Andreea Raluca Cozac-Szőke

The interaction between tumor cells and the host immune response plays a key role in the advancement of colorectal adenocarcinoma. The Klintrup–Mäkinen (KM) score represents a simple and efficient histological method for evaluating the inflammatory reaction at the invasive tumor front, but its relationship with specific T-cell populations remains incompletely defined. This study aimed to investigate the association between the KM score and T-cell infiltration, assessed by CD3, CD4, and CD8 immunohistochemical markers, as well as its correlation with clinicopathological parameters. A total of 150 patients diagnosed with colorectal adenocarcinoma between 2022 and 2025 were included. Cases were stratified into low KM (scores 0–1) and high KM (scores 2–3) groups. Immunohistochemical staining for CD3, CD4, and CD8 was performed and evaluated at the invasive front. Associations between KM score, immunohistochemical markers, and clinicopathological variables were analyzed using the chi-square or Fisher’s exact test, while age was assessed using the Mann–Whitney U test. High KM scores were significantly associated with increased expression of CD3 (p < 0.001), CD4 (p = 0.032), and particularly CD8 (p < 0.001). Low KM scores were more frequently associated with lymph node metastasis (p < 0.001) and poor tumor differentiation (p = 0.010). No significant differences were observed in relation to age, gender, pT stage, lymphovascular invasion, perineural invasion, tumor budding, necrosis, or distant metastasis. CD8 expression was significantly associated with lymph node status (p = 0.021), but not with other markers of tumor aggressiveness. The KM score correlates with the density of T lymphocytes at the invasive front, particularly CD8-positive cells, and is associated with relevant pathological features such as lymph node metastasis and tumor differentiation. These findings support its role as a simple histological indicator of the tumor immune microenvironment in colorectal adenocarcinoma.

Background/Objectives: Metatypical basal cell carcinoma (MTBCC) is a rare and aggressive variant of non-melanoma skin cancer (NMSC) characterised by overlapping histological features of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Owing to its increased propensity for local invasion, recurrence, and metastasis, MTBCC poses diagnostic and therapeutic challenges. This study aimed to characterise the epidemiological, histopathological, and clinical features of MTBCC and to evaluate temporal changes in tumour characteristics and aggressiveness before, during, and after the COVID-19 pandemic. Methods: A retrospective cohort study was conducted on 129 histologically confirmed MTBCC lesions diagnosed in the Pathology Department of the Mures Clinical County Hospital, Targu Mures, Romania, between January 2017 and December 2025. Demographic data, tumour location, histological subtypes, differentiation of the squamous component, aggressiveness parameters, and volumetric measurements of tumours and excision specimens were analysed. Volumetric analyses were restricted to cases with complete three-dimensional measurements. Statistical comparisons were performed across demographic variables and the following three time periods: pre-pandemic, pandemic, and post-pandemic. Results: The median age at diagnosis was 71 years, with a slight male predominance (p = 0.25) and a significant predominance of patients from urban areas (p < 0.001). Most tumours were located in the head and neck region. Mixed-type MTBCC was significantly associated with higher tumour aggressiveness (p = 0.0019) and with high-risk histological subtypes, particularly micronodular and adenoid–cystic variants. Tumour volume showed a significant inverse correlation with year of diagnosis (p = 0.0139; r = (−) 0.50), whereas excision specimen volume differed significantly according to year of diagnosis (p = 0.0425). Neither tumour volume nor excision specimen volume was associated with histopathological aggressiveness. Conclusions: Metatypical basal cell carcinoma is a rare skin malignancy in which biological behaviour appears to be determined primarily by histopathological architecture rather than tumour size. Mixed-type lesions were associated with significantly higher aggressiveness, underscoring the need for accurate histopathological assessment. These findings support a pathology-driven approach to management and emphasise the importance of adequate surgical treatment and long-term follow-up in patients with MTBCC.

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer (NMSC) and represents the leading cause of NMSC-related deaths. Despite its growing global burden, comprehensive epidemiological and clinicopathological data from Easter Europe remains limited. This study aimed to evaluate the epidemiological, clinical, histopathological, and surgical characteristics of cSCC diagnosed before, during and after the COVID-19 pandemic. Methods: We conducted a retrospective, descriptive observational study including 332 lesions diagnosed between January 2017 and December 2025 at the Clinical Pathology Department of the Mureș Clinical County Hospital. Demographic, epidemiological, topographic, histopathologic, surgical, and volumetric parameters were analyzed. Tumours were stratified into low-, high-, and very-high-risk categories according to the National Comprehensive Cancer Network (NCCN) criteria. Results: The cohort demonstrated a significant male predominance (n = 193 vs. n = 139; p = 0.0355), with females presenting a higher median age (77 vs. 75; p = 0.0489). Lesions were predominantly located in the head and neck region (n = 216; p < 0.0001), which was significantly associated with very-high-risk tumours (p = 0.0051). Low-risk tumours accounted for 62.35% of cases, while high-risk and very-high-risk lesions comprised 19.88% and 17.77%, respectively (p < 0.0001). Ulcerations were strongly associated with very-high-risk tumours (p < 0.0001). Poor differentiation was more frequent outside the head and neck region (p < 0.0001) and varied significantly across the pandemic periods (p = 0.0349). Tumoral and excision volumes were higher in very-high-risk (p = 0.0070; p = 0.0004) and ulcerated tumours (p < 0.001), with a peak in volume during the COVID-19 period (p < 0.0001). A decrease through the years of diagnosis was observed in tumoral volumes (r = −0.2295; p < 0.0001) and patients showed a weak positive correlation with diagnosis year (r = +0.13; p = 0.019). Conclusions: The study provides an epidemiological and clinicopathological characterization of cSCC within one of the largest Romanian cohorts to date. Tumour aggressiveness was primarily driven by histopathological and topographical features rather than demographic factors. While the COVID-19 pandemic did not induce persistent changes in tumour risk profiles or surgical outcomes, it influenced diagnosis timing and tumour burden. These findings highlight the importance of incorporating temporal and emerging systemic factors, such as pandemics, and infectious events, into future epidemiological models to improve preparedness, early detection, future treatment schemes, and risk stratification in cSCC.

Background: Persistent cardiovascular and multisystem manifestations remain an important concern following hospitalization for coronavirus disease 2019 (COVID-19). However, the spectrum of newly identified conditions during follow-up and their relationship with acute disease severity remain incompletely characterized. This study aimed to describe cardiovascular and multisystem diagnoses, identified during short-term and long-term follow-up and to evaluate the association between acute-phase clinical characteristics, biomarkers, and subsequent outcomes. Methods: We conducted a retrospective observational cohort study including 762 adults hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection between January 2021 and December 2022. Follow-up data were obtained from patients who re-presented to the same hospital during short-term follow-up (mean 4.33 months; n = 130) or long-term follow-up (mean 2.06 years; n = 186). Newly documented cardiovascular and non-cardiovascular diagnoses recorded during routine clinical care were analyzed separately for each follow-up cohort. Multivariable logistic regression was used to identify predictors of in-hospital mortality and cardiovascular outcomes. Results: At least one newly documented diagnosis was identified in 120/130 patients (92.3%) during short-term follow-up and in 175/186 patients (94.1%) during long-term follow-up. Cardiovascular diagnoses were identified in 32.3% and 45.2% of patients attending short-term and long-term follow-up, respectively. Hypertension and atherosclerosis were the most frequent cardiovascular diagnoses during short-term follow-up, whereas heart failure and ischemic heart disease predominated among patients attending long-term follow-up. Pulmonary fibrosis was the most common non-cardiovascular diagnosis at both follow-up periods. Elevated D-dimer and fibrinogen levels during acute COVID-19 were independently associated with in-hospital mortality, whereas acute-phase NT-proBNP was not independently associated with cardiovascular diagnoses identified during follow-up. Conclusions: Patients who re-presented for clinical evaluation after hospitalization for COVID-19 exhibited a substantial burden of newly documented cardiovascular and multisystem diagnoses. Given the retrospective design, independent follow-up cohorts, and absence of a non-COVID control group, these findings should be interpreted as observational post-hospitalization data rather than evidence of causal or progressive post-COVID-19 disease. Prospective controlled longitudinal studies are needed to better define the long-term health consequences of SARS-CoV-2 infection.

Inflammatory skin diseases are characterized by complex interactions between immune pathways, epidermal barrier function, and environmental triggers, leading to distinct clinical and histopathological features. This narrative review aims to integrate current knowledge on the cutaneous immune microenvironment across major inflammatory skin diseases, including atopic dermatitis, psoriasis, hidradenitis suppurativa, and vitiligo. A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus, focusing on studies published between 2021 and early 2026. The findings highlight disease-specific immune signatures, such as Th2-driven inflammation in atopic dermatitis, IL-23/Th17 axis activation in psoriasis, neutrophil-dominated responses in hidradenitis suppurativa, and cytotoxic T-cell-mediated melanocyte destruction in vitiligo. These molecular pathways are closely reflected in histopathological patterns, emphasizing the link between morphology and immunopathogenesis. Advances in targeted therapies, including biologics and Janus kinase inhibitors, demonstrate the clinical relevance of these pathways and support a transition toward mechanism-based treatment strategies. Dermatopathology is increasingly contributing to precision medicine approaches by supporting correlations between tissue features, immune pathways, and potential therapeutic targets. This review provides a framework for improved disease stratification and for the development of personalized treatment strategies in inflammatory skin diseases.

Background/Objectives: Tuberculosis and COVID-19 are two major infectious diseases with significant inflammatory and immunological impact on infected hosts and both conditions are independently associated with a prothrombotic state. However, evidence regarding their combined effect on in-hospital thrombotic risk remains limited. In this study, we aimed to explore whether patients with tuberculosis and COVID-19 coinfection are at a higher risk of developing thrombotic events during hospitalization than patients diagnosed with tuberculosis alone. Materials and Methods: We performed a retrospective, single-center cohort study, including adults hospitalized at the Pulmonology Clinic, Adult Tuberculosis ward of Mures County Clinical Hospital, between 2021 and 2023. Two groups were analyzed: patients with pulmonary tuberculosis who developed COVID-19 during hospitalization (n = 40) and patients with pulmonary tuberculosis without documented SARS-CoV-2 infection (n = 40). Demographic, clinical, laboratory, and imaging data were extracted from medical records. Padua and IMPROVE-DD scores were calculated retrospectively, a rapid mini-score was evaluated exploratorily. Comparisons between groups were performed using appropriate statistical tests and unadjusted odds ratios (ORs) with 95% confidence intervals (CIs) were reported. Given the limited number of events, an age-adjusted Firth penalized logistic regression model was used for multivariable analysis. Results: Thrombotic events occurred more frequently in the tuberculosis and COVID-19 co-infection group (22.5% vs. 10%), although statistical significance was not reached (p = 0.22; OR = 2.61). Patients with coinfection had significantly higher proportions of elevated Padua scores (55% vs. 20%, p = 0.002; OR = 4.88), while IMPROVE-DD showed values near the conventional threshold for statistical significance (37.5% vs. 17.5%, p = 0.07). D-dimer values did not reach statistical significance (p = 0.07) and platelet counts were significantly higher in patients with tuberculosis only (p = 0.001). Mortality did not differ significantly between groups (15% vs. 10%, p = 0.73). In age-adjusted multivariable analysis, tuberculosis and COVID-19 coinfection remained associated with higher odds of thrombotic events, with wide confidence intervals. Conclusions: Patients with concomitant tuberculosis and COVID-19 showed a higher thrombotic risk profile (Padua score) and numerically higher rates of in-hospital thrombotic events, without reaching statistical significance. Findings should be interpreted as exploratory and hypothesis-generating. Larger prospective studies with systematic imaging and multivariable adjustment are needed.

Background/Objectives: Colorectal cancer (CRC) shows significant molecular diversity influenced by tumor location. Right- and left-sided CRCs differ in terms of microsatellite instability (MSI), mutational burden, and actionable biomarkers. This study aimed to characterize the clinicopathological and molecular features of CRC stratified upon tumor location. Methods: A consecutive series of CRC cases was retrospectively analyzed. Tissue samples were obtained from primary tumors (71%) or metastatic lesions (29%). All cases were evaluated by histopathology, immunohistochemistry (IHC), and targeted next-generation sequencing (NGS). Tumor location was assigned based on the primary tumor (43 right-sided and 35 left-sided cases). Results: Right-sided CRCs were more frequent in older patients and females and showed higher rates of deficient MMR (42% vs. 17%, p = 0.02), MSI-H (39% vs. 14%, p = 0.02), and high tumor mutational burden (TMB-high, ≥10 Mutations/Mb, 56% vs. 28%, p = 0.02). The most frequent pathogenic class 5 mutations were TP53 (65%), APC (49%), and KRAS (44%). APC was the most frequently mutated gene in both pathogenic (class 5) and likely pathogenic (class 4) categories, with class 5 variants more common in left-sided tumors and class 4 variants predominating in right-sided tumors. BRAF mutations showed a statistically significant trend toward higher frequency in right-sided tumors (p = 0.05). HER2/neu overexpression (3+) was seen in 15% of patients, exclusively in MSS left-sided tumors. PD-L1 expression (CPS ≥ 1) was detected in 20% of patients, irrespective of location, and pan-TRK IHC was negative in all cases. The 29% of samples derived from metastatic lesions were predominantly MSS/pMMR (87%). Conclusions: Tumor location in CRC correlates with distinct molecular patterns. Right-sided tumors are associated with dMMR, MSI-H, and higher TMB, while left-sided CRCs display more ERBB2 alterations and class 5 APC mutations. The results highlight the importance of integrating tumor location into personalized molecular diagnostics and therapeutic planning for CRC patients.

Cutaneous melanoma is one of the most aggressive skin cancers. Over the years, multiple studies have focused on identifying novel treatment strategies, with increasing attention directed toward immune-modulating mechanisms within the tumor microenvironment. 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 melanoma, the ABCB5α isoform is predominantly expressed, particularly in tumor stem-like cells where it promotes chemoresistance through active drug efflux. ABCB5 has also been linked to the regulation of PI3K/Akt, BCL-2, and miR-145-associated pathways. Moreover, ABCB5-positive cells contribute to the formation of an immunosuppressive microenvironment by secreting cytokines (IL-6, IL-8, TGF-β) and expressing immune checkpoint ligands, such as PD-L1, thereby favoring tumor progression and a poor prognosis. This review integrates current data on the molecular and microenvironmental mechanisms underlying melanoma progression and therapy resistance, and positions ABCB5 within the broader landscape of melanoma resistance mechanisms, emphasizing both its potential and its current limitations as a biomarker and therapeutic target.

Although the SARS-CoV-2 pandemic no longer poses a global emergency, the virus continues to diversify and acquire immunoevasive properties. Understanding the molecular pathways that shape SARS-CoV-2 pathogenesis has become essential. In this paper, we summarize the most recent current evidence on how the spike protein structurally evolves, on changes in key non-structural proteins, such as nsp14, and on host factors, such as TMPRSS2 and neuropilin-1. These changes, together, shape viral entry, replication fidelity and interferon antagonism. Given the emerging Omicron variants of SARS-CoV-2, recent articles in the literature, cryo-EM analyses, and artificial intelligence-assisted mutational modeling were analyzed to infer and contextualize mutation-driven mechanisms. It is through these changes that the virus adapts and evolves, such as optimizing angiotensin-converting enzyme binding, modifying antigenic surfaces, and accumulating mutations that affect CD8⁺ T-cell recognition. Multi-omics data studies further support SARS-CoV-2 pathogenesis through convergent evidence linking viral adaptation to host immune and metabolic reprogramming, as occurs in myocarditis, liver injury, and acute kidney injury. By integrating proteomic, transcriptomic, and structural findings, this work presents how the virus persists and dictates disease severity through interferon antagonism (ORF6, ORF9b, and nsp1), adaptive immune evasion, and metabolic rewiring. All these insights underscore the need for next-generation interventions that provide a multidimensional framework for understanding the evolution of SARS-CoV-2 and guiding future antiviral strategies.

Cutaneous leiomyosarcoma is a rare, malignant tumor that arises from smooth muscle cells, accounting for less than 3% of all cutaneous sarcomas. Our case report details a 63-year-old male patient who presented with a rapidly growing, painful nodule in the popliteal region. The patient underwent initial surgical excision in September 2021, followed by three subsequent resections until March 2022 due to local recurrence. Histopathological analysis of all specimens revealed a dermal neoplasm composed of spindle cells arranged in intersecting fascicles with storiform patterns. The immunohistochemistry profile showed strong positivity for the markers SMA and desmin, confirming the diagnosis. Despite early interventions, the deep surgical margins were positive, and further surgeries were required until tumor-free margins were achieved. This case emphasizes the morphological characteristics, clinical behavior, and therapeutic challenges in managing cutaneous leiomyosarcoma. A favorable prognosis is achieved with long-term follow-up and a multidisciplinary approach.