Search Results (71)

Background: Lung adenocarcinoma is morphologically heterogeneous, composed of various histological patterns. The International Association for the Study of Lung Cancer (IASLC) grading system, based on the predominant pattern and the presence of high-grade components, underscores this heterogeneity’s prognostic relevance. However, the specific impact of the non-predominant “second component” on survival outcomes in early-stage disease remains inadequately characterized. Methods: We conducted a retrospective, single-center study including 95 patients with pathological stage 0, I, and II (TNM 8th edition) lung adenocarcinoma who underwent complete anatomical resection (lobectomy or segmentectomy) between January 2020 and December 2021. Histopathological evaluation followed the WHO 5th edition classification, with patterns quantified in 5% increments. The second predominant component was defined as the second most represented histological pattern, irrespective of a fixed percentage threshold. Overall survival (OS) and disease-free survival (DFS) were analyzed. Results: A second predominant component was identified in 55 patients (57.9%). The most common second components were lepidic (30.5%), solid (18.9%), and micropapillary (10.5%). With a median follow-up of 36 months, the presence of a lepidic second component was an independent factor for improved OS (Hazard Ratio [HR] 0.70, 95% CI 0.52–0.95, p = 0.022) and DFS (HR 0.62, 95% CI 0.41–0.93, p = 0.021). Conversely, a micropapillary second component was a strong independent predictor of worse OS (HR 1.81, 95% CI 1.24–2.64, p = 0.002) and DFS (HR 2.03, 95% CI 1.32–3.12, p = 0.001). The solid second component showed an intermediate adverse effect on DFS (HR 1.45, 95% CI 1.01–2.08, p = 0.043). Conclusions: The second predominant histological pattern provides additional prognostic information beyond the IASLC grading system and may improve postoperative risk stratification in early-stage lung adenocarcinoma. A lepidic second component portends a favorable prognosis, while micropapillary and solid components denote aggressive tumor biology and higher recurrence risk. Incorporating the evaluation of second components into routine pathological reporting and clinical decision-making could enhance postoperative risk stratification and personalize adjuvant therapy strategies. Full article

Background and Objectives: Renal cell carcinoma (RCC) exhibits heterogeneous and sometimes unpredictable metastatic behavior, involving both common and uncommon anatomic sites. Institutional analyses of histopathologically confirmed metastatic RCC may improve diagnostic recognition and clinical awareness. This study aimed to characterize the metastatic distribution and histopathologic features of RCC diagnosed in a single tertiary center over a five-year period. Materials and Methods: A retrospective review of the pathology database of the Department of Pathology, “Pius Brînzeu” Emergency County Hospital, Timișoara, was performed to identify all histologically confirmed cases of metastatic RCC diagnosed between January 2020 and December 2024. Case identification was based on pathology reports of metastatic lesions. In a subset of cases, corresponding pathology reports of the primary renal tumor were available and reviewed. Histopathological data collected included WHO/ISUP grade, tumor necrosis, sarcomatoid and/or rhabdoid differentiation, vascular invasion, surgical margin status, tumor size, and pathological T stage (pT). Exploratory analyses were performed to assess associations between metastatic site and selected histopathological features. Results: Thirty-two cases of metastatic RCC were identified, all demonstrating clear cell morphology. The mean patient age was 62.9 years, with a marked male predominance. Among cases with available primary tumor data, high WHO/ISUP grade and adverse histopathologic features were frequently observed. The most common metastatic sites in our institution were the brain and bone, followed by the adrenal gland, lymph nodes, and liver. Less frequent metastatic involvement included the pancreas, testis, vagina, skin, and peritoneum. Exploratory analyses did not demonstrate statistically significant associations between metastatic site and tumor grade, necrosis, or sarcomatoid/rhabdoid differentiation; however, descriptive trends were observed, including the association of brain metastases with high-grade tumors and the high prevalence of tumor necrosis across metastatic sites. Conclusions: This pathology-based retrospective series highlights the broad metastatic spectrum of RCC, including both typical and rare anatomic sites. The predominance of clear cell morphology and the frequent association with adverse histopathologic features support the link between aggressive tumor biology and metastatic disease. Although no statistically significant associations were identified, the observed patterns suggest potential relationships between metastatic distribution and tumor characteristics, warranting further investigation in larger studies. Full article

Background: Low anterior resection syndrome (LARS) is a frequent survivorship problem after sphincter-preserving rectal cancer surgery. Pelvic radiotherapy (RT), often combined with chemotherapy, is frequently implicated in LARS development, but its apparent effect may be confounded by low tumor location and diversion. We evaluated whether RT (±chemotherapy) separates the risk of postoperative LARS severity—especially major LARS—beyond classical anatomic and pathway determinants. Methods: We conducted a single-centre observational cohort study of operated rectal cancer patients managed between 2013 and 2024, who completed the Romanian-validated LARS score by standardized telephone interview after restoration of bowel continuity (up to 18 months postoperatively). Outcomes were postoperative LARS score, LARS category, and major LARS. Comparisons were performed by RT status and by oncologic treatment pattern. Multivariable logistic regression assessed associations with major LARS, adjusting a priori for tumor location and diverting ileostomy; furthermore, extended sensitivity models incorporated technical/pathway variables. Discrimination was explored using 5-fold cross-validated ROC/AUC. Item-level LARS responses were analyzed to characterize symptom phenotype. Results: Overall, 182 patients were included (RT: 106; no RT: 76); 43.4% had LARS (minor 14.8%, major 28.6%). RT-treated patients had higher postoperative LARS scores (median 21 vs. 12; p = 0.002) and a higher prevalence of major LARS (35.8% vs. 18.4%; p = 0.012). Across treatment patterns, LARS severity was highest in RT + chemotherapy. Item-level analyses indicated that RT-associated differences were driven mainly by urgency and clustering domains. In adjusted models, RT was not independently associated with major LARS, whereas low tumor location and diverting ileostomy were strong predictors. Discrimination for major LARS was modest: AUC 0.561 for RT alone, 0.643 for location + ileostomy, and 0.654 for location + ileostomy + RT (5-fold cross-validation). Conclusions: RT is associated with worse unadjusted postoperative bowel dysfunction after rectal cancer surgery and is linked to urgency/clustering-dominant symptom patterns. However, in this cohort, the risk of major LARS was predominantly explained by tumor location and diversion rather than RT alone, supporting integrated risk stratification and early symptom-directed survivorship care. Full article

Patterns of colon cancer recurrence demonstrate a high degree of anatomical reproducibility, consistently aligning with mesofascial planes and compartmentalized vascular and lymphatic territories, as evidenced by pathological, surgical and imaging studies. These frameworks describe recognized routes of spread but do not provide an integrated anatomical explanation for understanding why tumor progression often aligns with mesofascial planes, embryological boundaries and cavity-specific niches, nor for why preservation of structural integrity during surgery is associated with improved oncological outcomes. This work proposes a spatial containment model of colon cancer progression, in which tumor dissemination reflects sequential breaches of anatomically defined barrier systems. The Colon Cancer Containment System is proposed as a three-tier framework in which tumor progression reflects sequential breaches of containment at the tissue (microcontainment), mesenteric (mesocontainment) and peritoneal or systemic (macrocontainment) levels. At each stage, anatomical structures function as barrier systems that constrain tumor spread and shape directionality of progression. Disruption of these barriers, whether tumor-driven or iatrogenic, is associated with relatively consistent patterns of local, regional, and distant recurrence. Within this approach, established prognostic features such as tumor–node–metastasis (TNM) stage, extramural vascular invasion, perineural invasion and margin status may also be interpreted as markers of containment integrity, in addition to their established roles as indicators of tumor aggressiveness. Surgical plane preservation is reframed as a biologically meaningful act of containment maintenance. By organizing validated observations within an anatomically patterned architecture, the containment framework provides a coherent model for interpreting reproducible recurrence patterns and clarifies the biological significance of surgical integrity. This perspective complements existing oncological paradigms, supports anatomically informed risk stratification and generates testable hypotheses for future clinical and translational research. Full article

Pure mediastinal yolk sac tumor is an uncommon and aggressive malignant germ cell neoplasm that presents considerable diagnostic difficulties owing to its pronounced clinical and morphological variability. Mediastinal yolk sac tumors, in contrast to their gonadal equivalents, typically occur at later stages, are typically associated with mixed germ cell components, and have a diverse array of histologic patterns that may resemble both germ cell and somatic malignancies. Accurate identification of these types of cancer is essential since diagnostic misclassification may significantly impact treatment and prognosis. This review provides a comprehensive overview of the morphologic spectrum of mediastinal yolk sac tumor, with emphasis on both classic and variant histologic patterns, including reticular, solid, glandular, papillary, hepatoid, and other less common growth forms. The immunohistochemical correlations of these patterns and their role in resolving diagnostic dilemmas are discussed, along with key differential diagnoses encountered in small mediastinal biopsy specimens. Particular attention is given to the limitations of limited tissue sampling, the impact of post-chemotherapy morphologic changes, and the potential for misinterpretation in this challenging anatomic site. By integrating morphologic features with clinical, radiologic, and laboratory findings, this review aims to enhance diagnostic accuracy and improve recognition of mediastinal yolk sac tumor across its diverse presentations. Full article

Background and Clinical Significance: Pancreatic neuroendocrine tumors (pNETs) rarely exhibit intraductal growth, a pattern that may mimic intraductal papillary mucinous neoplasms (IPMNs) or pancreatic ductal adenocarcinoma (PDAC). Preoperative recognition is challenging, particularly when associated with anatomic variants such as pancreas divisum. Case Presentation: A 63-year-old man with a history of pancreatic duct dilation presented with pruritus, weight loss, and lymphadenopathy. Cross-sectional imaging revealed a cephalopancreatic mass with upstream ductal dilatation. EUS demonstrated a hypervascular lesion with intraductal extension into the dorsal duct in the setting of pancreas divisum. EUS-FNB confirmed a well-differentiated pNET (G1) with loss of DAXX expression and preserved ATRX. Ga-68 PET/CT showed intense uptake in the primary lesion and lower-grade uptake in two additional nodules, later proven non-neoplastic. A multidisciplinary tumor board recommended preoperative optimization with somatostatin analog therapy and supervised weight reduction, followed by pylorus-preserving duodenocephalopancreatectomy. Final pathology confirmed NET G1 with intraductal growth and full concordance with preoperative EUS-FNB findings. Conclusions: in this case, a pNET showed intraductal growth within the dorsal duct in the context of pancreas divisus, further expanding the range of its reported presentations. It underscores the diagnostic value of EUS-FNB for morphologic, proliferative, and molecular characterization, and highlights the importance of multidisciplinary evaluation in guiding preoperative optimization and tailored surgical management. Full article

Background and Clinical Significance: Urachal carcinoma (UrC) is an uncommon neoplasm derived from residual embryonic structures connecting the bladder to the umbilicus. Owing to its rarity, deep anatomic location, and histologic overlap with other glandular malignancies, accurate diagnosis remains challenging. Congenital anomalies of the lower urinary tract, including bladder exstrophy, are recognized as conditions that may predispose to malignant transformation of urachal remnants, although documented cases remain scarce. Case presentation: We describe the case of a 52-year-old male with bladder exstrophy and intellectual disability who presented with a progressively enlarging suprapubic mass and intermittent hematuria. Radiologic evaluation demonstrated a mass arising along the urachal tract. Surgical excision revealed a tumor composed of two morphologically distinct components: an enteric-type adenocarcinoma and a squamous carcinoma. Immunohistochemical profiling indicated urachal derivation and excluded other primary sites. Conclusions: This case expands the morphologic spectrum of UrC and emphasizes the diagnostic value of integrating clinical risk factors with detailed histologic and immunophenotypic assessment, particularly in tumors with mixed differentiation patterns. Full article

Background: Outcomes with enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) are influenced by tumor burden, disease kinetics, and host factors. We evaluated the relative prognostic impact of metastatic pattern, laboratory markers, and prostate-specific antigen (PSA) dynamics in a real-world cohort. Methods: We retrospectively analyzed 72 patients with mCRPC treated with enzalutamide. Progression-Free Survival (PFS) and Overall Survival (OS) were estimated using the Kaplan–Meier method. Multivariate Cox proportional hazards models were utilized to identify independent predictors of survival, incorporating clinical variables (visceral metastases, bone tumor burden), kinetic parameters (Time to Castration Resistance [TTCR], Time to PSA Nadir [TTN]), and host factors (Charlson Comorbidity Index [CCI], Eastern Cooperative Oncology Group Performance Status (ECOG PS), Systemic Immune-Inflammation Index [SII], HALP score). Results: Visceral metastasis was a dominant predictor of poor outcomes, increasing the risk of death by 4.0-fold (HR: 4.05; 95% CI: 1.84–8.89; p < 0.001). A high skeletal tumor burden (≥5 bone lesions) was identified as a critical threshold, associated with a 5.5-fold increase in mortality risk (HR: 5.53; p < 0.001). Delays in initiating enzalutamide significantly compromised survival, with each 1-month delay increasing the risk of death by 7.3% (HR: 1.07; p = 0.003). While early PSA decline (≥50% at 3 months) did not independently predict OS, a prolonged TTN (>12 months) was associated with superior survival. Notably, host-related factors, including age, CCI, and ECOG PS, were not found to be significantly associated with survival outcomes in this specific dataset. Conclusions: Our preliminary findings suggest that survival in real-world mCRPC patients treated with enzalutamide may be influenced predominantly by intrinsic tumor biology—specifically anatomical extent and resistance kinetics—rather than host frailty or comorbidity burden. However, given the retrospective and single-center nature of this study, these findings should be considered hypothesis-generating and require validation in larger, multi-center cohorts. Host-related variables (including age and CCI) were evaluated but were not retained as independent predictors in the final multivariable model. Early initiation of therapy and monitoring of kinetic markers like TTN and TTCR offer superior prognostic stratification compared to static baseline characteristics. Full article

V-set and immunoglobulin domain-containing 1 (VSIG1) is a member of the immunoglobulin superfamily that has attracted increasing attention as a differentiation-associated protein in gastrointestinal neoplasia. Although initially described as a gastric-specific marker, accumulating evidence indicates that VSIG1 more accurately reflects gastric-enriched epithelial differentiation rather than strict anatomical origin. This conceptual shift has implications for phenotype-oriented tumor classification and diagnostic interpretation in the context of lineage plasticity. A structured and transparently reported literature search was conducted in PubMed/MEDLINE, Web of Science, and Scopus, covering studies published between 2000 and 2024. Eligible studies included original research and relevant reviews evaluating VSIG1 expression in normal tissues and digestive tract tumors, with emphasis on immunohistochemical patterns and clinicopathological correlations. In gastric cancer, VSIG1 expression consistently correlates with preserved glandular architecture and epithelial differentiation, whereas reduced or absent expression accompanies dedifferentiation and architectural disorganization. Outside the stomach, VSIG1 positivity is uncommon but reproducible in tumors exhibiting gastric-type or mixed differentiation, including settings of hepato-gastric phenotypic overlap. These patterns support interpretation of VSIG1 as a context-dependent indicator of lineage engagement and differentiation state rather than tumor origin or aggressiveness. Current data on independent prognostic value are limited and partially conflicting, and predictive roles remain unsupported, while functional data remain limited. Full article

Background/Objectives: Spread through air spaces (STAS) represents an aggressive invasion pattern in lung cancer and is associated with unfavorable oncologic outcomes. As STAS is currently identifiable only on postoperative pathology, reliable preoperative, noninvasive prediction remains a clinical challenge. This study aimed to evaluate the feasibility of predicting STAS using ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT)-derived radiomic and clinicoradiomic models. Methods: In this retrospective study, patients who underwent surgical resection for lung cancer with available preoperative ¹⁸F-FDG PET/CT imaging were analyzed. Radiomic features were extracted from intratumoral and peritumoral regions. Clinical, radiomic-only, and combined clinicoradiomic models were developed using LASSO-based feature selection and multivariable logistic regression. Model performance was evaluated using nested cross-validation, receiver operating characteristic analysis, calibration assessment, and decision curve analysis. Results: Radiomic features reflecting intratumoral metabolic characteristics and peritumoral tissue heterogeneity were significantly associated with STAS. The combined clinicoradiomic model demonstrated superior discriminative performance compared with the clinical and radiomic-only models (mean AUC ≈ 0.75), along with favorable calibration (Brier score = 0.20) and improved clinical net benefit across relevant threshold probabilities. Lower eosinophil count, lower SUVmin_tumor, and lower intratumoral SUV skewness emerged as independent predictors of STAS. Conclusions: Preoperative prediction of STAS in lung cancer is feasible using PET/CT-based radiomic analysis integrating intratumoral, peritumoral, and clinical features. This noninvasive approach provides biologically relevant information beyond conventional anatomical assessment and warrants further validation in prospective, multicenter cohorts. Full article

Primary parapharyngeal space (PPS) tumors are rare neoplasms comprising 0.5% of head and neck tumors. Their complex anatomical location and proximity to critical neurovascular structures pose significant surgical challenges. While transcervical and transcervical-combined approaches represent the primary surgical techniques, no comprehensive systematic comparison exists. This systematic review compared surgical success, complications, functional outcomes, and recurrence rates between these approaches. Following PROSPERO registration (CRD420251037201), we searched PubMed, Cochrane, Web of Science, Google Scholar, and ScienceDirect without date restrictions. Independent dual screening identified retrospective cohort studies and case series comparing both approaches. Data extraction and risk of bias assessment employed standardized tools, with synthesis conducted per PRISMA 2020 guidelines using narrative analysis. Ten studies encompassing 505 patients with 508 tumors met inclusion criteria. Both approaches achieved excellent complete resection rates (95–100%). Transcervical approaches demonstrated lower overall complication rates (4.8–52.6%) versus transcervical-combined approaches (7.7–100%), though rates varied substantially by tumor type, and differences likely reflect case selection rather than approach-specific effects. Cranial nerve injuries (VII, X, XII) constituted predominant complications. Infratemporal fossa approaches showed the highest morbidity. Recurrence rates ranged from 0–30.3% without consistent patterns favoring either approach. Transcervical-combined approaches were essential for superior compartment extension and for skull base involvement. Both transcervical and transcervical-combined approaches achieve excellent tumor resection with acceptable morbidity when appropriately selected. For most benign PPS tumors, a transcervical approach may be preferred. Combined approaches may be considered in specific anatomic scenarios that require enhanced exposure, particularly when the superior compartment and skull base are involved, although the decision is always highly individual. Full article

Background: Postoperative pancreatic fistula (POPF) is a major source of morbidity following a pancreatoduodenectomy (PD), often delaying or precluding adjuvant chemotherapy and potentially compromising long-term oncologic outcomes. While established risk models focus on anatomical and biochemical factors, the role of biliary microbiota remains underexplored. This study aimed to assess relationship between bacteriobilia and the incidence of POPF, as well as its impact on overall survival (OS) in patients undergoing a PD for pancreatic ductal adenocarcinoma (PDAC). Methods: We analyzed the medical histories of 725 patients with a pancreatic tumor who were qualified for surgery between 2017 and 2022. This retrospective cohort study included 138 patients who underwent a PD for histologically confirmed PDAC. Intraoperative bile cultures were obtained and analyzed for microbial presence and resistance patterns. Results: Bacteriobilia was detected in 76.8% of patients, including bacteria with resistance mechanisms (BRM) present in 12.3% of bile samples. Bacterial bile colonization conferred an increased odds of POPF grade B (OR 5.11; p = 0.088), whereas BRM were strongly predisposed to POPF grade C (OR 4.97; p = 0.026). Upon a multivariate analysis, bacteriobilia independently drove clinically relevant POPF and POPF grade B (OR 5.50; p = 0.034 and OR 8.04; p = 0.048, respectively), while BRM remained a key determinant of POPF grade C (OR 6.17; p = 0.047). Beyond morbidity, bile colonization markedly impaired overall survival irrespective of tumor stage (26.7 vs. 54.7 months; log-rank p = 0.009). Conclusions: Bacterial bile colonization may contribute not only to higher rates of POPF but to a significantly reduced OS in patients undergoing a PD for PDAC. Bacteriobilia should be considered as a prognostic factor for worse survival after a PD. Full article

The sacrum is a common site for a wide range of pathological processes, including benign and malignant tumors as well as non-neoplastic conditions. Accurate diagnosis of sacral lesions remains challenging due to overlapping imaging features and the anatomical complexity of the region. This review provides a comprehensive overview of sacral lesions, with emphasis on imaging characteristics, diagnostic challenges, and clinical implications. Key imaging findings are highlighted to help narrow the differential diagnosis. While certain imaging patterns may suggest specific etiologies, image-guided biopsy is often necessary for definitive diagnosis. Familiarity with the spectrum of sacral pathologies is essential for radiologists to effectively contribute to diagnosis, patient management, and multidisciplinary care. Full article

Background and Clinical Significance: Phosphoglyceride crystal deposition disease (PCDD) is an extremely rare condition characterized by the deposition of phosphoglyceride crystals, occasionally forming tumor like lesions that present significant diagnostic challenges. Here, we report, to our knowledge, the first documented recurrent case of PCDD confined to the mandible, which clinically and radiologically mimicked a malignant bone tumor. Case Presentation: An 80-year-old female patient presented with a progressively enlarging mandibular mass, and imaging studies demonstrated an osteolytic lesion with cortical bone destruction and marked fluorodeoxyglucose uptake on positron emission tomography-computed tomography, raising a strong suspicion of malignancy. Histopathological examination revealed foreign-body granulomatous inflammation with characteristic crystal deposition, and the diagnosis of PCDD was definitively established through the combined use of gold hydroxamic acid staining, Raman spectroscopy, and ultrastructural analysis. Although surgical excision with curettage was initially achieved, local recurrence was observed 6 years later, indicating the potential for long-term disease persistence. In addition, a comprehensive literature review conducted in accordance with the PRISMA guidelines was performed to summarize previously reported cases of PCDD, with particular attention to anatomical distribution, radiological characteristics, recurrence patterns, and proposed pathogenic mechanisms. The review confirmed the extreme rarity of mandibular involvement and demonstrated that recurrence can occur apparently even after surgical treatment. Conclusions: This case underscores the importance of a multimodal diagnostic strategy integrating imaging, histopathology, and spectroscopic analyses for the accurate identification of PCDD and highlights the necessity of histopathological confirmation to prevent unnecessary aggressive treatment. Full article

The tumor immune microenvironment (TIME) is closely involved in tumor initiation, malignant progression, immune escape, and response to immunotherapy. With the continued development of high-throughput sequencing technologies, transcriptomic approaches have become essential for examining the cellular and molecular features of the TIME. Bulk RNA sequencing offers tissue-level gene expression profiles and allows the estimation of immune cell composition through computational deconvolution. Single-cell RNA sequencing provides finer resolution, revealing cellular heterogeneity, lineage relationships, and functional states. Spatial transcriptomics (ST) retains the native anatomical context, making it possible to localize gene expression patterns and cell–cell interactions within intact tissues. These approaches, when considered together, have shifted TIME research from averaged measurements toward a more detailed and mechanistic understanding. This review summarizes the principles, applications and limitations of bulk, single-cell and spatial transcriptomic methods, highlighting emerging strategies for integrative analysis. Such multi-scale frameworks are increasingly important for studying immune dynamics and may contribute to the development of more precise biotechnological and immunotherapeutic strategies. Full article