eMedicine Specialties > Obstetrics and Gynecology > General Gynecology

Nonneoplastic Epithelial Disorders of the Vulva

Michel E Rivlin, MD, Professor, Coordinator of Quality Assurance/Quality Improvement, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine

Updated: Jul 9, 2007

Introduction

Background

Symptoms related to vulvar disorders include pruritus, vulvodynia, superficial dyspareunia, or lesions that may be white, red, pigmented, raised, or ulcerated. These symptoms may be caused by infections, dermatologic disorders, or nonneoplastic or neoplastic vulvar diseases.

Successive meetings of several international societies have resulted in the development of a standardized nomenclature based on histopathologic findings. The older terms, such as vulvar dystrophy, kraurosis vulvae, leukoplakia, hyperplastic vulvitis, and lichen sclerosus et atrophicus, should no longer be used. In their places, nonneoplastic epithelial disorders were divided into 3 major categories: squamous cell hyperplasia, lichen sclerosus, and other dermatoses. Vulvar lesions with atypia were excluded from the classification.

Mixed epithelial disorders may occur and, in such cases, all conditions are reported. If atypia is present, the diagnosis is vulvar intraepithelial neoplasia (VIN), which may be differentiated or undifferentiated, depending on the degree of atypia. A further reclassification includes lichen sclerosus under inflammatory skin conditions, further grouped as a lichenoid disorder, while squamous hyperplasia is under psoriasiform disorders as lichenification, encompassing the term lichen simplex. Unfortunately, although the terminology may be comprehensive, it does not clarify the link with vulvar cancer.

Included in the differential diagnosis of lichen sclerosus and squamous cell hyperplasia are other dermatoses (eg, psoriasis, lichen planus), as well as benign lesions (eg, hidradenoma) and potentially malignant lesions (eg, Paget disease, VIN, melanoma).

Pathophysiology

Lichen sclerosus may involve the pudendum, perineum, and perianal areas. The skin is white and thin, although concurrent squamous cell hyperplasia with skin thickening may be present. Squamous cell carcinoma (SCC) may occur in these areas, with some studies reporting it as frequently as 3-5% in women with lichen sclerosus. Microscopically, skin atrophy is observed.

Squamous cell hyperplasia is usually asymmetrical, ranging from white to gray, with coarsely thickened skin. Microscopically, epithelial thickening is observed. The hyperplastic changes may be associated with the trauma of scratching caused by the intense pruritus, especially in untreated women. However, whether treatment lessens the risk of malignancy is not known.

In most cases, epithelial alterations are adjacent to invasive SCC of the vulva. Two distinct entities have been noted: (1) the common keratinizing SCC affecting an older population and arising in the background of a nonneoplastic epithelial disorder, lichen sclerosus, and/or squamous hyperplasia and (2) the human papillomavirus (HPV)–related carcinoma arising from undifferentiated VIN III, commonly in young women. Furthermore, a significant difference in prognosis has been observed, with HPV-related cases having better outcomes.

The nature of the interrelationship is obscure because lichen sclerosus and squamous hyperplasia appear to be benign conditions without malignant potential, being polyclonal and without allelic imbalance or p53 expression. However some cases have been shown to have monoclonality, increased p53 expression, allelic imbalance, and aneuploidy. It has been postulated that allelic alterations can occur in morphologically benign conditions producing clonal expansion. Additional molecular events, either host or viral, lead to atypia as dedifferentiated (HPV+) or differentiated (HPV-) VIN in the progression to invasive cancer.

Frequency

United States

The prevalence of lichen sclerosus is not known, but the condition is thought to be relatively uncommon. Most cases occur in postmenopausal women, although it is known to occur in prepubescent girls. Squamous cell hyperplasia, primarily a disease of older women, is relatively uncommon.

Mortality/Morbidity

• Mortality is associated with the rare occurrence of SCC that complicates lichen sclerosus or squamous cell hyperplasia.
• Morbidity is associated with severe symptomatology and interference with sexual function for both lichen sclerosus and squamous cell hyperplasia.

Race

No racial differences have been noted.

Sex

Vulval lichen sclerosus and squamous cell hyperplasia occur in female patients.

Age

These conditions usually occur in postmenopausal women, although lichen sclerosus is not uncommon in prepubertal girls

Clinical

History

Patients with lichen sclerosus and squamous cell hyperplasia usually present with pruritus vulvae, vulvodynia, superficial dyspareunia, or visible lesions.

Physical

Lichen sclerosus is characterized by "cigarette paper" skin, ie, skin that is thin, white, and crinkly. The introitus may shrink with fusion of the labia minora.

Squamous cell hyperplasia has a nonspecific appearance with thickened asymmetrical areas and a coloration ranging from white to gray.

Causes

The etiology of lichen sclerosis is unknown. Familial incidence is well recognized and may concern both sexes. The link with autoimmune disease is also established but relatively weak. Approximately 21% of patients have an autoimmune disease, most commonly a thyroid disorder. Twenty-two percent of patients have a family history, and 44% have one or more autoantibodies. Many studies, including those that relate to HLA findings, those that seek an infectious agent, and those that investigate cell kinetics, have not yielded any consistent theories regarding the etiology and pathophysiology of these disorders. Patients with a genetic predisposition or with associated autoimmune disorders do not differ clinically from those without such a background.

Differential Diagnoses

Other Problems to Be Considered

The diagnosis is entertained when symmetric white epithelium in a figure-of-eight pattern is noted. Vitiligo may be confused with lichen sclerosus, but the skin in this condition is not atrophic.

Lichen planus may mimic lichen sclerosus because lichen is a term used to describe many lesions that have closely set papules as their main characteristic; thus, terms such as lichen simplex, lichenification, lichen planus, and lichen sclerosus are used to describe lesions that resemble the mossy surface of lichen on a tree.

In differentiating lichen planus from lichen sclerosus, the former typically has an erosive vaginal component and a reticulate pattern at the introitus. In children, sexual abuse may have to be considered, especially when the lesions are hemorrhagic. Cicatricial pemphigoid is an important differential, especially when fusion is extreme; vaginal, ocular, or oral lesions, if present, are suggestive of that condition.

Workup

Other Tests

• Thyroid function tests are indicated because approximately 21% of women with lichen sclerosis have an autoimmune disease, most commonly a thyroid disorder.

Procedures

• If the diagnosis is not readily apparent, unaided (ie, naked-eye) or colposcopic examination of the vulva may define areas of abnormality that may warrant biopsy using a Keyes punch or biopsy forceps under local anesthesia.
• The mainstay of diagnosis is vulvar biopsy. Furthermore, all patients with a nonneoplastic vulvar epithelial disorder should be checked at regular intervals. Areas of ulceration or foci of granulation or nodularity that develop should be biopsied to exclude malignant change. The formation of hyperkeratotic plaques or erosions that do not respond to treatment should arouse suspicions of malignancy. Multiple biopsies may be necessary.
• Biopsy is indicated when the diagnosis is in doubt or if management strategies would be influenced by more information. An outpatient procedure with local anesthesia is almost always feasible. The request form should indicate the area from which the biopsy will be taken. Excisional biopsy is feasible for small lesions, but larger areas require sampling by punch biopsy.
• Preliminary application of lidocaine and prilocaine (EMLA Cream) that is left on for about 10 minutes is helpful. Lignocaine 1% is infiltrated in the areas to be biopsied. Disposable 2- to 6-mm punches are used (eg, Keyes punch biopsy instruments). The 6-mm punch is used for larger legions. A rotary motion of the instrument removes a core of tissue, which is removed by snipping off at the base with scissors. Hemostasis is usually satisfactorily achieved with pressure, chemicals such as silver nitrate or Monsel solution, or electrocautery. With larger biopsies, the use of absorbable sutures, such as 4-0 Vicryl, achieves hemostasis. As a rule, late bleeding is rare and healing is rapid.

Histologic Findings

• Lichen sclerosus is characterized by epidermal atrophy, hyalinized superficial dermis, and underlying lymphocytic infiltration.
• Squamous cell hyperplasia is characterized by epithelial thickening (hyperplasia), thickening of the keratin layer (hyperkeratosis), elongation and widening of the epithelial rete ridges (acanthosis), and retention of nuclear material in the keratin layer (parakeratosis).

Treatment

Medical Care

• Squamous cell hyperplasia
  • Topical steroids (eg, medium-strength betamethasone 0.1% ointment) are applied twice daily until symptoms are controlled, usually in 10-14 days. Use episodically as necessary thereafter. If unsuccessful, high-potency steroids (eg, clobetasol 0.05%) can be used in a similar fashion with return to a less potent steroid once a response is obtained.
  • Topical medium-strength corticosteroids (eg, 0.1% triamcinolone) can be applied twice daily and decreased to once daily when symptoms resolve.
• Lichen sclerosus
  • Patients with lichen sclerosis typically present with thin, parchmentlike skin, which is a poor barrier to the loss of moisture. Patients should avoid excessive drying of this skin after bathing. Bland emollients should be used to improve moisture retention. For instance, a thin layer of petrolatum (eg, Vaseline) may be helpful. Aqueous creams or emulsifying ointments are safe and cheap. Many proprietary preparations of moisturizing lotions, creams, or ointments are available.
  • Careful hygiene, avoidance of irritants and allergens, use of cotton underwear, and avoidance of constricting and heat-inducing clothing are sensible adjuncts of local care. The condition is independent of whether the patient is taking hormone replacement therapy.
• As definitive therapy, clobetasol propionate 0.05% ointment is applied twice daily. Note that a "one finger-tip unit" is about 0.5 g and should provide a single application. In using a potent corticosteroid, the amount used should be monitored, with 30 g over 3 months providing a dosage level below which few local or systemic adverse effects are likely to occur. Because the effect is usually very good, use is generally tapered off after 2-3 weeks. Indefinite maintenance with small amounts is satisfactory in most instances.
• Estrogen or testosterone creams have no role in the treatment of lichen sclerosus (Bornstein et al, 1998). Testosterone has been shown to be no better than petrolatum in treating lichen sclerosus.¹ Furthermore, it does not maintain the improvement brought about by clobetasol propionate.² When testosterone was used, it was provided as 2% testosterone propionate in petrolatum. This was applied 2-3 times a day for up to 6 months. Adverse effects, including masculinization, were not uncommon and included clitoromegaly and clitoral irritation. After completion of the initial phase, application frequency was reduced and then maintained indefinitely. Testosterone use is contraindicated in children because it is systemically absorbed and may cause androgenic adverse effects.
• Topical progesterone has been used for adults who did not respond to steroids or testosterone and for children. This agent is prepared by mixing 400 mg of progesterone in oil with 4 oz of Aquaphor and is applied twice daily. As with testosterone, pruritus must first be controlled with steroid cream before use of the progesterone cream.
• For patients with lichen sclerosus and coexistent squamous hyperplasia, therapy is as for lichen sclerosus. It may occasionally be necessary to excise hyperplastic or fissured areas of lichen sclerosus unresponsive to medical therapy, but patients must realize that recurrence rates after excision are high. This applies even after skin grafting, when lichen sclerosus may recur in the grafted skin.
• Difficult cases refractory to the usual therapies require consultation with a dermatologist and, on occasion, a plastic surgeon. Multidisciplinary management is helpful in such patients. For pruritus unresponsive to topical steroids, triamcinolone (Kenalog-10) may be injected locally at 1-cm grids. Because a retinoid has been shown to reduce connective tissue degeneration in lichen sclerosis, these agents are worth considering in resistant cases. Therapy with oral etretinate and tretinoin has been shown to be helpful. In view of adverse drug effects, topical therapy is preferable, and tretinoin has been used locally with good results. Encouraging results have been reported in small numbers of patients treated with 1% topical pimecrolimus (Elidel) administered twice daily for 3 months. Pimecrolimus is a topical macrolide immunosuppressant that inhibits T-cell activity and is US Food and Drug Administration–approved for eczema.³ A preliminary report from China suggested that focused ultrasound therapy may be efficacious and recommended further studies.⁴

Surgical Care

Surgery is reserved for patients in whom biopsy has identified associated vulvar intraepithelial neoplasia or invasive SCC. When introital stenosis is causing symptoms, vaginoplasty may be indicated. Simple vulvectomy has little or no place in the treatment of this disease because symptoms are not always relieved, signs recur, and cancer returns. The operation has significant physical and psychosexual complications.

Consultations

In some patients, difficulties in diagnosis or poor response to therapy requires consultation with a dermatologist. When introital stenosis is causing symptoms sufficient to necessitate surgery (eg, meticulous unsealing of tissue around the clitoris, careful vaginoplasty), consultation with a plastic surgeon may be indicated. In the event of a premalignant or malignant change on biopsy, referral to gynecologic oncologist is in order.

Activity

Sexual activity is contraindicated when it is uncomfortable for the patient or if it worsens pruritus, at the patient's discretion. No evidence supports the hypothesis that sexual activity interferes with healing, though abstinence during the initial phase of therapy in a symptomatic patient appears to be a sensible precaution. Dyspareunia is common, as is splitting at the introitus with intercourse. Lubricants, careful sexual technique, and application of clobetasol to heal the fissures are usually effective. Vulvoplasty is sometimes required.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Corticosteroids

Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli. Steroid creams are grouped according to anti-inflammatory activity as low- (eg, hydrocortisone 1%), medium-, or high-potency agents. Ointments are indicated for management of thick, chronic dermatitis. Inflamed skin requires lotions or creams.

Hydrocortisone (Cortaid, Dermacort, Westcort)

Adrenocorticosteroid derivative suitable for application to skin or external mucous membranes. Has mineralocorticoid and glucocorticoid effects resulting in anti-inflammatory activity.

Dosing

Adult

Apply sparingly to affected areas

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; viral, fungal, and bacterial skin infections

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Prolonged use, applying over large surface areas, application of potent steroids, and occlusive dressings may increase systemic absorption of corticosteroids and may cause Cushing syndrome, reversible HPA axis suppression, hyperglycemia, and glycosuria

Clobetasol (Temovate)

Very high-potency topical corticosteroid used to treat lichen sclerosus. Suppresses mitosis and increases synthesis of proteins that decrease inflammation and cause vasoconstriction.

Dosing

Adult

Initial: Apply thin film bid for 2-3 wk
Maintenance: Apply thin film 1-3 times/wk

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; viral or fungal skin infections

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

May suppress adrenal function in prolonged therapy

Triamcinolone (Aristocort)

Medium-potency agent that decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability. Treats squamous cell hyperplasia.

Dosing

Adult

Apply thin film bid until favorable response obtained; apply qd thereafter

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; fungal, viral, and bacterial skin infections

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Not for use in decreased skin circulation; prolonged use, applications over large areas, and use of potent steroids and occlusive dressings may result in systemic absorption; systemic absorption may cause Cushing syndrome, reversible HPA axis suppression, hyperglycemia, and glycosuria

Hormone therapy

May improve inflammatory reactions.

Progesterone (Crinone, Progestasert)

Prepared by mixing 400 mg of progesterone in oil with 4 oz of Aquaphor.

Dosing

Adult

Lichen sclerosus: Apply thin film bid

Pediatric

Not established

Interactions

May decrease effects of aminoglutethimide

Contraindications

Documented hypersensitivity, cerebral apoplexy, undiagnosed vaginal bleeding, thrombophlebitis, and liver dysfunction

Precautions

Pregnancy

X - Contraindicated in pregnancy

Precautions

Caution in asthma, depression, renal or cardiac dysfunction, or thromboembolic disorders

Follow-up

Further Outpatient Care

• Generally, patients should have follow-up visits at monthly intervals initially and at 3- to 6-month intervals after a sufficient degree of improvement is achieved.

Complications

• Lichen sclerosus may result in superficial vulvar atrophy with narrowing of the introitus sufficient to prevent satisfactory intercourse.
• Squamous cell carcinoma may occur.

Prognosis

• Lichen sclerosus usually responds to adequate therapy in a month or less. Long-term follow-up care is necessary.
• Squamous hyperplasia usually responds to adequate therapy within 2-3 weeks, and treatment usually is curative.

Patient Education

• Counsel patients regarding the importance of regular follow-up care.
• Early return for assessment is advised if a nodule enlarges or an ulcer remains unhealed.
• Persistent pruritus should be reassessed if not responding to adequate therapy.

Miscellaneous

Medicolegal Pitfalls

• Delay in diagnosis of squamous cell cancer may best be avoided by regular assessment and liberal recourse to diagnostic biopsy.

Special Concerns

• Lichen sclerosus may occur in prepubescent girls. In such cases, treatment should be coordinated with the pediatrician and/or pediatric dermatologist. The principals of therapy are similar to those in the adult with the exception of androgen therapy, which is contraindicated.

References

1. Sideri M, Origoni M, Spinaci L et al. Topical testosterone in the treatment of vulvar lichen sclerosus. Int J Gynaecol Obstet. Jul 1994;46(1):53-6. [Medline].

2. Cattaneo A, Carli P, De Marco A et al. Testosterone maintenance therapy. Effects on vulvar lichen sclerosus treated with clobetasol propionate. J Reprod Med. Feb 1996;41(2):99-102. [Medline].

3. Goldstein AT, Marinoff SC, Christopher K. Pimecrolimus for the treatment of vulvar lichen sclerosus: a report of 4 cases. J Reprod Med. Oct 2004;49(10):778-80. [Medline].

4. Li C, Bian D, Chen W. Focused ultrasound therapy of vulvar dystrophies: a feasibility study. Obstet Gynecol. Nov 2004;104(5 Pt 1):915-21. [Medline].

5. Abramov Y, Elchalal U, Abramov D, et al. Surgical treatment of vulvar lichen sclerosus: a review. Obstet Gynecol Surv. Mar 1996;51(3):193-9. [Medline].

6. Ayhan A, Guven ES, Guven S, Sakinci M, Dogan NU, Kucukali T. Testosterone versus clobetasol for maintenance of vulvar lichen sclerosus associated with variable degrees of squamous cell hyperplasia. Acta Obstet Gynecol Scand. 2007;86(6):715-9. [Medline].

7. Ayhan A, Guven S, Guvendag Guven ES, Sakinci M, Gultekin M, Kucukali T. Topical testosterone versus clobetasol for vulvar lichen sclerosus. Int J Gynaecol Obstet. Feb 2007;96(2):117-21. [Medline].

8. Bohl TG. Overview of vulvar pruritus through the life cycle. Clin Obstet Gynecol. Dec 2005;48(4):786-807. [Medline].

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10. Bornstein J, Heifetz S, Kellner Y et al. Clobetasol dipropionate 0.05% versus testosterone propionate 2% topical application for severe vulvar lichen sclerosus. Am J Obstet Gynecol. Jan 1998;178(1 Pt 1):80-4. [Medline].

11. Dalziel KL, Wojnarowska F. Long-term control of vulval lichen sclerosus after treatment with a potent topical steroid cream. J Reprod Med. Jan 1993;38(1):25-7. [Medline].

12. Djurdjevic S, Segedi D, Vejnovic T, Vejnovic, J. [Modern approach to classification of precancerous conditions and vulvar dystrophy]. Med Pregl. 1995;48(11-12):399-404. [Medline].

13. Fox H, Wells M. Recent advances in the pathology of the vulva. Histopathology. Mar 2003;42(3):209-16. [Medline].

14. Helm KF, Gibson LE, Muller SA. Lichen sclerosus et atrophicus in children and young adults. Pediatr Dermatol. Jun 1991;8(2):97-101. [Medline].

15. International Society for the Study of Vulvar Disease. New nomenclature for vulvar disease. Report of the Committee on Terminology of the International Society for the Study of Vulvar Disease. J Reprod Med. May 1990;35(5):483-4. [Medline].

16. Joura EA, Zeisler H, Bancher-Todesca D. Short-term effects of topical testosterone in vulvar lichen sclerosus. Obstet Gynecol. Feb 1997;89(2):297-9. [Medline].

17. MacLean AB, Reid WM. Benign and premalignant disease of the vulva. Br J Obstet Gynaecol. May 1995;102(5):359-63. [Medline].

18. Pinto AP, Lin MC, Sheets EE, et al. Allelic imbalance in lichen sclerosus, hyperplasia, and intraepithelial neoplasia of the vulva. Gynecol Oncol. Apr 2000;77(1):171-6. [Medline].

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20. Rolfe KJ, MacLean AB, Crow JC, et al. TP53 mutations in vulval lichen sclerosus adjacent to squamous cell carcinoma of the vulva. Br J Cancer. Dec 15 2003;89(12):2249-53. [Medline].

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22. Virgili A, Corazza M, Bianchi A. Open study of topical 0.025% tretinoin in the treatment of vulvar lichen sclerosus. One year of therapy. J Reprod Med. Sep 1995;40(9):614-8. [Medline].

Keywords

vulvar dystrophy, vulvar disease, kraurosis vulvae, leukoplakia, lichen sclerosus et atrophicus, squamous cell hyperplasia, squamous cell carcinoma, SCC, human papillomavirus, HPV

Contributor Information and Disclosures

Author

Michel E Rivlin, MD, Professor, Coordinator of Quality Assurance/Quality Improvement, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine
Michel E Rivlin, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Mississippi State Medical Association, and Royal College of Surgeons of Edinburgh
Disclosure: Nothing to disclose.

Medical Editor

Steven David Spandorfer, MD, Assistant Professor, Department of Obstetrics and Gynecology, New York Presbyterian Hospital, Weill Medical College-Cornell University
Steven David Spandorfer, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, and Endocrine Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

David Chelmow, MD, Professor of Obstetrics and Gynecology, Tufts University School of Medicine; Program Director, Tufts University Affiliated Hospitals Obstetrics/Gynecology Residency Program; Chair, Tufts University Health Sciences Campus Institutional Review Board; Vice Chair for Research and Education, Department of Obstetrics/Gynecology, Tufts Medical Center
David Chelmow, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Association of Professors of Gynecology and Obstetrics, Massachusetts Medical Society, Phi Beta Kappa, Sigma Xi, Society for Gynecologic Investigation, and Society for Medical Decision Making
Disclosure: Nothing to disclose.

CME Editor

Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Hancock Medical Center
Frederick B Gaupp, MD is a member of the following medical societies: American Academy of Family Physicians
Disclosure: Nothing to disclose.

Chief Editor

David Chelmow, MD, Professor of Obstetrics and Gynecology, Tufts University School of Medicine; Program Director, Tufts University Affiliated Hospitals Obstetrics/Gynecology Residency Program; Chair, Tufts University Health Sciences Campus Institutional Review Board; Vice Chair for Research and Education, Department of Obstetrics/Gynecology, Tufts Medical Center
David Chelmow, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Association of Professors of Gynecology and Obstetrics, Massachusetts Medical Society, Phi Beta Kappa, Sigma Xi, Society for Gynecologic Investigation, and Society for Medical Decision Making
Disclosure: Nothing to disclose.

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