Lymphoplasmacytic lymphoma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2]

Overview

Lymphoplasmacytic lymphoma (LPL) is an uncontrolled clonal proliferation of terminally differentiated B lymphocytes, which are normally involved in humoral immunity. Two main factors mediating this disease include IgM paraprotein secretion and tissue infiltration with neoplastic lymphoplasmacytic cells. Genes involved in the pathogenesis of LPL include MYD88-L265P, and CXCR4 along with various other cytogenetic and epigenetic abnormalities. In patients of lymphoplasmacytic lymphoma, there is an increased incidence of diffuse large B-cell lymphoma, myelodysplastic syndrome (acute myeloid leukemia), brain tumor, and renal MALT lymphoma. Two histologic subtypes include lymphoplasmacytoid and lymphoplasmacytic which invade the lymphoid organs such as spleen, lymph nodes and bone marrow. Bone marrow is infiltrated by small lymphocytes, well-formed plasma cells, and plasmacytoid lymphocytes in diffuse, interstitial, nodular, paratrabecular, nodular-interstitial and mixed paratrabecular-nodular patterns. Lymph nodes infiltration shows Dutcher and Russell bodies, mast cells, and hemosiderin-laden macrophages. Peripheral smear shows circulating malignant cells with a plasmacytoid appearance, having basophilic cytoplasm, perinuclear halo, and nucleus with "clock-face" chromatin without nucleoli. Immunohistochemistry shows pan B-cell surface antigens such as Ig+CD19+, CD20+, CD22+, CD79A+ and variable expression of some other antigens.

Pathophysiology

B lymphocytes

Development

Function

B cells are:[4]

Factors mediating lymphoplasmacytic lymphoma

Genetics

Cytogenetics

Epigenetics:

Associated Conditions

Several studies showed an increased incidence of following second cancers in patients with lymphoplasmacytic lymphoma:[22]

Microscopic Pathology

High-power field of peripheral blood smear revealing a large, atypical B cell with mild cytoplasmic expansion, coarse chromatin, multiple distinct nucleoli and peripheral vacuolation.Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.
Low-power magnification of the splenic tissue. This slide displays significant distortion and diffuse infiltration of the splenic parenchyma by lymphoid cells. Of particular note is the expansion of the white pulp by this infiltrate. Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.
Medium-power field of bone marrow aspirate demonstrating a population of small atypical lymphocytes admixed with normal cells of erythroid, myeloid and lymphoid lineage.Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.
(A) Rouleaux formation, plasmacytoid cells, and lymphoid cells in the PBF (Leishman, ×1000). (B) Uni-binucleated plasmacytoid cells in the PBF (Leishman, ×1000). Source: Sethi B. et al, Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India.
Photomicrograph showing hypercellular marrow with diffuse infiltration by lymphoid cells, plasmacytoid lymphocytes, a few plasma cells, and mast cells (hematoxylin and eosin stain, ×1,000); inset photomicrograph showing strong cytoplasmic positivity for CD20 in the majority of the lymphoid cells (immunohistochemical stain for CD20, ×400).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3786287_br-48-230-g002&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=25 Source: Pujani M. et al, Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India.
]
High-power magnification of splenic lymphoid infiltrate. This slide demonstrates that the infiltrate consists of small- and medium-sized atypical lymphocytes, which display dense chromatin clumping and prominent nucleoli. Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.
Photomicrograph showing hypercellular bone marrow smears with the presence of mostly bare nuclei, few lymphoid cells, and plasmacytic cells (Wright's stain, ×1,000).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3786287_br-48-230-g001&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=24 Source: Pujani M. et al, Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India.
]
(A) Plasmacytoid cells in the bone marrow aspirates (Leishman, ×1000). (B) Tetranucleated plasmacytoid/plasma cell and lymphoid cell in the bone marrow aspirates (Leishman, ×1000). Source: Sethi B. et al, Department of Pathology, VCSGGMS & RI Srinagar, Pauri Garhwal, Uttarakhand, India.
Electron Microscopy. There is marked thickening of the glomerular basement membrane due to the presence of numerous electron-dense deposits located at different levels. The deposits vary in size, tend to be spherical in shape and blend together. Under higher magnifications, they did not exhibit a fibrillary or micro-tubular substructure. Notice a thin subendothelial layer of the duplicated basement membrane, also containing electron-dense deposits, with cellular interposition. The capillary lumen appears significantly reduced in diameter. Also notice electron-dense deposits present in the basement membrane of Bowman's capsule on the right upper corner (Uranyl acetate & lead citrate × 35,000).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-3&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=33 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.
]
Electron Microscopy. This field illustrates a large subendothelial and several, much smaller, subepithelial electron-dense deposits. This pattern is similar to that originally described in MPGN type III and also often seen in proliferative lupus GN. Notice the duplication of the glomerular basement membrane with cellular interposition. The duplicated segment also contains electron-dense deposits. Occasionally giant, subendothelial, globular electron-dense deposits reduced the capillary loop to a pin-point lumen. Probably they correspond to the globules seen by light and fluorescence microscopy (Uranyl acetate and lead citrate × 40,000). [https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-4&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=34 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.
]
Light Microscopy. There is marked, global, homogeneous, eosinophilic thickening of the glomerular basement membrane with segmental accentuation. Homogeneous, eosinophilic globules are seen in the lumen of occasional capillary loops. The capillary lumina appear reduced in diameter but no inflammatory or proliferative changes are observed. The periglomerular interstitial space shows lymphocytic infiltration. The focal interstitial deposition of homogeneous eosinophilic material is present in the right upper corner of the picture (H&E × 400). Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.
Immunofluorescence. Global granular and homogeneous deposition of IgG along the glomerular basement membrane. Notice the presence of IgG containing globules in rare capillary loops. They seem to correspond to the eosinophilic globules seen by light microscopy and large electron-dense deposits detected by electron microscopy (FITC labeled anti-IgG × 400).Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.
Renal biopsy. (A) Immunofluorescent microscopic study showed a 2+ reaction for IgM. (B) On the electron microscopic (EM) findings (× 20,000), there are subendothelial (arrow) and mesangial electron-dense deposits revealing microtubular structures (25 nm in average diameter). Source: Kim YL. et al, Department of Internal Medicine, Eulji University College of Medicine, Seoul, Korea

Immunohistochemistry

Malignant cells in lymphoplasmacytic lymphoma have following immunophenotypic characteristics:[27][7]

References

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