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.
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).
lymph nodes; the pattern is diffuse or interfollicular, sparing the sinuses. The infiltrate consists of small lymphocytes, plasmacytoid cells and plasma cells Immunoblasts, epithelioid histiocytes and mast cells may be present.
bone marrow; diffuse, nodular or interstitial infiltration. The consensus panel requires bone marrow involvement for the diagnosis of WM4.
There may be circulating neoplastic cells, but the count is lower than for CLL
Immunohistochemistry
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negative0 |
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negative0 |
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positive0 |
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negative0 , 1/28 3 |
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positive |
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variable |
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positive |
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SIg |
positive, usually IgM0, sometimes IgG, rarely IgA |
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50% of cases |
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: 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
Gamma heavy chain disease: there is secretion of a truncated gamma chain lacking light chain binding sites. Patients are adults with constitutional symptoms, autoimmune manifestations, lymphadenopathy, involvement of Waldeyer's ring, hepatosplenomegaly and peripheral eosinophilia. The average age of patients is 60 years. The peripheral blood may show a CLL or plasma cell leukaemia-like appearance. Lymph nodes show a polymorphous infiltrate of lymphocytes, plasmacytoid lymphocytes, plasma cells, immunoblasts and eosinophils. In some cases the appearance resembles CLL. In others, plasma cell predominate, resembling plasma cell myeloma. Rarely, the appearances are those of a nodal large cell lymphoma.
Differential diagnosis
Other low grade non-Hodgkin's lymphomas: immunophenotypes Other low grade B-cell lymphomas may be associated with an IgM monoclonal paraproteinaemia.
Distinction from marginal zone B-cell lymphoma may be very difficult1. Bone marrow involvement and an IgM gammopathy favours lymphoplasmacytic lymphoma2. MZL is usually cyclin D1+/CD5+/CD23-.
Distinction from mantle cell lymphoma may be very difficult.
Small cell lymphocytic lymphoma; may include clonal plasma cells, but not lymphoplasmacytoid cells. in contrast to SLL/CLL, Lymphoplasmacytic lymphoma lacks proliferation centres. SLL/CLL uniquely manifest paraimmunoblasts. SLL/CLL is almost always positive for CD5 and commonly positive for CD23.
Follicular lymphoma usually shows paratrabecular bone marrow involvement. The cells are CD10+/bcl-6+.
Small cell myeloma; staining for IgM is helpful as less than 1% of myelomas are IgM positive. Myelomas are usually CD20 negative. Myeloma is favoured by lytic bone lesions, renal failure, and IgG or IgA paraproteinaemia. The plasma cells are CD138+/CD19-.
Monoclonal gammopathy of unknown significance (MGUS) and IgM-related disorders: there is a lack of significant bone marrow infiltration.
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.
This page last revised 14.7.2007.
©SMUHT/PW Bishop