Diffuse Large B-Cell Lymphoma



Diffuse Large B-Cell Lymphoma


Rima Koka, M.D., Ph.D.

Amy Duffield, M.D., Ph.D.



Clinical Characteristics

Diffuse large B-cell lymphoma (DLBCL) is a name given to a heterogeneous group of aggressive mature B-cell malignancies. DLBCLs have an increased propensity to arise in extranodal sites as compared to other B-cell lymphomas. While ˜25% of non-Hodgkin lymphomas present with primary involvement of an extranodal site, lung involvement is relatively rare with only 3% presenting primary in the lung and secondary involvement reported to be ˜7%.1,2,3 DLBCLs have a propensity for extranodal involvement with ˜40% occurring in extranodal sites, the majority of which involve the gastrointestinal tract. Primary lung DLBCL is exceedingly rare, and nearly all cases of DLBCL found in the lung represent secondary involvement.1

Because pulmonary involvement by DLBCL likely represents secondary involvement by an aggressive lymphoma, the clinical findings are similar to those seen in other patients with advanced-stage disease.1 The signs and symptoms of the disease are highly variable and depend on the growth rate of the neoplasm, organs involved, and presence of associated mass effects.4


Tissue Sampling

The diagnosis of DLBCL can often be made on a core biopsy of the mass. In the setting of secondary involvement of lung in a patient with a history of lymphoma, limited immunohistochemical studies can be employed. However, in the case of a primary diagnosis, multiple immunohistochemical and in situ hybridization studies may be required for further subclassification of the neoplasm to provide information about prognosis or therapeutic options, necessitating a larger biopsy. Furthermore, if sufficient tissue is obtained, then submission of a portion of fresh tissue for flow cytometric analysis may aid in the diagnosis.


Pathologic Findings

The subclassification of DLBCLs can be based on morphology, immunophenotypic differences, and clinical characteristics of the patients. Although in some cases further subclassification may not be clinically meaningful, if distinctions can be reliably made using one or more of the above criteria, then an effort should be made to distinguish between the distinct categories described in the World Health Organization’s classification of tumors of hematopoietic and lymphoid tissues (Table 89.1). When a large cell lymphoma cannot be specifically classified as one of these distinct entities, the preferred diagnosis becomes DLBCL, not otherwise specified (DLBCL, NOS). In lymph nodes, DLBCL, NOS, typically leads to diffuse effacement of nodal architecture and replacement of the normal node with atypical cells. The cell morphologies can vary, and three distinct variants have been described. Clinically, the distinction between the morphologic variants is unimportant; however, the appreciation of the morphologic spectrum of DLBCL, NOS, may be important for making an accurate diagnosis. The most common morphologic variant is the centroblastic variant in which the cells are intermediate to large and have oval to round, vesicular nuclei with a finely distributed chromatin pattern (Fig. 89.1). There may be up to four nucleoli, and the scant cytoplasm is amphophilic to basophilic. Cells of the immunoblastic variant have a highly prominent central nucleolus and a fair amount of basophilic cytoplasm. Recognition of the anaplastic variant can be of particular importance because it can be confused with a poorly differentiated
carcinoma (Fig. 89.2). The cells are highly pleomorphic and have bizarre nuclear contours and may also resemble cells of Hodgkin lymphoma and anaplastic large cell lymphoma.








TABLE 89.1 Classification of Large B-Cell Lymphomas

Clinical Features

Morphologic Characteristics and Variants

Immunohistochemical Features

EBV Status

Prognosis


DLBCL, NOS

Highly variable

Centroblastic


Immunoblastic


Anaplastic

Germinal center B-cell-like


Non-germinal center B-cell-like

Negative

Good


EBV-positive DLBCL of the elderly

Age >50

Hodgkin-like cells may be seen; frequent necrosis

Commonly MUM-1 positive. CD20 may be lacking if plasmablastic or immunoblastic.

Positive

Poor


T-cell/histiocyterich large B-cell lymphoma

Often present with fever, malaise, and hepatosplenomegaly

Dispersed large B cells among numerous T cells and histiocytes

BCL-6 with absent follicular dendritic networks (FDC) and lacking IgD-positive mantle cellsa

If positive, classify as EBV-positive DLBCL of the elderly

Poor


DLBCL associated with chronic inflammation

Involve body cavities, such as pleural cavity, in the context of prolonged inflammation

Mass with diffuse proliferation of large B cells of immunoblastic morphology

If plasmablastic variant, loss of CD20 with expression of MUM-1 and CD138

Positive

Poor


Lymphomatoid granulomatosis

Often associated with immunodeficiency

Angiocentric and angiodestructive polymorphous lymphoid infiltrate


Grade 1: Polymorphous without atypia


Grade 2: Occasional large cells in polymorphous background


Grade 3: Aggregates of large cells


Positive

Variable; often correlates with grade


Primary mediastinal large B-cell lymphoma

Often present with large mediastinal mass with involvement of secondary structures

Sheets of large B cells with clear cytoplasm separated by delicate collagen fibers

MUM-1 and CD23 frequently expressed while BCL-2 and BCL-6 are variable. CD30 is present in many cases but has a heterogeneous pattern of staining.

Negative

Good


Intravascular large B-cell lymphoma

Symptoms related to involved organ. B symptoms are common.

Atypical lymphoid cells restricted to lumina of small or intermediatesized vessels

MUM-1 is commonly expressed. Small proportion expresses CD5 or CD10

Negative

Poor; those with only cutaneous involvement have better prognosis


ALK-positive large cell lymphoma

Mostly involves lymph nodes but may present as mediastinal mass

Cells of immunoblastic or plasmablastic differentiation

Strongly positive for ALK-1 and CD138. CD30 is negative (unlike ALCL)b. CD20 may be weak or negative.

Negative

Poor


Primary effusion lymphoma

Associated with immunodeficiency. History of recurrent effusions with no evidence of lymphadenopathy or organomegaly

Cells of immunoblastic or plasmablastic differentiation

Lack CD19, CD20, and CD79a. Often express CD138

Positive


(Coinfection with HHV-8 also found)

Poor


a If present, nodular lymphocyte-predominant Hodgkin lymphoma must be considered.

b ALCL, anaplastic large cell lymphoma.

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Aug 19, 2016 | Posted by in CARDIOLOGY | Comments Off on Diffuse Large B-Cell Lymphoma

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