A comparison of the International Consensus and 5th World Health Organization classifications of mature B-cell lymphomas

Abstract

Several editions of the World Health Organization (WHO) classifications of lympho-hemopoietic neoplasms in 2001, 2008 and 2017 served as the international standard for diagnosis. Since the 4th WHO edition, here referred as WHO-HAEM4, significant clinico-pathological, immunophenotypic and molecular advances have been made in the field of lymphomas, contributing to refining diagnostic criteria of several diseases, to upgrade entities previously defined as provisional and to identify new entities. This process has resulted in two recent classifying proposals of lymphoid neoplasms, the International Consensus Classification (ICC) and the 5th edition of the WHO classification (WHO-HAEM5). In this paper, we review and compare the two classifications in terms of diagnostic criteria and entity definition, with focus on mature B-cell neoplasms. The main aim is to provide a tool to facilitate the work of pathologists, hematologists and researchers involved in the diagnosis and treatment of lymphomas.

Fig. 1. Morphological and immunohistochemical features of B-PLL, pleomorphic variant of classic mantle cell lymphoma and DLBCL of the testis.

A Peripheral blood smear showing typical prolymphocytes (May-Grunwald-Giemsa; ×1000). B Bone marrow trephine showing interstitial infiltration by CD79b positive prolymphocytes (immunoperoxidase staining; ×400). C Imprint from spleen involved by classic mantle cell lymphoma, pleomorphic variant (May-Grunwald-Giemsa; ×400). The tumor cells are medium to large in size and contain evident nucleoli. D Spleen paraffin section from the same case showing a high percentage of Ki-67 positive cells (immunoperoxidase staining; ×400). E Diffuse large B-cell lymphoma of the testis. The asterisk indicates the lumen of a seminiferous tubule (Hematoxylin-eosin; ×400). F The same case as D, showing strong positivity of tumor cells for CD20 (immunoperoxidase staining; 400); the asterisk indicates the lumen of a seminiferous tubule.

Fig. 2. Relationship between different types of B-cell lymphomas with prevalent spleen involvement among the ICC and WHO classifications.

B-cell prolymphocytic leukemia (B-PLL), a definite entity in ICC, and hairy cell leukemia variant (HCLv), a provisional entity in ICC, are named in the WHO-HAEM5 under the term of splenic B-cell lymphoma with prominent nucleoli (SBLPN). SBLPN is an heterogeneous category that also comprises cases of unrecognized leukemic mantle cell lymphoma and progressed B-CLL. SDRPL splenic diffuse red pulp small B-cell lymphoma, HCL hairy cell leukemia, SMZL splenic marginal zone lymphoma.

Fig. 3. DLBCL/HGBCL with 11q rearrangements.

A Lymph node imprint showing large-size tumor cells with basophilic cytoplasm and round nuclei with evident nucleoli (May-Grunwald-Giemsa; ×400). B Tumor cells are double stained for CD20 (green) and BCL6 (brown). C, D FISH reveals 11q aberrations.

Fig. 4. High-grade B-cell lymphoma of the heart with MYC and BCL2 rearrangement.

A Diffuse infiltration by large-size tumor cells (Hematoxylin-eosin; ×400) with evident nucleoli (inset; ×600). B The majority of the neoplastic cells strongly express TdT. C, D Tumor cells are CD79a negative but strongly express CD79b (TdT, CD79a, CD79b, Immunoperoxidase staining; ×400).

Fig. 5. Mediastinal gray zone lymphoma.

A Diffuse proliferation of large tumor cells with wide clear cytoplasm (Hematoxylin and eosin; ×400); B Neoplastic cells strongly express CD30 (immunoperoxidase staining ×400). C Double staining showing a small percentage of reactive CD3-positive T cells (red) together with many surface CD19-positive tumor cells (brown); D Tumor cells from the same case are also double stained for MUM1/IRF4 (brown) and surface CD20 (red) (×400) (C, D Double immunoperoxidase staining using different enzyme substrates).