Question

Discuss the diagnostic criteria for Waldenström’s macroglobulinemia (WM).

Hint:

The key diagnostic elements of WM are the presence of monoclonal IgM, bone marrow infiltration by lymphoplasmacytic cells, and hyperviscosity symptoms. Genetic testing for MYD88 and CXCR4 mutations aids in diagnosis.

Answer 1

Step 1: Understanding Waldenström’s Macroglobulinemia.
Waldenström’s macroglobulinemia (WM) is a rare, indolent B-cell lymphoma characterized by the presence of monoclonal IgM antibodies produced by malignant lymphoplasmacytic cells. WM typically affects older adults and is associated with symptoms like hyperviscosity, neurological symptoms, anemia, and organ infiltration. The disease is diagnosed by a combination of clinical, laboratory, and histological criteria.

Step 2: Diagnostic Criteria.
The diagnostic criteria for WM include: 1. Lymphoplasmacytic infiltration in the bone marrow: The presence of malignant lymphoplasmacytic cells infiltrating the bone marrow is a hallmark of WM. A bone marrow biopsy is performed to confirm this infiltration.
2. Monoclonal IgM paraprotein: A monoclonal spike in serum protein electrophoresis (SPEP) or immunofixation electrophoresis (IFE) is observed, indicating the presence of IgM paraprotein. Elevated serum IgM levels are seen in the majority of WM patients.
3. Presence of symptoms or organ involvement: Symptoms such as fatigue, weight loss, peripheral neuropathy, or organomegaly (liver or spleen) may be present. Hyperviscosity syndrome is common in WM and is a key diagnostic feature. A visual disturbance or neurological deficits might indicate hyperviscosity.

Step 3: Genetic and Molecular Testing.
Genetic mutations such as MYD88 L265P are found in the majority of WM patients and serve as a diagnostic marker. CXCR4 mutations, which are seen in a smaller proportion of patients, are associated with resistance to certain therapies. These mutations can be detected through next-generation sequencing (NGS) or polymerase chain reaction (PCR).