DOI: https://doi.org/10.5114/pm.2020.99570 Menopause Rev 2020; 19(3): 135-139 Review papeR Vulvar leukoplakia: therapeutic options Angel Yordanov1, Latchezar Tantchev2, Stoyan Kostov3, Stanislav Slavchev3, Strahil Strashilov4, Polina Vasileva5 1Department of Gynaecological Oncology, Medical University of Pleven, Bulgaria 2Obstetrics and Gynaecology Clinic, Acibadem City Clinic Hospital “Tokuda”, Sofia, Bulgaria 3Department of Gynecology, Medical University of Varna, Bulgaria 4Department of Plastic Restorative, Reconstructive and Aesthetic Surgery, Medical University of Pleven, Bulgaria 5Department of Obstetrics and Gynaecology, Medical University of Pleven, Pleven, Bulgaria Abstract Vulvar leukoplakia is not a histological diagnosis and involves several diseases. Most commonly, these are vulvar lichen sclerosus and squamous cell hyperplasia of the vulva. These two conditions have similar aetiol- ogy, clinical presentation and treatment but different histopathological changes. They both lead to significant impairment of quality of life, risk of malignancy, as well as recurrence after treatment. Treatment of these conditions includes topical corticosteroids as a first-line therapy, but they have their side effects and not all patients are receptive to this therapy. This requires the use of alternative therapeutic options such as topical calcineurin inhibitors, topical and systemic retinoids, other steroid creams, various destructive techniques and, as a last resort, surgical removal of affected tissues. Surgical treatment should be avoided, despite the malignant potential, because of recurrence risk in both diseases New therapeutic approaches are coming into effect in gynaecological practice due to potential risks of the above-mentioned methods. Platelet-rich plasma therapy, ablative and non-ablative laser treatment, and new topical medicines, are some of the new options applied to improve the efficacy of treatment avoiding the side effects of conventional medications. A number of them are still in their initial phase of application and time will tell their effectiveness. Key words: vulvar leukoplakia, vulvar lichen sclerosus, squamous cell hyperplasia of the vulva, treatment. Introduction rich plasma (PRP) therapy, various destructive tech- The term vulvar leukoplakia is not a histological but niques, e.g. ablative and non-ablative laser treatments, a descriptive diagnosis meaning “white spot”. It is used alcohol-mediated denervation and, in the last instance, for non-inflammatory diseases characterized by patho- surgical removal of the affected tissues. logical modification of external genitalia multilayered flat epithelium that is accompanied by skin and mucosa cornification [1]. It combines various atrophic and hy- Aetiology pertrophic diseases of the vulva classified in the past as The two major diseases leading to white skin color- vulvar dystrophies [2]. This group includes lichen sclero- ation in the external genitalia are VLS and SCHV. These sus (LS), squamous cell hyperplasia, condyloma acumi- are chronic conditions and their occurrence is deter- nata, psoriasis, lichen planus, mixed LS and atrophicus. mined by many factors such as immunity, sexual hor- White colouration is caused by excessive keratin, at mones, injuries, environment, enzymes, free radicals, times deep pigmentation, and relative avascularity [3]. and apoptosis. It is assumed that VLS and SCHV are Two non-neoplastic epithelial disorders of the vulva – genetic immune diseases [5]. vulvar LS (VLS) and squamous cell hyperplasia of the VLS is the most common chronic lesion of the vulva vulva (SCHV) – are generally referred to as vulvar leuko- and mainly affects the anogenital area [4, 5], but may plakia. They have different anatomical and pathological have extragenital location as well. In 20% of patients features, but similar clinical manifestations. The fre- with anogenital involvement extragenital involvement is quency is 1 in 300 to 1,000 [4]. Treatment involves dif- found too [6-9]; in 6-15% of LS cases disease manifesta- ferent approaches such as topical medications, platelet- tions have extragenital locations only [8, 9]. The classical Corresponding author: Angel Yordanov, PhD, Department of Gynaecological Oncology, Medical University of Pleven, Submitted: 2.03.2020 1 Sv. Kliment Ohridski St., 5800 Pleven, Bulgaria, e-mail: [email protected] Accepted: 10.05.2020 This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0). License (http://creativecommons.org/licenses/by-nc-sa/4.0/) 135 Menopause Review/Przegląd Menopauzalny 19(3) 2020 histological findings of LS are a thinned epidermis and/ ing and redness of the skin and the lesion can further or the loss of rete ridges, hyperkeratosis, oedema and/or progress to white, thin, dry, and chapped skin and mu- hyalinization, as well as chronic band-like inflammatory cosa with a loss of elasticity as the disease advances. cell infiltrate of the dermis [10]. However, there are many There can be atrophy or even a reduction in the labio- variations to these classical histological characteristics rum minus [5]. leading to a myriad of lesions that may be classified as VLS and SCHV may cause significant vulvar chang- LS [11]. Macroscopically, the vulva is shiny and dry, with es affecting quality of life. Anatomical changes that are no creases. Lesions are often symmetrical. The disease caused by both conditions, especially from VLS, may is more common in postmenopausal women, but there lead to sexual dysfunction [13]. Both conditions have is a peak in its development in pre-pubertal girls as well an opportunity to relapse after treatment, and this is [7, 9, 12]. It affects mostly women aged 50-59 [4]. It is as- related to the method of treatment and patients’ age sumed to be of autoimmune genesis with a genetic pre- [20, 21]. disposition [5, 13]. Autoimmune diseases are diagnosed They have a malignant potential: 3 to 6% for VLS in 21% of cases of VLS, and in 22% of cases family history and 2 to 4% for SCHV [5]. It has been established that of the disease [2] affects sisters, mothers and daughters, VLS patients can develop vulvar squamous cell carci- and twin sisters including both homozygotic and hetero- noma for several years – from 3.3 to 8.8 years [22, 23]. zygotic twins [5]. About 80% of the cases of invasive squamous cell carci- The aetiology of SCHV is not well known. It is sup- noma (SCC) of the vulva in elderly patients are associat- posed there is a role of chronic irritation of the skin. Ir- ed with untreated, long-term VLS conditions [4]. ritants might include perfumed soaps, fabric condition- Because of the malignant potential of these diseas- ers and detergents used in the laundry of underwear es, many clinicians advocate that active management or even excessive washing [14]. It is thought that SCHV of VLS and SCHV can reduce the risk of malignant trans- is an autoimmune condition and it has been associat- formation [22]. ed with other autoimmune diseases such as malignant anaemia, thyroid diseases, diabetes mellitus, systemic lupus erythematosus, primary biliary cirrhosis, and bul- Diagnosis lous pemphigoid [2]. There is thinning of the affected skin in VLS, while The diagnosis of both diseases is clinical, which is the opposite is observed in SCHV – an abnormal growth sufficient in routine clinical practice. It is very easy to of the skin of the vulva. The histological features are diagnosticate then when the clinical presentation is typ- as follows: widening of the rete ridges and irregular ical, especially for LVS [24-26]. In some cases such as thickening of the Malpighian layer of rete ridges (acan- atypical features, uncertainty of diagnosis, concern for thosis); hyperkeratosis and chronic inflammation in the malignancy, or in failed response to treatment, biopsy is dermis; possibly increased mitotic figures in basal and mandatory. The gold standard to differentiate these con- prickle cell layers but no atypia; possible parakeratosis. ditions is histological – biopsy [22, 27]. Because biopsy This condition is characterized by a pink-red vulva is the only way to exclude SCC of the vulva and vulvar with overlying grey-white keratin and involved labium intraepithelial neoplasia, it is necessary in our opinion. majus, nympholabial furrow, preputium clitoridis, and commissura labiorum posterior. In the early stage of the disease, the skin might appear dark red or pink, while Treatment hyperkeratotic skin might appear white. Both diseases have similar treatment, but different The disease is predominant in postmenopausal wom- therapeutic options are available as well. The main goal en but can be observed in any lifetime period [15-17]. The of therapy is to control genital itching, which is a major average age of its occurrence is between 42 and 53 years problem for the patient. Management of pruritus vul- of age according to research literature [18, 19]. vae can be divided into four stages: (1) identification of underlying disease; (2) restoration of the skin barri- er function; (3) reduction of any inflammatory compli- Clinical manifestation cation; and (4) elimination of the itch-scratch cycle by The clinical picture in both conditions is similar, and psychological methods [28]. Asymptomatic VLS cases its main manifestation is itching in the vulva which is should be treated too. more expressed in SCHV than in VLS [5]. Other less The first course of action in both conditions is to common symptoms