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Int J Womens Dermatol
Int J Womens Dermatol
JW9
International Journal of Women's Dermatology
2352-6475
Lippincott Williams & Wilkins Hagerstown, MD

IJWD-D-24-00025
00017
10.1097/JW9.0000000000000178
3
Images in Women’s Dermatology
Nonhealing vulvar ulcer associated with hyperkeratotic depigmented plaques
Jain Shivani MPhil, MSc a
Rivera Sydney MD a
Murphy Emily MD b
Mauskar Melissa M. MD ac*
a Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas
b Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia
c Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas
* Corresponding author. E-mail address: Melissa.Mauskar@UTSouthwestern.edu (M. M. Mauskar).
11 9 2024
10 2024
10 3 e178e178
29 3 2024
26 7 2024
Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Women’s Dermatologic Society.
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

dVIN
skin of color
topical corticosteroid
vulvar biopsy
vulvar SCC
vulvar ulcer
noneNot ApplicableOPEN-ACCESSTRUE
COUNTRYUNITED STATES
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pmcWhat is known about this subject in regard to women and their families?

Vulvar lichen sclerosus (VLS) is a chronic inflammatory dermatosis that when uncontrolled can lead to loss of normal vulvar architecture and vulvar squamous neoplasms, such as differentiated vulvar intraepithelial neoplasia (dVIN) and squamous cell carcinoma (SCC).

Pediatric VLS accounts for 10 to 15% of all VLS cases and frequently is misdiagnosed in early stages due to nonspecific symptoms.

Ultrapotent topical corticosteroid therapy is considered the mainstay of management and often leads to disease control and reduces the risk of malignant transformation.

What is new from this article as messages for women and their families?

Clinical presentation of VLS in those with darker skin types can differ, and there remains a lack of research on the presentation of vulvar disease in the skin of color patients.

It is imperative that pediatric VLS patients are monitored into adulthood, even if symptoms and clinical signs improve following menarche, as VLS can persist and evolve into dVIN and SCC.

Clinicians should maintain a low threshold to biopsy hyperkeratotic, nodular, erosive, or ulcerative disease, particularly areas that do not respond to topical steroids, to rule out SCC.

Case summary

A female in her mid-20s with vulvar lichen sclerosus (LS) presented with a nonhealing ulcer. Diagnosed in infancy, her LS improved during puberty but resurfaced at age 22 and remained active despite treatment with ultrapotent topical corticosteroids and CO2 laser ablation. Examination revealed thick, depigmented plaques on the perianal area and the vulva, a firm ulcerated plaque on the left clitoral hood, and agglutinated labia minora (Fig. 1). Punch biopsy of the left clitoral hood showed differentiated vulvar intraepithelial neoplasm (dVIN) with possible early stromal invasion. Immunohistochemical staining was negative for p16 but aberrant for p53. Given her age and the lesion’s location, she was conservatively started on imiquimod 5% cream daily for 6 weeks to the clitoris and betamethasone dipropionate 0.05% ointment twice daily to the remaining vulva and perianal skin. A 2-mm papule was found at a follow-up visit 4 months later. Biopsy revealed a new diagnosis.

Fig. 1. Clinical and histopathological evaluation. (A) Thick depigmented plaques around the perianal skin extending to the vulva, a firm ulcerated plaque on the left clitoral hood (see arrow), and agglutination of the labia minora. (B) Pathology showing a focus on keratinizing squamous cell carcinoma with superficial invasion measuring less than 1 mm in depth. Hematoxylin and eosin stain, ×200. (C) Immunohistochemical staining demonstrating p53 overexpression.

Question 1

What is your diagnosis?

A. Irritant contact dermatitis

B. Extramammary Paget disease

C. Squamous cell carcinoma

D. Aphthous ulcer

E. Behçet disease

Correct answer: C. Squamous cell carcinoma.

Discussion

Vulvar LS is a chronic inflammatory skin condition that is estimated to affect 1 in 100 women and can lead to squamous cell carcinoma (SCC) if left untreated.1 There is limited research on how LS is present in skin of color.

Pediatric LS accounts for 10 to 15% of cases and may be misdiagnosed due to nonspecific symptoms.1 It is imperative that pediatric patients are treated and monitored into adulthood, even if their disease improves postmenarche, as demonstrated by our case.1 Ultrapotent topical corticosteroids, often daily for 3 to 4 months followed by maintenance treatment, is considered the mainstay of management, leading to disease control and risk reduction for malignant transformation.1 The incidence of SCC in those with LS is between 0.3 and 4.9%.1 Any hyperkeratotic, nodular, erosive, or ulcerative areas should be biopsied to rule out dysplasia.1 Vulvar SCC is typically treated surgically, although other treatments such as radiotherapy and chemotherapy are also used based on location and disease extent.2 Topical corticosteroids are used as prophylaxis for future SCC.2 Five-year survival is approximately 70%; however, p53-mutated SCCs, as in our patient, have inferior clinical outcomes.2

The patient’s biopsy demonstrated superficially invasive SCC, arising from background dVIN, which suggests there may have been sampling error from the first biopsy. She underwent a simple partial vulvectomy with excision of the left clitoral hood. We have now followed this patient for a 5-year period, and her course has been complex.

At 12-month follow-up with gynecologic oncology, she had new hyperpigmentation adjacent to the clitoral hood and a repeat biopsy was done. This initial biopsy did not show signs of recurrent SCC. Although her vulvar LS is now well-controlled with clobetasol propionate 0.05% ointment 3 times weekly, she has since been diagnosed with systemic lupus erythematosus and is on several different immunosuppressive agents including mycophenolate mofetil, belimumab, hydroxychloroquine, prednisone, and cyclosporine. Likely because of this immunosuppression, she developed a new invasive SCC of the right vulva with subsequent partial vulvectomy and 3 recurrent dVIN lesions on the left clitoral hood with subsequent partial vulvectomies. Given these recurrences, we needed a strategy for SCC prophylaxis. Some clinicians utilize treatments such as acitretin to prevent recurrence; this was avoided in our reproductive-aged patient due to its teratogenicity. Instead, she was started on compounded 5-fluorouracil (5-FU) 5% and calcipotriene 0.005% cream for 5 days to the site of prior SCC, as well as oral nicotinamide 500 mg twice daily. The combination of 5-FU and calcipotriene has been shown to block DNA synthesis and induce long-acting T-cell immunity.3 We hoped this novel preventative measure may prevent further development of dVIN and SCC, similarly to how it is utilized for actinic keratosis.3 We hope this prophylactic treatment is effective in the setting of vulvar LS.

Question 2

What are you most likely to see on pathology?

A. Nests of melanocytes of variable size and shape with upward spread of cells through the epidermis

B. Large, pale cells in the epidermis, crushing the basal layer

C. Minimal nuclear atypia and exophytic and endophytic growth of bland-appearing squamous epithelium with deep pushing borders

D. Nests of blue cells in the dermis with retraction artifact

E. Keratin pearls and keratinocytes with high nuclear-to-cytoplasmic ratio

Correct answer: E. Keratin pearls and keratinocytes with high nuclear-to-cytoplasmic ratio.

Detailed answer

Keratin pearls and keratinocytes with high nuclear-to-cytoplasmic ratio are commonly seen on pathology for the keratinizing subtype of vulvar SCC, which is human papillomavirus-independent.3 Answer choice A describes vulvar melanoma, the second most common vulvar malignancy after SCC. Answer choice B is the pathology of extramammary Paget disease. Verrucous carcinoma shows findings of choice C on pathology. Pathology noted in choice D is seen in basal cell carcinoma, which accounts for <5% of all vulvar cancers and is predominantly seen in older white females.3

Conflicts of interest

None.

Funding

None.

Study approval

Clinical studies of patients with vulvar dermatoses were approved by UT Southwestern IRB, STU2019-0892.

Author contributions

SJ, SR, EM, and MMM had full access to all of the data in the study and take responsibility for the integrity of the data and accuracy of the data interpretation. SJ and SR performed data acquisition and interpretation. SJ, SR, EM, and MMM contributed to the drafting and revision of the manuscript.

Patient consent

Informed, written consent was received from all patients for whom photographs are present in the manuscript.

Acknowledgments

We would like to acknowledge Travis Vandergriff, MD, for help in preparing histopathology images, and Jayanthi Lea, MD, who provided some aspects of care for the patient discussed.

Published online 11 September 2024
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References

1. Fistarol SK Itin PH . Diagnosis and treatment of lichen sclerosus: an update. Am J Clin Dermatol 2013;14 :27–47.23329078
2. National Comprehensive Cancer Network. Vulvar Cancer (Version 3.2024). [Cited 2024 January 1]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/vulvar.pdf
3. Rosenberg AR Tabacchi M Ngo KH . Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insight 2019;4 :e125476.30895944
