: vimentin, ER, PgR, desmin, CD34; alpha smooth muscle actin (45%), muscle specific actin (25%)
Negative stains: S100, EMA, keratin
DD: fibroepithelial stromal polyp, angiomyofibroblastoma, aggressive angiomyxoma
Reference: Hum Path 2001;32:715
Tubulovillous adenoma
Resembles colonic adenoma
Malignant Neoplasms
Adenocarcinoma, NOS
May arise from adenosis
Case report of non-DES related tumor, Archives 1985;109:781
Subtypes below: clear cell, endometrioid, mesonephric, mucinous
Aggressive angiomyxoma
Bland appearing, slow growing tumor of vulva, vagina, pelvic floor, perineum
Usually teens/young adults, rarely children; occurs in men in scrotum
Low grade malignancy - recurs locally in ischiorectal or retroperitoneal space, perhaps due to incomplete excision, Hum Path 1985;16:621
Treatment: wide local excision
Gross: white, soft or gelatinous, ill defined masses with infiltrative borders, larger and deeper than fibroepithelial polyp; may present as protruding intravaginal mass
Micro: spindled and stellate cells in hypocellular myxomatous stroma, no/rare mitotic figures, no atypia; thick walled vessels with dilated lumina and occasional hyaline thickening of adventitia; extravasation of red blood cells common; often deep, prominent vascular pattern cuffed by myoid bundles; no bizarre stromal cells
Positive stains: actin
Negative stains: S100, factor 8, CEA, keratin
EM: primitive mesenchymal cells with fibroblastic features
Clear cell adenocarcinoma
Aka mesonephroid carcinoma
Usually upper vagina or cervix of children or adults
Mean age 17 years, rare before age 12 or after age 30
2/3 have history of prenatal DES exposure (stopped in 1971); risk of malignancy from DES exposure is only 1 per 1000
Associated with other DES related lesions: vaginal adenosis, cervical ectropion, transverse vaginal or cervical ridges, Archives 1977;101:1
Treatment: surgery (small tumors), radiation
Prognosis: relatively good, local recurrence if close to margins, 3 mm+ deep or large tumors; recurrences may be very late
Metastases to lungs, pelvic lymph nodes
16% died of disease in one series
Gross: may involve most of vagina; usually polypoid and nodular but may be flat/ulcerated; usually only superficially invasive at diagnosis
Micro: tubules, cysts, solid and papillary areas with clear cells that have abundant cytoplasm (glycogen, rarely fat), rare mucin; hobnail cells common; rare mitotic activity; associated with atypical tuboendometrial epithelium
EM: similar to clear cell carcinoma of ovary, endometrium
DD: microglandular hyperplasia, Arias Stella reaction (pregnancy, progestational agents)
Endometrioid adenocarcinoma
Presumed due to endometriosis
Granulocytic sarcoma
Vagina may be initial site of presentation
Often coexisting bone marrow involvement by AML
Micro: diffuse growth pattern, also cords and pseudoacinar spaces; often primitive cells with only rare myelocytes; sclerosis common
Positive stains: chloroacetate esterase, lysozyme, myeloperoxidase, CD68, CD43
DD: lymphoma, carcinoma, granulosa cell tumor
Reference: AJSP 1997;21:1156
Leiomyosarcoma
Tend to recur locally
Poorer prognosis if poorly differentiated
Gross: large, ulcerative
Micro: 5 or more mitotic figures/10 HPF; moderate to severe atypia
Lymphoma
top
Rare to involve vagina
Usually present with vaginal bleeding or vaginal mass
Eight primary lymphoma, low stage patients had mean age 42 years (range 26 to 66 years), one died of disease
Six secondary lymphoma patients had mean age 65 years (range 49 to 82 years), one died of disease, but short follow up
Almost all cases diffuse large B cell lymphoma, one secondary SLL/CLL
Micro: typical findings, but also sclerosis, rarely malakoplakia
References: AJSP 2000;24:719, Hum Path 1999;30:871
Malignant mixed tumor of vagina
Rare
Biphasic pattern of glands and spindle cells
Resembles synovial sarcoma
May arise from Gartner ducts or related mesonephric rests
Micro: not circumscribed, more atypia and higher mitotic rate than spindle cell epithelioma (benign mixed tumor)
Melanoma
Rare, primary vaginal tumor in elderly (more common in vulva)
Mean age 60 years, range 38 to 90 years
Present with vaginal bleeding or vaginal mass
Associated with melanosis, Archives 1991;115:950
Poor prognosis due to local recurrence or distant metastases, AJSP 2002;26:1450
Note: 3% of normal vaginas have melanocytes present
Treatment: wide local excision, extenteration with or without lymph node dissection, radiotherapy, chemotherapy
Gross: soft blue/black polypoid mass, often ulcerated
Micro: epithelioid or spindled cells, more anaplastic than cutaneous melanomas; junctional activity proves local origin although it may be destroyed by tumor
Positive stains: S100, HMB45 (73%), MART1 (77%), tyrosinase (81%), MiTF (77%)
Mesonephric adenocarcinoma
Rare, located along Gartner ducts
Metastases to vagina
Usually cervix, endometrium, ovary, colon, kidney
Endometrial carcinoma metastases often to upper third of vagina, reduced by radiation therapy
Mucinous adenocarcinoma
Middle aged/elderly patients
Similar to cervical counterpart
Other malignancies
Paget’s disease in 78 year old woman extensively involving genital tract, Archives 1988;112:941
Post-radiation angiosarcoma: case report 21 years after radiation for cervical carcinoma, Archives 1991;115:527
Rhabdomyosarcoma
Most common malignant soft tissue tumor in children and adolescents
6% of all malignancies in children; 20% occur in pelvic portion of GU tract
Usually embryonal or botyroid subtype
10 year survival is 73% for classic embryonal subtype
Histologic maturation after treatment often occurs, but these cells may be malignant
Positive stains: desmin, actin (usually)
Botyroid (embryonal) rhabdomyosarcoma
Aka sarcoma botyroides
Usually children < 5 years (2/3 under age 2) in anterior vaginal wall
Treatment: surgery, chemotherapy, radiation therapy
10 year survival is 91%, but may die due to direct extension, AJSP 2001;25:856
Gross: grapelike clusters that fill and project out vagina