A case report and genetic characterization of a massive acinic cell carcinoma of the parotid with delayed distant metastases

Abstract

We describe the presentation, management, and clinical outcome of a massive acinic cell carcinoma of the parotid gland. The primary tumor and blood underwent exome sequencing which revealed deletions in CDKN2A as well as PPP1R13B, which induces p53. A damaging nonsynonymous mutation was noted in EP300, a histone acetylase which plays a role in cellular proliferation. This study provides the first insights into the genetic underpinnings of this cancer. Future large-scale efforts will be necessary to define the mutational landscape of salivary gland malignancies to identify therapeutic targets and biomarkers of treatment failure.

Figure 1

Anterior (a) and lateral (b) pictures of the patient at presentation. Axial (c) and coronal (d) CT scan images of the primary tumor. Note extension of the tumor into the parapharyngeal space with occlusion of the jugular vein (black arrowhead) and skull base involvement (white arrowhead).

Figure 2

Intraoperative photographs demonstrating the radical parotidectomy with facial nerve sacrifice (a and b). (a) The large arrowhead indicates the divided jugular vein. (b) The single arrowhead (white) again marks the divided jugular vein, the double arrowhead (white) indicates residual tumor at the jugular foramen, and the black arrowhead indicates the divided end of the accessory nerve that was grafted to a cervical rootlet. (c) Temporal bone resection with surgicel occluding the sigmoid sinus (white arrowhead) and a fascia and muscle plug occluding the eustachian tube (black arrowhead). Demonstration of the primary tumor (d) and reconstruction with a large cervicofacial advancement flap and radial forearm free flap ((e) arrow marks forearm flap skin paddle).

Figure 3

Axial CT scan images of the thorax (panels (a) and (b)) demonstrating the interval development of pulmonary metastases (arrowheads).

Figure 4

Somatic whole exome sequencing results across the genome. Vertical lines represent the single-nucleotide variants, while the points represent copy-number variant calls. Significant CNVs are represented by the green dots with its size reflecting its significance. Segmented copy-number variants are depicted in red and show clear gains in chromosome 2 and chromosome 9.