Pleomorphic Adenoma with a Novel Gene Rearrangement-LINC01606::PLAG1

Abstract

Background: Pleomorphic adenoma is a well-known benign salivary gland neoplasm characterized by the presence of varying proportions of three different components, including bi-layered ducts, myoepithelial cells, and admixed within a chondromyxoid/fibrous stroma.

Method: We report an interesting case of an adult male who presented with bleeding from an extensively degenerated parotid gland mass, concerning for a vascular neoplasm versus primary malignant tumor. Microscopically, majority of the viable tumor exhibited diffuse proliferation of spindle to epithelioid cells, with focal areas depicting cribriform glands, ducts, and scant chondromyxoid stroma.

Result: Next-generation sequencing (NGS) RNA-based fusion panel analysis identified a gene rearrangement involving the pleomorphic adenoma gene 1 (PLAG1), with a novel, cryptogenic fusion partner known as LINC01606; [LINC01606::PLAG1; inv(8;8)(8q12.1;8q12.1)].

Conclusion: To the best of our knowledge, this is the first documented case of a long non-coding RNA (lnc-RNA) serving as a rearrangement partner with the PLAG1 gene. We reviewed the molecular characteristics of this entity and explored the potential role of LINC01606::PLAG1 in the tumorigenesis of pleomorphic adenoma.

Keywords: Gene rearrangement; LINC01606; PLAG1; Pleomorphic adenoma.

Fig. 1

Computed tomographic image shows an 8.7-cm right parotid circumscribed complex cystic mass (arrows) with heterogeneous internal enhancement

Fig. 2

Histologic section shows circumscribed mass with a thick fibrotic wall, hemorrhage, and cystic degeneration (2a, hematoxylin and eosin (H&E) stain, total magnification × 20). In viable areas, the lesional cells are spindle to epithelioid, without atypia, in the background of myxoid and hyalinized stroma (2b, H&E, × 100). In focal areas, cribriform nests and ducts/glands are identified (2c-d, H&E, × 100)

Fig. 3

Schematic representation of the structure of the human PLAG1 gene and its protein. On the top, chromosome 8 is shown with a red-highlighted area of band 8q12.1. The introns are represented by a line and exons by boxes. The orange-shaded area of exon 4 and exon 5 shows the translated region. Numbers refer to the number of base pairs. In the protein structure at the bottom, numbers refer to the number of amino acids and lightly shaded boxes indicated by ‘ZF’ represent the seven zinc finger domains. Structure is based on the Ensembl sequences ENST00000316981.8