Molecular profiling and utility of cell-free DNA in nonsmall carcinoma of the lung: Study in a tertiary care hospital.

BACKGROUND: Lung carcinoma accounts to the most common cause of cancer globally. Optimal management of nonsmall cell lung carcinoma (NSCLC) requires prognostic biomarkers that help in targeted therapy and identification of tumor subsets with a distinctive molecular profile that can foretell response to therapy. Quantitative analysis of circulating cell-free DNA is considered as a possible aid for lung cancer screening. AIMS AND OBJECTIVES: The main aim of our study was detection of the clinicopathological spectrum of NSCLC, immunohistochemical (IHC) study of lung adenocarcinoma with epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and molecular expression of EGFR mutation using Formalin fixed paraffin embedded tissue (FFPE) and cell-free DNA (cfDNA) from blood samples. MATERIALS AND METHODS: It was a prospective and observational study conducted in the Department of Pathology in association with the Department of Chest Medicine in a tertiary care hospital for 18 months, done on 50 patients. Histological subtyping of lung carcinomas was done, followed by IHC analysis using P40, thyroid transcription factor (TTF1), EGFR, and ALK. Molecular analysis for EGFR mutation was done using FFPE and cfDNA from the patient's blood samples. RESULTS AND ANALYSIS: On histological subtyping, majority (66%) of the cases were found to be adenocarcinoma. All adenocarcinoma (66%) cases show TTF1 positivity and all squamous cell carcinoma (32%) cases show P40 positivity. All the ALK-positive (6%) cases were never smokers and histologically diagnosed as adenocarcinoma. About 58% of the NSCLC cases were found to be EGFR IHC positive. Formalin-fixed paraffin tissue (FFPE) showed EGFR mutation in 32% cases, of which majority were deletion (19, 28%) and rest (4%) of the cases involving mutation in exon 21. From cfDNA, mutations were noticed in 16% of the cases where majority involved deletion 19 (12%), whereas the rest of the cases were positive for missense mutation in exon 21 of the EGFR gene (2%) and compound heterozygous mutation involving deletion 19 and missense mutation for exon 21 (2%). On correlation of EGFR mutation studies from FFPE with that of cfDNA analysis, the study was statistically significant (P = 0.000). CONCLUSION: This study reports clinicopathological, immunochemical, and molecular analysis of EGFR among NSCLC cases. EGFR mutation detection from cfDNA has its advantage of being a noninvasive technique to avoid rebiopsy in cases of the progressive disease to detect resistance to a drug and emergence of a newer mutation. Mutation detection from FFPE samples still remains the gold standard for targeted therapy using EGFR tyrosine kinase inhibitors. ALK rearrangement detection using IHC serves as an adjunct to EGFR diagnosis.

Clinicopathological Study of Primary Pediatric Gastrointestinal Lymphomas.

BACKGROUND: Primary gastrointestinal lymphomas (PGIL) are uncommon in children and account for <5% of all pediatric malignancies. The objective of our study was to analyze the prognostic factors of pediatric PGILs with reference to its histological subtypes, stage, and outcomes using immunohistochemistry. MATERIALS AND METHODS: Twenty cases were studied over 11 years. Clinicopathological profiles, histological details, and immunohistochemical (IHC) profiles were analyzed. RESULTS: The mean age at the presentation was 6 years. Using IHC stains (CD CD10, CD19, CD20, CD3, terminal deoxynucleotidyl transferase, BCL 2 and 6, PAX 5, and MUM1), diffuse large B-cell lymphoma (DLBCL) was most prevalent (45%), followed by Burkitt lymphoma (35%) and lymphoblastic lymphoma (20%). DLBCLs (9) were classified using the Han's algorithm. Six were activated B-cell and 3 were germinal center B-cell subtypes. The cases of lymphoblastic lymphoma and those in Stage I disease had the best prognosis. CONCLUSION: Pediatric PGILs have variable presentation, outcomes, and diverse treatment modalities depending on the histological subtypes. A panel of IHC stains can be a useful adjunct for the categorization and prognosis of pediatric PGILs.

Pleuropulmonary Blastoma Developing in a Case of Misinterpreted Congenital Pulmonary Airway Malformation: a Case Report.

BACKGROUND: Pleuropulmonary blastoma (PPB) is a childhood malignancy known to be associated with congenital pulmonary airway malformation (CPAM). CASE REPORT: An 18 months boy presented with respiratory distress. Computed tomography (CT) scans revealed a large right-sided lung mass. Fine needle aspiration cytology (FNAC) showed sheets and clusters of small round to oval cells with scanty cytoplasm. The possibility of PPB was suggested. Trucut biopsy from the mass confirmed the diagnosis of PPB, of at least type II. The child had earlier been diagnosed as CPAM for which he had undergone lobectomy at six months, which on review was diagnosed as PPB I. CONCLUSION: We describe the cytological and histological findings of a case of PPBII/III evolving from a PPB I originally thought to be a CPAM type IV. This supports the theory that PPB I may progress to a more aggressive type II with time, and highlights the importance of the adequately treating the PPB I to prevent this transformation.

Cytological diagnosis of adrenocortical carcinoma: A report of 2 cases in children.

Adrenocortical carcinoma (ACC) is a rare tumour, which sometimes affects pediatric age group. Fine needle aspiration cytology (FNAC) is a rarely performed technique in adrenal cortical tumours. There is sparse literature available describing the cytological findings of ACCs in children. Here we describe the cytological findings of 2 cases of ACCs in children. The first case describes the FNAC findings in a 4 year old girl who presented with a large abdominal mass. The second case narrates the intra-operative imprint cytology findings in a 2-year-old boy who came with precocious puberty. However, diagnosis of adrenocortical tumours based on cytology alone can be difficult and definitive diagnosis should be made after correlating cytological features with the clinical profile, radiology, histopathology, and immunohistochemistry.

Cytodiagnosis of inflammatory myofibroblastic tumor: A report of three cases in infants.

Inflammatory myofibroblastic tumor is a tumor of intermediate grade with a low rate of metastasis. The tumor often mimics malignancy. There is sparse literature available describing the cytological findings of this rare condition. It often presents in infancy and childhood as an intra-abdominal mass. Here, we describe the cytological findings of three cases of inflammatory myofibroblastic tumor in infants aged 10 months, 4 months, and 15 months, respectively. While the first two cases are fine needle aspiration cytology (FNAC) smears, the third case is that of an intraoperative imprint cytology. All the three smears showed low cellularity with small clusters of bland spindle cells, along with sprinkling of inflammatory cells, suggestive of an inflammatory myofibroblastic tumor. The diagnosis was later confirmed on histopathology and positive immunostaining for ALK.