Abstract
Purpose
This study was to investigate clinicopathologic characteristics and prognostic factors in adenoid cystic carcinoma of head and neck minor salivary glands.
Materials and methods
We conducted a retrospective review of 130 patients with adenoid cystic carcinoma of head and neck minor salivary glands that were evaluated between 2000 and 2013 in Beijng Tongren Hospital.
Results
Five-year overall survival and disease-free survival rates were 80.8% and 55.6%. Local recurrence rate was 40%, regional recurrence 3.8%, and distant metastasis was 28.5%. On univariate analysis, solid histological subtype, perineural invasion, positive surgical margins and advanced stages were found to be poor prognostic indicators. On multivariate analysis, solid histological subtype and positive surgical margins were significant prognostic factors of worse overall survival.
Conclusions
Solid histological subtype and positive surgical margins were the most important predictors of poor outcome in adenoid cystic carcinoma of minor salivary glands. Surgery with postoperative radiation were recommended treatment and offered durable local control.
1
Introduction
Adenoid cystic carcinoma (ACC) is a rare tumor that originates within salivary glands. ACC comprises approximately one-quarter of all salivary gland tumor, which accounts for 3 to 5% of all head and neck malignancies . Approximately 42–61% of ACC arises within the minor salivary glands, of which the palate is the most common site of origin . The clinical behavior of ACC is unique among salivary gland tumors. It has a distinct natural history characterized by slow-growing but extensive local invasion and perineural spread, with late development of distant metastasis.
Due to its rarity, there is some controversy over the clinical and histological factors that affect the survival of patients with ACC. Gender, perineural invasion (PNI), efficacy of adjuvant treatment, and the site of origin were found to be significant prognostic factors by some authors, whereas others found that they had no impact on survival . Since that prognostic factors are important in guiding treatment as well as counseling patients, and there are few large case series that specifically address the prognostic factors of ACC of minor salivary gland . We conducted this retrospective study to report our experience to determine the clinicopathologic characteristics and prognostic factors in patients with ACC of the head and neck minor salivary gland.
2
Materials and methods
The study was approved by the institutional review board of Beijing Tongren hospital. Data concerning patient characteristics, clinical and pathologic tumor characteristics, and treatment modalities were obtained through a retrospective review of the medical records.
All specimens were reviewed by pathologists at our institution. The specimens were analyzed for the following criteria: subtypes, surgical margin status, perineural invasion and nodal status. Tumors were classified into predominately tubular, cribriform, or solid if the tubular or cribriform pattern exceeded 80%, and they were classified as solid when ≥ 30% of this growth pattern was present. Disease was classified using the tumor, nodal, and metastasis (TNM) staging in according to 7th edition of the tumor-node-metastasis staging system .
Follow-up time was the time from initial presentation at our institution for the tumor of interest until the date of last contact or death for overall survival (OS) and disease-free survival (DFS) measurements. For DFS, the follow-up time was from the conclusion of treatment for the primary tumor of concern until the date of first recurrence, death, or last contact. Recurrences were diagnosed by pathological biopsy. Distant metastases were determined by chest x-rays, computed tomography scans and laboratory work. Patients with incomplete medical records were excluded from the study.
Statistical calculations were performed using the statistical software package SPSS (version 17.0; SPSS Inc., Chicago, IL, USA). Curves describing OS and DFS were generated by the Kaplan-Meier product limit method. The statistical significance of differences between the actuarial curves was tested by the log-rank test. Hazard ratios (HRs) and confidence interval (CI) were calculated according to the multivariable Cox regression technique. Statistical tests were considered significant when P < 0.05.
2
Materials and methods
The study was approved by the institutional review board of Beijing Tongren hospital. Data concerning patient characteristics, clinical and pathologic tumor characteristics, and treatment modalities were obtained through a retrospective review of the medical records.
All specimens were reviewed by pathologists at our institution. The specimens were analyzed for the following criteria: subtypes, surgical margin status, perineural invasion and nodal status. Tumors were classified into predominately tubular, cribriform, or solid if the tubular or cribriform pattern exceeded 80%, and they were classified as solid when ≥ 30% of this growth pattern was present. Disease was classified using the tumor, nodal, and metastasis (TNM) staging in according to 7th edition of the tumor-node-metastasis staging system .
Follow-up time was the time from initial presentation at our institution for the tumor of interest until the date of last contact or death for overall survival (OS) and disease-free survival (DFS) measurements. For DFS, the follow-up time was from the conclusion of treatment for the primary tumor of concern until the date of first recurrence, death, or last contact. Recurrences were diagnosed by pathological biopsy. Distant metastases were determined by chest x-rays, computed tomography scans and laboratory work. Patients with incomplete medical records were excluded from the study.
Statistical calculations were performed using the statistical software package SPSS (version 17.0; SPSS Inc., Chicago, IL, USA). Curves describing OS and DFS were generated by the Kaplan-Meier product limit method. The statistical significance of differences between the actuarial curves was tested by the log-rank test. Hazard ratios (HRs) and confidence interval (CI) were calculated according to the multivariable Cox regression technique. Statistical tests were considered significant when P < 0.05.
3
Results
A total of 130 patients with ACC of head and neck met the inclusion criteria between January 2000 and July 2013. Clinical and histopathologic characteristics are presented in Table 1 . The mean patient age at presentation was 51 years (range, 8–82 years). There were 60 (46.2%) males and 70 (53.8%) females (ratio, 1:1.2). The median length of follow-up was 36 months (range, 21–168 months).
| Characteristic | No. (%) of patients |
|---|---|
| Total no. | 130 |
| Sex | |
| Male | 60(46.2) |
| Female | 70(53.8) |
| Median age, y | 51(8–82) |
| ≤ 50 | 61(46.9) |
| > 50 | 69(53.1) |
| Tumor location | |
| Nasal cavity and nasal sinus | 51(39.2) |
| Oral cavity/oropharynx | 26(20) |
| External auditory canal | 17(13) |
| Lacrimal gland | 13(10) |
| Larynx and trachea | 5(4) |
| Other | 18(13.8) |
| Tumor stage | |
| T1–T2 | 55(42.3) |
| T3–T4 | 75(57.7) |
| Nodal stage | |
| N0 | 125(96.2) |
| N + | 5(3.8) |
| Metastatic disease | |
| M0 | 127(97.7) |
| M1 | 3(2.3) |
| Clinical stage | |
| I–II | 52(40) |
| III–IV | 78(60) |
| Treatment | |
| Surgery only | 43(33.1) |
| Surgery and radiation | 77(59.2) |
| Radiation and/or chemotherapy | 10(7.7) |
| Surgical margins | |
| Negative | 75(57.7) |
| Positive | 55(42.3) |
| PNI | |
| No | 61(46.9) |
| Yes | 69(53.1) |
| Histologic subtype | |
| Cribriform | 74(56.9) |
| Tubular | 30(23.1) |
| Solid | 26(20) |
The site of origin of the tumor was the nasal cavity and paranasal sinuses in 51 patients (39.2%), the oral cavity and oropharynx in 26 patients (20%), the external auditory canal in 17 patients (13%), the lacrimal gland in 13 patients (10%), the larynx and trachea in 5 patients (4%) and other sites in 18 patients (13.8%). Fifty-four patients (42.3%) had T1 or T2 disease, 75 patients (57.7%) had T3 or T4 disease. Five patients (3.8%) had cervical lymph node metastasis (N +), and 3 patients (2.3%) had distant metastases at the time of original staging.
Forty-three patients (33.1%) were treated with surgery alone, 77 patients (59.2%) were treated with surgery and radiation therapy (XRT), and 10 patients (7.7%) were treated with XRT and/or chemotherapy as palliative treatment. The agents used for chemotherapy included 5-fluorouracil and cisplatin.
Fifty-seven patients (43.8%) had a recurrence after treatment for their original disease, with 52 patients (40%) had local recurrence and 5 patients (3.8%) had regional recurrence. Thirty-seven patients (28.5%) had distant metastases. Twenty-three patients (17.7%) died of their disease.
Outcome data are presented in Table 2 . Univariate analysis revealed advanced stages, positive surgical margins, PNI and solid histological subtype as indicators of poor prognosis by the log-rank test. By contrast, there was no statistically significant difference in OS or DFS according to the levels of gender and age.
| Variable | OS(%) | P | DFS(%) | P |
|---|---|---|---|---|
| Sex | ||||
| Male | 84.2 | 52.5 | ||
| Female | 83.8 | 0.396 | 59.2 | 0.255 |
| Age, y | ||||
| ≤ 50 | 79.6 | 0.238 | 60.6 | 0.82 |
| > 50 | 88.9 | 64.7 | ||
| Clinical stage | ||||
| I–II | 95.2 | 0.009 | 87.5 | < 0.001 |
| III–IV | 75.6 | 46.6 | ||
| Treatment | ||||
| Surgery | 82.8 | 63.3 | ||
| Surgery and radiation | 89 | 70.4 | ||
| Radiation and/or chemotherapy | 38.6 | 10 | ||
| Surgical margins | ||||
| Negative | 95.3 | 76.7 | ||
| Positive | 68.8 | 0.001 | 40.2 | < 0.001 |
| PNI | ||||
| No | 95.4 | 0.018 | 72.7 | 0.003 |
| Yes | 76.4 | 53.5 | ||
| Histologic subtype | ||||
| Cribriform | 91.1 | 69.1 | ||
| Tubular | 92.8 | 65.5 | ||
| Solid | 57.4 | 31.2 | ||
Multivariate analysis was used to evaluate the relative weights of the parameters by the Cox regression models. Solid histological subtype and positive surgical margins were found to be significant poor prognostic factors. Multivariate analyses revealed worse prognosis in solid histological subtype compared with cribriform and tubular subtype (HR: 2.548; 95% CI: 1.569–4.139), and in positive surgical margins compared with negative surgical margins (HR: 3.443; 95% CI: 1.403–8.447).
Recurrence data are presented in Table 3 . There was a significant increase in incidence of local recurrence and distant metastasis in patients with solid subtype tumor compared with the combined group of patients with cribriform and tubular subtype tumor ( P < 0.05). Patients with positive surgical margins were also noted to have significantly increased rates of local recurrence and distant metastasis ( P < 0.05).
| Feature | Local | Regional | Distant |
|---|---|---|---|
| (%) | (%) | (%) | |
| Histological grade | |||
| Cribriform | 36.5 | 4 | 23 |
| Tubular | 23.3 | 0 | 23.3 |
| Solid | 69.2 | 7.7 | 50 |
| P | < 0.01 | 0.7 | 0.03 |
| Surgical margins | |||
| Negative | 16 | 5.3 | 21.3 |
| Positive | 72.7 | 1.8 | 38.2 |
| P | < 0.01 | 0.3 | 0.04 |
The overall survival and disease-specific survival rates at 5 years for patients with ACC of minor salivary glands were 80.8% and 55.6%, respectively ( Fig. 1 ). Patients with stage I and II disease had an OS and DFS of 95.2% and 87.5% ( Fig. 1 ), respectively, whereas those III and IV disease indicated significantly worse OS and DFS of 75.6% and 46.6%, respectively ( P < 0.01, P < 0.01).
