Skin Biopsy Research Articles

Inflammatory Foot Dermatoses: The Correlation Among Morphological Patterns, Histopathological Findings, and Patch Test Positivity.

Objective In this study, we aimed to investigate the correlation between the clinical diagnosis, histological diagnosis, and patch test positivity among patients with foot dermatoses receiving treatment at the Department of Dermatology, MES Medical College, Perinthalmanna. Methodology A hospital-based cross-sectional observational diagnostic evaluation was carried outfrom January 1, 2019, to December 31, 2019, among 44 patients with foot dermatoses who met the inclusion criteria. A thorough general physical and cutaneous examination was performed to determine the type, extent, and morphology of lesions after obtaining the written informed consent; sociodemographic informationand a thorough recording of patient history were gathered. In all cases, a potassium hydroxide (KOH) mount, skin biopsy, and patch testing were performed. Additionally, pus culture and sensitivity tests were conducted in pertinent cases. Results Our study found that the most prevalent foot dermatosis, based on clinical diagnosis, was allergic contact dermatitis (ACD) foot, affecting 26 patients (59.0%). This was followed by plantar psoriasis, observed in 13 patients (29.5%), and lichen planus, present in two patients (4.5%). The predominant histological diagnosis was ACD foot in 11 patients (25.0%),followed by plantar psoriasis in 10 patients (22.7%), spongiotic dermatitis in seven patients (15.9%), atopic dermatitis (AD) and psoriasiform dermatitis in four patients (9.1%) each, and tinea pedis in two patients (4.5%). The sensitivity of patch testing in detecting ACD foot was 90.91%, whereas its specificity was 57.58%. The positive and negative predictive values(PPV and NPV) were 41.67% and 95.0% respectively. Conclusions Based on our findings, histopathological evaluation is a highly effective diagnostic technique for foot dermatoses, as it demonstrated exceptional diagnostic accuracy (p<0.001). The sensitivity of patch testing in identifying ACDof the foot was 90.91% (p<0.05). This highlighted the usefulness of patch testing as a confirmatory diagnostic tool along with histopathological evaluation for precise diagnosis of ACD of the foot. While laboratory testing can increase diagnostic precision, it cannot replace a clinical examination.

The healing effect of nano emulsified Plantago major L extract on oral wounds in a wistar rat model

IntroductionOral lesions are a common clinical symptom arising from various etiologies and disrupt the patient’s quality of life. However, no definite treatment is not yet possible, due to the constantly changing environment of the mouth. In recent years, herbal treatments have gained popularity among patients and physicians due to their availability, safety, affordability, and antimicrobial properties. This research aims to investigate the therapeutic effects of a nano-emulsion of Plantago major standardized extract (PMSE) on oral ulcers in a Wistar rat model using histomorphometry and stereological parameters.Materials and MethodsThe study involved 72 Wistar rats divided randomly into 24 groups of 3 each: groups A1 to A4 received one dose to 4 doses of 5% PMSE nano emulsion, groups B1 to B4 received one dose to 4 doses of 10% PMSE nano emulsion, and groups C1 to C4 received one dose to 4 doses of 20% PMSE nano emulsion, groups D1 to D4 received one dose to 4 doses of nano-emulsion without PMSE, groups E1 to E4 received one dose to 4 doses of PMSE, and group F served as the control group. An incision measuring 2 mm in diameter was made in the animals’ hard palate using a biopsy punch. A swab containing the necessary material was used to administer the medication orally to the wound. Histological samples were collected on days 2, 4, 6, and 8 and sent to the pathology laboratory for examination. Data analysis was performed using SPSS 26 and setting statistical significance at p < 0.05.ResultsGroup A showed a high rate of complete and normal re-epithelialization of the wound at 66.7%, compared to the other groups. Group D had a re-epithelialization rate of 50%, while groups C, E, and F had rates of 7.41% and group B had 7.16%. In terms of inflammation reduction, 23.88% of group A had no inflammation, a higher percentage compared to the other groups. Group B and D had no inflammation in 3.33% of cases, lower than the other groups. The study evaluated frequency of re-epithelialization and inflammation levels in different groups on days 2, 4, 6, and 8 after four doses of the drug with no significant differences found among the groups.ConclusionNone of the nano emulsions or PMSE enhanced the healing rate of oral ulcers. However, a 5% PMSE nano emulsion displayed an increase in lesion re-epithelialization.

Accessory Axillary Breast Management: Is Primary Skin Excision Necessary?

AbstractAxillary breasts are a common entity with a reported incidence of 2 to 6% in women and 1 to 3% in men. They are more common amongst Asians than Caucasians, namely amongst South East Asians and Indians, with the highest incidence amongst Japanese. While modalities like CoolScupting™, Kybella™ injections, and BodyTite™ have been used by surgeons for management of axillary breasts, the most effective treatment for this condition remains surgical management involving a combination of liposuction of the axillary breast with excision of the gland and skin. In the author's experience, primary skin excision always leaves a long visible scar that widens over time, at times leading to contractures and restricted axillary movements even when closure looks tension free on the table. Any skin excess is best dealt with secondarily. The author uses a modified protocol without any primary skin excision in axillary breast management to achieve excellent results with minimal scars.

Calcific uraemic arteriolopathy: A rare but devastating complication of end-stage renal failure

Calcific uraemic arteriolopathy is a rare complication of end-stage renal failure. It has a grave prognosis with 1-year survival of under 50%. It occurs due to subcutaneous small vessel calcification, thrombosis, with subsequent tissue necrosis. Calcific uraemic arteriolopathy is a rare complication of end-stage renal failure. It carries a grave prognosis with 1-year survival of under 50%. It occurs due to subcutaneous small vessel calcification, thrombosis, with subsequent tissue necrosis. We described a case of calcific uraemic arteriolopathy in a 58-year-old man who presented with violaceous indurations over bilateral lower limbs, as well as large necrotic ulcer with adjacent eschars at the lower abdomen. Although skin biopsy is the gold standard for diagnosis, it is often avoided due to potential poor wound healing. On the other hand, in radiographs or computed tomography, fine linear or serpiginous subcutaneous calcifications are typical manifestations, which represent underlying small vessel calcifications. Radiological examinations, therefore, play an important role to establish the diagnosis.

A rare case of early onset lewy body dementia with parkinsonism associated with chronic exposure to copper contaminated drinking water.

There is a well-recognized relationship between a person's body burden of essential trace elements such as copper and their neurological function in which both deficiencies and exposures to excessive concentrations are associated with adverse clinical outcomes. Preclinical studies indicate chronic excess copper exposure is associated with altered motor function, dopaminergic neuronal loss, astrocytosis, and microgliosis. Copper also promotes oligomerization and fibrilization of α-synuclein suggesting it may hasten the course of an α-synucleinopathy. Here we report a rare case of early onset Lewy Body Dementia with Parkinsonism in a 53-year-old Caucasian woman exposed to copper contaminated drinking water for more than 10 years. Her hair and that of her daughter had streaks of blue-green discoloration as did the porcelain sinks in their home. Testing confirmed copper contamination of the drinking water. A neurologist diagnosed her with Lewy Body Dementia with Parkinsonism. Skin biopsy for phosphorylated α was consistent with a diagnosis of an α-synucleinopathy. These findings suggest chronic exposure to excessive copper may act as disease modifying factor in Lewy Body Dementia with Parkinsonism. It has previously been recommended that individuals at risk of Alzheimer's disease (AD) avoid excessive intake of copper. Genetic studies indicate that Lewy Body Dementia shares risk factors and pathways with AD. Based on the observations in this patient we recommend that individuals at risk for an α-synucleinopathy based on a positive family history, genetic testing, and/or positive results on a skin biopsy for phosphorylated α-synuclein avoid exposure to excess copper.

540. INFILTRATION OF RESECTED OESOPHAGEAL ADENOCARCINOMA WITH ANTIGEN-EXPERIENCED PD-1 AND CD39 POSITIVE CD8+ TISSUE RESIDENT MEMORY CELLS CORRELATE WITH IMPROVED SURVIVAL

Abstract Background The development of novel treatments for oesophageal adenocarcinoma (OAC) represents an area of significant unmet need. Despite the application of immune checkpoint blockade alongside chemotherapy as standard of care for some patients with metastatic OAC, responses to immunotherapies are modest and 5-year survival is 17%. The reasons for this remains unclear and while tumour infiltration with CD8+ T lymphocytes (TILs) at the time of resection is associated with improved outcomes, this heterogeneous population remains incompletely characterised in OAC. Tissue resident memory cells (TRM) are increasingly understood as key mediators of immunotherapy response but their role in OAC is poorly understood. Methods Tumour samples were accessed by punch biopsy from the central portion of cancers resected from 44 patients undergoing curative surgery for OAC. Samples were assessed by multi-parametric flow cytometry for the presence of antigen-experienced TILs and markers of activation and exhaustion. Populations of antigen-experienced PD-1 and CD39 positive CD8+ OAC TILs were sorted, and bulk RNA sequencing (RNAseq) undertaken using a modified SmartSeq2 protocol allowing differential gene expression analysis and gene set enrichment analysis. Flow cytometric assessment of functionality was completed. Results Resected OAC are often highly infiltrated with antigen experienced CD8+ TILs expressing high levels of PD-1 and CD39 and an abundance of this population correlates with improved survival (%PD-1/CD39+ &amp;gt;Median, OS HR 0.12). RNAseq of sorted TILs identified this PD-1+ and CD39+ lymphocyte population as enriched for precursor exhausted-like CD8+ TRM (NES 2.01 p=0.00). This is correlated by their CD103+ and TIM3- predominance on flow cytometry in keeping with TRMsassociated with immunotherapy response in other cancers. This population demonstrated a maintained proliferative potential, an ability to degranulate and produce the key effector molecules IFN-γ, TNF-α and Granzyme B. Conclusions An abundance of a PD-1 and CD39 positive CD8+ TIL population, consistent with a precursor exhausted-like TRM population with maintained proliferative and functional capacity, is observed to correlate with improved outcomes following curative surgery for OAC. This TRM population is consistent with analogous populations observed to be responsible for immunotherapy response in other cancers and their identification may predict benefit from such approaches in OAC and allow better patient selection for treatment with immune checkpoint inhibitors.

Comparing GBA1-Parkinson's disease and idiopathic Parkinson's disease: α-Synuclein oligomers and synaptic density as biomarkers in the skin biopsy.

The main genetic risk factors for Parkinson's disease (PD) are presently represented by variants in GBA1 gene encoding for the β-glucocerebrosidase (GCase). Searching for a peripheral biomarker that can be used for selecting and monitoring patients in clinical trials targeting GBA1-associated PD (GBA1-PD) is a current challenge. We previously demonstrated that α-synuclein oligomers expressed as proximity ligation assay (PLA) score in synaptic terminals of skin biopsy are a reliable biomarker for distinguishing idiopathic PD (iPD) from healthy controls (HC). This cross-sectional study investigates an unexplored cohort of GBA1-PD (n = 27) compared to 28 HC, and 36 iPD cases to (i) analyze α-synuclein oligomers and quantify them throughout PLA score, (ii) investigate GCase expression in brain and synaptic terminals targeting the sweat gland, (iii) unravel indicators that could differentiate patients with specific GBA1 mutations. PLA score discriminates GBA1-PD from HC with sensitivity = 88.9% (95% CI 70.84-97.65), specificity = 88.5% (95% CI 69.85-97.55), and PPV = 88.9% (95% CI 73.24-95.90), AUC value = 0.927 (95% CI 0.859-0.996). No difference was found between GBA1-PD patients and iPD, suggesting a common pathological pathway based on α-synuclein oligomers. GCase score did not differ in GBA1-PD, iPD, and HC in the synaptic terminals, whereas a positive correlation was found between PLA score and GCase score. Moreover, a significant increase in synaptic density was observed in GBA1-PD compared to iPD and HC (P < 0.0001). Employing ROC curve to discriminate GBA1-PD from iPD, we found an AUC value for synaptic density = 0.855 (95% CI 0.749-0.961) with sensitivity = 85.2% (95% CI 66.27%-95.81%), specificity = 77.1% (95% CI 59.86%-89.58%), and PPV = 74.19% (60.53%-84.35%). The highest synaptic density values were observed in p.N409S patients. This work points out to the value of both PLA score and synaptic density in distinguishing GBA1-PD from iPD and to their potential to stratify and monitor patients in the context of new pathway-specific therapeutic options.

The utility of the normal thin section skin biopsy in the assessment of systemic/extracutaneous disease and small fiber neuropathy

Diseases reflective of multiorgan vascular injury of diverse etiology, peripheral nerve disease, dysautonomia syndromes, and intravascular lymphoma may exhibit abnormalities on a normal skin biopsy that may be instrumental in establishing a diagnosis. A retrospective review of our database was conducted to uncover cases where a normal skin biopsy was performed to rule in or out such systemic diseases as complement-driven thrombotic microvascular disease (including atypical hemolytic uremic syndrome, posttransplant thrombotic microangiopathy, and severe or critical COVID-19), systemic capillary leak syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) intravascular B cell lymphoma, small fiber neuropathy, dysautonomia syndromes, and mast cell activation syndrome. Among the special studies were immunohistochemical staining to detect C5b-9, CD56, and myxovirus resistance protein A, as well as mast cell, B and T cell markers. Characteristic patterns were critical in establishing diagnoses such as : increased C5b-9 microvascular deposition in the deltoid area (atypical hemolytic uremic syndrome, posttransplant thrombotic microangiopathy, catastrophic antiphospholipid antibody syndrome, and severe or critical COVID-19); enhanced type I interferon signaling (systemic capillary leak syndrome); ultrastructural arteriopathic changes (CADASIL); reduced cutaneous autonomic innervation in the lower extremities (small fiber neuropathy and postural orthostatic tachycardia syndrome); presence of intravascular lymphocytes on biopsy of abdominal, thigh, and buttock skin (intravascular B cell lymphoma); and a higher than normal density of mast cells in the absence of other inflammatory cell types (mast cell activation syndrome). The skin is clearly a critical window for understanding extracutaneous disease, a concept well exemplified by the myriad of diseases suggested by the microscopic and/or ultrastructural examination of clinically normal skin and therefore establishing the normal skin biopsy as an important tool for understanding certain extracutaneous reactive, neoplastic and paraneoplastic syndromes as well as small fiber neuropathy.

Abstract P101: Surgical and not medical treatment of Primary Aldosteronism increase skin K + levels: pathophysiological and clinical implications

Introduction: Primary aldosteronism (PA), the most common curable salt-dependent form of arterial hypertension, features renal K + loss and enhanced Na + reabsorption. Hypothesis: We assessed the hypothesis that alterations of electrolyte, water, and Tonicity-responsive Enhancer Binding Protein/NFAT5 mRNA content occur in the skin of PA patients and are corrected by surgical cure. Methods: We obtained skin biopsies in 80 subjects: 49 consecutive consenting PA patients, optimally treated with a mineralocorticoid receptor antagonist (MRA) before adrenalectomy; 6 patients with essential hypertension, and 25 normotensive controls. We measured Na + , K + and water content with atomic absorption spectrometry after ashing and NFAT5 mRNA with digital droplet PCR. The PA patients were retested after adrenalectomy. Results: We discovered that the skin biopsy specimen dry weight (DW) was higher at surgery than follow-up (p&lt;0.001) and correlated directly with electrolyte and water content (all p&lt;0.01), indicating the need for adjusting electrolyte and water data for DW. Surgical cure of PA markedly increased skin DW-adjusted K + (from 1.14±0.1 µg/mg to 2.81±0.27 µg/mg, p&lt;0.001) and water content (from 2.92±1.4 mg/mg to 3.85±0.23 mg/mg, p&lt;0.001), but left DW-adjusted skin Na + content unaffected. In the PA patients NFAT5 mRNA copy number was higher (p=0.03) than in the normotensive controls and decreased after surgery (p=0.03). Conclusions: In conclusion, surgical cure, but not optimal MRA treatment corrected the prominent skin cell K + depletion that occurred despite normal serum K + levels. The lack of overt skin Na + accumulation in PA patients during MRA treatment could be explained by enhanced skin Na + lymphatic drainage due to the documented activation of the skin NFAT5/TonEBP pathway.

“Histopthological Spectrum Of Leprosy In A Tertiary Care Centre”

Background: Leprosy affects skin and peripheral nerves, muscles, eyes, bones, testis and internal organs. Histopathology and demonstration of lepra bacilli is a vital role to supplement clinical examination and diagnosis for correct classification and therefore for patients treatment. Aim- To study the Histopathology spectrum of Leprosy in a tertiary care centre. Materials &amp;Methods: All the skin biopsy with clinically suscipious of leprosy and sent for histopathological examination during the year Jan 2020 to Dec 2024 were included in the study. Results: A total of 60 cases were studied out of them 61% are male and 39% are female. With M:F ratio1.56: 1, majority of them belongs to 41-50 age group. The commonest histological type was borderline TB leprosy followed by Borderline lepromatous leprosy, least common cases were of lepromatous leprosy and histoid leprosy. Conclusion: Histopathological examination is the important investigation for accurate diagnosing and typing of leprosy

Deep Learning–Based Classification of Early-Stage Mycosis Fungoides and Benign Inflammatory Dermatoses on H&E-Stained Whole-Slide Images: A Retrospective, Proof-of-Concept Study

The diagnosis of early-stage mycosis fungoides (MF) is challenging due to shared clinical and histopathological features with benign inflammatory dermatoses (BIDs). Recent evidence has shown that deep learning (DL) can assist pathologists in cancer classification, but this field is largely unexplored for cutaneous lymphomas. This study evaluates DL in distinguishing early-stage MF from BIDs using a unique dataset of 924 hematoxylin and eosin-stained whole-slide images from skin biopsies, including 233 early-stage MF and 353 BID patients. All MF patients were diagnosed after clinicopathological correlation. The classification accuracy of weakly-supervised DL models was benchmarked against three expert pathologists. The highest performance on a temporal test set was at 200x magnification (0.25 μm per pixel resolution), with a mean area-under-the-curve of 0.827 ± 0.044 and a mean balanced accuracy of 76.2 ± 3.9%. This nearly matched the 77.7% mean balanced accuracy of the three expert-pathologists. Most (63.5%) attention heatmaps corresponded well with the pathologists’ region-of-interest. Considering the difficulty of the MF versus BID classification task, the results of this study show promise for future applications of weakly-supervised DL in diagnosing early-stage MF. Achieving clinical-grade performance will require larger multi-institutional datasets and improved methodologies, such as multimodal DL with incorporation of clinical data.

Epidemiologic, clinicopathologic, and diagnostic findings in pet rabbits with myxomatosis caused by the California MSW strain of myxoma virus: 11 cases (2022-2023).

To determine epidemiologic features of naturally occurring myxomatosis in domestic rabbits in California and to characterize clinicopathologic and diagnostic findings. 11 client-owned rabbits, Oryctolagus cuniculus subsp domesticus. A prospective study of pet rabbits with myxomatosis seen at an exotic animal specialty clinic in Santa Cruz county, California, was conducted between January 1, 2022, and December 31, 2023. Rabbits were included in the study if they had bilateral blepharedema and were PCR positive for myxoma virus. All infected rabbits had spent time outdoors. Common clinical signs included bilateral blepharedema (11/11), anogenital edema (10/11), rectal temperature ≥ 39.7 °C (5/9), and sudden death (4/11). Eyelid biopsies from all rabbits (11/11) were positive for myxoma virus by qualitative PCR followed by Sanger sequencing (100% nucleotide identity to strain MSW, also known as California/San Francisco 1950 [Genbank accession KF148065]). Most rabbits had keratinocytes containing eosinophilic intracytoplasmic viral inclusions in biopsies of edematous skin (8/11) and lymphocyte necrosis in the spleen (10/11). Immunohistochemistry identified myxoma virus in samples of skin, heart, lung, ileum, spleen, and lymph node. Clinical signs of myxomatosis caused by the MSW strain of myxoma virus are distinctive but subtle. Cases occur regularly in the Santa Cruz and San Jose regions of California. As infection with this virus is almost 100% fatal and no vaccine is available in the US, owners of domestic rabbits in endemic areas should keep their pets indoors or behind mosquito screens. Myxomatosis is a reportable disease in the US, and the appropriate state or federal agencies should be contacted when outbreaks occur.

Identifying Genetic Mutations in Vascular Anomalies Using a Sequencing Panel for Childhood Cancers: A Pilot Study

Introduction: Genetic mutations have been identified in the pathogenesis of vascular anomalies. Due to overlaps in genetic variants causing vascular anomalies and cancer, we used a next-generation sequencing panel for genomic profiling of childhood cancers to detect somatic mutations in children with vascular anomalies. We aim to review the utility of an oncology panel for the molecular diagnosis of vascular anomalies. Methods: Nine patients with histologically confirmed vascular anomalies were included. DNA was extracted from formalin-fixed paraffin-embedded tissue specimens obtained from affected tissue following diagnostic punch biopsies of the skin and core biopsies of the vascular malformation or tumor during sclerotherapy or surgical excision. Molecular analysis of the tissue samples was performed using AmpliSeq for Childhood Cancer DNA Assay Panel. Results: Two patients had antenatally detected vascular anomalies. The median age at diagnosis for the remaining patients was 7.0 years (IQR, 0.6–10.0 years). Seven were diagnosed with vascular malformations, while 2 had vascular tumors. Pathological somatic mutations were identified in 4 patients, leading to a diagnostic yield of 44.4%. Two different PIK3CA mutations were identified in 3 cases: 1 in a case of macrocystic lymphatic malformation, the other in a case of Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevus, Spinal/Skeletal anomalies syndrome and Klippel–Trenaunay syndrome. BRAF mutation was identified in a patient with a veno-lymphatic malformation. Conclusion: An oncology next-generation sequencing panel can be used for genetic profiling of vascular anomalies. However, a more customized and sensitive panel may be of better diagnostic yield, as detection of somatic mutations in vascular anomalies is challenging due to tissue mosaicism, low-abundant genetic variants, and specimen limitations.

Volumetric changes of the enteric nervous system under physiological and pathological conditions measured using x-ray phase-contrast tomography.

Full-thickness biopsies of the intestinal wall may be used to study and assess damage to the neurons of the enteric nervous system (ENS), that is, enteric neuropathy. The ENS is difficult to examine due to its localization deep in the intestinal wall and its organization with several connections in diverging directions. Histological sections used in clinical practice only visualize the sample in a two-dimensional way. X-ray phase-contrast micro-computed tomography (PC-μCT) has shown potential to assess the cross-sectional thickness and volume of the ENS in three dimensions (3D). The aim of this study was to explore the potential of PC-μCT to evaluate its use to determine the size of the ENS. Full-thickness biopsies of ileum obtained during surgery from five controls and six patients clinically diagnosed with enteric neuropathy and dysmotility were included. Punch biopsies of 1 mm in diameter and 1 cm in length, from an area containing myenteric plexus, were extracted from paraffin blocks, and scanned with synchrotron-based PC-μCT without any staining. The microscopic volumetric structure of the neural tissue (consisting of both ganglia and fascicles) could be determined in all samples. The ratio of neural tissue volume/total tissue volume was higher in controls than in patients with enteric neuropathy (P = 0.013). The patient with the longest disease duration had the lowest ratio. The assessment of neural tissue can be performed in an objective, standardized way, to ensure reproducibility and comparison under physiological and pathological conditions. Further evaluation is needed to examine the role of this method in the diagnosis of enteric neuropathy.

51346 Use of mRNA and miRNA sequencing to demonstrate the clinical senomorphic and anti-aging activity of a combination of niacinamide and hyaluronic acid on human skin biopsies

51346 Use of mRNA and miRNA sequencing to demonstrate the clinical senomorphic and anti-aging activity of a combination of niacinamide and hyaluronic acid on human skin biopsies

Single-cell sequencing delineates T-cell clonality and pathogenesis of the parapsoriasis disease group

BackgroundMycosis fungoides (MF), the most common cutaneous T-cell lymphoma, is often underdiagnosed in early stages due to similarities with benign dermatoses such as atopic dermatitis (AD). Furthermore, the delineation from so-called “parapsoriasis en plaque,” a disease that can appear either in a small- or large-plaque form, is still controversial. ObjectiveTo characterize the parapsoriasis disease spectrum. MethodsWe performed single-cell RNA sequencing of skin biopsies from patients within the parapsoriasis-to-early-stage MF spectrum, stratified for small and large plaques, and compared them to AD, psoriasis and healthy control skin. Results6 out of 8 large-plaque lesions harbored either an expanded alpha/beta or gamma/delta T-cell clone with downregulation of CD7 expression, consistent with a diagnosis of early-stage MF. By contrast, 6 out of 7 small-plaque lesions were polyclonal in nature thereby lacking a lymphomatous phenotype, and also revealed a less inflammatory microenvironment than early-stage MF or AD. Of note, polyclonal small- and large-plaque lesions characteristically harbored a population of NPY+ innate lymphoid cells and displayed a stromal signature of complement upregulation and antimicrobial hyperresponsiveness in fibroblasts and sweat gland cells, respectively. These conditions were clearly distinct from AD or psoriasis, which uniquely harbored CD3+CRTH2+ IL13-expressing “Th2A” cells or strong type 17 inflammation, respectively. ConclusionThese data position polyclonal small- and large-plaque dermatitis lesions as a separate disease entity, that characteristically harbors a so far undescribed ILC population. We thus propose the new term “polyclonal parapsoriasis en plaque” to this kind of lesions, as they can be clearly differentiated from early and advanced-stage MF, psoriasis and AD on several cellular and molecular levels.

Histopathologic and Clinical Characterization of Brentuximab Vedotin-associated Rash.

Rash is one of the commonly observed adverse events with brentuximab vedotin (BV), a CD30-targeted antibody-drug conjugate used to treat cutaneous T-cell lymphoma (CTCL). However, clinical and histopathologic characterization of BV-associated rash (BVAR) is limited. Distinguishing BVAR from a patient's underlying CTCL can be challenging and can lead to treatment interruptions or even premature drug discontinuation. We performed a thorough clinical and histopathologic retrospective characterization of BVAR from a single institution. Utilizing polymerase chain reaction (PCR) and T-cell receptor high-throughput sequencing (TCR-HTS), we were able to isolate skin biopsy specimens from rash clinically suggestive of BVAR that also lacked a dominant TCR clone. A retrospective evaluation was performed of 26 biopsy specimens from 14 patients. Clinical features of BVAR included predominantly morbilliform or maculopapular morphology, delayed onset, and the trend toward moderate to severe classification, often requiring oral steroids. Most histopathologic specimens (25/26) showed spongiotic dermatitis as the primary reaction pattern. Many cases showed subtle findings to support a background interface or lichenoid eruption. Langerhans cell microabscesses were seen in one-fourth of specimens, and eosinophils were present in over one-half of the specimens. There were focal features mimicking CTCL, but these were not prominent. In 17 specimens with immunohistochemistry, the CD4:CD8 ratio in intraepidermal lymphocytes was relatively normal (1-6:1) in 65% (11/17) and 1:1 in 35% (6/17), demonstrating a trend toward increased CD8-positive cells compared with baseline CTCL. We have identified features that can help distinguish BVAR from a patient's CTCL, which can, in turn, help guide appropriate clinical management.

50126 Improving patient comfort with waiting for contact from clinicians regarding skin biopsy results

50126 Improving patient comfort with waiting for contact from clinicians regarding skin biopsy results

CERS1 is a biomarker of Staphylococcus aureus abundance and atopic dermatitis severity

BackgroundAtopic dermatitis (AD) is an inflammatory skin condition characterized by widely variable cutaneous Staphylococcus aureus abundance that contributes to disease severity and rapidly responds to type 2 immune blockade (i.e., dupilumab). The molecular mechanisms regulating S. aureus levels between AD subjects remain poorly understood. ObjectiveTo investigate host genes that may be predictive of S. aureus abundance and correspond with AD severity. MethodsData derived from the NIH/NIAID-funded (NCT03389893 [ADRN-09]) randomized, double-blind, and placebo-controlled multicenter study of dupilumab in adults (n=71 subjects) with moderate-severe AD. Bulk RNA-sequencing of skin biopsies (n=57 lesional, 55 non-lesional) was compared to epidermal S. aureus abundance, lipidomics, and AD clinical measures. ResultsS. aureus abundance and ceramide synthase 1 (CERS1) expression positively correlated at baseline across both non-lesional (r=0.29, p=0.030) and lesional (r=0.41, p=0.0015) skin. Lesional CERS1 expression also positively correlated with AD severity (i.e., SCORing AD [SCORAD] r=0.44, p=0.0006) and skin barrier dysfunction (transepidermal water loss area under the curve [TEWL AUC] r=0.31, p=0.025) at baseline. CERS1 expression (forms C18:0-sphingolipids) was negatively associated with elongation of very long chain fatty acids (ELOVL6; C16:0→C18:0) expression and corresponded with a shorter chain length sphingolipid composition. Dupilumab rapidly reduced CERS1 expression (day 7) and ablated the relationship with S. aureus abundance and ELOVL6 expression by day 21. ConclusionCERS1 is a unique molecular biomarker of S. aureus abundance and AD severity that may contribute to dysfunctional skin barrier and shorter chain sphingolipid composition through fatty acid sequestration as a maladaptive compensatory response to reduced ELOVL6.

53190 Patient pain, anxiety, and post-procedure function associated skin biopsy procedures

53190 Patient pain, anxiety, and post-procedure function associated skin biopsy procedures