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

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.

Expression of the Activating Receptor, NKp46 (CD335), in Human Natural Killer and T-Cell Neoplasia

“…Regardless, given that CD16 was always coexpressed on CD335dim nonneoplastic NK cell populations detected in our study, the pattern of dim CD335 expression on CD3-CD16-NK cells may be quite useful for distinguishing ENKL from reactive NK cell populations as well as from ANKL and CLPD-NK, although a more targeted analysis of ENKL, ANKL, and CLPD-NK with a larger number of samples evaluated by flow cytometry will be needed to draw more definite conclusions. In contrast, the immunophenotypic features of CLPD-NK likely overlap with reactive NK cell populations that are CD3-CD16+ 15,37 and may downregulate CD335. Therefore, additional ancillary testing, such as killer cell immunoglobulin-like receptor phenotyping and STAT3 gene sequencing analysis, may be necessary to further evaluate putative cases of CLPD-NK.…”

“…15,27,28 They pose additional diagnostic challenges because of their rarity and their lack of specific markers that separate them from reactive Diminished CD335 expression was also detected on atypical and neoplastic NK cell populations in our study, suggesting that the loss of CD335 surface staining, although not specific for NK neoplasia, may provide an important addition to the armamentarium of the clinical diagnostician evaluating atypical NK cell proliferations. 37 The 2008 WHO classification of hematopoietic malignancies describes three neoplasms of mature NK cells: ENKL, aggressive NK cell leukemia (ANKL), and CLPD-NK. 15 Whereas ENKL is usually CD16-, ANKL and CLPD-NK are usually CD16+.…”

Rare aggressive natural killer cell leukemia presented with bone marrow fibrosis - a diagnostic challenge

“…Abnormal NK cells are similar to normal NK cells in immunophenotype, they express CD2, CD7, CD11c, CD16, and CD56. CD3 and CD4 are not expressed in all NK cells (Jiang et al 2013). …”

“…20 more cases were studied in a Chinese study published in 2012 (Zhang et al 2012), 3 more Japanese cases were reported in 2012 (Okuno et al 2012), one case was reported in Danish study (Boysen et al 2011) and additional 43 cases of ANKL were involved in another large Chinese study conducted in the time period between 2006–2012 and published in 2013 (Jiang et al 2013). Up to our knowledge this is the first case report in Qatar.…”

“…The first entity (CLPD-NK) is more indolent compared to fulminating prognostically adverse extranodal NK/T-cell lymphoma of the nasal type (ENKL) and aggressive natural killer leukemia (ANKL). Immunophenotypically, the latter exhibit stronger CD56-expression, larger forward scatter (FSC) and usually more CD7 negative and CD16 negative, compared to the former subtype which is CD56 dim/negative CD16 positive (Jiang et al 2013; Trotta et al 2005). However, all of them are associated with EBV infection (Chan et al 2008; Nava & Jaffe 2005).…”