Molecular analysis using SalvGlandDx improves risk of malignancy estimation and diagnosis of salivary gland cytopathology: An exploratory multicenter study

Abstract

BackgroundDiagnosis of salivary gland neoplasms is challenging, especially on cytological specimens acquired by fine‐needle aspiration. The recently implemented standardized Milan system for reporting salivary gland cytopathology provides an estimated risk of malignancy (ROM); yet, for two of the categories, the diagnosis of the lesion remains unclear. However, a precise diagnosis is desirable for optimal patient management, including planning of surgery and imaging procedures.MethodsCytological specimens (n = 106) were subjected to molecular analysis using the SalvGlandDx panel. The risk of malignancy was calculated for each detected alteration based on the diagnosis of the resection specimen. By taking into account the molecular alterations, their associated ROM, the clinical and cytological features, and the current literature, the Milan category was evaluated.ResultsOf n = 63 technically valid cases, 76% revealed a molecular alteration. A total of 94% of these molecularly altered cases could be assigned to a different Milan category when additionally taking molecular results into account. In only 2% of the salivary gland neoplasms of uncertain malignant potential, in which a molecular alteration was detected, the classification remained salivary gland neoplasms of uncertain malignant potential.ConclusionMolecular analysis of cytological specimens provides a benefit in classifying salivary gland neoplasms on fine‐needle aspiration. It can improve the ROM estimation and thus help to assign cases of formerly unknown malignant potential to clearly benign or malignant categories.

Is molecular testing of salivary gland FNA specimens ready for prime time?

“…Interestingly, only five cases of Milan category III (atypia of undetermined significance) were included in the study, and the single analyzable case by NGS, corresponding to nodular oncocytic hyperplasia as final diagnosis, revealed no molecular alteration. 19 This highlights the difficulty of performing successful ancillary studies in this indeterminate diagnostic category, in which samples are often compromised by the scant cellularity, and supporting the role of a repeat FNA for these challenging cases. 1 In summary, the study by Freiberger et al 19 contributes to characterizing the molecular spectrum of indeterminate lesions in salivary gland FNA.…”

“…19 This highlights the difficulty of performing successful ancillary studies in this indeterminate diagnostic category, in which samples are often compromised by the scant cellularity, and supporting the role of a repeat FNA for these challenging cases. 1 In summary, the study by Freiberger et al 19 contributes to characterizing the molecular spectrum of indeterminate lesions in salivary gland FNA. However, it represents only a limited selection of challenging/indeterminate cases and additional studies are necessary to validate these findings and especially when determining the ROM for certain genetic alterations (e.g., PLAG1).…”

“…9,19 PLAG1 fusions have been also described in approximately 40% of myoepitheliomas and myoepithelial carcinomas, showing the molecular similarities of these tumors and emphasizing the importance of molecular-morphological correlation. 3,4,19 Although only a few cases of MAML2, ETV6, and MYB rearranged neoplasms were included in their study, the ROM associated with these alterations was 100%. 19 Regarding gene mutations, the most common one in their series was HRAS, and all cases were subsequently diagnosed as malignant in the resection specimens, including epithelial-myoepithelial carcinoma, salivary duct carcinoma, or intraductal carcinoma.…”

“…3,4,19 Although only a few cases of MAML2, ETV6, and MYB rearranged neoplasms were included in their study, the ROM associated with these alterations was 100%. 19 Regarding gene mutations, the most common one in their series was HRAS, and all cases were subsequently diagnosed as malignant in the resection specimens, including epithelial-myoepithelial carcinoma, salivary duct carcinoma, or intraductal carcinoma. 18 Thus, the ROM for HRAS mutations in their cohort was 100%.…”

“…In their exploratory multicenter study, Freiberger et al 19 1 The only malignant case in their series was a salivary duct carcinoma ex pleomorphic adenoma (PA) with HMGA2 rearrangement. However, the case demonstrated cytologic atypia, and was therefore morphologically classified as Milan V. Although nonspecific for PA, the PLAG1-positive cases were most frequently found in PA.…”