Lymphoplasmacytic lymphoma differential diagnosis

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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 must be differentiated from multiple myeloma, chronic lymphocytic leukemia/small lymphocytic lymphoma, b-cell prolymphocytic leukemia, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma.

Differentiating Lymphoplasmacytic lymphoma from other Diseases

Lymphoplasmacytic lymphoma must be differentiated from other B cell lymphoid neoplasms including:

  • Always express CD5
  • Usually CD23 positive[1]
  • Express CD10, HLA-DR, pan B-cell antigens (CD19, CD20, CD79a), CD21, and surface IgM, IgG, or IgA
  • Rearrangement of Bcl-2[4][5]
  • Express CD138, CD38, CD79a, VS38c and CD56 (70%)
  • Presence of plasmacytic cell infiltration of bone marrow, osteolytic lesions, and renal insufficiency
  • Translocation involving chromosome 11 (t11;14)[6]
  • Expresses CD5+ and CD23+
  • Expresses surface IgM, IgD, and cyclin D1 in majority of cases
  • Infiltration of bone marrow by monomorphous small lymphoid cells with irregular nuclei[7][8]
  • Expresses B cell markers CD19, CD20, and CD22
  • Infiltrates the bone marrow with a characteristic intertrabecular and intrasinusoidal pattern
  • Most common cytogenetic abnormalities are loss of 7q (19%) along with +3q (19%) and +5q (10% )[9][10]


Histopathology, immunophenotype, and genetic features of differential diagnosis of lymphoplasmacytic lymphoma
Disease entity Histopathology Immunophenotype Genetic or other features
Lymphoplasmacytic lymphoma ≥10 percent infiltration by small lymphocytes, plasmacytoid lymphocytes, and plasma cells, with variable numbers of admixed immunoblasts. Has a characteristic (but not pathognomonic) hyperplasia of mast cells in marrow. Lymph nodes are usually diffusely effaced. Absence of proliferation centers and marginal zone type differentiation. Expression of pan B-cell antigens (CD19, CD20, CD22, CD79a), failure to express CD5 in mostly cases and variable expression of CD11c, CD43, CD25. Mostly cases have IgM expression with only fewer expressing IgG or IgA. There's no CD10 and cyclin D1 expression. Majority have a monoclonal IgM paraprotein. No specific chromosomal abnormalities.
Chronic lymphocytic leukemia/small lymphocytic lymphoma "Typical" CLL/SLL cells are small mature appearing lymphocytes with a dense nucleus, partially aggregated chromatin, no discernible nucleoli, and a narrow border of clear to slightly basophilic cytoplasm. Always express CD5, usually CD23 positive with a dim expression of CD20 and surface Ig. Del13q, del 11q, del17p, trisomy 12
B-cell prolymphocytic leukemia Prolymphocytes comprise >55 percent of the neoplastic cells. Bone marrow has interstitial pattern of infiltration. Lymph nodes may show vague nodularity, but proliferation centers are absent. Express bright surface IgM +/- IgD and bright CD20 as well as other B-cell antigens (CD19, CD22, CD79a, FMC7). t(11;14) must be excluded. There's no associated paraproteinemia.
Follicular lymphoma Nodular growth pattern of follicle center cells (centrocytes and centroblasts). Typically express CD10, HLA-DR, pan B-cell antigens (CD19, CD20, CD79a), CD21, and surface IgM, IgG, or IgA. t(14;18)
Multiple myeloma Infiltration of plasma cells in the bone marrow. Surface Ig is absent. Express CD138, CD38, CD79a, and VS38c. Infrequently express CD19. Approximately 70 percent of myeloma cells will express CD56. Cytogenetics usually abnormal, although there is no specific cytogenetic abnormality.
Mantle cell lymphoma Monomorphous small to medium-sized B lymphocytes with irregular nuclei. CD5+ and CD23-; typically co-express surface IgM and IgD; the vast majority over-express cyclin D1. t(11;14)
Marginal zone lymphoma Polymorphous infiltrate of small cells with paler-appearing marginal zone-type differentiation in lymph nodes. Expresses B cell markers CD19, CD20, and CD22, and not CD5, CD10, and CD23. Chromosomal abnormalities, usually trisomy 3 or t(11;18), are found in most cases. May demonstrate mixed cryoglobulinemia +/- hepatitis C infection.
GC-associated lymphoid clones infiltrating the BM osteoblastic niche exhibit mesenchymal features in common with SLO germinal centers.(A–D) Histological examination of B-cell non-Hodgkin lymphoma (B-NHL) patient specimens. (A) The frequency of para-trabecular/osteoblastic localization of lymphoid malignant clones in 197 cases of B-NHL with bone marrow (BM) infiltration. Lymphoid clones of germinal center (GC)-derivation exhibiting preferential tropism for the BM osteoblastic niche include: follicular lymphoma (FL), T-cell rich histiocyte rich diffuse large B-cell lymphoma (TCRBCL), and diffuse large B-cell lymphoma of GC type (DLBCL-GC). Non-GC-related lymphoid clones include: DLBCL- activated B-cell type (ABC); mantle-cell lymmphoma, (MCL); marginal-zone lymphoma, (MZL); lymphoplasmacytic lymphoma, (LPL). (B) Para-trabecular (left panel) and inter-trabecular (right panel) localization of two representative cases of FL with BM infiltration. The distribution of the lymphomatous infiltrates around bone trabeculae or in the inter-trabecular lacunae is highlighted by CD20 immunostaining (inserts). (C–D) FL lymphoid infiltrates localizing within the osteoblastic niche area (left panels) and inter-trabecular BM (right panels) display a stromal architecture reminiscent of that of secondary lymphoid organ (SLO) GCs and are characterized by the expression of BM-MSC markers SPARC (C) and CD146 (right D).Source: Sangaletti S. et al, Molecular Immunology Unit; Department of Experimental Oncology and Molecular Medicine; Fondazione IRCCS Istituto Nazionale Tumori; Milan, Italy.
Expression of CD19 and CD20 in B-cell lineage.Notes: Illustrative representation of B-cell differentiation, maturation, antigen expression and B-cell neoplasm associated with different stages of B-cell development. Cell lines used in the research study.47–51Abbreviations: GC, germinal center; ALL, acute lymphoblastic leukemia; MCL, Mantle cell lymphoma; FL, follicular lymphoma; BL, Burkitt lymphoma; DLBCL, Diffuse Large B-Cell Lymphoma; MZL, Marginal Zone Lymphoma; CLL/SLL, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; MALT, Mucosa-Associated lymphoid tissue; WM, Waldenstrom macroglobulinemia; MM, plasma cell myeloma; WSU-BL, Wayne State University-Burkitt lymphoma cell line; WSU-FSCCL, Wayne State University-follicular small cleaved cell lymphoma Cell line; WSU-NHL, Wayne State University-FL grade 3 Cell line; WSU-DLCL and WSU-DLCL2, Wayne State University-Diffuse large B-Cell lymphoma cell line; WSU-WM, Wayne State University-Waldenstrom macroglobulinemia Cell line.Source: Raufi A. et al, Lymphoma Research Laboratory, Wayne State University School of Medicine (WSU-SOM), Gordon Scott Hall for Basic Medical Sciences, Detroit, MI, USA.

References

  1. ↑ Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, Hillmen P, Keating MJ, Montserrat E, Rai KR, Kipps TJ (2008). "Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines". Blood. 111 (12): 5446–56. doi:10.1182/blood-2007-06-093906. PMC 2972576. PMID 18216293.
  2. ↑ Del Giudice I, Davis Z, Matutes E, Osuji N, Parry-Jones N, Morilla A, Brito-Babapulle V, Oscier D, Catovsky D (2006). "IgVH genes mutation and usage, ZAP-70 and CD38 expression provide new insights on B-cell prolymphocytic leukemia (B-PLL)". Leukemia. 20 (7): 1231–7. doi:10.1038/sj.leu.2404238. PMID 16642047.
  3. ↑ Ravandi F, O'Brien S (2005). "Chronic lymphoid leukemias other than chronic lymphocytic leukemia: diagnosis and treatment". Mayo Clin. Proc. 80 (12): 1660–74. doi:10.4065/80.12.1660. PMID 16342661.
  4. ↑ Karube K, Guo Y, Suzumiya J, Sugita Y, Nomura Y, Yamamoto K, Shimizu K, Yoshida S, Komatani H, Takeshita M, Kikuchi M, Nakamura N, Takasu O, Arakawa F, Tagawa H, Seto M, Ohshima K (2007). "CD10-MUM1+ follicular lymphoma lacks BCL2 gene translocation and shows characteristic biologic and clinical features". Blood. 109 (7): 3076–9. doi:10.1182/blood-2006-09-045989. PMID 17138820.
  5. ↑ Anderson KC, Bates MP, Slaughenhoupt BL, Pinkus GS, Schlossman SF, Nadler LM (1984). "Expression of human B cell-associated antigens on leukemias and lymphomas: a model of human B cell differentiation". Blood. 63 (6): 1424–33. PMID 6609729.
    • Bone marrow infiltration of small, cleaved cells that are usually paratrabecular
  6. ↑ Pangalis GA, Kyrtsonis MC, Kontopidou FN, Vassilakopoulos TP, Siakantaris MP, Dimopoulou MN, Kittas C, Angelopoulou MK (2003). "Differential diagnosis of Waldenstrom's macroglobulinemia from other low-grade B-cell lymphoproliferative disorders". Semin. Oncol. 30 (2): 201–5. doi:10.1053/sonc.2003.50046. PMID 12720136.
  7. ↑ Dorfman DM, Pinkus GS (1994). "Distinction between small lymphocytic and mantle cell lymphoma by immunoreactivity for CD23". Mod. Pathol. 7 (3): 326–31. PMID 8058704.
  8. ↑ DiRaimondo F, Albitar M, Huh Y, O'Brien S, Montillo M, Tedeschi A, Kantarjian H, Lerner S, Giustolisi R, Keating M (2002). "The clinical and diagnostic relevance of CD23 expression in the chronic lymphoproliferative disease". Cancer. 94 (6): 1721–30. PMID 11920534.
  9. ↑ Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD (1999). "World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997". J. Clin. Oncol. 17 (12): 3835–49. PMID 10577857.
  10. ↑ Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC (1994). "A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group". Blood. 84 (5): 1361–92. PMID 8068936.

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