Initial clinical and laboratory evaluation of WM
| . | Comments . |
|---|---|
| Clinical evaluation | |
| History and physical examination | Headache, blurred vision: consider HVS |
| Familial history for WM and other B-cell lymphoproliferative disorders | Skin rash: cryoglobulinemia (palpable purpura), Schnitzler syndrome (urticaria, bone pain, fever) |
| Review of systems for the presence of B symptoms, organomegaly, hyperviscosity symptoms, neuropathy, Raynaud’s disease, rash, peripheral edema, skin abnormalities, dyspnea | Symptoms of peripheral neuropathy: consider neurologist consultation |
| Funduscopic examination by an experienced ophthalmologist if IgM is high (ie, >3000 mg/dL) or hyperviscosity is suspected; photographic documentation may be useful for appreciation of future changes | Dyspnea, edema: consider amyloidosis |
| Laboratory evaluation | |
| Complete blood count | Additional tests may be required for evaluation of anemia, especially if it is the only indication of symptomatic disease (consider other causes such as iron deficiency or other) |
| Complete metabolic panel (including LDH, serum albumin) | Hemolysis should be considered if increased bilirubin and LDH |
| Serum Ig levels (IgA, IgG, IgM) | Urine evaluation at baseline is advised; if renal dysfunction or proteinuria is present, consider additional tests (cryoglobulins, FLCs etc) |
| Serum and urine electrophoresis with immunofixation | |
| Serum B2M level | |
| Viral serology (hepatitis B and C and HIV) | |
| Histology and molecular tests | |
| BM aspiration and biopsy | MYD88 testing not standardized; |
| IHC (required for diagnosis) | BM is preferable for testing MYD88, but other methods may also be useful |
| Flow cytometry (optional; consider if IHC not available) | The laboratory should report the sensitivity of MYD88 detection |
| Testing for MYD88L265P | Testing for CXCR4WHIM not helpful for diagnosis; not standardized, should be considered optional and not used for clinical decisions |
| There are limited data on the prognostic effect of cytogenetics by interphase fluorescence in situ hybridization or karyotype, although in some cases it may be helpful in differential diagnosis in addition to other findings | |
| Optional tests, if clinically indicated | |
| In case of Raynaud’s, renal dysfunction, hematuria, skin rash, hyperviscosity consider evaluation for cryoglobulins | Cryoglobulins may require special communication with the laboratory |
| Hemolysis, hyperviscosity: consider cold agglutinin titer | In the presence of cryoglobulins, the assessment of IgM and response may be challenging |
| Serum viscosity (not always correlated with symptoms) | |
| Bleeding diathesis with prolonged aPTT and PT: screening for acquired von Willebrand disease | |
| Suspicion of amyloidosis: 24-hour urine protein quantification, Serum FLCs, NTproBNP, Cardiac troponins | |
| Symptoms of peripheral neuropathy are reported: nerve conduction studies, myelin-associated globulin antibodies, anti-ganglioside M1, other antibodies (consultation with neurologist strongly advised) | |
| Central nervous system symptoms: consider Bing-Neel syndrome, brain/spine magnetic resonance imaging, cerebrospinal fluid testing (also for MYD88L265P) | |
| Renal dysfunction: consider renal biopsy if indicated. Several renal pathologies have been described such as amyloidosis, cryoglobulinemic glomerulonephritis, immunoglobulin deposition disease, cast nephropathy, etc21,22 |
| . | Comments . |
|---|---|
| Clinical evaluation | |
| History and physical examination | Headache, blurred vision: consider HVS |
| Familial history for WM and other B-cell lymphoproliferative disorders | Skin rash: cryoglobulinemia (palpable purpura), Schnitzler syndrome (urticaria, bone pain, fever) |
| Review of systems for the presence of B symptoms, organomegaly, hyperviscosity symptoms, neuropathy, Raynaud’s disease, rash, peripheral edema, skin abnormalities, dyspnea | Symptoms of peripheral neuropathy: consider neurologist consultation |
| Funduscopic examination by an experienced ophthalmologist if IgM is high (ie, >3000 mg/dL) or hyperviscosity is suspected; photographic documentation may be useful for appreciation of future changes | Dyspnea, edema: consider amyloidosis |
| Laboratory evaluation | |
| Complete blood count | Additional tests may be required for evaluation of anemia, especially if it is the only indication of symptomatic disease (consider other causes such as iron deficiency or other) |
| Complete metabolic panel (including LDH, serum albumin) | Hemolysis should be considered if increased bilirubin and LDH |
| Serum Ig levels (IgA, IgG, IgM) | Urine evaluation at baseline is advised; if renal dysfunction or proteinuria is present, consider additional tests (cryoglobulins, FLCs etc) |
| Serum and urine electrophoresis with immunofixation | |
| Serum B2M level | |
| Viral serology (hepatitis B and C and HIV) | |
| Histology and molecular tests | |
| BM aspiration and biopsy | MYD88 testing not standardized; |
| IHC (required for diagnosis) | BM is preferable for testing MYD88, but other methods may also be useful |
| Flow cytometry (optional; consider if IHC not available) | The laboratory should report the sensitivity of MYD88 detection |
| Testing for MYD88L265P | Testing for CXCR4WHIM not helpful for diagnosis; not standardized, should be considered optional and not used for clinical decisions |
| There are limited data on the prognostic effect of cytogenetics by interphase fluorescence in situ hybridization or karyotype, although in some cases it may be helpful in differential diagnosis in addition to other findings | |
| Optional tests, if clinically indicated | |
| In case of Raynaud’s, renal dysfunction, hematuria, skin rash, hyperviscosity consider evaluation for cryoglobulins | Cryoglobulins may require special communication with the laboratory |
| Hemolysis, hyperviscosity: consider cold agglutinin titer | In the presence of cryoglobulins, the assessment of IgM and response may be challenging |
| Serum viscosity (not always correlated with symptoms) | |
| Bleeding diathesis with prolonged aPTT and PT: screening for acquired von Willebrand disease | |
| Suspicion of amyloidosis: 24-hour urine protein quantification, Serum FLCs, NTproBNP, Cardiac troponins | |
| Symptoms of peripheral neuropathy are reported: nerve conduction studies, myelin-associated globulin antibodies, anti-ganglioside M1, other antibodies (consultation with neurologist strongly advised) | |
| Central nervous system symptoms: consider Bing-Neel syndrome, brain/spine magnetic resonance imaging, cerebrospinal fluid testing (also for MYD88L265P) | |
| Renal dysfunction: consider renal biopsy if indicated. Several renal pathologies have been described such as amyloidosis, cryoglobulinemic glomerulonephritis, immunoglobulin deposition disease, cast nephropathy, etc21,22 |
FLC, free light chains; HVS, hyperviscosity syndrome.