Objectives: Adenoid cystic carcinoma (ACC) of the minor salivary glands is rare. Perineural invasion and distant metastasis are hallmark features that characterize ACC in major salivary glands, but little is known about minor salivary gland clinicopathological behavior. The most important cause of morbidity and mortality associated with ACC is distant metastatic disease. Predicting patients at high risk will allow tailored surveillance.
Methods: Following IRB approval, a retrospective analysis of all adenoid cystic carcinomas of the minor salivary glands in the head and neck at our institution was performed. Data were collected on patient and tumor characteristics including age, comorbidities, TNM stage and pathological details. Predictive factors were investigated by calculating Hazard ratios using univariate and multivariable Cox regression.
Results: Between 1979 and 2015, there were 143 patients with ACC of the minor salivary glands treated with primary surgery at our institution, of which 62 (43%) were male. There were 83 (58%) patients with tumors in the oral cavity, 24 (16.8%) in the nasal cavity and paranasal sinuses, 29 (20.3%) in the pharynx and 7 (4.9%) in the larynx / trachea.
Forty-three (30%) patients developed distant metastases. These were located in the lung in 29 patients, bone in 5 patients, liver in 3, brain in 2, liver and lung in 3 and 1 patient had a lung and kidney metastasis. The median time to distant metastases was 35.15 months (range 1.41-303.11 months). The five and ten-year distant recurrence free survival were 75.7% and 62.0%, respectively.
On univariate analysis, clinical factors predictive of outcome were clinical T-stage (p=0.026) and clinically positive node status (p<0.001). Pathological factors predictive of outcome were pT-stage (p=0.007) and positive lymph nodes (p=0.009). The presence of microscopic perineural invasion was associated with 3.45 increased risk of distant failure (95% CI 0.82-14.50), but this was not significant (p=0.09). On multivariable analysis, patients with clinical T3 and T4 tumors were 2.25 times more likely to have a distant recurrence (95% CI 1.21-4.17, p=0.010), while patients with a clinically positive neck were 7.07 times more likely (95% CI 3.18-15.73, p<0.001). For pathological T and N stage, multivariable analysis showed patients with T3 and T4 tumors were 2.98 times more likely to fail distantly than early stage tumors (95% CI 1.53-5.82, p=0.001). And, patients with a pathologically positive neck were 2.81 times more likely to have a distant recurrence (95% CI 1.29-6.14, p=0.010).
Conclusions: The occurrence of distant metastases from minor salivary gland tumors is common, occurring in 30% of patients. For this rare cohort of patients, advanced t-stage and positive neck disease were the most important predictive factors.