The ABO blood group antigens in patients with oral lichenoid reaction.

Evaluating the association of ABO blood group with different delayed hypersensitivity reactions, such as oral lichenoid reaction (OLR), can provide a new perspective for clinical practice. Therefore, this study designed to investigate ABO blood group antigens in OLR patients. In this case-control study, the ABO blood group of 112 OLR patients and 117 individuals without oral lesions were included. Gender, age, characteristics of the lesions, medications and restorative materials recorded. Chi-square test used to compare the frequency of ABO blood groups in OLR patients with controls. The O blood group was significantly higher in OLR patients and all its subtypes. Also, there were significant relation between O blood group, and severity of lesions. The frequency of dysplasia was non-statistically significant higher in OLR patients with O blood group than other blood group. Based on the results of the present study, O blood group was significantly more in patients with lichenoid reaction than control group, and AB blood group was the lowest. Also, O blood group showed a positive association with the more severe form of OLR lesions and frequency of dysplasia.

ALDH1 immunoexpression in epithelial and stromal cells of oral lichen planus and lesions with lichenoid inflammatory infiltrate.

BACKGROUND: Oral Lichen Planus is a potential malignant disorder and shares clinical and histopathological features with other similar lesions. ALDH1 is a specific biomarker for stem cells identification, however its role in stromal cells of immune inflammatory infiltrate has not been explored. The aim of this study was to investigate the ALDH1 immunoexpression in epithelial and stromal cells of Oral Lichen Planus and other lesions with lichenoid inflammatory infiltrate. MATERIAL AND METHODS: 64 samples of Oral Lichen Planus, Oral Lichenoid Lesions, Oral Leukoplakia and Unspecific Chronic Inflammation were included. ALDH1 was evaluated in both epithelium and stromal cells. ALDH1+ cells ≥ 5% were considered positive in epithelium. Stromal cells were evaluated semi quantitatively. Fields were ranked in scores, according to criteria: 1 (0 to 10%); 2 (11 to 50%) and 3 (>50%). The mean value of the sum of the fields was the final score. Statistical differences among groups were investigated, considering p < 0.05. RESULTS: ALDH1 expression in epithelium was low in all groups without difference among them. ALDH1+ cells in the lamina propria were higher for Lichen Planus [2.0], followed by Leukoplakia [1.3], Lichenoid lesions [1.2] and control [1.1] (p<0.05). CONCLUSIONS: ALDH1 immunoexpression in epithelium of lichenoid potential malignant disorders did not show a contributory tool, however ALDH1 in stromal cells of lichen planus might be involved in the complex process of immune regulation associated with the pathogenesis of this disease.

Cytotoxic dermatitis: Review of the interface dermatitis pattern in veterinary skin diseases.

Interface dermatitis or lichenoid interface dermatitis refers to a cutaneous inflammatory pattern in which keratinocyte cell death is the essential feature. These terms have evolved from the originally described lichenoid tissue reaction. These lesions are the basis for an important group of skin diseases in animals and people where cytotoxic T-cell-mediated epidermal damage is a major pathomechanism. Yet, for largely historical reasons these commonly used morphological diagnostic terms do not reflect the essential nature of the lesion. An emphasis on subsidiary lesions, such as the presence of a lichenoid band, and definitions based on anatomical features, such as location at the dermo-epidermal location, may cause confusion and even misdiagnosis. This review covers historical aspects of the terminology, including the origin of terms such as "lichenoid." The types of cell death involved and the histopathologic lesions are described. Etiopathogenesis is discussed in terms of aberrations of immune/inflammatory mechanisms focusing on cutaneous lupus erythematosus, erythema multiforme, and Stevens-Johnson syndrome/toxic epidermal necrolysis. Mechanisms have most extensively been studied in humans and laboratory animals and the discussion is centered on these species. As interface dermatitis is firmly entrenched in dermatological parlance, rather than using "cytotoxic" as its substitute, the terminologies "interface cytotoxic dermatitis" and "panepidermal cytotoxic dermatitis" are recommended, based on location and extent of epithelium affected.

ADVERSE DRUG EVENTS: LICHEN PLANUS OF THE PENIS AFTER INTAKE OF NEBIVOLOL- FIRST REPORTED CASE IN THE WORLD LITERATURE.

The pathogenesis of lichen planus and lichenoid-type reactions remains shrouded in mystery to this day, precisely because of the inability to perform acute/specific tests for reproduction of a particular type of reaction (in this case lichenoid) in order to prove a causal relationship. Nevertheless, the concept of molecular mimicry/antigen mimicry as a possible important pathogenetic inducer for lichen planus and lichenoid-type reactions, is increasingly becoming a topic of discussion and remains more than relevant at present. Disturbances in the integrity of tissue homeostasis- in one form or another, in fact, become a powerful generator of cross-mediated immunity, possibly directed at tissue-localized structures/structural elements/proteins or amino acids. The observation and reporting of this kind of disorders (even in the absence of the mentioned tests), as well as their parallel manifestation with a disease such as lichen planus (or lichenoid-type reaction), has led over the years to the validation of the now universal belief that the disease is multifactorially determined. And the causes of disruption of this integrity can be both external- infectious, meicamentous as well as internal- tumoral, paraneoplastic, etc. Medication induction or triggering of lichen planus by beta blockers has been observed and reported frequently over the years, and the clinical picture can vary and be extremely heterogeneous. We describe the first case in the world literature of a lichen planus after nebivolol administration that developed in the strictly restricted area of the glans penis. According to a reference in the medical literature, this is also the second case in the world literature of penile localized lichen planus after beta blocker intake. The other analogous one was recorded and described back in 1991 after propranolol intake.

Clinical and epidemiological profile of lichen striatus in children-Experience from a tertiary care hospital.

We analyzed records of 30 patients with lichen striatus (age < 18 years) in this retrospective study. Seventy percent were females and 30% were males with a mean age of diagnosis of 5.38 ± 4.22 years. The most common age group affected was 0-4 years. The mean duration of lichen striatus was 6.66 ± 4.22 months. Atopy was present in 9 (30%) patients. Although LS is a benign self-limited dermatosis, long-term prospective studies with a greater number of patients will help in better understanding of the disease including its etiopathogenesis and association with atopy.

PRAME immunohistochemistry can distinguish melanocytic pseudonests of lichenoid reactions from melanoma in situ.

BACKGROUND: Distinguishing melanocytic pseudonests encountered in lichenoid dermatoses or lichenoid keratoses from melanoma in situ (MIS) with brisk lichenoid inflammation can prove challenging. METHODS: We designed a case-control study to evaluate the accuracy metrics of PRAME immunohistochemistry to distinguish melanocytic pseudonests in lichenoid dermatoses or keratoses from inflamed MIS. Immunostaining for PRAME was performed on paraffin-embedded formalin-fixed diagnostic tissue using a rabbit monoclonal antibody to PRAME (Abcam), with a 1:3200 dilution on a Leica Bond detection system. RESULTS: Our search identified 21 cases of melanocytic pseudonests (n = 21, 46%) encountered in lichenoid dermatoses and 24 cases of inflamed MIS (n = 24, 53%). Each method of evaluating PRAME immunohistochemistry (PRAME+ clusters, PRAME % of melanocytes by four categories and PRAME+ melanocyte counts per linear mm of epidermal basal layer) showed statistically significant differences between the MIS and the pseudonest cohorts (respectively, p < 0.001; p < 0.001; and p < 0.001). Receiver operating characteristics analysis for PRAME+ melanocyte counts per linear mm of epidermal basal layer revealed an area under the curve of 0.9 ± 0.05 (95% confidence interval 0.9-1.0). When determining an optimal cut-off point for the best Youden index [sensitivity (%) + specificity (%) - 100], the cut-off of 1.0 PRAME+ melanocytes per linear mm showed a sensitivity of 79.2% and specificity of 85.7% (Youden index 0.65) to distinguish MIS from pseudonests. CONCLUSION: PRAME immunohistochemistry may constitute an additional tool for this challenging differential diagnosis.

Occult squamous cell carcinoma within lichenoid dermatitis: three examples of cryptic cancer detection.

Lichenoid dermatitis can be a perplexing entity encompassing an array of cutaneous disorders. Two hundred forty-three (243) cases of otherwise unclassifiable lichenoid dermatitis were examined histologically employing a special cytokeratin stain. Occult squamous cell carcinoma was detected in three of the 243 cases, uncovered by special immunohistochemistry staining within histologic specimens of lichenoid dermatitis. We recommend staining for cutaneous cancer becoming a routine practice in evaluating cutaneous lichenoid dermatitis.

Lichenoid drug eruption associated with imatinib mesylate therapy.

INTRODUCTION: Imatinib Mesylate (IM), a tyrosine kinase inhibitor, has been reported to cause several adverse reactions, most of them with cutaneous involvement. Non- Lichenoid IM associated skin reactions have been sufficiently- recorded. To our knowledge, Lichenoid Drug Eruption (LDE) is recorded in a minority of registries. CASE REPORT: To describe an LDE induced case by IM treatment. TREATMENT AND OUTCOME: Histological Confirmation and promptly dermatological consultation relieved successfully the cutaneous adverse event. DISCUSSION: Ongoing expansion of IM usage in a wide spectrum of new indications is more likely to make physicians experience such LDE cutaneous side effects more often. Hence, they should be highly suspicious to early detect these distinct histologic entities, handle these undesired complications and guarantee satisfactory immediate outcomes, avoiding frivolous IM dosage modifications.

Oral lichenoid lesion in association with chemotherapy treatment for non-Hodgkin lymphoma or lichen planus? Review of the literature and report of two challenging cases.

BACKGROUND: The diagnosis of oral lichenoid lesions (OLL) remains a challenge for clinicians and pathologists. Although, in many cases, OLL cannot be clinically and histopathologically distinguishable from oral lichen planus (OLP), one important difference between these lesions is that OLL has an identifiable etiological factor, e.g. medication, restorative material, and food allergy. The list of drugs that can cause OLL is extensive and includes anti-inflammatory drugs, anticonvulsants, antihypertensives, antivirals, antibiotics, chemotherapeutics, among others. This work aimed to perform a literature review of OLL related to chemotherapy drugs and to report two cases of possible OLL in patients with B-cell and T-cell non-Hodgkin lymphomas in use of chemotherapy and adjuvant medications. We also discuss the challenge to clinically and histopathologically differentiate OLL and OLP. CASE PRESENTATION: In both cases, oral lesions presented reticular, atrophic, erosive/ulcerated, and plaque patterns. The diagnosis of OLL was initially established in both cases by the association of histopathology and history of onset of lesions after the use of medications. Although the patients have presented a significant improvement in the oral clinical picture for more than 2 years of follow-up, they still have some lesions. CONCLUSION: A well-detailed anamnesis associated with the drug history, temporal relationship of the appearance of the lesions, and follow-up of patients are fundamental for the diagnosis of OLL related to drugs. Nevertheless, its differentiation from OLP is still a challenge.

Clinical features of oral lichen planus and oral lichenoid lesions: an oral pathologist's perspective.

The clinicopathological features that precisely characterize oral lichen planus (OLP) and oral lichenoid lesions (OLL) still represent a challenge. The aim of the present study was to analyze, from an oral pathologist perspective, the clinical features from OLP and OLL. Specimens fullfilling the histological criteria for OLP and OLL, and also compatible with OLP (OLP-C), were selected and clinical information was retrieved from the laboratory forms. The final sample was composed by 221 cases, including 119 OLP (53.8%), 65 OLP-C (29.4%) and 37 OLL (16.7%). Females were more affected in the three groups, but the number of males was higher in OLL. Mean age was lower in OLP (52.3 years) in comparison with OLL (57.9 years) (p=0.020). Buccal mucosa and tongue involvement was more frequent in OLP; gingival involvement was uncommon in OLL. The reticular pattern was more frequently found in OLP, while the association of reticular and atrophic/erosive/ulcerated patterns was more common in OLP-C and OLL (p=0.025). In conclusion, gender and mean age of the patients, and anatomical location and clinical manifestation of OLL are different from OLP, and could help to better characterize this group of conditions. Specimens diagnosed as OLP-C showed clinical parameters close to OLP.

Immunoexpression of oral brush biopsy enhances the accuracy of diagnosis for oral lichen planus and lichenoid lesions.

BACKGROUND: This study assessed the efficacy of using oral liquid-based brush cytology (OLBC) coupled with immunostained cytology-derived cell-blocks, quantified using machine-learning, in the diagnosis of oral lichen planus (OLP). METHODS: Eighty-two patients diagnosed clinically with either OLP or oral lichenoid lesion (OLL) were included. OLBC samples were obtained from all patients before undergoing surgical biopsy. Liquid-based cytology slides and cell-blocks were prepared and assessed by cytomorphology and immunocytochemistry for four antibodies (Ki-67, BAX, NF-κB-p65, and AMACR). For comparison purposes, a sub-group of 31 matched surgical biopsy samples were selected randomly and assessed by immunohistochemistry. Patients were categorized according to their definitive diagnoses into OLP, OLL, and clinically lichenoid, but histopathologically dysplastic lesions (OEDL). Machine-learning was utilized to provide automated quantification of positively stained protein expression. RESULTS: Cytomorphological assessment was associated with an accuracy of 77.27% in the distinction between OLP/OLL and OEDL. A strong concordance of 92.5% (κ = 0.84) of immunostaining patterns was evident between cell-blocks and tissue sections using machine-learning. A diagnostic index using a Ki-67-based model was 100% accurate in detecting lichenoid cases with epithelial dysplasia. A BAX-based model demonstrated an accuracy of 92.16%. The accuracy of cytomorphological assessment was greatly improved when it was combined with BAX immunoreactivity (95%). CONCLUSIONS: Cell-blocks prepared from OLBC are reliable and minimally-invasive alternatives to surgical biopsies to diagnose OLLs with epithelial dysplasia when combined with Ki-67 immunostaining. Machine-learning has a promising role in the automated quantification of immunostained protein expression.

Protein disulfide isomerase family A member 3 expression is upregulated in tissue-derived extracellular vesicles in oral lichen planus and oral lichenoid lesions.

OBJECTIVES: The aim of this study was to identify the tissue-derived extracellular vesicles immunogen involved in the pathogenesis of oral lichen planus (OLP) and its variation oral lichenoid lesions (OLL). DESIGN: Six pooled tissue-derived extracellular vesicles from participants with OLP/OLL and three from healthy controls were isolated and enriched. The extracellular vesicles were characterized with transmission electronic microscopy, nanoparticle tracking analysis and western blotting. Proteins from extracellular vesicles were identified with proteomics analysis and differentially expressed proteins (DEPs) were further identified with a 2-fold (p < 0.05) increase or a 0.5-fold decrease. RESULTS: A total of 1805 peptides and 141 proteins were identified. Ten DEPs were further identified, with five upregulated proteins of fibrinogen alpha chain, lamin isoform A, 40S ribosomal protein, protein disulfide isomerase family A member 3 (PDIA3) and elongation factor 1-alpha 1, and five downregulated proteins of plakophilin-1, katanin p80 repeat-containing subunit B1, collagen alpha-3 chain, mitochondrial 2-oxoglutarate/malate carrier protein and guanine nucleotide-binding protein subunit gamma-12. PDIA3 was found to be immune-associated and to be involved in the antigen processing and presentation pathway. The upregulation of PDIA3 was confirmed in a verification cohort composed of three pairs of OLP/OLL-extracellular vesicles and healthy controls-extracellular vesicles with western blotting. CONCLUSIONS: Protein disulfide isomerase family A member 3 in extracellular vesicles may play a significant role in the local immune responses and the pathogenesis of oral lichen planus and oral lichenoid lesions.

Lichenoid drug eruption on the lower lip caused by anti-PD-1 monoclonal antibody: a case report and literature review.

Anti-PD-1/PD-L1 monoclonal antibodies result in a unique spectrum of side effects, widely known as immune-related adverse events. Toripalimab is an anti-PD-1 monoclonal antibody used for the treatment of some cancers. Here we report the first case, to our knowledge, of oral lichenoid drug reaction triggered by toripalimab. A 78-year-old man who was diagnosed with systemic metastatic prostate cancer presented with ulcers on the lower lip after the fifth cycle of toripalimab. We diagnosed him with oral lichenoid drug reaction based on clinical manifestation, histopathological findings and the history of anti-PD-1 therapy. The patient responded well to oral corticosteroids combined with helium-neon laser therapy. The anti-PD-1 therapy was not restarted because of stable disease, and the eruptions did not recur.

Histopathologic Spectrum of Findings Associated With Tattoos: Multicenter Study Series of 230 Cases.

IMPORTANCE: Reactions to tattoo may simulate common dermatosis or skin neoplasms. Histopathology allows diagnosis and helps determining the level and degree of inflammation associated, consequently orientating treatment. OBJECTIVE: To describe the histological features found in biopsies of cutaneous reactions to tattoo. DESIGN: This study was designed as a multicenter case series. SETTING: All consecutive histopathological samples of tattoos referred from 1992 to 2019 to the Hospital General de Catalunya, Hospital Germans Trias i Pujol, and a private practice, all in Barcelona, Spain, and from the Kempf und Pfaltz Histologische Diagnostik in Zurich, Switzerland were retrieved from the files. PARTICIPANTS AND EXPOSURE: The inclusion criteria were all cosmetic/permanent makeup, artistic/professional, and traumatic tattoos associated with either inflammatory reactions alone and/or with tumors and/or infections. Exclusion criteria were cases without any associated pathologic finding in the place of the ink, amalgam tattoos, and medical or temporary tattoos. MAIN OUTCOMES AND MEASURES: In all patients, clinical features (age, sex, location, tattoo color, and presentation) were recorded. Histological features evaluated included ink color, associated tumors or infections, and inflammatory reaction pattern. Inflammation was graded in low to moderate or severe. RESULTS: From 477 biopsies diagnosed as tattoos, 230 cases from 226 patients met the inclusion criteria. Samples corresponded to 107 male and 120 female subjects and 3 of unknown gender. Median age was 39 years (ranging from 9 to 84 years). Fifty-three samples were referred from centers in Spain and 177 from the center in Switzerland. The series was analyzed in 2 parts: tattoos associated only with inflammatory reactions (117/230) and tattoos associated with tumors or infections (113/230). The most common form of inflammatory pattern associated with tattoo was the fibrosing reaction (79/117, 68%), followed by granulomatous reaction (56/117, 48%), lichenoid reaction (33/117, 28%), epithelial hyperplasia (28/117, 24%), pseudolymphoma (27/117, 23%) and spongiotic reaction (27/117, 23%). Combined features of 2 or more types of inflammatory patterns were seen in 64% cases. CONCLUSIONS AND RELEVANCE: Our series confirms that cutaneous reactions to tattoos are polymorphous. Inflammation tends to present with combined patterns. Infections are tending to decline, and pathologic findings are not specific to ink color or clinical features.

Oral submucous fibrosis presenting with histopathological lichenoid changes as predominant feature: Report of five cases and review of the literature.

Oral submucous fibrosis (OSF) is a precancerous condition of the oral cavity associated with habitual chewing of quid, with a high incidence among populations of the Indian subcontinent and Southeast Asia. Clinically, its initial manifestation may mimic oral lichen planus or lichen sclerosus. If the habit is not halted, the mucosa gets leathery and thickened, and fibrous bands form causing significant morbidity. Microscopically, it is characterized by atrophic epithelium, loss of rete ridges, and hyalinization of lamina propria. Of note, these hallmark histopathological features may be overlooked in the unusual presence of lichenoid interface changes, which may lead to the wrong diagnosis. We present herein five cases in which the rare joint appearance of OSF and lichenoid reaction features posed a diagnostic challenge. Due to its progressive nature and malignant potential, the presence of oral lichenoid changes overlying submucous hyalinization, in the right clinical and demographic setting, should raise suspicion of OSF and prompt actions directed at quid-chewing discontinuation.

Paraneoplastic pemphigus: Revised diagnostic criteria based on literature analysis.

BACKGROUND: Paraneoplastic pemphigus (PNP) is a rare autoimmune bullous disease classically associated with an underlying neoplasm. The heterogeneous clinical and histopathologic features of the disease make diagnosis challenging for clinicians. There are no formally accepted diagnostic criteria, and newer techniques for identifying antibodies directed against plakin proteins have largely replaced immunoprecipitation, the historic gold standard. METHODS: An analysis of 265 published cases of PNP was performed. The clinical, histopathologic, and immunologic features of PNP were assessed. RESULTS: Based on this review, we modified previous diagnostic criteria to capture 89.4% of PNP cases compared to 71.2% of cases captured by the most commonly referenced criteria devised by Camisa and Helm (p-value < 0.01, z-test; 95% CI [10.2, 33.6]). CONCLUSION: These revised diagnostic criteria address the variable clinical, histopathologic, and biochemical features of PNP, allowing physicians to have greater confidence in diagnosis of this rare and often fatal disease. The revised criteria include three major criteria and two minor criteria, whereby meeting either all three major criteria or two major and both minor criteria would fulfill a diagnosis of paraneoplastic pemphigus. The major criteria include (a) mucous membrane lesions with or without cutaneous involvement, (b) concomitant internal neoplasm, and (b) serologic evidence of anti-plakin antibodies. The minor criteria include (a) acantholysis and/or lichenoid interface dermatitis on histopathology and (b) direct immunofluorescence staining showing intercellular and/or basement membrane staining.

Narrowband ultraviolet B therapy for refractory immune-related lichenoid dermatitis on PD-1 therapy: a case report.

Treatment with programmed cell death 1 inhibitors is associated with a wide range of cutaneous immune-related adverse events, with lichenoid eruptions representing one of the major cutaneous toxicities. We describe the case of an 81-year-old man with metastatic melanoma treated with pembrolizumab who subsequently developed a delayed-onset generalized lichenoid dermatitis. After failing multiple lines of systemic immunosuppression, narrowband ultraviolet B (NBUVB) phototherapy three times per week for 17 sessions resulted in a significant clinical response in his cutaneous eruption and was well tolerated. NBUVB is a safe, lower-cost modality that induces local, skin-specific immunosuppression without the toxicities of traditional systemic immunosuppressive agents. To date, this is the first report of use of NBUVB in immune-related lichenoid dermatitis resistant to multiple standard therapies.

Erythema ab igne with features resembling keratosis lichenoides chronica.

Erythema ab igne (EAI) is an asymptomatic dermatosis that develops in response to chronic exposure to low-grade heat. Characteristic findings on histopathology include epidermal atrophy, dermal elastosis, atypical histiocytes, and melanin and hemosiderin deposition. Reactive endothelial changes and prominent vascular proliferation are variable. Keratosis lichenoides chronica (KLC) is a rare lichenoid hyperkeratotic dermatosis. Acanthosis with parakeratosis and a lichenoid interface dermatitis with lymphocytes, histiocytes, and plasma cells are characteristic findings of KLC. Although its etiology remains unclear, KLC has been reported to occur in response to heat. Herein, we report a case of EAI with features resembling KLC.