Salivary Gland Secretory Carcinoma With High-Grade Transformation, CDKN2A/B Loss, Distant Metastasis, and Lack of Sustained Response to Crizotinib

Int J Surg Pathol. 2017 Oct;25(7):613-618. doi: 10.1177/1066896917709350. Epub 2017 May 12.


Background: Salivary gland secretory carcinoma is usually a low-grade neoplasm. However, high-grade transformation can occur and has important implications for clinical outcome.

Methods: A patient presented with an enlarging buccal mass. Magnetic resonance imaging (MRI) showed a tumor with a biphasic appearance along the right parotid duct. Local excision and histopathologic examination confirmed the diagnosis of secretory carcinoma with high-grade transformation. ETV6-NTRK3 translocation and loss of CDKN2A/B were identified.

Results: The patient subsequently presented with cough and dyspnea and was found to have pleural metastases. Carboplatin and paclitaxel exacerbated the symptoms. Crizotinib resulted in initial symptomatic and radiographic improvement; however, the patient soon succumbed to progressive intrathoracic disease.

Conclusions: High-grade salivary gland secretory carcinoma can have a biphasic appearance on MRI. Diagnosis is confirmed by the histologic appearance and associated ETV6-NTRK3 fusion. Additional molecular genetic events leading to transformation are unknown; however, loss of CDKN2A/B may have contributed. Treatment with multimodal chemotherapy was of limited benefit.

Keywords: CDKN2A/B; MRI; crizotinib; high grade; metastatic; salivary gland; secretory carcinoma.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma, Clear Cell / diagnosis
  • Adenocarcinoma, Clear Cell / pathology
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Crizotinib
  • Cyclin-Dependent Kinase Inhibitor p15 / deficiency
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18 / deficiency
  • Cyclin-Dependent Kinase Inhibitor p18 / genetics
  • Diagnosis, Differential
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Fatal Outcome
  • Gene Rearrangement
  • Humans
  • Immunohistochemistry
  • Magnetic Resonance Imaging
  • Male
  • Mammary Analogue Secretory Carcinoma / diagnosis
  • Mammary Analogue Secretory Carcinoma / genetics
  • Mammary Analogue Secretory Carcinoma / secondary*
  • Mammary Analogue Secretory Carcinoma / therapy
  • Myoepithelioma / diagnosis
  • Myoepithelioma / pathology
  • Oncogene Proteins, Fusion / genetics
  • Parotid Gland / pathology
  • Parotid Gland / surgery
  • Pleural Neoplasms / diagnosis
  • Pleural Neoplasms / genetics
  • Pleural Neoplasms / secondary*
  • Pleural Neoplasms / therapy
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use
  • Pyridines / pharmacology
  • Pyridines / therapeutic use
  • Salivary Gland Neoplasms / diagnosis
  • Salivary Gland Neoplasms / genetics
  • Salivary Gland Neoplasms / pathology*
  • Salivary Gland Neoplasms / therapy
  • Translocation, Genetic
  • Treatment Outcome


  • CDKN2A protein, human
  • CDKN2B protein, human
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18
  • ETV6-NTRK3 fusion protein, human
  • Oncogene Proteins, Fusion
  • Pyrazoles
  • Pyridines
  • Crizotinib