Correction. "The 5th edition of The World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms" Leukemia. 2022 Jul;36(7):1720-1748

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms

Characteristics and classification of high-grade B-cell lymphomas in resource-limited settings

The aim of this study is to confirm the guild line of pathological diagnosis of BMFS. Materials and method: The registered 1000 cases of Japanese Pediatric MDS/AA central review system were reviewed by board members and used in this study. Bone marrow biopsy and clot materials of paraffin sections were used for immunohistochemistry (IHC). Results: Aplastic anemia cases showed very severe hypoplastic marrow without megakaryocyte and scarce granulopoiesis. Lymphocytes, especially CD8 þ T-cells, were predominant. RCC cases were hypoplastic marrow with patchy pattern. Ery- thropoiesis were mainly composed by large erythroblasts with left shift and baring hemoglobin fetal type (HbF). A few marrow cells were stained p53. Megakaryocytes with single small nuclei or micromegakaryocytes were demonstrated by IHC. RCMD was hypo-normocellular marrow and distinctive erythropoiesis with left shift. P53 þ cells were relatively more than RCC. RAEB or AML with MRC had increased number of p53 þ cells and CD34 þ blasts. Small and micromegakaryocytes were frequently observed. No evidence of AA or MDS cases were categorized into secondary dyshematopoiesis of unknown causes or inherited BMFS. Conclusion: Bone marrow pathology with IHC were useful for the definite diagnosis of childhood BMFS

Diffuse large B-cell lymphoma with concurrent high MYC and BCL2 expression shows evidence of active B-cell receptor signaling by quantitative immunofluorescence

<div><p>B-cell receptor (BCR)-mediated signaling plays an important role in the pathogenesis of a subset of diffuse large B-cell lymphoma (DLBCL), and novel agents targeting this pathway are now in clinical use. We have previously identified a signature of active BCR signaling on formalin-fixed paraffin-embedded specimens using quantitative immunofluorescence, allowing for identification of patients who might benefit from anti-BCR therapies. We sought to characterize the clinicopathologic significance of active BCR signaling in DLBCL by correlating measures of signaling intensity with clinical features and various tumor cell characteristics. High MYC and concurrent high MYC and BCL2 double-expression was positively correlated with individual markers of active BCR signaling and cases with MYC/BCL2 double-expression showed overall greater BCR activation compared to cases lacking double-expression. Our findings suggest that the BCR signaling pathway may be more active in MYC/BCL2 double-expressor DLBCL and may represent a rational therapeutic target in this aggressive DLBCL subgroup.</p></div

Association of DEL with BCR (transformed) and of BCR (transformed) with <i>F</i>_cyt classification.

<p>Association of DEL with BCR (transformed) and of BCR (transformed) with <i>F</i>_cyt classification.</p

Logistic transform of BCR signaling markers in DLBCL specimens.

<p>Pairwise scatterplots of transformed (logit) data for pLYN⁺CD20⁺, pSYK⁺CD20⁺, pBTK⁺CD20⁺ and the untransformed ratio of FOXO1 cytoplasmic staining (<i>F</i>_cyt) in 93 primary DLBCL cases. Cases are classified as BCR+ (red) or BCR- (black) based on a hyperplane based upon normal mixture modeling of BCR activation in ten DLBCL cell lines (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172364#pone.0172364.s001" target="_blank">S1 Text</a>).</p

Association of DEL with BCR classification according to logit transformation.

<p>Association of DEL with BCR classification according to logit transformation.</p

Kaplan-Meier analysis of overall survival (OS) based on DEL and BCR classification.

<p>(A) OS for DEL (solid) vs. non-DEL (dashed) cases (<i>p</i> = 0.03) among all patients with available follow-up. (B) OS for DEL (solid) vs. non-DEL (dashed) cases restricted to R-CHOP-treated patients. (C) OS for BCR+ (solid) vs. BCR- (dashed) cases according to the revised definition for BCR positivity. (D) OS for cases with <i>F</i>_cyt>50 (solid) vs. <i>F</i>_cyt<50 (dashed).</p

Differences in MYC and BCL2 expression by IHC in a BCR-negative and a BCR-positive case.

<p>Bar graph of percent positive (+ve) for BCR phosphomarkers pLYN, and <i>F</i>_cyt and representative images of H&E stain and MYC and BCL2 immunohistochemical stains for two representative cases. (A) A BCR-negative case that was negative for MYC and positive for BCL2 expression. This patient responded to R-CHOP therapy and was alive with no evidence of disease 10 years following diagnosis. (B) A BCR-positive case with MYC/BCL2 double-expression. This patient expired within several months of diagnosis despite receiving R-CHOP.</p