[Cytomorphology and molecular characterization of CLTC-ALK rearrangement in 2 cases of ALK-positive diffuse large B-cell lymphoma with extensive bone marrow involvement].

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
The Korean Journal of Laboratory Medicine (Impact Factor: 1.31). 05/2008; 28(2):89-94. DOI: 10.3343/kjlm.2008.28.2.89
Source: PubMed

ABSTRACT Aanaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is an unusual disease entity first reported in 1997 as DLBCL with expression of full-length ALK protein. The World Health Organization classification enlists the disease as a rare variant of DLBCL. Herein we describe two cases of ALK-positive DLBCL with cytomorphologic and molecular characteristics for the first time in Korea. The patients were 35-yr-old and 24-yr-old male patients. Immunohistochemical studies on the lymph nodes revealed large sized neoplastic cells with plasmablastic differentiation, which were negative for CD30 and positive for ALK with the characteristic granular staining in the cytoplasmic region. Extensive involvement of bone marrow was observed in both cases showing large, extremely atypical cells. Fluorescence in situ hybridization and molecular studies on the bone marrow aspirate specimens led to the detection of a clathrin (CLTC)/ALK rearrangement. Despite aggressive chemotherapy, the patients died 15 and 17 months after the diagnosis, indicating poor prognosis of the disease entity. This is the first report demonstrating the cytomorphologic findings of ALK-positive DLBCL cells on bone marrow aspirates.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) with plasmablastic features associated with t(2;17)(p23;q23) and characteristic granular cytoplasmic anaplastic lymphoma kinase-1 (ALK1) protein expression is a rare lymphoma subtype. Nodal and extranodal involvement has been reported. Our case is a 32-year-old man with right cervical adenopathy. Lymph node biopsy showed large atypical cells with prominent plasmablastic differentiation, abundant amphophilic cytoplasm, and prominent central nucleoli. Paraffin immunohistochemistry showed finely granular cytoplasmic ALK1 expression, positive CD138, IgA, p63 (VS38), focal positive epithelial membrane antigen and CD4, and lambda light chain restriction whereas negative CD20 and CD30 staining. While reports show detection of the unique CLTC-ALK fusion by either reverse transcription-polymerase chain reaction or fluorescence in situ hybridization, our case represents the second case in the literature to detect the t(2;17)(p23;q23) translocation by multiplex karyotyping (multiplex fluorescence in situ hybridization) and the usefulness of this technique to detect hidden translocations not seen by G-banding. An add(2)(p23) was also seen not previously reported. Differential diagnoses of neoplasms with plasmablastic differentiation and a comprehensive molecular/cytogenetic literature review of ALK+DLBCL is discussed.
    Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 04/2009; 17(2):172-7. · 1.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We report 2 ALK-positive large B-cell lymphoma cases showing granular cytoplasmic and cytoplasmic/nuclear ALK immunostaining in which cryptic ALK rearrangements were identified by fluorescent in situ hybridization and molecular analysis. In the first case, the ALK-involving t(2;3)(p23;q27) masked the cryptic SEC31A-ALK fusion generated by an insertion of the 5' end of SEC31A (4q21) upstream of the 3' end of ALK. This rearrangement was associated with loss of the 5' end of ALK and duplication of SEC31A-ALK on der(20). In the second case with complex rearrangements of both chromosomes 2, a submicroscopic NPM1-ALK fusion created by insertion of the 3' end of ALK into the NPM1 locus was evidenced. Further studies of SEC31A-ALK showed that this variant fusion transforms IL3-dependent Ba/F3 cells to growth factor independence, and that the ALK inhibitor TAE-684 reduces cell proliferation and kinase activity of SEC31A-ALK and its downstream effectors ERK1/2, AKT, STAT3 and STAT5.
    Haematologica 03/2010; 95(3):509-13. · 5.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma (ALK-positive DLBCL) is a rare subtype of DLBCL. In this review, the authors discuss the potential lymphomagenetic role of ALK gene rearrangements, address the distinct clinical and pathological characteristics, and evaluate potential prognostic factors for survival of 77 cases of ALK-positive DLBCL reported in the literature. Pathologically, ALK-positive DLBCL shows a plasmablastic appearance and CD20 negativity in the tumor cells, making this lymphoma a challenging diagnosis. ALK-positive DLBCL can be seen at any age but shows a bimodal incidence. ALK-positive DLBCL is also characterized by a clinical aggressive behavior and poor response to both standard and highly intensive therapies, with a 5-year overall survival of 27%. Finally, advanced clinical stage, age older than 18 years, and extranodal disease are associated with worse survival.
    European journal of clinical & medical oncology 01/2010;


Available from