Introduction

• Cause: clonal proliferation of malignant plasma cells. In ferrets, two clinical presentations have been described: multiple myeloma where there is systemic proliferation of malignant plasma cells or their precursors involving multiple bone marrow sites; and solitary osseous plasmacytoma where there is a solitary collection of malignant plasma cells in a bone.
• Signs: hindlimb ataxia or paresis, urinary tract abnormalities and overt pain on palpation are considered the most common signs. However, non-specific signs such as lethargy, reduced food intake and weight loss are also reported. Signs may have an acute onset.
• Diagnosis: bloodwork may demonstrate anemia, leukopenia, hyperproteinemia, hyperglobulinemia. Monoclonal gammopathy on serum protein electrophoresis. Evidence of osteolysis in one or more regions, lymphadenopathy, splenomegaly. Large numbers of atypical plasma cells with neoplastic changes on cytology and/or histopathology of masses, osteolytic lesions, and/or bone marrow biopsies. Cases of solitary osseous plasmacytoma may show little to no systemic abnormalities.
• Treatment: limited options described. Radiation therapy and chemotherapy suggested as possible therapies for multiple myeloma. Solitary osseous plasmacytoma may respond favorably to surgical excision and adjunctive chemotherapy.
• Prognosis: generally poor.

Pathogenesis

Etiology

• Largely undetermined in veterinary medicine.
• Multiple myeloma has been attributed to exposure to petroleum products and antigenic stimulants in humans.

Predisposing factors

General

• Older animals.

Pathophysiology

• There are various neoplasias described with plasma cell morphology including plasmacytoma, lymphoplasmacytic lymphoma, plasmablastic lymphoma and multiple myeloma.
• Plasma cell neoplasia in ferrets have been reported to cause two clinical syndromes: multiple myeloma and solitary osseous plasmacytoma.

Multiple myeloma

• Describes a clonal proliferation of malignant plasma cells that originates in bone marrow resulting in systemic disease.
• Normal B cells are transformed into malignant plasma cells in a multi-step process that includes cumulative mutational damage and multiple genetic abnormalities.
• Malignant plasma cells produce large quantities of an identical immunoglobulin protein, known as the monoclonal (M) component. The M-component may represent a complete immunoglobulin or a portion of an immunoglobulin.
• Subsequent bone marrow destruction and hypergammaglobulinemia contributes to the clinical and pathologic changes.
• Hyperviscosity syndrome:
  • Associated with increased blood viscosity due to high concentration of circulating protein.
  • Clinically manifests as neurologic signs, retinopathy and cardiomyopathy.
• Osteolysis:
  • Increased osteoclastic bone resorption and decreased osteoblastic bone formation.
  • May be associated with bone pain, spinal cord compression, pathological fracture(s), and hypercalcemia.
• Hemorrhagic diathesis: hemostatic disorders may result from M protein-induced thrombocytopathy, interference with clotting factors, abnormalities in the formation and action of fibrin, increased tissue fragility caused by amyloidosis, hypervolemia associated with hyperviscosity, and thrombocytopenia.
• Cytopenias:
  • Pancytopenia due to myelophthisis.
  • Anemia can also result from chronic disease, hemorrhage caused by coagulopathy and erythrocyte destruction.
• Hypercalcemia: caused by osteoclastic bone resorption, hypercalcemia of malignancy and/or increased calcium-binding to the M-component.
• Renal disease:
  • Renal tubular casts and resultant obstruction by M-component: secondary cytokine release and inflammation.
  • Renal amyloidosis.
  • Pyelonephritis.
  • Decreased renal perfusion due to hyperviscosity syndrome.
• Bacterial infection: immunodeficiency secondary to myelophthisis due to leukopenia, decreased production of functional immunoglobulin and compromised B-cell function.

Solitary osseous plasmacytoma

• Describes a collection of monoclonal malignant plasma cells in a solitary bony location.
• A vertebra was involved in the two reported ferret cases.
• Typically results in lysis and local destruction. Depending on the location, bone pain, spinal cord compression and pathological fracture(s) may result.
• In dogs, disease progression may involve development of other plasma cell tumors at distant sites or may progress to multiple myeloma. Not described in ferrets.

Timecourse

• Limited studies are available but suggest that disease, particularly multiple myeloma, is often advanced on diagnosis.
• Usually rapidly progressive and is fatal with a relatively short survival time (<107 days in one study) following diagnosis.

Epidemiology

• All ferrets were older than five years in one case series.
• Co-morbidities, eg adrenocortical disease, insulinoma Insulinoma, lymphoma Lymphoma overview were a frequent finding.

Diagnosis

Treatment

Outcomes