Abstract Prostatic adenocarcinoma is a common malignancy with variable histologic patterns and clinical behavior. Although NKX3.1 is an established marker of prostatic origin, region-specific validation data, particularly in Indian populations and in routine diagnostic settings, remain limited. This study aimed to evaluate the diagnostic utility of NKX3.1 in prostatic adenocarcinoma in an Indian cohort, assess its expression across different Gleason grade groups including high-grade tumors, and determine its specificity in differentiating prostatic adenocarcinoma from histologic mimics and nonprostatic carcinomas encountered in routine practice. This 2-year prospective observational study included 100 formalin-fixed, paraffin-embedded tissue blocks comprising 50 prostatic adenocarcinomas, 10 histologic mimics, and 40 carcinomas from various nonprostatic primary sites. NKX3.1 immunohistochemistry was performed and evaluated semiquantitatively for percentage positivity and staining intensity. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. All 50 prostatic adenocarcinoma cases demonstrated nuclear NKX3.1 positivity (100% sensitivity), including tumors across higher Gleason grade groups. Most cases showed diffuse (> 76%) staining with predominantly moderate intensity. Histologic variants encountered included foamy gland morphology and prostatic intraepithelial neoplasia-like features, and one high-grade tumor with neuroendocrine-like morphology with retained NKX3.1 expression while being negative for neuroendocrine markers. NKX3.1 was negative in all histologic mimics and in 39 of 40 nonprostatic carcinomas, yielding a specificity of 98%. A single salivary gland intraductal papillary mucinous neoplasm showed focal nuclear positivity, highlighting a potential diagnostic pitfall. This study provides regional validation of NKX3.1 as a highly sensitive marker for prostatic adenocarcinoma in an Indian population, including high-grade tumors. NKX3.1 is a highly sensitive marker of prostatic epithelial lineage and is particularly useful for confirming prostatic origin in high-grade, poorly differentiated, and metastatic tumors. While it has a limited role in distinguishing benign from malignant glands in routine primary prostate biopsies, its strong and consistent nuclear expression supports its use in diagnostically challenging and metastatic settings.
Introduction Despite maximal surgical resection and adjuvant chemoradiotherapy, glioma recurrence remains frequent, mandating robust prognostic biomarkers. Ferritin light chain (FTL) has been implicated in reprogramming the immune microenvironment and aggravating glioma progression. Objectives We therefore interrogated the prognostic value of FTL in low-grade glioma (LGG) and explored its association with immune microenvironment features. Materials and Methods The specimens in this study were obtained from 14 patients with LGG. FTL messenger ribonucleic acid expression was quantified by quantitative real-time polymerase chain reaction, and protein levels were assessed by Western blotting. Bioinformatics analyses were conducted using The Cancer Genome Atlas-LGG and GTEx data sets, with validation in the Chinese Glioma Genome Atlas cohort. Immune infiltration patterns were characterized by integrated analyses of TIMER, CIBERSORT, TISIDB, and GSVA. Survival outcomes were evaluated using Cox multivariate models, with FTL expression dichotomized at the median. Results The results showed that FTL is highly expressed in LGG and is associated with shorter survival of LGG patients. Further analysis revealed that M2-tumor-associated macrophages (M2-TAMs) were positively correlated with FTL expression and were collectively associated with the overall survival of LGG patients. Additionally, FTL expression correlated with molecules and signaling pathways associated with M2-TAM polarization. Conclusion High FTL expression is associated with both poor prognosis in LGG and M2-TAM-related immunosuppressive signatures.
Introduction Hepatic dysfunction is frequently encountered during treatment of pediatric acute lymphoblastic leukemia (ALL), particularly during induction chemotherapy. Data from low- and middle-income countries remain limited, where children often present with advanced disease and baseline biochemical abnormalities. Objective This article aims to evaluate the frequency, severity, and temporal trends of hepatic biochemical abnormalities and clinically meaningful hepatic dysfunction during induction chemotherapy in children with ALL. Materials and Methods In this prospective cohort study, 62 children aged 1 to 12 years with newly diagnosed B cell ALL treated on the ICiCLe ALL-14 protocol were evaluated. Liver function parameters were assessed serially at predefined time points during induction. Hepatic parameters were analyzed as (1) biochemical abnormalities (including aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], bilirubin, albumin, prothrombin time [PT]/international normalized ratio [INR]) and (2) clinically meaningful hepatic dysfunction, defined using liver-specific indicators (bilirubin and ALT >= CTCAE grade 2). Results At baseline, 88.7% of patients had at least one abnormal biochemical parameter, predominantly elevated AST and ALP, which are not liver-specific in children. Clinically meaningful hepatic dysfunction (based on bilirubin and ALT criteria) was observed in similar to 6 to 8% of patients at presentation. During induction, bilirubin and ALT levels increased, while AST abnormalities declined over time. Although biochemical abnormalities were frequent (up to 95.1% by day 29), most were mild (grade: 1-2) and transient. Clinically significant hepatotoxicity remained uncommon, and no patient developed acute liver failure or required permanent modification of chemotherapy. Conclusion Although hepatic biochemical abnormalities are common during induction therapy in pediatric ALL, they are largely driven by nonspecific parameters such as AST and ALP. When assessed using liver-specific indicators, clinically meaningful hepatic dysfunction is infrequent. These findings highlight the importance of distinguishing nonspecific biochemical abnormalities from true hepatotoxicity to avoid overestimation of liver injury and improve interpretation of liver function tests during therapy.
Introduction High-dose methotrexate (HDMTX) constitutes a critical component of modern pediatric acute lymphoblastic leukemia (ALL) protocols, significantly improving disease control and survival. However, treatment-related toxicities frequently interrupt therapy and influence outcomes, particularly in resource-constrained environments. Objective This article studies the incidence, spectrum, and predictors of HDMTX-related toxicities in children with ALL.Materials and Methods A prospective cohort study was conducted over 18 months, including 40 children aged 1 to 12 years receiving HDMTX therapy, contributing a total of 138 HDMTX cycles for analysis. Toxicities were graded using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Serial hematological, hepatic, and renal parameters were assessed at baseline, 24 hours, 48 hours, and day 7 postinfusion. Risk factors were evaluated using multivariate logistic regression, with analyses performed at the cycle level to account for repeated observations per patient. Results Across 138 HDMTX cycles derived from 40 patients, anemia was the most common hematological toxicity (94.9%), followed by thrombocytopenia (31.9%) and febrile neutropenia (23.2%). Hepatotoxicity occurred in 89.1% of cycles, but renal toxicity was infrequent (1.4%). The T-cell immunophenotype independently predicted febrile neutropenia (adjusted odds ratio [OR] 2.84, 95% confidence interval [CI] 1.19-6.77; p = 0.018) and mucositis (adjusted OR 3.21, 95% CI 1.39-7.41; p = 0.006). Female gender was associated with elevated transaminases (adjusted OR 2.57, 95% CI 1.25-5.29; p = 0.011), while the first HDMTX cycle predicted thrombocytopenia (adjusted OR 2.33, 95% CI 1.09-4.98; p = 0.028). Hematological parameters showed transient nadirs at 48 hours with recovery by day 7.Conclusion HDMTX demonstrates acceptable safety when delivered with standardized supportive care. Early identification of clinical risk factors enables individualized toxicity monitoring and optimization of treatment delivery in pediatric ALL.
Metastatic lesions to the skull base are uncommon, with colorectal cancer being a rare primary. Orbital metastases are infrequent, often presenting with nonspecific symptoms that can delay diagnosis. The involvement of the greater wing of sphenoid (GWS) is especially unusual, making early detection challenging. We present a unique case of a young woman in her early 20s who initially presented with ocular symptoms due to a metastatic lesion in the GWS. Radiological investigations revealed a lytic lesion with orbital and middle cranial fossa extension. Histopathological analysis confirmed adenocarcinoma with immunohistochemical markers indicative of colorectal origin. Postoperative positron emission tomography-computed tomography scan identified the primary rectal tumor and widespread metastases. This case emphasizes the importance of maintaining a high degree of suspicion for rare metastatic sites, particularly in young patients, and the critical role of advanced imaging and comprehensive histopathological assessment in diagnosis and management.
