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ALK-positive large B-cell lymphoma: identification of EML4-ALK and a review of the literature focusing on the ALK immunohistochemical staining pattern

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Abstract

Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+LBCL) is a rare, aggressive B-cell lymphoma with ALK fusion genes. Histopathologically, the ALK immunohistochemical staining pattern is suggestive of the fusion partner of ALK. Here, we examined an ALK+LBCL case showing a unique diffuse cytoplasmic ALK staining pattern and identified EML4-ALK, which has not previously been reported in ALK+LBCL. Furthermore, to clarify whether the prognosis differs depending on the staining pattern, we reviewed 112 previously reported cases, and analyzed immunohistochemical markers and clinical data stratified by the staining pattern. We found that ALK staining can be classified into a granular cytoplasmic staining (GCS) or a non-GCS patterns. Sixty-four adult cases for which both the ALK staining pattern and survival time were reported were further analyzed for survival trends. The non-GCS pattern was significantly associated with inferior overall survival (P = 0.031). This difference remained significant after adjusting for age and clinical stage (hazard ratio 5.08, 95 % CI 1.88–13.7, P = 0.0013). Given that the ALK immunohistochemical staining pattern is associated with the ALK fusion partner, the present results suggest that the prognosis for ALK+LBCL differs depending on the ALK fusion partner.

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Acknowledgments

The authors thank Drs. Camille Laurent and Pierre Brousset for providing us with the data regarding their cases reported in Journal of Clinical Oncology. We also thank Ms. Sayuri Sengoku for administrative assistance.

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Authors and Affiliations

  1. Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan

    Kana Sakamoto, Yuki Togashi, Seiji Sakata, Satoko Baba, Akito Dobashi, Reimi Asaka & Kengo Takeuchi

  2. Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan

    Kana Sakamoto, Hideki Nakasone & Yoshinobu Kanda

  3. Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan

    Yuki Togashi, Naoko Tsuyama, Reimi Asaka & Kengo Takeuchi

  4. Department of Anatomical Pathology, Far Eastern Memorial Hospital, New Taipei, Taiwan

    Chien-Chen Tsai

  5. Department of Pathology, Chi-Mei Medical Centre, Tainan, Taiwan

    Shih-Sung Chuang

  6. Department of Pathology, Taipei Medical University, Taipei, Taiwan

    Shih-Sung Chuang

  7. National Taiwan University, Taipei, Taiwan

    Shih-Sung Chuang

  8. Department of Hematology, Toranomon Hospital, Tokyo, Japan

    Koji Izutsu

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  1. Kana Sakamoto
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Correspondence to Kengo Takeuchi.

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This work was supported in part by The Ministry of Education, Culture, Sports, Science and Technology, the Japan Society for the Promotion of Science KAKENHI (25250020, 25871073) and the Japan Agency for Medical Research and Development. The authors declare that they have no conflict of interest with regard to this study.

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Sakamoto, K., Nakasone, H., Togashi, Y. et al. ALK-positive large B-cell lymphoma: identification of EML4-ALK and a review of the literature focusing on the ALK immunohistochemical staining pattern. Int J Hematol 103, 399–408 (2016). https://doi.org/10.1007/s12185-016-1934-1

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