Primary Isolated Lymphoplasmacytic Lymphoma (LPL) of the Stomach: A Case Report.

BACKGROUND Lymphoplasmacytic lymphoma (LPL) is a mature B cell lymphoma that mostly involves the bone marrow, spleen, and lymph nodes. Involvement of extramedullary sites is very rare and has not been reported as the primary site before. CASE REPORT A 47-year-old man presented with reflux symptoms. Gastroscopy revealed a 1.5-cm gastroesophageal junction (GEJ) polyp and oesophageal ulcer. A biopsy was performed and histopathology showed active chronic inflammation with focal intestinal metaplasia and reactive epithelial changes. A CT abdomen showed eccentric thickening of the lower oesophagus and GEJ, with periesophageal, gastro-hepatic ligament, and coeliac lymph node (LN) enlargement. A laparoscopic biopsy showed no peritoneal disease. EUS showed a large ulcerated lesion in the GEJ and proximal stomach. Both were biopsied, showing squamous-columnar mucosa with edema and a population of plasma cells, small lymphocytes, and histiocytes. These expressed CD20, PAX5, CD79a, IgM, and were lambda light chain-restricted. Lymphocytes were negative for CD3, IgG, IgA, and IgD. The MIB-1 index was low. LPL was diagnosed. PET showed an increased uptake of the gastric cardia and GEJ. LNs were not metabolically active. Bone marrow was negative. Evaluation of MYD 88 mutational status failed. Serum immunofixation showed no paraprotein. These results led to a diagnosis of primary isolated LPL of the stomach. CONCLUSIONS Primary lymphoplasmacytic lymphoma may present as an isolated gastric tumor. This can be unassociated with a paraprotein in serum and increased lymphocyte/plasma cell populations within the bone marrow. Gastric LPL is rare. Physicians and pathologists need to be aware of this rare presentation.

Distal Tibia and Foot Involvement in a Patient With Waldenstrom's Macroglobulinemia.

Bone lesions are a rare presentation in Waldenstrom's macroglobulinemia patients. Although lytic bone lesions and generalized osteoporosis have been described variably in literature on Waldenstrom's macroglobulinemia patients, distal long bone and foot involvement has not been described to our knowledge. We report a patient with Waldenstrom's macroglobulinemia with IgM monoclonal spike, plasmacytic infiltration of bone marrow, and symptoms of foot pain, and found to have distal tibia and foot involvement. The symptoms of bone lesions in our patient were significantly improved with radiation treatment. The possibility of distal involvement of long bones in a clinically relevant presentation should be kept in mind in these patients.

Splenic re-irradiation for waldenstrom's macroglobulinemia.

We report on a case of Waldenström's macroglobulinemia (WM) treated with splenic re-irradiation. To the best of our knowledge this has not been reported before. A 69-year-old Asian female patient with WM received a three-dimensional conformal radiotherapy, with 24 Gy in 12 treatment fractions in the first stage. She tolerated the treatment well, with a 37% reduction of the monoclonal immunoglobulin, an impalpable spleen, and improved hematological laboratory tests for 4 months. She was then treated with splenic re-irradiation up to 24 Gy for tumor progression. She showed no evidence of progression one year after re-irradiation, with a 55% reduction of the monoclonal immunoglobulin. Our experience demonstrates that splenic irradiation is an effective treatment to control the progression of WM.

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.

Waldenstrom's macroglobulinemia presenting with spinal cord compression: a case report.

Waldenstrom's macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma characterized by a wide range of clinical presentations related to direct tumor infiltration and the production of IgM. Most commonly it presents with cytopenia, hepatosplenomegaly, lymphadenopathy, constitutional symptoms, and hyperviscosity syndrome. We report a case of WM in an 81-year-old man who initially presented with severe back pain. The patient had no peripheral lymphadenopathy or hepatosplenomegaly and his peripheral blood smear was normal. MRI of the spine revealed an epidural mass causing spinal cord compression at T9. Surgical decompression was performed and pathological analysis of the mass revealed a lymphoproliferative B-cell process. The diagnosis of WM was established after cytomorphologic and immunohistochemical analysis of the patient's bone marrow revealed the presence of a lymphoid/lymphoplasmacytoid-like bone marrow infiltrate along with an elevated serum IgM level. The patient responded both clinically and serologically to local radiotherapy. This case is unusual because the patient lacked all common clinical features of WM. This is the first reported case of epidural spinal cord compression as the initial manifestation of WM, adding to the spectrum of clinical presentations seen in this disease.

Use of iodine 131I-tositumomab radioimmunotherapy in a patient with Waldenstrom's macroglobulinemia.

Waldenstrom's macroglobulinemia is an indolent B-cell malignancy that is characterized by high levels of IgM paraprotein production and is incurable with standard chemotherapy. Iodine 131I-Tositumomab (iodine-131-labeled murine anti-CD20 monoclonal antibody; Bexxar) is a novel radioimmunotherapeutic agent that has a high response rate in relapsed or chemotherapy refractory, CD20-positive, low grade or transformed B-cell non-Hodgkin's lymphomas. There are no data on the use of radioimmunotherapy in Waldenstrom's macroglobulinemia. We report a patient with Waldenstrom's macroglobulinemia with transformation to a large B-cell lymphoma, who was treated successfully with iodine 131I-tositumomab. The patient had a complete response to the treatment, including disappearance of any detectable IgM paraprotein. This case report demonstrates the potential for radioimmunotherapy in CD20 positive B-cell malignancies.

Clinostatic syndrome in Waldenström macroglobulinemia.

We report a case of Waldenström macroglobulinemia revealed by clinostatic syndrome in an 81-year-old woman. A lytic lesion was found in the ilium and acetabulum. There was no evidence of transformation to high-grade lymphoma. Radiation therapy ensured complete resolution of the clinostatic syndrome within 1 month of treatment completion.

Radioimmunotherapy for Waldenstrom's macroglobulinemia.

Radioimmunotherapy targeting CD20 is a promising novel treatment for lymphoma. Prior trials have established the safe dose of Zevalin ((90)Y-ibritumomab tiuxetan; IDEC Pharmaceuticals) for patients with no more than 25% bone marrow (BM) involvement. Zevalin is expected to be an effective treatment for WM; however, the safe dose has not been defined. A phase I clinical trial has been designed to define the maximum-tolerated dose (MTD) of Zevalin in patients with WM and BM involvement up to 50%. Eligible patients need to have adequate hematologic indices (absolute neutrophil count [ANC] > 1,500/microL, platelets > 100,000/microL). The starting dose of (90)Y-Zevalin is 0.08 mCi/kg. Dose escalation by 0.04 mCi/kg in cohorts of three to six patients will be performed. Patients will be re-treated at 12 weeks if there is no complete response, no progression, and no dose-limiting toxicity. If the degree of BM involvement remains in the 20% to 50% range, re-treatment will involve a similar dose of Zevalin; if it is <20%, patients will receive Zevalin to the maximum allowed cumulative dose of 0.4 mCi/kg (or 0.3 mCi/kg for mild thrombocytopenia). Despite the phase I design, the re-treatment provision is expected to result in significant clinical benefit.

Radiation therapy and combination of cladribine, cyclophosphamide, and prednisone as treatment of Bing-Neel syndrome: Case report and review of the literature.

Waldenström's macroglobulinemia is a low-grade lymphoma that produces monoclonal IgM. Central nervous system symptoms are frequent in Waldenström's macroglobulinemia, mostly associated with blood hyperviscosity. Nevertheless, central nervous system infiltration by malignant cells (Bing-Neel syndrome) has rarely been reported. We describe the case of a 72-year-old man with Waldenstrom's macroglobulinemia and central nervous system infiltration by malignant cells with tumor formation. All similar cases reported in the literature are reviewed and the different therapeutic approaches discussed.

Intracerebral infiltration by monoclonal plasmacytoid cells in Waldenstrom's macroglobulinemia--case report.

A 68-year-old female presented with Waldenstrom's macroglobulinemia with infiltration into the cerebral parenchyma manifesting as increased confusion, memory loss, and disorientation. She had a past history of Waldenstrom's macroglobulinemia treated 3 years before. Magnetic resonance imaging showed a high intensity area on T2-weighted images in the left frontal lobe extending to the corpus callosum which was well enhanced by gadolinium-diethylenetriaminepenta-acetic acid. Direct infiltration of neoplastic cells was confirmed by biopsy. Immunohistochemical examination showed that mature plasmacytoid cells in the cerebral parenchyma were immunoglobulin M and lambda light chain antigen positive, but immature lymphocytes in Virchow-Robin space were negative. Monoclonal proliferation was confirmed by southern blot analysis. She became symptom free and the size of the lesion was dramatically reduced after 40 Gy irradiation. She showed no evidence of recurrence 3 years after irradiation. As no effective chemotherapy regimen for Bing-Neel syndrome has been established, irradiation is worth considering when neuroimaging suggests intracranial infiltration of neoplastic cells.

Cutaneous Waldenström's macroglobulinemia. A report of a case successfully treated with radiotherapy.

Waldenström's macroglobulinemia is a lymphoproliferative disorder that only rarely exhibits specific cutaneous findings. The authors present a case of Waldenström's macroglobulinemia in which the patient developed cutaneous lesions while his systemic disease seemed to be under control with chlorambucil therapy. A review of the scant literature regarding the response of cutaneous Waldenström's to treatment suggests that the skin lesions do not respond well to systemic therapy. This case was successfully treated with radiotherapy.

Waldenstrom macroglobulinaemia treated with sequential hemibody irradiation.

A 40-year-old man presented with symptoms of anaemia and blurred vision. Waldenstrom macroglobulinaemia was diagnosed on the basis of plasmacytoid lymphocytes in the peripheral blood, extensive bone marrow involvement, and an IgM kappa monoclone in the plasma of 48 g/liter. Symptoms were immediately reversed by isovolaemic continuous-flow plasmapheresis coupled with red cell transfusion. Specific therapy was undertaken with sequential hemibody irradiation. At two years of follow-up the patient enjoys excellent health, has improved haematopoietic reserve in the bone marrow, and the only therapy required is intermittent plasmapheresis to control symptoms relating to rising viscosity. Thus, systemic irradiation, which is well tolerated and objectively reduces marrow tumour bulk, offers an alternative to chemotherapy in the palliative management of active macroglobulinaemia and may diminish but not prevent the need for intermittent plasmapheresis.

Hemibody irradiation in lymphomas and related malignancies.

Between 1979 and 1984, 34 patients with advanced lymphoma or leukemia resistant to other treatments have been treated with single or sequential hemibody irradiation (HBI). Good symptomatic relief was obtained in the majority of patients, with minimal acute toxicity. Disease regression occurred in the majority of patients and was maintained in those achieving a complete remission. Stage III disease and 'good risk' histology predicted a good outcome. Marrow toxicity was marked only in those patients with marrow involvement. HBI is recommended as a worthwhile palliative treatment particularly in nodal nodular disease.

[Polychimiotherapy and Waldenström's macroglobulinemia (author's transl)]. / Polychimiothérapie et macroglobulinémie de Wadenström.

A 63-year-old man, with a Waldenström's disease discovered by cryoglobulinemia (ischemic lesions of fingers) was quickly aggravating (hyperviscosity syndrome) under treatment by chlorambucil in a dosage of 8 mg daily. We obtained a dramatic remission with combination of cyclophosphamide, vincristine, adriamycin and prednisone surrounding a total body irradiation. A new trial of polychimiotherapy (with lower dosage) for severe Waldenström's disease is actually on study.