High‐grade salivary gland carcinoma with the ETV6‐NTRK3 gene fusion: A case report and literature review of secretory carcinoma with high‐grade transformation

Abstract

Secretory carcinoma or mammary analog secretory carcinoma is an entity of salivary gland carcinoma that is characterized by the ETV6‐NTRK3 gene fusion. Although it is generally considered to be a low‐grade malignancy, some cases of secretory carcinoma with high‐grade transformation (SCHG) have been reported. We herein describe a case of SCHG composed almost exclusively of the high‐grade component. The patient presented with a growing mass in the buccal mucosa and underwent surgery. Tumor cells showing high‐grade nuclear atypia were arranged in solid or cribriform nests with comedo‐like necrosis. A differential diagnosis included high‐grade salivary gland carcinoma, such as salivary duct carcinoma. Immunohistochemically, tumor cells were focally positive for S‐100 and negative for mammaglobin and showed nuclear positivity for pan‐Trk. A reverse transcription polymerase chain reaction assay showed that the tumor harbored the ETV6‐NTRK3 gene fusion. A histological review of microscopic slides of the tumor did not reveal a typical secretory carcinoma component, except for a very focal area. We ultimately diagnosed this tumor as SCHG. This case underscores the importance of recognizing the histological spectrum of SCHG and the utility of pan‐Trk immunohistochemistry to detect secretory carcinoma, which may be targeted by tyrosine kinase inhibitors.

Pleural metastasis from parotid secretory carcinoma: First report of morphology on effusion cytology, and role of pan‐TRK immunohistochemistry

“…With increasing access to genetic testing, clinical outcomes of molecularly confirmed SC cases are better documented. Lymph node metastases occur in 5%–25% of cases, but distant metastases are rare, as summarized in Table 2 1,3–16 . Fifteen patients (68%) had metastasis to lungs and/or pleura.…”

“…Lymph node metastases occur in 5%-25% of cases, but distant metastases are rare, as summarized in Table 2. 1,[3][4][5][6][7][8][9][10][11][12][13][14][15][16] Fifteen patients (68%) had metastasis to lungs and/or pleura. Ten (48%) patients died of disease, while 4 (19%) had no evidence of disease at last follow-up; three of the latter had resectable lung metastases.…”

“…Local radiation is administered for large tumors, positive margins or perineural invasion. Regional lymph node metastasis has been described in 5%-25%, [3][4][5][6] while distant metastasis has been documented in 23 patients (Table 1) 1,[3][4][5][6][7][8][9][10][11][12][13][14][15][16] ; systemic chemotherapy may be implemented in these settings. 7,8 ETV6::NTRK3 rearrangement results in overexpression of tropomyosin receptor kinase C encoded by NTRK3.…”

Clinicopathological characteristics and outcomes of 23 patients with secretory carcinoma of major salivary glands

“…This may be related to differences in pathological features at different ages and the characteristically poor immune function of older patients 39 . In addition, prognosis becomes worse with increasing clinical stage and HG transformation 40 . HG-transformed SCSG is a considerably more aggressive tumor that follows an accelerated clinical course, resulting in local recurrences, cancer dissemination, and death 29 .…”

Liquid Biopsy in Head and Neck Cancer: Current Evidence and Future Perspective on Squamous Cell, Salivary Gland, Paranasal Sinus and Nasopharyngeal Cancers

“…Very few studies have been published regarding the use of liquid biopsy in salivary gland cancers, despite their frequently redundant hotspot alterations in certain entities such as salivary duct carcinoma (SDC), mucoepidermoid carcinoma (MEC), NTRK-driven mammary analog secretory carcinoma (MASC) or adenoid cystic carcinoma (ACC). Common alterations include HER2 amplification, androgen receptor (AR) overexpression, MYC amplification, PIK3CA mutations and NTRK fusions [ 57 , 58 , 59 , 60 ]. In a pilot study of 8 patients with ACC using a spiral microfluidics-based isolation method and detection by immunofluorescence, 3 patients (32.5%) were positive for CTC, each patient with either metastatic or recurrent disease [ 61 ].…”