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The RAS-RAF-MEK-ERK signaling cascade is the most frequently affected signaling pathway in colorectal cancer. BRAFV600E mutations serve as a drug-treatable hotspot and KRAS mutations as a predictor of susceptibility to anti-epidermal growth factor receptor therapy. Concomitant non-V600E BRAF and KRAS mutations may coexist and are rarely reported in the literature. We report a patient of colorectal carcinoma with inguinal lymph node metastases harboring mutations at the KRAS and BRAF non-V600E mutation codon detected by next-generation sequencing with an emphasis on clinical, pathological, and therapeutic implications of the mutation and review of the literature. [ABSTRACT FROM AUTHOR]

Byline: Kiran. Malhotra, Mohammad. Kaif, Hardeep. Malhotra, Nuzhat. Husain Intramedullary location is seldom seen in spinal cord neoplasms. Ependymomas and astrocytomas comprise the vast majority of these intramedullary lesions. Primary [...]

Small cell lung carcinoma (SCLC) is characterized by rapid growth and an aggressive clinical course. Standard therapy regimes have limited effects on disease course; therefore the prognosis of SCLC is poor. In the current study, the frequency of programmed death ligand 1 (PD-L1) expression in SCLC and its correlation with clinico-pathological features were evaluated. The study included 100 cases of SCLC wherein testing for PD-L1 was done with the SP263 clone on the Ventana benchmark XT system. Cases with > 1% PD-L1 expression in tumour cells or immune cells were categorized as positive. PD-L1 expression was identified in 14% of cases using the cut-off of ≥ 1%. The tumour proportion score was 10% and the immune proportion score was 9.78% using a cut-off of ≥ 1%. PD-L1 positive expression was more frequent in the male population with age > 40 years. All the patients with positive PD-L1 expression were smokers. In the PD-L1 positive group, presence of necrosis was identified in 71.4% of cases and when compared with the PD-L1 negative subgroup this finding was statistically significant (p = 0.010). Personalized targeted therapy for cases of SCLC is still under evaluation. The use of immunotherapeutic targets, such as PD-L1, may help to define a new treatment strategy for SCLC. Development of new treatment strategies may improve prognosis and survival. [ABSTRACT FROM AUTHOR]

Byline: Saumya. Shukla, Nuzhat. Husain, Mohammed. Kaif, Rupali. Awale, Sridhar. Mishra, Kiran. Malhotra Background: Gliomas are aggressive tumors with limited treatment options. Immunotherapy targets are under evaluation as new therapeutic [...]

Byline: Kiran. Malhotra, Hardeep. Malhotra, Rakesh. Singh, Shivi. Mohini, Nuzhat. Husain Sir, An 18-year-old male patient presented with recurrent headaches for one year. He had two previous episodes of complex [...]

Background: Immunotherapy currently stands as a novel treatment option, specifically in cases of advanced non-small cell lung carcinoma (NSCLC). Expression of programmed death ligand-1 (PD-L1) in tumor cells forms the mainstay for the use of anti-PD-L1 monoclonal antibodies in the treatment of NSCLC. Aims: The objectives of the study were to assess utility of cell blocks for testing of PD-L1 in adenocarcinoma lung and to compare the expression of PD-L1 in cell blocks and the corresponding biopsy specimens. Materials and Methods: The current study was a prospective case series that included 20 cases of NSCLC–adenocarcinoma lung. Cases included in the study had biopsies performed from lung masses, along with which cell blocks were prepared from fine needle aspiration cytology (FNAC) samples. Testing for PD-L1 was done using the monoclonal PD-L1 antibody, SP-263 clone on the Ventana Benchmark XT system. PD-L1 expression was assessed only in the tumor cells, and cases with >1% expression, cytoplasmic or membranous, in tumor cells were categorized as positive. Results: PD-L1 expression was identified in the biopsy samples of tumor cells of 20% of cases (n = 4/20). In the corresponding cell blocks, PD-L1 expression was identified in the tumor cells of 15% of cases (n = 3/20). Sensitivity and specificity of cell blocks were 75% and 100%, respectively. Positive and negative predictive values were 100% and 94.12%, respectively. Conclusion: PD-L1 testing has both predictive and prognostic implications. PD-L1 testing in cell block samples is a potential alternative, specifically in cases where biopsy tissue is minimal or unavailable. [ABSTRACT FROM AUTHOR]

Malignant melanoma of the gall bladder is rare. Most cases are metastatic and primary gall bladder melanoma is even more rare. We report a case of primary malignant melanoma of the gall bladder which illustrates the diagnostic challenge posed by this condition. Histopathology and immunohistochemistry play a pivotal role in making a diagnosis and ruling out conditions which mimic it such as xanthogranulomatous cholecystitis and other relatively common epithelial malignancies. We tested for prognostic and predictive markers including BRAF and PD-L1 and immunohistochemistry showed positive staining for BRAF. The tumour cells expressed HMB-45 and were negative for cytokeratin and CD68, favouring a diagnosis of malignant melanoma and excluding the possibility of xanthogranulomatous cholecystitis and carcinoma. On follow-up at 3 months there was no evidence of recurrence of metastasis. [ABSTRACT FROM AUTHOR]