ALK-positive diffuse large B-cell lymphoma: Report of four cases and review of the literature

Department of Pathology, University of New Mexico, Albuquerque, NM 87131, USA.
Modern Pathology (Impact Factor: 6.19). 04/2007; 20(3):310-9. DOI: 10.1038/modpathol.3800742
Source: PubMed


We report detailed clinical and pathologic features of four cases of anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma (ALK-DLBCL), a rare entity with only 29 currently reported cases. This study is the third largest of all reported series. Biopsies from four adult patients aged 41, 49, 53, and 71 years (three lymph nodes and one nasopharyngeal mass) exhibited immunoblastic/plasmablastic morphology. By immunohistochemistry and/or flow cytometry, they expressed cytoplasmic ALK-1, CD138, VS38 (3/3), monoclonal cytoplasmic light chain, CD45, EMA, CD4, and CD57 (2/3), and were negative for CD3, CD30, CD56, and TIA-1. Two showed variable CD79a expression, and one had rare CD20(+) cells. Two of three cases exhibited rare CD43(+) reactivity. One case showed scattered cytokeratin(+) cells, which could possibly lead to a misdiagnosis of carcinoma. After CHOP and radiotherapy, two stage I patients were free of disease at 58 and 36 months, whereas a stage IV patient was dead of disease at 22 months.

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Available from: Kaaren K Reichard, Aug 13, 2014
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    • "Although extranodal sites, including the nasopharynx and stomach, may be involved (7,9,10), it is the lymph nodes that are consistently primarily involved in cases of ALK+ DLBCL. The present study reports, to the best of our knowledge, the first case of primary extranodal ALK+ DLBCL presenting as a duodenal mass. "
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    ABSTRACT: Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (ALK(+) DLBCL) is characterized by the presence of immunoblastic or plasmablastic cells with a strong ALK protein expression that is frequently associated with t(2;17)(p23;q23). The present study reports a case of ALK(+) DLBCL in a 26-year-old male with a duodenal mass. Histologically, the neoplastic cells demonstrated prominent plasmablastic differentiation with abundant amphophilic cytoplasma and central nucleoli. Paraffin immunohistochemistry revealed: an exclusively cytoplasmic granular expression of ALK; CD138, immunoglobulin A (IgA) and CD79α positivity; and focal expression of multiple myeloma oncogene 1 (Mum-1), CD30 and epithelial membrane antigen (EMA). However, the immunohistochemical staining was negative for CD3, CD38 and CD20. Fluorescence in situ hybridization (FISH) analysis using an ALK break-apart probe revealed the presence of ALK gene rearrangements in the patient. To the best of our knowledge, the current case represents the first example of primary extranodal ALK(+) DLBCL presenting as a duodenal mass.
    Experimental and therapeutic medicine 08/2014; 8(2):409-412. DOI:10.3892/etm.2014.1786 · 1.27 Impact Factor
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    • "Considering the primary refractoriness towards standard CHOP treatment and the possibility of ALK-positive LBCL, which is associated with a poor prognosis,10 we discussed with the patient an individual treatment plan, consisting of the anti-CD30 drug conjugate, brentuximab vedotin and the classical lymphoma salvage regimen DHAP11 (brentuximab vedotin 1.2 mg/kg [day 0], cisplatin 70 mg/m2 [day 1] over a period of 22 hours, cytarabine [2 × 2,000 mg/m2 on day 2] and dexamethasone [40 mg on days 2–5]) (Figure 3). Standard supportive care was administered. "
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    ABSTRACT: Anaplastic large cell lymphoma (ALCL) is a common subtype of the heterogeneous group of peripheral T-cell lymphomas, which is characterized by large pleomorphic cells with strong expression of CD30. Translocations involving ALK, the anaplastic lymphoma kinase gene, are associated with a favorable clinical outcome. Such ALK-positive ALCLs are usually responsive to a multidrug chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). However, there is no general consensus on the optimal therapy for relapsed or refractory ALCL. We report the case of a 24-year-old male suffering from ALK-positive ALCL with an uncommon manifestation of only extranodal disease in the gastric cardia region that showed primary refractoriness to standard CHOP chemotherapy. A combination therapy consisting of the anti-CD30 drug conjugate, brentuximab vedotin, and classical lymphoma salvage regimen DHAP (cisplatin, high-dose cytarabine and dexamethasone) was administered. Following two treatment cycles in 21-day intervals, the lymphoma showed considerable regression based on imaging diagnostics and no evidence of vital lymphoma in a subsequent biopsy. We did not observe any increase in toxicity; in particular, polyneuropathy and febrile neutropenia were not observed. In summary, we report that the antibody-drug conjugate brentuximab vedotin and a classical regimen used for aggressive lymphoma, DHAP, could be combined as salvage therapy in a case of refractory ALK-positive ALCL. Phase I/II studies will be required for safety and efficacy analysis.
    OncoTargets and Therapy 06/2014; 7:1123-7. DOI:10.2147/OTT.S59795 · 2.31 Impact Factor
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    • "Thus, no substantial CGH data is available [1,10]. Patients are unresponsive to rituximab and have a poor clinical outcome [72]. "
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    ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin Lymphoma comprising of greater than 30% of adult non-Hodgkin Lymphomas. DLBCL represents a diverse set of lymphomas, defined as diffuse proliferation of large B lymphoid cells. Numerous cytogenetic studies including karyotypes and fluorescent in situ hybridization (FISH), as well as morphological, biological, clinical, microarray and sequencing technologies have attempted to categorize DLBCL into morphological variants, molecular and immunophenotypic subgroups, as well as distinct disease entities. Despite such efforts, most lymphoma remains undistinguishable and falls into DLBCL, not otherwise specified (DLBCL-NOS). The advent of microarray-based studies (chromosome, RNA, gene expression, etc) has provided a plethora of high-resolution data that could potentially facilitate the finer classification of DLBCL. This review covers the microarray data currently published for DLBCL. We will focus on these types of data; 1) array based CGH; 2) classical CGH; and 3) gene expression profiling studies. The aims of this review were three-fold: (1) to catalog chromosome loci that are present in at least 20% or more of distinct DLBCL subtypes; a detailed list of gains and losses for different subtypes was generated in a table form to illustrate specific chromosome loci affected in selected subtypes; (2) to determine common and distinct copy number alterations among the different subtypes and based on this information, characteristic and similar chromosome loci for the different subtypes were depicted in two separate chromosome ideograms; and, (3) to list re-classified subtypes and those that remained indistinguishable after review of the microarray data. To the best of our knowledge, this is the first effort to compile and review available literatures on microarray analysis data and their practical utility in classifying DLBCL subtypes. Although conventional cytogenetic methods such as Karyotypes and FISH have played a major role in classification schemes of lymphomas, better classification models are clearly needed to further understanding the biology, disease outcome and therapeutic management of DLBCL. In summary, microarray data reviewed here can provide better subtype specific classifications models for DLBCL.
    Journal of Hematology & Oncology 09/2012; 5(1):54. DOI:10.1186/1756-8722-5-54 · 4.81 Impact Factor
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