Lymphoplasmacytic Lymphoma: A Case Report

Introduction

Lymphoplasmacytic lymphoma (LPL) is a neoplasm of small B lymphocytes, plamacytoid lymphocytes, and plasma cells with involvement of bone marrow, sometimes lymph node, and spleen which does not fulfill the criteria for any other B-cell lymphoid neoplasm but shows plasmacytic differentiation.¹ Lymphoplasmacytic lymphoma is one of the indolent lymphomas. Waldenstrom macroglobinemia (WM) is present in a significant number of the patients with LPL and is defined as LPL with bone marrow involvement and an IgM gammopathy of any concentration.^1,2 Clinical complications of LPL/WM are related to the presence of elevated IgM in serum and tissue infiltration by LPL. It includes serum hyperviscosity, cryoglobulinemia, bleeding diathesis, amyloidosis, and pancytopenia.^3,4

Case report

A 65-year-old male patient came to the St. John’s Medical College and Hospital, Bengaluru, with a history of diarrhea and hematochezia from one week. He gave history of weakness and fatigue from 1 year. There was no history of abdominal pain, vomiting, or melena. He was diagnosed to be having ischemic heart disease a year ago and was on medication. On examination, he appeared moderately built and nourished. There was severe pallor, mild hepatomegaly, and splenomegaly but no lymphadenopathy.

A complete blood count revealed anemia with hemoglobin of 5.3 g/dl, hematocrit of 15% and mean corpuscular volume, (MCV) 85.9 fl. Total white blood cell count was 10.6 x 10³ /ul with a differential count of 17% neutrophils, 1% blasts, 3% myelocytes, 4% metamyelocytes, 3% band form, 46% lymphocytes, 17% plasmacytoid lymphocytes, 4% eosinophils, 4% monocytes, and 1% basophils. The platelet count was 7x10⁶ /ul and Erythrocyte Sedimentation Rate (ESR) >150 mm in the first hour. A liver function test revealed normal transaminases with low serum albumin of 25 g/L and elevated serum globulin of 61 g/L. Serum calcium was 3.75mmol/L. Peripheral smear (Figure 1) showed lymphocytosis, lymphoplasmacytoid cells, and marked thrombocytopenia. The serum cryoglobulin test was positive. Urine examination showed trace albumin. 

Ultrasound of the abdomen showed fatty liver and multiple hyperechoic lesions, suspicious of infiltrative disease with splenomegaly and bilateral grade I-II renal parenchymal changes. He received 2 units of packed cells and 4 units of platelet transfusion.

Bone marrow aspirate (Figure 2) showed 77% lymphoid cells, 20% plasmacytoid lymphocytes, and 3% erythroid series suggestive of LPL. Flow cytometry of the bone marrow sample showed CD20 80%, CD5 12%, CD3 12%, CD19 7%, and CD10 0%. Bone marrow trephine biopsy was inadequate. The hematological profile of the patient showed anemia and thrombocytopenia with elevated ESR. The peripheral smear and bone marrow aspirate smear showed lymphoplasmacytoid cells which are defined as cells with eccentric nuclei, condensed chromatin, and distinct nucleoli. The typical paranuclear clear region (hof) of plasma cells was usually not present..

Discussion:

The diagnosis of LPL was made based on the morphology with a limited panel of markers. Further workup with serum electrophoresis with subsequent immunofixation studies and a skeletal survey was suggested. Because of the financial constraint, the patient refused further intervention and was discharged against medical advice

Lymphoplasmacytic lymphoma is a low-grade,B-cell lymphoma. It represents 2.3% of all B-cell non-Hodgkin lymphomas.⁵ The clinical course of LPL is typically indolent with a median survival of 5 to 10 years.^6,7 Most cases involve the bone marrow but in some cases,lymph nodes and extranodal sites are also involved.¹ Majority of the patients present with weakness and generalized fatigue usually related to anemia and bleeding manifestations.

The paraprotein may lead to hyperviscosity syndrome (in 30% of the cases), mixed cryoglobulinemia (in about 20% of patients with WM), deposits in the skin or gastrointestinal tract, or coagulopathies.¹ Serum chemical analysis shows elevated ß2 microglobulin or lactate dehydrogenase (LDH) levels in a subset of patients, and ß2 microglobulin is included in prognostic models.⁸ Hepatitis C virus (HCV) is associated with type II cryoglobulinemia and with LPL in some but not all cases, perhaps related to geographic differences.^1,8 Waldenstrom macroglobinemia is present in a significant subset of the patients with LPL and is defined as LPL with bone marrow involvement and an IgM gammopathy of any concentration.^1,2 Three morphologic variants of LPL/WM in the bone marrow have been described in the literature which includes lymphoplasmacytoid, lymphoplasmacytic, and polymorphous variants.⁹ The lymphoplasmacytoid and lymphoplasmacytic variants have no prognostic significance. The prognostic value of the polymorphous variant is controversial.⁸

The immunophenotype of most of the cases of LPL/ WM are negative for CD5, CD10, CD103, and CD 23, although rare (<5%) cases may be positive for CD 5 and CD10. The World Health Organization (WHO) classification describes LPL/WM cells as usually negative for CD23.

Histological overlap between lymphoplasmacytic lymphoma and other mature B-cell malignancies with plasmacytic differentiation, such as marginal zone B-cell lymphoma (MZL), a generic diagnosis of’ low-grade B-cell malignancy with plasmacytic differentiation is often rendered.¹⁰

Marginal zone B-cell lymphoma is usually positive for cyclin D1 and negative for CD5 and CD23.¹¹ Chronic lymphocytic leukemia (CLL) may include clonal plasma cells, but not lymphoplasmacytoid cells. Slow growing lymphoblastic lymphoma/ Chronic lymphocytic leukemia (SLL/CLL) is always positive for CD5 and commonly positive for CD23. Few studies have shown that transformation to diffuse large B cell lymphoma occurs in a small proportion of cases and is associated with a poor prognosis.¹²

It is important to make the pathologic distinction from other low-grade B-cell lymphomas because lymphoplasmacytoid lymphoma carries different clinical implications.

Lymphoplasmacytic lymphoma in the symptomatic phase is treated with alkylating agents. Rituximab is given on a trial basis for LPL.⁴ Prognostic factors include advancing age, pancytopenia, weight loss, and high β2 microglobulin levels.⁶

Although the bone marrow features of lymphoplasmacytic lymphoma vary, in many cases, the disease process can be recognized morphologically in the peripheral smear and the bone marrow aspirate. Because of the high association of this lymphoma with monoclonal gammopathies and in particular with WM, its diagnosis should alert the clinician of the possibility of serum paraproteinemia, with or without clinically evident hyperviscosity symptoms.

Conflicts of Interest

None