Waldenström's macroglobulinemia

From Dog
Rouleaux formation, plasmacytoid cells, and lymphoid cells associated with Waldenström's macroglobulinemia[1]

Waldenström's macroglobulinemia (lymphoplasmacytic lymphoma) is a variant B-cell IgM-producing lymphoma of older dogs.

The World Health Organization classification defines Waldenström's macroglobulinemia as lymphoplasmacytic lymphoma with bone marrow involvement and an IgM monoclonal gammopathy of any concentration[2]. In humans, deletion of the long arm of chromosome 6, trisomy 4 and 13q14 and 17p13 deletion are the most common abnormality associated with this disease, with up to 50% of patients having the genetic abnormality, emphasizing a genetic underpinning to the etiology of this disease[3].

In dogs, symptoms can be due to infiltration of bone marrow and other tissue sites by malignant lymphoplasmacytic cells or due to the effects of elevated serum IgM levels.

Clinical signs include gradual weight loss, lethargy, retinopathy, epistaxis, cutaneous masses, anemia, proteinuria and hemorrhagic diarrhea.

Unlike other forms of lymphoma, lymphadenopathy is not a consistent finding.

In humans, peripheral neuropathy[4] and nephrotic syndrome[5] are sometimes observed, but have not been reported in the dog.

Hematologically, these dogs present with varying degrees of anemia, lymphopenia, neutropenia, rouleaux formation, marked hyperglobulinemia and normoalbuminemia, hypercalcemia, markedly increased serum urea concentration and prolonged thrombin time[6]. Secondary hyperviscosity syndrome is a consistent finding and peliosis hepatis may be observed.

Diagnosis usually requires bone marrow biopsy, showing a propensity of small lymphocytes, lymphoplasmatoid cells and plasma cells within the marrow matrix at different stages of maturation[7].

Electrophoresis of serum or urine protein is usually confirmatory for a monoclonal IgM gammopathy.

A differential diagnosis of hyperglobulinemia due to plasmacytoma (multiple myeloma) can be elucidated by showing the absence of Bence-Jones proteins[8].

Treatment is usually successful with prednisolone and chlorambucil[9].

Experimental use of everolimus[10], bortezomib and rituximab[11] has shown good promise in human Waldenström's macroglobulinemia.

Although a cure is unlikely, the prospect of the animal having a fairly normal, healthy life for an extended period of time (over a year in the majority of cases) is good[12].

References

  1. Sethi B et al (2012) A Diagnostic Dilemma: Waldenström's Macroglobulinemia/Plasma Cell Leukemia. Case Report Pathol 2012:271407
  2. Jaffe ES (2009) The 2008 WHO classification of lymphomas: implications for clinical practice and translational research. Hematology Am Soc Hematol Educ Program pp:523-531
  3. Nguyen-Khac F et al (2012) Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenstrom macroglobulinemia. Haematologica Oct 12
  4. Wang CR et al (1988) Waldenstróm's macroglobulinemia with peripheral neuropathy - the role of IgM M-protein in autoimmune mechanism. Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi 21(1):9-15
  5. Sayegh J et al (2012) Steroid-resistant minimal change nephrotic syndrome in Waldenström macroglobulinemia. Ann Hematol Oct 4
  6. Jaillardon L & Fournel-Fleury C (2011) Waldenström's macroglobulinemia in a dog with a bleeding diathesis. Vet Clin Pathol 40(3):351-355
  7. Treon SP et al (2005) Report of the third International Workshop on Waldenström’s Macroglobulinemia. Clinical Lymphoma 5(4):215–216
  8. Mejia EB et al (1979) Case report: Macroglobulinemia in a dog. Can Vet J 20(1):28-33
  9. Greenberg CB et al (2008) Effect of chemotherapy schedule on response in Waldenström's macroglobulinemia in a dog. J Vet Intern Med 22(1):223-226
  10. Roccaro AM et al (2012) Mechanisms of activity of the TORC1 inhibitor everolimus in Waldesntrom's macroglobulinemia. Clin Cancer Res Oct 9
  11. Treon SP et al (2012) Familial Disease Predisposition Impacts Treatment Outcome in Patients With Waldenström Macroglobulinemia. Clin Lymphoma Myeloma Leuk Oct 16
  12. Matus RE & Leifer CE (1985) Immunoglobulin-producing tumors. Vet Clin North Am Small Anim Pract 15(4):741-753