IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Intracytoplasmic filamentous inclusions and IGHV rearrangements in a patient with chronic lymphocytic leukemia
Autor/es:
BUSSI CLAUDIO; IRIBARREN PABLO; STANGANELLI CARMEN; SASTRE DARÍO; RODRIGUEZ CECILIA M; ARROYO DANIELA S; SLAVUTSKY IRMA
Revista:
LEUKEMIA AND LYMPHOMA
Editorial:
TAYLOR & FRANCIS LTD
Referencias:
Año: 2017 vol. 3 p. 1 - 5
ISSN:
1042-8194
Resumen:
Chronic lymphocytic leukemia (CLL) represents the most common leukemia in the Western world. The presence of cytoplasmic inclusions of different structures is an uncommon event in lymphoproliferative and plasmacytic disorders. We report a case of a 68 year old woman diagnosed as CLL, Rai stage 0, after a routine follow up analysis that showed a total white blood cell count of 25.6 x109/L, 87% lymphocytes, with no anemia, thrombocytopenia or organomegaly. May-Grünwald-Giemsa stained peripheral blood smear examination revealed mature lymphocytosis with moderate?sized lymphocytes with crystal inclusions, seen as rectangular unstained structures, in around 50% of total lymphocytes. Flow cytometry analysis showed a clonal B cell population with atypical CLL phenotype. Thus, a diagnostic of CLL, Rai stage 0, without treatment requirement was done. After nine years of follow up the disease progressed to Rai stage III, with anemia, organomegaly and weight loss. The analysis of prognostic markers showed 74% CD38 positive leukemic cells. The cytogenetic study presented a normal karyotype: 46,XX, while fluorescence in situ hybridization analysis found trisomy 12 and 13q14 deletion (7.4% and 11.3% of cells, respectively). IGHV mutational status study showed two IGHV rearrangements: one unproductive comprising the segments IGHV3-13*03, IGHD4-23*01 and IGHJ4*02, carrying a stop codon and missing IMGT 2nd-Cys 104, and the other productive expressing IGHV3-48*03, IGHD3-10*01 and IGHJ1*01, both mutated (85.7% and 94.4% homology with the germ line, respectively), that would support the presence of a biallelic condition. Transmission electron microscopy studies revealed one or more electron-dense, rectangular or rhomboid crystalline structures within lymphocytes as well as a high density of ribosomes in the cytoplasm but it could not definitely identify a clear reticulum endoplasmic or another type of limiting membrane around the crystals. The analysis by confocal microscopy showed the presence of anti-lysosomal associated membrane protein 1 (LAMP1) around the crystals and also detected a high degree of co-localization between IgM or lambda light chain with LAMP-1, suggesting a lysosomal localization for these inclusions not previously reported in CLL. The prognostic significance of these inclusions is unknown, but they do not appear to have clinical impact.