Chapter 70: Macroglobulinemia

DEFINITION

• Waldenström macroglobulinemia (WM) is a lymphoid neoplasm resulting from the accumulation, predominantly in the marrow, of a clonal population of lymphocytes, lymphoplasmacytic cells, and plasma cells, which secrete a monoclonal immunoglobulin (Ig) M.

• WM corresponds to lymphoplasmacytic lymphoma (LPL) as defined in the Revised European-American Lymphoma (REAL) and World Health Organization classification systems.

• Most cases of LPL are WM; less than 5 percent of cases are IgA-secreting, IgG-secreting, or nonsecreting LPL.

EPIDEMIOLOGY

• The age-adjusted incidence rate of WM is 3.4 per 1 million among males and 1.7 per 1 million among females in the United States.

• The incidence rate is higher among Americans of European descent. Americans of African descent represent approximately 5 percent of all patients.

• Approximately 20 percent of patients are of Eastern European descent, specifically of Ashkenazi-Jewish ethnic background.

• Approximately 20 percent of 257 sequential patients with WM presenting to a tertiary referral center had a first-degree relative with either WM or another B-cell disorder.

PATHOGENESIS

Cytogenetic Findings

• Loss of all or part of chromosomes 17, 18, 19, 20, 21, 22, X, and Y have been commonly observed, and gains in chromosomes 3, 4, and 12 also occur.

• Chromosome 6q deletions encompassing 6q21–25 have been observed in up to half of WM patients.

Nature of the Tumor Cell

• The marrow B-cells in WM undergo maturation from small lymphocytes with large focal deposits of surface immunoglobulins, to lymphoplasmacytic cells or to plasma cells that contain intracytoplasmic immunoglobulins.

CLINICAL FEATURES

• Table 70–1 lists clinical and laboratory features at the time of diagnosis for 356 patients in a large study.

• Presenting symptoms most commonly are fatigue, weakness, weight loss, episodic bleeding, and manifestations of the hyperviscosity syndrome.

• Physical findings include:

  — Lymphadenopathy.

  — Hepatosplenomegaly.

  — Dependent purpura and mucosal bleeding.

  — Dilated tortuous retinal veins.

  — Multiple flesh-colored papules on extensor surfaces (deposits of IgM reacting to epidermal basement membrane antigens).

  — Peripheral sensory neuropathy.

  — Raynaud phenomenon, especially upon exposure to cold.

  — Splenomegaly and lymphadenopathy are uncommon.