INCLUSIONES INTRACITOPLASMÁTICAS Y REARREGLO DE IGHV EN UN PACIENTE CON LLC

RODRIGUEZ, CECILIA M.; CARMEN STANGANELLI; CLAUDIO BUSSI; DANIELA ARROYO; HELLER VB; IRIBARREN, PABLO; SLAVUTSKY I

Mar del Plata

Congreso; XXIII Congreso Argentino de Hematología; 2017

Chronic lymphocytic leukemia (CLL) represents the mostcommon leukemia in the Western world, accounting for30?40% of all adult leukemias. The disease is characterizedby a highly variable clinical course, ranging fromindolent cases to patients with aggressive and rapidlyprogressing disease. Although staging systems are reliablepredictors of outcome, they do not fully explain theheterogeneity in treatment response and survival. In thelast decades, several prognostic biomarkers have beenidentified, allowing the subdivision of this heterogeneousdisease into clinical relevant subgroups. Among them,genomic alterations and the IGHV (immunoglobulin heavychain variable region) mutational status are of significance.Particularly, recurrent cytogenetic abnormalitiesnamely deletions of chromosomes 11q, 13q and 17p and,trisomy 12, define subgroups of patients with differentclinical behavior and response to treatment while IGHVmutational status permits to distinguish two major CLLsubtypes, mutated (M) associated with a good prognosis,and unmutated (UM), characterized by a poor clinicalevolution [1].The presence of cytoplasmic inclusions of differentstructures is an uncommon event in lymphoproliferativeand plasmacytic disorders. In CLL, the estimated incidenceof crystals formation varies between 3 and 18% ofcases [2,3]. These inclusions can present multiple morphologiesincluding vacuoles, crystals, and pseudocrystals,and they are mainly localized within the rough endoplasmicreticulum (RER) compartment. Besides, most of thereported cases indicate that these inclusions representimmunoglobulin (Ig) deposits and usually the surface Ig,when it is demonstrable, is identical to the one found inthe inclusion bodies [3?6]. However, the mechanismrelated to the inclusions formation remains to bedetermined.In this article, we report a case of a 68-year-oldwoman referred to our Hospital on January 2003. At thattime, routine analysis showed a total white blood cellcount of 25.6109/L (normal range: 4.5?10109/L), 87%lymphocytes (normal range: 20?45%), with no anemia,thrombocytopenia or organomegaly. May-Gr?unwald-Giemsa (MGG) stained peripheral blood smear examinationrevealed mature lymphocytosis with moderate-sizedlymphocytes, round nucleus, medium clumped chromatinand moderate cytoplasm with crystal inclusions, seen asrectangular unstained structures, in around 50% of totallymphocytes (Figure 1(A)). No bone marrow examinationwas performed. Serum protein electrophoresis andimmunoelectrophoresis had a normal pattern. Lactatedehydrogenase (LDH) and b2-microglobulin (b2M) valueswere: 431 UI/L and 2.4 mg/L, respectively (reference values:LDH: 180?450 UI/L; b2M: 0.8?2.20 mg/L). Flow cytometryanalysis revealed a clonal B cell population withatypical CLL phenotype. B cells were positive for CD19,CD20 (dim), CD5, CD200, CD22 (dim), CD79b (dim), IgM,lambda light chain restriction (dim), but negative forCD23, CD10 and FMC7. Prognostic markers analysisshowed 63% ZAP-70 positive cells; while CD38 andCD49d were negative. Thus, a diagnostic of CLL, Rai stage0, without treatment requirement was done.After nine years of follow up, the disease progressedto Rai stage III, with anemia, organomegaly and weightloss. As previously described, the MGG blood smearsshowed intracytoplasmic inclusions in 60% of thelymphocyte population. No significant changes on LDHand b2M values were observed. At that moment, flowcytometry analysis showed two B cell populations, one ofthem similar to the first study and the other (5% of Bcells) exhibiting higher lambda surface expression. In addition,the analysis of prognostic markers showed 74%