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Aggressive natural killer-cell neoplasm presenting in the marrow: a report of two cases including one with gains of chromosomes 4q and 9p.

Jhuang JY, Clipson A, Hsieh YC, Yang CC, Chang ST, Du MQ, Chuang SS - Diagn Pathol (2015)

Bottom Line: Both patients passed away in a month.One case showed gains of chromosomes 4q and 9p by array comparative genomic hybridization.Our cases demonstrate that lymphoma should be considered in patients with fever of unknown origin and bone marrow aspiration/biopsy should be performed as early diagnosis and novel therapeutic regimens may benefit these patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomic Pathology, Far Eastern Memorial Hospital, New Taipei City, Taiwan.

ABSTRACT
Aggressive nature killer (NK)-cell neoplasm includes aggressive NK-cell leukemia (ANKL) and extranodal NK/T-cell lymphoma (ENKTL), nasal type. ANKL is rare and is characterized by a systemic neoplastic proliferation of NK-cells, usually with a leukemic presentation. ENKTL is a predominantly extranodal lymphoma, occurring mainly in the upper aerodigestive tract. Both are aggressive neoplasms strongly associated with Epstein-Barr virus (EBV). Here we report two patients with aggressive NK-cells neoplasms localized in the bone marrow (BM) who presented as prolonged fever, anemia, and thrombocytopenia. Both were treated initially as infectious disease. Imaging studies revealed splenomegaly without any nodular lesion or lymphadenopathy. BM examination revealed extensive involvement by EBV-positive NK-cells in both cases. Staging workup including nasal examination/biopsy was negative. Both patients passed away in a month. One case showed gains of chromosomes 4q and 9p by array comparative genomic hybridization. Both tumors were diagnostically challenging due to the unusual clinical presentation and absence of leukemic change, tumor mass or lymphadenopathy. Our cases demonstrate that lymphoma should be considered in patients with fever of unknown origin and bone marrow aspiration/biopsy should be performed as early diagnosis and novel therapeutic regimens may benefit these patients.

No MeSH data available.


Related in: MedlinePlus

Case 1. Flow cytometric analysis of the marrow aspirate shows that the gated atypical lymphocytes express surface CD2 and CD56 but not CD3 or CD7 (a-c). In addition, they express cytoplasmic CD3 but not TdT, indicating an NK-cell phenotype. Marrow trephine shows a hypercellular marrow with extensive infiltration by small to medium-sized atypical lymphocytes (d and e, HE stains; original magnifications × 200 and × 1000, respectively). The tumor cells express cytoplasmic CD3 (f), TIA-1 (g) and EBER (h). Analyses of genomic copy number alteration using the HumanCytoSNP-12 Beadchip (Illumina). i and j, These two panels show evidence of gain of one copy at 4q21-q35 (i) and 9p24-p13 (j) respectively. B allele frequency (BAF) plot in both panels demonstrates an altered pattern of BAF (0.0, 0.33, 0.67 and 1.0), which is highlighted in a blue background. Log R ratio plot displays no apparent alteration and this is most likely due to the presence of mosaicism in the region of chromosomal gain
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Fig1: Case 1. Flow cytometric analysis of the marrow aspirate shows that the gated atypical lymphocytes express surface CD2 and CD56 but not CD3 or CD7 (a-c). In addition, they express cytoplasmic CD3 but not TdT, indicating an NK-cell phenotype. Marrow trephine shows a hypercellular marrow with extensive infiltration by small to medium-sized atypical lymphocytes (d and e, HE stains; original magnifications × 200 and × 1000, respectively). The tumor cells express cytoplasmic CD3 (f), TIA-1 (g) and EBER (h). Analyses of genomic copy number alteration using the HumanCytoSNP-12 Beadchip (Illumina). i and j, These two panels show evidence of gain of one copy at 4q21-q35 (i) and 9p24-p13 (j) respectively. B allele frequency (BAF) plot in both panels demonstrates an altered pattern of BAF (0.0, 0.33, 0.67 and 1.0), which is highlighted in a blue background. Log R ratio plot displays no apparent alteration and this is most likely due to the presence of mosaicism in the region of chromosomal gain

Mentions: Table 1 summaries the pathological and immunophenotypic features. By flow cytometry, the marrow lymphocytes expressed CD2, CD56 and cytoplasmic CD3 but not surface CD3, CD5, CD7, CD8 or terminal deoxynucleotidyl transferase, indicating an NK-cell phenotype (Fig. 1a-c). The marrow trephine was hypercellular with a diffuse infiltrate of atypical small to medium-sized lymphocytes accompanied by stromal fibrosis (Fig. 1d and e). Immunohistochemically, the atypical lymphocytes expressed CD3 (Fig. 1f), CD45 and T-cell intracellular antigen (TIA)-1 (Fig. 1g) but not CD2, CD4, CD5, CD7, CD8, CD20, CD30, CD56, βF1, T-cell receptor (TCR)-γ or granzyme B. EBV in situ hybridization (EBER) showed positive signals in around 70 % tumor cells (Fig. 1h). For Infinium genotyping assay, 200 ng DNA isolated from marrow aspirate was hybridized to the HumanCytoSNP-12 Beadchip (Illumina) according to the manufacturer’s instructions. Data were analyzed using the genotyping module of the GenomeStudio software (version 1.9.0; Illumina). Copy-number analysis was performed using the cnvPartition copy-number variation (CNV) analysis plug-in for GenomeStudio software (version 3.2.0; Illumina). A confidence value of greater than 100 was used to determine true copy number changes. The copy number analysis indicated a gain of 1 copy at chromosome 4:83644676 – 4:190742692 (CNV Confidence: 22884.3; Fig. 1i) and a gain of 1 copy in chromosome 9:46587 – 9:21925855 (CNV Confidence: 1630.9) and 9:22098574 – 9:33228189 (CNV Confidence: 2317.0; Fig. 1j) B allele frequency (BAF) plot in both panels demonstrated an altered pattern of BAF (0.0, 0.33, 0.67 and 1.0), while Log R ratio plot displayed no apparent alteration. This was most likely due to the presence of mosaicism in the region of chromosomal gain [4].Table 1


Aggressive natural killer-cell neoplasm presenting in the marrow: a report of two cases including one with gains of chromosomes 4q and 9p.

Jhuang JY, Clipson A, Hsieh YC, Yang CC, Chang ST, Du MQ, Chuang SS - Diagn Pathol (2015)

Case 1. Flow cytometric analysis of the marrow aspirate shows that the gated atypical lymphocytes express surface CD2 and CD56 but not CD3 or CD7 (a-c). In addition, they express cytoplasmic CD3 but not TdT, indicating an NK-cell phenotype. Marrow trephine shows a hypercellular marrow with extensive infiltration by small to medium-sized atypical lymphocytes (d and e, HE stains; original magnifications × 200 and × 1000, respectively). The tumor cells express cytoplasmic CD3 (f), TIA-1 (g) and EBER (h). Analyses of genomic copy number alteration using the HumanCytoSNP-12 Beadchip (Illumina). i and j, These two panels show evidence of gain of one copy at 4q21-q35 (i) and 9p24-p13 (j) respectively. B allele frequency (BAF) plot in both panels demonstrates an altered pattern of BAF (0.0, 0.33, 0.67 and 1.0), which is highlighted in a blue background. Log R ratio plot displays no apparent alteration and this is most likely due to the presence of mosaicism in the region of chromosomal gain
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4491245&req=5

Fig1: Case 1. Flow cytometric analysis of the marrow aspirate shows that the gated atypical lymphocytes express surface CD2 and CD56 but not CD3 or CD7 (a-c). In addition, they express cytoplasmic CD3 but not TdT, indicating an NK-cell phenotype. Marrow trephine shows a hypercellular marrow with extensive infiltration by small to medium-sized atypical lymphocytes (d and e, HE stains; original magnifications × 200 and × 1000, respectively). The tumor cells express cytoplasmic CD3 (f), TIA-1 (g) and EBER (h). Analyses of genomic copy number alteration using the HumanCytoSNP-12 Beadchip (Illumina). i and j, These two panels show evidence of gain of one copy at 4q21-q35 (i) and 9p24-p13 (j) respectively. B allele frequency (BAF) plot in both panels demonstrates an altered pattern of BAF (0.0, 0.33, 0.67 and 1.0), which is highlighted in a blue background. Log R ratio plot displays no apparent alteration and this is most likely due to the presence of mosaicism in the region of chromosomal gain
Mentions: Table 1 summaries the pathological and immunophenotypic features. By flow cytometry, the marrow lymphocytes expressed CD2, CD56 and cytoplasmic CD3 but not surface CD3, CD5, CD7, CD8 or terminal deoxynucleotidyl transferase, indicating an NK-cell phenotype (Fig. 1a-c). The marrow trephine was hypercellular with a diffuse infiltrate of atypical small to medium-sized lymphocytes accompanied by stromal fibrosis (Fig. 1d and e). Immunohistochemically, the atypical lymphocytes expressed CD3 (Fig. 1f), CD45 and T-cell intracellular antigen (TIA)-1 (Fig. 1g) but not CD2, CD4, CD5, CD7, CD8, CD20, CD30, CD56, βF1, T-cell receptor (TCR)-γ or granzyme B. EBV in situ hybridization (EBER) showed positive signals in around 70 % tumor cells (Fig. 1h). For Infinium genotyping assay, 200 ng DNA isolated from marrow aspirate was hybridized to the HumanCytoSNP-12 Beadchip (Illumina) according to the manufacturer’s instructions. Data were analyzed using the genotyping module of the GenomeStudio software (version 1.9.0; Illumina). Copy-number analysis was performed using the cnvPartition copy-number variation (CNV) analysis plug-in for GenomeStudio software (version 3.2.0; Illumina). A confidence value of greater than 100 was used to determine true copy number changes. The copy number analysis indicated a gain of 1 copy at chromosome 4:83644676 – 4:190742692 (CNV Confidence: 22884.3; Fig. 1i) and a gain of 1 copy in chromosome 9:46587 – 9:21925855 (CNV Confidence: 1630.9) and 9:22098574 – 9:33228189 (CNV Confidence: 2317.0; Fig. 1j) B allele frequency (BAF) plot in both panels demonstrated an altered pattern of BAF (0.0, 0.33, 0.67 and 1.0), while Log R ratio plot displayed no apparent alteration. This was most likely due to the presence of mosaicism in the region of chromosomal gain [4].Table 1

Bottom Line: Both patients passed away in a month.One case showed gains of chromosomes 4q and 9p by array comparative genomic hybridization.Our cases demonstrate that lymphoma should be considered in patients with fever of unknown origin and bone marrow aspiration/biopsy should be performed as early diagnosis and novel therapeutic regimens may benefit these patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomic Pathology, Far Eastern Memorial Hospital, New Taipei City, Taiwan.

ABSTRACT
Aggressive nature killer (NK)-cell neoplasm includes aggressive NK-cell leukemia (ANKL) and extranodal NK/T-cell lymphoma (ENKTL), nasal type. ANKL is rare and is characterized by a systemic neoplastic proliferation of NK-cells, usually with a leukemic presentation. ENKTL is a predominantly extranodal lymphoma, occurring mainly in the upper aerodigestive tract. Both are aggressive neoplasms strongly associated with Epstein-Barr virus (EBV). Here we report two patients with aggressive NK-cells neoplasms localized in the bone marrow (BM) who presented as prolonged fever, anemia, and thrombocytopenia. Both were treated initially as infectious disease. Imaging studies revealed splenomegaly without any nodular lesion or lymphadenopathy. BM examination revealed extensive involvement by EBV-positive NK-cells in both cases. Staging workup including nasal examination/biopsy was negative. Both patients passed away in a month. One case showed gains of chromosomes 4q and 9p by array comparative genomic hybridization. Both tumors were diagnostically challenging due to the unusual clinical presentation and absence of leukemic change, tumor mass or lymphadenopathy. Our cases demonstrate that lymphoma should be considered in patients with fever of unknown origin and bone marrow aspiration/biopsy should be performed as early diagnosis and novel therapeutic regimens may benefit these patients.

No MeSH data available.


Related in: MedlinePlus