Correlation of immunohistochemical staining p63 and TTF-1 with EGFR and K-ras mutational spectrum and diagnostic reproducibility in non small cell lung carcinoma.

For treatment purposes, distinction between squamous cell carcinoma and adenocarcinoma is important. The aim of this study is to examine the diagnostic accuracy on lung cancer small biopsies for the distinction between adenocarcinoma and squamous cell carcinoma and relate these to immunohistochemical and KRAS and EGFR mutation analysis. An interobserver study was performed on 110 prospectively collected biopsies obtained by bronchoscopy or transthoracic needle biopsy of patients with non-small cell lung cancer. The diagnosis was correlated with immunohistochemical (IHC) analysis for markers of adeno- (TTF1 and/or mucin positivity) and squamous cell differentiation (P63 and CK5/6) as well as KRAS and EGFR mutation analysis. Eleven observers independently read H&E-stained slides of 110 cases, resulting in a kappa value of 0.55 ± 0.10. The diagnosis non-small cell lung cancer not otherwise specified was given on average on 29.5 % of the biopsies. A high concordance was observed between hematoxylin-eosin-based consensus diagnosis (≥8/11 readings concordant) and IHC markers. In all cases with EGFR (n = 1) and KRAS (n = 20) mutations, adenodifferentiation as determined by IHC was present and p63 staining was absent. In 2 of 25 cases with a consensus diagnosis of squamous cell carcinoma, additional stainings favored adenodifferentation, and a KRAS mutation was present. P63 is most useful for distinction between EGFR/KRAS mutation positive and negative patients. In the diagnostic work-up of non-small cell lung carcinoma the limited reproducibility on small biopsies is optimized with immunohistochemical analysis, resulting in reliable delineation for predictive analysis.

Florid granulomatous reaction in Epstein-Barr virus-positive nonendemic Burkitt lymphomas: report of four cases.

Epithelioid cell granulomas have been reported in association with a wide range of neoplasms including malignant lymphomas. In lymphoma, this refers mainly to Hodgkin disease and T-cell-derived non-Hodgkin lymphomas where a granulomatous reaction is probably evoked by aberrant cytokine production in the tumor cells or other cells composing the tumor background. Here we report on four cases of sporadic Burkitt lymphoma with unusual florid granulomatous reaction. In all samples, the tumor cells were admixed with numerous epithelioid cells that formed clusters and granulomatous lesions. No microorganisms could be detected at the tissue level, and there were no clinical or laboratory indications of an underlying immunodeficiency. The lymphomas harbored a specific morphology and immunophenotype of Burkitt lymphoma, and the presence of translocation breakpoint in MYC gene was confirmed by interphase fluorescence in situ hybridization. In all four patients, the lymphoma was associated with Epstein-Barr virus infection, detected by EBER in situ hybridization and the latency I phenotype as defined by lack of expression of LMP1. All four patients were treated with polychemotherapy, achieved a complete remission, and are alive without evidence of disease. We draw attention to this unusual phenomenon as it caused difficulties in interpretation and delayed diagnosis and hypothesize on the possible role of Epstein-Barr virus products.