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Case Report Peripheral Blood Polyclonal Plasmacytosis Mimicking Int J Clin Exp Pathol 2011;4(4):416-420 www.ijcep.com /IJCEP1103011 Case Report Peripheral blood polyclonal plasmacytosis mimicking plasma cell leukemia in patients with angioimmunoblastic T-cell lymphoma: report of 3 cases and review of the literature Arshad N. Ahsanuddin1, Russell K. Brynes2, Shiyong Li1 1Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA and 2Depart- ment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA Received March 31, 2011; accepted April 12, 2011; Epub April 18, 2011; published April 30, 2011 Abstract: Angioimmunoblastic T-cell lymphoma (AITL) is a unique type of peripheral T-cell lymphoma. Patients with AITL may have occasional reactive plasma cells present in the peripheral circulation. Prominent peripheral blood poly- clonal plasmacytosis mimicking plasma cell leukemia, however, is distinctly uncommon. Here we describe 3 such cases from two large tertiary medical centers and discuss the role of ancillary studies in the differential diagnosis of peripheral blood plasmacytosis. Keywords: Angioimmunoblastic T-cell lymphoma, peripheral blood, plasmacytosis, flow cytometric immunopheno- typing Introduction with moderate amounts of clear cytoplasm and follicular dendritic cell networks. Admixed are Angioimmunoblastic T-cell lymphoma (AILT) is small reactive lymphocytes and occasional large the second most common peripheral T-cell lym- immunoblasts of B-cell lineage, as well as eosi- phoma with a constellation of clinical signs and nophils, histiocytes and plasma cells. In the symptoms including fever, weight loss, chills, bone marrow, the disease is characterized by a skin rash, pruritus, lymphadenopathy, hepa- nodular or interstitial pattern of hypocellular tosplenomegaly, anemia, thrombocytopenia and fibrovascular proliferations, infiltrated by lym- polyclonal hypergammaglobulinemia [1, 2]. It phoid cells, eosinophils and reactive plasma was first described by Frizzera et al in the early cells [4, 5]. 1970s as “angio-immunoblastic lymphad- nopahy with dysproteinemia (AILD),” and was In the peripheral blood, patients with AITL fre- originally thought to be a benign, albeit prema- quently present with anemia, thrombocytopenia lignant, atypical T-cell proliferation [3]. AILD was and absolute lymphopenia. Occasional circulat- reclassified in the Revised European and Ameri- ing plasma cells, plasmacytoid lymphocytes and can classification of Lymphoid neoplasms, and immunoblasts have been reported in about one in the 2008 World Health Organization classifi- third of patients with AITL. Exuberant reactive cation of hematolymphoid neoplasms, as a dis- plasmacytosis mimicking plasma cell leukemia, tinct type of peripheral T-cell lymphoma. however, has only rarely been described [5-7]. Here we present 3 such cases from two large In the lymph node, AITL is characterized by pro- tertiary medical centers, and discuss the differ- liferation of high-endothelial venules sur- ential diagnosis of peripheral blood plasmacyto- rounded by a polymorphous infiltrate of medium sis in light of ancillary studies that are now rou- -sized lymphoid cells of follicular T-cell origin tinely available. Peripheral blood polyclonal plamacytosis in AITL Materials and methods (20%) showing large size, occasional multiple nuclei, small nucleoli, and frequent mitoses. Case report Flow cytometric immunophenotyping Case #1: A 76 year-old woman presented with hypercalcemia, fever and diffuse lymphade- Flow cytometric immunophenotyping was per- nopathy. Serum protein electrophoresis demon- formed as previously described. Intracellular strated hypoalbuminemia and polyclonal hyper- staining for kappa and lambda immunoglobulin gammaglobulinemia. Peripheral blood findings light chains was performed after membrane included an elevated total white blood cell count permeablization. Stained cells were acquired (16,000 cells/µL) with absolute lymphopenia with FACSCanto™ II flow cytometer and the list- (1,600 cells/µL) and normochromic normocytic mode data was analyzed with Diva software (BD anemia (hematocrit 28.6%). The peripheral Biosciences). blood smear demonstrated Rouleaux formation, and numerous circulating plasma cells, plas- Results macytoid lymphocytes and scattered immuno- blasts, accounting for about 30% of all white Review of the peripheral blood smear from all 3 blood cells. Platelets were normal in number patients revealed a prominent population of and appearance. plasma cells, plasmacytoid lymphocytes and immunoblasts (more than 2 x 103 cells/µL or Case #2: A 43 year-old woman had a past medi- 20% of the nucleated cells on manual differen- cal history of AITL status six years post treat- tial). Mitosis is occasionally observed. Rouleaux ment. She was subsequently diagnosed with formation is prominent. Representative images stage IIC ovarian cancer and treated with che- are shown in Figure 1. motherapy, which was stopped early due to de- velopment of idiopathic thrombocytopenic pur- Flow cytometric immunophenotyping of the pe- pura. She presented with hemolytic anemia and ripheral blood from all 3 cases showed that ap- thrombocytopenia refractory to plasmapheresis, proximately 10-30% of the white blood cells intravenous pooled immunoglobulin, and ster- expressed CD19, CD38 (high density) and CD45 oid treatment. She underwent emergent sple- (low density). Other B cells markers including nectomy and was admitted to the Medical Inten- CD20 were negative. CD56 expression was ab- sive Care Unit. sent. Surface and intracytoplasmic light chains showed a mixed pattern of expression, confirm- Peripheral blood findings included an elevated ing the polyclonal nature of the plasma cells white count (18,100 cells/µL) with marked ane- and plasmacytoid lymphocytes. Representative mia (hematocrit 12.7%) and thrombocytopenia scatter plots of the flow cytometric immunophe- (5,000 platelets/µL). The peripheral smear notypic findings are shown in Figure 2. No aber- demonstrated moderate Rouleaux formation rant T-cell populations were detected. Serum with increased numbers of circulating nucleated protein electrophoresis in 2 patients showed red blood cells, plasmacytoid lymphocytes and polyclonal hypergammaglobulinemia. plasma cells. A manual differential count dem- onstrated 63% segmented neutrophils and 6% Molecular assay of the peripheral blood sam- lymphocytes, with 13% plasmacytoid lympho- ples showed a polyclonal pattern for the immu- cytes and plasma cells. noglobulin heavy chain gene and an oligoclonal pattern for the T-cell receptor gamma gene Case #3: A 60 year-old man presented with gen- (data not shown). Lymph node and bone mar- eralized lymphadenopathy and splenomegaly. row biopsies were subsequently performed in all Peripheral blood counts were significant for nor- 3 patients and the morphologic, immunopheno- mochromic, normocytic anemia (hematocrit typic and molecular findings were diagnostic of 27.6%), absolute lymphopenia (700 cells/µL), de novo (cases #1 and #3) and recurrent (case and thrombocytopenia (12,000 platelets/µL). #2) AITL (data not shown). Serum protein electrophoresis demonstrated polyclonal hypergammaglobulinemia. The pe- Discussion ripheral smear demonstrated moderate Rouleaux formation with a marked increase in We report here a prominent peripheral blood plasma cells and plasmacytoid lymphocytes plasmacytosis in 3 patients prior to the diagno- 417 Int J Clin Exp Pathol 2011;4(4):416-420 Peripheral blood polyclonal plamacytosis in AITL sis of de novo or recurrent AITL. All patients had generalized lymphadenopathy and/or splenomegaly. A mixture of plasma cells, plas- macytoid lymphocytes and immunoblasts meet- ing the diagnostic criterion of plasma cell leuke- mia was present in the peripheral blood, as de- termined by smear morphology and manual differential. These cells were polyclonal by flow cytometric immunophenotyping, serum protein electrophoresis, and/or molecular assay for immunoglobulin heavy chain gene rearrange- ment, consistent with a reactive process. No evidence of circulating lymphoma cells was de- tected in the blood samples. Plasma cell leukemia is defined by a neoplastic proliferation of clonal plasma cells in excess of 2 x 103 cells/µL or 20% of the white blood cells in the peripheral blood. The clonality of these cells can be demonstrated by serum protein electrophoresis and/or flow cytometric immuno- phenotyping. In rare cases of nonsecretory plasma cells, molecular studies for immu- noglobulin heavy chain gene rearrangement might be needed. Patients with plasma cell leu- kemia have a dismal prognosis with a median survival less than 1 year in most cases. Figure 1. Representative images of peripheral blood Prominent peripheral blood plasmacytosis mim- film (Wright and Giemsa stain) showing anemia with marked Rouleaux formation (A; 10x) and circulating icking plasma cell leukemia in patients with AITL plasma cells, plasmacytoid lymphocytes and im- was first reported by Pangalis et al in 1978.[8] munoblasts (B; 100x). Among the 38 AITL cases reported, about a third had circulating “immunocytes”, which were defined as plasma cells, plasmacy- toid lymphocytes, and immuno- blasts. One patient demonstrated a prominent plasmacytosis with as many as 32,000 cells/ µL. It has been reported that a variable num- ber of circulating lymphoma cells are present in the peripheral blood in approximately 30% of patients with AITL [9]. It is unclear whether some of these plasmacytoid or immuoblastic cells reported by Pangalis et
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