Cystic Salivary Gland Neoplasms: Diagnostic Approach With a Focus on Ancillary Studies

Abstract

Cystic salivary gland cytology can be challenging due to the fact that a cystic mass can be the clinical presentation of both non-neoplastic and neoplastic conditions. Neoplastic lesions consist of both benign and malignant neoplasms. The cytomorphologic features of these entities can overlap and the cystic background may additionally contribute to the complexity of these lesions and their interpretation. Ancillary studies have been reported in several studies to be beneficial in further characterization of the cellular components and subsequent diagnosis of the cystic lesions of the salivary gland. Fluorescence in situ hybridization, real-time polymerase chain reaction, and next-generation sequencing are now being utilized to detect molecular alterations in salivary gland neoplasms. MALM2 rearrangement is the most common gene fusion in mucoepidermoid carcinoma. PLAG1 rearrangement is present in more than half of pleomorphic adenomas. AKT1:E17K mutation is the key diagnostic feature of the mucinous adenocarcinoma. NR4A3 overexpression is highly sensitive and specific for the diagnosis of acinic cell carcinoma. MYB fusion is noted in adenoid cystic carcinoma. ETV6:NTRK3 fusion is helpful in diagnosis of secretory carcinoma. p16 and human papillomavirus (HPV) studies differentiate HPV-related squamous cell carcinoma from non-HPV-related neoplasms with overlapping features. NCOA4:RET fusion protein is the main fusion in intraductal carcinoma.

Macrocystic and non-necrotic salivary duct carcinoma of the submandibular gland: A case report

“…However, in this case, we investigated whether it was possible to arrive at a qualitative diagnosis based on findings of CT images. Clinically, differential diagnoses of cystic lesions in major salivary glands includes various benign and malignant conditions, including human immunodeficiency virus (HIV) infection, Sjögren syndrome [11] , lymphoepithelial cyst [12] , cystadenoma, adenoid cystic carcinoma, acinic cell carcinoma, intraductal carcinoma, mucoepidermoid carcinoma, and secretory carcinoma [ 6 , 13 , 14 ]. CT findings of cystic lesions in major salivary glands are summarized in Table 1 .…”

“…No similar cases have been reported in the past. The clinicopathological findings of our case are presented and discussed in relation to distinguishing features from cystic salivary gland neoplasms [6] , including intraductal carcinoma.…”

Pitfalls in Salivary Gland Cytology

“…Differential diagnosis for ADCa encompasses several benign entities, such as PA, basal cell adenoma, myoepithelioma, lymphadenoma, and cystadenoma [17,28,34,36,37]. Basal cell adenoma is characterized by large fragments of cohesive basaloid cells surrounded by a rim of basement-like matrix such as Figure 3d.…”

“…It is important to be aware that these benign entities might exhibit high nuclear-to-cytoplasmic ratios and matrix material on cytological examination, potentially leading to overdiagnosis. Basaloid neoplasms, in particular, have demonstrated limited interobserver agreement and can pose diagnostic challenges overall [37,38]. Distinctions are also important when attempting to differentiate between PA and ADCa.…”

“…Several ancillary studies can aid in the diagnosis of ADCa. For instance, most cases of ADCa display positivity for CD117, with a sensitivity of 82-89% and a specificity of approximately 87% [34,37]. Additionally, ADCa is characterized by a MYB gene fusion, which can be detected using various methods such as IHC, FISH, or RT-PCR [7, 11,35].…”