Page 1389 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 76 Origin of Non-Hodgkin Lymphoma 1235

A E I
CD10 BCL6 MUM1 CD138 CD30

B C F G J

D H K
Fig. 76.4 THREE TYPES OF DIFFUSE LARGE B-CELL LYMPHOMA DELINEATED BY HISTO-
LOGIC PATTERNS. Germinal center B cell–like (GCB), activated B-cell–type, and primary mediastinal
B-cell lymphoma (PMBCL) type. GCB, or germinal center (GC)–derived large B-cell lymphomas usually have
+
a centroblastic morphology (A), are CD20 , and express the GC markers CD10 (B) and BCL6 (C). In this
case, the patient’s staging bone marrow (D) showed paratrabecular involvement by small cleaved cells (centro-
cytes), indicating that the large B-cell lymphoma likely arose from a lower grade follicular lymphoma. Activated
B cell–like large B-cell lymphoma can sometime have an immunoblastic morphology (E) and can typically
express MUM1 (F) and CD138 (G). These post-GC cell types of lymphomas can also have a plasmablastic
morphology (H), as sometimes seen in HIV-related cases. PMBCLs are frequently composed of multilobated
+
+
+
centroblasts (I). They are typically CD45 , CD20 , and usually CD30 (J) but CD15-negative. Surface
immunoglobulin may be negative on such cases. PMBL is commonly associated with fibrosis, which is present
in broad bands (K) or surrounding individual cells (as in I).
microenvironment may play a role in the origin and progression of Conclusions
DLBCL. Tumor-infiltrating T cells have been correlated with longer
survival in patients with DLBCL, and failure of immune editing is Diffuse large B-cell lymphoma represents a heterogeneous group
likely responsible for the increase in NHL in HIV-positive and of B-cell neoplasms with a distinct underlying biology, prognosis,
immunosuppressed persons. Gene expression profiling has been used and response to therapy. Recent genomic approaches to studying
to define stromal elements related to DLBCL progression. In one DLBCL have identified a number of interesting potential targets
series, hierarchical clustering was used to define three groups among for better prognostic stratification and treatment of patients afflicted
DLBCL samples by GEP. Clusters identifying gene signature termed with this disease. More work is needed to this end and to better
oxidative phosphorylation, BCR proliferation, and host response were understand the origin of DLBCL and the role of stromal factors in
identified; notably, the host response group exhibited gene expression disease progression.
profiles associated with T and natural killer cells, dendritic cells, and
macrophages. This work illustrates that patterns of stromal involve-
ment in DLBCL could play a key role in pathogenesis. In another BURKITT LYMPHOMA
series involving biopsy specimens from 414 patients treated with
chemotherapy and immunochemotherapy, two gene signatures Burkitt lymphoma (BL) is a highly aggressive lymphoma entity
characterizing patterns of tumor stroma best predicted survival. characterized by a high mitotic rate, extranodal spread, and early
Improved survival was noted with a pattern that included genes death, but it is frequently curable with high-intensity multi-agent
associated with the extracellular matrix and histiocytic infiltration. chemotherapy. It was first described more than 50 years ago as a
The converse was true for gene profiles correlating to angiogenesis disease in young Africans in association with EBV infection. Since
because these were associated with far worse overall survival. then, sporadic and immunodeficiency-related forms of the disease
Although it is not known what roles distinct lymph node have been described. Subsequent work has shown that translocation
subsets play in the pathogenesis of lymphoma, it is clear from these of the MYC gene on chromosome 8q24 to the Ig locus occurs in
studies that the tumor microenvironment plays a role in the origin virtually all cases of BL (see Figs. 76.6 and 76.7 for an overview of
of NHL. BL). Given the high prevalence of MYC rearrangements and the high