Design and implementation of a new apparatus for astrochemistry: Kinetic measurements of the CH + OCS reaction and frequency comb spectroscopy in a cold uniform supersonic flow.

We present the development of a new astrochemical research tool, HILTRAC, the Highly Instrumented Low Temperature ReAction Chamber. The instrument is based on a pulsed form of the CRESU (Cinétique de Réaction en Écoulement Supersonique Uniforme, meaning reaction kinetics in a uniform supersonic flow) apparatus, with the aim of collecting kinetics and spectroscopic information on gas phase chemical reactions important in interstellar space or planetary atmospheres. We discuss the apparatus design and its flexibility, the implementation of pulsed laser photolysis followed by laser induced fluorescence, and the first implementation of direct infrared frequency comb spectroscopy (DFCS) coupled to the uniform supersonic flow. Achievable flow temperatures range from 32(3) to 111(9) K, characterizing a total of five Laval nozzles for use with N2 and Ar buffer gases by impact pressure measurements. These results were further validated using LIF and direct frequency comb spectroscopy measurements of the CH radical and OCS, respectively. Spectroscopic constants and linelists for OCS are reported for the 1001 band near 2890-2940 cm-1 for both OC32S and OC34S, measured using DFCS. Additional peaks in the spectrum are tentatively assigned to the OCS-Ar complex. The first reaction rate coefficients for the CH + OCS reaction measured between 32(3) and 58(5) K are reported. The reaction rate coefficient at 32(3) K was measured to be 3.9(4) × 10-10 cm3 molecule-1 s-1 and the reaction was found to exhibit no observable temperature dependence over this low temperature range.

A case of erythema ab igne with histopathological features resembling keratosis lichenoides chronica.

This case describes a pediatric patient with a history of ichthyosis vulgaris and global anhidrosis who was diagnosed with erythema ab igne (EAI), a rare dermatosis resulting from chronic heat exposure. After developing progressive, reticulated brown patches on his extremities and abdomen, extensive diagnostic investigations were conducted to rule out autoimmune, vascular, and genetic etiologies. Bloodwork was unrevealing and biopsies showed histologic features closely resembling keratosis lichenoides chronica. Ultimately, after discovering the patient had prolonged exposure to a space heater, the diagnosis of EAI was made. This case underscores the diagnostic challenges in pediatric EAI cases and emphasizes the importance of careful history taking as part of a comprehensive evaluation.

Linear IgA bullous dermatosis of childhood: Retrospective single-center cohort.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disorder impacting children and adults. In this single-center retrospective chart review of pediatric patients with LABD at a large tertiary referral center, we report the unifying and unique clinical features of 10 pediatric patients. Patients typically presented with the "cluster of jewels" sign (n = 6; 60%), mucous membrane involvement (n = 5; 50%) and had a mean disease duration of 38 months; six patients (60%) required inpatient admission for management of their skin disease, including all five patients who had mucous membrane involvement. Our findings suggest that pediatric LABD may be a disease with high morbidity and may be associated with severe complications when mucous membranes are involved.

Differential proteomic expression in indolent versus transforming oral lichen planus.

Oral lichen planus (OLP) confers an approximately 1% risk of transformation to oral squamous cell carcinoma (OSCC). Early identification of high-risk OLP would be very helpful for optimal patient management. We aimed to discover specific tissue-based protein biomarkers in patients with OLP who developed OSCC compared to those who did not. We used laser capture microdissection- and nanoLC-tandem mass spectrometry to assess protein expression in fixed lesional mucosal specimens in patients with indolent OLP (no OSCC after at least 5-year follow-up, n = 6), transforming OLP (non-dysplastic epithelium with lichenoid inflammation marginal to OSCC, n = 6) or normal oral mucosa (NOM, n = 5). Transforming OLP protein profile was enriched for actin cytoskeleton, mitochondrial dysfunction and oxidative phosphorylation pathways. CA1, TNNT3, SYNM and MB were overexpressed, and FBLN1 was underexpressed in transforming OLP compared with indolent OLP. Integrin signalling and antigen presentation pathways were enriched in both indolent and transforming OLP compared with NOM. This proteomic study provides potential biomarkers, such as CA1 overexpression, for higher-risk OLP. While further validation studies are needed, we propose that epithelial-mesenchymal transition may be involved in OLP carcinogenesis.

Differential proteomic expression profiles in vulvar lichen planus as compared to normal vulvar tissue, vulvar lichen sclerosus, or oral lichen planus: An exploratory study.

Vulvar lichen planus (VLP) is a chronic inflammatory disease which adversely affects patients' quality of life. The pathogenesis of VLP is unknown although Th1 immune response has been implicated. We aimed to discover specific tissue-based protein biomarkers in VLP compared to normal vulvar tissue (NVT), vulvar lichen sclerosus (VLS) and oral lichen planus (OLP). We used laser capture microdissection-liquid chromatography- tandem mass spectrometry to assess protein expression in fixed lesional mucosal specimens from patients with VLP (n = 5). We then compared proteomic profiles against those of NVT (n = 4), VLS (n = 5), OLP (n = 6) and normal oral mucosa (n = 5), previously published by our group. IL16, PTPRC, PTPRCAP, TAP1 and ITGB2 and were significantly overexpressed in VLP compared to NVT. Ingenuity pathway analysis identified antigen presentation and integrin signalling pathways. Proteins overexpressed in both VLP versus NVT and OLP versus NOM included IL16, PTPRC, PTPRCAP, TAP1, HLA-DPB1, HLA-B and HLA-DRA. This proteomic analysis revealed several overexpressed proteins in VLP that relate to Th1 autoimmunity, including IL16. Overlapping pathways, including those involving IFNγ and Th1 signalling, were observed between VLP, VLS, and OLP.

Experimental, theoretical, and astrochemical modelling investigation of the gas-phase reaction between the amidogen radical (NH2) and acetaldehyde (CH3CHO) at low temperatures.

The first experimental study of the low-temperature kinetics of the gas-phase reaction of NH2 with acetaldehyde (CH3CHO) has been performed. Experiments were carried out using laser-flash photolysis and laser-induced fluorescence spectroscopy to create and monitor the temporal decay of NH2 in the presence of CH3CHO. Low temperatures relevant to the interstellar medium were achieved using a pulsed Laval nozzle expansion. Rate coefficients were measured over the temperature and pressure range of 29-107 K and 1.4-28.2 × 1016 molecules per cm3, with the reaction exhibiting a negative temperature dependence and a positive pressure dependence. The yield of CH3CO from the reaction has also been determined at 67.1 and 35.0 K, by observing OH produced from the reaction of CH3CO with added O2. Ab initio calculations of the potential energy surface (PES) were combined with Rice-Rampsberger-Kessel-Marcus (RRKM) calculations to predict rate coefficients and branching ratios over a broad range of temperatures and pressures. The calculated rate coefficients were shown to be sensitive to the calculated density of states of the stationary points, which in turn are sensitive to the inclusion of hindered rotor potentials for several of the vibrational frequencies. The experimentally determined rate coefficients and yields have been used to fit the calculated PES, from which low-pressure limiting rate coefficients relevant to the ISM were determined. These have been included in a single-point dark cloud astrochemical model, in which the reaction is shown to be a potential source of gas-phase CH3CO radicals under dark cloud conditions.

Development and multicenter international validation of a diagnostic tool to differentiate between pemphigoid gestationis and polymorphic eruption of pregnancy.

BACKGROUND: Pemphigoid gestationis (PG) and polymorphic eruption of pregnancy (PEP) may be similar morphologically but confer different maternal and fetal risks. Direct immunofluorescence is the gold standard test used to differentiate between the 2 diagnoses but is not always available. OBJECTIVE: To develop and validate a clinical scoring system to differentiate PG from PEP. METHODS: After developing a scoring system based on differentiating clinical factors reported in existing literature, we tested its diagnostic accuracy in a retrospective international multicenter validation study in collaboration with the European Academy of Dermatology and Venereology's Skin Diseases in Pregnancy Taskforce. RESULTS: Nineteen pregnancies (16 patients) affected by PG and 39 pregnancies (39 patients) affected by PEP met inclusion criteria. PG had a mean score of 4.6 (SD, 2.5) and PEP had a mean score of -0.3 (SD, 2.0). The area under the curve was 0.93 (95% CI, 0.86-1.00). Univariate analysis revealed that almost all criteria used in the scoring system were significantly different between the groups (P < .05), except for skip pregnancy and multiple gestations, which were then removed from the final scoring system. LIMITATIONS: Small retrospective study. CONCLUSION: The Pregnancy Dermatoses Clinical Scoring System may be useful to differentiate PG from PEP in resource-limited settings.

Optical frequency comb-based measurements and the revisited assignment of high-resolution spectra of CH2Br2 in the 2960 to 3120 cm-1 region.

Brominated organic compounds are toxic ocean-derived trace gases that affect the oxidation capacity of the atmosphere and contribute to its bromine burden. Quantitative spectroscopic detection of these gases is limited by the lack of accurate absorption cross-section data as well as rigorous spectroscopic models. This work presents measurements of high-resolution spectra of dibromomethane, CH2Br2, from 2960 cm-1 to 3120 cm-1 by two optical frequency comb-based methods, Fourier transform spectroscopy and a spatially dispersive method based on a virtually imaged phased array. The integrated absorption cross-sections measured using the two spectrometers are in excellent agreement with each other within 4%. A revisited rovibrational assignment of the measured spectra is introduced, in which the progressions of features are attributed to hot bands rather than different isotopologues as was previously done. Overall, twelve vibrational transitions, four for each of the three isotopologues CH281Br2, CH279Br81Br, and CH279Br2, are assigned. These four vibrational transitions are attributed to the fundamental ν6 band and the nearby nν4 + ν6 - nν4 hot bands (with n = 1-3) due to the population of the low-lying ν4 mode of the Br-C-Br bending vibration at room temperature. The new simulations show very good agreement in intensities with the experiment as predicted by the Boltzmann distribution factor. The spectra of the fundamental and the hot bands show progressions of strong QKa(J) rovibrational sub-clusters. The band heads of these sub-clusters are assigned and fitted to the measured spectra, providing accurate band origins and the rotational constants for the twelve states with an average error of 0.0084 cm-1. A detailed fit of the ν6 band of the CH279Br81Br isotopologue is commenced after assigning 1808 partially resolved rovibrational lines, with the band origin, rotational, and centrifugal constants as fit parameters, resulting in an average error of 0.0011 cm-1.

Experimental and theoretical study of the low-temperature kinetics of the reaction of CN with CH2O and implications for interstellar environments.

Rate coefficients for the reaction of CN with CH2O were measured for the first time below room temperature in the range 32-103 K using a pulsed Laval nozzle apparatus together with the Pulsed Laser Photolysis-Laser-Induced Fluorescence technique. The rate coefficients exhibited a strong negative temperature dependence, reaching (4.62 ± 0.84) × 10-11 cm3 molecule-1 s-1 at 32 K, and no pressure dependence was observed at 70 K. The potential energy surface (PES) of the CN + CH2O reaction was calculated at the CCSD(T)/aug-cc-pVTZ//M06-2X/aug-cc-pVTZ level of theory, with the lowest energy channel to reaction characterized by the formation of a weakly-bound van der Waals complex, bound by 13.3 kJ mol-1, prior to two transition states with energies of -0.62 and 3.97 kJ mol-1, leading to the products HCN + HCO or HNC + HCO, respectively. For the formation of formyl cyanide, HCOCN, a large activation barrier of 32.9 kJ mol-1 was calculated. Reaction rate theory calculations were performed with the MESMER (Master Equation Solver for Multi Energy well Reactions) package on this PES to calculate rate coefficients. While this ab initio description provided good agreement with the low-temperature rate coefficients, it was not capable of describing the high-temperature experimental rate coefficients from the literature. However, increasing the energies and imaginary frequencies of both transition states allowed MESMER simulations of the rate coefficients to be in good agreement with data spanning 32-769 K. The mechanism for the reaction is the formation of a weakly-bound complex followed by quantum mechanical tunnelling through the small barrier to form HCN + HCO products. MESMER calculations showed that channel generating HNC is not important. MESMER simulated the rate coefficients from 4-1000 K which were used to recommend best-fit modified Arrhenius expressions for use in astrochemical modelling. The UMIST Rate12 (UDfa) model yielded no significant changes in the abundances of HCN, HNC, and HCO for a variety of environments upon inclusion of rate coefficients reported here. The main implication from this study is that the title reaction is not a primary formation route to the interstellar molecule formyl cyanide, HCOCN, as currently implemented in the KIDA astrochemical model.

Ab Initio and Statistical Rate Theory Exploration of the CH (X2Π) + OCS Gas-Phase Reaction.

The first theoretical results regarding the gas-phase reaction mechanism and kinetics of the CH (X2Π) + OCS reaction are presented here. This reaction has a proposed importance in the removal of OCS in regions of the interstellar medium (ISM) and has the potential to form the recently observed HCS/HSC isomers, with both constitutional isomers having recently been observed in the L483 molecular cloud in a 40:1 ratio. Statistical rate theory simulations were performed on stationary points along the reaction potential energy surface (PES) obtained from ab initio calculations at the RO-CCSD(T)/aug-cc-pV(Q+d)Z//M06-2X-D3/aug-cc-pV(Q+d)Z level of theory over the temperature and total density range of 150-3000 K and 1011-1024 cm-3, respectively, using a Master Equation analysis. Exploration of the reaction potential energy surface revealed that all three pathways identified to create CS + HCO products required surmounting barriers of 16.5 kJ mol-1 or larger when CH approached the oxygen side of OCS, rendering this product formation negligible below 1000 K, and certainly under low-temperature ISM conditions. In contrast, when CH approaches the sulfur side of OCS, only submerged barriers are found along the reaction potential energy surface to create HCCO + S or CO + HCS, both of which are formed via a strongly bound OCC(H)S intermediate (-358.9 kJ mol-1). Conversion from HCS to HSC is possible via a barrier of 77.8 kJ mol-1, which is still -34.1 kJ mol-1 below the CH + OCS entrance channel. No direct route from CH + OCS to H + CO + CS was found from our ab initio calculations. Rate theory simulations suggest that the reaction has a strong negative temperature dependence, in accordance with the barrierless addition of CH to the sulfur side of OCS. Product branching fractions were also determined from MESMER simulations over the same temperature and total density range. The product branching fraction of CO + HCS reduces from 79% at 150 K to 0.0% at 800 K, while that of HCS dissociation to H + CS + CO increases from 22% at 150 K to 100% at 800 K. The finding of CO + HCS as the major product at the low temperatures relevant to the ISM, instead of H + CS + CO, is in opposition to the current supposition used in the KIDA database and should be adapted in astrochemical models as another source of the HCS isomer.

Histopathological features of pemphigoid gestationis and polymorphic eruption of pregnancy: A blinded retrospective comparative study of 31 cases.

BACKGROUND: Pemphigoid gestationis (PG) and polymorphic eruption of pregnancy (PEP) are pregnancy-related dermatoses. Definitive diagnosis often relies upon histopathology and direct immunofluorescence (DIF). PG is associated with fetal and neonatal risks, while PEP confers minimal risk. OBJECTIVE: We aimed to compare histopathologic features to determine key differentiators. METHODS: A retrospective cohort study of PG and PEP cases, with accompanying DIF, conducted from 1995 to 2020. Skin biopsies were examined independently in a blinded fashion by two dermatopathologists for a list of histopathological features. RESULTS: Twenty-one cases of PG and 10 cases of PEP were identified. PG had significantly denser eosinophils than PEP (mean 155 vs. 48 cells/5 hpf; p < 0.018). PG was also noted to have eosinophilic spongiosis and eosinophils at the dermal-epidermal junction more frequently compared to PEP (80% PG vs. 10% PEP; p < 0.001). A mean cutoff value of 86 eosinophils and a mean optimal sensitivity and specificity of 81% and 83%, respectively, for eosinophils density's diagnostic power of PEP versus PG were achieved. Subepithelial separation was exclusively seen in PG (40% vs. 0%; p < 0.007). CONCLUSION: Eosinophilic spongiosis, eosinophilic epitheliotropism, and dense superficial dermal eosinophils were diagnostic of PG. Given overlapping clinicopathologic features, however, DIF results with clinicopathologic correlation, remain the gold standard.

Histopathologic features predictive of perivascular deposition of IgA on direct immunofluorescence in cases of leukocytoclastic vasculitis: A retrospective study of 112 specimens.

IgA vasculitis is a small-vessel vasculitis subtype with increased risk of systemic involvement. We aimed to investigate if any light-microscopic features can predict the presence of perivascular granular IgA deposits on direct immunofluorescence (DIF) microscopy. We performed a retrospective search of cutaneous pathology reports from our internal and consultation practice (January 1, 2010-October 5, 2021) with a diagnosis of leukocytoclastic vasculitis and accompanying DIF. A blinded dermatopathologist reviewed standard microscopy slides for predetermined histopathological features. Fifty-six biopsies (48 patients) and 56 biopsies (42 patients) met inclusion criteria for IgA+ and IgA-, respectively. The presence of eosinophils and mid and deep dermal inflammation were statistically more associated with IgA- (41/56 [73.2%] and 31/56 [55.4%], respectively) than IgA+ cases (28/56 [50.0%] and 14/56 [25.0%]; p = 0.049 and 0.006, respectively, chi-squared test). Other microscopic criteria recorded were not significantly different between the two groups (p > 0.05, chi-squared and Fisher's exact tests). In this retrospective study of 112 cases, we found that while the absence of eosinophils and absence of mid- and deep inflammation were correlated with increased likelihood of IgA perivascular deposition on DIF, no other histopathological features on light microscopy tested could reliably predict the presence of IgA perivascular deposition on DIF. Therefore, DIF remains a necessary component for the accurate diagnosis of cutaneous IgA vasculitis.

Pediatric lichen planus: A single-center retrospective review of 26 patients with follow up.

BACKGROUND/OBJECTIVES: Pediatric lichen planus (LP) is rare with variable prevalence and atypical presentations compared to adults. Data on LP are lacking for the pediatric population in the United States. We present demographics, presentations, and treatments for a pediatric LP cohort. METHODS: We reviewed 26 patients diagnosed with LP at 20 years or younger. Treatment responses were defined as no response, partial response, and complete response. RESULTS: Demographics included 54% females and median diagnosis age of 16 years (range 6-20). Most patients presented with cutaneous LP (65%), with fewer having associated oral (23%), nail (7.7%), or genital (3.8%) involvement. Some had cutaneous-only LP (38%) or strictly mucosal LP (oral-only 19% and genital-only 15%). LP lesions were pruritic (50%), painful (19%), and/or asymptomatic (35%). Complete/partial responses occurred with medium-potency topical corticosteroids in cutaneous (n = 7; 64%), oral (n = 3; 75%), and genital LP (n = 3; 100%), with high/ultra-high potency topical corticosteroids in oral LP (n = 6; 86%), and with topical calcineurin inhibitors in genital LP (n = 2; 100%). Side effects were clobetasol-related oral candidiasis and biopsy-related penile depressed scar. Most patients with available follow-up achieved remission (n = 17; 81%). CONCLUSIONS: Pediatric LP usually presents in adolescence with cutaneous involvement and is symptomatic. However, patients frequently can have oral, genital, or nail lesions or may be asymptomatic, so they need thorough examinations and follow-up. Long-term remission is common due to treatment or natural disease course. Medium-potency corticosteroids are recommended for cutaneous, oral, and genital LP. Various other local and systemic therapies exist with successful treatment responses.

Insights from the IronTract challenge: Optimal methods for mapping brain pathways from multi-shell diffusion MRI.

Limitations in the accuracy of brain pathways reconstructed by diffusion MRI (dMRI) tractography have received considerable attention. While the technical advances spearheaded by the Human Connectome Project (HCP) led to significant improvements in dMRI data quality, it remains unclear how these data should be analyzed to maximize tractography accuracy. Over a period of two years, we have engaged the dMRI community in the IronTract Challenge, which aims to answer this question by leveraging a unique dataset. Macaque brains that have received both tracer injections and ex vivo dMRI at high spatial and angular resolution allow a comprehensive, quantitative assessment of tractography accuracy on state-of-the-art dMRI acquisition schemes. We find that, when analysis methods are carefully optimized, the HCP scheme can achieve similar accuracy as a more time-consuming, Cartesian-grid scheme. Importantly, we show that simple pre- and post-processing strategies can improve the accuracy and robustness of many tractography methods. Finally, we find that fiber configurations that go beyond crossing (e.g., fanning, branching) are the most challenging for tractography. The IronTract Challenge remains open and we hope that it can serve as a valuable validation tool for both users and developers of dMRI analysis methods.

Differential proteomic expression in indolent vulvar lichen sclerosus, transforming vulvar lichen sclerosus and normal vulvar tissue.

Vulvar lichen sclerosus (VLS) confers approximately 3% risk of malignant transformation to vulvar squamous cell carcinoma (VSCC). We used unbiased proteomic methods to identify differentially expressed proteins in tissue of patients with VLS who developed VSCC compared to those who did not. We used laser capture microdissection- and nanoLC-tandem mass spectrometry to assess protein expression in individuals in normal vulvar tissue (NVT, n = 4), indolent VLS (no VSCC after at least 5 years follow-up, n = 5) or transforming VSCC (preceding VSCC, n = 5). Interferon-γ and antigen-presenting pathways are overexpressed in indolent and transforming VLS compared to NVT. There was differential expression of malignancy-related proteins in transforming VLS compared to indolent VLS (CAV1 overexpression, AKAP12 underexpression), particularly in the EIF2 translation pathway, which has been previously implicated in carcinogenesis. Results of this study provide additional molecular evidence supporting the concept that VLS is a risk factor for VSCC and highlights possible future biomarkers and/or therapeutic targets.

Updates and Proposed Diagnostic Approach to Psoriasiform Dermatoses.

Psoriasiform dermatoses represent a wide array of skin diseases commonly encountered by clinicians and pathologists. While they may present a diagnostic challenge, thorough observation coupled with proper interpretation of subtle additional clinical or histopathologic features provide clues to the correct diagnosis. In this review, we provide updates on emerging entities and develop a systemic approach to establish the pathologic diagnosis, with emphasis on the importance of clinicopathologic correlation.

Deep learning for dermatologists: Part II. Current applications.

Because of a convergence of the availability of large data sets, graphics-specific computer hardware, and important theoretical advancements, artificial intelligence has recently contributed to dramatic progress in medicine. One type of artificial intelligence known as deep learning has been particularly impactful for medical image analysis. Deep learning applications have shown promising results in dermatology and other specialties, including radiology, cardiology, and ophthalmology. The modern clinician will benefit from an understanding of the basic features of deep learning to effectively use new applications and to better gauge their utility and limitations. In this second article of a 2-part series, we review the existing and emerging clinical applications of deep learning in dermatology and discuss future opportunities and limitations. Part 1 of this series offered an introduction to the basic concepts of deep learning to facilitate effective communication between clinicians and technical experts.

Deep learning for dermatologists: Part I. Fundamental concepts.

Artificial intelligence is generating substantial interest in the field of medicine. One form of artificial intelligence, deep learning, has led to rapid advances in automated image analysis. In 2017, an algorithm demonstrated the ability to diagnose certain skin cancers from clinical photographs with the accuracy of an expert dermatologist. Subsequently, deep learning has been applied to a range of dermatology applications. Although experts will never be replaced by artificial intelligence, it will certainly affect the specialty of dermatology. In this first article of a 2-part series, the basic concepts of deep learning will be reviewed with the goal of laying the groundwork for effective communication between clinicians and technical colleagues. In part 2 of the series, the clinical applications of deep learning in dermatology will be reviewed and limitations and opportunities will be considered.

Whole-exome sequencing of transforming oral lichen planus reveals mutations in DNA damage repair and apoptosis pathway genes.

BACKGROUND: Oral lichen planus confers a 1% risk of transformation to oral squamous cell carcinoma. While prior exome sequencing studies have identified multiple genetic mutations in oral squamous cell carcinoma, mutational analyses of lichen planus-derived OSCC are lacking. We sought to clarify genomic events associated with oral lichen planus transformation. METHODS: Using rigorous diagnostic criteria, we retrospectively identified patients with non-transforming oral lichen planus (i.e., known to be non-transforming with 5 years of clinical follow-up; n = 17), transforming oral lichen planus (tissue marginal to oral squamous cell carcinoma, n = 9), or oral squamous cell carcinoma arising in lichen planus (n = 17). Gene mutational profiles derived from whole-exome sequencing on fixed mucosal specimens were compared among the groups. RESULTS: The four most frequently mutated genes in transforming oral lichen planus and oral squamous cell carcinoma (TP53, CELSR1, CASP8, and KMT2D) identified 12/17 (71%) of oral squamous cell carcinomas and 5/9 (56%) of transforming oral lichen planus but were absent in non-transforming oral lichen planus. We identified other known oral squamous cell carcinoma mutations (TRRAP, OBSCN, and LRP2) but also previously unreported mutations (TENM3 and ASH1L) in lichen planus-associated oral squamous cell carcinomas. CONCLUSIONS: These findings suggest alterations in DNA damage response and apoptosis pathways underlie lichen planus-related oral squamous cell carcinoma transformation and are supported by mutational signatures indicative of DNA damage. This study characterized patterns of mutational events present in oral lichen planus associated with squamous cell carcinoma and in squamous cell carcinoma associated with oral lichen planus but not in non-transforming oral lichen planus.

Utilization of skin biopsy for diagnosis in a case of Lafora disease.

Lafora disease is a rare inherited neurodegenerative disease with onset in adolescence. Patients present with progressive myoclonic seizures and cognitive decline. The disease is linked to mutations in either of the two genes encoding malin and laforin, and it is associated with the accumulation of polyglucosan inclusions (Lafora bodies [LBs]) in various tissues, such as brain, liver, muscle, and skin, with the skin being particularly accessible for biopsy. Histopathologic examination of affected tissue with demonstration of LBs, together with the presence of pathologic mutation in EPM2A or NHLRC1 genes, is sufficient for diagnosis of this neurologic disorder when clinically suspected. Here, we report the case of a 16-year-old female with progressive neurologic symptoms and homozygous mutation in the NHLRC1 gene encoding malin. The skin biopsy was instrumental in reaching the final diagnosis by showing LBs in sweat glands by histopathologic and electron microscopic examination.