Search Results (4,464)

Background and Clinical Significance: Lymph node metastases from carcinoma of unknown primary origin (CUP) are a rare and diagnostically challenging entity, particularly when arising from thoracic malignancies with atypical clinical presentations. This study aims to illustrate the essential nature of multidisciplinary integration, with a particular emphasis on the role of the pathologist in identifying occult thoracic tumors. Case Presentation: We report three cases of patients presenting with cervical or systemic lymphadenopathy as the initial clinical manifestation. Comprehensive diagnostic workups included advanced imaging (CT, MRI, and PET), comprehensive histopathological analysis, and next-generation sequencing of circulating tumor DNA. Case one and case two were diagnosed as occult primary non-mucinous lung adenocarcinomas, based on the integration of morphological features and immunohistochemical co-expression of TTF-1 and Napsin A, despite the absence of identifiable lung lesions. One case harbored an ALK rearrangement, guiding effective targeted therapy with alectinib. Case three involved metastatic pleural epithelioid mesothelioma, which presented with systemic lymphadenopathy and was initially misclassified as metastatic adenocarcinoma. Diagnosis was confirmed by the loss of BAP1 expression by immunohistochemistry and the detection of a BAP1 S160fs*1 mutation, emphasizing the role of molecular pathology. Conclusions: Lymphadenopathy as the first manifestation of thoracic malignancy is a rare but clinically significant occurrence. In such atypical presentations, pathologists play a pivotal role in diagnosis, often leading the process when clinical or radiological clues are minimal or absent. Accurate histopathological assessment is essential to establish a correct diagnosis and guide appropriate therapy. A multidisciplinary approach remains the cornerstone of diagnostic precision in CUP cases. Full article

Background: Desmoid tumors (DT) are rare, locally aggressive neoplasms characterized by an unpredictable clinical course. Although anatomical localization has been associated with tumor behavior, its relationship with systemic inflammatory response remains insufficiently explored. This study aimed to evaluate the impact of tumor localization on systemic inflammatory markers and to investigate CD47 expression in DT. Methods: This retrospective cohort study included 127 patients diagnosed with DT between 2010 and 2023. Demographic, clinicopathological, and laboratory data were collected. Systemic inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), HALP score, and pan-immune-inflammation value (PIV), were calculated. Tumor localization was categorized as trunk, extremity, or head and neck. CD47 expression was evaluated by immunohistochemistry. Results: Tumors were most frequently located in the trunk (50.4%), followed by extremities (40.9%) and head and neck region (8.7%). Significant differences in inflammatory markers were observed according to tumor localization. The head and neck group demonstrated lower neutrophil counts (p = 0.020), NLR (p = 0.009), PLR (p < 0.001), and PIV (p = 0.003), while showing higher PNI (p = 0.043) and HALP scores (p = 0.001) compared to trunk-localized tumors. Additionally, smaller tumors (<49 mm) were associated with lower NLR (p = 0.041) and neutrophil counts (p = 0.015). No detectable CD47 expression was observed in any tumor samples. Conclusions: Anatomical localization is closely associated with distinct systemic inflammatory profiles in patients with DT. These findings suggest that tumor location may influence host immune–inflammatory interactions and contribute to the biological heterogeneity of DT. The absence of CD47 expression indicates that alternative immune-related mechanisms may play a role in DT biology. Easily accessible inflammatory markers may provide valuable insights for risk stratification in clinical practice. Full article

Desmoplastic small round cell tumor (DSRCT) is a rare and highly malignant tumor that mostly occurs in young males. Due to its extremely strong invasiveness and poor prognosis, the treatment of DSRCT remains a major challenge in current medical research. The comprehensive treatment strategy based on surgery, combined with chemotherapy, targeted therapy, immunotherapy has become a clinical consensus. This review summarizes the main pathogenic mechanisms of DSRCT, as well as the targets involved in treatment and their applications, including targeted therapy targets (PDGF, VEGFR, FGFR4, IGF1R, HER2, c-KIT, mTOR, AR), immunotherapy targets (PD-1, PD-L1, B7H3, GD2), and treatments related to DNA damage response. Studies have shown that treatments targeting specific targets can inhibit tumor progression and prolong patient survival to a certain extent, but the efficacy has individual differences and is still limited. Therefore, future research still needs to further explore the molecular mechanism of DSRCT and discover more accurate and effective therapeutic targets. Full article

Background/Objectives: KRAS mutations are among the most common oncogenic driver alterations in non-small cell lung cancer (NSCLC) and define a biologically heterogeneous disease. In the current era of molecular oncology, with targeted therapies increasingly incorporated into clinical practice, the prognostic relevance of individual KRAS mutation subtypes and their relationship with immune biomarkers such as programmed cell death ligand 1 (PD-L1) require further clarification. This study aimed to evaluate the prognostic impact of KRAS mutation subtypes and their association with PD-L1 expression in patients with NSCLC. Methods: In this retrospective analysis, 150 patients with KRAS-mutant NSCLC who underwent next-generation sequencing at Trakya University Faculty of Medicine between January 2015 and December 2023 were included. Clinicopathological features, KRAS mutation subtypes, PD-L1 expression, and survival outcomes were assessed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method, and prognostic factors were evaluated using Cox regression analyses. Results: KRAS G12C was the most frequent subtype (40.7%), followed by G12V (20.7%) and G12D (14.7%). OS differed significantly among KRAS mutation subtypes (log-rank p = 0.007), with median OS values of 18 months for G12D, 11 months for G12C, 11 months for other rare variants, 9 months for G12A and G12V, and 5 months for G13. PD-L1 positivity was significantly higher in KRAS G12C tumors compared with non-G12C subtypes and remained independently associated with improved OS in multivariate Cox regression analysis (HR = 0.622; 95% CI, 0.426–0.907; p = 0.014). In multivariate analysis, age, ECOG performance status, disease stage, and PD-L1 positivity were independent prognostic factors, whereas KRAS mutation subtype did not retain independent prognostic significance. Conclusions: These findings suggest that KRAS-mutant NSCLC represents a clinically and molecularly heterogeneous subgroup and that integrating KRAS mutation subtypes with immune biomarkers may support more refined prognostic stratification. Full article

Background: Soft-tissue sarcomas (STSs) are rare and heterogeneous malignancies with generally poor and unpredictable prognosis. Tertiary lymphoid structures (TLSs) have been identified as favorable prognostic indicators in several cancer types, yet their role in STS remains poorly defined. This study investigates the prognostic relevance of TLS presence, maturity, location and density in resected STSs. Methods: We retrospectively analyzed 219 cases of primary STS surgically resected at the Bergonié Institute (France) between 1990 and 2020. TLSs were assessed for presence, spatial distribution, semi-quantitative density and degree of maturity using CD20 and CD23 immunohistochemistry, categorizing tumors as fully mature TLS-positive (fmTLS⁺) or -negative (fmTLS⁻). RNA sequencing was performed on 126 formalin-fixed paraffin-embedded samples to characterize immune microenvironment profiles. Survival outcomes—including overall survival (OS), time to locoregional progression (TTLRP), and time to distant progression (TTDP)—were analyzed using Kaplan–Meier estimates and Cox proportional hazards models. Results: The presence of fmTLS was significantly associated with improved 5-year OS (p = 0.012) and cause-specific survival (p = 0.006). Unexpectedly, fmTLS⁺ tumors showed a higher rate of local recurrence (22.9% vs. 8.1%, p = 0.002). On multivariate analysis, high-density fmTLS⁺ tumors conferred a 2.68-fold increased risk of locoregional progression (95% CI: 1.28–5.59, p = 0.009). Transcriptomic profiling confirmed a significant correlation between fmTLS⁺ status and a high-immune phenotype (Φ = 0.30, p < 0.001). Conclusions: STSs with fmTLS are associated with improved OS but increased risk of local recurrence. These findings support fmTLS as a dual prognostic biomarker and highlight the need for tailored surveillance and adjuvant strategies in fmTLS⁺ patients. Full article

Background: Uterine sarcomas are rare, heterogeneous malignancies with distinct pathological behaviors. This study aimed to identify clinicopathological characteristics, prognostic risk factors, and potential therapeutic targets to enhance clinical management. Methods: A retrospective analysis was conducted on 148 patients with uterine sarcoma treated at Peking University People’s Hospital between 1996 and 2025. Clinical outcomes, pathological subtypes, and immunohistochemical profiles were assessed. Additionally, bioinformatics analyses from RNA bulk sequencing of GEO datasets (GSE87581, GSE85383, GSE222045 and GSE64763) were performed to elucidate molecular characteristics across subtypes. Results: The most prevalent subtypes were uterine leiomyosarcoma (uLMS; 38.5%) and low-grade endometrial stromal sarcoma (LG-ESS; 29.7%). The 5-year recurrence rate was 50.5%, with frequent metastases to the pelvis and lungs. LG-ESS demonstrated the most favorable 5-year survival rate (90.3%), significantly higher than that of uLMS (61.8%) and undifferentiated uterine sarcoma (50.0%). Multivariate analysis identified histological subtype, stage, and coagulative necrosis as independent prognostic factors for overall and progression-free survival. Transcriptomic profiling revealed immunosuppression (CSF1R/CSF3R expression) in high-grade ESS, while uLMS exhibited activation of cell cycle and homologous recombination pathways. Conclusions: Histological subtype, stage, and coagulative necrosis were critical prognostic factors in uterine sarcoma. The findings suggest that vigilant pulmonary surveillance and further investigation into tailored therapeutic strategies may be warranted-including endocrine therapy for hormone-receptor-positive tumors, immunotherapy for high-grade ESS, and PARP inhibitors for uLMS. However, these hypotheses require thorough preclinical and clinical validation. Additionally, caution should be exercised to avoid overtreatment of chemotherapy in early-stage uLMS. Full article

Cellular senescence and polyploidy are fundamental stress responses that shape cancer progression and therapeutic outcomes. While senescence initially suppresses tumor growth, senescent cells accumulate in aging and therapy-exposed tissues and actively remodel the tumor microenvironment through the senescence-associated secretory phenotype (SASP) and extracellular matrix (ECM) reorganization. Senescent stromal cells increase collagen deposition and generate disordered matrix architectures, as evidenced by enhanced second harmonic generation (SHG) signal and increased anisotropic variation across in vitro systems, 3D co-culture models, and fibrotic lung tissues. These biochemical and mechanical alterations promote cancer cell plasticity and create conditions permissive for disease progression. Polyploid giant cancer cells (PGCCs) are a rare but highly resilient cancer cell population enriched under genotoxic stress. PGCCs arise through mitotic failure, including mitotic slippage and cytokinesis defects, and can survive chemotherapy and radiation due to their altered cell-cycle regulation. Emerging evidence indicates that senescence-driven microenvironments promote the formation of PGCCs and multinucleated cells, linking ECM remodeling and mechanical stress to polyploidization. Functionally, PGCCs exhibit abnormal cytoskeletal and nuclear mechanics that support migratory persistence and enable survival within hostile tumor environments. In addition, PGCCs can promote the survival of neighboring cancer cells during treatment, suggesting a stromal-like role in establishing therapy-resistant niches. These cells can persist in a dormant state and later generate proliferative progeny, contributing to tumor recurrence and metastasis. Together, these findings support a model in which senescent niches may promote PGCC formation, persistence, and tumor repopulation. Targeting both senescence-associated microenvironments and PGCC-specific survival mechanisms may improve long-term therapeutic outcomes. Full article

Background: Desmoplastic fibroma (DF) is a rare, benign, but locally aggressive intraosseous tumor with a predilection for the mandible in pediatric patients. Owing to its low incidence, evidence guiding management remains limited. Objective: To provide a comprehensive review of the clinical presentation, radiographic features, treatment strategies, and outcomes of pediatric DF of the jaws. Methods: A comprehensive literature review was conducted using PubMed/MEDLINE, Embase, Cochrane Library, and IEEE Xplore to identify relevant studies published between 2000 and 2026. Given the rarity of this entity, a broad search strategy was applied. Eligible studies were analyzed to extract data on patient demographics, clinical features, imaging findings, treatment modalities, and outcomes. Results: A total of 32 studies comprising 45 pediatric cases were identified. The mandible was involved in 86.7% of cases. The most common presentation was painless swelling or facial asymmetry (68.9%). Wide or segmental resection was the primary treatment in 68.9% of cases. Recurrence data were available for 75.6% of cases, with an overall recurrence rate of 2.9%, occurring following incomplete resection. Conclusions: Pediatric DF of the jaws is a rare but locally aggressive tumor requiring accurate diagnosis and individualized surgical management. Complete resection with clear margins appears to provide the most reliable outcomes. However, interpretation of outcomes is limited by the predominance of case reports, heterogeneous reporting, and incomplete follow-up. Future multicenter studies and standardized reporting are needed to better define optimal management strategies. Full article

Background and Clinical Significance: Extramammary Paget disease (EMPD) is a rare cutaneous adenocarcinoma that frequently involves apocrine-rich regions and may extend beyond clinically apparent margins through adnexal structures. Surgical excision remains the standard of care; however, management can be challenging in elderly patients and in anatomically sensitive areas such as the scrotum, where morbidity and functional impairment are significant concerns. Despite increasing use of radiation-based therapies, optimal superficial radiation therapy (SRT) parameters, particularly with respect to depth of penetration, remain poorly standardized. Case Presentation: An 88-year-old male with a history of melanoma, non-melanoma skin cancer, and remote prostate cancer presented with biopsy-proven EMPD involving the scrotum and perineum. Imaging demonstrated no evidence of underlying or metastatic malignancy. Given lesion size (9 × 4 cm), anatomic location, and patient preference to avoid surgery, SRT was selected. The patient underwent treatment with 70 kV energy, delivering a total dose of 5440 cGy in 17 fractions (320 cGy per fraction) administered twice weekly. Energy selection was guided by the known propensity of EMPD for adnexal extension, with the aim of improving treatment coverage of potential subclinical disease. Conclusions: This case highlights the importance of incorporating tumor depth and adnexal involvement into treatment planning for EMPD. Depth-guided SRT may represent a viable non-surgical management strategy in carefully selected patients, particularly when surgical morbidity is a concern. These findings support a more individualized, mechanism-based approach to optimizing radiation therapy in cutaneous malignancies. Full article

Background: Megaprosthetic reconstruction is the standard of care for limb salvage after tumor resection around the knee, but the full burden of unplanned revision surgery is rarely reported as a structured composite outcome. We evaluated 241 consecutive patients over 21 years at a tertiary orthopedic oncology center. Methods: This retrospective cohort included 241 patients (160 distal femur, 78 proximal tibia, three combined) treated between 2003 and 2024. Revision-free survival (RFS, composite of any unplanned revision or amputation) and amputation-free survival were estimated by Kaplan–Meier analysis; independent predictors were identified by Cox regression. A pre-specified major-event composite (amputation, implant removal, or recurrence resection) was used for sensitivity analysis. Results: Mean age was 34.9 ± 19.5 years; mean follow-up was 120.2 months. Negative resection margin (R0) was achieved in 85.5% (206/241). Unplanned revision was required in 25 patients (10.4%); overall limb salvage was 92.9%. Five-year RFS was 73.8% (distal femur) vs. 65.0% (proximal tibia; p = 0.084), and 5-year limb salvage was 88.9% vs. 84.3% (p = 0.081). Surgical margin was strongly associated with outcome: 5-year RFS 75.4% (R0) vs. 48.7% (R1/R2; p < 0.001); 5-year limb salvage 90.6% vs. 71.5% (p = 0.003). On exploratory multivariate Cox analysis, proximal tibia site and positive margin were associated with worse revision-free survival; within the proximal tibia subgroup, absence of gastrocnemius flap coverage was also associated with worse outcome (interpreted with caution given the small flap subgroup, n = 11, and limited event count). Conclusions: In this single-center series, megaprosthetic reconstruction around the knee achieved acceptable revision-free survival and limb salvage. Surgical margin status was the strongest independent predictor of both endpoints, reinforcing the well-established importance of oncologic margin quality and site-specific soft tissue strategies. Full article

Background: Solid pseudopapillary neoplasms of the pancreas (SPN-P) are rare, low-grade malignancies primarily affecting young women. While surgical resection is definitive, the optimal balance between oncological radicality and functional preservation remains a clinical challenge. This study evaluates tailored surgical strategies utilizing minimally invasive and parenchyma-preserving techniques. Patients and Methods: We conducted a multi-institutional retrospective analysis of SPN-P cases treated between March 2020 and May 2023. Out of 167 pancreatic resections, five paradigmatic cases were identified. We analyzed the decision-making process for preoperative staging (CT/MRI/EUS-FNB), surgical approach (open, laparoscopic, or robotic), and the implementation of parenchyma-preserving versus formal resections. Results: The cohort included four females and one male (mean age 40.6 years; range 13–73). Surgical approaches were tailored to tumor location and patient characteristics: two patients underwent pancreatoduodenectomy (one laparotomic, one laparoscopic), two underwent distal pancreatectomy (one robotic, one laparoscopic), and one pediatric patient underwent laparoscopic parenchyma-preserving central pancreatectomy. R0 resection was achieved in all cases. No Grade B/C postoperative pancreatic fistulas (POPF) or complications Clavien-Dindo ≥III occurred. At a mean follow-up (FU) of 38.4 months (range 20–58), the disease-free survival rate was 100%. One patient developed new-onset diabetes mellitus following distal pancreatectomy. Conclusions: A tailored surgical approach—integrating robotic, laparoscopic, and parenchyma-preserving techniques—may enable excellent oncological outcomes while minimizing morbidity. For SPN-P, the choice of procedure should prioritize the preservation of pancreatic function, particularly in young patients, without compromising surgical margins. Full article

Background: Pathological N1 (pN1) non-small cell lung cancer (NSCLC) presents variable survival; yet, the TNM system lacks N1 subclassification. While studies focus on numerical nodal burden, the prognostic impact of anatomical location remains unclear. Surgically, completion lobectomy is advised after sublobar resection for N1-positive disease. However, for hilar/interlobar involvement—where residual lymphatic pathways remain post-lobectomy—extension to pneumonectomy is rarely performed, raising uncertainty about the optimal extent of resection in different pN1 subgroups. Methods: This retrospective study evaluated 150 patients with pN1 NSCLC who underwent curative-intent anatomical lung resection and systematic nodal dissection (2012–2023). The follow-up period extended from the date of surgery to death or last follow-up, with survival status assessed until March 2026. Clinicopathological variables, including anatomical N1 level, nodal burden, tumor characteristics, and surgical extent, were analyzed alongside survival outcomes. Results: Peripheral N1 involvement (stations 12–14) yielded significantly longer survival than hilar/interlobar metastasis (stations 10–11) (p = 0.019). Nodal count and multiple-station involvement did not impact survival. Age (HR: 1.036, p = 0.026) and interlobar station 11 pN1 positivity (HR: 1.912, p = 0.044) emerged as independent negative prognostic factors for overall survival. Perineural invasion worsened survival in Stage III disease. Extended resections offered no survival benefit and worsened outcomes in hilar/interlobar disease. Conclusions: The anatomical level of N1 metastasis is a key prognostic factor in pN1 NSCLC. Standard lobectomy appears sufficient across all subgroups, including hilar/interlobar disease, while extended resections do not improve survival. Future studies should clarify systemic/adjuvant treatment strategies. Full article

Background/Objectives: Laryngeal cancer has a high incidence and mortality rate, especially in advanced stages. Stoma recurrence after total laryngectomy is rare but lethal, and its risk factors remain controversial. We aimed to assess whether the presence of a tracheotomy performed prior to surgical treatment for advanced laryngeal cancer represents a risk factor for recurrence of the disease in the stoma and interferes with patient survival. Methods: A retrospective study was carried out in 138 patients who underwent total laryngectomy. Clinical-pathological variables were related to the presence of a preoperative tracheotomy. Results: Fifty-two patients without and 86 patients with preoperative tracheotomy were studied. There was a significant predominance of transglottic tumors (p = 0.02) and no patients with early-stage disease (T1 and T2, p = 0.002) in the tracheotomy group. There was no statistically significant difference in stoma recurrence (p = 0.53). On multivariate analysis, the risk of stoma recurrence was not significantly associated with the presence of a preoperative tracheotomy. Conclusions: The presence of a tracheotomy prior to total laryngectomy was not a risk factor for disease recurrence in the stoma or for reduced survival in the group. Full article

Introduction: Giant retroperitoneal liposarcomas (GRPLs) are rare tumors that often reach considerable size before diagnosis due to their indolent growth and deep anatomical location. Surgery represents the only potentially curative treatment, yet recurrence rates remain high. While histological subtype is a recognized predictor of recurrence, the prognostic role of tumor size, particularly in giant tumors, remains controversial. This study evaluates the impact of tumor size and histological subtype on recurrence risk in a literature-based retrospective cohort. Materials and Methods: Data were extracted from a literature-based database of GRLPs published between 2004 and 2023. Only tumors >20 cm treated without positive surgical margins were included; patients receiving adjuvant therapy or with missing follow-up were excluded. Histological subtype (well-differentiated vs. other) was the main variable of interest. Recurrence-free survival (RFS) was defined as the primary endpoint and estimated using the Kaplan–Meier method. The association between histological subtype and recurrence risk was evaluated using a Cox proportional hazards model. A sensitivity analysis was performed to explore the potential interaction between tumor size and histological subtype. Results: Our final cohort yielded a total of 81 patients, of whom 47 (58%) had a well-differentiated GRLPs. The median tumor size was 38 cm and median follow-up was 16 months, with 24 recurrences observed. At 24 months, RFS was higher in well-differentiated tumors than in other histological subtypes (81% vs. 41%). In multivariable Cox analysis, histology was independently associated with recurrence risk (HR 3.2, 95% CI 1.28–8.17, p = 0.01), whereas tumor size showed no association with recurrence. Interaction analysis confirmed no differential effect of tumor size across histological subtypes. Conclusions: In this literature-based cohort of GRLPs treated with surgery, histological subtype independently predicted recurrence, whereas tumor size showed no prognostic value, either overall or within individual histological subtypes. Full article

We report an extremely rare case of intra-articular myopericytoma of the knee. A 66-year-old man presented with a 10-year history of knee pain and a slowly enlarging soft, tender, and elastic mass. Magnetic resonance imaging revealed a well-enhanced intra-articular lesion; however, the findings were nonspecific and raised a broad differential diagnosis of vascular, perivascular, and malignant soft-tissue tumors. Incisional biopsy followed by marginal excision confirmed the diagnosis of myopericytoma. Although typically benign and indolent, myopericytomas can mimic both benign and malignant lesions, necessitating histopathological evaluation. At 5 years after surgery, the patient remained recurrence-free. Full article