title: ALK-positive large B-cell lymphoma: identification of EML4-ALK and a review of the literature focusing on the ALK immunohistochemical staining pattern.
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.
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan.|Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakasone
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan.|Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Togashi
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Sakata
authors.affiliation: Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Tsuyama
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Baba
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Dobashi
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan.|Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Reimi
authors.initials: R
authors.lastname: Asaka
authors.affiliation: Department of Anatomical Pathology, Far Eastern Memorial Hospital, New Taipei, Taiwan.
authors.forename: Chien-Chen
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: Department of Pathology, Chi-Mei Medical Centre, Tainan, Taiwan.|Department of Pathology, Taipei Medical University, Taipei, Taiwan.|National Taiwan University, Taipei, Taiwan.
authors.forename: Shih-Sung
authors.initials: SS
authors.lastname: Chuang
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Izutsu
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kanda
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan. kentakeuchi-tky@umin.net.|Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan. kentakeuchi-tky@umin.net.
authors.forename: Kengo
authors.initials: K
authors.lastname: Takeuchi
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000473:pathology*; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000032:analysis; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*
chemical_list: D015514:Oncogene Proteins, Fusion; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: Anaplastic lymphoma kinase; Anaplastic lymphoma kinase-positive large B-cell lymphoma; EML4-ALK; Fusion partner; Immunohistochemistry