A Rare Presentation of Lichen Sclerosus Involving the Vaginal Canal After Radiation Therapy: A Case Report and Review of the Literature

Vaginal lichen sclerosus (LS) is an extremely rare entity. Classically, LS is referred to as a chronic, inflammatory skin disease with a distinct predilection for the anogenital skin that is observed in post-menopausal women and typically manifests clinically as white, atrophic plaques. Here, we report a case of a 61-year-old patient who presented for a follow-up visit three years after vaginal brachytherapy as an adjuvant treatment for endometrial adenocarcinoma. This lesion was biopsied and confirmed to be vaginal LS on histological analysis. While LS has been previously observed to impact mucosal areas outside of the anogenital region, such as the mouth, reported cases of vaginal LS are very rare in the literature. Our case highlights both the underrecognized location of this disease as well as radiation as a potential risk factor.


Introduction
Lichen sclerosus (LS) is a chronic, inflammatory disorder that can lead to scarring, loss of normal architecture of external genitalia, sexual dysfunction, and even malignancy [1].While LS can be found in both men and women, it primarily tends to affect the female anogenital epithelium [1].The etiology of LS remains unclear, but some reports suggest that it may involve an autoimmune and genetic component [2].Physical examination generally reveals white, atrophic-appearing plaques with epidermal thinning (also termed: "cigarette paper" appearance), hyper-or hypo-pigmentation, resorption of the labia minora, clitoral phimosis, and narrowing of the introitus [1].LS is described as primarily an epithelial disease and is thought to rarely involve the vaginal mucosa [1].There are only a few reported cases of vaginal or urethral LS [3,4], indicating that vaginal LS is either truly a rare entity or is grossly underreported and/or underdiagnosed.Moreover, in patients with prior radiation exposure, reports of vaginal LS are even more lacking, and, therefore, this case may help shed further insight into radiation as a possible risk factor for LS.

Case Presentation
A 61-year-old patient, with a history of chronic obstructive pulmonary disease (COPD), hypertension, obesity, and hypercholesterolemia, presented three years after her treatment for endometrial cancer with post-coital vaginal bleeding and dyspareunia.Of note, the patient had initially undergone an exam under anesthesia, robotic-assisted total laparoscopic hysterectomy (RA-TLH), and bilateral salpingooophorectomy (BSO) for persistent vaginal pain.Pathology was incidentally positive for grade 1 endometrioid adenocarcinoma with stromal invasion of the cervix and >50% myometrial invasion.She was subsequently referred to gynecologic oncology and opted for complete surgical staging via a laparoscopic bilateral sentinel lymph node biopsy.Her final diagnosis was a stage II, grade 1 endometroid adenocarcinoma for which she completed adjuvant vaginal brachytherapy and declined whole pelvic radiation.
At her three-year surveillance visit, the patient complained of post-coital bleeding.A pelvic exam at this time revealed normal external female genitalia with papillary, friable tissue adjacent to the vaginal cuff.This mass was biopsied with Tischler forceps and was noted to be hemostatic with the use of silver nitrate.
The biopsy of the lesion was sent for pathology.Under the microscope at low power view, the overall morphology demonstrated chronic irritational changes with homogenization of the subepithelial compartment with deep sclerosis.A minor focus of perivascular lymphoplasmacytic infiltrate was noted in addition to a bounded layer of atrophic surface epithelium (Figures 1-2).The surface epithelium lacked any atypia of significance.In conjunction with histopathology, a final diagnosis of LS was rendered.The findings in this location are highly unusual and are typical of a vulvar process.However, in view of prior radiation history to this site, radiation-induced LS was considered an alternative diagnosis.Lichen planus, lichen simplex chronicus, and squamous cell carcinoma were also considered but ruled out given tissue morphology.The slide was sent for outside consultation by an expert dermatopathologist who agreed with the above interpretation.unable to use these successfully due to persistent dyspareunia within three months of her initial diagnosis of vaginal LS.Therefore, the patient was then started on clobetasol per vagina with the use of a syringe applicator and vaginal estrogen cream.At the most recent visit, the patient continues to tolerate the above therapy and appears to have improved sexual function.On physical examination, the papillary, friable tissue notable on exam remains stable and will continue to be closely monitored with pelvic examinations every three months.

Discussion
LS, also called lichen sclerosus et atrophicus or chronic atrophic vulvitis, is a chronic inflammatory skin disease that affects the anogenital area in 85-95% of cases [1,5].While there are pathognomonic features on physical exam, a biopsy can confirm this disorder histologically.On clinical presentation, LS can affect a singular region or the entire region of the vulva, anogenital skin, and even extend to the genitocrural folds and buttock region [5,6].The characteristic findings include well-demarcated erythema, tissue fragility with erosions, fissuring and purpura, loss of normal labial architecture, clitoral phimosis, and a "crinkling appearance" of the genital skin [7].LS generally has a bimodal age distribution and can affect both premenopausal girls and menopausal women [1,8].
Histologically, the diagnosis of LS includes a demonstration of a vacuolar interface reaction pattern at the basal epidermal layer in conjunction with dermal sclerosis.The subepithelial compartment becomes homogenized with a further appreciation of hyalinized eosinophilic collagen bundles admixed with chronic inflammation [9].The overlying epidermis is characteristically atrophic, but, on occasion, it may show foci of hyperplasia [10].
Vaginal involvement by LS is an uncommon entity with less than seven reported cases in the literature, as demonstrated below in Table 1.The etiology is unclear, but it is thought that autoimmune and genetic factors may predispose to its development.In other circumstances, chronic inflammation may lead to squamatization of the epithelium, which can later progress to LS [5].While LS has now been accepted as a risk factor for the development of vulvar precancerous lesions and squamous cell carcinoma, the risk of neoplasia with vaginal LS is not well defined [1].Therefore, it is imperative to closely surveil patients with this diagnosis and be liberal with the decision to obtain another biopsy as indicated for clinical changes.There is an absence of elastic fibers.

Reported Cases in the
follow up visit, the vulvar and vaginal lichen sclerosus were noted to be unchanged, but the patient was now asymptomatic.Treatment of her vaginal lichen sclerosus was not described in this case report.

(at the initially
Vulvar  Interestingly, our case also highlights prior radiation as a potential risk factor for the development of vaginal LS.Radiation-induced vulvar LS was identified in one case report in a woman with prior external pelvic radiation and brachytherapy for vaginal cancer [11].However, most cases of radiation-induced LS have been reported as extragenital LS, such as with radiation to the breast [12,13].Importantly, this highlights that LS can preferentially arise in a previously irradiated region.In most reported cases, the time from radiation to the onset of symptomatic LS ranged from two to 12 years [12][13][14], which corresponds to our patient's clinical presentation.This shows that radiation may indeed lead to changes in the epithelium and mucosal surfaces and, therefore, potentially induce LS development.

Conclusions
In conclusion, vaginal LS is an unusual presentation with less than seven reported cases in the literature.Our case underscores the importance of not only recognizing this diagnosis in the vaginal canal but also highlights the potential role of radiation as a risk factor.While the risk of subsequent progression to cancer is not well-established, precaution should be maintained to follow up patients with this diagnosis clinically, and, if any examination changes are noted, one should be especially vigilant about obtaining a histopathological diagnosis.

FIGURE 1 :
FIGURE 1: (A) Low power view (4x), demonstrating lichen sclerosus of the vagina evidenced by the widespread hypocellular edematous zone bounded by thin, atrophic epithelium on the surface and inflamed stroma showing chronic inflammatory infiltrate (arrow).(B) Medium power view (10x) highlighting a thin atrophic surface epithelium (arrow); the opposite side reveals normal stratified squamous epithelium.

FIGURE 2 :
FIGURE 2: High-power review (20x) of the vaginal biopsy demonstrating eosinophilic homogenization of the collagen in the subepithelial layer, including edema and chronic inflammatory infiltrates.A minor component of the vacuolar interface reaction pattern can be appreciated below the basal epithelium.
history of a rectocele.She also had a five-year prior history of what became clinically diagnosed as vulvar lichen sclerosus with involvement of the labia minora and the perineal body previously unresponsive to vaginal estrogen cream, topical and vaginal antifungal creams,