Search Results (1,005)

Background: Sentinel lymph node biopsy (SLNB) is the standard axillary staging procedure in clinically node-negative breast cancer but remains invasive, non-therapeutic and increasingly questioned in contemporary de-escalation algorithms. After neoadjuvant chemotherapy (NACT), however, the safety of omitting SLNB solely on the basis of a negative axillary ultrasound (AUS) is uncertain, particularly across molecular subtypes with heterogeneous chemosensitivity. This study evaluated the diagnostic performance of preoperative AUS after NACT and explored clinicopathological and biological factors associated with SLNB positivity in ultrasound-negative axillae. Methods: In this single-centre retrospective cohort, 135 women with invasive breast cancer who received NACT followed by surgery (2022–2024) were analysed. To avoid spectrum bias, 77 patients with clipped, cytologically or histologically proven node-positive disease at baseline were excluded from the main analysis. All patients underwent preoperative AUS and definitive axillary staging. Ninety-six women with ultrasound-negative axillae who proceeded to SLNB constituted the primary study population. Oestrogen receptor (ER), progesterone receptor (PR), HER2, Ki-67 and immunohistochemistry-based molecular subtype were recorded. Receiver operating characteristic (ROC) analysis and uni/multivariable logistic regression were used as exploratory tools to identify factors associated with SLNB positivity. Results: In the overall cohort, AUS sensitivity, specificity, negative predictive value and false-negative rate for axillary metastasis were 47.8%, 90.9%, 62.5% and 52.2%, respectively. Among ultrasound-negative axillae, SLNB was positive in 37.5%. Compared with SLNB-negative patients, those with SLNB metastases more frequently harboured an intratumoural ductal carcinoma in situ (DCIS) component, showed higher ER/PR expression and lower Ki-67, and were predominantly luminal A or luminal B/HER2−, whereas AUS performance appeared more favourable in HER2-enriched and triple-negative tumours. ROC-derived cut-offs for ER (82.5%), PR (25.0%) and Ki-67 (17.5%) provided only moderate discrimination (area under the curve 0.68–0.70). In multivariable analysis, absence of a DCIS component and low PR expression were independently associated with reduced odds of SLNB positivity, suggesting that DCIS and high PR may act as indicators of residual nodal risk in ultrasound-negative axillae. All estimates are limited by sample size and wide confidence intervals and should be interpreted as hypothesis-generating. Conclusions: Preoperative AUS alone cannot reliably exclude sentinel lymph node metastasis after NACT, particularly in luminal A and luminal B/HER2− tumours with strong hormone receptor expression and a low proliferative index. Until prospective, biology-stratified trials confirm the safety of omission, SLNB should not be withheld solely on the basis of a negative AUS in these subtypes. Axillary management after NACT should systematically integrate both imaging findings and tumour biology when considering further de-escalation of surgery. Full article

Background/Objectives: Fibrillarin (FBL) is a key nucleolar methyltransferase involved in ribosome biogenesis through 2′-O-ribose methylation of rRNA. While its oncogenic role has been reported in several cancer types, its expression and function in human colorectal cancer (CRC) have remained largely unexplored. This study aims to investigate the expression of FBL in human CRC tissues and cell lines and to determine its functional role in tumor progression and metastasis. Methods: We examined FBL expression in paired human CRC primary tumors and liver metastases using immunohistochemistry. Functional studies were performed using SW-480 (primary tumor) and SW-620 (lymph node metastasis) CRC cell lines derived from the same patient. Cell migration, invasion, and 3D spheroid growth were analyzed following FBL downregulation. In vivo tumor growth was assessed in SCID mice xenografted with FBL-deficient cells. Molecular changes were explored through phosphorylation arrays and Western blotting. Results: FBL expression was significantly higher in human metastatic lesions than in primary tumors. FBL downregulation impaired migration, invasion, and spheroid growth in SW-480 and SW-620 cells and reduced tumor growth in vivo. Mechanistically, FBL inhibition decreased activation of MAPK/ERK, PI3K/AKT, and JNK/p38 pathways and reduced phosphorylation of the transcription factor CREB. Conclusions: Our study identifies FBL as a potential contributor to colorectal cancer progression, with elevated expression associated particularly with metastatic disease. By demonstrating that FBL expression is elevated in patient-derived metastatic tissues and functionally promotes migration, invasion, and tumor growth, our findings expand the role of ribosome biogenesis factors beyond protein synthesis. The observed suppression of key oncogenic pathways and CREB phosphorylation upon FBL inhibition suggests that FBL integrates ribosomal regulation with cancer cell signaling. These insights open new avenues for targeting nucleolar activity in advanced CRC and highlight FBL as a potential biomarker and therapeutic target in metastatic disease. Full article

Primary urethral cancer is an extremely rare malignancy, accounting for less than 1% of all cancers. Due to its rarity, evidence-based treatment recommendations are lacking. We report the case of a 44-year-old woman with metastatic squamous cell urethral carcinoma and paraneoplastic Sweet syndrome. The tumor was p16-positive with strong PD-L1 expression (CPS > 50%). Following surgery and adjuvant chemoradiotherapy, the patient developed hepatic and lymph node metastases. Pembrolizumab was initiated as first-line systemic therapy because of prior hematologic toxicity with cisplatin. After four cycles, complete radiologic remission of metastases and full resolution of the Sweet syndrome were achieved. This case highlights the potential benefit of immune checkpoint inhibitors in metastatic urethral SCC, particularly in p16-positive and PD-L1-high tumors, suggesting an inflamed and immunogenic microenvironment. To our knowledge, this is the first reported case of paraneoplastic Sweet syndrome successfully treated with pembrolizumab. These findings underscore the need for further investigation of immunotherapy in this rare and challenging malignancy. Full article

In non-small cell lung cancer (NSCLC), [¹⁸F]FDG-PET/CT is limited in pretherapeutic lymph node (LN) staging by false-positives. We previously demonstrated that a machine learning (ML) classifier using routine [¹⁸F]FDG-PET/CT and clinical variables can improve diagnostic accuracy compared to visual assessment. The present study aimed at independent validation. Cohort 1 (Charité) included 87 NSCLC patients (surgical and non-surgical), prospectively enrolled at our institution. Cohort 2 (TCIA) comprised 124 patients with primary surgery from the multi-institution NSCLC Radiogenomics dataset. Our ML classifier for differentiating N0/1 vs. N2/3 status was applied without modification. As comparator, the combined standard PET/CT criterion of “mediastinal LN uptake > mediastinum and/or short-axis > 10 mm” was used. Histology of N2/3 LNs served as reference standard. Prevalence of pN2/3 differed significantly between cohorts (Charité: 40%, TCIA: 12%; p < 0.001). Specificity was similar between ML and the standard PET/CT criterion in the Charité cohort (65% vs. 60%; p = 0.5) but significantly higher with ML in TCIA (90% vs. 70%; p < 0.001). Sensitivity for pN2/3 was comparable between the two comparators in both the Charité cohort (97% each; p = 1.0) and TCIA (27% vs. 33%; p = 1.0). Lower sensitivity in TCIA patients reflects the preselection of surgical patients who had already been clinically staged and deemed suitable for surgery. The diagnostic performance of the ML classifier and its (potentially) superior specificity were thus successfully validated in two independent cohorts. Full article

Background/Objectives: Melanomas may develop de novo or in association with a pre-existing nevus (nevus-associated melanoma, NAM). Whether these subtypes differ in their clinical and biological behavior remains uncertain. We aimed to compare the clinicopathologic features and outcomes of NAM and de novo melanoma (DNM) in a large single-center cohort. Methods: We retrospectively analyzed 378 patients with invasive melanoma diagnosed between 2007 and 2021 at a tertiary referral center. Tumors were classified as NAM when histopathologic continuity with a nevus was present, and as DNM otherwise. Clinical, histologic, and prognostic variables were compared using univariate and multivariate analyses. Results: Of 378 melanomas, 90 (24%) were NAM and 288 (76%) were DNM. Patients with NAM were slightly younger (mean 52 vs. 54 years) and more often presented with tumors on the trunk (65.6% vs. 51.7%). NAMs exhibited lower Breslow thickness (0.55 vs. 0.84 mm), reduced mitotic activity (0.17 vs. 1.21/mm²), and less frequent ulceration (2.2% vs. 9.4%). Distant metastases occurred only in DNM (6.6%). Sentinel lymph node positivity (1.1% vs. 6.3%) and melanoma-specific mortality (0% vs. 0.69%) did not differ significantly. Multivariate analysis identified Breslow thickness and mitotic rate as independent predictors of subtype. Conclusions: NAMs present with more favorable histopathologic features than DNMs, yet long-term outcomes appear similar. These findings support divergent pathways of melanoma development and underscore the need for molecular and imaging studies to refine risk stratification and guide management. Full article

Canine apocrine gland anal sac adenocarcinoma (AGASAC) is an aggressive malignancy with a high incidence of regional lymph node metastasis at diagnosis. Platelet-derived growth factor receptor beta (PDGFRβ) is a receptor tyrosine kinase involved in oncogenic signaling and angiogenesis, representing a potential therapeutic target. Its expression in different AGASAC histotypes has not been fully defined. This study evaluated microscopic patterns and PDGFRβ immunohistochemical expression in three normal anal gland sacs, 51 primary AGASACs (12 non-metastatic, 39 metastatic), and 33 corresponding nodal metastases. PDGFRβ expression was semi-quantitatively scored and statistically analyzed. Histotypes included 26 mixed with solid prevalence, 11 pure solid (including 1 comedo-carcinoma), 9 mixed with tubular prevalence, 4 tubular, and 1 neuroendocrine-like. PDGFRβ was expressed in normal anal sac glands and in 43/51 tumors (5–100% positive cells): 19/26 mixed with solid prevalence, 10/11 solid, 9/9 mixed with tubular prevalence, 4/4 tubular, and 1 neuroendocrine-like. PDGFRβ labeled 27/33 nodal metastases. PDGFRβ expression was highest and more intense in tumors with a tubular pattern. The statistical trend indicated a correlation of AGASAC dedifferentiation to reduced PDGFRβ expression, but no statistical significance was found. Rare AGASAC variants (solid comedo-carcinoma and neuroendocrine-like) were described for the first time. PDGFRβ expression was higher in tubular tumors and commonly detected in primary and metastatic lesions. These findings support exploring TKI therapy for specific AGASAC histotypes. Further studies integrating receptor activation and treatment outcomes are warranted to clarify predictive and prognostic relevance. Full article

Background and Clinical Significance: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine cutaneous malignancy with increasing incidence among elderly, immunocompromised patients or individuals exposed to ultraviolet radiation. Case Presentation: We present the case of an 84-year-old Caucasian male with no history of immunosuppression, who was admitted for asthenia, dysphagia, weight loss, and generalized weakness. Clinical and imaging investigations revealed a violaceous tumor on the right arm and disseminated metastases affecting the liver, spleen, bones and lymph nodes. A liver biopsy confirmed a small round blue cell neoplasm suggestive for MCC, although immunohistochemistry could not be performed due to the patient’s fulminant deterioration and death within 12 days of admission. Conclusions: This case is notable for its exceptionally rapid progression, particularly splenic involvement, and absence of known immunosuppressive factors. It highlights the existence of highly proliferative MCC subtypes with potential for bypassing classical metastatic pathways. Early clinical suspicion and prompt histological evaluation are essential for diagnosis, although the prognosis remains poor in advanced stages. Due to fulminant deterioration, immunohistochemistry could not be performed; therefore, the diagnosis is highly suggestive based on clinical, imaging, and morphological correlation. Full article

Breast cancer rarely metastasizes to the parotid gland. Early recognition in patients with a history of malignancy is critical for timely diagnosis and treatment. We report the case of a 60-year-old female who presented with a two-month history of a left periauricular mass, 18 months after completing treatment for breast carcinoma. Despite the patient’s oncologic history, initial evaluation by our maxillofacial surgery service showed no evidence of distant metastasis, and we initially ruled out metastatic disease. Clinical evaluation, contrast-enhanced computed tomography (CT), fine-needle aspiration cytology (FNAC), PET-CT, and histopathological analysis were performed. Given the persistent and progressive nature of the mass, surgical excision was undertaken to obtain a definitive diagnosis and provide local control. Immunohistochemical analysis of the resected mass and adjacent node confirmed metastatic breast carcinoma infiltrating the parotid parenchyma and an intra-parotid lymph node, with strong positivity for progesterone receptor (PR) and carcinoembryonic antigen (CEA). Unfortunately, several months later, the patient developed pulmonary metastases and subsequently died. Full article

Background/Objectives: Advanced gastric cancer usually has an unfavorable prognosis. Stroma AReactive Invasion Front Area (SARIFA) is a newly recognized biomarker of aggressiveness, easily recognized as five tumor cells in direct contact with adipocytes in perigastric, submucosal, and perivascular adipose tissue. We investigated this phenomenon and correlated it with other pathohistological variables. Material and Methods: The sample includes 102 Croatian patients with locally advanced gastric cancer, who underwent total gastrectomy/lymphadenectomy between 2012–2018 and in 2023 at University Hospital Split, Croatia, and had pathological stage pT3 or pT4. Representative histological specimens were analyzed for SARIFA, and results were compared with other variables and overall survival. External validation and gene expression analysis of CD36 and FABP4 were performed using the TCGA-STAD cohort. Results: SARIFA was significantly associated with positive pN status (p = 0.009) and perineural invasion (p = 0.043). Patients with SARIFA had a more than fivefold increased risk of nodal involvement (OR = 6.35; 95% CI: 1.35–29.84; p = 0.019). Lymphovascular invasion (LVI) was associated with nodal disease (OR = 4.39; 95% CI: 1.194–16.143; p = 0.026), and SARIFA was marginally associated (OR = 4.886; 95% CI: 0.985–24.241; p = 0.052). Patients who had both LVI and SARIFA had a higher proportion of affected lymph nodes (p = 0.009). SARIFA status did not significantly affect overall survival. Gene expression analysis showed a significant increase in CD36 expression, while FABP4 expression was elevated but not statistically significant, in SARIFA-positive cases. Conclusions: SARIFA could be used as a marker for invasiveness and further investigated due to its predictive potential. Full article

Canine prostatic carcinoma is a highly aggressive neoplasm with a strong tendency to metastasize, most commonly to regional lymph nodes, lungs, and bones. However, skeletal muscle and myocardial involvement are rarely reported. This report describes an 11-year-old intact male Maltese dog with a two-month history of anorexia and lethargy, referred for further evaluation after failing to respond to piroxicam therapy. Diagnostic imaging revealed a prostatic mass and multiple rim-enhancing lesions in the epaxial musculature and left ventricular wall, without evidence of metastasis to the lymph nodes, lungs, or other visceral organs. Hemostatic analysis indicated a hypercoagulable state. Postmortem examination confirmed metastatic prostatic carcinoma involving the semispinalis, multifidus, and myocardium. Histologically, the neoplastic cells exhibited similar morphology at the primary and metastatic sites. Immunohistochemistry revealed strong cytokeratin expression and absence of uroplakin III, consistent with a non-urothelial epithelial origin. No evidence of lymphatic involvement was observed. To the best of our knowledge, this is the first documented case of canine prostatic carcinoma with exclusive myotropic and myocardial metastases. These findings suggest a possible hematogenous metastatic route and highlight the importance of including muscle and cardiac tissues in staging protocols for canine prostatic carcinoma, even when lymphadenopathy or pulmonary lesions are absent. Full article

Aims: The purpose of this study was to evaluate survival outcomes and recurrence patterns following curative-intent resection of pancreatic neuroendocrine tumours (PNETs) at a UK tertiary centre. The secondary aims included identifying prognostic clinicopathological factors that influenced survival. Methods: Patients undergoing curative-intent surgical resection for PNETs between August 2010 and March 2024 were retrospectively reviewed. The data collated included demographics, histopathology, recurrence, and survival outcomes. Results: Eighty-six patients were included, with a median age of 61.5 years (IQR: 50–71) and an equal sex distribution. Most tumours were solitary (88.4%) and located in the pancreatic tail (57%), with distal pancreatectomy performed in 75% of cases. The median tumour size was 25 mm (IQR: 13–40). Lymph node metastases were observed in 23.3% of patients, and R0 resection was achieved in 67%. Most of the PNETs resected were WHO grade 1 tumours (65.1%), followed by grade 2 tumours (26.7%). Postoperative morbidity occurred in 37.2% of cases, while the 30-day postoperative mortality rate was 1.5%. Recurrence was observed in 13.95% of patients, with a median time to recurrence of 36.3 months. The 5-year overall survival (OS) was 83.0%, with a median OS and disease-free survival (DFS) of 143.3 months and 147.0 months, respectively. Multivariable analysis revealed that poorer DFS was associated with larger tumours (p = 0.009), higher tumour grade (p = 0.006), male sex (p = 0.039), vascular invasion (p = 0.003), perineural invasion (p = 0.042) and lymph node metastases (p = 0.015). OS was significantly influenced by the Charlson Comorbidity Index (p < 0.001) and tumour grade (p = 0.025). Conclusions: PNETs are associated with excellent long-term survival following curative-intent resection. However, adverse pathological features are linked to an increased risk of recurrence and a poorer prognosis. Full article

Background/Objectives: The implementation of adaptive radiation therapy (ART) is increasingly becoming widely available in the clinical practice of radiotherapy (RT). For patients with pharyngeal cancer receiving RT, this study aimed to develop a deep learning (DL) model by merging baseline and ART simulation computed tomography (CT) images to predict treatment outcomes. Methods: Clinical and imaging data from 162 patients of newly diagnosed oropharyngeal or hypopharyngeal cancer were analyzed. All completed definitive treatment and their baseline and ART non-contrast simulation CTs were utilized for training. After augmentation of the CT images, a deep contrastive learning model was employed to predict the occurrence of local recurrence (LR), neck lymph node relapse (NR), and distant metastases (DM). Receiver operating characteristic curve analysis was conducted to evaluate the model’s performance. Results: Over a median follow-up period of 34 months, 53 (32.7%), 36 (22.2%), and 23 (14.0%) patients developed LR, NR, and DM, respectively. Following the integration of prediction results from baseline and ART simulation CTs, the area under the curve for predicting the occurrence of LR, NR, and DM reached 0.773, 0.747, and 0.793. At the same time, the accuracy for the three endpoints was 72.4%, 74.7%, and 75.7%, respectively. Conclusions: For patients with pharyngeal cancer ready to receive RT-based treatment, our proposed models can predict the development of LR, NR, or DM through baseline and ART simulation CTs. External validation needs to be conducted to confirm the model’s performance. Full article

Background & Objectives: Current guidelines recognize a subgroup of favorable intermediate-risk (FIR) ISUP grade group (GG) 2 prostate cancer (PCa) that may be eligible for active surveillance (AS). However, upgrading and upstaging to more aggressive disease are frequently observed. We aimed to identify risk factors for adverse pathology in this cohort to better define clinical scenarios where AS may need to be reconsidered. Methods: We retrospectively analyzed 170 patients diagnosed with ISUP GG2 PCa by multiparametric MRI (mpMRI)/TRUS fusion biopsy, all treated with radical prostatectomy (RP). Patients with FIR disease were evaluated for upstaging to ≥pT3 or upgrading to ISUP GG of ≥3 at RP. Multivariable logistic regression identified predictors of adverse pathology. Key Findings and Limitations: Among 170 FIR patients, median PSA was 5.6 ng/mL. Most had PI-RADS 4 (57%) or 5 (20%) lesions; 13% were diagnosed by systematic biopsy only. At RP, 28% showed adverse pathology, including 5 patients (2.9%) with lymph node metastases. Independent predictors were a PI-RADS Score of ≥4, PSA of >7 ng/mL, and clinical T-stage on digital rectal examination. Conclusions and Clinical Implications: Nearly 1/3 of FIR PCa patients were upstaged to high-risk PCa at RP. Based on these findings, AS in clinical practice should only be considered after thorough patient counseling and performed using a stringent follow-up and staging regimen to minimize the risk of further disease progression. A key limitation is the lack of the percentage of Gleason pattern 4. Full article

Background: Lymph node (LN) involvement is a negative prognostic factor for patients with cholangiocarcinoma (CCA). Preoperative assessment of the LN could potentially aid therapy decision making. Endoscopic ultrasound (EUS) can be used to sample suspicious LN. The aim of this study was to evaluate the clinical impact of EUS for suspicious LN in patients with presumed resectable CCA. Methods: In this single-center cohort study, patients with potentially resectable CCA who underwent preoperative linear EUS between 2019 and 2024 were retrospectively included. The primary aims were the percentage of malignant LN detected and the clinical impact of EUS, which was defined as the percentage of patients who were precluded from surgical exploration due to pathologically confirmed LN metastases found with EUS tissue acquisition (EUS-TA). The secondary aim was the complication rate of EUS-TA. Results: A total of 135 patients were included, of whom 12 (8.9%) had intrahepatic CCA (iCCA), 65 (48.1%) had perihilar CCA (pCCA), 13 had (9.6%) middle bile duct CCA (mCCA), and 45 (33.3%) had distal CCA (dCCA). Across 148 EUS procedures, 139 LNs were identified, and EUS-TA was performed on 63 LNs among 55 patients. LN metastases were detected by EUS-TA for iCCA, pCCA, mCCA, and dCCA, in 25%, 6.2%, 15.4%, and 4.4%, respectively. EUS and EUS-TA influenced surgical work-up for iCCA, pCCA, mCCA, and dCCA in 25%, 1.5%, 15.4%, and 0.0%, respectively. No complications associated with EUS were noted. Conclusions: Preoperative EUS for nodal staging had an important clinical impact in patients with presumed resectable iCCA and mCCA, but less for pCCA and dCCA. Further prospective studies should investigate whether systematic nodal staging with EUS could improve preoperative decision making even further. Full article

Background: This study aimed to evaluate the prognostic significance of para-aortic lymph node dissection (PALND) during pancreatic head resection and the impact of para-aortic lymph node metastasis (PALN+) on survival outcomes in patients with resected pancreatic ductal adenocarcinoma (PDAC). Methods: A retrospective analysis was conducted on 198 patients who underwent primary pancreatic head resection for PDAC at the University Hospital Erlangen between 2003 and 2022. Patients were stratified based on the presence or absence of PALND and PALN metastases, and their clinicopathological characteristics and survival outcomes were compared. Results: Of the 198 patients, 113 (57%) underwent additional PALND. PALND itself had no significant impact on overall survival (OS) or disease-free survival (DFS) compared to those without PALND. Among patients who underwent PALND, 17 (15%) had PALN metastases (PALN+). PALN+ patients exhibited significantly worse pathological features, including a higher rate of regional lymph node metastases (pN+), lymphovascular invasion (L1) and vascular invasion (V1). Survival analysis showed that PALN+ was associated with significantly poorer OS (8.7 vs. 29.3 months, p < 0.001) and DFS (3.8 vs. 17.0 months, p < 0.001). In multivariate analysis, PALN+ was confirmed as an independent prognostic factor for both OS (HR 1.9 [1.0–3.6], p = 0.035) and DFS (HR 2.2 [1.2–4.0], p = 0.006). Conclusions: While PALND does not impact survival outcomes in PDAC, it plays a crucial role in identifying PALN+ patients, who have significantly worse prognoses. PALN status should be integrated into clinical decision-making, particularly when considering intensified adjuvant therapy. Full article