Blastic Natural Killer Cell Lymphoma Research Articles

A Case of Blastic Natural Killer Cell Lymphoma with Rapidly Progressive Multi-Organ Involvement

Wir berichten den Fall eines 72 Jahre alten Mannes mit einem blastischen NK-Zell-Lymphom mit initialem Befall der Haut und der axillären Lymphknoten. Die Behandlung erfolgte zunächst mit Cyclophosphamid, Doxorubicin, Vincristin und Prednison (CHOP). Es konnte lediglich ein partielles Ansprechen für 2 Monate erreicht werden. Das erste Rezidiv präsentierte sich mit einer Splenomegalie, einer leukämischen Generalisation und einem multifokalen Hautbefall. Unter der Behandlung mit Dexamethason und Cyclophosphamid trat eine spontane Milzruptur und ein Hämoperitoneum auf Nach einer Notfallsplenektomie kam es zur spontanen Rückbildung einer zuvor bestehenden Thrombozytopenie. In Anlehnung an ein Standard-Therapieprotokoll für die akute lymphatische Leukämie (ALL) wurde die Behandlung wieder aufgenommen (Standarddosis - Cytosinarabinosid, Cyclophosphamid und Steroide). Ein therapeutischer Effekt wurde nicht dokumentiert. Der Einsatz von Dexamethason, Carmustin, Etoposid, Doxorubicin und Melphalan (DexaBEAM) führte zu einer sechswöchigen Remission. Ein meningealer Rückfall wurde mit hochdosiertem Methotrexat behandelt. Es konnte eine Blasten-Clearance des zerebrospinalen Liquors und eine partielle Remission erreicht werden. Schließlich verstarb der Patient unter dem Bild profuser Blutungen aus dem oberen Aerodigestivtrakt neun Monate nach der Erstdiagnose. NK-Zell-Lymphome sind aggressive lymphoproliferative Erkrankungen mit besonderer Neigung zu einem extranodalen Befall an verschiedenen Stellen des Körpers. Bislang konnte keine Standardtherapie definiert werden. Aus diesem Grunde sollte frühzeitig während der Erkrankung der Einsatz auch experimenteller Therapieverfahren erwogen werden.

Blastic natural killer cell and extranodal natural killer cell-like T-cell lymphoma presenting in the skin: report of six cases from the UK.

Some lymphomas express natural killer (NK)-cell markers such as the neural cell adhesion molecule, which is recognized by the CD56 antibody. These lymphomas may present in the skin, but do not represent a homogeneous group. The new World Health Organization classification of lymphoma/leukaemia recognizes several types of NK/T-cell neoplasm, including blastic NK-cell lymphoma, which characteristically presents with cutaneous lesions. To describe the clinical, pathological and molecular features in six cases of CD56+ lymphoma with cutaneous presentation. The clinical, histopathological and immunophenotypic features of six patients were reviewed. In addition, in situ hybridization (ISH) to identify Epstein-Barr virus (EBV) mRNA, and polymerase chain reaction analysis to identify the presence of a clonal population of T cells or B cells were performed on lesional skin. All patients presented with widespread nodules and plaques, which in five cases were a characteristic purple colour. Four patients developed disseminated disease, three with neurological involvement. These four patients died between 14 and 46 months following diagnosis (median 30 months). In four of six cases the histopathological and immunohistological features were in keeping with a blastic NK-cell lymphoma. No clonal immunoglobulin heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement was detected in the four cases consistent with an origin from NK cells. A further case fitted the criteria for an extranodal NK/T-cell lymphoma of nasal type and was also the only case to show evidence of EBV mRNA by ISH. A clonal T-cell population was identified in the final case. This patient also exhibited molecular evidence of a clonal B-cell population and a t(14;18) translocation confirmed by sequence analysis. Our data confirm that NK-cell lymphomas presenting in the skin are a heterogeneous group, and that in the U.K., blastic NK-cell lymphoma is more common than extranodal NK/T-cell lymphoma of nasal type. These lymphomas pursue an aggressive course, with rapid development of disseminated disease, and resistance to chemotherapy. Detailed immunophenotyping is needed to distinguish the different types. Our molecular data indicate that blastic NK-cell lymphoma cases lack clonal TCR/IgH gene rearrangements consistent with an NK-cell origin. Our ISH findings indicate that EBV plays a pathogenetic role only in extranodal NK/T-cell lymphoma of nasal type.

Leukemia and lymphoma of natural killer lineage cells.

Natural killer (NK) cells are lymphocytes with a large granular lymphocyte morphology, a CD3- CD56+ phenotype, a non-major histocompatibility complex-restricted cytotoxicity, and germline configuration T-cell receptor genes. NK cell lineage tumors originate from either precursor NK cells or mature NK cells. Tumors originating conceivably from precursor NK cells include myeloid/NK cell precursor acute leukemia, precursor NK cell acute lymphoblastic leukemia, and blastic NK cell lymphoma. However, because the developmental pathway of normal NK cells and the characteristics of these NK precursors are not fully understood, the definition and characterization of the tumors are only provisional. Tumors of mature NK cell origin include aggressive NK cell leukemia/lymphoma, nasal-type NK cell lymphoma, and chronic NK lymphocytosis, but the last disorder seems to be reactive in most cases. Because NK cell tumors are rare and difficult to manage, vigorous studies are required for their understanding and management.

Ｂｌａｓｔｉｃ ＮＫ Ｃｅｌｌ Ｌｙｍｐｈｏｍａ 鼻腔内浸潤を伴ったＢｌａｓｔｉｃ ＮＫ ｃｅｌｌ ｌｙｍｐｈｏｍａの１例

Blastic natural killer (NK) cell lymphoma is a neoplasm of NK origin with aggressive behavior. Blastic morphology, an NK cell immunophenotype, and a lack of association with Epstein-Barr virus are the clues for the diagnosis. We report the case of a 67-year-old man who has maintained complete remission for 3 months after CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chernotherapy. However, he died 10 rnonths after his first visit. In addition to blastic NK cell lyrnphoma, he had a nasopharynx tumor and cutaneous tumors when he visited our clinic. [Skin Cancer (Japan) 2003; 18: 66-69]

Molecular analysis of tumor suppressor genes, Rb, p53, p16INK4A, p15INK4B and p14ARF in natural killer cell neoplasms.

Natural killer (NK) cell neoplasms, which are derived from mature or precursor NK cells, are rare diseases and are observed predominantly in Asian countries. We analyzed the status of the Rb, p53, p15INK4B, p16INK4A and p14ARF genes in these diseases by Southern blot, polymerase chain reaction–single strand conformational polymorphism (PCR–SSCP) and western blot analysis. We used 31 NK cell neoplasms, including four cell lines derived from NK cell neoplasms, 3 myeloid/ NK cell precursor acute leukemias, 4 blastic NK cell lymphoma/leukemias, 4 aggressive NK cell leukemia/lymphomas, 4 nasal NK cell lymphomas, and 12 chronic NK lymphocytosis. We found gene amplification of the p53 gene in one nasal NK cell lymphoma, and point mutations of the p53 gene in one blastic NK cell lymphoma/leukemia and one chronic NK lymphocytosis. In addition, homozygous deletions ofpl5,p16 andp14 genes in 5 out of 31 samples were detected; 3 were from nasal NK cell lymphoma and 2 from blastic NK cell lymphoma/leukemia. Also hemizygous deletion of the Kb gene in one blastic NK cell lymphoma was detected. Rb proteins were highly expressed in one cell line as well as two myeloid/NK cell precursor acute leukemias. In other cell lines, complete loss and an aberrant migration pattern of Rb protein expression were observed. Comparative genomic hybridization suggested that the homozygous deletions of the p15, p16 and p14 were subtle chromosomal deletions and could not be identified by standard karyotyping in some cases. Although the number of cases we analyzed was not large, alterations identified in the Rb, p53, p16, p15 and p14 genes are of significance and might be associated with tumorigenesis in NK cell neoplasms