ABSTRACT
Introduction 560 Diffuse large B cell lymphoma of the usual type 560 Morphology 560 Immunophenotype 562 Genetic features 562 Molecular features – gene expression profiling 564 Prognostic biomarkers 565 T cell/histiocyte-rich large B cell lymphoma 567 Plasmablastic lymphoma 568 Anaplastic lymphoma kinase-positive large 569
B cell lymphoma
Primary mediastinal (thymic) large B cell lymphoma 569 Primary effusion lymphoma 571 Other HHV8-positive lymphomas 571 Diffuse large B cell lymphoma associated with 572
chronic inflammation Intravascular large B cell lymphoma 573 EBV-positive diffuse large B cell lymphomas 574 EBV-positive DLBCL of the elderly 574 Lymphomatoid granulomatosis 575 Key points 576 References 576
Diffuse large B cell lymphoma (DLBCL) is the most common adult non-Hodgkin lymphoma worldwide,1 accounting for 30-40 percent of all cases. This group of tumors encompasses marked biologic heterogeneity and highly variable clinical course. Median age at presentation is in the seventh decade, but the disease also affects children or younger adults. DLBCL may occur de novo, or arise as a transformation from an underlying small B cell lymphoma. Patients present with variable combinations of nodal and/or extranodal involvement (Fig. 33.1), and present variable responses to therapy. Although most patients respond initially to chemotherapy, less than half are cured by currently available therapy.2 Pathologically, the biologic heterogeneity of DLBCL is reflected in variable morphology, immunophenotype, cytogenetic alterations and molecular genetic features. Accordingly, in the World Health Organization (WHO) classification, in addition to the ‘usual’ form of DLBCL (DLBCL, not otherwise specified) which comprises the majority of the cases, several variants have been separated as distinct entities by virtue of distinctive immunophenotypic and/or clinical and patho3
DLBCL is defined as a diffuse proliferation of large neoplastic lymphoid cells with nuclear size equal or exceeding normal macrophage nuclei or more than twice the size of a normal lymphocyte.3 Grossly, DLBCL appears as a mass-forming tissue with ‘fish-flesh’ white homogeneous appearance. Lymph nodes involved by DLBCL are typically enlarged, often with completely obliterated tissue architecture, although partial involvement may be seen. The centroblastic, immunoblastic and anaplastic variants of DLBCL represent the usual morphologic types, with centroblastic being the most common (about 75 percent of cases).3 Centroblasts are large noncleaved lymphoid cells resembling the proliferating cells of the germinal center with oval to round vesicular nuclei, with fine chromatin and multiple membrane-bound nucleoli, and scanty amphophilic to basophilic cytoplasm. Immunoblasts have an oval or round nucleus with opened chromatin and a large central solitary nucleolus, and abundant deeply
10 percent centroblasts fall into the category of centroblastic lymphoma, which includes the monomorphic and polymorphic variants (Fig. 33.2A). Centroblastic lymphomas may harbor multilobulated nuclei, a feature encountered frequently in primary osseous DLBCL.4 Tumors comprising 90 percent immunoblasts or more are classified as immunoblastic (Fig. 33.2B). Immunoblastic tumors may show plasmacytic differentiation (Fig. 33.2C). The anaplastic variant of DLBCL (Plate 51, see plate section) is characterized by large pleomorphic cells, sometimes resembling Reed-Sternberg cells, forming cohesive sheets and showing a sinusoidal pattern of growth that may mimic carcinoma.
