Rare presentation of Waldenström's macroglobulinaemia requiring bilateral above-knee amputations: a case report.

BACKGROUND: Waldenström's macroglobulinaemia is a rarely encountered B-lymphocytic malignancy. Waldenström's macroglobulinaemia-associated paraproteinaemia is linked to an increase in serum viscosity, which results in a hypercoagulable state. Burning bilateral foot pain in a man with alcohol dependence and controlled atrial fibrillation presenting to the emergency department was attributed to peripheral neuropathy, given satisfactory angiographic evidence of bilateral foot arterial blood supply. Subsequently, his presentation as an emergency with acute bilateral critical lower limb ischemia that was managed by bilateral above-knee amputations, prompted a wider search for other etiologies. We present a hitherto unreported case of Waldenström's macroglobulinaemia-related acute bilateral lower limb ischemia, which required bilateral above-knee amputations. CASE PRESENTATION: A 50-year-old Caucasian man, who was an alcohol dependent heavy smoker, presented with burning pain in his right foot that was deemed to be related to alcoholic neuropathy. A computerized tomographic angiogram demonstrated an occluded right distal anterior tibial artery but a patent posterior tibial artery supplying the foot arch, findings that were associated with noncritical ischemia. After multiple presentations within a week, he was admitted following sudden clinical deterioration with acute confusion, hyponatremia, and bilateral foot pain. Over the course of 24 hours, the patient deteriorated rapidly, with bilateral lower limb ischemia requiring bilateral above-knee amputations. Subsequent investigations revealed a diagnosis of Waldenström's macroglobulinaemia. CONCLUSIONS: To the best of our knowledge, this is the only reported case of Waldenström's macroglobulinaemia-induced bilateral lower limb ischemia requiring major bilateral amputations.

MYD88 L265P MUTATION DETECTION IN THE AQUEOUS HUMOR OF PATIENTS WITH VITREORETINAL LYMPHOMA.

PURPOSE: To detect the presence of MYD88 L265P mutation in the aqueous humor of patients with cytologically proven vitreoretinal lymphoma. METHODS: Eight consecutive patients with bilateral vitreoretinal lymphoma (16 eyes) were prospectively evaluated. Genomic DNA was extracted from aqueous samples after paracentesis and vitreous humor samples after diagnostic vitrectomy. MYD88 codon 265 mutation was investigated by both amplification-refractory mutation system polymerase chain reaction approach and pyrosequencing assay in the aqueous humor of all patients and in the vitreous of 6 patients. A control group of 8 age-matched patients with established diagnosis of noninfectious uveitis was also tested for the presence of MYD88 L265P mutation in the aqueous humor. RESULTS: Eight patients (three men, five women) with mean age of 69.5 years (range 50-85 years) were considered. All the patients tested for MYD88 L265P in the vitreous (six) were positive, and this result was consistent with cytological examination in all samples but one. The MYD88 L265P mutation was found in the aqueous of 6 patients (75%), and in 3 of them, the mutation was present in both eyes. Results of MYD88 L265P mutation in aqueous and vitreous sample were consistent in 7 of the 8 eyes with available samples. The aqueous humor of the noninfectious uveitis control group was negative for the detection of MYD88 L265P mutation. CONCLUSION: MYD88 mutation was detected in the aqueous humor of 75% of patients with cytologically proven vitreoretinal lymphoma. This technique may be considered as an additional diagnostic tool in the detection of the disease.

Normothermic Cardiopulmonary Bypass in Patient With Waldenström's Macroglobulinemia and Cryoglobulinemia: A Case Report.

Waldenström's macroglobulinemia (WM) manifests as hyperviscosity syndrome. Cryoglobulinemia, which may increase blood viscosity or induce thrombosis in association with decreased body temperature, can occur in combination with WM. We describe the management of an 82-year-old woman with WM, hyperviscosity syndrome, and cryoglobulinemia who required open aortic valve replacement. Decreased body temperature in this patient was prevented during cardiopulmonary bypass by using a forced air warming system and normothermic cardioplegia with continuous warm blood cardioplegia perfusion.

Clinical features and diagnosis of hairy cell leukemia.

Significant advances in the diagnosis and treatment of hairy cell leukemia (HCL) have recently been made. Improved distinction of HCL from its mimics though clinical presentations, morphologic and immunophenotypic features, and more recently molecular biology, has highlighted marked differences in treatment response and overall prognosis between these disorders. As our understanding of the unique pathobiology of HCL has grown, exciting new avenues of treatment as well as insight into immune function have been obtained. This review provides an overview of the clinical features and diagnostic attributes of HCL, with contrast to other mature B cell lymphoproliferative disorders with overlapping features.

A tale of the unexpected: Amyloidoma associated with intracerebral lymphoplasmacytic lymphoma.

Amyloidoma is a rare cause for intracranial space-occupying lesions diagnosed on brain imaging. Histology of excised tissue usually reveals the presence of a discrete, λ-light chain secreting plasmacytoma adjacent to an amyloid mass comprising aggregated monoclonal immunoglobulin light chains. We described a patient with intracerebral amyloidoma associated with a localised lymphoplasmacytic lymphoma and no systemic paraproteinaemia, tumour or amyloid deposits.

Splenectomy Followed by Hepatectomy for Hepatocellular Carcinoma with Hypersplenism and Portal Hypertension Caused by Macroglobulinemia.

AIM: To describe a patient with hepatocellular carcinoma (HCC), accompanied by hypersplenism and portal hypertension caused by macroglobulinemia, who underwent splenectomy followed by hepatectomy. CASE REPORT: A 74-year-old man was admitted to our Hospital. He had previously developed primary macroglobulinemia, which had been completely cured by chemotherapy. At admission, he had a low platelet count (52 × 10(3)/µl), and his liver function was impaired. Imaging showed a 5-cm-sized tumor, an esophageal varix, and splenomegaly, but not liver cirrhosis. The patient underwent splenectomy for hypersplenism and portal hypertension; the weight of his spleen was 2,400 g. After splenectomy, his platelet count increased to 259 × 10(3)/µl and his liver function was improved. He safely underwent hepatectomy for HCC. The patient was discharged 14 days later without morbidity. CONCLUSION: These findings suggest that hepatectomy following splenectomy for hypersplenism and portal hypertension caused by macroglobulinemia, may effectively cure HCC in patients with liver dysfunction and thrombocytopenia.

[Case of primary lymphoplasmacytic lymphoma limited to the paratracheal mediastinum].

A 54 year old Japanese man was introduced to Saiseikai General hospital for an evaluation of an abnormal chest X-ray film. Abnormal soft tissue area was observed in the mediastinum surrounding anterior area of the trachea on chest CT. Because the mediastinal tumor showed slow enlargement after temporal decrease and surgical resection of the tumor was performed 3 years after the first visit. Pathologically, diffuse proliferation of oval-shaped plasmacytic or small lymphocytic cells with eccentrically-located nuclei with rough chromatin were observed in the tumor. Immunohistochemically, these cells were positive for CD20, weakly positive for IgM, negative for CD3, CD5, CD10, suggesting lymphoplasmacytic lymphoma (LPL). The patient was treated with rituximab after the surgical treatment, and showed no exacerbation for 3.5 years after surgery. LPL localized to the paratracheal mediastinum is rare, and a surgical approach is important for prompt and proper diagnosis.

Stem cell transplant for Waldenström macroglobulinemia: an underutilized technique.

Waldenström macroglobulinemia is a highly chemosensitive lymphoplasmacytic lymphoma with response rates of 90% to first-line chemotherapy. The fraction of patients undergoing stem cell transplant for this disorder appears to be lower than that of patients with multiple myeloma. The indolent nature and favorable genetic profile should make Waldenström an ideal disorder for autologous stem cell transplant, with high response rates that are durable. We review the literature on autologous and allogeneic transplants for Waldenström macroglobulinemia and conclude that autologous transplant is effective and underutilized in the management of this disorder. Allogeneic transplant should be considered investigational and used only in the context of a clinical trial or when other chemotherapeutic options have been exhausted.

High-dose therapy and autologous stem-cell transplantation in Waldenstrom macroglobulinemia: the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.

PURPOSE: The role of autologous stem-cell transplantation (ASCT) in Waldenström macroglobulinemia (WM) is not defined. The aim of this study was to analyze the results of ASCT in patients with WM and to determine the prognostic factors that have a significant impact on outcome. PATIENTS AND METHODS: We analyzed 158 adult patients with WM reported to the European Group for Blood and Marrow Transplantation (EBMT) between January 1991 and December 2005. Median time from diagnosis to ASCT was 1.7 years (range, 0.3 to 20.3 years), 32% of the patients experienced treatment failure with at least three lines of therapy, and 93% had sensitive disease at the time of ASCT. Conditioning regimen was total-body irradiation-based in 45 patients. Median follow-up for surviving patients was 4.2 years (range, 0.5 to 14.8 years). RESULTS: Nonrelapse mortality was 3.8% at 1 year. Ten patients developed a secondary malignancy, with a cumulative incidence of 8.4% at 5 years. Relapse rate was 52.1% at 5 years. Progression-free survival (PFS) and overall survival were 39.7% and 68.5%, respectively, at 5 years and were significantly influenced by number of lines of therapy and chemorefractoriness at ASCT. The achievement of a negative immunofixation after ASCT had a positive impact on PFS after ASCT. When used as consolidation at first response, ASCT provided a PFS of 44% at 5 years. CONCLUSION: ASCT is a feasible procedure in young patients with advanced WM. ASCT should not be offered to patients with chemoresistant disease and to those who received more than three lines of therapy.

Atypical mucosa-associated lymphoid tissue lymphoma in the transverse colon associated with macroglobulinemia.

We herein present a quite atypical case of primary gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma in the transverse colon. Computed tomography and endoscopic ultrasonography revealed diffuse thickening of the wall, and colonoscopy showed a white-colored mucosa with reduced superficial vessels in the entire transverse colon. The lesion was diagnosed as MALT lymphoma by pathological examination of the biopsied specimen. Secondary macroglobulinemia of IgM-kappa type was also found in the present case. After chemotherapy and radiation, the lesions in the transverse colon improved and the patient has been in good condition without any evidence of recurrence for more than 1 year.

Correlation between survival and number of mobilized CD34+ cells in patients with multiple myeloma or Waldenström macroglobulinemia.

High-dose chemotherapy followed by autologous stem cell transplantation is the established treatment for symptomatic multiple myeloma (MM) or Waldenström macroglobulinemia (WM). We retrospectively analyzed the impact of mobilized CD34+ cell number on clinical outcomes in patients with MM or WM who underwent autologous stem cell transplantation in our hospital from 1997 to 2007. A total of 39 patients were identified. All patients received peripheral stem cell support after a conditioning regimen. We defined patients with collection of a large number (≥ 8 × 10(6)/kg) of CD34+ cells as super mobilizers (SM), and all others as normal mobilizers (NM). Although hematological engraftment was earlier in the SM group, overall survival did not differ significantly between groups (P = 0.392). Likewise, no significant differences were seen in progression-free survival (P = 0.201) or survival after relapse (P = 0.330). In conclusion, our retrospective study could not find any correlation between survival and number of mobilized CD34+ cells, in contrast to previously reported results.

Allogeneic hematopoietic stem cell transplantation allows long-term complete remission and curability in high-risk Waldenström's macroglobulinemia. Results of a retrospective analysis of the Société Française de Greffe de Moelle et de Thérapie Cellulaire.

BACKGROUND: Patients with poor-risk Waldenström's macroglobulinemia have suboptimal response and early post-treatment relapse with conventional therapies. Hence, new therapeutic approaches such as allogeneic stem cell transplantation should be evaluated in these patients. DESIGN AND METHODS: We examined the long-term outcome of allogeneic stem cell transplantation in Waldenström's macroglobulinemia by studying the records of 24 patients reported in the SFGM-TC database and one transplanted in the bone marrow unit in Hamburg. RESULTS: Median age at the time of transplant was 48 years (range, 24-64). The patients had previously received a median of 3 lines of therapy (range, 1-6) and 44% of them had refractory disease at time of transplant. Allogeneic stem cell transplantation after myeloablative (n=12) or reduced-intensity (n=13) conditioning yielded an overall response rate of 92% and immunofixation-negative complete remission in 50% of evaluable patients. With a median follow-up of 64 months among survivors (range, 11-149 months), 5-year overall survival and progression-free survival rates were respectively, 67% (95% CI: 46-81) and 58% (95% CI: 38-75). The 5-year estimated risk of progression was 25% (95% CI: 10-36%), with only one relapse among the 12 patients who entered complete remission, versus 5 in the 12 patients who did not. Only one of the 6 relapses occurred more than three years post-transplant. CONCLUSIONS: Allogeneic stem cell transplantation yields a high rate of complete remissions and is potentially curative in poor-risk Waldenström's macroglobulinemia.

Pulmonary lymphoma of mucosa-associated lymphoid tissue type followed as a long-standing indeterminate lesion in immunoglobulin M-type paraproteinemia.

An 82-year-old woman with monoclonal immunoglobulin (Ig) M-type paraproteinemia had a large opacity in the right lung field. The abnormal shadow on roentgenogram had persisted for more than 6 years since the initial diagnosis of paraproteinemia, which had been diagnosed as Waldenström's macroglobulinemia (WM). Computed tomography revealed the lesion as a pulmonary tumor which was finally diagnosed as a marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) after surgical removal. MALT lymphoma constitutes the majority of primary pulmonary lymphomas and is often associated with monoclonal IgM-type paraproteinemia as well as WM, a distinctive lymphoproliferative disorder. Pulmonary MALT lymphoma should frequently be suspected in case of an indeterminate pulmonary tumor with IgM-type paraproteinemia.

How we treat Waldenström's macroglobulinemia.

Waldenström's macroglobulinemia (WM) is a lymphoplasmacytic lymphoma which produces monoclonal immunoglobulin M (IgM). Over the last decade, new treatment modalites have been developed for the management of this disorder. Our objective is to provide treatment recommendations for WM. A review of published reports was facilitated by a MEDLINE computer search and by a manual search of Index Medicus. Other sources included abstracts and conference proceedings. Most patients with WM who are diagnosed by chance without symptoms should not be treated. Initiation of treatment should not be based on level of serum monoclonal protein per se. The presence of cytopenia, significant adenopathy or organomegaly, symptomatic hyperviscosity, severe neuropathy or cryoglobulinemia indicates the need for treatment. The main choices for primary treatment of symptomatic patients with WM include alkylating agents, the nucleoside analogs fludarabine or cladribine and the monoclonal antibody rituximab or combinations of these programs. There are no data from prospective randomized studies to recommend the use of one program over another. Nevertheless, the need for rapid disease control may favor the use of nucleoside analogs, whereas the presence of significant cytopenia may favor rituximab. High dose therapy with autologous stem cell transplantation may induce responses even in patients with resistance to all three class of agents. It may be prudent to avoid nucleoside analogs in patients who are candidates for high dose therapy. Despite the lack of randomized trials, a rational approach to the treatment of patients with WM is possible. Several factors, including the presence of cytopenias, need for rapid disease control, candidacy for autologous stem cell transplantation, age and co-morbid conditions, should be taken into consideration when choosing the most appropriate primary treatment.

Durable remission after splenectomy for Waldenström's macroglobulinemia with massive splenomegaly in leukemic phase.

A patient with M-proteinemia (IgM, kappa type), lymphocytosis, anemia, and massive splenomegaly, was diagnosed as having Waldenström's macroglobulinemia (WM). Since this case was refractory to chemotherapy, splenic irradiation was performed, which effectively reduced the serum IgM level, spleen size, and lymphocyte counts; however, its effect was transient. Splenectomy was then carried out. The spleen contained abundant IgM-producing lymphocytes, and after splenectomy, the serum IgM values decreased and the peripheral blood counts returned to near normal. The transient increases of serum IgM occurred during two infectious episodes postoperatively. The patient has now been in a satisfactory remission for six years after splenectomy. The removal of an IgM-producing/secreting site and release from hypersplenism may be the major mechanisms involved in achieving the durable remission after splenectomy. In individual cases of WM with massive splenomegaly, we recommend splenectomy as part of the management of this disorder.

Durable complete remission of macroglobulinemia after splenectomy: a report of two cases and review of the literature.

Two patients with macroglobulinemia (monoclonal IgM in the serum) and massive splenomegaly were incapacitated by progressive disease refractory to standard chemotherapy. In each case, palliative splenectomy was followed by a prompt, complete, and unexpected clinical remission with disappearance from the serum of the monoclonal IgM component. One patient remains free of disease 12 years after splenectomy. The other patient remained free of detectable macroglobulinemia for 13 years after splenectomy. A review of the literature revealed other cases of remission of macroglobulinemia attributable to splenectomy alone. Data in humans and animals suggest that the spleen may facilitate IgM secretion by normal and malignant B lymphocytes. Splenectomy should be considered a possible treatment option for patients with massive splenomegaly and macroglobulinemia who progress on chemotherapy.