Predictors of Outcome in Adenoid Cystic Carcinoma of Salivary Glands: A Clinicopathologic Study With Correlation Between MYB Fusion and Protein Expression

Abstract

Adenoid cystic carcinoma (ACC) is the second most common salivary gland malignancy and it has a high rate of recurrences and a poor long-term prognosis. Our aim was to assess the prognostic factors in ACC and study MYB-NFIB fusion and MYB protein expression in a large retrospective cohort of 135 patients with a median follow-up of 6.3 years. The 5- and 10-year local recurrence-free survival (RFS) rate of 94% and 78%, 5- and 10-year distant metastasis survival rate of 77% and 58%, and 5- and 10-year RFS of 66% and 44%. The following features were identified as adverse prognostic factors of RFS on univariate analysis: large tumor size, solid growth pattern, increased mitoses, positive margin, American Joint Committee on Cancer clinical staging, high-grade transformation, vascular invasion, nuclear atypia, open chromatin, prominent nucleoli, and tumor necrosis. However, on multivariate analysis, only increased mitoses (≥5/10 high-power fields), any solid growth pattern, and advanced American Joint Committee on Cancer TNM staging were independent adverse predictors for RFS. MYB immunoexpression and MYB-NFIB translocation were common findings in ACC, occurring in 72% and 59% of the tested ACCs, respectively. The sensitivity and specificity of MYB immunohistochemistry in detecting MYB-NFIB fusion was relatively low at 78% sensitivity and 50% specificity. The high prevalence of alterations leading to high expression of the MYB transcription factor family suggests that targeted approaches developed to suppress the expression of these oncogenic transcription factors and/or the transcriptional activity of these proteins would be a rational therapeutic approach to investigate in ACC.

Figure 1. Histologic features of adenoid cystic carcinoma

(A,B) An adenoid cystic carcinoma exhibited predominantly tubular (T) and cribriform (Cr) growth patterns (hematoxylin an eosin stain, magnification 100x in panel A and C, 200X in panels B, D, and F, and 400X in panel E). Myxoid and hyalinized basement membrane material is noted in the cribriform area. (C) Solid growth pattern (So) of adenoid cystic carcinoma. (D,E) High grade transformation of adenoid cystic carcinoma, showing comedo-type tumor necrosis (N), brisk mitotic activity (arrow heads), nuclear atypia and loss of biphasic ductal-myoepithelial differentiation. (F) MYB immunostain is strongly positive in myoepithelial cells.

Figure 2. Kaplan Meier curves for recurrence free survival

Univariate and multivariate analyses showed that solid growth pattern (A), an elevated mitotic index (B) their co-occurrence (C) and advanced AJCC clinical staging (D) were adverse prognostic factors in adenoid cystic carcinoma.

Figure 3. The prognostic significance of solid pattern (A/B) and mitotic index (C/D)

Adenoid cystic carcinomas with any solid growth pattern were associated with significantly worse disease specific survival (p < 0.001, A) and recurrence free survival (p < 0.001, B). Tumors with >30% of solid architectures had similar prognosis compared to tumors with 1–30% of solid component (p = 0.36). (C/D) Mitotic index predicted DSS and RFS.