Clinicobiological, Immunophenotypic, and Molecular Characteristics of Monoclonal CD56 −/+dim Chronic Natural Killer Cell Large Granular Lymphocytosis

• Published in: The American journal of pathology Vol. 165; no. 4; pp. 1117 - 1127
• Main Authors: Lima, Margarida, Almeida, Julia, Montero, Andrés García, Teixeira, Maria dos Anjos, Queirós, Maria Luís, Santos, Ana Helena, Balanzategui, Ana, Estevinho, Alexandra, Algueró, Maria del Cármen, Barcena, Paloma, Fonseca, Sónia, Amorim, Maria Luís, Cabeda, José Manuel, Pinho, Luciana, Gonzalez, Marcos, Miguel, Jesus San, Justiça, Benvindo, Orfão, Alberto
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01-10-2004; ASIP; American Society for Investigative Pathology
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - analysis; Blotting, Southern; CD56 Antigen - metabolism; Chronic Disease; Cytokines - biosynthesis; Female; Flow Cytometry; Gene Rearrangement, T-Lymphocyte; Hematologic Diseases - complications; Humans; Immunophenotyping; Investigative techniques, diagnostic techniques (general aspects); Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Lymphocytosis - complications; Lymphocytosis - genetics; Lymphocytosis - immunology; Male; Medical sciences; Middle Aged; Neoplasms - complications; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymerase Chain Reaction; Regular; Virus Diseases - complications; Natural killer cell; Anatomic pathology; Chronic; Immunophenotype; Characteristics; Lymphocytosis; Monoclonal immunoglobulin
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)63373-1

Indolent natural killer (NK) cell lymphoproliferative disorders include a heterogeneous group of patients in whom persistent expansions of mature, typically CD56
+, NK cells in the absence of any clonal marker are present in the peripheral blood. In the present study we report on the clinical, hematological, immunophenotypic, serological, and molecular features of a series of 26 patients with chronic large granular NK cell lymphocytosis, whose NK cells were either CD56
− or expressed very low levels of CD56 (CD56
−/+dim NK cells), in the context of an aberrant activation-related mature phenotype and proved to be monoclonal using the human androgen receptor gene polymerase chain reaction-based assay. As normal CD56
+ NK cells, CD56
−/+dim NK cells were granzyme B
+, CD3
−, TCRαβ/γδ
−, CD5
−, CD28
−, CD11a
+bright, CD45RA
+bright, CD122
+, and CD25
− and they showed variable and heterogeneous expression of both CD8 and CD57. Nevertheless, they displayed several unusual immunophenotypic features. Accordingly, besides being CD56
−/+dim, they were CD11b
−/+dim (heterogeneous), CD7
−/+dim (heterogeneous), CD2
+ (homogeneous), CD11c
+bright (homogeneous), and CD38
−/+dim (heterogeneous). Moreover, CD56
−/+dim NK cells heterogeneously expressed HLA-DR. In that concerning the expression of killer receptors, CD56
−/+dim NK cells showed bright and homogeneous CD94 expression, and dim and heterogeneous reactivity for CD161, whereas CD158a and NKB1 expression was variable. From the functional point of view, CD56
−/+dim showed a typical Th1 pattern of cytokine production (interferon-γ
+, tumor necrosis factor-α
+). From the clinical point of view, these patients usually had an indolent clinical course, progression into a massive lymphocytosis with lung infiltration leading to death being observed in only one case. Despite this, they frequently had associated cytopenias as well as neoplastic diseases and/or viral infections. In summary, we describe a unique and homogeneous group of monoclonal chronic large granular NK cell lymphocytosis with an aberrant activation-related CD56
−/+dim/CD11b
−/+dim phenotype and an indolent clinical course, whose main clinical features are related to concomitant diseases.