Search

Histological transformation (HT) to an aggressive lymphoma results from a rare evolution of Waldenström macroglobulinemia (WM). A higher incidence of transformation events has been reported in MYD88 wild-type WM patients. HT in WM can be histologically heterogeneous, although the diffuse large B-cell lymphoma of activated B-cell subtype is the predominant pathologic entity. The pathophysiology of HT is largely unknown. The clinical suspicion of HT is based on physical deterioration and the rapid enlargement of the lymph nodes in WM patients. Most transformed WM patients present with elevated serum lactate dehydrogenase (LDH) and extranodal disease. A histologic confirmation regarding the transformation to a higher-grade lymphoma is mandatory for the diagnosis of HT, and the choice of the biopsy site may be dictated by the findings of the 18fluorodeoxyglucose-positron emission tomography/computed tomography. The prognosis of HT in WM is unfavorable, with a significantly inferior outcome compared to WM patients without HT. A validated prognostic score based on 3 adverse risk factors (elevated LDH, platelet count < 100 × 109/L and any previous treatment for WM) stratifies patients into 3 risk groups. The most common initial treatment used is a chemo-immunotherapy (CIT), such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). The response duration is short and central nervous system relapses are frequent. Whether autologous stem cell transplantation could benefit fit patients responding to CIT remains to be studied. [ABSTRACT FROM AUTHOR]

We aimed to detect the MYD88L265P and CXCR4S338X mutations in cell-free DNA (cfDNA) in patients with Waldenström macroglobulinemia (WM). We collected peripheral blood and paired bone marrow aspirates from 27 WM patients (including 16 patients with newly diagnosed WM, 3 patients with WM in relapse and 8 patients with WM during treatment). cfDNA was extracted from peripheral blood using a QIAamp Circulating Nucleic Acid Kit. The MYD88L265P and CXCR4S338X mutations were detected by real-time allele-specific PCR (AS-PCR) in cfDNA and genomic DNA (gDNA) extracted from bone marrow aspirates. The sensitivity of real-time AS-PCR for detecting MYD88L265P in cfDNA was determined using a serial dilution of 10%, 2%, 0.4% and 0.08% MYD88L265P cfDNA in wild-type cfDNA. Among the 27 patients, MYD88L265P was detected in 88.9% of them in gDNA and in 85.2% of them in cfDNA, with a concordance rate of 96.3%. The concordance rates were 93.8%, 100% and 100% in patients with newly diagnosed WM, patients with WM in relapse and patients with WM during treatment, respectively. The sensitivity of real-time AS-PCR for detecting MYD88L265P in cfDNA was 0.4%. CXCR4S338X was detected in 6.3% of the 16 newly diagnosed WM patients in both gDNA and cfDNA, with a concordance rate of 100.0%. It is feasible to apply cfDNA to detect MYD88L265P and CXCR4S338X in WM patients with a high concordance rate. [ABSTRACT FROM AUTHOR]

• CXCL13 levels were significantly elevated in the serum and bone marrow of patients with WM. • In patients with WM, serum CXCL13 levels were correlated with tumor load. • Detection of serum CXCL13 may aid the differential diagnosis of WM. To explore the value of elevated CXCL13 levels in Waldenström macroglobulinemia (WM). We collected serum samples from 41 patients and bone marrow tissues from 14 patients with newly diagnosed symptomatic WM. Serum and bone marrow samples from patients with other indolent B-cell lymphomas and MGUS were also collected for comparison. Serum CXCL13 levels were measured by enzyme-linked immunosorbent assay, and bone marrow tissues were examined by immunohistochemistry. The median serum level of CXCL13 in patients with symptomatic WM was 2483.0 (range 36.8–5644.0) pg/ml, which was significantly higher than in patients with other indolent B-cell lymphomas with monoclonal IgM (median 380.9 pg/ml, range 23.8–5518.0 pg/ml) (p = 0.01). Serum CXCL13 >3250 pg/ml and serum M-protein >38 g/l diagnosed WM with a sensitivity of 98% and specificity of 85%. Serum CXCL13 was strongly correlated with hemoglobin levels (ρ=−0.46, p = 0.002), serum M-protein (ρ=0.47, p = 0.002), and IgM levels (ρ=0.30, p = 0.05) in patients with symptomatic WM. Immunohistochemistry analysis indicated that CXCL13 and activated mast cell levels were also higher in the bone marrow of WM patients compared to patients with IgM-MGUS or other indolent B-cell lymphomas with monoclonal IgM. Serum CXCL13 levels were significantly elevated in patients with WM and correlated with tumor load. Detection of serum CXCL13 may therefore be helpful in the differential diagnosis of WM. [ABSTRACT FROM AUTHOR]

Cutaneous manifestations of Waldenström macroglobulinemia (WM) may occur because of several mechanisms, the least common being direct skin infiltration by neoplastic cells. We report a case of patient that after 4-year history of indolent WM developed skin infiltration by lymphoplasmacytoid cells in the form of a small, mildly indurated plaque on the anterior chest. MYD88 L265P mutation was detected both in the previous bone marrow biopsy and in the cutaneous lesion. We review the impact of this new genetic tool in the diagnosis and treatment of lymphoplasmacytic proliferations. [ABSTRACT FROM AUTHOR]