The Histopathology of Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic Syndrome: Report of 12 Skin Biopsies From 6 Patients.

ABSTRACT: We present the histopathology of 12 skin biopsies from 6 patients with vacuoles, enzyme E1, X-linked, autoinflammatory, somatic syndrome and review the literature. The age of these 6 men ranges from 62 to 83 years (median of 70 years). UBA1 mutation was documented in all 6 patients. Multiple organ systems were involved with constitutional symptoms noted in 4 of 6 patients (67%), cutaneous involvement in 6 of 6 patients (100%), hematologic abnormalities in 6 of 6 patients (100%), pulmonary involvement in 4 of 6 patients (67%), musculoskeletal abnormalities in 3 of 6 patients (50%), vascular thrombosis in 2 of 6 patients (33%), ocular involvement in 2 of 6 patients (33%), and gastrointestinal involvement in 5 of 6 patients (83%). Of the 6 presented patients, neutrophilic dermatosis was seen in 3 biopsies, histiocytoid neutrophilic dermatosis in 1 biopsy, neutrophilic dermatosis with vasculitis in 1 biopsy, neutrophilic and granulomatous dermatitis in 2 biopsies, septal panniculitis consistent with erythema nodosum in 2 biopsies, and nonspecific patterns in 3 biopsies. In summary, neutrophilic dermatosis, small-vessel vasculitis, and panniculitis are frequent histopathologic patterns noted in decreasing frequency in skin biopsies of the patients with vacuoles, enzyme E1, X-linked, autoinflammatory, somatic syndrome. However, the histopathologic findings can be diverse, nonspecific in some instances, and varied among different biopsies obtained from the same patient.

Predictors of Local Invasion in Infiltrative Basal Cell Carcinoma: Tumour Budding Outperforms the WHO Subtyping.

Tumour budding (TB) correlates with increased local invasion in various neoplasms. Certain basal cell carcinomas (BCCs) exhibit local aggressiveness. Detecting adverse prognostic factors in partial biopsies could aid in identifying cases with heightened local risk. The absolute number of TB (≤ 3 tumour cells) in excision specimens of 271 infiltrative BCCs (0: absent; 1: 1-2 foci; 2: ≥ 3 foci; 3: ≥ 10 foci), the histopathological subtype and depth of infiltration, perineural invasion, and other histological features were evaluated. A significant correlation was found between TB and both depth of infiltration (rho 0.445, p < 0.001) and perineural invasion (p = 0.009). In the multivariate analysis of depth and perineural invasion (multiple regression, stepwise), TB was identified as a significant covariate together with diameter, inflammation, and perineural invasion for the former, and depth for the latter. Conversely, no correlation existed between the WHO histological subtypes (infiltrating, sclerosing, and micronodular), and depth of infiltration or perineural invasion. This study demonstrates the value of TB as a biomarker for local invasiveness in BCC. In routine practice, a count of ≥ 3 TB foci in lesions incompletely excised or with narrow tumour-free surgical margins would be a straightforward and reproducible method to guide BCC treatment.

Principales tipos de quistes en dermatopatología: Parte 2 / Main Types of Cysts in Dermatopathology: Part 2

Este es el segundo artículo de una serie de dos publicados en esta revista, en los que examinamos las características histopatológicas, así como el diagnóstico diferencial, de las principales entidades que se presentan en forma de estructuras quísticas y pseudoquísticas en la biopsia cutánea. En este segundo artículo, abordamos los quistes cutáneo ciliado, branquial, de Bartholino, onfalomesentérico, tímico, del conducto tirogloso, sinovial, y del rafe medio, así como el mucocele, el ganglión y los pseudoquistes auricular y mixoide digital. (AU)

This is the second article in a two-part series published in this journal, in which we examine the histopathological characteristics, as well as the differential diagnosis, of the main entities that present as cystic and pseudocystic structures in cutaneous biopsy. In this second article, we address ciliated cutaneous cysts, branchial cysts, Bartholin's cysts, omphalomesenteric cysts, thymic cysts, thyroglossal duct cysts, synovial cysts, and median raphe cysts, as well as mucocele, ganglion, and auricular and digital myxoid pseudocysts. (AU)

[Main Types of Cysts in Dermatopathology: Part 2]. / Principales tipos de quistes en dermatopatología: Parte 2.

This is the second article in a two-part series published in this journal, in which we examine the histopathological characteristics, as well as the differential diagnosis, of the main entities that present as cystic and pseudocystic structures in cutaneous biopsy. In this second article, we address ciliated cutaneous cysts, branchial cysts, Bartholin's cysts, omphalomesenteric cysts, thymic cysts, thyroglossal duct cysts, synovial cysts, and median raphe cysts, as well as mucocele, ganglion, and auricular and digital myxoid pseudocysts.

Principales tipos de quistes en dermatopatología: parte 1 / Main Types of Cysts in Dermatopathology: Part 1

Las estructuras quísticas son uno de los hallazgos más frecuentes en dermatopatología. Se trata de tumores quísticos y de pseudoquistes por acumulación de ciertas sustancias, por ejemplo, mucina. En una serie de dos artículos (de los cuales este es el primero) hemos revisado los principales tipos de quistes y pseudoquistes que pueden verse en la biopsia cutánea, examinando sus aspectos histopatológicos y los principales diagnósticos diferenciales. En esta primera parte, se abordan los quistes infundibulares, dermoides, vellosos eruptivos, foliculares pigmentados, pilonidales, tricolemales, de milium, híbridos y broncogénicos, así como el esteatocistoma, el hidrocistoma y los comedones. (AU)

Cystic structures represent one of the most common findings in dermatopathology. These encompass both cystic tumors and pseudocysts resulting from the accumulation of certain substances, such as mucin. In a two-part series (of which this is the first part), we have reviewed the principal types of cysts and pseudocysts that may be observed in cutaneous biopsies, examining their histopathological features and primary differential diagnoses. This first part encompasses infundibular cysts, eruptive dermoid cysts, pigmented follicular cysts, pilonidal cysts, tricholemmal cysts, milium cysts, hybrid cysts, bronchogenic cysts, as well as steatocystoma, hydrocystoma, and comedones. (AU)

Principales tipos de quistes en dermatopatología: parte 1 / Main Types of Cysts in Dermatopathology: Part 1

Las estructuras quísticas son uno de los hallazgos más frecuentes en dermatopatología. Se trata de tumores quísticos y de pseudoquistes por acumulación de ciertas sustancias, por ejemplo, mucina. En una serie de dos artículos (de los cuales este es el primero) hemos revisado los principales tipos de quistes y pseudoquistes que pueden verse en la biopsia cutánea, examinando sus aspectos histopatológicos y los principales diagnósticos diferenciales. En esta primera parte, se abordan los quistes infundibulares, dermoides, vellosos eruptivos, foliculares pigmentados, pilonidales, tricolemales, de milium, híbridos y broncogénicos, así como el esteatocistoma, el hidrocistoma y los comedones. (AU)

Cystic structures represent one of the most common findings in dermatopathology. These encompass both cystic tumors and pseudocysts resulting from the accumulation of certain substances, such as mucin. In a two-part series (of which this is the first part), we have reviewed the principal types of cysts and pseudocysts that may be observed in cutaneous biopsies, examining their histopathological features and primary differential diagnoses. This first part encompasses infundibular cysts, eruptive dermoid cysts, pigmented follicular cysts, pilonidal cysts, tricholemmal cysts, milium cysts, hybrid cysts, bronchogenic cysts, as well as steatocystoma, hydrocystoma, and comedones. (AU)

[Main Types of Cysts in Dermatopathology: Part 1]. / Principales tipos de quistes en dermatopatología: parte 1.

Cystic structures represent one of the most common findings in dermatopathology. These encompass both cystic tumors and pseudocysts resulting from the accumulation of certain substances, such as mucin. In a two-part series (of which this is the first part), we have reviewed the principal types of cysts and pseudocysts that may be observed in cutaneous biopsies, examining their histopathological features and primary differential diagnoses. This first part encompasses infundibular cysts, eruptive dermoid cysts, pigmented follicular cysts, pilonidal cysts, tricholemmal cysts, milium cysts, hybrid cysts, bronchogenic cysts, as well as steatocystoma, hydrocystoma, and comedones.

Gastric metaplasia as a precursor of nonconventional dysplasia in inflammatory bowel disease.

Gastric metaplasia in colonic mucosa with inflammatory bowel disease (IBD) develops as an adaptation mechanism. The association between gastric metaplasia and nonconventional and/or conventional dysplasia as precursors of colitis-associated colorectal cancer is unknown. To address this question, we retrospectively reviewed a series of 33 IBD colectomies to identify gastric metaplasia in 76 precursor lesions. We obtained 61 nonconventional and 15 conventional dysplasias. Among nonconventional dysplasia, 31 (50.8 %) were low-grade (LGD), 4 (6.5 %) were high-grade (HGD), 9 (14.8 %) had both LGD and HGD, and 17 (27.9 %) had no dysplasia (ND), while 14 (93 %) conventional dysplasias had LGD, and 1 (7 %) had LGD and HGD. Gastric metaplasia was assessed by concomitant immunoexpression of MUC5AC and loss of CDX2 staining. Expression of a p53-mut pattern was considered as a surrogate for gene mutation, and complete loss of MLH1 staining as presence of MLH1 hypermethylation. In nonconventional dysplasia, MUC5AC immunoexpression decreased as the degree of dysplasia increased, being 78 % in LGD and 39 % in HGD (p = 0.006). CDX2 was lost in epithelial glands with high expression of MUC5AC (p < 0.001). The p53-mut pattern was observed in 77 % HGD, 45 % LGD, and in 6 % with ND (p < 0.001). Neither nonconventional nor conventional dysplasia showed complete loss of MLH1 staining. Gastric metaplasia was also present in mucosa adjacent to nonconventional dysplasia with chronic changes or active inflammation. Our results show that gastric metaplasia appears in IBD-inflamed colon mucosa, it is the substrate of most nonconventional dysplasia and occurs prior to p53 alterations.

Fast-Growing Frontal Subcutaneous Nodule in a Young Woman.

A woman in her 20s presented with a firm, mobile, painful, fast-growing subcutaneous nodule in the glabella. What is your diagnosis?

Approach to the so-called "Invisible Dermatosis": When Subtle Histopathological Findings Guide Diagnosis.

ABSTRACT: Invisible dermatosis is a concept that can be applied either to clinical or histopathological findings. We will focus on the dermatopathological aspect of this invisible dermatosis that can be seen as dermatosis with subtle histopathological findings that are mandatory to known to stablish the diagnosis. With a proper approach facing in depth the different skin layers from stratum corneum to subcutaneous tissue combined with some especial stains, special investigations and mostly a proper clinicopathological correlation, the problem of missing out a diagnosis can be decreased. We will review the general aspects for diagnosis and the peculiar findings of an in-depth review of them because it is important to note that minor changes on a skin biopsy do not mean it is disease free. We will review classic clues, we will add some new useful ones, and we will also provide a guide on the special stains helpful, such as periodic acid-Schiff when facing fungi, orcein-Giemsa and van Gieson when altered elastic fibers are suspected, or Pearl and Masson Fontana when an altered skin pigmentation is suspected.

Spanish cohort of VEXAS syndrome: clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism.

BACKGROUND: The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. OBJECTIVES: To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. METHODS: Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. RESULTS: Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. CONCLUSION: Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms.

A 3-dimensional histology computer model of malignant melanoma and its implications for digital pathology.

BACKGROUND: Historically, cancer diagnoses have been made by pathologists using two-dimensional histological slides. However, with the advent of digital pathology and artificial intelligence, slides are being digitised, providing new opportunities to integrate their information. Since nature is 3-dimensional (3D), it seems intuitive to digitally reassemble the 3D structure for diagnosis. OBJECTIVE: To develop the first human-3D-melanoma-histology-model with full data and code availability. Further, to evaluate the 3D-simulation together with experienced pathologists in the field and discuss the implications of digital 3D-models for the future of digital pathology. METHODS: A malignant melanoma of the skin was digitised via 3 µm cuts by a slide scanner; an open-source software was then leveraged to construct the 3D model. A total of nine pathologists from four different countries with at least 10 years of experience in the histologic diagnosis of melanoma tested the model and discussed their experiences as well as implications for future pathology. RESULTS: We successfully constructed and tested the first 3D-model of human melanoma. Based on testing, 88.9% of pathologists believe that the technology is likely to enter routine pathology within the next 10 years; advantages include a better reflectance of anatomy, 3D assessment of symmetry and the opportunity to simultaneously evaluate different tissue levels at the same time; limitations include the high consumption of tissue and a yet inferior resolution due to computational limitations. CONCLUSIONS: 3D-histology-models are promising for digital pathology of cancer and melanoma specifically, however, there are yet limitations which need to be carefully addressed.

Pancreatic panniculitis revisited: A series of 34 patients.

BACKGROUND: Pancreatic panniculitis is a rare form of panniculitis generally associated with acute or chronic pancreatitis, and less frequently with pancreatic carcinoma. Clinically, it presents with subcutaneous nodules usually located in the lower extremities, however, it presents an almost pathognomonic histopathological finding with enzymatic fat necrosis in the adipose tissue. METHODS: In this retrospective case series of five hospitals, biopsy specimens of cutaneous lesions of pancreatic panniculitis were reviewed. Clinical information was obtained through medical records. RESULTS: A total of 34 cases were included, 23 women and 11 men, aged between 31 and 92 years. The most common associated pancreatic disease was acute pancreatitis (23 cases) and its main triggering cause was gallstones (17 cases). In two patients it was related to chronic pancreatitis and six cases were associated with malignancy. Histopathological findings were always the key to diagnosis. In the biopsies reviewed, mostly lobular panniculitis with the characteristic necrosis of the adipocytes was observed. In addition, nine of the cases presented with Splendore-Hoeppli phenomenon. CONCLUSIONS: We present the largest series of pancreatic panniculitis. Clinically, the female predominance and biliary lithiasis as the main cause of acute pancreatitis are to be emphasized. Histopathologically, a peripheral eosinophilic striated rim surrounding aggregates of ghost adipocytes consistent with Splendore-Hoeppli is an additional clue to its diagnosis.

Hemosiderotic Xanthelasmas. A New Clinicopathological Variant of Xanthelasma Palpebrarum or a Localized Variant of Xanthosiderohistiocytosis of the Eyelids?

ABSTRACT: Xanthelasma palpebrarum represent the most common subtype of cutaneous plane xanthomas. Xanthosiderohistiocytosis is considered a rare variant of xanthoma disseminatum, with only 4 cases reported to date. We report the case of a man with progressive pigmented lesions on the 4 eyelids that could correspond to hemosiderotic xanthelasmas or a localized variant of xanthosiderohistiocytosis.

[Validation of a gender awareness scale in health sciences students]. / Validación de una escala de conciencia de género en el alumnado de ciencias de la salud.

OBJECTIVE: Given the need to promote gender equity in healthcare, this research aimed to adapt and validate a short version of the Nijmegen Gender Awareness Scale (N-GAMN), that assesses attitudes and gender stereotyping of health sciences students. METHOD: A cross-sectional study was carried out using a questionnaire among health sciences students from the universities of Barcelona, Cantabria, Cartagena de Indias and the National Autonomous University of Nicaragua. Nine hundred fifty-six students filled out the questionary. A confirmatory factor analysis was performed to establish the relationship between the observed variables and the latent dimensions. RESULTS: The factorial analysis evaluated the validity of the scale and confirmed the existence of a three-dimensional structure composed of: (F1) gender stereotypes towards patients, (F2) gender stereotypes towards professionals and (F3) gender sensitivity in the healthcare (fit data: CFI=0.917, TFI=0.899, RMSEA=0.08 and SRMEA=0.06). Descriptive statistics showed relatively high levels of gender awareness among the participants. Fewer stereotypes were observed towards professionals than towards patients. Women and students from Spanish universities showed a higher level of awareness. However, the significance values of the Mann-Whitney U test allow us to infer the existence of differences based on geographical area, but not based on gender. CONCLUSIONS: The results suggest the potential application of the scale to assess the attitudes of students and professionals towards gender stereotypes and biases associated with clinical practice, as well as to assess the impact of gender awareness actions.

Alterations in p53, Microsatellite Stability and Lack of MUC5AC Expression as Molecular Features of Colorectal Carcinoma Associated with Inflammatory Bowel Disease.

Colitis-associated colorectal carcinoma (CAC) occurs in inflammatory bowel disease (IBD) because of the "chronic inflammation-dysplasia-cancer" carcinogenesis pathway characterized by p53 alterations in the early stages. Recently, gastric metaplasia (GM) has been described as the initial event of the serrated colorectal cancer (CRC) process, resulting from chronic stress on the colon mucosa. The aim of the study is to characterize CAC analyzing p53 alterations and microsatellite instability (MSI) to explore their relationship with GM using a series of CRC and the adjacent intestinal mucosa. Immunohistochemistry was performed to assess p53 alterations, MSI and MUC5AC expression as a surrogate for GM. The p53 mut-pattern was found in more than half of the CAC, most frequently stable (MSS) and MUC5AC negative. Only six tumors were unstable (MSI-H), being with p53 wt-pattern (p = 0.010) and MUC5AC positive (p = 0.005). MUC5AC staining was more frequently observed in intestinal mucosa, inflamed or with chronic changes, than in CAC, especially in those with p53 wt-pattern and MSS. Based on our results, we conclude that, as in the serrated pathway of CRC, in IBD GM occurs in inflamed mucosa, persists in those with chronic changes and disappears with the acquisition of p53 mutations.