Skip to main content
Erschienen in: Annals of Hematology 1/2013

01.01.2013 | Original Article

Flow cytometric immunophenotyping is of great value to diagnosis of natural killer cell neoplasms involving bone marrow and peripheral blood

verfasst von: Neng-gang Jiang, Yong-mei Jin, Qian Niu, Ting-ting Zeng, Jun Su, Huan-ling Zhu

Erschienen in: Annals of Hematology | Ausgabe 1/2013

Einloggen, um Zugang zu erhalten

Abstract

Natural killer (NK) cell neoplasms are unusual disorders. In this study we compared results of flow cytometric immunophenotype (FCI) with cytomorphology, histopathology and clinical findings in a series of patients with NK cell neoplasms with peripheral blood and/or bone marrow involvement, and the FCI of neoplastic and normal NK cells were compared. Retrospective data and specimens (bone marrow aspiration or peripheral blood) from 71 cases of NK cell neoplasms were obtained. All patients have been demonstrated laboratory and clinical features consistent with NK cell neoplasms, and the subtypes were determined by integrated clinical estimation. Routine 4-color flow cytometry (FCM) using a NK/T cell related antibody panels was performed. NK cell neoplasms were divided into two major subtypes by FCI, namely malignant NK cell lymphoma, including extranodal nasal type NK cell lymphoma (ENKL, 11 cases) and aggressive NK cell lymphoma/leukemia (ANKL, 43 cases), and relative indolent chronic lymphoproliferative disorder of NK cell (CLPD-NK, 17 cases). The former exhibited stronger CD56-expressing, larger forward scatter (FSC) and more usually CD7- and CD16-missing. FCI of CLPD-NK was similar to normal NK cells, but CD56-expressing was abnormal, which was negative in five cases and partially or dimly expressed in eight cases. Cytomorphologic abnormal cells were found on bone marrow slides of 4 cases of ENKL and 30 cases of ANKL. Eight cases of ENKL were positive in bone marrow biopsies, and other three cases were negative. In 32 cases of ANKL which bone marrow biopsies were applied, 21 cases were positive in the first biopsies. Lymphocytosis was found only in six cases of CLPD-NK by cytomorphology, and biopsy pathology was not much useful for diagnosing CLPD-NK. These results suggest that FCM analysis of bone marrow and peripheral blood was superior to cytomorphology, bone marrow biopsy, and immunohistochemistry in sensitivity and early diagnosis for ANKL, stage III/IV ENKL and CLPD-NK. FCI could not only define abnormal NK cells but also determine the malignant classification. It is beneficial for clinical management and further study of NK cell neoplasms.
Literatur
2.
Zurück zum Zitat Chan JK, Sin VC, Wong KF et al (1997) Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm. Blood 89(12):4501–4514PubMed Chan JK, Sin VC, Wong KF et al (1997) Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm. Blood 89(12):4501–4514PubMed
3.
Zurück zum Zitat Au WY, Ma SY, Chim CS et al (2005) Clinicopathologic features and treatment outcome of mature T-cell and naturalkiller-cell lymphomas diagnosed according to the World Health Organization classification scheme: a single center experience of 10 years. Ann Oncol 16(2):206–214PubMedCrossRef Au WY, Ma SY, Chim CS et al (2005) Clinicopathologic features and treatment outcome of mature T-cell and naturalkiller-cell lymphomas diagnosed according to the World Health Organization classification scheme: a single center experience of 10 years. Ann Oncol 16(2):206–214PubMedCrossRef
4.
Zurück zum Zitat Kwong YL (2005) Natural killer-cell malignancies: diagnosis and treatment. Leukemia 19(12):2186–2194PubMedCrossRef Kwong YL (2005) Natural killer-cell malignancies: diagnosis and treatment. Leukemia 19(12):2186–2194PubMedCrossRef
5.
Zurück zum Zitat Ryder J, Wang X, Bao L et al (2007) Aggressive natural killer cell leukemia: report of a Chinese series and review of the literature. Int J Hematol 85(1):18–25PubMedCrossRef Ryder J, Wang X, Bao L et al (2007) Aggressive natural killer cell leukemia: report of a Chinese series and review of the literature. Int J Hematol 85(1):18–25PubMedCrossRef
6.
Zurück zum Zitat Kwong YL, Chan AC, Liang RH (1997) Natural killer cell lymphoma/leukemia: pathology and treatment. Hematol Oncol 15(2):71–79PubMedCrossRef Kwong YL, Chan AC, Liang RH (1997) Natural killer cell lymphoma/leukemia: pathology and treatment. Hematol Oncol 15(2):71–79PubMedCrossRef
7.
8.
Zurück zum Zitat Steven HS, Elias C, Nance LH, et al. (2008) WHO classification of tumors of haematopoietic and lymphoid tissues. International agency for research on cancer. Lyon; pp: 274–288 Steven HS, Elias C, Nance LH, et al. (2008) WHO classification of tumors of haematopoietic and lymphoid tissues. International agency for research on cancer. Lyon; pp: 274–288
9.
Zurück zum Zitat Suzuki R, Suzumiya J, Nakamura S et al (2004) Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells. Leukemia 18:763–770PubMedCrossRef Suzuki R, Suzumiya J, Nakamura S et al (2004) Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells. Leukemia 18:763–770PubMedCrossRef
10.
Zurück zum Zitat Lima M, Almeida J, Montero AG et al (2004) Clinicobiological, immunophenotypic, and molecular characteristics of monoclonal CD56−/+dim chronic natural killer cell large granular lymphocytosis. Am J Pathol 165(4):1117–1127PubMedCrossRef Lima M, Almeida J, Montero AG et al (2004) Clinicobiological, immunophenotypic, and molecular characteristics of monoclonal CD56−/+dim chronic natural killer cell large granular lymphocytosis. Am J Pathol 165(4):1117–1127PubMedCrossRef
11.
Zurück zum Zitat Kämmerer U, Kapp M, Gassel AM et al (2001) A new rapid immunohistochemical staining technique using the EnVision antibody complex. J Histochem Cytochem 49(5):623–630PubMedCrossRef Kämmerer U, Kapp M, Gassel AM et al (2001) A new rapid immunohistochemical staining technique using the EnVision antibody complex. J Histochem Cytochem 49(5):623–630PubMedCrossRef
12.
Zurück zum Zitat Morice WG (2007) The immunophenotypic attributes of NK cells and NK-cell lineage lymphoproliferative disorders. Am J Clin Pathol 127(6):881–886PubMedCrossRef Morice WG (2007) The immunophenotypic attributes of NK cells and NK-cell lineage lymphoproliferative disorders. Am J Clin Pathol 127(6):881–886PubMedCrossRef
13.
Zurück zum Zitat Carson WE, Fehniger TA, Caligiuri MA (1997) CD56bright natural killer cell subsets: characterization of distinct functional responses to interleukin-2 and the c-kit ligand. Eur J Immunol 27(2):354–360PubMedCrossRef Carson WE, Fehniger TA, Caligiuri MA (1997) CD56bright natural killer cell subsets: characterization of distinct functional responses to interleukin-2 and the c-kit ligand. Eur J Immunol 27(2):354–360PubMedCrossRef
14.
Zurück zum Zitat Chan A, Hong DL, Atzberger A et al (2007) CD56bright human NK cells differentiate into CD56dim cells: role of contact with peripheral fibroblasts. J Immunol 179(1):89–94PubMed Chan A, Hong DL, Atzberger A et al (2007) CD56bright human NK cells differentiate into CD56dim cells: role of contact with peripheral fibroblasts. J Immunol 179(1):89–94PubMed
15.
Zurück zum Zitat Björkström NK, Riese P, Heuts F et al (2010) Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK-cell differentiation uncoupled from NK-cell education. Blood 116(19):3853–3864PubMedCrossRef Björkström NK, Riese P, Heuts F et al (2010) Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK-cell differentiation uncoupled from NK-cell education. Blood 116(19):3853–3864PubMedCrossRef
16.
Zurück zum Zitat Trotta R, Parihar R, Yu J et al (2005) Differential expression of SHIP1 in CD56bright and CD56dim NK cells provides a molecular basis for distinct functional responses to monokine costimulation. Blood 105(8):3011–3018PubMedCrossRef Trotta R, Parihar R, Yu J et al (2005) Differential expression of SHIP1 in CD56bright and CD56dim NK cells provides a molecular basis for distinct functional responses to monokine costimulation. Blood 105(8):3011–3018PubMedCrossRef
17.
Zurück zum Zitat Li YX, Fang H, Liu QF et al (2008) Clinical features and treatment outcome of nasal-type NK/T-cell lymphoma of Waldeyer ring. Blood 112(8):3057–3064PubMedCrossRef Li YX, Fang H, Liu QF et al (2008) Clinical features and treatment outcome of nasal-type NK/T-cell lymphoma of Waldeyer ring. Blood 112(8):3057–3064PubMedCrossRef
18.
Zurück zum Zitat Kwong YL (2009) High-dose chemotherapy and hematopoietic SCT in the management of natural killer-cell malignancies. Bone Marrow Transplant 44(11):709–714PubMedCrossRef Kwong YL (2009) High-dose chemotherapy and hematopoietic SCT in the management of natural killer-cell malignancies. Bone Marrow Transplant 44(11):709–714PubMedCrossRef
19.
Zurück zum Zitat Lanier LL, Chang C, Azuma M et al (1991) Molecular and functional analysis of human natural killer cell-associated neural cell adhesion molecule (N-CAM/CD56). J Immunol 146(12):4421–4426PubMed Lanier LL, Chang C, Azuma M et al (1991) Molecular and functional analysis of human natural killer cell-associated neural cell adhesion molecule (N-CAM/CD56). J Immunol 146(12):4421–4426PubMed
20.
Zurück zum Zitat Raspadori D, Damiani D, Lenoci M et al (2001) CD56 antigenic expression in acute myeloid leukemia identifies patients with poor clinical prognosis. Leukemia 15(8):1161–1164PubMedCrossRef Raspadori D, Damiani D, Lenoci M et al (2001) CD56 antigenic expression in acute myeloid leukemia identifies patients with poor clinical prognosis. Leukemia 15(8):1161–1164PubMedCrossRef
21.
Zurück zum Zitat Aloysius MM, Zaitoun AM, Awad S et al (2010) Mucins and CD56 as markers of tumour invasion and prognosis in periampullary cancer. Br J Surg 97(8):1269–1278PubMedCrossRef Aloysius MM, Zaitoun AM, Awad S et al (2010) Mucins and CD56 as markers of tumour invasion and prognosis in periampullary cancer. Br J Surg 97(8):1269–1278PubMedCrossRef
22.
Zurück zum Zitat Liang R (2000) Diagnosis and management of primary nasal lymphoma of T-cell or NK-cell origin. Clin Lymphoma 1(1):33–37PubMedCrossRef Liang R (2000) Diagnosis and management of primary nasal lymphoma of T-cell or NK-cell origin. Clin Lymphoma 1(1):33–37PubMedCrossRef
23.
Zurück zum Zitat Todd JA, Lubomir S (2007) Diseases of large granular lymphocytes. Cancer Control 14(2):141–150 Todd JA, Lubomir S (2007) Diseases of large granular lymphocytes. Cancer Control 14(2):141–150
24.
Zurück zum Zitat Lopez-Vergès S, Milush JM, Pandey S et al (2010) CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset. Blood 116(19):3865–3874PubMedCrossRef Lopez-Vergès S, Milush JM, Pandey S et al (2010) CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset. Blood 116(19):3865–3874PubMedCrossRef
25.
Zurück zum Zitat Falcão RP, Rizzatti EG, Saggioro FP et al (2007) Flow cytometry characterization of leukemic phase of nasal NK/T-cell lymphoma in tumor biopsies and peripheral blood. Haematologica 92(2):e24–e25PubMedCrossRef Falcão RP, Rizzatti EG, Saggioro FP et al (2007) Flow cytometry characterization of leukemic phase of nasal NK/T-cell lymphoma in tumor biopsies and peripheral blood. Haematologica 92(2):e24–e25PubMedCrossRef
26.
Zurück zum Zitat Ohshima K, Suzumiya J, Shimazaki K et al (1997) Nasal T/NK cell lymphomas commonly express perforin and Fas ligand: important mediators of tissue damage. Histopathology 31(5):444–450PubMedCrossRef Ohshima K, Suzumiya J, Shimazaki K et al (1997) Nasal T/NK cell lymphomas commonly express perforin and Fas ligand: important mediators of tissue damage. Histopathology 31(5):444–450PubMedCrossRef
27.
Zurück zum Zitat Oshimi K (1996) Lymphoproliferative disorders of natural killer cells. Int J Hematol 63(4):279–290PubMedCrossRef Oshimi K (1996) Lymphoproliferative disorders of natural killer cells. Int J Hematol 63(4):279–290PubMedCrossRef
Metadaten
Titel
Flow cytometric immunophenotyping is of great value to diagnosis of natural killer cell neoplasms involving bone marrow and peripheral blood
verfasst von
Neng-gang Jiang
Yong-mei Jin
Qian Niu
Ting-ting Zeng
Jun Su
Huan-ling Zhu
Publikationsdatum
01.01.2013
Verlag
Springer-Verlag
Erschienen in
Annals of Hematology / Ausgabe 1/2013
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-012-1574-3

Weitere Artikel der Ausgabe 1/2013

Annals of Hematology 1/2013 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.