Journal of Hematopathology

Mantle cell lymphoma (MCL) is a clinically heterogeneous B cell malignancy for which a variety of prognostic factors have been proposed. Previously, a digital gene expression profiling “proliferation signature” capable of risk stratifying MCL was identified and subsequently developed into a multi-analyte prognostic assay, known as the “MCL35” assay. In this study, we sought to explore the performance characteristics of the MCL35 assay in a clinical laboratory and compare results with the Ki67 proliferation marker. The results describe the clinical validation of the MCL35 assay for molecular risk stratification of MCL including accuracy, sensitivity, specificity, use in acid-decalcified bone marrow core biopsies, fixatives, lower limit of RNA input, quality metrics, and other laboratory parameters. The resulting data indicate that this is a robust technique with outstanding reproducibility. Overall, the data support the concept of molecular signatures, as assessed with digital gene expression profiling, for improved standardization and reproducibility for proliferation assessment in MCL.

Pure erythroid leukemia (PEL) is a rare, aggressive subtype of acute myeloid leukemia with a poor prognosis. The diagnosis of PEL is often medically urgent, quite challenging, and is typically a diagnosis of exclusion requiring meticulous distinction from non-neoplastic erythroid proliferations, particularly florid erythroid hyperplasia/regeneration. Given the frequency of TP53 mutations in the molecular signature of PEL, we hypothesize that differential p53 expression by immunohistochemistry (IHC) may be useful in distinguishing PEL versus non-neoplastic erythroid conditions. We performed p53 IHC on 5 normal bone marrow, 46 reactive erythroid proliferations, and 27 PEL cases. We assessed the positivity and intensity of nuclear staining in pronormoblasts and basophilic normoblasts using a 0–3+ scale with 0 being absent (with internal positive controls) and 3 being strong nuclear positivity. A total of 26/27 PEL cases showed strong, uniform, diffuse intense staining by the neoplastic pronormoblasts versus 0/5 and 0/46 normal and reactive controls, respectively. The control cases show various staining patterns ranging from 0 to 3+ in scattered erythroid precursor cells. Uniform, strong p53 positivity is unique to PEL and discriminates this entity from a benign erythroid mimic. Thus, p53 IHC may be a useful marker in urgent medical cases to assist in the confirmation of a malignant PEL diagnosis while awaiting the results of additional ancillary studies such as cytogenetics.