Large granular lymphocyte proliferation with the natural killer-cell phenotype.
Lymphoproliferated disorders involving large granular lymphocytes (LGL) can be divided into a common T-cell subset (CD3+, CD8+) and a rarer natural killer (NK)-cell subset (CD2+, CD3-). The immunophenotype, clinical pathologic features, and cytogenetic and molecular genetic analyses are reported for seven patients with NK-cell-LGL proliferation. The typical immunophenotype was CD2+, CD3-, CD4-, CD11b+, and CD16+ or CD56+. A low but variable percentage of cells were CD8+ or CD57+. Unusual phenotypes with CD2- (1 of 7), CD11b- (1 of 7), or CD16-/CD56- (1 of 7) cells were seen. Strong NK-cell activity was observed in all cases, indicating that none of the NK-cell markers (CD11b, CD16, CD56, CD57) is essential for NK-cell activity. One patient died shortly after diagnosis from coexistent refractory multiple myeloma and another patient died within 1 month from the LGL proliferation. The other patients had been followed for 12 to 70 months, with a median follow-up period of 38 months. There was no progression of their LGL proliferation. Lymphocyte counts varied from 3.3 x 10(3)/microL to 58.4 x 10(3)/microL at the time of diagnosis. Unexplained anemia and neutropenia were observed in one patient. Cytogenetic abnormalities were detected in two of four patients studied with t(6;12) in one and der(5), der(6), and der(11) in the other. The approximately T gamma and T beta genes were in the germline configuration and Epstein-Barr virus DNA was undetectable in five of five patients studied. Natural killer-cell LGL proliferations were morphologically indistinguishable from T-cell LGL proliferations. However, the two were immunophenotypically and genotypically distinct and NK-cell activity was consistently observed in the former. Most of the NK-cell proliferations also were chronic indolent disorders and the incidence of associated cytopenias seemed to be lower than T-cell LGL proliferations.
Chan
W C
WC
Department of Pathology/Microbiology, University of Nebraska Medical Center, Omaha 68198-3135.
Gu
L B
LB
Masih
A
A
Nicholson
J
J
Vogler
W R
WR
Yu
G
G
Nasr
S
S
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D002455:Cell Division; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006098:Granulocytes / Q000166:cytology* / Q000276:immunology / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology*; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D015703:Antigens, CD