Histopathological Features Research Articles

50302 Distinguishing features of presentation, clinical and histopathological features between indolent Primary Cutaneous B-Cell Lymphomas.

50302 Distinguishing features of presentation, clinical and histopathological features between indolent Primary Cutaneous B-Cell Lymphomas.

Respiratory performance in Duchenne muscular dystrophy: Clinical manifestations and lessons from animal models.

Duchenne muscular dystrophy (DMD) is a fatal genetic neuromuscular disease. Lack of dystrophin in skeletal muscles leads to intrinsic weakness, injury, subsequent degeneration and fibrosis, decreasing contractile function. Dystropathology eventually presents in all inspiratory and expiratory muscles of breathing, severely curtailing their critical function. In people with DMD, premature death is caused by respiratory or cardiac failure. There is an urgent need to develop therapies that improve quality of life and extend life expectancy in DMD. Surprisingly, there is a dearth of information on respiratory control in animal models of DMD, and respiratory outcome measures are often limited or absent in clinical trials. Characterization of respiratory performance in murine and canine models has revealed extensive remodelling of the diaphragm, the major muscle of inspiration. However, significant compensation by extradiaphragmatic muscles of breathing is evident in early disease, contributing to preservation of peak respiratory system performance. Loss of compensation afforded by accessory muscles in advanced disease is ultimately associated with compromised respiratory performance. A new and potentially more translatable murine model of DMD, the D2.mdx mouse, has recently been developed. Respiratory performance in D2.mdx mice is yet to be characterized fully. However, based on histopathological features, D2.mdx mice might serve as useful preclinical models, facilitating the testing of new therapeutics that rescue respiratory function. This review summarizes the pathophysiological mechanisms associated with DMD both in humans and in animal models, with a focus on breathing. We consider the translational value of each model to human DMD and highlight the urgent need for comprehensive characterization of breathing in representative preclinical models to better inform human trials.

Diagnostic Values of Ki67, Cox2, CD31, E-cadherin, VEGF, MMP2, and MMP9 Protein Expression in Human Melanoma

Background: Cutaneous melanoma, the most severe form of skin cancer, has an unpredictable behavior and a high mortality rate. Recent research has identified new biomarkers and their associations with certain histopathological features, offering essential insights into diagnosis, prognosis, and therapeutic strategies. Material and method: In this meticulously designed and executed study, we analyzed 85 formalin-fixed, paraffin-embedded (FFPE) tissue samples using the gold standard technique of immunohistochemistry (IHC) to characterize the protein expression profiles. We used a comprehensive panel of Ki67, Cox2, CD31, VEGF, MMP2, MMP9, and E-cadherin antibodies. Clinical stages were meticulously determined according to TNM classification, the thickness of the Breslow depth, and Clark levels. We employed robust statistical methods such as one-way ANOVA and curve estimation regression to analyze the data. The STRING database, a trusted resource, was used to identify protein-protein interactions and related pathways. Results: The results of our study unveiled novel pairwise positive correlations between CD31 and Ki67 (r = 0.72), and between VEGF and Ki67 protein expression (r = 0.63). We also found a significant inverse relationship between the expression of E-cadherin and some biomarkers, such as Ki67, CD31, and VEGF (p < 0.001 for all). Additionally, our findings revealed a strong positive association between the extent of tumor invasion and the expression levels of Ki67, CD31, and VEGF. The overexpression of these proteins was significantly correlated with advanced clinical stages (p < 0.001 for all). Conclusion: Our study suggests that the biomarkers we examined could be reliable potential diagnostic and prognostic biomarkers for cutaneous melanoma. These findings have the potential to significantly impact the diagnosis, prognosis, and treatment of this deadly disease, offering new avenues for improved patient care.

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.

Squamous cell carcinoma of the nail apparatus: Histopathology and immunohistochemistry correlation study.

Nail squamous cell carcinoma (NSCC) is the most frequent ungual malignant tumor, but its incidence remains low. The histopathological description is sparse. We aim to characterize NSCC histopathological aspects, search for a correlation with clinical subtypes, and investigate immunohistochemistry expression of p16, p53, and Ki67. This retrospective study collected NSCC diagnosed in our dermatology department between 2007 and 2021. The histopathological features were correlated with the clinical signs and immunohistochemistry. A total of 48 patients were included, and immunohistochemistry was available for 36 of them. Two histopathological patterns became prominent: a blue-basaloid type characterized by koilocytosis (p < 0.001), and a pink-keratinizing type. Mean ages were similar when comparing basaloid and periungual versus keratinizing and subungual (p < 0.001). p16 was positive in 31 of 36 cases: 18 basaloid and 13 keratinizing (p = 0.167). p53 and Ki67 were all abnormal. Our study described two histopathological NSCC subtypes and associated them with the two clinical subtypes: the blue-basaloid type, HPV-induced, in situ, of periungual localization in younger males; and the pink-keratinizing type, non-HPV-induced, invasive, of subungual site, in elderly. Immunohistochemistry was not contributing on its own, but p16 positivity associated with basaloid histopathological profile helps support HPV etiology.

366.11: A novel antibody-mediated rejection model for mouse intestinal transplantation and its histopathological characteristics.

366.11: A novel antibody-mediated rejection model for mouse intestinal transplantation and its histopathological characteristics.

Impact of molecular and histopathological findings on FIGO 2009 stage I endometrial cancer: Transition to FIGO 2023 staging system.

This study aims to investigate the impact of integrating molecular and histopathological findings into the revised International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system on patients initially diagnosed with stage I endometrial cancer (EC) according to the FIGO 2009 criteria. A cohort of 197 EC patients, initially classified as stage I under FIGO 2009, underwent restaging based on the updated FIGO 2023 criteria. The patients' molecular and histopathological characteristics were documented, and their impact on upstaging was analyzed. Molecular profiling was conducted for 81.2% (160/197) of the patients, revealing that 55.3% (109/197) were classified as non-specific molecular profile, 14.7% (29/197) as mismatch repair deficiency, 11.2% (22/197) as p53 abnormality (p53abn), and 18.8% (37/197) as unknown. Upstaging was identified in 26.9% (43/160) of the 160 patients with known molecular profiles. Among the upstaged patients, 51.2% experienced upstaging due to p53 abnormality, 20.9% due to substantial lymphovascular space invasion (LVSI), 20.9% due to aggressive histological types, and 6.9% due to high grade. The introduction of the molecular profile into the revised FIGO 2023 staging system for stage I EC has led to notable changes in the staging of approximately one-fifth of patients. While p53 abnormalities have emerged as the most influential factor contributing to the upstaging, LVSI and aggressive histological types also represent significant contributing factors.

The surgical, histopathological characteristics, and survival outcome of ovarian clear cell carcinoma: a retrospective case series sharing the experience of a tertiary cancer centre.

Ovarian clear cell carcinoma (OCCC) is a rare and distinct subtype of epithelial ovarian cancer (EOC). It is unique in several biological aspects. This study analyzes the clinicopathological features and survival outcome of patients with OCCC, aiming to identify factors affecting recurrence, progression-free survival (PFS) and overall survival (OS). A retrospective study included 49 women with OCCC between January 2009 and December 2021 at Oxford Cancer Center. All demographic and pathological characteristics, pre-operative biomarkers, surgical procedure, complications, hospital stay, chemotherapy regimen, and disease status on follow-up, were collected from electronic medical records. No residual disease (R0) was achieved in 39 out of 49 women who underwent cytoreductive surgery. The follow-up time had a mean of 8.75 years. The 3-year OS was 73.4%, and the 3-year PFS was 81.3% [95% confidence interval (CI): 84.63-118.93]. Women with stage 1 disease had the best outcome. There was a marked difference (P<0.001) in OS in the presence of residual disease. No residual disease conferred a 3-year OS of 88.6% (95% CI: 108.6-141.8), compared to only 12.5% in the presence of residual disease (95% CI: 4.48-32.11). In multivariant analysis, the International Federation of Gynecology and Obstetrics (FIGO) stage was the only independent prognostic indicator of OS with (P<0.05), including carbohydrate antigen (CA) 125, hemoglobin, albumin, associated endometriosis, ascites, residual disease and FIGO staging. Surgery to achieve no residual disease is necessary to improve the prognosis in advanced OCCC. The true challenge is to predict which patients with early-stage disease at higher risk of recurrence and would most benefit from adjuvant treatments.

Mucosal Melanoma: Review from a Pathologist Point of View

Mucosal melanomas are rare malignant tumors arising from the epithelia lining the inner mucosal surfaces of the body. Unlike cutaneous melanoma, we have a limited understanding of mucosal melanomas is currently limited. Mucosal melanomas are characterized by genetic alterations quite distinct from cutaneous melanomas; however, their causative and promoting factors are unknown. These melanomas are characteristically diagnosed at a later stage due to their occult locations, leading to a worse prognosis. Dedicated staging systems for mucosal melanomas exist only for sinonasal and conjunctival melanomas. Therefore, risk stratification of patients with mucosal melanomas, particularly those arising from the anogenital area, is challenging. Recent studies have shown that minor modifications of the AJCC 8th Edition cutaneous melanoma staging system can group patients fairly robustly; however, the proposed T-categorization systems have yet to be validated in larger cohorts. We summarize the demographic, clinical, histopathologic, and molecular features of common subtypes of mucosal melanomas and highlight the outstanding needs in this field.

Desmoplastic Melanoma

Desmoplastic melanoma is a rare fibrosing variant of melanoma. It typically affects elderly patients but can occasionally affect young or middle-aged individuals. Desmoplastic melanoma is relevant as a diagnostic pitfall for pure tumor variants' distinct histopathologic and clinical features. The latter includes a lower regional lymph node involvement frequency and a more favorable prognosis among thick melanomas. Classic cases of desmoplastic melanoma tend to carry a high mutation burden. Patients with metastases from those tumors tend to respond favorably to novel immunotherapies.

Survival in Patients with Uveal Melanoma Is Linked to Genetic Variation at HERC2 Single Nucleotide Polymorphism rs12913832

Uveal melanoma (UM) is a rare disease, with the highest incidence in people with fair skin and light eyes. Eye color is largely genetically determined and is defined by a set of single nucleotide polymorphisms (SNPs). We set out to determine whether we could identify a SNP related to prognosis. We sequenced DNA from peripheral blood mononuclear cells of 392 patients with UM and obtained the genotype of 6 common eye color-related SNPs. Clinical and histopathologic tumor characteristics, tumor chromosome status, and patient survival were compared among patients with different genotypes. Three hundred ninety-two patients who underwent enucleation for UM at the Leiden University Medical Center, Leiden, The Netherlands. We isolated DNA from peripheral blood leukocytes of 392 patients with UM and performed sequencing, using 6 eye color SNPs from the HIrisPlex-S assay (Erasmus MC, Walsh lab). The genotypes extracted from the sequencing data were uploaded onto the HIrisPlexwebtool (https://hirisplex.erasmusmc.nl/) for eye color prediction. We tested the association of eye color SNPs with tumor characteristics and chromosome aberrations using Pearson's chi-square test and the Mann-Whitney U test and evaluated survival with Kaplan-Meier curves with the log-rank test and Cox regression. Uveal melanoma-related survival. Of 392 patients with analyzable genotype data, 307 patients (78%) were assigned blue eyes, 74 patients (19%) were assigned brown eyes, and 11 patients (3%) could not be assigned to either blue or brown. Patients with a genetically blue eye color showed worse survival (P= 0.04). This was related to 1 genotype: patients with the G/G genotype of rs12913832 (HERC2), which codes for blue eye color showed a worse prognosis (P= 0.017) and more often had high-risk tumors (monosomy of chromosome 3; P= 0.04) than in patients with an A/G or A/A genotype. The G/G genotype of rs12913832 (HERC2), which is related to blue eye color, not only is a genetic factor related to the risk of UM develop, but also is linked to a worse prognosis because of an association with a higher risk of a high-risk UM developing (carrying monosomy of chromosome 3). The author(s) have no proprietary or commercial interest in any materials discussed in this article.

From organs to algorithms: Redefining cancer classification in the age of artificial intelligence.

Traditional cancer classification based on organ of origin and histology is increasingly at odds with precision oncology. Tumors in different organs can share molecular features, while those in the same organ can be heterogeneous. This disconnect impacts clinical trials, drug development, and patient care. Recent advances in artificial intelligence (AI), particularly machine learning and deep learning, offer promising avenues for reclassifying cancers through comprehensive integration of molecular, histopathological, imaging, and clinical characteristics. AI-driven approaches have the potential to reveal novel cancer subtypes, identify new prognostic variables, and guide more precise treatment strategies for improving patient outcomes.

Focal myositis: a literature review of clinical and immunopathological aspects.

Focal myositis (FM) is a rare and restricted skeletal muscle inflammation, presenting as a solid mass with a typical lower leg localization and benign prognosis. In most cases the process solves spontaneously or after immunosuppressant therapy, but sometimes it recurs or progresses to a systemic inflammation. The basis of the disease are mostly unknown. Hence, we provide an update of histopathological features of FM, in order to better define the underlying pathomechanisms of this disorder. A PubMed literature search was focused on the case reports published in English from July 1977 to December 2023. FM and other myositis may show similar morphological features. Emerging studies on MMP molecules and future eventual research on microRNAs (miRNAs) could help in differential diagnosis. Clinical, laboratory, neurophysiological and imaging findings can allow a correct diagnosis. However, muscle biopsy seems to be the only diagnostic tool to differentiate among FM and other localized soft tissue masses.

50743 Histopathologic Features of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

50743 Histopathologic Features of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

The Assessment of Female Breast Cancer Tumors Using Some Biomarkers in Attendees of Federal Medical Centre, Yenagoa, Bayelsa State, Nigeria

Breast cancer has remained a major public health issue globally but predominantly affects women in developing nations. The overall survival rate of Nigerian women with breast cancer is low and patients with early breast cancer tend to have better survival than those with advanced distic basis and pathology. These changes are leading to revisions in the management of the disease with a positive impact on prognosis.The current research was done to describe the epidemiological and histopathological features of breast cancer amongst females attending the Federal Medical Center, Yenagoa, Bayelsa State, Nigeria. In this retrospective study, 178 breast specimens were used, spanned from 2010 to 2022. Results presented an age at diagnosis lower to the Western population and invasive ductal carcinoma as the main histological type. In this study, the prevalence of breast cancer amongst females attending Federal Medical Center, Yenagoa, Bayelsa State, Nigeria was analyzed using Hematoxylin and Eosin staining techniques on breast cancer samples collected over the study period. The pathophysiology of breast cancer is not very clear; however, some risk factors are. While some common risk factors are advancing age and the female gender, genetic mutations—namely BRCA 1 and 2—account for only about 10% of breast cancers. The role played by biomarkers, such as estrogen receptors, progesterone receptors, and human epidermal growth factor receptors, in the detection and management of patients with breast cancer. Human breast cancer is known to be dependent on sexual hormones for its growth, as it is derived from breast tissue that normally responds to endogenous hormones. Despite improvements in early detection and therapy, Breast Cancer remains one of the major burdens to healthcare systems and societies.

Dissemination of Retinoblastoma Post-Enucleation: Histopathological Risk Factors Review

Introduction: Examining the histopathological markers indicative of high risk in retinoblastoma is imperative for evaluating the potential for post-enucleation recurrence and metastatic spread. Purpose: This article seeks to elucidate diverse definitions of high-risk histopathological features in advanced retinoblastoma, which confer susceptibility to recurrence and metastasis following enucleation. Review: Reducing mortality rates associated with retinoblastoma poses a significant clinical challenge. It is well-established that post-laminar optic nerve invasion, extensive choroidal invasion, and scleral invasion are key features commonly observed in advanced retinoblastoma cases requiring enucleation. Conclusion: The presence of these features in advanced retinoblastoma necessitates adjunctive therapeutic interventions to reduce the risk of orbital recurrence or metastatic spread, thereby enhancing patient survival rates.

Primary Dermal Melanoma

Primary dermal melanoma (PDM) is a rare subtype of melanoma with an estimated incidence of less than 1%. PDM presents entirely in the dermis or subcutis and histopathologically mimics cutaneous metastases of melanoma due to its lack of connection to the overlying epidermis. A thorough history and examination, including imaging evaluation for metastatic disease, will reveal no prior history or concurrent lesion of primary cutaneous or metastatic melanoma. Despite its histopathologic similarities to melanoma metastasis, PDM is associated with an unexpectedly favorable prognosis. This review discusses the clinical and histopathologic features of PDM as a distinct subtype of melanoma, as well as the current approach to clinical staging and management.

CSF1-dependent macrophage support matrisome and epithelial stress-induced keratin remodeling in Eosinophilic esophagitis

Atopic diseases such as Eosinophilic Esophagitis (EoE) often progress into fibrosis (FS-EoE), compromising organ function with limited targeted treatment options. Mechanistic understanding of FS-EoE progression is confounded by the lack of preclinical models and the heavy focus of research on eosinophils themselves. We found that macrophage accumulation precedes esophageal fibrosis in FS-EoE patients. We developed a FS-EoE model via chronic administration of oxazalone allergen, in a transgenic mouse over-expressing esophageal epithelial hIL-5 (L2-IL5OXA). These mice display striking histopathologic features congruent with that found in FS-EoE patients. Unbiased proteomic analysis, using a unique extracellular-matrix (ECM) focused technique, identified an inflammation-reactive provisional basal lamina membrane signature and this was validated in two independent EoE patient RNA-sequencing/proteomic cohorts, supporting model significance. A wound healing signature was also observed involving hemostasis-associated molecules previously unnoted in EoE. We further identified the ECM glycoprotein, Tenascin-C (TNC), and the stress-responsive keratin-16 (KRT16) as IL-4 and IL-13 responsive mediators, acting as biomarkers of FS-EoE. To mechanistically address how the immune infiltrate shapes FS-EoE progression, we phenotyped the major immune cell subsets that coalesce with fibrosis in both the L2-IL5OXA mice and in FS-EoE patients. We found that macrophage are required for matrisome and cytoskeletal remodeling. Importantly, we show that macrophage accumulation precedes esophageal fibrosis and provide a novel therapeutic target in FS-EoE as their depletion with anti-CSF1 attenuated reactive matrisome and cytoskeletal changes. Thus, macrophage-based treatments and the exploration of TNC and KRT16 as biomarkers may provide novel therapeutic options for patients with fibrostenosis.

Clinically significant portal hypertension in patients with primary biliary cholangitis: Clinicopathological features and prognostic value

Introduction and ObjectivesPrimary biliary cholangitis (PBC) may progress to clinically significant portal hypertension (CSPH) before the development of cirrhosis. This study aimed to investigate CSPH incidence as well as the clinicopathological characteristics and predictive value of these features for the prognosis of patients with PBC, especially at early histologic stage. Patients and MethodsPatients diagnosed with PBC between January 2013 and April 2022 were retrospectively enrolled. The prognostic value of baseline clinicopathological characteristics for long-term outcomes in PBC patients with CSPH was assessed using Kaplan–Meier survival analysis and COX regression analysis. ResultsAmong 280 patients with PBC, 104 underwent liver biopsy and 68 were at early histologic stage. CSPH was present in 47.2 % of participants with 20.6 % at early histologic stage. CSPH was a risk factor for predicting the liver transplant-free survival in PBC patients (hazard ratio [HR], 6.78; 95 % CI, 2.94–15.63), especially those at early stage. Perisinusoidal fibrosis and nodular regenerative hyperplasia (NRH) were common histopathological features in PBC patients with CSPH at the early stages. Fibrous septa formation in the hepatic lobules (HR, 4.85; 95 % CI, 1.51–15.52) and cholestasis (HR, 7.70; 95 % CI, 2.56–23.18) were independent predictors of adverse outcomes. ConclusionsCSPH indicates an increased risk of adverse outcomes in PBC patients, especially those in early histologic stage. Perisinusoidal fibrosis and NRH are valuable histological features of CSPH in patients with early-stage PBC. Identification of clinicopathological features and assessment of portal hypertension (especially at early stage), contribute to the development of personalized strategies.

BioFusionNet: Deep Learning-Based Survival Risk Stratification in ER+ Breast Cancer Through Multifeature and Multimodal Data Fusion.

Breast cancer is a significant health concern affecting millions of women worldwide. Accurate survival risk stratification plays a crucial role in guiding personalised treatment decisions and improving patient outcomes. Here we present BioFusionNet, a deep learning framework that fuses image-derived features with genetic and clinical data to obtain a holistic profile and achieve survival risk stratification of ER+ breast cancer patients. We employ multiple self-supervised feature extractors (DINO and MoCoV3) pretrained on histopathological patches to capture detailed image features. These features are then fused by a variational autoencoder and fed to a self-attention network generating patient-level features. A co-dual-cross-attention mechanism combines the histopathological features with genetic data, enabling the model to capture the interplay between them. Additionally, clinical data is incorporated using a feed-forward network, further enhancing predictive performance and achieving comprehensive multimodal feature integration. Furthermore, we introduce a weighted Cox loss function, specifically designed to handle imbalanced survival data, which is a common challenge. Our model achieves a mean concordance index of 0.77 and a time-dependent area under the curve of 0.84, outperforming state-of-the-art methods. It predicts risk (high versus low) with prognostic significance for overall survival in univariate analysis (HR=2.99, 95% CI: 1.88-4.78, p 0.005), and maintains independent significance in multivariate analysis incorporating standard clinicopathological variables (HR=2.91, 95% CI: 1.80-4.68, p 0.005).