Background/Objectives: Immunotherapy has improved outcomes for selected patients with advanced non-small-cell lung cancer (NSCLC), yet the predictive value of individual biomarkers such as PD-L1 remains limited. Systemic inflammatory indices derived from routine blood tests may complement molecular and immunohistochemical features, offering a broader view of host–tumor immunobiology. Methods: We conducted a retrospective study of 298 patients with stage IIIB–IV NSCLC treated with immune checkpoint inhibitors (ICIs) at a tertiary oncology center between 2022 and 2024. Baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune–inflammation index (SII) were collected alongside PD-L1 expression and molecular alterations (EGFR, KRAS, ALK, TP53). Patients were stratified into inflammatory–molecular clusters integrating these parameters. Associations with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated using Kaplan–Meier and multivariate Cox analyses. Results: Four distinct inflammatory–molecular clusters demonstrated significantly different outcomes (p < 0.001). Patients with low NLR and high PD-L1 expression (Cluster A) showed the highest ORR (41%), longest median PFS (13.0 months), and OS (22.5 months). The EGFR/ALK-driven, inflammation-dominant cluster (Cluster C) exhibited poor response (ORR 7%) and shortest survival (PFS 4.3 months). High NLR (HR 2.12), PD-L1 < 1% (HR 1.91), and EGFR mutation (HR 2.36) independently predicted shorter PFS. A combined model incorporating NLR, PD-L1, and molecular status outperformed individual biomarkers (AUC 0.82). Conclusions: Integrating systemic inflammatory indices with PD-L1 expression and molecular alterations identifies clinically meaningful NSCLC subgroups with distinct immunotherapy outcomes. This multidimensional approach improves prediction of ICI response and may enhance real-world patient stratification, particularly in settings with limited access to extended molecular profiling.

Background: Non-small-cell lung cancer (NSCLC) is often diagnosed at stage IV, when prognosis depends on metastatic spread. The impact of histopathology on the first metastatic site remains underexplored. Methods: We retrospectively analyzed 364 patients with stage IV NSCLC diagnosed at OncoHelp Medical Center, Timișoara, Romania (2020–2024). All underwent baseline CT chest–abdomen–pelvis, whole-body FDG PET-CT, and brain MRI within seven days of histological confirmation. Patients were stratified into adenocarcinoma (n = 164), squamous cell carcinoma (n = 112), and large-cell carcinoma (n = 88). The first metastatic site was defined as the earliest confirmed location. Associations were evaluated using Fisher’s exact test and multinomial logistic regression. Results: Histology was associated with the first metastatic site (global p = 0.013). Adenocarcinoma was more likely than squamous carcinoma to present with brain metastases (RRR 3.74, 95% CI 1.48–9.45; p = 0.005; p_FDR = 0.053) and showed directional signals toward bone and adrenal involvement. Squamous carcinoma more frequently spread to the pleura as the first site (adjusted p = 0.008). Large-cell carcinoma showed no consistent differences compared to squamous carcinoma. In adenocarcinoma subgroups, EGFR-mutant tumors most often metastasized to the brain (55.6%), KRAS-mutant tumors to the liver (44.4%), and ALK-rearranged tumors to bone (100%). Conclusions: The first metastatic site in NSCLC follows histology-specific patterns, with adenocarcinoma favoring hematogenous spread and squamous carcinoma showing locoregional involvement. Molecular status further refines these patterns in adenocarcinoma. Incorporating histology into baseline staging may improve diagnostic efficiency and prognostic accuracy.

Background and Objectives: Systemic inflammatory markers from an ordinary complete blood count (CBC) may foreshadow where non-small-cell lung cancer (NSCLC) will first spread, but organ-specific signatures remain poorly defined. Materials and Methods: We retrospectively reviewed 302 adults (mean age 60.7 ± 13.4 years; 80.8% men) with stage IV NSCLC managed at OncoHelp Medical Center, Timișoara, between January 2022 and December 2024. Eligibility demanded a single radiologically confirmed distant site at diagnosis and pre-treatment CBC. Neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and lymphocyte-to-monocyte (LMR) ratios were compared across pleural (n = 52), bone (n = 86), liver (n = 66), and brain (n = 98) metastases using Kruskal–Wallis tests with Bonferroni adjustment; z-standardized logistic models identified independent predictors. Results: Metastases clustered most often in brain (32.5%), followed by bone (28.5%), liver (21.9%), and pleura (17.2%). Median PLR rose selectively in pleural disease (274 vs. 217–253 in other sites; p = 0.006). LMR fell to 2.0 in bone but climbed to 2.8 in brain lesions (p = 0.032 and 0.008, respectively). NLR was globally elevated (6.7–7.6), yet differed significantly only for bone and liver deposits. Logistic modeling showed that each standard-deviation rise in absolute neutrophil count quadrupled the odds of hepatic involvement (Odd Ratio (OR) 4.26; 99% Confidence inerval (CI) 2.20–6.25), monocytosis nearly doubled bone risk (OR 1.83; 1.01–3.33), while higher erythrocytes, eosinophils, and lymphocytes independently protected against pleural seeding (all p < 0.01). Age-stratified analysis revealed that osseous and cerebral metastases predominated in patients ≤ 50 years, whereas inflammatory indices were age-invariant. Conclusions: Routine CBC ratios encode distinct “inflammatory fingerprints” that mirror the first metastatic destination in NSCLC: platelets herald pleural spread, neutrophils favor liver and bone, and divergent lymphocyte–monocyte balances separate bone from brain. Although no substitute for cross-sectional imaging, these low-cost markers could refine clinical suspicion, guide targeted work-up, and illuminate the biology of organ-selective dissemination, particularly in resource-limited settings.

Background/Objectives: The fundamental classification based on white, brown, pink, and beige adipose tissue morphology together with fat vacuole content released into the tumor microenvironment incompletely defines breast cancer-associated adipose tissue (BCAAT) heterogeneity and does not sufficiently explain its controversial impact on invasion, recurrence, or survival in breast cancer (BC). We aim to expand BCAAT characterization by systematically evaluating stromal cellular elements within peritumoral adipose tissue, including CD34-positive fibroblasts, smooth muscle actin (SMA)-positive myofibroblasts, inflammatory cells, and microvascular structures to define distinct BCAAT subgroups. Methods: CD34 and smooth muscle actin (SMA) double immunohistochemistry was performed on 109 BC tissue specimens from patients aged 35 to 79 years old, followed by microscopic evaluation of cellular and vascular components inside peritumor adipose tissue. Microscopic findings were then correlated to age, body mass index (BMI), lymphovascular (LVI) and perineural invasion (PnI), recurrence (R), and tertiary lymphoid structures (TLSs). Results: Four BCAAT subtypes have been identified as fibroblast-rich (F^Rich_BCAAT), myofibroblast-rich (MyoF^Rich_BCAAT), vascular-rich (V^Rich_BCAAT), and mixed-vascular and inflammatory-rich (VI^Rich_BCAAT). The F^Rich_BCAAT subtype predominates for the age subgroup 35 to 49 years old and is a significantly worse prognostic factor for survival (p = 0.022). For the age subgroup of 50 to 69 years old, the VI^Rich_BCAAT subtype significantly influences PnI (p = 0.05) but not survival (Log-rank test, z = 0.57, p = 0.57). V^Rich_BCAAT was significantly impactful for BC patient survival aged 70 to 75 years old (p = 0.043). BMI did not correlate with any of the BCAAT subtypes but was strongly correlated with prognostic markers for each BCAAT subtype. Conclusions: Based on immunohistochemically detected cellular and vascular components, four microscopic BCAAT subtypes were identified. Three of four BCCAT subtypes specifically affect BC patient prognosis and survival depending on age.

Background/Objectives: Acinic cell carcinoma (ACC) is a rare lung neoplasm that can affect both children and adults as a parenchymal or endobronchial mass. It is histologically similar to this kind of tumor described in salivary glands, but with a different immunophenotype. In general, it poses a reduced degree of malignancy, with indolent growth and a favorable prognosis, with exceptionally rare cases associated with recurring disease or lymph node metastases. Methods: When clinicians are facing puzzling symptomatology in their patients, the main role of the multidisciplinary team in their review of oncological cases is to recommend imagistic-guided biopsies. Tissues samples were routinely processed, stained with hematoxylin-eosin (HE) and periodic acid–Schiff (PAS), and submitted to complementary immunohistochemistry tests. Results: Histopathological reports were consistent for lung ACC with regional lymph node involvement and remote metastases. Oncological therapies followed. Conclusions: Postponements of the presentation to the doctor at the onset of symptoms, as well as a lack of periodic health control for people insured by national health insurance companies, often lead to medical, human and financial complications that are difficult to manage. The pathologist involved in the discussion of oncological cases brings his expertise in solving cases, certifying the evolution of tumors considered less aggressive, such as in the case of lung ACCs.

Background: Medullary thyroid carcinoma (MTC) is a rare but aggressive neuroendocrine thyroid malignancy in which early diagnosis is essential for improving clinical outcomes. Although calcitonin (CT) remains the standard diagnostic biomarker, its interpretation may be limited by false-positive elevations, assay variability, and indeterminate cut-off values. Consequently, alternative biomarkers such as procalcitonin (PCT), circulating microRNA-375 (miR-375), and fine-needle aspiration washout calcitonin (FNA-CT) have gained increasing interest. Methods: A systematic review and diagnostic meta-analysis were conducted to evaluate the diagnostic performance of circulating and tissue-related biomarkers for MTC. Eligible studies reporting sufficient diagnostic accuracy data were included. Pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR−), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves were calculated using a bivariate random-effects model. Methodological quality was assessed using the QUADAS-2 tool. Results: Five diagnostic datasets were included in the quantitative synthesis. The pooled sensitivity and specificity were 0.90 (95% CI: 0.84–0.94) and 0.99 (95% CI: 0.97–0.997), respectively. The pooled LR+ was 84.78, while the pooled LR− was 0.10. The pooled diagnostic odds ratio was 857.30, indicating excellent discriminatory diagnostic performance. SROC analysis demonstrated near-perfect overall diagnostic accuracy with an area under the curve (AUC) of 0.986. Procalcitonin-based approaches showed the most consistent diagnostic performance across studies, while combined CT + PCT strategies achieved the highest overall diagnostic accuracy. Emerging biomarkers such as miR-375 and FNA-CT also demonstrated promising results, although evidence remains limited. Conclusions: Biomarker-based diagnostic strategies demonstrate excellent diagnostic accuracy for medullary thyroid carcinoma. Among the evaluated biomarkers, procalcitonin-based approaches, particularly combined CT + PCT strategies, showed the most robust and clinically relevant diagnostic performance. These findings support the potential integration of procalcitonin into future diagnostic algorithms for MTC. Further large-scale prospective studies are required to validate diagnostic thresholds and standardize biomarker assessment protocols.