Primary Pulmonary B-Cell Lymphoma: A Review and Update

Abstract

Primary pulmonary B-cell lymphomas (PP-BCLs) comprise a group of extranodal non-Hodgkin lymphomas of B-cell origin, which primarily affect the lung without evidence of extrapulmonary disease at the time of diagnosis and up to 3 months afterwards. Primary lymphoid proliferations of the lung are most often of B-cell lineage, and include three major entities with different clinical, morphological, and molecular features: primary pulmonary marginal zone lymphoma of mucosa-associated lymphoid tissue (PP-MZL, or MALT lymphoma), primary pulmonary diffuse large B cell lymphoma (PP-DLBCL), and lymphomatoid granulomatosis (LYG). Less common entities include primary effusion B-cell lymphoma (PEL) and intravascular large B cell lymphoma (IVLBCL). A proper workup requires a multidisciplinary approach, including radiologists, pneumologists, thoracic surgeons, pathologists, hemato-oncologists, and radiation oncologists, in order to achieve a correct diagnosis and risk assessment. Aim of this review is to analyze and outline the clinical and pathological features of the most frequent PP-BCLs, and to critically analyze the major issues in their diagnosis and management.

Keywords: BALT; MALT lymphoma; diffuse large B-cell lymphoma; intravascular large B-cell lymphoma; lymphomatoid granulomatosis; primary effusion lymphoma; pulmonary B-cell lymphoma.

Figure 1

The stepwise progression from BALT to MALT lymphoma.

Figure 2

Primary pulmonary MALT lymphoma. (A,B). A dense infiltrate of mostly centrocyte-like lymphocytes effaces the lung parenchyma (A H&E stain, 40×; B H&E stain, 400×). (C,D). Neoplastic cells are CD20+ with a minor population of reactive CD3+ T-cells; both antibodies feature a membranous staining ((C) CD20 immunostain, 200×; (D) CD3 immunostain, 100×). (E). Lymphoepitelial lesions due to neoplastic cells infiltrating the epithelium are highlighted by cytokeratins (CK-AE1/AE3 immunostain, 200×). (F). The proliferative index, i.e., the percentage of Ki-67 stained nuclei, is low in the neoplastic cells, but higher in residual germinal centers (Ki-67 immunostain, 100×).

Figure 3

Primary pulmonary diffuse large B-cell lymphoma. (A,B). At low and high power, respectively, a heavy infiltrate of large tumor cell, the majority with centroblastic morphology (A H&E stain, 40×; B H&E stain, 400×). (C,D). Neoplastic cells show diffuse and intense expression of CD20, with fewer reactive CD3+ T-cells ((C) CD20 immunostain, 200×; (D) CD3 immunostain, 100×). (E). In this GCB-type PP-DLBCL there is diffuse nuclear expression of BCL6 (BCL6 immunostain, 200×). (F). Tumor cells are intensely positive for CD30 in another case with immunoblastic morphology (CD30 immunostain, 100×).

Figure 4

Lymphomatoid granulomatosis. (A). A number of atypical medium- to large- lymphoid cells within a polymorphous infiltrate (H&E stain, 200×). (B,C). Neoplastic cells show diffuse and intense expression of CD20 in this case of grade 3 LYG, with fewer reactive CD3+ T-cells ((B) CD20 immunostain, 200×; (C) CD3 immunostain, 200×). (D,E). Few cells show positivity for CD30 in another case of grade 2 LYG (CD30 immunostain, 400×); the same cells are intensely positive for EBER (EBER ISH, 400×). (F). Grade 3 LYG has a high proliferation index, i.e., >50% tumor cells showing nuclear immunoreactivity (Ki-67 immunostain, 400×).

Figure 5

Primary effusion lymphoma. (A). Large tumor cells are abundant in this pleural fluid sample (Papanicolau stain, 400×). (B). There is diffuse and intensemembranous and cytoplasmic staining for CD45 (Leukocyte Common Antigen) (CD45 immunostain, 400×).

Figure 6

Intravascular large B-cell lymphoma. (A). Large neoplastic cells fill the vessels within the interstitial spaces (H&E stain, 200×). (B–D). Tumor cells are positive for CD45 (B), CD20 (C), and show a high proliferative index, i.e., >90% tumor cells showing nuclear immunoreactivity (D) ((B) CD45 immunostain, 200×; (C) CD20 immunostain, 200×; (D) Ki-67 immunostain, 400×).