Allelic loss in amalgam-associated oral lichenoid lesions compared to oral lichen planus and mucosa.

BACKGROUND: The amalgam-associated oral lichenoid lesion (AAOLL) shows clinical and histopathological features similar to oral lichen planus (OLP). Molecular researches to improve knowledge of pathogenesis and clinical behavior of AAOLL are still scarce. OBJECTIVE: We investigated for the first time the use of loss of heterozygosity (LOH) as a molecular approach for genetic characterization of AAOLL in comparison with OLP and evaluated the cell proliferation index. MATERIALS AND METHODS: The sample comprised nine AAOLLs, 10 OLPs, and eight NOMs matched by patients' gender and age. LOH was assessed using polymorphic microsatellite markers at chromosomes 9p (D9S157, D9S162, D9S171), 11q (D11S1369), and 17p (TP53, AFM238WF2). Cell proliferation was assessed by immunohistochemical expression of Ki-67 (MIB-1). The association between LOH and Ki-67 was investigated. RESULTS: Loss of heterozygosity occurred in 5/9 AAOLLs and in 2/10 OLPs in at least one marker each, while NOM showed no LOH. Cell proliferation index in AAOLL ranged from 2 to 23%. There was no association between cell proliferation and LOH, independent of the marker. CONCLUSION: Our study shows that the profile of molecular changes in AAOLL and OLP, evaluated by LOH and Ki-67 expression, is similar. Additional studies including larger samples should be performed to confirm or to refute our findings.

Genomewide miRNA profiling of oral lichenoid disorders and oral squamous cell carcinoma.

OBJECTIVE: To dissect the aberrant microRNA profile of oral lichenoid disorders (OLD) by analyzing the larger set of OLD samples tested so far. MATERIALS AND METHODS: MicroRNA expression profiles were assessed using TLDA card in 32 samples (16 OLD, 8 OSCC, and 8 control). The findings were validated using RT-qPCR in an independent cohort of 91 samples. RESULTS: We identified 20 differentially expressed microRNAs in OLD, of which several are functionally related to cell proliferation, response to organic substances, or immune processes. Further validation of the top-ranked microRNAs revealed that they were all aberrantly expressed in OLD. CONCLUSION: We have identified a new microRNA signature associated with OLD that may provide a meaningful basis for better understanding the physiopathology of the disease. In addition, we validated seven microRNAs whose expression was shown to be higher in OLD tissue in comparison with the control and OSCC tissues.

FGFR3, PIK3CA and RAS mutations in benign lichenoid keratosis.

BACKGROUND: Benign lichenoid keratoses (BLKs) are solitary skin lesions which have been proposed to represent a regressive form of pre-existent epidermal tumours such as solar lentigo or seborrhoeic keratosis. However, the genetic basis of BLK is unknown. OBJECTIVES: FGFR3, PIK3CA and RAS mutations have been shown to be involved in the pathogenesis of seborrhoeic keratosis and solar lentigo. We thus investigated whether these mutations are also present in BLK. METHODS: After manual microdissection and DNA isolation, 52 BLKs were screened for FGFR3, PIK3CA and RAS hotspot mutations using SNaPshot(®) multiplex assays. RESULTS: We identified 6/52 (12%) FGFR3 mutations, 10/52 (19%) PIK3CA mutations, 6/52 (12%) HRAS mutations and 2/52 (4%) KRAS mutations. FGFR3 and RAS mutations were mutually exclusive. One BLK showed a simultaneous PIK3CA and HRAS mutation. In nine BLKs with a mutation, nonlesional control tissue from the epidermal margin and the dermal lymphocytic infiltrate were wild-type, indicating that these mutations are somatic. To demonstrate that these findings are specific, 10 samples of lichen planus were analysed without evidence for FGFR3, PIK3CA or RAS mutations. CONCLUSIONS: Our results indicate that FGFR3, PIK3CA and RAS mutations are present in approximately 50% of BLKs. These findings support the concept on the molecular genetic level that at least a proportion of BLKs represents regressive variants resulting from former benign epidermal tumours such as seborrhoeic keratosis and solar lentigo.

Comparison of biomarker expression in oral lichen planus and oral lichenoid lesions.

BACKGROUND: Oral lichen planus (OLP) and oral lichenoid lesions (OLL) comprise a group of oral mucosal disorders that have similar clinical and histological features. OBJECTIVES: To compare the levels of investigated biomarkers in biopsied OLP and OLL, and to determine the pattern of biomarkers, which could be useful for the biological characterization of these 2 disorders. MATERIAL AND METHODS: A total of 56 biopsy specimens in 2 groups were analyzed in this study. One group consisted of 25 idiopathic OLP lesions, and the other included 31 OLL from patients treated with antihypertensive and cardiac medications. The expression of protein p53, topoisomerase I (topo I), heat shock protein 90 (HSP90), and E-cadherin was analyzed using immunohistochemistry. RESULTS: The p53 protein expression showed a trend to a positive correlation with topo I expression in the total sample (p = 0.067, R = 0.25). The p53 protein and HSP90 expression was higher in the OLL group compared to the OLP group, but the difference was not statistically significant. No association was found between topo I and E-cadherin expression for either the OLP or OLL group. CONCLUSIONS: The findings of this study suggest that the slightly higher protein p53 and HSP90 expression in the OLL group might be caused by the medications used. The slight association between p53 and topo I expression indicates that the cooperation between these proteins might be essential for the growth of OLP/OLL in general. We conclude that the overexpression of p53 protein and high expression of topo I found in both types of lesions might induce their biologically aggressive behavior.

Unilateral acrokeratoelastoidosis--second reported case.

Acrokeratoelastoidosis (AKE) is a rare disease that manifests as wartlike papules along the dorsal palmar junction. It is characterized by orthohyperkeratosis in the horny layer and elastorrhexis in the reticular dermis. Both sporadic and familial cases following autosomal dominant inheritance have been reported. Currently, no effective treatments exist for AKE, which can have a significant cosmetic impact. Here we present the second reported case of unilateral AKE in a 5-year-old African American girl and hypothesize that the mechanism for the unilateral nature of AKE in this patient is genetic mosaicism.

[Galli-Galli disease presenting as lichenoid papules in the flexures]. / Presentación de enfermedad de Galli-Galli como pápulas liquenoides flexurales.

Galli-Galli disease is a rare genodermatosis currently regarded as an acantholytic variant of Dowling-Degos disease. The 2 diseases have the same clinical features: reticular hyperpigmented macules in the great skin folds, erythematous scaly papules and plaques, comedo-like lesions, and pitted perioral scars, and the only differentiating characteristic is the histological finding of acantholysis, usually without dyskeratosis. We describe the case of a patient with hyperpigmented papules in the skin folds as the only sign of Galli-Galli disease, and we present a review of the literature.

Annular lichenoid dermatitis of youth ... and beyond: a series of 6 cases.

Annular lichenoid dermatitis of youth (ALDY) is a clinico-pathologic entity described in children and young patients, clinically reminiscent of morphea, annular erythema, vitiligo or mycosis fungoides. We report on six patients presenting single or multiple lesions, distributed particularly on the flanks and abdomen, with clinical and histologic features consistent with ALDY. Two patients were young girls and four were adults males. Three patients received topical therapy and four showed complete resolution of the lesions after a 24-65 months follow-up. Analogously to the cases reported so far, immunohistochemistry showed a T cell infiltrate with a predominance of CD8+ lymphocytes, while T cell receptor rearrangement was absent in all cases. It seems appropriate to include annular lichenoid dermatitis of youth among the dermatoses with a lichenoid pattern. For the first time, we found that it can affect also adult patients, therefore we propose to rename the disease annular lichenoid dermatitis. The differential diagnosis with mycosis fungoides, especially in adult patients, is particularly crucial for their proper management and treatment.

[Keratosis lichenoides chronica in two siblings with marked response to UVB phototherapy]. / Deux cas de kératose lichénoïde chronique dans une même fratrie. Réponse favorable à la photothérapie UVB.

BACKGROUND: Keratosis lichenoides chronica (KLC) is a rare chronic keratinisation disorder. Out of almost 60 published cases of KLC, only two report its occurrence in siblings. We report a new case in which a brother and sister present KLC that improved markedly with UVB phototherapy. PATIENTS AND METHODS: A 10-year-old girl presented with hyperkeratotic papules symmetrically arranged in a reticular pattern on the face and the extremities. Onset occurred at the age of six months. For a number of years, minimum sunlight was allowed owing to a diagnosis of lupus. However, KLC was our first diagnostic assumption, confirmed by an elbow lesion biopsy sample. The patient's brother, one and a half years old, had been presenting similar lesions since the age of two months. Sibship was demonstrated by DNA analysis using short tandem repeat markers. No consanguinity was found. After one month of narrow-band UVB phototherapy, most of the papules had flattened. DISCUSSION: KLC is uncommon in childhood and familial occurrence is very rare. Clinically, thick keratotic papules arranged in parallel lines or small networks cover the dorsal aspects of the limbs symmetrically. The face may be affected by a seborrhoea-like dermatitis. Histology typically shows alternating acanthosis and atrophy, with focal parakeratosis. An extensive lichenoid lymphohistiocytic and plasmocytic infiltrate is demonstrated in the dermis. The course is chronic. Spontaneous resolution may occur. Sunlight has been shown to be effective in the few paediatric cases reported. Narrow-band UVB phototherapy appears to be an effective therapeutic option.

Keratosis lichenoides chronica in pediatric patients: a different disease?

Keratosis lichenoides chronica (KLC) is a rare acquired disease of adulthood, of unknown etiology, characterized by keratotic parallel linear lesions, retiform plaques, and keratotic, often follicular papules, chronicity and lichenoid histopathologic features. KLC of pediatric onset is considered extremely rare. Its features and relationship to adult onset KLC are unknown. We studied 8 cases of pediatric-onset KLC in the literature and 6 personal cases and compared them with 40 reported adult-onset KLC patients. The following features characterize pediatric-onset KLC: familial occurrence; probable autosomal recessive inheritance; early or congenital onset with facial erythemato-purpuric macules; forehead, eyebrow, and eyelash alopecia; pruritus; and a low frequency of other cutaneous and systemic abnormalities. Pediatric-onset KLC may represent a different disease or a subset of adult-onset KLC, with special genetic and clinical characteristics. Determining its precise nosology will have prognostic and therapeutic implications.

"Pediatric blaschkitis": expanding the spectrum of childhood acquired Blaschko-linear dermatoses.

We describe two young children who developed relapsing, pruritic, papulovesicular eruptions in multiple bands along Blaschko lines on the neck, trunk, and extremities. Skin specimens in both revealed spongiotic dermatitis. This represents the first report of "blaschkitis" in children, providing further evidence that lichen striatus and blaschkitis are related acquired Blaschko-linear dermatoses that exist on a spectrum rather than as the childhood and adult form of a single disease entity. We highlight the features that differentiate blaschkitis from lichen striatus, review the potential roles of cutaneous mosaicism, environmental triggers, and background immunologic state in their pathogenesis, and discuss the spectrum of inflammatory dermatoses that can follow Blaschko lines.

Genetic linkage between the collagen type VII gene COL7A1 and pretibial epidermolysis bullosa with lichenoid features.

Pretibial epidermolysis bullosa is a rare form of dominant dystrophic epidermolysis bullosa. The disease was diagnosed after considerable delay in a large Belgian family and was remarkable for its late age at onset and its misleading clinical presentation in the proband, which strongly resembled keratosis lichenoides chronica. Both recessively and dominantly inherited forms of dystrophic epidermolysis bullosa have been shown to be linked to the collagen type VII gene, COL7A1. Two-point linkage analysis with two intragenic polymorphisms (PvuII, AluI) in COL7A1 was performed. Strong genetic linkage between the disease in this family and COL7A1 was demonstrated by a lod score of 4.45 (theta = 0) for the AluI polymorphism. The observed intrafamilial variability of clinical phenotypes contradicts the presently proposed classification of dominantly inherited dystrophic epidermolysis bullosa.

RET mutation screening in familial cutaneous lichen amyloidosis and in skin amyloidosis associated with multiple endocrine neoplasia.

In several families, multiple endocrine neoplasia type 2A (MEN 2A) has been found in association with cutaneous lichen amyloidosis. It has been debated, however, whether the skin amyloidosis found in MEN 2A families, localized exclusively in the interscapular area, represents the same anomaly as that found in autosomal dominant familial cutaneous lichen amyloidosis, which is more generalized. We screened two MEN 2A families with associated skin amyloidosis for germline mutations in the RET gene responsible for the MEN 2A cancer syndrome, and found the same mutation characteristic of MEN 2A in both families. We also screened probands from three pedigrees with familial cutaneous lichen amyloidosis for RET mutations. In none of the RET coding and flanking intronic sequences was a mutation detected. This most probably indicates that skin amyloidosis found in some MEN 2A families and familial cutaneous lichen amyloidosis are different conditions. Consequently, patients with apparent familial cutaneous lichen amyloidosis do not appear to be at risk for MEN 2A.

Further evidence for Borrelia burgdorferi infection in morphea and lichen sclerosus et atrophicus confirmed by DNA amplification.

We present further evidence in support of the notion that Borrelia burgdorferi is possibly involved in the pathogenesis of morphea and lichen sclerosus et atrophicus (LSA). Running a nested polymerase chain reaction (PCR) with a primer set specific for the flagellin gene of B. burgdorferi enabled us to demonstrate the presence of Borrelia DNA in skin biopsies of patients with morphea (nine of nine) of LSA (six of six). Biopsy specimens obtained from patients with erythema chronicum migrans (two patients, four of four samples) and acrodermatitis chronica atrophicans (one patient, one of one sample) also showed positive PCR results. By contrast, there was no amplification of Borrelia DNA in control biopsies either from patients with chronic eczema (three of three) or psoriasis (two of two) or from normal skin (three of three). Antibodies directed against B. burgdorferi were only detected in the serum of patients with erythema chronicum migrans (two of two) and acrodermatitis chronica atrophicans (one of one) but were not present in cases of morphea (five of five), LSA (three of three), or in control subjects (three of three). These data suggest that B. burgdorferi may play a role in the pathogenesis of both morphea and LSA. Furthermore, we conclude that PCR analysis provides an important diagnostic tool, even in seronegative Borrelia infections.

Lichenoid eruptions in children.

Lichenoid eruptions are quite common in children and can result from many different origins. In most instances the precise mechanism of disease is not known, although it is usually believed to be immunologic in nature. Certain disorders are common in children, whereas others more often affect the adult population. Lichen striatus, lichen nitidus, Gianotti-Crosti syndrome, and lichen spinulosus are examples of lichenoid lesions that are more common in children than adults. Distinguishing these diseases is necessary for prediction of the course of the eruption and for optimal management. In most cases, certain clinical characteristics enable the clinician to reach a diagnosis, whereas in other cases biopsy is required for a definitive answer. Many of these lesions are self-limited and only require symptomatic treatment, although corticosteroids can hasten resolution in certain disorders. Discontinuation of the medication is often sufficient for resolution of lichenoid drug eruptions.

Multiple endocrine neoplasia 2 (MEN 2)/MEN 2A (Sipple syndrome).

Multiple endocrine neoplasia type 2A (MEN 2A, Sipple syndrome) is an autosomal dominant phakomatosis and is most likely a paracrinopathy. The cardinal manifestations of MEN 2A--medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism--indicate that the condition is one of the inherited cancer syndromes. Cutaneous, lichen amyloidosis-like lesions place MEN 2A among the genodermatoses. The gene of MEN 2A, designated as MEN2A, is in the pericentromeric region of chromosome 10; this allows for reliable prenatal and presymptomatic DNA diagnosis.

Tenascin expression in mucocutaneous diseases and related lesions of human oral mucosa.

The expression of tenascin was assessed immunohistochemically. In normal oral mucosa, immunoreactivity for tenascin was seen either as a delicate line underlining the epithelium or in the stromal papillae. In oral lichen planus, a marked enhancement of tenascin immunoreactivity in the lamina propria was associated with focal infiltrates of inflammatory cells and seemed to reflect the intensity of inflammation. In lichenoid reactions in which only a sparse inflammatory infiltrate was present a band-like tenascin reactivity was seen. Oral psoriform reactions and chronic hyperplastic candidosis showed a prominent tenascin reaction in the connective tissue papillae among infiltrates of inflammatory cells. The results show that tenascin content is increased in oral mucocutaneous diseases and related lesions and that the abundance of tenascin reflects the intensity of the inflammatory reaction.