Page 1106 - Clinical Immunology_ Principles and Practice ( PDFDrive )

1070 ParT EIGhT Immunology of Neoplasia

Histologically, the spleen shows expansion of the white pulp In terms of morphology and phenotype, DLBCL is one of
with a characteristic biphasic pattern—central zone of small the most heterogeneous categories in the WHO classification;
lymphocytes surrounded by a peripheral zone of larger cells currently, several morphological variants as well as specific
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resembling marginal zone cells. The residual polytypic mantle subtypes are recognized. There has been a great interest in
is not present in this instance. The abundant pale cytoplasm identifying DLBCL features that might be prognostically relevant.
evident in tissue sections may also be seen in peripheral blood To address issues traditionally not resolved by morphological
smears, and the cytological features may be mistaken for those or immunophenotypic features, DLBCL was among the first
of hairy-cell leukemia. The phenotype resembles other marginal lymphomas to be analyzed by complementary DNA (cDNA)
zone B-cell lymphomas with a more frequent sIgD expression. microarray. Based on the differential expression of a large set of
Deletion of 7q31 has been described in SMZL; although it genes by GEP, germinal-center B cell–like (GCB) group and
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can also be seen in isolated cases of splenic B-cell lymphoma or activated B cell–like (ABC) group have been identified, in
leukemia unclassifiable, it has not been detected in other splenic addition to the previously recognized primary mediastinal (thymic)
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lymphomas. Studies of the Ig variable genes and IgD expression large B-cell lymphoma (PMBCL). GCB DLBCLs express a set of
have revealed two groups of naïve and memory B-cell origin. genes that are associated with normal germinal-center B cells,
whereas ABC DLBCLs show downregulation of these genes and
CLINICaL PEarLS share similarities with post–germinal-center B cells.
The t(14;18) translocation involving BCL2 and immunoglobu-
Aggressive Lymphomas lin heavy-chain gene has been detected in the GCB subtype, but
not in the other subtypes. Previous studies have shown reduced
• Natural history: survival measured in months. disease-free survival in DLBCL cases with BCL2 overexpression,
• Successful therapy can be achieved with combination chemotherapy.
• Relapses from chemotherapy-induced remission may be cured with irrespective of the translocation. Although no absolute correlation
high-dose chemotherapy with hematopoietic support. between morphology and GEP has been established, interestingly,
• In addition to the International Prognostic Index (IPI), gene expression the majority of DLBCLs with centroblastic morphology falls
profiling can be useful in predicting prognosis and survival of individual into the GCB subtype, whereas those with immunoblastic
patients. morphology usually correlate with the ABC subtype.
DLBCL has an aggressive natural history but generally responds
well to chemotherapy. The complete remission rate with modern
Diffuse Large B-Cell Lymphoma, Not regimens is 75–80%. Currently, with R-CHOP (rituximab–
Otherwise Specified cyclophosphamide, doxorubicin, vincristine, and prednisone)
Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, regimen, the 10-year progression-free and overall survival rates
NOS) is one of the more common subtypes of non-HL, represent- for older patients with advanced-stage DLBCL are 36.5% and
ing up to 40% of cases. This diagnosis is used for both primary 43.5%, respectively. 23
DLBCL as well as for cases that transformed from a low-grade Immunophenotype-based algorithms using CD10/BCL6
lymphoma. It may be nodal or involve extranodal sites, including positivity for GCB and MUM1/IRF4 expression for the
bone, skin, the thyroid gland, the GI tract, and lungs. ABC subtype have been proposed as surrogates for cDNA
DLBCL, NOS is composed of large transformed lymphoid microarray; additionally, BCL2 and IPI are also informative to
cells with nuclei at least twice the size of a small lymphocyte stratify the DLBCL cases. Because of the therapeutic impact, in
(Fig. 79.3). The nuclei generally have vesicular chromatin, the recent publication of the proposed changes in the WHO
prominent nucleoli, and basophilic cytoplasm—resembling either 2016 classification, it has been recommended that these two
centroblasts or immunoblasts, albeit with an overall greater subtypes be identified, on the basis of either commonly used
cellular pleomorphism. immunophenotype-based algorithms or GEP.
T cell/histiocyte–rich large B-cell lymphoma (THRLBCL) is a
distinct clinicopathological entity, rather than a morphological
variant. THRLBCL tends to occur in younger patients compared
with other DLBCL, NOS, and often presents with advanced stage
and bone marrow involvement with an aggressive clinical
behavior.
The WHO classification recognizes that lymphomas arising
from certain anatomical sites may have distinctive clinical and
biological features. Among these are primary DLBCL of the central
nervous system (CNS) and primary cutaneous DLBCL, leg type.
Primary DLBCL of the CNS with some distinctive GEP features
shares some similarities with DLBCL arising in other immune-
privileged sites, such as the testis. Primary cutaneous DLBCL,
leg type, has a GEP resembling the ABC subtype of DLBCL,
presents most often in older females, and generally has an aggres-
sive clinical course.
Several Epstein-Barr virus (EBV)–positive B-cell lymphopro-
liferations are often grouped with DLBCL. In the revised WHO
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FIG 79.3 Diffuse Large-Cell Lymphoma. The neoplastic cells 2016 classification, EBV-positive DLBCL, NOS has now replaced
have large round to oval nuclei with vesicular chromatin and a previous provisional entity “EBV-positive DLBCL of the elderly”
multiple eosinophilic nucleoli. Numerous mitoses are also present. in the 2008 WHO classification, since it may occur in younger