The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications

Abstract

The World Health Organization classification of lymphoid neoplasms updated in 2008 represents a worldwide consensus on the diagnosis of these tumors and is based on the recognition of distinct diseases, using a multidisciplinary approach. The updated classification refined the definitions of well-recognized diseases, identified new entities and variants, and incorporated emerging concepts in the understanding of lymphoid neoplasms. However, some questions were unresolved, such as the extent to which specific genetic or molecular alterations define certain tumors, and the status of provisional entities, categories for which the World Health Organization working groups felt there was insufficient evidence to recognize as distinct diseases at this time. In addition, since its publication, new findings and ideas have been generated. This review summarizes the scientific rationale for the classification, emphasizing changes that have had an effect on practice guidelines. The authors address the criteria and significance of early or precursor lesions and the identification of certain lymphoid neoplasms largely associated with particular age groups, such as children and the elderly. The issue of borderline categories having overlapping features with large B-cell lymphomas, as well as several provisional entities, is reviewed. These new observations chart a course for future research in the field.

Figures

Figure 1

Large B-cell lymphomas with a phenotype of terminal B-cell differentiation. This group of tumors is characterized by a down-regulation of the mature B-cell differentiation program and expression of plasma cell markers. Most of these tumors appear in immunocompromised patients. The tumor cells are often infected by EBV, human herpesvirus 8 (HHV8), or both. ALK+ large B-cell lymphoma (LBCL) occurs in immunocompetent patients and is not virally transformed. LyG indicates lymphomatoid granulomatosis; DLBCL, diffuse large B-cell lymphoma; PBL, plasmablastic lymphoma; PEL, primary effusion lymphoma; LBCL-MCD, large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease.

Figure 2

In situ follicular lymphoma and mantle cell lymphoma. (A) Lymph node with a reactive appearance. (B) BCL2 staining shows strong positive cells in some germinal centers (arrows) but not in others (arrowheads). (C) Lymphoid follicle with reactive appearance. (D) Cyclin D1 staining highlights a corona of positive cells in the mantle area. Photographic images were acquired with a Nikon Eclipse 50i microscope equipped with an Olympus (Olympus America Inc) DP71 camera and software. Final image preparation was performed with Adobe Photoshop CS4 extended Version 11.0.2. Original magnifications as follows: panel A(20×/0.1 NA); panel B (20×/0.1 NA); panel C (200×/0.75 NA); panel D (200×/0.75 NA).

Figure 3

B-cell lymphoma unclassifiable, intermediate between diffuse large B-cell lymphoma and Hodgkin lymphoma. (A) Neoplastic cells resemble Hodgkin/Reed-Sternberg cells (H&E) but show retention of a full B-cell program. (B) CD20 is uniformly positive. (C) CD30 is positive, but CD15 (D) is negative. Both PAX5 (E) and OCT-2 (F) are strongly expressed. Photomicrographic images were acquired with a Nikon Eclipse 50i microscope equipped with an Olympus (Olympus America Inc) DP71 camera and software. Final image preparation was performed with Adobe Photoshop CS4 extended Version 11.0.2. Original magnifications as follows: panels A-F (400×/0.95 NA).

Figure 4

B-cell lymphoma unclassifiable, intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, with translocations involving MYC and BCL2 (double hit). (A) A high-grade lymphoma involves the gastric mucosa of a patient with a history of low-grade follicular lymphoma (H&E). (B) At higher magnification, the cells are medium-sized and monomorphic with a high mitotic rate (H&E). (C) The cells are strongly positive for Bcl2 (Bcl2 immunoperoxidase stain). (D) FISH on interphase nuclei using a dual-color dual fusion probe for the BCL2 and IGH loci (top) shows one abnormal (yellow) signal in most cells, indicating a translocation involving the BCL2 and IGH genes. FISH on interphase nuclei with the use of a dual-color break-apart probe for the MYC locus (bottom) shows 1-2 yellow signals (normal) and 2-3 red signals, indicating a break at the MYC locus, with loss of the 3′ end of MYC, consistent with an unbalanced or complex MYC rearrangement. Panels A, B, and C were provided by Dr Aliyah Sohani, Department of Pathology, Massachusetts General Hospital. Panel D is reprinted from Snuderl et al.