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IMAJ • VOL 11 • november 2009 Case Communications

Transformation of MALT to Pure Histology: Possible Association with Anti-CD20 Treatment Noa Klein MD1*, Avishay Elis MD1,4*, Judith Radnay PhD2, Ruth Zemer MSc3, Ami Klein PhD3,4 and Michael Lishner MD1,4

1Department of Internal Medicine, 2Cytohematology Laboratory and 3Molecular Biology Laboratory, Meir Medical Center, Kfar Saba, Israel 4Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel

and who presented with a new pleural and shortness of breath. Physical exami- Key words: MALT lymphoma, plasma cell, effusion rich in monoclonal pathologi- nation revealed decreased breathing rituximab, transformation cal plasma cells. Data suggesting that the sounds over the right lung. All blood IMAJ 2009; 11: 703–704 two are clonally related are tests remained within the normal range, discussed, as is the possible association except for an increase of the serum with rituximab treatment. monoclonal IgMk levels to 631 mg/dl ucosa-associated lymphoid tissue and lactate dehydrogenase to 511 u/L. M lymphoma is a distinct subtype of Repeat PET-CT showed no change in non-Hodgkin's lymphoma that belongs Patient Description the primary tumor but demonstrated to the group of marginal zone B cell A 59 year old man was diagnosed with a new right pleural effusion with an [1]. MALT lymphoma arises MALT lymphoma of the lung. The patient elevated uptake of fluorodeoxyglucose. from lymphoid tissues that are exposed to complained of abdominal pain and night The fluid was aspirated and shown to persistent inflammatory stimulation, most sweats, but physical examination was be an exudate containing monoclonal commonly in the gastric mucosa, and has unremarkable. Laboratory tests, including pathological plasma cells. Recurrent unique pathogenetic, histological and blood count, serum electrolytes, liver and aspiration revealed 10% clinical features [1,2]. MALT lymphoma of kidney function tests, except for serum mature lymphocyte cells without any the lung comprises 14% of the non-gastric monoclonal immunoglobulin Mk (311 pathological plasma cells. Lytic lesions primary sites and accounts for 70–80% of mg/dl), were all within the normal range. were not found on skeletal survey. the primary lymphomas of the lung [1]. Chest X-ray and chest computed tomog- Gene rearrangement was obtained A prominent plasma cell component raphy revealed extensive consolidation by polymerase chain reaction, followed among MALT lymphoma cells is a well- with air bronchograms, involving most by the differential fluorescence detec- known phenomenon called plasmacytic of the middle and lower lobes of the right tion method of the heavy chains of the differentiation. It presents in up to 30% lung and the lingula. Total body posi- mononuclear cells. The results revealed of patients with MALT lymphoma and its tron emission tomography-CT showed that the heavy chains of the mononu- main differential diagnosis is extramedul- focally elevated uptake in the right lower clear cells isolated from the lung biopsy lary plasmacytoma [1,3]. However, trans- and middle lobes of the lung and in the tissue at presentation and those isolated formation of MALT lymphoma to mul- lingula area. Open lung biopsy revealed from the pleural fluid, bone marrow and tiple myeloma or pure plasma cell histol- malignant low grade B cell lymphoma of peripheral blood during the reevaluation ogy is rare [2]. MALT type, without plasmacytic differen- had the same band in the JH area. An Since MALT lymphoma cells express tiation. The tumor cells stained positively additional band was found in the cells CD20, the anti-CD20 antibody, ritux- for CD20 and CD 79-9. Bone marrow isolated from the pleural fluid [Figure]. imab, was recently introduced into aspiration and biopsy were normal. The treatment with R-COP was dis- chemotherapeutic regimens [2]. In this Treatment consisted of the chemo- continued. Eight months later the patient report we describe a patient with MALT therapeutic regimen R-COP (cyclophos- is asymptomatic while repeat chest X- lymphoma of the lung whose cytotoxic phamide, prednisone, vincristine and rays revealed significant decrease in the treatment regimen included rituximab rituximab). Just before the fourth course, amount of the pleural effusion. the patient began to complain of cough *The first two authors contributed equally to PET-CT = positron emission tomography- the study MALT = mucosa-associated lymphoid tissue computed tomography

703 Case Communications IMAJ • VOL 11 • november 2009

A bp C bp Gene rearrangement results obtained by PCR followed by the differential fluorescence detection method. The following patient's specimens were investigated: [A] biopsy of lung (at presentation), [B] pleural effus- ion, [C] bone marrow, and [D] periphe- Fluorescence Fluorescence ral blood (during reevaluation). The Fluorophor-conjugated PCR primers were of the conserved framework region (FR2 and FR3) of the immunoglobulin VH region and B bp D bp of the joining (J) region. The 240 bp peak, found in all four preparations, characterizes the same type of monoclonality in all. (The 220 bp peak, of the pleural effusion preparation, is not relevant since it is out of the frame of gene rearrangement peaks Fluorescence Fluorescence 230-280 bp.)

reported a patient with retrobulbar evolved into a plasma cell , and Comment MALT lymphoma who developed mul- not that two separate B cell malignan- We describe a patient with MALT lym- tiple myeloma. The authors found that cies had developed in the same patient. phoma of the lung who developed a new despite the fact that both malignancies In conclusion, we describe a rare case pleural effusion containing monoclonal are derived from mature B cells, they of MALT lymphoma that was trans- pathological plasma cells during treat- had different immunophenotypic and formed into pure plasma cell histology. ment with R-COP. The most important molecular cytogenetic characteristics. Our data suggest that the two neoplasms differential diagnosis of MALT lymphoma They therefore concluded that the devel- are clonally related. We hypothesize that with extensive plasmacytic differentiation opment of the two malignancies in the treatment with rituximab may have is extramedullary plasmacytoma. The same patient was coincidental. induced these histological changes. latter is characterized by infil- The pathophysiological involvement tration of monoclonal plasma cells but, of rituximab in the transformation of Correspondence: in contrast to , there MALT lymphoma into pure plasma Dr. M. Lishner is no bone marrow , bone cell histology is compelling. Woehrer Head, Dept. of Medicine A, Meir Medical Center, destruction or evidence of , hyper- and team [2] described a patient with Kfar Saba 44281, Israel Phone: (972-9) 747-2516 calcemia or impaired renal function [3]. MALT lymphoma of the lung and the Fax: (972-9) 746-0781 MALT lymphoma with extensive stomach that transformed into a pure email: [email protected] plasmacytic differentiation has similar plasma cell tumor after treatment with clinical and histological features to rituximab. The authors assumed that the References extramedullary plasmacytoma. Hussong anti-CD20 antibody induced the histo- 1. Cohen SM, Petryk M, Varma M, et al. Non- et al. [4] reviewed the data of five pa- logical changes on the primary MALT Hodgkin's lymphoma of mucosa-associated tients with extramedullary plasmacy- lymphoma by eradication of the CD20- lymphoid tissue. Oncologist 2006; 11: 1100-17. 2. Woehrer S, Streubel B, Chott A, et al. Trans- toma and two patients with MALT lym- positive cells and "overgrowth" of the formation of MALT lymphoma to pure plasma phoma. They concluded that extramed- CD20-negative plasmacellular compo- cell histology following treatment with the anti- ullary plasmacytoma and MALT nent of the tumor. This hypothesis may CD20 antibody rituximab. Leuk Lymphoma 2005; 46: 1645-9. lymphoma with extensive plasmacytic be applied to our case. Furthermore, the 3. Tanimoto A, Hamada T, Yamamoto T, et al. differentiation may represent the same results obtained from the PCR exami- MALT lymphoma with extreme plasma cell disease. Tanimoto and collaborators nation of our patient indicate that the differentiation of the rectum. Am J Gastroenterol 2002; 97: 1860-2. [3] described a patient with MALT MALT lymphoma cells and the plasma 4. Hussong JW, Perkins SL, Schnitzer B, et al. lymphoma of the rectum with extreme cells are clonally related. It may suggest Extramedullary plasmacytoma. A form of marg- plasma cell differentiation. Nevertheless, that following the administration of inal zone cell lymphoma? Am J Clin Pathol 1999; transformation of MALT lymphoma rituximab the initial MALT lymphoma 111: 111-16. 5. Wohrer S, Raderer M, Streubel B, et al. Concomitant into multiple myeloma or pure plasma occurrence of MALT lymphoma and multiple cell histology is rare. Wohrer et al. [5] PCR = polymerase chain reaction myeloma. Ann Hematol 2004; 83: 600-3.

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