Abstract:

Background/Objectives: Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is an autosomal recessive lysosomal storage disorder caused by deficiencies in enzymes required for heparan sulfate degradation. While primarily recognized for its devastating neurodegenerative course, the systemic extent of glycosaminoglycan (GAG) accumulation remains under-characterized. This study aims to provide a detailed multisystemic pathological mapping of MPS III to challenge the traditional "brain-only" disease paradigm and highlight the clinical relevance of extracerebral involvement. Methods: We present a comprehensive clinicopathological analysis of a 15-year-old female patient with a history of profound neuropsychomotor delay, refractory epilepsy, and spastic tetraplegia. Following her death due to terminal bronchopneumonia during palliative care, a complete forensic and pathological autopsy was conducted. Tissue samples from all major organ systems were processed using routine Hematoxylin-Eosin (HE) staining alongside specialized histochemical stains to identify intracellular storage products. Results: Macroscopic evaluation revealed significant diffuse cerebral atrophy, meningoencephalic edema, cardiac valvulopathy with compensatory myocardial remodeling, and hepatosplenomegaly. Furthermore, erosive gastrointestinal lesions and degenerative renal changes were identified. Histopathological examination confirmed widespread cytoplasmic vacuolization across diverse cell populations, including neurons, hepatocytes, renal tubular cells, and the reticuloendothelial system. These findings demonstrate that GAG deposition is a generalized process affecting nearly every parenchymal structure. Conclusions: Although neurological decline dominates the clinical phenotype, our findings underscore that MPS III is a true systemic storage disorder. Significant involvement of the cardiovascular and visceral systems contributes to the disease's complexity and mortality. This case reinforces the critical diagnostic value of a comprehensive autopsy in delineating the full morphological spectrum of Sanfilippo syndrome, providing essential insights for multidisciplinary management.

Abstract: Diffuse large B-cell lymphoma (DLBCL) is one of the most frequent lymphomas. This proof-of-concept study predicted the prognosis of DLBCL using hematoxylin and eosin (H&E) histological images, computer vision and deep learning. The series included 114 DLBCL cases, split into 2 prognostic groups according to the overall survival, and 44 reactive lymphoid tissue. The curve fitting and slope analysis showed a point of inflection at 2 years, which differentiated patients with aggressive clinical evolution (“Dead < 2 years”, b1 = -0.024), from the rest with moderate clinical evolution (“Others”, b1 = -0.003). Twenty different convolutional neural networks (CNNs) were used, and explainable artificial intelligence (XAI) was also applied. The final model based on DarkNet-19 predicted prognosis groups with high performance (test set accuracy = 96.3%). The other performance parameters were precision (94.5%), recall (95.0%), false positive rate (3.1%), specificity (96.9%), and F1 score (94.7%). XAI, including grad-CAM, occlusion sensitivity, and image-LIME, confirmed that the CNN focused on the correct areas. Hybrid partitioning to prevent information leakage with patient-based analysis, image classification between DLBCL and 44 cases of reactive lymphoid tissue, and hyperparameter tuning were also successfully performed. Correlation with the clinicopathological characteristics found that the Dead < 2 years group was correlated with stage III-IV, International Prognostic Index (IPI) High + High/intermediate, progressive disease, non-GCB cell-of-origin, CD10-, BCL2+, and Epstein-Barr virus (EBER)+. Analysis of the microenvironment, immune checkpoint, cell cycle, and germinal center markers showed that Dead < 2 years had higher IL10, PD-L1, and CD163, and lower E2F1 protein expressions. No differences were found for Ki67, CSF1R, CASP8, TNFAIP8, LMO2, MYC, MDM2, CDK6, and TP53 markers at quantitative level. In conclusion, the DLBCL overall survival can be predicted using H&E histological images and deep learning using 2 years point (similar to POD24). This trained CNN can be used as a pretrained model for transfer learning in the future.

Abstract: Background/Objectives: Critical limits represent quantitative thresholds of life-threatening diagnostic test results that require immediate clinician notification and may necessitate life-saving intervention to prevent adverse outcomes. Our goals are to report point-of-care critical limits for adults and newborns from a comprehensive U.S. national database, to identify POC instruments associated with the critical limits, and to support the harmonization of POCT practice. Methods: We gathered critical limit notification lists from 417 hospitals across all 50 states and Washington D.C., comprising university hospitals, trauma and heart centers, centers of excellence, community hospitals, and network hospitals. We extracted point-of-care critical limits, central laboratory critical limits (at hospitals with POC), adult international normalized ratio (INR) data, and instrument usage. Results: Low and high glucose critical limits (median values of 50 and 450 mg/dL, respectively) were the most frequently listed, reported by 73 hospitals (17.5%). Troponin was listed by ten hospitals, specified as troponin (n = 4), troponin I (n = 5), or “troponin TnI” (n = 1). Rarely, we encountered notification lists that assigned different critical limits to different instruments measuring the same analyte. Fifty-five hospitals did not specify instrument usage for any measurand on their notification list. The median differences in matched pairs of laboratory versus POC critical limits differed significantly (Wilcoxon signed-rank, P< 0.05) for low and high ionized calcium (N=21), low hemoglobin (N=23) and high INR critical limits for adults (N=27) and newborns (N=10). In some cases, matched pair analytes demonstrated identical critical limits. Conclusions: Harmonizing critical limit notification thresholds across point-of-care testing and different devices may improve consistency in clinical decision-making and patient outcomes. Despite the potential of POCT to shorten time to urgent intervention, relatively few hospitals currently include POCT critical limits on notification lists. Broader inclusion and transparent sharing of POCT critical values could harmonize practices across institutions, facilitate inter-institutional collaboration, and promote more timely and reliable responses to life-threatening diagnostic results.

Abstract: Vitamin B12 is an essential water-soluble vitamin required for critical biological processes such as DNA synthesis, erythrocyte maturation, and maintenance of nervous system integrity. Deficiency of vitamin B12 can lead to serious clinical outcomes, including megaloblastic anemia, and potentially irreversible neurological damage. Conversely, hypercobalaminemia may be associated with severe disorders, including solid neoplasms, hematological malignancies and, in some cases, may result from inappropriate supplementation or immunoglobulin–B12 macro-complexes. Although current guidelines recommend total serum vitamin B12 and holotranscobalamin (holoTC) as first-line biomarkers, total serum vitamin B12 remains the most widely used test in routine clinical practice. However, since holoTC represents the biologically active fraction of vitamin B12 available for receptor-mediated cellular uptake, it appears to provide a more reliable assessment of cobalamin status, particularly in specific clinical contexts. Compared with total vitamin B12 measurement, holoTC is assessed using a more limited number of analytical methods and the majority of available kit are aligned with the WHO reference standard, thereby improving inter-assay harmonization. This review explores literature data about the role of vitamin B12 and holoTC, discussing analytical challenges and clinical interpretation, highlights the potential advantages of holoTC over total serum B12.

Abstract: Although oral leukoplakia (OL) is recognized as a precancerous lesion, only a proportion of cases undergo malignant transformation (7,2 % to 9.5%). That's why recently, increasing attention has been directed toward molecular biomarkers that may better reflect the biological behaviour of OL Infiltration density of T and B lymphocytes, macrophages, plasma cells were assessed semi-quantitatively using a 4-point scale adapted from Nankivel study. CD9 antigen was assessed in epithelial and immune cells by counting them in three 400x fields. CD138 and CD68 biomarkers were associated with significantly elevated expression across both clinical types of OL where dysplasia was diagnosed. The increase in infiltration density with CD3 and CD20 labelled lymphocytes was statistically reliably confirmed only in non-homogeneous OL with dysplasia. CD9, as a protein reflecting the exosome compartments, revealed the interaction between the epithelium and immune cells. A moderate, statistically significant positive correlation was found only in leukoplakia with dysplasia between CD9+ immune cell levels and the number of epithelial layers expressing this antigen. Assessment of combinations of CD3, CD9, CD20, CD68, and CD138 biomarker expression, cons idering clinical type of leukoplakia, particularly non-homogeneous, appears to improve the accuracy of determining the risk of malignancy in individuals with oral dysplasia.

Abstract: Background and Objectives: Metaplastic breast carcinoma (MBC) is a rare, aggressive malignancy often resistant to conventional chemotherapy and characterized by a triple-negative phenotype. While immune checkpoint inhibition shows promise, the prognostic significance and distribution of programmed death-ligand 1 (PD-L1) expression within the heterogeneous architecture of MBC remain poorly understood. This study aimed to evaluate PD-L1 expression and the density of tumor-infiltrating lymphocytes (TILs) to clarify their roles in patient stratification and overall survival (OS). Materials and Methods: We retrospectively analyzed 48 MBC cases diagnosed between 2010 and 2025. PD-L1 expression was quantified using the Combined Positive Score (CPS) with the 22C3 antibody clone across diverse histological components. The density of stromal TILs density was assessed following internationally standardized guidelines. Clinical outcomes and clinicopathological parameters, including metastasis, lymphovascular invasion (LVI), and histological subtype were correlated with biomarker status using Kaplan-Meier survival analysis and Cox proportional hazards regression models. Results: PD-L1 positivity (CPS ≥1) was identified in 72.9/% of cases, one of the highest rates documented in literature. Notably, an inverse relationship was observed with PD-L1 negative tumors exhibited significantly higher rates of distant metastasis (46.2% vs. 17.1%; p=0.039). Multivariate analysis confirmed that low density of TILs (HR=9.66; p=0.016), metastasis (HR=4.40; p=0.023), and the presence of LVI (HR=3.84; p=0.047) were strong independent predictors of mortality. While PD-L1 status alone did not directly dictate overall survival, mean overall survival was markedly reduced in the low TILs cohort (32.2 months) compared to the high TILs group (114.2 months). Conclusion: The high prevalence of PD-L1 expression supports routine screening for immunotherapy eligibility in MBC. Our findings suggest that PD-L1 negative cases represent a high-risk biological subset driven by alternative immune evasion mechanisms. Integrating TILs density with conventional pathological parameters provides a more robust prognostic framework, enabling personalized therapeutic strategies for this challenging malignancy.

Abstract: Lipoblastomas are rare, rapidly growing benign tumors rising from embryonic white fatty cells that continue to proliferate in the postnatal period. We presented a case of a toddler with an undifferentiated myxoid neoplasm with features of a minimally differentiated lipoblastoma. Our patient was an 18-month-old female with a painless solid tumefaction in the middle third of the right leg. Histopathologically, the nodular tumor mass consisted of lipobastic cells embedded in a myxoid stroma. Immunohistochemistry showed strong diffuse positivity for vimentin, S100, CD34, CD56, NSE and rare Ki67+ cells. FOXO1 polyploidy was detected in 30% of cells by FISH. Using target RNA sequencing, we detected a fusion gene, CHCHD7-PLAG1, in the tumor sample. Sequence analysis showed that the first exons of CHCHD7 were fused to either exon 2 or exon 3 of PLAG1. Our case demonstrates that due to the histomorphologic overlaps, the molecular diagnostics is essential for confirmation of lipoblastomas.

Abstract: Background/Objectives: Conventional lymphatic invasion assessments may fail to identify lymph node metastasis (LNM) in breast cancer. We evaluated periarterial or perivenous invasion (periA/V), using Elastica–van Gieson (EVG)-stained sections, as a histological marker associated with LNM in invasive breast carcinoma of no special type (IBC-NST), focusing on the impact of invasive tumor size. Methods: We retrospectively analyzed 213 IBC-NST cases. PeriA/V was defined as tumor nests in direct contact with perivascular elastic fibers on EVG-stained sections. Diagnostic performance was compared with that of conventional LI markers (hematoxylin and eosin and D2-40), with stratified analyses by pathological T category (pT1 vs. pT2–4) and pT1 subcategories (pT1a, pT1b, and pT1c). Results: LNM was observed in 87 cases (40.8%). Overall, periA/V demonstrated high sensitivity (97.7%) and negative predictive value (NPV; 93.5%). In pT1 tumors (n = 130), periA/V achieved 100% sensitivity and 100% NPV (27/27), and was consistently present in all node-positive pT1b–c tumors. In multivariate analyses, periA/V remained independently associated with LNM in the pT1 group (odds ratio [OR]: 16.08, P = 0.003) and pT1c subgroup (OR: 14.7, P = 0.010). In pT2–4 tumors, periA/V became frequent regardless of nodal status, indicating reduced discriminatory value. Conclusions: EVG-based periA/V is a robust and highly sensitive surrogate marker for LNM in small IBC-NSTs. In pT1 tumors, periA/V negativity effectively ruled out nodal involvement. Incorporating periA/V assessment may provide a cost-effective and objective approach for nodal risk stratification in early-stage breast cancer.

Abstract: Objective: Primary extranodal lymphomas of the head and neck region relatively rare and represent a biologically distinct subset. The diagnosis and differential diagnosis of head and neck lymphomas are important and deserve special attention. The aim of the present study was to retrospectively evaluate patients diagnosed with primary head and neck lymphomas at the Department of Pathology between January 2020 and January 2026. Histopathological subtypes, localization, relative frequencies, overall survival were analyzed. Material and Method: This retrospective study included 31 cases diagnosed with lymphoma involving the head and neck region. Medical records were reviewed. Histopathological slides re-evaluated under light microscopy by experienced pathologists. All cases were classified according to the current World Health Organization (WHO) classification of tumors of haematopoietic and lymphoid tissues. An extensive immunohistochemical panel was applied. Statistical analyses were performed using SPSS statistical software. Results: The study group included 31 patients with head-and-neck lymphoma. The most common histological type was diffuse large B-cell lymphoma (DLBCL) (54.8%). Other histological subtypes included follicular lymphoma (FL), mantle cell lymphoma (MCL), extranodal natural killer/T-cell lymphoma (NKTCL), anaplastic large cell lymphoma (ALCL), and Hodgkin lymphoma (HL). Most common location was tonsil (38.7%). Other locations were nasopharynx, oral cavity, nasal cavity, salivary gland and thyroid. Epstein–Barr virus (EBV) positivity was detected in two patients (6.5%), and human immunodeficiency virus (HIV) infection was identified in two patients (6.5%). At the time of last follow-up, 27 patients (87.1%) were alive, whereas four patients (12,9%) had died. The mortality rate of 6.5%. The median overall survival was 28 months (95% CI: 10–45). Conclusions: Malignant lymphoma should be kept in mind when evaluating head and neck masses, and histopathological assessment of the affected tissue remains the cornerstone of diagnosis.

Abstract:

PTEN is a well-established tumor suppressor that plays a central role in the regulation of cell growth, metabolism, and survival. As a protein-lipid dual phosphatase, PTEN negatively regulates the PI3K/AKT signaling pathway, which in turn modulates autophagy, a conserved catabolic process that allows cells to degrade and recycle intracellular components, through the downstream effector mTORC1. While this represents the canonical mechanism by which PTEN influences autophagy, here we show that PTEN also regulates autophagy through an alternative, AKT-independent pathway. Specifically, through genetic manipulations of PTEN expression in thyroid cancer cells, we identify BECLIN-1 as a direct target of PTEN protein phosphatase activity. PTEN physically associates with BECLIN-1 under both basal and nutrient-deprived conditions, promoting its dephosphorylation at serine 295, thus relieving AKT inhibition resulting in autophagy activation. This regulatory event correlates with increased autophagic flux under starvation, as reflected by enhanced LC3 I to LC3 II conversion. Importantly, BECLIN-1 dephosphorylation is mediated by PTEN protein phosphatase activity and does not require its lipid phosphatase function. Furthermore, bioinformatic analyses reveal that high PTEN expression, together with enhanced autophagic activity (MAP1LC3B), is associated with improved clinical outcome in cancer patients. These findings uncover a direct, AKT-independent mechanism by which PTEN controls autophagy by modulating BECLIN-1 phosphorylation status. Together, our results provide novel insight into how PTEN coordinates cellular adaptation to metabolic stress and highlight an additional pathway through which PTEN regulates the autophagic machinery in cancer cells.

Abstract: Background and Clinical Significance: Plexiform fibromyxoma (PFM) is a rare benign gastric mesenchymal neoplasm characterized by multinodular plexiform growth of bland spindle cells in a myxoid or fibromyxoid stroma. We report a case of the cellular form of PFM with limited myxoid stroma and aberrant KIT expression, resulting in diagnostic difficulty by biopsy. Case presentation: A 59-year-old woman presented with a slowly enlarging 15-mm gastric antral submucosal tumor. A resected specimen by laparoscopic and endoscopic cooperative surgery revealed spindle cell proliferation forming plexiform nodules with a myxoid background in limited areas. Positive immunoreactivity of a subset of spindle cells for KIT suggested a diagnosis of gastrointestinal stromal tumor (GIST), although DOG1 was negative. In addition, diffuse staining for CD10, smooth muscle actin, and D2-40 were confusing. MALAT1::GLI1 fusion was detected by next-generation sequencing analysis. Consequently, a diagnosis of PFM was established. Conclusions: This case expands the morphologic and immunophenotypic spectrum of PFM and indicates the possible diagnostic utility and biological significance of D2-40 expression. Although molecular confirmation of MALAT1::GLI1 fusion is definitive for diagnosis of PFM, the findings of present case may aid diagnosis in challenging cases that mimic GIST.

Abstract: Background: Artificial intelligence (AI) shows promising results in lymphoma detection, prediction, and classification. However, translating these findings into practice requires a rigorous assessment of potential biases, clinical utility, and further validation of research models. Objective: The goal of this study was to summarize existing studies on artifi- cial intelligence models for the histopathological detection of lymphoma. Design: This study adhered to the PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines. A systematic search was conducted across three major databases (Scopus, PubMed, Web of Science) for English-language articles and reviews published between 2016 and 2025. Seven precise search queries were applied to identify relevant publications, accounting for variations in study modality, algorithmic architectures, and disease-specific terminology. Results: The search identified 615 records, of which 36 articles met the inclusion criteria. These studies presented 36 AI models, comprising 30 diagnostic and 6 prognostic applica- tions, with Convolutional Neural Networks (CNNs) being the predominant architecture. Regarding data sources, 83% (30/36) of datasets utilized Hematoxylin and Eosin (H&E) stained images, while the remainder relied on diverse modalities, including IHC stained slides, bone marrow smears, and other tissue preparations. Studies predominantly utilized retrospective, private cohorts with sample sizes typically ranging from 50 to 400 patients; only a minority leveraged open-access repositories (e.g., Kaggle, TCGA). The primary appli- cation was slide-level multi-class classification, distinguishing between specific lymphoma subtypes and non-neoplastic controls. Beyond diagnosis, a subset of studies explored advanced prognostic tasks, such as predicting chemotherapy response and disease progres- sion (e.g., in CLL), as well as automated biomarker quantification (c-MYC, BCL2, PD-L1). Reported diagnostic performance was generally high, with accuracy ranging from 60% to 100% (clustering around 90%) and AUC values spanning 0.70 to 0.99 (predominantly >0.90). Conclusions: While AI models demonstrate high diagnostic accuracy, their translation into practice is limited by unstandardized protocols, morphological complexity, and the "black box" nature of algorithms. Critical issues regarding data provenance, image noise, and lack of representativeness raise risks of systematic bias, hence the need for rigorous validation in diverse clinical environments.

Abstract: Mesonephric-like adenocarcinoma is a rare uterine neoplasm recognized in the fifth edition of the World Health Organization Classification of Female Genital Tumors and poses diagnostic challenges due to its morphologic and immunophenotypic overlap with other endometrial carcinomas. We retrospectively reviewed three cases diagnosed at our institution, evaluating clinical presentation, histologic features, immunohistochemical profile, and available molecular findings, and performed a literature review of approximately 200 reported cases with emphasis on comorbidities and potential predisposing factors. All three patients presented with abnormal uterine bleeding and had hypothyroidism, and one patient had Down syndrome, representing the first reported case in this population. Tumors consistently expressed thyroid transcription factor 1, showed variable GATA3 expression, and demonstrated limited or absent hormone receptor expression. Literature review revealed frequent association with Müllerian-type lesions and recurrent KRAS mutations, while thyroid disease was not identified as a consistent comorbidity. These findings support a Müllerian origin for mesonephric-like adenocarcinoma and suggest that hypothyroidism is unlikely to represent a defining association. The occurrence in a patient with Down syndrome raises the possibility of an underlying genetic susceptibility that warrants further investigation.

Abstract: Backgraund/Objectives: Transient receptor potential melastatin 7 (TRPM7), a unıque ion channel protein, has important effects for the proliferation of many cancer cell lines and tumor progression in various cancers. This study aimed to investigate whether TRPM7 expression has an effect on the prognosis of patients with colorectal cancer (CRC). Methods: TRPM7 expression was evaluated in paraffin-embedded tu-mor tissues of 259 CRC patients, immunohistochemically. In addition, the ratio of CD4+/CD8+ lymphocytes in the tumor microenvironment was determined semi-quantitatively. Results: According to our data, tumor size was clearly higher in cases with high TRPM7 expression than those with low expression. TRPM7 overex-pression was closely related to high depth of tumor invasion, increased lymph node metastasis and high distant metastasis rate. These findings exposed that high TRPM7 expression is effective in the progression and aggressiveness of CRC. While there was a negative correlation between TRPM7 overexpression and the density of CD8+ TILs, a positive correlation was revealed between TRPM7 expression and the CD4+/CD8+ TILs ratio. This result aroused curiosity for further studies on what kind of connection is between the TRPM7 channel protein and TILs. Also, high TRPM7 expression was closely associated with low overall (OS) and disease-free survival (DFS) times. Fur-thermore, multivariate analyses revealed TRPM7 overexpression was independently related with short OS and DFS. Conclusions: In conclusion, the high TRPM7 expres-sion and CD4+/CD8+ TILs ratio are independent poor prognostic indicators in CRC. In the future, TRPM7 may be a promising biomolecule for new targeted treatment options for CRC.

Abstract: The dichotomous outcomes of chronic lung inflammation, represented by either pulmonary emphysema or interstitial fibrosis, involve poorly understood overlapping mechanisms. Recent insights from network theory suggest that percolation phenomena, coupled with the dynamics of extracellular matrix crosslinking, play an important role in determining these divergent pathological trajectories. This review examines how critical percolation thresholds at which local damage or repair transitions to system-wide structural failure or rigidification determine the changes in lung tissue during chronic inflammation. We examine the mechanisms of collagen and elastin crosslinking, the feedback loops that amplify initial perturbations, and the threshold behaviors that push inflamed lung tissue toward either emphysematous destruction or fibrotic consolidation. Understanding these percolation-dependent transitions provides new insights into why similar inflammatory insults can produce opposite structural outcomes and suggests novel therapeutic strategies targeting the crosslinking mechanisms that underlie these critical transitions.

Abstract: Cutaneous melanoma is one of the most aggressive skin cancers known. Over the years, multiple studies have focused on researching novel treatment options. For this purpose, numerous areas have been analyzed, and the focus has shifted toward the mechanisms by which immune-modulating molecules act within the microenviron-ment. Among these, ATP-binding cassette transporters and stem-associated pathways have been shown to influence drug response and immune escape. ABCB5 is a gene with multiple isoforms that significantly influences the immune response. In melano-ma, the ABCB5α isoform is predominantly expressed, primarily in tumor stem-like cells. Thus, it can alter the effects of medications by promoting chemoresistance via ac-tive drug efflux. The gene also regulates pathways PI3K/Akt, BCL-2, and miR-145, leading to overexpression. ABCB5 positive cells create an immunosuppressive micro-environment via cytokines (IL-8, IL-6, TGF-β) and death ligands (PD-L1), favoring tumor progression, thus correlating with poor prognosis. This review integrates cur-rent data on the molecular and microenvironmental mechanisms, underlying mela-noma progression and therapy resistance, highlighting ABCB5 as one of the several emerging biomarkers with potential prognostic and therapeutic relevance.

Abstract: Small molecules either derived from cell metabolic reactions or produced by gut bacterial flora have shown the potential of affecting gene expression, which suggests the possibility of interactions able to modulate cellular functions. In this context, the reported experi-ments were aimed at verifying a possible interplay between lactate and butyrate in modu-lating the efficacy of antineoplastic drugs. Butyrate is a product of gut bacterial flora, shown to be endowed with anticancer properties; conversely, increased lactate levels in cancer cells were found to be associated with higher proliferation and drug resistance. For the reported experiments, we adopted two cell cultures from clinically relevant, but dif-ferent cancer forms: pancreatic and triple-negative mammary adenocarcinomas. In spite of their different tissue origin, the two cell cultures appeared to similarly respond to the effects of the two metabolites, which were found to modulate in opposite ways the expres-sion of key genes involved in DNA repair by homologous recombination. As a conse-quence, changed efficacy of this repair pathway and modified response to PARP inhibi-tors were observed. Notably, our results also suggest that the counteracting effect between these two metabolites may be leveraged to address additional challenges limiting the suc-cess of anticancer therapies.

Abstract: Thrombocytopenia is a frequent complication of patients presenting emergently across the world for a wide array of etiologies. From patients who develop thrombocytopenia due to invasive neoplastic disease affecting the bone marrow to patients who developed immune-complications secondary to formation of auto-antibody responses that drive patients’ platelets counts lower or even infection, stress the clearest need of prompt tests to discern the more likely thrombocytopenic-inducing cause. It is in this setting that looking at other platelet variables easily obtainable from modern hematology analyzers have gained traction. One of these elements found in extended platelet profiles are immature platelets (youngest and newly released platelets) also known as reticulated platelets depending upon the platform performing the measurement. Among the advantages of obtaining these counts is that it represents the immediate responses by the bone marrow to the thrombocytopenia and depending on etiology inducing the thrombocytopenia it also provides information of the marrow response to therapeutic approaches. It is in this context that this review will present information of how these relatively novel platelet parameters can be used in clinical practice and how they can be a rapid gauge of the body’s response to disease processes leading to thrombocytopenia. Thrombocytopenias resulting from infection (sepsis), autoantibody formation (immune thrombocytopenia and immune-mediated thrombotic thrombocytopenic purpura), immune dysregulation (systemic lupus erythematosus), and iatrogenic (drug-induced) will be discussed and be used to explain how these young platelet measurements can provide valuable clinical information.

Abstract: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating multi-system illness with heterogeneity that complicates identifying the pathophysiology, biomarkers, and therapeutic targets. Evidence indicates the importance of immune dysregulation, including the complement system, in ME/CFS. This study investigates the contribution of genetic drivers to potential dysregulation of the complement pathway in ME/CFS. We used protein quantitative trait loci (pQTL) analyses, adjusted for covariates using linear and logistic regression, to identify genetic variants significantly associated with plasma complement protein levels in a study sample identified from the general population (50 ME/CFS and 121 non-fatigued). ME/CFS patients carrying certain pQTLs exhibited dysregulation of the alternative complement pathway, which defined an inflammatory subgroup with a high C3/low Bb profile and established a genetic link to dysregulation of the alternative complement pathway. Six of the significant pQTLs were also found associated with fatigue-related phenotypes in the UK biobank, 4 of which were complement-associated, providing some validation in an independent population. Our findings highlight a mechanism by which risk alleles contribute to ME/CFS heterogeneity, providing evidence of a genetic basis for complement dysregulation in a subgroup. This approach could identify pathway-focused subgroups in ME/CFS and similar illnesses to inform personalized approaches to diagnosis and treatments.

Abstract: Background: Mammary ductal hyperplasia represents a spectrum of benign proliferative breast lesions, some of which pose elevated risks for malignant transformation into ductal carcinoma in situ and invasive breast cancer. This narrative review explores why only specific types, particularly those with atypia, exhibit higher progression potential, synthesizing epidemiologic, histopathologic, molecular, and environmental insights. Methods: We reviewed key literature from databases, including PubMed, focusing on classification, risk stratification, genetic/epigenetic mechanisms, tumor microenvironment dynamics, and modifiable factors influencing progression. Results: Benign breast lesions are categorized into non-proliferative, proliferative without atypia, and proliferative with atypia, such as atypical ductal hyperplasia and atypical lobular hyperplasia. Atypia represents a morpho-logic continuum toward low-grade ductal carcinoma in situ, driven by genetic alterations, epigenetic reprogramming, and changes in the tumor microenvironment, including stromal remodeling, immune infiltration, hypoxia-induced angiogenesis, and extracellular matrix degradation. Dietary factors, such as high-fat intake and obesity, exacerbate progression through inflammation, insulin resistance, and adipokine imbalance, while environmental toxins, including endocrine disruptors, pesticides, and ionizing radiation, amplify genomic instability. Conclusions: Understanding differential risks and mechanisms underscores the need for stratified surveillance, biomarker-driven interventions, and lifestyle modifications to mitigate progression. Future research should prioritize molecular profiling for personalized prevention in high-risk hyperplasia.