Malignant transformation of salivary gland pleomorphic adenoma: proof of principle

Abstract

Supposed risk of malignant transformation of salivary gland pleomorphic adenoma (SGPA) is an important reason for aggressive retreatment in recurrent pleomorphic adenoma (RPA). However, although the diagnostic category ‘carcinoma ex‐pleomorphic adenoma’ suggests that malignant transformation of a pleomorphic adenoma is a regular event, this has to date not been shown to occur in sequential lesions of one patient. Here, we show the molecular events in transformation to malignancy of a pleomorphic adenoma of the parotid gland. Detailed molecular analysis revealed an LIFR/PLAG1 translocation characteristic for pleomorphic adenoma and, next to this, a PIK3R1 frameshift mutation and several allelic imbalances. In subsequent malignant recurrences, the same LIFR/PLAG1 translocation, PIK3R1 frameshift mutation, and allelic imbalances were present in addition to TP53 mutations. Thus, this case not only shows malignant transformation of SGPA, but also demonstrates that molecular analysis can be of help in recognising malignancy in the rare instance of RPA.

Frequent apocrine changes in pleomorphic adenoma with malignant transformation: a possible pre-malignant step in ductal carcinoma ex pleomorphic adenoma

“…We could not find any characteristic patterns of p53 overexpression in this series between PA and CPA, in contrast to a previous report on p53 positivity in focal carcinoma and atypical tumor cells in PA [ 3 ]. Other studies revealed that TP53 mutations were accompanied by malignant transformation of PA [ 5 , 30 ], but protein expression was ubiquitous in both PAs and CPAs in our study. Expression of p53 alone did not indicate carcinomatous transformation.…”

Surgical Treatment of a Giant Pleomorphic Adenoma of the Submandibular Gland: A Case Report

“…What should not be neglected is that in 5–10% of patients, a pleomorphic adenoma can transform into a carcinoma (known as carcinoma ex pleomorphic adenoma), which most often develops in the parotid gland and represents 2–3% of all parotid neoplasms ( 3 , 24 ). This malignant transformation is more common in recurrent pleomorphic adenomas.…”

La celularidad y su relación con las características capsulares como factor influyente en las estrategias operatorias del adenoma pleomorfo

“…TP53 mutations are also related to malignant transformation of pleomorphic adenoma. The identified mutations p.R248Q and p.Y220C are known to exert a dominantnegative effect on the complete inactivation of TP53 31 . Loss of TP53 function is the most common molecular initiation and progression in human malignancies.…”