Division of Cytopathology, Department of Pathology, The Johns Hopkins Medical Institution, Johns Hopkins Hospital, Baltimore, Maryland, USA.
Acta Cytol. 2024;68(3):194-205. doi: 10.1159/000538069. Epub 2024 Feb 28.
Salivary gland lesions possess diagnostic challenges on fine-needle aspiration (FNA) material. They are relatively uncommon, yet present with a wide spectrum of cytomorphology. Herein, we review common salivary gland neoplasms, their cytomorphologic features, their diagnostic pitfalls, and ancillary studies helpful in achieving an accurate diagnosis.
There are many cytomorphologic overlaps between benign and malignant salivary gland entities. Moreover, metaplasia, cystic changes, and degenerative changes are common findings adding to diagnostic dilemmas. These complicating factors contribute to a minute risk of malignancy in salivary gland lesions that are interpreted as benign on FNA. In rare cases, even malignant salivary gland neoplasms are misinterpreted as benign on aspirated material due to the many cytomorphologic overlaps. For example, benign and malignant neoplasms containing stroma such as myoepithelioma and adenoid cystic carcinoma may be misinterpreted as pleomorphic adenoma. Moreover, diagnosis of salivary gland neoplasms with basal cell features can be confusing on FNA materials; for example, basal cell adenoma can be misinterpreted as adenoid cystic carcinoma. Mucoepidermoid carcinomas have many different appearances on aspirated material due to variable amounts of mucin, degree of nuclear atypia, cellular content, and squamous metaplasia. Acinic cell carcinoma exhibits large cells with abundant cytoplasm on FNA, which can be mistaken for oncocytic cells in oncocytoma or Warthin tumor. Salivary duct carcinoma shows distinct features of malignancy and thus can be mistaken for secondary tumors involving the salivary glands or other malignant salivary gland tumors. The presence of tumor-associated lymphocytes is another underlying cause of misdiagnosis, especially when considering the differential diagnosis of an intraparotid lymph node. Ancillary studies such as immunohistochemistry and molecular studies are gaining more attention to be utilized on FNA cases. PLAG1 immunostaining, CD117, DOG1, mammaglobin, and androgen receptor (AR) are examples of commonly used immunostains in diagnosis of salivary gland lesions. MYB gene fusion, rearrangements of the MAML2 gene, and ERBB2/HER2 are examples of molecular alterations useful in diagnosis of salivary gland neoplasms. In conclusion, the aim of salivary gland cytology is to differentiate benign entities from the malignant ones and to prevent unnecessary aggressive treatments.
The diagnostic pitfalls are enormous in salivary gland cytology. Familiarity with cytomorphology of different entities and their cytomorphologic overlaps, and application of ancillary studies improves the diagnostic yield, patient management and prevents unnecessary aggressive procedures.
在细针吸取细胞学（FNA）标本中，唾液腺病变具有诊断挑战。它们相对少见，但具有广泛的细胞形态学特征。在此，我们回顾了常见的唾液腺肿瘤，它们的细胞形态学特征、诊断陷阱以及有助于做出准确诊断的辅助研究。
良性和恶性唾液腺实体之间存在许多细胞形态学重叠。此外，化生、囊性变和退行性变是常见的发现，增加了诊断的困境。这些复杂因素导致在 FNA 中被诊断为良性的唾液腺病变中存在微小的恶性风险。在极少数情况下，即使是恶性唾液腺肿瘤也会因许多细胞形态学重叠而在抽吸材料上被误诊为良性。例如，含有间质的良性和恶性肿瘤，如肌上皮瘤和腺样囊性癌，可能被误诊为多形性腺瘤。此外，在 FNA 标本中，具有基底细胞特征的唾液腺肿瘤的诊断可能会令人困惑；例如，基底细胞腺瘤可能被误诊为腺样囊性癌。由于黏液含量、核异型性程度、细胞含量和鳞状化生程度的不同，黏液表皮样癌在抽吸物中有许多不同的表现。在 FNA 中，分泌细胞癌表现为大细胞，富含细胞质，可能被误诊为嗜酸细胞瘤中的嗜酸细胞瘤或沃辛瘤。涎腺导管癌具有明显的恶性特征，因此可能被误诊为累及唾液腺的继发性肿瘤或其他恶性唾液腺肿瘤。肿瘤相关淋巴细胞的存在是误诊的另一个潜在原因，特别是在考虑腮腺内淋巴结的鉴别诊断时。免疫组织化学和分子研究等辅助研究越来越受到重视，并在 FNA 病例中得到应用。PLAG1 免疫染色、CD117、DOG1、乳球蛋白和雄激素受体（AR）是诊断唾液腺病变常用的免疫染色方法的例子。MYB 基因融合、MAML2 基因重排和 ERBB2/HER2 是诊断唾液腺肿瘤有用的分子改变的例子。总之，唾液腺细胞学的目的是区分良性实体和恶性实体，并防止不必要的侵袭性治疗。
唾液腺细胞学的诊断陷阱是巨大的。熟悉不同实体的细胞形态学及其细胞形态学重叠，并应用辅助研究可提高诊断率、患者管理，并防止不必要的侵袭性程序。
