Clinicopathologic features of aggressive natural killer cell leukemia
To study the clinicopathologic features of aggressive natural killer cell leukemia (ANKL).
The clinical and pathologic features were analyzed in 10 patients with ANKL. The complete blood count, peripheral blood smears, bone marrow aspirates and bone marrow biopsies were studied. Immunophenotypic analysis was carried out by flow cytometry and immunohistochemistry. T-cell receptor (TCR) γ gene rearrangement was studied by PCR method.
The most frequent hematologic abnormalities observed were anemia (7 cases) and thrombocytopenia (9 cases). Large granular lymphocytes were found on peripheral blood smears of 6 patients. In bone marrow aspirates, lymphocytosis (> 20.0%) was demonstrated in 8 cases and large granular lymphocytes in 6 cases. Bone marrow biopsies revealed various degrees of neoplastic infiltration, as follows: mild (5 cases), moderate (3 cases) and severe (2 cases). The neoplastic cells were mainly interstitial in distribution in 8 cases and diffuse in 2 cases. Hemophagocytosis was observed in 4 cases. Flow cytometry showed CD2+ sCD3- CD4- CD56+ CD57- in all cases, CD7+ in 9 cases, CD16+ in 5 cases, CD8+ in 4 cases and CD5+ in 1 case. Immunohistochemistry performed in 8 cases showed the following results: cCD3+ in 4 cases, CD56+ in 6 cases, TIA-1+ in 6 cases, granzyme B+ in 4 cases and perforin+ in 2 cases. PCR study revealed germline TCRγ gene configuration in all cases.
ANKL is a highly aggressive NK cell-derived lymphoid neoplasm. Comprehensive morphologic, immunophenotypic and molecular analysis are essential in arriving at a correct diagnosis. ANKL needs to be distinguished from other types of NK-cell and T-cell lymphomas.
Available from: Margarida Lima
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ABSTRACT: Mature natural killer (NK) cell neoplasms are classified by the World Health Organization into NK/T cell lymphoma, nasal type (NKTCL), aggressive NK-cell leukemia (ANKCL) and chronic lymphoproliferative disorders of NK-cells, the latter being considered provisionally. NKTCL and ANKCL are rare diseases, with higher prevalence in Asia, Central and South America. Most NKTCL present extranodal, as destructive tumor affecting the nose and upper aerodigestive tract (nasal NKTCL) or any organ or tissue (extranasal NKTCL) whereas ANKCL manifests as a systemic disease with multiorgan involvement and naturally evolutes to death in a few weeks. The histopathological hallmark of these aggressive NK-cell tumors is a polymorphic neoplastic infiltrate with angiocentricity, angiodestruction and tissue necrosis. The tumor cells have cytoplasmatic azurophilic granules and usually show a CD45+bright, CD2+, sCD3-, cytCD3epsilon+, CD56+bright, CD16-/+, cytotoxic granules molecules+ phenotype. T-cell receptor genes are in germ-line configuration. Epstein-Barr virus (EBV) -encoded membrane proteins and early region EBV RNA are usually detected on lymphoma cells, with a pattern suggestive of a latent viral infection type II. Complex chromosomal abnormalities are frequent and loss of chromosomes 6q, 11q, 13q, and 17p are recurrent aberrations. The rarity of the NK-cell tumors limits our ability to standardize the procedures for the diagnosis and clinical management and efforts should be made to encourage multi-institutional registries.
Orphanet Journal of Rare Diseases 07/2013; 8(1):95. DOI:10.1186/1750-1172-8-95 · 3.36 Impact Factor
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Malignant tumors of the lung are predominantly derived from epithelial tissue, such as squamous cell carcinoma and adenocarcinoma, while pulmonary lymphatic and hematopoietic tumor is relatively rare. Extranodal NK/T-cell lymphoma (ENKTL), nasal type, originates in nasal and extra-nasal sites anatomically. This distinct non-Hodgkin lymphoma is endemic and is characterized by a highly aggressive clinical course and dismal survival outcome. Extra-nasal ENKTL, especially pulmonary ENKTL, is rare compared with nasal type ENKTL and has received relatively little attention. Therefore, this study was conducted to assess the clinicopathological features of pulmonary ENKTL and to promote awareness of this malignancy.
Materials and methods:
All cases of ENKTL, nasal type diagnosed from January 2008 to June 2014 in our institution were collected, and those with pulmonary involvement were selected for further study. The eligible cases were analyzed retrospectively: medical recordings, imaging manifestations, pathological features, immunophenotypes, EBER1/2 hybridizations in situ and other related literatures were reviewed.
Results and conclusions:
A total of 1105 cases were diagnosed as ENKTL, nasal type, in this period, and 8 cases (7.2‰) had lung involvement. Seven cases had core biopsy, and for 1 case, a resected tissue specimen was available. The group was composed of 6 men and 2 women (gender ratio 3:1) with ages ranging from 19 to 44 (average age of 33.5) years. In this group, 2 cases were secondary and 5 cases were primary. The clinical symptoms and computed tomography (CT) manifestations were nonspecific. Histologically, the neoplasms presented angiocentric and angiodestructive growth patterns with different degrees of inflammatory response and necrosis. The neoplastic cell sizes were heterogeneous with spectra of small to large or mixed-composition types. For the immunophenotypes, all cases were positive for CD3ɛ and cytotoxic granule (granzyme B or TIA-1). The positive ratios of CD56 and CD30 were 6/8 and 4/5 respectively. All 8 cases showed positive in situ hybridization for Epstein-Barr virus-encoded small RNA (EBER). TCR-γ gene rearrangement was tested in 4 cases, and only 1 of these cases was monoclonal. Laboratory testing demonstrated that the whole blood was decreased while the average level of LDH was elevated. Six bone marrow biopsy specimens were negative and showed no neoplastic cells infiltration. For treatment, 4 individuals accepted chemotherapy and 1 patient underwent localized tumor resection surgery. The follow-up information was available for 6 patients, 1 of whom was alive and the other 5 cases survived shortly between 20 days and 4 months. ENKTL, nasal type of lung is very rare, and the diagnosis is challenging due to nonspecific clinical symptoms and imaging results. The diagnosis of pulmonary ENKTL should be based on comprehensive clinical, imaging, histopathological and molecular examination. More effective treatment strategies are required for this disease.
Pathology - Research and Practice 04/2015; 211(7). DOI:10.1016/j.prp.2015.04.002 · 1.40 Impact Factor
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