Usefulness of translocation-associated immunohistochemical stains in the fine-needle aspiration diagnosis of salivary gland neoplasms

Background: Fine-needle aspiration diagnosis of pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) is challenging due to cytologic overlap with one another and with other salivary gland tumors having prominent epithelial and myoepithelial components. Recognition of characteristic chromosomal aberrations in several salivary gland tumors, including PA and ACC, has the potential to resolve diagnostic uncertainty, but molecular diagnostics are not routinely available. To leverage these molecular alterations, the authors examined a panel of commercially available immunostains directed at commonly overexpressed proteins in translocation-associated PA (PLAG1 and HMGA2) and ACC (MYB) to assess their diagnostic usefulness.

Methods: Immunohistochemistry was performed on cell block samples from 74 patients, including 11 ACC specimens and 31 PA specimens with antibodies to MYB, PLAG1, and HMGA2 as well as KIT (previously considered useful in the diagnosis of ACC).

Results: ACCs demonstrated significantly greater staining for KIT compared with non-ACCs, while PAs had significantly greater staining for PLAG1 than non-PAs. MYB trended toward significance for ACC (P=.097) and HMGA2 trended toward significance for PA (P=.094). No ACC exhibited positive staining for PLAG1 or HMGA2. Only 12% of PAs were found to be positive for MYB or KIT. Combined positivity for MYB and KIT with negative PLAG1 and HMGA2 demonstrated a specificity and positive predictive value of 1.0 for ACC, whereas a positive PLAG1 or HMGA2 stain with negative MYB and KIT stains showed a sensitivity of 0.75, a specificity of 0.96, and a positive predictive value of 0.95 for PAs.

Conclusions: An immunohistochemical panel of MYB, KIT, PLAG1, and HMGA2 on fine-needle aspiration cell blocks is useful in distinguishing ACCs and PAs from each other and other salivary gland neoplasms. Cancer Cytopathol 2016;124:397-405. © 2016 American Cancer Society.