Lymphoplasmacytic lymphoma / Waldenström macroglobulinaemia (LPL/WM)

Definition

A neoplasm of small B lymphocytes, plasmacytoid lymphocytes and plasma cells, usually involving bone marrow, lymph nodes and spleen, usually negative for CD5, with an IgM monoclonal serum protein with hyperviscosity or cryoglobulinaemia. Plasmacytoid/plasmacytic variants are excluded. Although the clinical manifestations of Waldenström macroglobulinaemia may also occur with a variety of other B-cell lymphomas, the WHO classification and subsequent International Workshops now define LPL/WM as a clinicopathological entity.

Synonyms

Epidemiology

A rare disease (1.5% of nodal lymphomas) occurring in the elderly.

Clinical features

There is commonly involvement of bone marrow, spleen and lymph nodes. There may be extranodal involvement of lung, gastrointestinal tract or skin, but most cases previously diagnosed as LPL are MALT lymphomas. The serum monoclonal protein is usually IgM (Waldenström macroglobulinaemia), resulting in hyperviscosity in 10-30% of patients. 10% of patients develop neuropathies. IgM deposition occurs in the skin, and in the GI tract resulting in diarrhoea. There may be a coagulopathy. The IgM level usually exceeds 30g/l. and cut offs between 10g/l and 30 g/l have been proposed4. 15-20% of patients present with lymphadenopathy, which is usually not prominent4. 10-20% have splenomegaly4.

Histopathology

There is maturation to plasmacytoid cells, but lacking the features of other lymphomas (pseudofollicles, neoplastic follicles, monocytoid B cells).

Immunohistochemistry

CD5

negative0

 

CD10

negative0

CD19†

positive0

CD20

positive0

CD22

positive

CD23

negative0 , 1/28 3

CD38

positive

CD43

variable

CD79a

positive

SIg

positive, usually IgM0, sometimes IgG, rarely IgA

BSAP

50% of cases

VS38

positive

 

†: fresh frozen tissue only. Note that higher rates of positivity for CD5, CD10 and CD23 are obtained by flow cytometry3.

Cytogenetics

The prevalence of the t(9;14)(p13;q32) translocation is disputed4. 6q deletion is common but not specific, being found in other types of lymphoma4.

Variants

Differential diagnosis

Prognosis

The course is typically indolent with a median survival of five years. There may be progression to diffuse large B-cell lymphoma, which is associated with a poor prognosis. At this point, serum IgM levels may fall. In some cases, patients may develop Classical Hodgkin lymphoma.

References

0 World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

Wotherspoon AC, Hasserjian RP. Immunophenotyping in the differential diagnosis of histologically low grade B cell lymphomas. Current Diagnostic Pathology 2000;6:55-63.

1 A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood 1997;89(11): 3909-18.

2 Lin, P., C. Bueso-Ramos, et al. (2003). "Waldenstrom macroglobulinemia involving extramedullary sites: morphologic and immunophenotypic findings in 44 patients." Am J Surg Pathol 27(8): 1104-13.

3 Konoplev S, Medeiros LJ, Bueso-Ramos CE, et al. Immunophenotypic profile of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia. Am J Clin Pathol 2005; 124:414-20

4 Lin P,Medeiros LJ. Lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia: an evolving concept. Adv Anat Pathol 2005; 12:246-55

This page last revised 14.7.2007.

©SMUHT/PW Bishop