> Table of Contents > Vaginal Adenosis
Vaginal Adenosis
Maeve K. Hopkins, MA, MD
Michael P. Hopkins, MD, MEd
image BASICS
DESCRIPTION
  • The normal vagina is lined with squamous epithelium. Adenosis is characterized by the presence of columnar epithelium or glandular tissue in the wall of the vagina.
  • Around week 15 of embryologic development, the müllerian system, which forms the upper 2/3 of the vagina, fuses with the invaginating cloaca or urogenital sinus to form the lower 1/3 of the vagina. Squamous metaplasia from the cloacal region then produces squamous epithelium within the vagina (1).
  • Adenosis occurs when this squamous epithelium fails to epithelialize the vagina completely.
  • Three main types of adenosis epithelium described
    • Endocervical
    • Endometrial
    • Tubal
  • System(s) affected: reproductive
Geriatric Considerations
  • Adenosis is a disorder of the young female. By menopause, the vagina and cervix should be completely epithelialized.
  • The presence of glandular epithelium in the postmenopausal patient is an indication for excision and close evaluation for the possibility of a welldifferentiated adenocarcinoma.
Pregnancy Considerations
Pregnancy produces a wide eversion of the transformation zone of the cervix. This occasionally will become so widely everted that it will extend onto the vaginal fornices, leading to the impression of adenosis. This will resolve after the pregnancy is completed.
EPIDEMIOLOGY
Incidence
  • Although the cumulative incidence of vaginal adenosis is unknown, the incidence of cloacal malformations is 1/20,000 to 1/25,000 live births.
  • Although spontaneous vaginal adenosis appears to be fairly common (10% of adult women), it is mostly an insignificant coincidental finding. Widespread symptomatic involvement is rare (2).
Prevalence
  • In the United States, adenosis is relatively common; affecting 10-20% of young females studied. As maturation progresses with puberty, epithelialization occurs.
  • Predominant age
    • Age <1 month: 15%
    • Prepubertal: typically absent
    • Age 13 to 25 years: 13%
    • Age >25 years: decreasing prevalence, uncommon beyond age 30 years (2)
ETIOLOGY AND PATHOPHYSIOLOGY
  • In most young females, the etiology is incomplete squamous metaplasia or epithelialization. This occurs as a natural phenomenon and resolves with age.
  • Described as congenital or acquired (2)
    • Congenital: proliferation of the remnant müllerian epithelium in the vagina due to exposure to diethylstilbestrol (DES) in utero (DES daughters)
    • Transformation-related protein 63 (TRP63/p63) marks the cell fate decision of müllerian duct epithelium to become squamous epithelium in the cervix and vagina. DES disrupts the TRP63 expression and induces adenosis lesions (3). It has also been suggested that DES induces vaginal adenosis by inhibiting the BMP4/Activin A-regulated vaginal cell fate decision through a downregulation of RUNX1 (4).
    • Acquired: trauma and inflammation causing spontaneous de novo changes or changes in an acquired lesion in the vaginal epithelium
    • Additional reports have documented adenosis occurring subsequent to sulfonamide-induced Stevens-Johnson syndrome and after treatment of vaginal condylomas with 5-fluorouracil (5).
RISK FACTORS
Adenosis of the vagina/cervix may arise in up to 90% of DES daughters, and there is a 40-fold increased risk of the subsequent development of clear cell adenocarcinoma (6).
GENERAL PREVENTION
None: last DES exposure in the 1970s
COMMONLY ASSOCIATED CONDITIONS
DES exposure
  • Adenosis from DES exposure should lead to an evaluation of other DES-related abnormalities.
  • Müllerian tract anomalies associated with DES exposure include cervical hood, cervical ridge, shortened cervix, incompetent cervix, and T-shaped uterine cavity.
  • Patients with known DES exposure should have their reproductive tract evaluated prior to conception.
  • Most patients with adenosis have not been DES-exposed and do not require evaluation of the reproductive system.
  • DES is a synthetic, nonsteroidal estrogen that was used to prevent spontaneous abortions or premature deliveries from 1938 to 1971 (6). An estimated 5 million women were prescribed DES during this period (3).
  • The FDA issued a drug bulletin in 1971 advising physicians to stop prescribing DES to pregnant women because of its link to vaginal clear cell adenocarcinoma in DES daughters (6).
image DIAGNOSIS
PHYSICAL EXAM
On pelvic exam, adenosis appearance is varied: patchy or diffuse red stippling, granularity or nodularity, single or multiple cysts, erosions, ulcers, or warty protuberances that may even extend to the vulva.
DIFFERENTIAL DIAGNOSIS
  • Erosive lichen planus
  • Fixed drug eruption
  • Erythema multiforme
  • Bullous skin disease
  • Adenocarcinoma
    • A thorough evaluation for adenocarcinoma of the vagina arising in adenosis should be done.
    • A biopsy may be necessary to ensure that the process represents only benign adenosis.
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
Four-quadrant Pap smear should be used liberally to isolate quadrants of the vagina that may contain abnormalities. No imaging is indicated, unless diagnosed with underlying malignancy.
Follow-Up Tests & Special Considerations
Pap smear can be followed by colposcopy and biopsy.
P.1099

Diagnostic Procedures/Other
Colposcopy should be used to outline areas of adenosis to ensure that no malignancy is present.
Test Interpretation
  • Biopsy will show benign glandular epithelium.
  • Biopsies in the areas of ongoing squamous metaplasia are typical (7).
image TREATMENT
GENERAL MEASURES
  • Unless malignancy is present, conservative treatment is indicated.
  • In most young females with this condition, it will resolve with expectant management (2).
  • Treatment is warranted in women with severe subjective symptoms that impair the quality of life (8).
  • For patients with focal lesions and no history of DES exposure, simple excision appears to be an effective modality of treatment (5)
ISSUES FOR REFERRAL
Malignancy found on biopsy warrants referral to gynecologic oncology specialist.
SURGERY/OTHER PROCEDURES
  • Aggressive therapy, such as laser or surgical excision, is necessary if premalignant or malignant changes arise (4).
  • Symptomatic treatment with carbon dioxide laser coagulation, unipolar coagulation, or, lastly, vaginal resection (2)
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Outpatient management
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
If the initial colposcopy is normal, a yearly fourquadrant Pap smear of the vagina and of the cervix is all that is necessary.
DIET
No special diet
PATIENT EDUCATION
  • No limitations
  • It is not necessary to avoid intercourse or placing objects in the vagina.
  • The patient should be educated to keep normal guideline-recommended pelvic and Pap smear appointments. In most situations, this is benign, and expectant management is all that is necessary.
  • http://www.acog.org/
PROGNOSIS
  • It is expected that most patients will have squamous metaplasia and epithelialization with complete resolution of the adenosis.
  • The rare patient, 1/1,000 to 1/10,000, may develop adenocarcinoma in the adenosis and will require definitive therapy as for vaginal cancer.
    • Cumulative incidence of progression of adenosis to adenocarcinoma is 1.5/1,000 for DES daughters (6).
REFERENCES
1. Reich O, Fritsch H. The developmental origin of cervical and vaginal epithelium and their clinical consequences: a systematic review. J Low Genit Tract Dis. 2014;18(4):358-360.
2. Kranl C, Zelger B, Kofler H, et al. Vulval and vaginal adenosis. Br J Dermatol. 1998;139(1):128-131.
3. Laronda MM, Unno K, Butler LM, et al. The development of cervical and vaginal adenosis as a result of diethylstilbestrol exposure in utero. Differentiation. 2012;84(3):252-260.
4. Larondo M, Unno K, Ishi K, et al. Diethylstilbestrol induces vaginal adenosis by disrupting SMAD/RUNX1-mediated cell fate decision in the Müllerian duct epithelium. Dev Biol. 2013;381(1):5-16.
5. Martin AA, Atkins KA, Lonergan CL, et al. Vaginal adenosis as a dermatologic complaint . J Am Acad Dermatol. 2013;69(2):e92-e93.
6. National Toxicology Program, Department of Health and Human Services. Diethylstilbestrol. Report on Carcinogens. 12th ed. Research Triangle Park: National Toxicology Program, U.S. Department of Health and Human Services. 2011:159-161.
7. Chattopadhyay I, Cruickshan DJ, Packer M. Non diethylstilbestrol induced vaginal adenosis—a case series and review of literature. Eur J Gynaecol Oncol. 2001;22(4):260-262.
8. Cebesoy FB, Kutlar I, Aydin A. Vaginal adenosis successfully treated with simple unipolar cauterization. J Natl Med Assoc. 2007;99(2):166-167.
Additional Reading
&NA;
  • Bamigboye AA, Morris J. Oestrogen supplementation, mainly diethylstilbestrol, for preventing miscarriages and other adverse pregnancy outcomes. Cochrane Database Syst Rev. 2003;(3):CD004353.
  • Sandberg EC. The incidence and distribution of occult vaginal adenosis. Am J Obstet Gynecol. 1968;101(3):322-334.
See Also
&NA;
Vaginal Malignancy
Codes
&NA;
ICD10
  • Q52.4 Other congenital malformations of vagina
  • N89.8 Other specified noninflammatory disorders of vagina
  • T38.5X5A Adverse effect of other estrogens and progestogens, initial encounter
Clinical Pearls
&NA;
  • Adenosis is characterized by the presence of columnar epithelium or glandular tissue in the wall of the vagina.
  • Adenosis is more common among the daughters of women exposed to DES.
  • Adenosis is rarely associated with an underlying vaginal malignancy.