Clinicopathological definition of Waldenstrom's macroglobulinemia: Consensus Panel Recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia

doi:10.1053/sonc.2003.50082

Seminars in Oncology

Volume 30, Issue 2, April 2003, Pages 110-115

https://doi.org/10.1053/sonc.2003.50082 Get rights and content

Abstract

This presentation represents consensus recommendations for the clinicopathological definition of Waldenstrom's macroglobulinemia (WM), which were prepared in conjunction with the Second International Workshop held in Athens, Greece during September 2002. WM is an uncommon lymphoproliferative disorder characterized primarily by bone marrow infiltration and IgM monoclonal gammopathy. It should be considered a distinct clinicopathological entity rather than a clinical syndrome secondary to IgM secretion. The underlying pathological diagnosis in WM is lymphoplasmacytic lymphoma as defined by the World Health Organization (WHO) and Revised European-American Lymphoma (REAL) classification criteria. The concentration of monoclonal IgM can vary widely in WM and it is not possible to define a concentration that reliably distinguishes WM from monoclonal gammopathy of undetermined significance (MGUS) and other lymphoproliferative disorders. A diagnosis of WM can therefore be made irrespective of IgM concentration if there is evidence on a bone marrow trephine biopsy of bone marrow infiltration by lymphoplasmacytic lymphoma with predominantly an intertrabecular pattern, supported by appropriate immunophenotypic studies. Simple criteria to distinguish patients with symptomatic WM who require therapy from those with asymptomatic WM and MGUS were also proposed. Patients with clinical features attributable to IgM monoclonal gammopathy but no overt evidence of lymphoma are considered to constitute a distinct clinical group and the term “IgM-related disorders” is proposed. Semin Oncol 30:110-115. © 2003 Elsevier Inc. All rights reserved.

Section snippets

Statement 1

WM is an uncommon B-cell lymphoproliferative disorder characterized primarily by bone marrow infiltration with a predominately intertrabecular pattern along with demonstration of an IgM monoclonal gammopathy. WM should be regarded as a distinct clinicopathological entity and not a clinical syndrome secondary to IgM secretion irrespective of the underlying pathological diagnosis. In WM this is considered to be lymphoplasmacytic lymphoma as defined by the Revised European-American Lymphoma (REAL)

Statement 2

The clinicopathological definition of WM should be confined to those patients with lymphoplasmacytic lymphoma who have demonstrable IgM monoclonal gammopathy.

Statement 3

The demonstration of an IgM monoclonal protein is not synonymous with a diagnosis of WM as they are demonstrable in other lymphoproliferative disorders and monoclonal gammopathy of undetermined significance (MGUS). The concentration of IgM varies widely in WM and it is not possible to define a concentration that reliably distinguishes WM from MGUS and other lymphoproliferative disorders. A diagnosis of WM can therefore be made irrespective of IgM concentration if there is evidence of bone

Statement 4

Central to the diagnosis of WM is the demonstration of bone marrow infiltration by lymphoplasmacytic lymphoma. This is defined as a tumor of small lymphocytes showing evidence of plasmacytoid/plasma cell differentiation without any of the clinical, morphological, or immunophenotypic features of other lymphoproliferative disorders.7, 8 A trephine biopsy should be regarded as a mandatory requirement for the assessment of patients while lymph node biopsies are encouraged in patients with

Statement 5

Clearly defined and reproducible criteria that distinguish MGUS and WM are required to facilitate a better understanding of the outcome and natural history of the IgM gammopathies. Patients with an IgM monoclonal protein and unequivocal evidence of bone marrow infiltration by lymphoplasmacytic lymphoma should be considered to have WM irrespective of the IgM concentration. Patients should be considered to have MGUS if they have IgM monoclonal gammopathy but no morphological evidence of bone

Statement 6

The faculty supported the position that the development of a prognostic scoring system for WM was more appropriate than the adoption of a staging system and deferred considerations to Consensus Panel 2.

Statement 7

Immunophenotyping is of great value in the differential diagnosis of B-cell lymphoproliferative disorders and its application in all cases of suspected WM is strongly recommended. The characteristic immunophenotypic profile for lymphoplasmacytic cells in WM should include the expression of the

Statement 8

There are currently no disease defining cytogenetic abnormalities in WM. Cytogenetic criteria cannot therefore be included in the clinicopathological definition of WM at this time.

Conclusions

WM is a distinct entity characterized by bone marrow infiltration by lymphoplasmacytic lymphoma and IgM monoclonal gammopathy. It can be confidently diagnosed through a combination of clinical features, cytomorphology, pattern of bone marrow infiltration, and immunophenotype. It is to be hoped that the proposed diagnostic criteria (summarized in Table 2.) will be incorporated into future clinical trials and that they will be refined as more phenotypic and genotypic data become available.

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^☆: Address reprint requests to Waldenstrom's Macroglobulinemia Program, Dana Farber Cancer Institute, Harvard Medical School, LG100, 44 Binney St, Boston, MA 02115. Email: [email protected].

^☆☆: 0093-7754/03/3002-0002$30.00/0

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Waldenstrom's MacroglobulinemiaClinicopathological definition of Waldenstrom's macroglobulinemia: Consensus Panel Recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia☆,☆☆

Abstract

Section snippets

Statement 1

Statement 2

Statement 3

Statement 4

Statement 5

Statement 6

Statement 7

Statement 8

Conclusions

Blood

Mayo Clin Proc

Clin Lymph

Blood

Blood

Semin Oncol

Semin Oncol

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Blood

Blood

Incipient myelomatosis or essential hyperglobulinemia with fibrinogenopenia—A new syndrome?

Acta Med Scand

Waldenström's macroglobulinemia: Clinical features, complications, and management

J Clin Oncol

Waldenström's macroglobulinaemia: Laboratory diagnosis and treatment

Hematol Oncol

B-cell lymphoma accompanying monoclonal macroglobulinemia with features suggesting marginal zone B-cell lymphoma

Int J Hematol

Low-grade MALT lymphoma mimicking Waldenström's macroglobulinemia

Leukemia

Waldenström macroglobulinemia caused by extranodal marginal zone B-cell lymphoma

Am J Clin Pathol

World Health Organization Classification of Tumours

Paraprotein status in lymphoplasmacytoid lymphoma/immunocytoma: Do all cases correspond to Waldenström's macroglobulinaemia?

Br J Haematol

Immunocytoma: A retrospective analysis from St Bartholomew's Hospital—1972 to 1996

J Clin Oncol

Waldenstrom's Macroglobulinemia
Clinicopathological definition of Waldenstrom's macroglobulinemia: Consensus Panel Recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia☆,☆☆