Head and neck squamous cell carcinoma (HNSC) present a significant treatment challenge due to variability in radiotherapy response, where glycolysis may play a pivotal role in modulating sensitivity. This study aimed to develop a glycolysis-associated biomarker for radiotherapy sensitivity.

We analyzed gene expression and clinical data from 491 HNSC patients and single-cell RNA sequencing to assess glycolysis activity in HNSC. A glycolysis-associated radiosensitivity index (RI) was developed using Cox regression analysis of glycolysis-related genes. Immune microenvironment profiles, functional pathways, and therapeutic responses were analyzed via using ssGSEA, CIBERSORT, TIDE, and pRRophetic. In vitro experiments validated glycolytic activity and radiosensitivity in HNSC cell lines.

The study identified that low glycolytic activity significantly correlates with improved overall survival in HNSC patients following radiotherapy, while high glycolytic activity is associated with radio-resistance. Using a RI based on glycolysis-related gene expression, we successfully stratified patients into RS and RR groups. RS tumors exhibited significantly higher immune cell infiltration and lower TIDE scores, indicating a better response to immunotherapy. In contrast, RR tumors showed increased sensitivity to chemotherapy agents, including platinum and EGFR/HER2 inhibitors. Single-cell RNA sequencing revealed that high-glycolysis tumors had diminished immune cell infiltration, particularly lacking CD8+ T cells, supporting the notion of immune evasion. In vitro validation further demonstrated that radioresistant CAL-27IR cells displayed elevated glycolytic activity and upregulation of key genes associated with the RI, showing the link between glycolysis and radiation resistance.

This study emphasizes the importance of glycolytic activity in influencing radiotherapy sensitivity and highlights the potential of the RI as a predictive biomarker, paving the way for improved personalized treatment strategies in HNSC.

Adenoid cystic carcinoma (ACC) of the head and neck is a rare malignancy with high rates of perineural invasion (PNI) and distant metastasis. Although the tumor-node-metastasis (TNM) staging system provides a crucial anatomical foundation, it may not fully capture the biological heterogeneity of ACC. Existing predictive models often lack robust external validation or contain too many variables for routine clinical use. This study aimed to develop and validate a simplified prognostic model using a multi-algorithm machine learning (ML) consensus approach.

This retrospective study included patients with pathologically confirmed primary head and neck ACC and complete follow-up data from two cohorts: a training cohort from the Surveillance, Epidemiology, and End Results (SEER) database (n=2,870) and an external validation cohort from Sichuan Cancer Hospital (n=172). The primary endpoint was overall survival (OS), defined as a binary outcome (all-cause mortality vs. survival). Clinical variables were extracted from SEER via database queries and from the external cohort via medical records and telephone interviews. The SEER cohort was divided into training and internal testing sets at a 7:3 ratio. Traditional Cox regression was first applied to establish a prognostic baseline and construct a clinical nomogram. Subsequently, four ML algorithms-logistic regression (LR), classification and regression tree (CART), random forest (RF), and support vector machine (SVM)-were used to build prognostic models. A SHapley Additive exPlanations (SHAP)-based consensus strategy was then applied across the four algorithms specifically for objective feature selection to identify a minimal set of core prognostic features.

A total of 3,042 patients were analyzed. In the external cohort, the median follow-up was 86.0 months, with 49 mortality events (28.5%) observed. Six core prognostic features were identified: M stage, age, brain metastasis, T stage, surgery, and N stage. The simplified LR model achieved the best performance among all tested algorithms, with an area under the curve (AUC) of 0.825 in the internal testing set. In the external validation cohort, it achieved an AUC of 0.817, outperforming the other three algorithms, with good calibration observed.

This study developed a simplified prognostic model for head and neck ACC based on six core features. The model showed promising discrimination in both the internal testing set (AUC =0.825) and the external validation cohort (AUC =0.817). However, the external cohort was relatively small (n=172), which limits our ability to fully assess the model's generalizability. These findings should therefore be interpreted with caution. Future prospective studies with larger, multi-center cohorts are needed to confirm these results before the model can be recommended for routine clinical use.

Pancreatic granulomas are uncommon and typically classified based on the presence or absence of caseation. Caseating granulomas are most often associated with tuberculosis, while non-caseating granulomas are usually secondary to systemic conditions such as sarcoidosis. Idiopathic cases are rare and can pose a significant diagnostic challenge, particularly when mimicking malignancy. We present a unique case initially suspected to be a neuroendocrine tumor, ultimately diagnosed as an idiopathic non-caseating pancreatic granuloma.

A 75-year-old female was evaluated for left upper quadrant abdominal discomfort accompanied by chronic diarrhea and intermittent palpitations. Initial laboratory studies were notable for a markedly elevated chromogranin A level of 3123 ng/mL, with normal urinary metanephrine levels Cross-sectional imaging with magnetic resonance imaging demonstrated a 2.5-cm cystic lesion communicating with the main pancreatic duct and an additional hypointense lesion involving the pancreatic tail. Despite clinical concern for a neuroendocrine neoplasm, ^68Ga-DOTATATE PET/CT demonstrated no radiotracer uptake within the pancreatic lesion. Subsequent endoscopic ultrasound revealed a 2.7-cm well-defined, homogeneous hypoechoic pancreatic mass with multiple enlarged peripancreatic lymph nodes. Cytologic examination of fine-needle aspiration specimens showed non-caseating granulomatous inflammation in the setting of otherwise benign pancreatic and lymphoid tissue. Comprehensive evaluation failed to identify an underlying infectious, inflammatory, or systemic cause, supporting the diagnosis of an idiopathic non-caseating pancreatic granuloma.

Non-caseating granulomas of the pancreas are rare, with sarcoidosis being the most frequently reported cause. Clinical presentation may include epigastric pain, weight loss, jaundice, fever, or nausea. Due to the potential overlap with malignancies, comprehensive diagnostic workup-including imaging, tissue sampling, and occasionally surgical intervention-is essential for accurate diagnosis and management.

Idiopathic non-caseating pancreatic granuloma is an exceptionally rare entity. A timely and thorough evaluation is critical to exclude malignancy and ensure appropriate patient management.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a rare, highly virulent neoplasm lacking a standardized therapeutic protocol. Because current evidence is scarce, systemic management guidelines are not well-defined. We aimed to address this lack of data by synthesizing individual patient-level data from case reports and retrospective series. Our goal was to characterize treatment patterns and survival, focusing on combination strategies using immune checkpoint inhibitors (ICIs).

A systematic literature search was performed in PubMed, Embase, and Web of Science from database inception to November 30, 2024, in accordance with PRISMA guidelines. Individual patient data were extracted from eligible published case reports and case series and pooled for unified survival analysis. Aggregated survival data from retrospective cohort studies were summarized for cross-study comparison. Overall survival (OS) was analyzed using the Kaplan-Meier method, and treatment-specific outcomes were visualized using swimmer plots and forest plots.

A total of 32 studies comprising 239 patients with thoracic SMARCA4-UT were included, consisting of 26 patients with individual-level data and 8 retrospective cohort studies. Patients were mostly male heavy smokers, and most cohort studies consisted of advanced-stage disease. In the pooled individual patient dataset, 46.2% of patients received first-line chemotherapy plus immunotherapy (Chemo-IO). The median OS (mOS) of pooled cases was 15.0 months, exceeding that reported in most retrospective cohorts treated predominantly with chemotherapy or immunotherapy monotherapy (mOS range, 4.0-7.7 months). Long-term survival was observed almost exclusively in patients receiving Chemo-IO or multimodal treatment. Clinical benefit from Chemo-IO was also observed in patients with negative PD-L1 expression.

Our analysis suggests that combination therapy based on ICIs correlates with better survival in thoracic SMARCA4-UT, regardless of PD-L1 expression. Data support using immunotherapy-based regimens early as a first-line treatment for this aggressive disease. These real-world findings offer guidance for clinical decision-making while prospective trials are unavailable.

Adult-onset Langerhans cell histiocytosis (LCH) involving the hypothalamic-pituitary region (HPR) is a rare and diagnostically challenging neoplasm, often presenting with severe neuroendocrine dysfunction. This report details the case of a young adult female who presented with panhypopituitarism and central diabetes insipidus (CDI) as the initial manifestation of multisystem LCH. The diagnostic journey, complicated by non-specific radiological findings mimicking common sellar pathologies, ultimately required histopathological confirmation via CD1a and S-100 immunohistochemistry. Management involved a multidisciplinary approach, yet the patient exhibited a suboptimal response to initial systemic chemotherapy, reflecting the refractory nature of adult multisystem disease. Partial remission was eventually achieved following salvage radiotherapy to the residual hypothalamic lesion. This case underscores the critical need to include LCH in the differential diagnosis of sellar masses with extensive endocrine dysfunction, highlights the diagnostic imperative of immunohistochemistry, and illustrates the therapeutic challenges and the enduring role of radiotherapy in managing refractory adult HPR-LCH, thereby contributing to the optimization of individualized management strategies for this complex disorder.

Primary neuroendocrine neoplasms (NENs) of the gallbladder are rare entities with a generally unfavorable prognosis. Among the subtypes of gallbladder neuroendocrine neoplasms (GB-NENs), gallbladder mixed adenoneuroendocrine carcinoma (GB-MANEC) is exceptionally rare and associated with a poor prognosis, representing a diagnostic and therapeutic challenge due to its dual differentiation. This article presents a rare case of GB-MANEC and reviews the pertinent literature on clinicopathological management in GB-MANEC.

A 51-year-old female patient presented with non-specific abdominal complaints and unexplained anemia. Preoperative imaging with abdominal ultrasonography and contrast-enhanced computed tomography (CT) demonstrated an irregular mass within the gallbladder lumen accompanied by wall thickening. The level of carbohydrate antigen 125 (CA125) was mildly elevated (77.10 U/mL; normal level, 0.0-35.0 U/mL). A gallbladder mass measuring approximately 3.0 cm × 2.5 cm × 2.0 cm was identified during the cholecystectomy. Intraoperative frozen section revealed findings consistent with gallbladder adenocarcinoma (GB-AC) accompanied by a component of neuroendocrine carcinoma (NEC). Consequently, a radical surgery (cholecystectomy, partial liver resection, and regional lymphadenectomy) was undertaken. Postoperative histopathological examination confirmed the diagnosis of a GB-MANEC, specifically a tubular adenocarcinoma combined with a NEC, and each component accounted for more than 30%, which was confirmed by immunohistochemistry, represented as positive for synaptophysin (Syn), chromogranin A (CgA), and Ki-67 (90%). Critically, all surgical margins were free of tumor involvement. Postoperative high-throughput sequencing of the tumor identified a pathogenic amplification of the gene ERBB2 Human Epidermal Growth Factor Receptor 2 (HER2); gene mutations of TP53, NOTCH1, and KIT; and a gene fusion of SDHC. Based on these findings, adjuvant chemotherapy was initiated with a combination of cisplatin, gemcitabine, and etoposide, alongside the HER2-targeted monoclonal antibody trastuzumab. During 7 months of postoperative follow-up, imaging studies and blood biochemical assessments showed no evidence of recurrence or metastasis, and the patient has remained free of recurrence.

This systematic review underscores the rarity and aggressive nature of GB-MANEC. A definitive diagnosis is primarily established through postoperative histopathology and immunohistochemistry. Surgical treatment remains the cornerstone of potentially curative treatment, while the dismal prognosis is often due to the high aggressiveness. Currently, the role of adjuvant chemotherapy remains undefined due to the extreme rarity of MANEC, thus highlighting the critical need for a multidisciplinary approach and further research to establish standardized postoperative management guidelines for the diagnosis and management of GB-MANEC.

Sentinel lymph node biopsy (SLNB) using [99mTc]Tc-albumin nanocolloid has emerged as a minimally invasive staging technique for selected patients with oral squamous cell carcinoma (OSCC). This study evaluates the feasibility of SLNB, the quality of patient selection, and radiation exposure during the procedure.

This retrospective single-center study included patients with oral squamous cell carcinoma clinically staged as cT1-cT2 cN0 who underwent SLNB using [99mTc]Tc-albumin nanocolloid. Sentinel lymph nodes were identified by preoperative imaging and intraoperative gamma probe detection. Histopathological findings guided further treatment. Radiation exposure to the surgeon was estimated using a point-source approximation. Clinical, pathological, and follow-up data were analyzed descriptively.

A total of 16 patients were included (11 males, 5 females; mean age 70.9 ± 11.1 years). Occult lymph node metastases were detected in 3 of 16 patients (18.8%), while tumor upstaging (pT>cT) occurred in 1 patient (6.3%). Sentinel lymph nodes were successfully identified in all patients. The mean administered technetium-99m activity was 100.9 ± 2.1 MBq, and surgery was performed after a mean interval of 26 h 03 min. The mean duration of surgery was 111.5 min. During surgery, the remaining radioactive activity averaged 5.1 MBq, and the surgeon's mean radiation exposure was 2.3 μSv. During follow-up, no regional nodal recurrences or delayed nodal failures were observed, and all patients were alive at the time of database lock.

Sentinel lymph node biopsy may represent a feasible staging approach in carefully selected patients with early-stage oral squamous cell carcinoma and clinically negative lymph nodes (cN0). The procedure demonstrated a high identification rate, low estimated radiation exposure, and successful detection of occult nodal metastases. However, the limited sample size and follow-up duration warrant cautious interpretation of the oncologic outcomes, and further prospective studies are required before the role of SLNB relative to elective neck dissection can be established.

Glioblastoma (GBM) represents the most prevalent primary malignant neoplasm of the central nervous system, frequently presenting with clinical manifestations such as elevated intracranial pressure, focal neurological deficits, and seizures. The incidental detection and diagnosis of glioblastoma two months subsequent to surgical intervention for traumatic brain injury (TBI) is exceptionally uncommon, and a causal link between TBI and subsequent glioma development remains unsubstantiated. To our knowledge, reports of low intracranial pressure hydrocephalus as a consequence of tumor resection surgery are very limited. In this report, we detail the case of a 50-year-old female patient who underwent surgical management for TBI. Two months postoperatively, space-occupying lesions were identified, prompting surgical resection, which confirmed the diagnosis of GBM through pathological examination. Following surgery, the patient received standard radiotherapy and chemotherapy. During her treatment course, she was hospitalized due to complications related to bone marrow suppression and suspected low-pressure hydrocephalus. Despite exhaustive therapeutic interventions, the patient ultimately succumbed to diffuse cerebral edema and brain herniation. This rare case involves a patient who, two months post-surgery for traumatic brain injury, unexpectedly identified a space-occupying lesion in the brain. Subsequent diagnostic evaluation confirmed the lesion as glioblastoma. Despite comprehensive treatment, the patient ultimately succumbed to tumor recurrence, bone marrow suppression, and low intracranial pressure. This case serves as a reference for the incidental discovery and subsequent treatment strategies in asymptomatic GBM patients, while also providing insights into treatment and research approaches for suspected low-pressure hydrocephalus occurring during the disease course. While noting that only a temporal association-not causation-can be inferred between TBI and GBM based on this single report.

The clinical significance of human epidermal growth factor receptor 2 (HER2)-low breast cancer remains controversial, particularly in early-stage, treatment-naïve patients. Because neoadjuvant therapy may alter tumor biology and nodal status, we specifically evaluated patients who underwent upfront surgery without prior systemic treatment. We also investigated whether the recently recognized HER2-ultralow subgroup exhibited differences in axillary metastatic involvement.

In this multicenter observational study, we retrospectively analyzed 407 patients with hormone receptor-positive early-stage breast cancer who underwent upfront surgery between 2017 and 2023 without neoadjuvant therapy. Patients were categorized as HER2-ultralow (immuno-histochemistry [IHC] 0), HER2-low (IHC 1+ or 2+ with fluorescence in situ hybridization [FISH] negative), or HER2-positive (IHC 3+ or 2+ with FISH positive). Groups were compared for sentinel lymph node (SLN) positivity. Multivariable logistic regression and receiver operating characteristic (ROC) analyses were used to identify predictors of axillary metastasis.

SLN positivity rates were similar across the HER2-ultralow (29.0%, n = 288), HER2-low (30.6%, n = 80), and HER2-positive groups (31.3%, n = 39) (p = 0.941). HER2 expression was not an independent predictor of SLN positivity. Lymphovascular invasion (LVI) was the strongest determinant (odds ratio = 5.42; 95% confidence interval: 3.13-9.39; p < 0.001). Larger tumor size and higher proliferative activity were independently associated with increased axillary involvement. ROC analysis showed higher discrimination for LVI (AUC = 0.68) than Ki-67 (AUC = 0.53) and tumor size (AUC = 0.61). Exploratory survival analyses demonstrated no statistically significant differences among groups; however, these findings should be interpreted cautiously because of the limited follow-up duration and low number of events.

In hormone receptor-positive early-stage breast cancer treated with upfront surgery, HER2 expression was not independently associated with axillary metastasis risk in this treatment-naïve cohort. Classical pathological factors, particularly lymphovascular invasion, larger tumor size, and higher proliferative activity, remained the principal determinants of axillary involvement.

Solid papillary carcinoma of the breast is a rare papillary neoplasm with distinctive morphology and frequent neuroendocrine differentiation. However, when an invasive component is sampled in a limited core needle biopsy specimen, its solid and nested architecture may mimic invasive ductal carcinoma. We report a case of invasive solid papillary carcinoma of the breast that was initially diagnosed as invasive ductal carcinoma and was ultimately confirmed by comprehensive histopathological and immunohistochemical evaluation.

A 53-year-old woman was referred to our hospital for treatment of right breast cancer detected by screening. Ultrasonography showed a 1.3-cm mass in the upper outer quadrant of the right breast. CT showed no distant metastasis, and breast MRI showed no apparent intraductal extension. The clinical stage was cT1N0M0, stage I. Core needle biopsy at the referring hospital was interpreted as invasive ductal carcinoma. Pathological review at our institution showed relatively uniform epithelial cells arranged in small nests and solid structures. The tumor was strongly positive for estrogen receptor and progesterone receptor, negative for human epidermal growth factor receptor 2, showed a low Ki-67 labeling index of 5%, and was positive for synaptophysin, suggesting invasive solid papillary carcinoma with neuroendocrine differentiation. The patient underwent breast-conserving surgery and sentinel lymph node biopsy. The resected specimen confirmed invasive solid papillary carcinoma. Postoperative Oncotype DX testing showed a recurrence score of 4. Adjuvant chemotherapy was omitted, and the patient received postoperative radiotherapy followed by endocrine therapy with anastrozole. She remains free of recurrence 1 year after surgery.

Invasive solid papillary carcinoma can mimic invasive ductal carcinoma on core needle biopsy. Careful morphological assessment combined with appropriate immunohistochemical evaluation is essential for an accurate diagnosis. In the present low-risk luminal case, adjuvant chemotherapy would probably not have been indicated even if the lesion had remained classified as invasive ductal carcinoma of no special type; however, preoperative recognition of this special subtype may still be clinically relevant for biopsy planning, axillary staging, surgical margin planning, and consideration of minimally invasive local treatment.