|Year : 2019 | Volume
| Issue : 2 | Page : 67-74
A retrospective study of clinical and histopathological spectrum of genital lichen sclerosus in a tertiary care center
Sunanda A Mahajan, Shubhangi H Mahajan, Uday S Khopkar, Vidya D Kharkar
Department of Dermatology, Seth G. S. Medical College, K. E. M. Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||28-Nov-2019|
Dr. Shubhangi H Mahajan
Department of Dermatology, Seth G. S. Medical College, K. E. M. Hospital, Parel, Mumbai - 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Genital lichen sclerosus (LS) is a chronic, autoimmune, inflammatory dermatosis of genitalia more common in females than males. Diagnosis of early genital LS is difficult clinically; hence, histopathology may help to confirm the diagnosis. Aims: The aim of this retrospective study was to elucidate the epidemiology of genital LS and to correlate the clinical and histopathological features of genital LS. Methods: Records of 30 clinically diagnosed patients of genital LS with 27 biopsies included in the study. Clinical data from the records reviewed. Histopathological parameters noted and accordingly cases classified into early, evolved, and mature LS and correlated with clinical features. Results: Genital LS was more common in females with early age of onset. Adult patients had longer duration of disease. Pruritus was the most common symptom and females were more symptomatic. Hypothyroidism was the associated autoimmune disease in two cases. Out of thirty patients, six had genital with perianal involvement and two had genital with the extragenital disease. Phimosis was the most common complication in males, while introital stenosis was the most common in females. Lymphohistiocytic infiltrate was the most common histopathological finding followed by hyperkeratosis, dilated blood vessels and lymphatics, and collagen homogenization. Duration, symptoms, and clinical features were found to be independent of the histopathology findings. Limitations: It is a retrospective study with limited patient information. Association of genital LS with other autoimmune diseases cannot be commented as required investigations were not done. Our data are cross-sectional without follow-up, hence the disease course and treatment outcome could not be commented. Conclusions: Genital LS is prevalent in adult females but childhood occurrence is uncommon. Perianal affection occurs almost exclusively in women with genital LS. Understanding variations in histopathologic features is vital to appropriate clinicopathologic correlation. Long-term follow-up is recommended.
Keywords: Balanitis xerotica obliterans, lichen sclerosus, lichen sclerosus et atrophicus
|How to cite this article:|
Mahajan SA, Mahajan SH, Khopkar US, Kharkar VD. A retrospective study of clinical and histopathological spectrum of genital lichen sclerosus in a tertiary care center. Indian J Dermatopathol Diagn Dermatol 2019;6:67-74
|How to cite this URL:|
Mahajan SA, Mahajan SH, Khopkar US, Kharkar VD. A retrospective study of clinical and histopathological spectrum of genital lichen sclerosus in a tertiary care center. Indian J Dermatopathol Diagn Dermatol [serial online] 2019 [cited 2020 Jun 1];6:67-74. Available from: http://www.ijdpdd.com/text.asp?2019/6/2/67/271940
| Introduction|| |
Lichen sclerosus (LS) is an uncommon, chronic, autoimmune, inflammatory dermatosis first described by Hallopeau,,, and it comprises the disorders LS et atrophicus, balanitis xerotica obliterans (LS of the male glans and prepuce), and kraurosis vulvae (LS of the female labia major, labia minora, perineum, and perianal region). It is a mucocutaneous disorder with predilection for the anogenital region., Genital LS is more common than extragenital LS, but its incidence is unknown and probably underestimated., The etiology of genital LS is complex, but many genetic, physiologic, and environmental factors have been mentioned in the literature. It has a clear female preponderance, with a female:male ratios ranging from 5:1 to 10:1,,, and a bimodal peak in early childhood and postmenopausal females is described.,,,
Symptomatically genital LS can be disabling due to chronic pruritus, dysuria, and significant sexual dysfunction in adults. It has a chronic relapsing course leading to atrophy, destructive scarring, functional impairment, and malignant evolution., The fully developed genital LS is diagnosed clinically without much difficulty, but early forms or atypical presentations require histopathology for confirmation of the diagnosis. Studies correlating the clinical and histopathological features of genital LS are scarce in the literature. Furthermore, the literature studying LS spectrum in India is minimal. Hence, we decided to study the clinical and histopathological spectrum of genital LS and its clinicohistopathological correlation in the Indian population.
| Methods|| |
All cases who presented to the dermatology outpatient department with classical clinical features of genital LS and cases with atypical clinical features which were confirmed on biopsy over a period of 3 years (January 2014–December 2016) were included in the study. Permission of institutional ethics committee was obtained before the commencement of the study.
Records of the cases of genital LS fulfilling inclusion criteria were reviewed and available clinical data in the records was noted. The detailed histologic findings were noted and further categorized into three stages as evolving, mature, and late on the basis of nature of inflammatory infiltrate, the extent of dermal sclerosis, and dermal edema., All responses were tabulated by using Microsoft Excel Software. Data analysis was done using descriptive statistics. Clinical and histopathological data were correlated using Pearson correlation coefficient (r).
| Results|| |
The study included a total of 30 patients of genital LS out of which 11 were male and 19 were female. The age ranged from 3 to 89 years. Age distribution graph showed a bimodal peak in children and adults between the age group of 0–20 and 41–60 years [Figure 1]. The age of onset ranged from 18 months to 87 years with the mean age of onset being 39.62 years. The mean duration of disease was 26.91 months. Pruritus was the most common symptom seen in 23 out of 24 (95.83%) symptomatic patients.
Associated comorbidities seen were hypothyroidism in two female patients and eczema, atopic diathesis, hypertension, diabetes mellitus, nephritis, uterine prolapse, and rectovaginal fistula in one case each.
In our study, genital LS was associated with perianal (6, 20%) [Figure 2] and extragenital (2, 6.67%) [Figure 3]a and b] involvement. Depigmentation (30, 100%) was the most common sign followed by atrophy (24, 80%), ulcers, erosions, and fissures (7, 23.33%). Agglutination of labia minora and clitoris was present in seven females (36.84%) [Figure 4]. In males, phimosis was the most common complication found in 5 out of 11 cases (45.45%) [Figure 5]. In females, genital LS was extensive, involving labia majora, labia minora, clitoris, and vaginal introitus in most of the patients, while in male patients, lesions were restricted to the prepuce and glans [Figure 6].
|Figure 2: Vulval lichen sclerosus showing extensive perianal involvement in a child|
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|Figure 3: Genital lichen sclerosus with extragenital involvement (a) Hypopigmented atrophic patches of lichen sclerosus on neck with (b) Atrophic depigmented patch of lichen sclerosus on the penis in same patient|
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|Figure 4: Vulval lichen sclerosus with agglutination of clitoris and labia minora along with depigmented patch with sclerosis involving labia majora and mons pubis|
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|Figure 5: Genital lichen sclerosus in males (balanitis xerotica obliterans) with phimosis, depigmentation, and fissuring|
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|Figure 6: Extent of genital involvement in female and male patients of lichen sclerosus|
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Our study included eight children, out of which six were girls and two were boys. Age of children ranged from 3 to 14 years and the average age of onset was 5.84 years with 1–2 years of diagnostic delay., Common symptoms noted were pruritus in 7 (87.5%), dysuria in 3 (37.5%), and constipation in 1 (12.5%) patient. Associated perianal area involvement was seen in 5 (62.5%) girls and depigmentation (7, 87.5%) and atrophy (4, 50%) were the common signs on examination in children.
Out of 30 patients, biopsy was performed in 28 patients and in 2 children biopsy was not done due to lack of consent, but both patients had classical clinical features of LS. One biopsy could not be reviewed for technical reasons. The inflammatory infiltrate was seen in 26 (96.29%) cases. Hyperkeratosis (25, 92.6%) was the next common finding followed by lymphovascular ectasia (22, 81.48%), dermal hyalinization (20, 74.07%), epidermal atrophy (17, 62.96%), basal cell vacuolization (16;, 59.25%), and dermal edema (14, 51.85%). The infiltrate was lymphohistiocytic in all the samples (26, 96.29%) [Figure 7] and eosinophils (8, 29.62%) and plasma cells (5, 19.23%) were the other cell types found. Band-like (9, 33.33%) pattern of inflammatory infiltrate was most commonly found followed by perifollicular (6, 22.22%) and perivascular (6, 22.22%) patterns. Other histopathological features found in our study were parakeratosis (3, 11.53%), hypergranulosis (4, 15.38%), acanthosis (7, 26.92%), spongiosis (7, 26.92%), dyskeratosis (4, 15.38%), exocytosis (7, 26.92%), basement membrane thickening (7, 26.92%), and follicular plugging (5, 19.23%).
|Figure 7: Histopathological photomicrograph of lymphohistiocytic inflammatory infiltrate in evolving lichen sclerosus (×40; H and E stain)|
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The histopathology was divided into three stages as; evolving LS with a band-like lymphohistiocytic infiltrate focally separated from the dermal–epidermal junction with mild edema and/or sclerosis in the upper and mid dermis [Figure 8] and [Figure 9]; mature LS with band-like infiltrate separated from the epidermis by a band of dermal sclerosis, involving the papillary dermis with varying degrees of edema [Figure 10] and [Figure 11]; and late LS as broad zone of dermal sclerosis in papillary and upper part of reticular dermis with minimal or absent inflammatory infiltrate [Figure 12].,, Dermal hyalinization is commonly seen at papillary dermis and some part of reticular dermis in mature LS. Mature LS was the most common stage seen [Table 1]; however, clinical and histopathological findings did not correlate using Pearson correlation coefficient test (r = 0.38).
|Figure 8: Histopathological photomicrograph of evolving genital lichen sclerosus with diffuse inflammatory infiltrate (×10; H and E stain)|
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|Figure 9: Histopathological photomicrograph of evolving lichen sclerosus showing upper dermal hyalinization with periadnexal inflammatory infiltrate (×10; H and E stain)|
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|Figure 10: Histopathological photomicrograph of mature lichen sclerosus with hyperkeratosis, follicular plug, upper dermal edema, and a zone of hyalinization (×10; H and E stain)|
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|Figure 11: Histopathological photomicrograph of mature lichen sclerosus with hyperkeratosis, basal cell vacuolization, a zone of hyalinization, and a band of inflammatory infiltrate below it (×10; H and E stain)|
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|Figure 12: Histopathological photomicrograph of late lichen sclerosus showing diffuse hyalinization involving papillary and reticular dermis with minimal inflammatory infiltrate (×10; H and E stain)|
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| Discussion|| |
LS is an autoimmune inflammatory dermatosis commonly affecting the anogenital area (85%–98%). The prevalence of LS may range between 0.1% and 3% for children and elderly women, respectively., The exact prevalence of LS is difficult to estimate or probably underestimated as the patient may visit specialties such as dermatologist, gynecologist, pediatrician, or urologist. Sometimes, physicians do not recognize LS or patients do not report due to social stigma or the disease may remain asymptomatic.,
The incidence of genital LS shows a bimodal peak that includes the prepubertal children and postmenopausal women., Both these peaks occur in the nonreproductive age groups and are thought to be associated with low estrogen and androgen levels. Similar bimodal peak was also found in our study. Female-to-male ratio was approximately 1.72:1 (19 females, 11 males) slightly lower as of previous data in the literature., Females showed an early age of onset compared to males and disease duration was longer in adults.
Pruritus was the most common symptom observed similar to other studies and women were more symptomatic than men. Dysuria (10, 33.33%), dyspareunia (6, 27.27%), and constipation (6, 27.27%) were other common symptoms. Maronn and Esterly has emphasized the high incidence of constipation (67%) associated with anogenital LS in his study population.
The etiology of LS is multifactorial. Recent literature showed genetic, immunological, hormonal factors, infectious agents, drugs, and trauma as causative factors besides autoimmunity , and its association with other autoimmune dermatoses is also known. In a study by Kreuter et al., autoimmune thyroid disease (65; 12.2%) was the most common association similar to our study (2, 6.66%) and its frequency was more in females compared to males. The nephritis was found in 5-year-old male child, but its cause could not be commented upon. Association of kidney disease with LS is also documented by Lagerstedt et al. in a study of 44 girls with LS. In our study, a female child had a history of being operated for rectovaginal fistula on day 10 of life and a postmenopausal woman had uterine prolapse. The associations of rectovaginal fistula and uterine prolapse may be due to chance. Association of psoriasis, atopic dermatitis, Langerhans cell histiocytosis, and other bladder, bowel, and pain comorbidities have been described with genital LS.,,,, All the above associations are more common in females (19%–54%) than in males (3%–5%).,,
Genital LS is usually a chronic progressive condition that leads to scarring of genitalia. In adult women, it may lead to mutilation or fusion of labia minora, entrapment of the clitoris under scar tissue (buried clitoris), and introital stenosis., In men, the involvement of the preputial skin leads to a progressive phimosis, ulceration of the glans or inner preputial surface, and meatal stenosis., Introital stenosis in females and phimosis in males were the most common complications observed in our study along with the history of dyspareunia in six patients. Above complications have a detrimental effect on the quality of life, including sexual life, as it may lead to dyspareunia, apareunia, and difficulty achieving orgasm.,
Anogenital LS is more common compared to extragenital one. Six (20%) patients had genital and perianal area involvement showing a figure-of-eight appearance and all of them were females which suggests noninvolvement of the perianal area in male genital LS which has been mentioned earlier. Furthermore, two patients (6.66%) had genital with extragenital area involvement, neck in one patient and groin in another. In a study of the 60 patients of LS by Knio et al., three (5%) patients had genital along with extragenital disease.
Our study confirms the literature data that prepuce and glans are the most common sites of involvement in male genital LS , and labia majora, labia minora, and clitoris in females. Females showed more extensive involvement compared to males. Depigmentation, atrophy, and erythema were the most common clinical findings similar to the study by Knio et al.
LS is also common in prepubertal children, and it almost always affects the genital area. Almost 5%–15% of cases of LS occur in prepubertal girls., All the girls had the onset of disease before the onset of menarche as in a study by Lagerstedt et al. The symptoms and appearance of genital LS in children are same as in adults. Although childhood genital LS resolves at onset of puberty in a few cases, it has relapsing course and total remission is uncommon.,,
Although the diagnosis of genital LS can be made clinically, histopathological examination is required in early cases with a diagnostic dilemma, cases with the atypical clinical presentation or when there is suspicion of malignant change., A nonspecific biopsy does not rule out LS, but classic histologic findings confirm the diagnosis.
The salient histologic findings of LS are hyperkeratosis with follicular plugging, atrophy of the stratum malpighii with hydropic degeneration of basal cells, pronounced edema, and homogenization of the collagen in the upper dermis and an inflammatory infiltrate in the mid-dermis.,, The histopathology of fully developed LS classically exhibits epidermal atrophy, dermal sclerosis, and an underlying band-like lymphocytic infiltrate. Early lesions usually reveal more intense and superficial inflammatory infiltrate with the absence of both epidermal atrophy and well-developed sclerosis posing a diagnostic challenge., Additional microscopic features of genital LS reported in the literature are elastic fiber loss,, epidermal hyperplasia,,, presence of eosinophils,, perineural inflammation, angiokeratoma-like changes, epidermotropic lymphocytes mimicking cutaneous T-cell lymphoma, and milia formation.,
We found hyperkeratosis (25, 92.59%) as the most common epidermal finding with inflammatory infiltrate (26, 96.29%) and lymphovascular dilatation (22, 81.48%) as the most common dermal findings. In a study by Knio et al., dermal hyalinization and lymphovascular dilatation were present in all cases (65, 100%) followed by hyperkeratosis (64; 98.46%) and inflammatory infiltrate (59, 90.75%). A study by Dalal et al. showed lymphovascular dilatation and inflammatory infiltrate as most common findings (7; 100%) followed by hyperkeratosis (6, 86%) and dermal hyalinization (6, 86%) [Table 2].
|Table 2: Comparison of histopathology findings of lichen sclerosus with other studies|
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In our study, 9 (33.33%) patients were in evolving stage of LS, 13 (48.14%) were in mature stage, and 5 (18.51%) patients were of late LS [Table 1]. Histopathological grading did not correlate with the duration, age of onset, symptoms, or clinical signs of disease. Being a retrospective study, it is difficult to comment that each biopsy sample has been taken from the most active site of lesion and that can be one of the reason for clinicohistopathological noncorrelation. Hence, awareness of variations in histopathology is necessary to make the clinicopathologic correlation.
Genital LS is known to have a premalignant potential. Based on literature, there is around 5% risk of developing squamous cell carcinoma (SCC) in patients with genital LS., Worldwide, about 50% of penile and vulval carcinomas develop often in the background of chronic inflammatory skin diseases such as LS and lichen planus. Furthermore, the role of oncogenic human papillomavirus, altered p53 oncogene expression, and oxidative stress have been postulated to induce malignant transformation in patients with genital LS. One of our patients had SCC of the penis and one showed Bowenoid features on histopathology. Both of them had undergone circumcision for phimosis about 10 years before presenting to us. This was followed by the development of whitish patch on the glans which progressed to an ulcerative lesion in the first case and verrucous growth in the second case. Here, in spite of circumcision, both the patients developed LS on the circumcised skin which progressed to SCC and Bowenoid changes. Hence, a continuation of medical treatment is required despite circumcision to prevent complications. Carlson et al. postulated that LS with SCC is not restricted to the later years of life.
As genital LS has a detrimental course due to its complications; long-term follow-up is highly recommended, especially in childhood LS, because it has a huge impact on the quality of life of the patient and their families.
In spite of studying a good number of genital LS patients, our study has some limitations as it is a retrospective study with limited patient information. Association of genital LS with other autoimmune diseases cannot be commented upon as required investigations were not done. Our data are cross-sectional without follow-up, hence the disease course and treatment outcome could not be commented upon.
| Conclusions|| |
Genital LS is prevalent in adult females, but childhood occurrence is uncommon. Perianal affection occurs almost exclusively in women with genital LS. Clinical features of genital LS hint to the diagnosis, but histopathology acts as confirmatory investigation. Understanding variations in histopathologic features are vital to appropriate clinicopathologic correlation. Long-term follow-up is recommended even after surgical excision.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12]
[Table 1], [Table 2]