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AimsMantle cell lymphoma (MCL) has a highly heterogeneous clinical course ranging from indolent, to aggressive and rapidly progressive disease. Proliferation is a strong predictor for disease outcome. In routine clinical practice, Ki-67 expression is used as a measure of proliferation. However, several studies have documented a high degree of inter-laboratory and inter-observer variation with Ki-67 immunohistochemistry. Phosphorylation of histone H3 occurs specifically during mitosis and hence serves as a specific marker for cells in mitosis.Methods and resultsWe investigated phosphohistone H3 (PHH3) immunohistochemistry as a proliferation maker in 28 tissue biopsies of MCL and compared the PHH3 results (as evaluated by direct microscopic visualisation and image analysis-aided scoring) with morphological subtyping, mitotic counts and Ki-67 index. We found PHH3-mitotic count was about sixfold higher than H&E-mitotic count (mitoses in 10 high power fields). Furthermore, PHH3-mitotic count in aggressive morphological variants of MCL was significantly higher than in usual MCL. The PHH3-mitotic count showed a strong linear correlation with PHH3-mitotic index (percentage positive cells).ConclusionsWe found PHH3 immunohistochemistry, a reliable mitosis-specific marker, in MCL. Performing precise counts and evaluating precise proliferation indices is easier with PHH3 immunohistochemistry. This contrasts with the conventional estimation of Ki-67 percentages by ‘eye-balling’.

Background: Lung cancer is the most common cause of cancer-related death worldwide and unfortunately up to 80% of patients amongst newly diagnosed are inoperable therefore the cytological sample is often the only material available for diagnosis and assessment of molecular characteristics driving the treatment.Recently immunotherapy has shown promising results in tumors expressing Program Death Ligand 1 (PD-L1). The expression of PDL1 can routinely be detected by immunohistochemistry. However, the presence of several antibodies with different cut-off and the expression of this marker by normal immune cells are generating confusion in interpretation and the need for harmonization amongst pathologists. Materials and methods:We assessed the suitability of 74 consecutive cell blocks from cytology samples for PDL1 testing and evaluate the concordance between two different antibodies (Ventana assay SP263 and Dako 223C pharmDx assay) and amongst different pathologists from two different tertiary referral center for thoracic pathology. The degree of agreement was measured by Fleiss K statistic (FKS) for categorical scores after dichotomization based on specifi ed cutoffs. A review of discordant cases was also performed.Results: Review of the slides stained with both antibodies showed substantial agreement within our department and moderate agreement with results from the other institution. Overall less than 10% of cases were deemed inadequate. Discordant cases showed a decreased amount of tumor cells, therefore, tumor heterogeneity could be responsible for the variation in the reading. Conclusions:Our results show overall concordance between the two antibodies and the suitability of cytology material for PDL-1 testing.