Clinicopathological investigation of secretory carcinoma cases including a successful treatment outcome using entrectinib for high-grade transformation: a case report

BMC Medical Genomics

Hiroshi Harada¹  Akihiko Kawahara²  Masayuki Takeda³  Akira Kanda⁴  Shunsuke Sawada⁴  Kensuke Suzuki⁴  Hiroshi Iwai⁴  Chisato Ohe⁵  Yoshiko Uemura⁵  Bhaswati Sengupta⁶ 

[1] Department of Diagnostic Pathology and Cytology, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, 541-8567, Osaka, Japan;Department of Diagnostic Pathology, Kurume University Hospital, 67 Asahi-machi, 830-0011, Kurume, Fukuoka, Japan;Department of Medical Oncology, Kinki University, 377-2, Ono-higashi, 589-8511, Osaka-Sayama, Osaka, Japan;Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, 2-5-1, Shin-machi, 573-1010, Hirakata, Osaka, Japan;Department of Pathology, Kansai Medical University, 2-5-1, Shin-machi, 573-1010, Hirakata, Osaka, Japan;IVD Assay Development Department, ArcherDX, LLC, an Invitae Company, 2477 55th Street, Suite 202, 80301, Boulder, CO, USA;

关键词: Secretory carcinoma;    Salivary gland;    High-grade transformation;    Next-generation sequencing;    ETV6-NTRK3;    Entrectinib;   

DOI  :  10.1186/s12920-022-01155-6

来源: Springer

【 摘 要 】

BackgroundSecretory carcinoma (SC) of the salivary gland is a recently described malignant tumor harboring characteristic ETV6-NTRK3 gene fusion. SC generally has a favorable clinical course, and is currently regarded as a low-grade carcinoma. However, a small subset of SCs demonstrates aggressive clinical features with histologically high-grade transformed morphology, the molecular pathogenesis of which has not yet been elucidated. In this study, we performed a clinicopathological and molecular genetic study of patients with SC of the head and neck displaying various clinical characteristics to investigate the differences of pathological and molecular genetics between low-grade and high-grade components of SC.Case presentationThree cases with SC of the head and neck, including a conventional low-grade SC and two high-grade transformed SCs are described. High-grade transformed SCs with histological features such as nuclear polymorphism, distinctive nucleoli and increased mitotic activity developed locoregional recurrence and distant metastasis. Immunohistochemical analysis revealed that low- and high-grade components showed different expression patterns for S-100 protein and mammaglobin, whereas all examined components were positive for p-STAT5. p53-positive cell population was markedly higher in one case with high-grade transformed SC. The proliferative activity of high-grade components was markedly increased, with the Ki-67 labeling index ranging up to 30–32%. A fluorescence in situ hybridization study with an ETV6 (12p13) break apart probe revealed split signals in the nuclei in all 3 cases. A targeted next-generation sequencing-based fusion assay demonstrated that all 6 clinical samples from the 3 patients showed the presence of the ETV6-NTRK3 fusion transcripts. One patient with high-grade transformed SC showed a dramatic clinical response to the pan-TRK inhibitor, entrectinib, for the treatment of locoregional recurrence and pulmonary metastasis.ConclusionsHigh-grade transformed SC showed aggressive clinical and pathological features with increased Ki-67 labeling index. Molecular genetic study of gene rearrangement appears to be beneficial treatment as the presence of ETV6-NTRK3 translocation may represent a therapeutic target in SC, particularly the high-grade transformed type.

【 授权许可】

CC BY