Elderly female presents with asymptomatic leukocytosis
An 84-year-old woman presented to her hematologist’s office with an asymptomatic leukocytosis and associated lymphocytosis seen on routine blood work. She noted complaints of fatigue and had an unintentional weight loss of 15 lb within 1 year. At the time of initial consultation, her blood work showed a total white blood cell count of 25,000 cells/mcL with 75% lymphocytes, which fluctuated to as high as 33,000 cells/mcL with 76% lymphocytes. She also had a normocytic anemia and normal renal function, but workup revealed an elevated serum globulin level, elevated lactate dehydrogenase, and a beta-2 microglobulin of 7,303. Peripheral smear exam was consistent only with small lymphocytes
Serum protein electrophoresis showed a polyclonal gammopathy. Flow cytometry analysis of peripheral blood showed a population of cells that expressed a monoclonal lambda pattern, which were CD5+, CD23–, CD20+ and cyclin D1+. Lambda was brightly expressed. To note, CD10, CD11C and CD56 were all negative. Peripheral blood fluorescence in situ hybridization (FISH) analysis was positive for an 11:14 (CCND1/IGH) translocation in 81.5% of the cell population, which is typical of mantle cell lymphoma. The probes were negative for bcl-2 and bcl-6.
Photo courtesy of Munir Ghesani, MD
PET/CT performed in June 2010 showed evidence of lymphadenopathy in the neck, chest, abdomen and pelvis, with associated increased SUV activity; diffuse hypermetabolic enlarged spleen; heterogeneous uptake throughout the axial and appendicular skeleton; bilateral palatine tonsils associated with hypermetabolic activity; and a stable left adrenal nodule. She is currently being evaluated for further treatment considerations.
Mantle cell lymphoma (MCL) is associated with or discussed with the indolent forms of NHL, although its behavior is more often that of an aggressive lymphoma. Mantle cell lymphoma comprises about 6% of all adult NHLs in the United States. The ratio of males to females affected is about 4:1.
About 70% of patients present with stage IV disease, with 40% of patients having symptoms consisting of fevers, night sweats and weight loss. Other symptoms include generalized lymphadenopathy, abdominal distention from hepatosplenomegaly, fatigue from anemia or bulky disease. Less common symptoms are caused by extranodal involvement of the gastrointestinal tract, lungs and central nervous system.
Tumor cells are monoclonal B cells that express surface immunoglobulin, IgM or IgD. Cells are characteristically CD5+ and pan B-cell antigen positive (eg, CD19, CD20, CD22) but lack expression of CD10 and CD23. Cyclin D1 is overexpressed. Immunophenotyping helps differentiate MCL from other small B-cell lymphomas.
Genetic studies reveal immunoglobulin heavy and light chain genes rearrangement. Overexpression of cyclin D1 in MCLs is strongly associated with the t(11;14)(q13;q32), a translocation between the cyclin D1 (BCL-1,CCND1, PRAD1) locus and the immunoglobulin heavy chain (IgH) locus. Only 50% to 65% of MCLs will show the t(11;14) by cytogenetics, but by FISH, a much higher fraction of cases with cyclin D1 overexpression contain the BCL-1/IgH fusion gene.
Not all patients with MCL require immediate treatment. The decision to treat is based on numerous variables, including lab studies, bone marrow analysis, disease burden and/or imaging studies. Combination chemotherapy remains the main treatment modality. The most frequently used conventional chemotherapy regimens for MCL are standard or modified CHOP, CVP (cyclophosphamide, vincristine, prednisone) and FC (fludarabine and cyclophosphamide). The anti-CD20 monoclonal antibody rituximab, used as a single agent, has activity in MCL, yielding a response rate of 35%, a complete response rate of 10% to 15%, and a median duration of response of approximately 1 year in rituximab-naive patients.
In one study, PET and CT findings were investigated in 37 patients with MCL (239 scans) and categorized following standardized response criteria for CT evaluation (IWC-criteria), PET evaluation (EORTC-criteria) and combined PET/CT evaluation (IWC + PET-criteria). FDG-PET showed a high sensitivity for the detection of deposits of MCL and a higher FDG-uptake was shown in patients with the more aggressive blastoid-variant MCL vs. common MCL. However, routine use of PET for end-of-treatment response assessment in MCL cannot be recommended because CT- and PET-based designation systems had equivalent prognostic value. PET-based end-of-treatment response assessment only provided additional information over CT-based response assessment in a subpopulation of patients with highly FDG-avid MCL. PET allowed early detection of preclinical relapse during post-therapy surveillance, but the therapeutic consequences of such information are currently unclear.
Munir Ghesani, MD, is an attending radiologist at St. Luke’s-Roosevelt Hospital Center, and Beth Israel Medical Center and a HemOnc Today section editor. He is an associate clinical professor of radiology at Columbia University College of Physicians and Surgeons.
Rami Daya, MD, is a practicing oncologist in Brooklyn, New York.
Amit A. Patel, MD, is a fellow in hematology/oncology at St. Luke’s-Roosevelt Hospital.
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