Lichen sclerosus et atrophicus (LSEA) is a relatively common skin condition. It is more common in women, commonly found on genital skin. Itching and soreness are common findings. There may be an association with autoimmune diseases.
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DISEASE ASSOCIATIONS CHARACTERIZATION GRAFT VERSUS HOST DISEASE
J Am Acad Dermatol. 2005 Oct;53(4):591-601. Abstract quote
Chronic cutaneous graft-versus-host disease (GVHD) is classically divided into two major clinical categories--lichenoid and sclerodermoid. Although diffuse areas of sclerosis as in scleroderma characterize the more advanced stages of the sclerodermoid form, the initial circumscribed plaques would be more correctly described as morpheaform. Eosinophilic fasciitis (EF) (a fibrosing disorder related to deep morphea) and lichen sclerosus (LS) have also been reported as manifestations of sclerodermoid GVHD. However, these two presentations of GVHD have not been emphasized in the dermatologic literature.
We describe 6 patients, all of whom developed LS and two of whom also developed EF in the context of chronic GVHD. Each patient presented clinically with hypopigmented plaques that exhibited wrinkling, scaling, and follicular plugging. These lesions demonstrated the classic histologic features of LS including epidermal atrophy; a subepidermal zone of pale-staining, homogenized collagen; and a bandlike lymphocytic infiltrate. Although all patients eventually developed morpheaform and/or sclerodermoid GVHD, LS was a prominent part of the initial presentation of chronic cutaneous GVHD in every case. The LS lesions tended to occur on the neck and upper to mid aspect of the trunk, whereas morpheaform lesions favored the lower aspect of the trunk. EF involved the extremities (sparing the hands and feet), and was characterized clinically by an acute onset of pain and edema followed by induration with a rippled appearance.
This case series serves to expand the spectrum of sclerodermoid GVHD, with LS as the most superficial and EF as its deepest manifestation.
Melanocytic Proliferations Associated With Lichen Sclerosus
J. Andrew Carlson, MD, FRCPC; Xiao C. Mu, MD, PhD; Andrzej Slominski, MD, PhD; Kaare Weismann, MD, PhD; A. Neil Crowson, MD; John Malfetano, MD; Victor G. Prieto, MD, PhD; Martin C. Mihm, Jr, MD
Arch Dermatol. 2002;138:77-87 Abstract quote
To describe the clinicopathologic features of melanocytic proliferations associated with lichen sclerosus (LS) and to compare these findings with those in controls. Design Cohort study.
Academic and private practice dermatology and dermatopathology services.
Cases of melanocytic proliferations associated with LS and consecutive controls with persistent (recurrent) melanocytic nevi, persistent malignant melanomas, and compound melanocytic nevi.
Main Outcome Measures
Diagnostic criteria and disease recurrence.
Eleven patients, all female, with a mean age of 40 years (range, 8-83 years), presented with pigmented lesions clinically suspected to be malignant melanoma or atypical melanocytic nevi affecting the vulva (7 patients), perineum (3 patients), or chest (1 patient). Lichen sclerosus was first identified in the biopsy specimen and subsequently confirmed clinically. In 10 cases, a melanocytic nevus was superimposed on LS (overlying or entrapped by sclerosis), whereas LS was found at the periphery of vulvar malignant melanoma. After complete excision, no recurrences have been reported for the melanocytic nevi in LS (mean follow-up, 29 months; range, 4-60 months). Compared with control lesions, the LS melanocytic nevi most closely resembled persistent melanocytic nevi and could be distinguished from persistent malignant melanoma histologically. Melanocytes, nevoid or malignant, proliferating contiguously with fibrotic or sclerotic collagen, contained abundant melanin, diffusely expressed HMB-45, and had a higher Ki-67 labeling index than ordinary melanocytic nevi. However, persistent malignant melanoma exhibited mitotic figures, significantly higher Ki-67 labeling index, and deep dermal HMB-45 expression compared with LS melanocytic nevi and persistent melanocytic nevi.
Melanocytic nevi occurring in LS have features in common with persistent melanocytic nevi and can mimic malignant melanoma. An "activated" melanocytic phenotype is seen in LS melanocytic nevi, implicating a stromal-induced change.
PATHOGENESIS CHARACTERIZATION BASEMENT MEMBRANE ALTERATIONS
Am J Dermatopathol. 2005 Dec;27(6):489-96. Abstract quote
The aim of this study was to compare alterations of the basement membrane zone (BMZ) and to visualize changes within the skin vascular network in morphea and extragenital lichen sclerosus with the use of laser scanning confocal microscopy.
This work was performed in eight plaques of morphea (three active and five inactive) and eight of lichen sclerosus (three of short duration and five long-lasting). Biopsy specimens from six healthy individuals served as controls. The biopsies were cut into 40-mum-thick sections, labeled with antibodies against beta4-intergin (a lamina lucida marker), collagen IV, and the N-terminal end of collagen VII (lamina densa markers) and C-terminal end of collagen VII (a sublamina densa marker) and studied using laser scanning confocal microscopy. Three-dimensional reconstruction of various regions of the BMZ showed a decreased number and size of the dermal papillae both in morphea and lichen sclerosus compared with normal skin. In morphea, the continuity of the BMZ at the level of lamina lucida, lamina densa, and sublamina densa was preserved whereas in LS numerous invaginations and holes were present in the BMZ at the level of the lamina lucida and lamina densa. Thus the alterations of the BMZ in morphea differ from those in lichen sclerosus.
Three-dimensional reconstruction of the skin vascular network showed increased angiogenesis only in the early inflammatory stage of morphea, whereas in inactive morphea and lichen sclerosus various numbers of enlarged vessels were visible. The changes in the vascular network in morphea appear to be related to the activity of the disease.
Alterations of basement membrane zone in bullous and non-bullous variants of extragenital lichen sclerosus.
Kowalewski C, Kozlowska A, Zawadzka M, Wozniak K, Blaszczyk M, Jablonska S.
Department of Dermatology, University of Medicine, Warsaw, Poland
Am J Dermatopathol. 2004 Apr;26(2):96-101. Abstract quote
The aim of the study was to compare alterations of various regions of the basement membrane zone (BMZ) in lichen sclerosus (LS) using laser scanning confocal microscopy.
The study included three cases of bullous LS, one case of bullous LS that developed in the course of graft-versus-host disease (GVHD), and six cases of non-bullous LS. Three cases of morphea served as a control. Biopsies from patients' skin and control biopsies from normal human skin were cut into 30-microm thick slides and labeled with antibodies against beta4-intergin (lamina lucida marker), collagen IV, and the N-terminal end of collagen VII (lamina densa markers) and the C-terminal end of collagen VII (sublamina densa marker) using routine immunofluorescence (IF). Three-dimensional (3D) reconstruction of various regions of the BMZ showed a decrease in the number and size of the dermal papillae in LS and morphea as compared with normal skin. In LS numerous invaginations and holes were present in the BMZ at the level of the lamina lucida and lamina densa. Computer animation of 3D projections revealed that the thickness of the lamina densa observed under the light microscopy is an optical artifact dependent on periodical tortion of the lamina densa along its axis. Torsions and invaginations of the BMZ are equally responsible for the phenomenon of artificial reduplication of the lamina densa observed at the ultrastructural level. IF labeling with antibody against the N-terminal end of collagen VII disclosed the presence of a large hole (up to 25 microm) in the lamina densa and the presence of granular material in deep dermis suggestive of partial degradation of lamina densa at the level of anchoring fibers. An IF mapping study showed blister formation below the lamina densa in three patients with bullous LS, whereas in a case of LS associated with GVHD, a blister formed through the basal layer of the epidermis.
In morphea, there was flattening of BMZ at the level of lamina lucida, lamina densa, and sublamina densa but the continuity of BMZ was preserved. Three-dimensional reconstruction of dermal-epidermal junction in LS revealed alterations of the BMZ, most pronounced at the level of the lamina densa and sublamina densa.
Possible mechanisms of hypopigmentation in lichen sclerosus.
Carlson JA, Grabowski R, Mu XC, Del Rosario A, Malfetano J, Slominski A.
Department of Pathology, Albany Medical College (J.A.C., R.G., X.C.M., A.D.R.) and Associates in Gynecologic Care (J.M.), Albany, New York; and Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee (A.S.).
Am J Dermatopathol 2002 Apr;24(2):97-107 Abstract quote
Lichen sclerosus (LS) shares with vitiligo a milky-white appearance. By biopsy, pathognomonic dermal sclerosis readily distinguishes LS from vitiligo and other causes of leukoderma.
To determine what the mechanism of hypopigmentation is in LS, we examined samples from LS cases for alterations in melanin content (Fontana-Masson stain) and melanocyte number (HMB-45 [PMEL-17/gp100], Mel-5 [TRP-1], Mart-1 [Melan A]) and compared these findings with those in controls of normal skin, acute scars, vitiligo, and lichen planus (LP; a common inflammatory cause of hyperpigmentation).
The degree and extent of melanization found in LS overlapped with that in acute scars showing predominantly hypomelanized keratinocytes, with that in LP containing regions with numerous melanophages, and with that in vitiligo exhibiting focal regions of keratinocytes devoid of melanin pigment. By hematoxylin-eosin staining and immunocytochemistry for Mel-5 and Mart-1, LS had a lower mean count of melanocytes than acute scars, LP, and normal skin per 200 basal keratinocytes. In addition, a few LS cases had a significant loss of melanocytes comparable to that of vitiligo. Surprisingly, Mart-1 identified rare melanocytes in 67% of vitiligo cases and a significantly larger pool of melanocytes in LS and controls other than those labeled by Mel-5. Furthermore, LP and evolving lesions of LS contained the highest Mart-1 counts. HMB-45-immunoreactive melanocytes were found in the majority of acute scars and in LP and late-stage LS lesions at significantly lower levels than Mel-5- and Mart-1- labeled melanocytes, but they were not found in vitiligo or normal skin.
We propose that several mechanisms may play a role in the production of leucoderma in LS: 1) decreased melanin production; 2) block in transfer of melanosomes to keratinocytes; and 3) melanocyte loss. The latter finding may be the pathogenic connection (lichenoid dermatitis of LS triggering an autoimmune reaction to melanocytes) that underlies the documented association of LS with vitiligo.
INTER ALPHA TRYPSIN INHIBITOR
Abnormal accumulation of inter-alpha-trypsin inhibitor and hyaluronic acid in lichen sclerosus.
Kuroda K, Fujimoto N, Tajima S.
Department of Dermatology, National Defense Medical College, Tokorozawa, Japan.
J Cutan Pathol. 2005 Feb;32(2):137-40. Abstract quote
Inter-alpha-trypsin inhibitor (ITI) is a recently identified extracellular hyaluronic acid (HA)-binding protein which greatly improves extracellular HA stability. In lichen sclerosus (LS), a broad hyalinized zone of superficial dermis is the most prominent pathological change.
To assess the pathogenic role of ITI in accumulation of HA in a broad hyalinized zone in LS, we examined the expression and localization of ITI and HA immunohistochemically. In LS lesional skin sections, ITI staining revealed a strong, diffuse immunoreactivity predominantly in the upper dermis, whereas no staining was detected in normal skin sections. HA staining clearly showed positive reactivity in the superficial dermis, the epidermis, and occasionally the perivascular inflammatory infiltrate in LS skin sections. In normal skin, HA was present only in the epidermis. Double staining for ITI and HA demonstrated that ITI was localized in the areas where HA was abnormally deposited in the superficial dermis of LS. Other HA-binding proteins, CD44 and versican, did not show enhanced staining in the upper dermis of LS compared to normal skin specimens.
These findings strongly suggest that ITI is closely implicated in the accumulation of HA in a broad hyalinized zone of the superficial dermis of LS.
Alterations of the p16/Rb/cyclin-D1 pathway in vulvar carcinoma, vulvar intraepithelial neoplasia, and lichen sclerosus.
Lerma E, Esteller M, Herman JG, Prat J.
Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.
Hum Pathol 2002 Nov;33(11):1120-5 Abstract quote
Three different alterations in the p16/pRb/cyclin-D1 pathway (p16(INK4a)-promoter hypermethylation and expression of pRb and cyclin-D1) were investigated in a series of 38 cases of vulvar carcinoma (VC), 13 cases of vulvar intraepithelial neoplasia (VIN), and 21 cases of lichen sclerosus (LS).
Paraffin blocks from 72 patients were selected for investigation of DNA methylation patterns in the CpG island of p16(INK4a) by methylation-specific polymerase chain reaction. Immunohistochemical studies for pRb and cyclin-D1 were performed using the standard avidin-biotin-peroxidase complex method. Epigenetic silencing of p16(INK4a) was detected in 68% of VC, 69.2% of VIN, and 42.8% of LS cases. Lack of pRb protein was found in 21% of VC, 0% of VIN, and 0% of LS cases. Overexpression of cyclin-D1 was found in 21% of VC, 30.8% of VIN, and 0% of LS cases.
We conclude (1) that p16(INK4a) epigenetic inactivation most likely represents an early event, insufficient for malignant transformation, that may occur in clinically benign lesions such as LS; (2) that lack of pRb was only detected in fewer than one quarter of the carcinomas and could be considered a late secondary event; and (3) that cyclin-D1, which was overexpressed in VC and VIN, could contribute to the malignant transformation in association with p16 hypermethylation.
CHARACTERIZATION General VARIANTS
Childhood vulvar lichen sclerosus: An increasingly common problem
Jenny Powell, etal.
J Am Acad Dermatol 2001;44:803-6. Abstract quote
Background: Lichen sclerosus (LS) of the vulva in children is presenting more commonly, but its origin is unknown.
Objective: The purpose of this study was to assess the prevalence of childhood vulvar LS, to examine factors that may play a role in its cause, and to attempt to define the current optimal treatment.
Methods: We surveyed 70 cases of LS currently being treated in the pediatric vulvar clinic to collect information on presentation, family history, associated disease, and typical course of the disorder. We looked retrospectively and prospectively at treatments for LS.
Results: We found a prevalence of premenarchal LS of 1 in 900 and confirmed an increasing incidence. In a high proportion of cases (77%), the question of sexual abuse had been raised. A family history of LS was found in a minimum of 17% of cases. Associated autoimmune disease occurred in 14%, but 64% told of a family history, and atopy occurred in 59%. Potent topical steroid ointments appear to alleviate symptoms most effectively, with minimal side effects.
Conclusion: Although the cause of LS remains uncertain, it is not a rare disease in prepubertal girls. Current optimal management includes prompt diagnosis and institution of treatment with a potent topical steroid.
HISTOLOGICAL TYPES CHARACTERIZATION General
Early disease begins as an interface dermatitis with vacuolar alteration at the dermo-epidermal junction
As the disease progresses, there is characteristic hyalinization and edema of the papillary dermis and ensuing epidermal atrophy
A lichenoid infiltrate develops below the area of hyalinization usually composed of melanophages, lymphocytes, and plasma cells
Clinicopathologic comparison of vulvar and extragenital lichen sclerosus: histologic variants, evolving lesions, and etiology of 141 cases.
Carlson JA, Lamb P, Malfetano J, Ambros RA, Mihm MC Jr.
Division of Dermatopathology and Dermatology, Albany Medical College, New York 12208, USA.
Mod Pathol 1998 Sep;11(9):844-54 Abstract quote
Lichen sclerosus (LS) is a persistent inflammatory dermatosis of unknown etiology with a predilection for the vulva, where it is a risk factor for carcinoma.
We performed a clinicopathologic study on 121 cases of vulvar LS and 20 of extragenital LS, and we reviewed 49 vulvectomy specimens with LS to define morphologic findings, identify the earliest lesions, and correlate outcomes with histologic findings.
The vulvar LS lesions were pruritic/burning, white/red, ill-defined patches predominately affecting the labia, perineum, introitus, and perianal region. The extragenital LS lesions were asymptomatic, pink to ivory white, coalescing macules or patches with well-defined borders. All of the LS cases showed dermal sclerosis, vacuolar interface changes, and a lymphocytic infiltrate underlying the sclerosis, but vulvar LS showed changes of lichen simplex chronicus or spongiotic dermatitis, dermal eosinophils, and a frequent absence of atrophy.
The presence of eosinophilic spongiosis, marked lymphocyte exocytosis, dermal eosinophils, and excoriations predicted poor symptomatic response to treatment. Patch testing is recommended for these individuals as these findings suggest an allergic contact dermatitis. Examination of vulvectomy specimens revealed either a lichenoid interface or a spongiotic dermatitis in continuity with pathognomonic LS. Additionally, in these contiguous regions, we identified histologic changes that might represent evolving lesions of LS, suggesting a multifactorial etiology.
In conclusion, vulvar LS was significantly different clinicopathologically from extragenital LS, and if only classic features of LS were used for pathologic diagnosis, many cases of vulvar LS would be missed.
Therefore, we proposed as the minimal histologic criterion for LS the presence of a vacuolar interface reaction pattern in conjunction with dermal sclerosis (homogenized and hyalinized eosinophilic collagen bundles) of any thickness intervening between the inflammatory infiltrate and epithelium and or vessel walls.
Histology of Lichen Sclerosus Varies According to Site and Proximity to Carcinoma
James Scurry, M.D.; Julie Whitehead, M.R.A.C.O.G.; Martin Healey, F.R.A.C.O.G.
From the Departments of Pathology (J.S.) and Obstetrics and Gynecology (J.W., M.H.), Mercy Hospital for Women, Melbourne, Australia.
Am J Dermatopathol 2001;23:413-418 Abstract quote
To investigate why vulvar but not extragenital lichen sclerosus is associated with squamous cell carcinoma, we performed a histologic study of extragenital lichen sclerosus, vulvar lichen sclerosus without carcinoma, and vulvar lichen sclerosus with carcinoma adjacent to and distant from the carcinoma.
We compared epidermal thickness, rete ridge length, mitotic activity, atypia, dermal collagen change, dermal inflammation, and presence of other dermatoses in 30 women in each group.
Extragenital lichen sclerosus showed thinner epidermis (mean thickness of 0.13 mm versus 0.41 mm; P < 0.0005), shorter rete ridges ( P = 0.0001), more dermal edema ( P = 0.16), and absence of associated dermatoses of spongiotic dermatitis and lichen planus ( P < 0.005) compared with vulvar lichen sclerosus. The epidermal thickening seen in vulvar lichen sclerosus was indistinguishable from lichen simplex chronicus. Vulvar lichen sclerosus without carcinoma was generally similar to that distant from carcinoma. Vulvar lichen sclerosus adjacent to carcinoma showed increased epidermal thickness (0.61 mm versus 0.26 mm; P < 0.005), more dermal fibrosis ( P < 0.0005), more inflammation ( P < 0.0005), and more simplex (differentiated) vulvar intraepithelial neoplasia (18 cases versus 1 case; P < 0.0005) compared with that distant from carcinoma.
We concluded that (1) the classic histologic features of lichen sclerosus are seen in both vulvar and extragenital sites; (2) vulvar lichen sclerosus without associated carcinoma has a mean epidermal thickness more than three times that of extragenital lichen sclerosus; (3) the epidermal thickening is histologically indistinguishable from lichen simplex chronicus; (4) there is a tendency for vulvar lichen sclerosus to have a more sclerotic and inflamed dermis; (5) lichen sclerosus 10 mm from cancer is more similar to vulvar lichen sclerosus without carcinoma than lichen sclerosus 1 mm from carcinoma; and (6) lichen sclerosus adjacent to carcinoma tends to show exaggerated epidermis thickness, basal atypia, and loss of the edematous-hyaline layer.
VARIANTS ANGIOKERATOMA-LIKE CHANGES
J Cutan Pathol 2009:36;540-542 Abstract quote
Hemorrhagic blisters have rarely been described developing in the background of either genital or extragenital lichen sclerosus and have invariably been designated clinically as telangiectatic, hemorrhagic or bullous lichen sclerosus.
We describe three patients with extragenital and genital lichen sclerosus, who presented clinically with hemorrhagic plaques and/or papules. In addition to the classical histology of lichen sclerosus, dilated, congested and focally thrombosed vascular channels lined by flat endothelium were seen within the sclerotic dermal collagen. They were in close proximity to and even in contact with the overlying epidermis and thus mimicked an angiokeratoma. Angiokeratoma-like changes in lichen sclerosus represent secondary features because of damage to the dermis by lichen sclerosus and are characterized histologically by ectatic thin-walled vascular spaces in the papillary dermis intimately associated with the epidermis.
Increased venous pressure, local trauma, degenerative changes in the elastic tissue of the vessel wall and/or surrounding supportive tissue, as well as abnormalities in the extracellular protein network, appear to be implicated in their pathogenesis.
MORPHEA CO-EXISTING MYCOSIS FUNGOIDES LIKE CHANGES
Lichen sclerosus with histopathologic features simulating early mycosis fungoides.
Citarella L, Massone C, Kerl H, Cerroni L.
Department of Dermatology, University of Graz, Austria.
Am J Dermatopathol. 2003 Dec;25(6):463-5 Abstract quote.
Mycosis fungoides (MF) is a cutaneous T-cell lymphoma characterized in its early stages by a superficial band-like infiltrate with epidermotropism of lymphocytes without particularly atypical cytologic features. Even though clinicopathologic presentation is diagnostic in typical cases, some inflammatory skin disorders can simulate the histopathologic features of early MF.
In this study we present data on 9 patients affected by lichen sclerosus (LS) (M:F ratio 8:1; age range 7-75 years; mean age 31.3 years; median age 13 years), who presented with histopathologic features simulating early lesions of MF. The histopathologic picture was characterized in all cases by a dense, band-like infiltrate of lymphocytes within the superficial dermis, with exocytosis of lymphocytes within the lower part of the epidermis. The papillary dermis was expanded and showed focally coarse bundles of collagen simulating MF. The typical signs of LS were either absent or present only focally. Molecular analyses of the TCRgamma gene rearrangement performed with the polymerase chain reaction (PCR) technique revealed a polyclonal smear in eight cases, and a monoclonal band in one.
Our study shows that LS can present with histopathologic features simulating early MF. Especially in cases revealing a monoclonal population of T lymphocytes by PCR, the correct diagnosis may be overlooked without proper clinical information and clinicopathologic correlation. Lichen sclerosus should be added to the list of cutaneous T-cell pseudolymphomas.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS VULVAR LESIONS Pseudohyperplastic Squamous Cell Carcinoma of the Penis Associated With Lichen Sclerosus. An Extremely Well-differentiated, Nonverruciform Neoplasm That Preferentially Affects the Foreskin and Is Frequently Misdiagnosed: A Report of 10 Cases of a Distinctive Clinicopathologic Entity.
Cubilla AL, Velazquez EF, Young RH.
*Instituto de Patologia e Investigacion and Facultad de Ciencias Medicas, Asuncion, Paraguay; the daggerNew York University Medical Center, New York, NY; and double daggerThe James Homer Wright Pathology Laboratories of Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Am J Surg Pathol. 2004 Jul;28(7):895-900. Abstract quote
We present 10 cases of well-differentiated, squamous cell carcinoma of the penis with pseudohyperplastic features. At presentation, the median age was 69 years. Seven of the tumors were multicentric, and the majority preferentially involved the foreskin inner mucosal surface. Grossly the tumors were typically flat or slightly elevated, white and granular, and measured approximately 2 cm. Characteristic histologic features included keratinizing nests of squamous cells with minimal atypia surrounded by a reactive fibrous stroma. In biopsies or individual areas of resected specimens, the differential diagnosis with pseudoepitheliomatous hyperplasia was difficult but when samples of adequate size were available, obvious evidence of infiltration was present. The adjacent squamous epithelium typically showed changes that are known to be associated with squamous cell carcinoma ranging from squamous hyperplasia to low-grade, and in a few cases high-grade, squamous intraepithelial lesions. Well-developed lichen sclerosus was seen in all cases. Patients were treated by circumcision or partial penectomy.
With the exception of 1 patient who developed a glans recurrence 2 years after initial circumcision, follow-up after the initial surgical procedure has been uneventful. The majority of penile carcinomas with the high degree of differentiation seen in these cases are in the category of the verruciform tumors, either the verrucous or papillary carcinoma, not otherwise-specified subtypes.
Experience with the cases reported in this series indicates that a subset of nonverruciform, often multicentric, tumors with a high degree of differentiation and pseudohyperplastic features occur and preferentially involve the foreskin. Because it was present in all cases, lichen sclerosus may play a precancerous role.
Vulvar lichen sclerosus and squamous cell carcinoma: a cohort, case control, and investigational study with historical perspective; implications for chronic inflammation and sclerosis in the development of neoplasia.
Carlson JA, Ambros R, Malfetano J, Ross J, Grabowski R, Lamb P, Figge H, Mihm MC Jr.
Department of Pathology, Albany Medical College, NY 12208, USA.
Hum Pathol 1998 Sep;29(9):932-48 Abstract quote
The histological changes of lichen sclerosus (LS) are frequently found in association with vulvar squamous cell carcinoma (SCC). The importance of chronic inflammation and scarring in oncogenesis is well recognized.
Thirty-two patients with symptomatic vulvar LS and 60 with vulvar SCC were studied. Paraffin sections of vulvar LS, and three controls groups (acute scars, normal vulva, and vulvar lichen simplex chronicus [LSC]) were investigated with a panel of seven tissue markers and for DNA content in areas without vulvar intraepithelial neoplasia (VIN). All published cases to date of vulvar LS associated with SCC were reviewed. Of the cohort of symptomatic vulvar LS patients (mean/median age, 60 years), 9% developed VIN lesions and 21% invasive SCC; symptomatic LS preceded the carcinoma by a mean of 4 years (range, 1 to 23 years). Second and third primary tumors developed in three of these patients. Of the series of 60 patients presenting with vulvar SCCa, the clinical setting and histological features of SCCs associated with LS were significantly distinctive compared with SCCas without LS: SCCs associated with LS occurred in an older age-group (74 v 65 years; P = .01), were located on the clitoris (41% v 5%; P = .003), were of conventional SCCa type (85% v 57%; P = .02), were associated with a prominent fibromyxoid stromal response (46% v 10%; P = .004), were not associated with VIN 3 (SCC in situ) (5% v 67%; P = .02) and diffusely expressed tumor suppressor gene product p53 (43% v 19%; P = .01) and cytokine TGF-beta (33% v 9%; P = .05).
The epidermis of vulvar LS was similar to that of acute scars and differed significantly compared with normal vulva with respect to keratinocytic expression of markers to keratin AE 1, involucrin and filaggrin, epidermal thickness (0.13 mm [LS] v 0.05 mm [normal]; P < .03), and proliferative index by PCNA and Mib-1 labeling (53/60 [LS] v 15/19 [normal] per 200 basal cells [bc]; P < .003). Vulvar LS showed significantly higher expression of p53 than all three control groups (80 [LS] v 3 [normal]/44 [acute scar]/28 [LSC] per 200 bc; P < .008), and aneuploidy (33% v diploid controls) in the absence of VIN. Comparing LS with and without associated SCCa found significant increases in age of patients (74 v 66 years; P = .001), and DNA aneuploidy (52% v 11%; P = .0001) and no differences in epidermal thickness, sclerotic thickness, proliferative index, or p53 expression. However, those cases of LS with an aneuploid DNA content showed significantly elevated p53 expression (88 v 60/200 bc; P = .01) and epidermal thickness (0.16 v 0.11 mm; P = .005) compared with LS with a diploid DNA content.
Review of published cases supports an association between LS and vulvar SCC. The phenomenon of chronic inflammation and scarring giving rise to carcinoma has been well documented. Vulvar lichen sclerosus (LS) is an inflammatory dermatosis characterized by clinicopathologic persistence and hypocellular fibrosis (sclerosis).
A subset of vulvar SCCs is significantly associated with the presence of LS and diffusely express the p53 gene product. Keratinocytes affected by LS show a proliferative phenotype and can exhibit markers of neoplastic progression such as increased p53 expression and DNA aneuploidy. As a chronic scarring inflammatory dermatosis, vulvar LS could act as both "initiator and promoter" of carcinogenesis, explaining the frequent coexistence of these diseases. Because keratinocytes of LS significantly express tumor suppressor gene p53 protein, the p53 gene may be involved early in this proposed pathway of carcinogenesis.
Potent topical steroid ointment (clobetasol proprionate 0.05%) daily for 3 months is the treatment of choice for vulvar LS at all ages
Vulvar Lichen Sclerosus
Effect of Long-term Topical Application of a Potent Steroid on the Course of the Disease
Catherine Renaud-Vilmer, MD; Bénédicte Cavelier-Balloy, MD; Raphaël Porcher, PhD; Louis Dubertret, MD, PhD
Arch Dermatol. 2004;140:709-712. Abstract quote Background Lichen sclerosus is an inflammatory disease of unknown etiology affecting the anogenital skin and associated with the development of squamous cell carcinoma. It is not known whether long-term topical treatment with a potent steroid can cure this disease and thus prevent malignant evolution.
Objectives To analyze the rates of remission, recurrence, and chronic evolution of vulvar lichen sclerosus (VLS) treated with 0.05% clobetasol propionate ointment and determine whether this treatment can decrease the risk of malignant evolution.
Design Prospective study, conducted between 1981 and 2001, of 83 women with VLS who were treated until complete clinical and histologic remission and followed up for evidence of clinical and histologic recurrence (median follow-up, 4.7 years).
Setting Dermatology department of a large urban teaching hospital.
Results Complete remission was obtained in 45 patients (54%). The probability of remission was significantly associated with age (P<.001). The estimated incidence of remission at 3 years was 72% in women younger than 50 years, 23% in women aged between 50 and 70 years, and 0% in women older than 70 years. The incidence of relapse was estimated to be 50% at 16 months (95% confidence interval, 30%-64%) and 84% at 4 years (95% confidence interval, 57%-94%). Age had no effect on relapse prevalence. The 8 observed vulvar squamous cell carcinomas (9.6%) occurred in previously untreated or irregularly treated VLS lesions.
Conclusions Treatment with a potent steroid cream can improve but does not cure VLS in women older than 70 years, probably because of a long disease evolution. In younger patients who achieve complete remission, it seems to have only a temporary effect. Although a protective effect from malignant evolution is suggested (carcinoma developed only in nontreated or irregularly treated VLS lesions), the number of seemingly protected patients was too small to be statistically significant.
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