International Collaborative Validation of Intraneural Invasion as a Prognostic Marker in Adenoid Cystic Carcinoma of the Head and Neck

Abstract

Background. The purpose of this study was to characterize the incidence, pattern of spread, and prognostic correlation of nerve invasion in patients with adenoid cystic carcinoma (ACC). Methods. Using 3 different pathological categories of perineural invasion, intraneural invasion, and perineural inflammation, we investigated the prognostic value of nerve invasion in a total of 495 ACCs from 9 international patient cohorts with median follow-up 90 months (range, 12-288 months). Results. Of 239 patients (48%) with nerve invasion, 174 (73%) had perineural invasion, 65 (27%) intraneural invasion, and 37 (15%) perineural inflammation. Multivariate Cox regression analysis identified tumor site (p 5 .008; hazard ratio [HR] 5 1.8; 95% confidence interval[CI] 5 0.07-3.7) and intraneural invasion (p < .001; HR 5 5.9; 95% CI 5 0.8-12.3) as independent prognostic markers for both overall survival (OS) and disease-specific survival (DSS), but not of distant metastases. Conclusion. Although perineural invasion has no impact on survival, intraneural invasion is an independent predictor of poor prognosis. Recognition of intraneural invasion may help optimize treatment of patients with head and neck ACC.

Adenoid Cystic Carcinoma in a Mexican Population

“…According to previous studies, ACC is located mainly in intraoral minor salivary glands, followed by extraoral minor glands and by major salivary glands; however, we had a predominance of cases originating in extraoral minor glands, as maxillary sinus was the most frequently affected region [1,6]. The sites reported as those with the worse prognosis are nasal cavity and larynx, possibly because in these areas tumors have attained a larger size at diagnosis and are more complex for surgical management and to get free margins [7]; however, in this study differences in location was not found as a prognostic factor [8].…”

“…Only 5.6 % of our cases had positive adenopathy at surgery. Recent reports [7,14] have shown no survival advantage for patients undergoing elective neck dissection for ACC. Positive margins are also considered a prognostic factor for recurrence.…”

“…This situation opens to debate whether an elective neck dissection is warranted, in the absence of clinical suspicion of N?. This problem is illustrated in the study of Amit et al [7], in which one may consider that there was overtreatment in a significant number of cases, as only 29 out of 38 patients who had N1 at diagnosis were histopathologically positive when they performed 272 neck dissections considered as therapeutic and elective procedures. Despite this, the authors claim that these were justified.…”

“…However, it has not been associated with a worse prognosis in terms of overall survival. It remains to determine whether perineural invasion is indeed associated with positive margins and recurrence, or if it is an independent focal phenomenon, but some results suggest that the tendency of a tumor to disseminate along nerves is not associated with its ability for local invasion and proliferation, but is rather associated with positive margins [7]. These facts were also found in our analysis, where perineural invasion had no impact on survival, a finding which we consider was because worse prognosis is not due to local recurrence, but due to metastatic disease, and this is particularly important when the lung is the preferred site, which has significant prognostic value, as has been previously reported in the literature [1,7,15,17].…”

Schwann cells promote EMT and the Schwann-like differentiation of salivary adenoid cystic carcinoma cells via the BDNF/TrkB axis

“…A prominent hallmark of SACC is perineural invasion (PNI), which is the process of cancer cell invasion in, around and through the nerves. PNI of SACC is the key factor responsible for the incomplete surgical resection and the striking characteristic of SACC that distinguishes it from other salivary gland malignancies (3). The mechanisms involved in the PNI of SACC are still ambiguous although it has been investigated over a long period of time.…”