Insulin-like Growth Factor II mRNA-binding Protein 3 is a Highly Sensitive Marker for Intravascular Large B-cell Lymphoma

Author:

Saka Manduwa1,Fujimoto Masakazu1,Mizoguchi Kai1,Tsujimura Marina1,Saeki Miho1,Hirata Masahiro1,Shibuya Shinsuke2,Odani Kentaro3,Sakurai Takaki3,Yuba Yoshiaki4,Moriyoshi Koki5,Nakajima Naoki6,Sumiyoshi Shinji7,Kono Fumihiko8,Ono Kazuo9,Shirase Tomoyuki10,Watanabe Chihiro11,Yoshizawa Akihiko112,Haga Hironori1

Affiliation:

1. Department of Diagnostic Pathology, Kyoto University Hospital

2. Department of Diagnostic Pathology, Kyoto Katsura Hospital

3. Department of Diagnostic Pathology, Osaka Red Cross Hospital

4. Department of Pathology, Medical Research Institute, Kitano Hospital

5. Department of Diagnostic Pathology, National Hospital Organization Kyoto Medical Center

6. Department of Diagnostic Pathology, Toyooka Hospital, Hyogo

7. Department of Diagnostic Pathology, Tenri Hospital, Tenri

8. Department of Diagnostic Pathology, Uji-Tokushukai Medical Center, Kyoto

9. Department of Diagnostic Pathology, Japanese Red Cross Wakayama Medical Center, Wakayama

10. Department of Pathology, Otsu Red Cross Hospital, Shiga, Japan

11. Department of Diagnostic Pathology, Takatsuki Red Cross Hospital, Osaka

12. Department of Diagnostic Pathology, Nara Medical University, Nara

Abstract

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of aggressive extranodal large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumina of blood vessels, particularly capillaries. IVLBCL lacks mass formation, and its diagnosis can be challenging. We analyzed the utility of insulin-like growth factor II mRNA-binding protein 3 (IMP3) immunohistochemistry for IVLBCL diagnosis in various organs. Double staining with paired box 5 (PAX5) was performed for validation. Overall, 152 pathological specimens (111 positive and 41 negative for IVLBCL) obtained from 88 patients with a diagnosis of IVLBCL were stained for IMP3 and IMP3/PAX5. As negative controls, 40 pathology specimens from 38 patients with no history of IVLBCL or other B-cell lymphomas were stained for IMP3, which comprised 31 benign pathological specimens from 29 patients in whom malignancy was suspected, 7 cases of appendicitis with intravascular and/or intralymphatic lymphoid proliferations, and 2 cases of intravascular natural killer/T-cell lymphoma. All mononuclear cells with cytoplasmic staining were considered positive for IMP3 expression, but expression restricted to germinal center B cells was excluded from evaluation. All 111 IVLBCL pathological specimens were positive for IMP3 and IMP3/PAX5. In addition, 11 of the 41 specimens originally diagnosed as IVLBCL-negative showed IMP3/PAX5 double-positive cells, raising the suspicion of IVLBCL. However, of the 40 negative control samples, IMP3-positive non–germinal center B cells were detected in only 2 samples (P = 0.0131) and no intravascular IMP3-positive B cells suspicious for IVLBCL were identified. Altogether, IMP3 immunohistochemistry is a highly sensitive marker of IVLBCL and can be a helpful adjunct for IVLBCL diagnosis.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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