Abstract
Adenoid cystic carcinoma (ACC) is an infrequent malignant neoplasm that originates most commonly in the major and minor salivary glands of the head and neck region. This study provides new information on head and neck ACC with cervical lymph node metastasis. Of 616 patients who underwent primary tumour resection from 1995 to 2008 in the authors’ hospital, 62 cases with cervical lymph node metastasis were analyzed. The general incidence of cervical lymph node metastasis in ACC was approximately 10%. The base of tongue, mobile tongue and mouth floor were the most frequent sites of lymph nodes metastasis, with incidences of 19.2%, 17.6% and 15.3%, respectively. Most cases occurred via a classic ‘tunnel-style’ metastasis and the level Ib and II regions were the most frequently involved. Primary site and lymphovascular invasion were significantly associated with lymph node metastasis. High patient mortality was significantly correlated with lymph node positive cases. The tongue–mouth floor complex has a high propensity for cervical lymph node metastasis, which occurs through a classic ‘tunnel-style’ metastasis. Peritumoral lymphovascular invasion could be taken as strong predictor for lymph node metastasis, which ultimately leads to poor prognosis of ACC patient. Selective neck dissection should be considered in such cases.
Adenoid cystic carcinoma (ACC) is an infrequent malignant neoplasm that originates most commonly in the major and minor salivary glands of the head and neck region, and represents approximately 1–2% of all malignant neoplasms of the head and neck. Sites other than the head and neck region can also be involved, including the breast, prostate and cuticulum.
As an epithelial malignant tumour, ACC is characterized by infiltrative growth and perineural spread, which results in a high rate of recurrence despite aggressive surgical resection. It has been labelled as ‘one of the most biologically destructive and unpredictable tumours of the head and neck’. Metastasis is another important biological property of ACC, which makes treatment difficult. Clinical investigation showed that the incidence of ACC with distant metastasis, ranged from 35% to 50% in all cases, and leads to a low long-term survival rate. Follow-up investigations have confirmed that metastasis is the leading cause of death in ACC patients.
Numerous reports have been devoted to the study of lung metastasis in ACC patients, which is the most common organ involved. The biological behaviour of lymph node metastases has seldom been studied owing to limited cases. Based on the latest literature review, most information on ACC with cervical lymph node metastasis is derived from case reports and clinical series, with the largest series reporting fewer than 10 cases.
To gain insight into the pattern of behaviour of cervical lymph node metastasis in head and neck ACC, the authors undertook a large sample-based study in an attempt to provide new information on incidence, distribution, clinicopathological parameters and the potential correlation between lymph node metastasis and clinical outcome.
Materials and methods
A retrospective study involving patients with ACC of the head and neck region who underwent primary tumour resection with curative intent at the Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University was conducted. All patients were treated between 1995 and 2009. 616 patients with confirmed histological diagnoses of ACC were included in the study. Medical records were reviewed to evaluate clinical parameters, treatment and clinical outcomes. Two experienced pathologist reviewed histological slides for tumour growth pattern, histological grade, surgical resection margin and the presence of peri-tumoral lymphatic, vascular and neural invasion. The histologic grade was determined according to the following criteria: Grade 1, a tubular and cribriform pattern but no solid component; Grade 2, tubular, cribriform, and solid pattern but solid component <30%; and Grade 3, tubular, cribriform, and solid pattern but solid component ≥30%. Ultrasound was used as a routine method to evaluate the state of the lymph node in the bilateral neck region for most ACC patients during follow-up.
Statistical calculations were performed using the statistical software package SPSS (version 13.0; SPSS, Chicago, IL, USA). Paired sample t -tests and χ 2 analyses were performed to determine statistically significant differences between the clinicopathological features and lymph nodes metastasis. Postoperative survival was estimated using the Kaplan–Meier method and logistic regression analysis was used to determine any correlation between lymph node metastasis and postoperative outcomes. This study was approved by the Shanghai 9th People’s Hospital IRB (2011-022).
Results
616 patients with ACC of the head and neck were included in the study. Their median age was 51.6 years (range 11–89 years). There were 302 males and 314 females; a ratio of almost 1:1. The incidence of ACC in the minor salivary glands (68.5%) was more than twice greater than those arising in the major salivary glands (31.5%). The most frequently affected sites were the hard/soft palate, followed by the submandibular gland and parotid gland ( Table 1 ).
| Primary sites | N | Percentage (%) |
|---|---|---|
| Major salivary gland | 194 | 31.5 |
| Parotid gland | 68 | 11.0 |
| Submandibular gland | 80 | 13.0 |
| Sublingual gland | 46 | 7.5 |
| Minor salivary gland | 422 | 68.5 |
| Hard/soft palate | 166 | 26.9 |
| Maxillary sinus | 60 | 9.7 |
| Mobile tongue | 17 | 2.8 |
| Base of tongue | 52 | 8.4 |
| Floor of the mouth | 59 | 9.6 |
| Buccal mucosa | 31 | 5.0 |
| Lip | 10 | 1.6 |
| Other sites * | 27 | 4.4 |
* Mandible, gingival, retromolar area, orbit, trachea, acoustic duct.
Incidence of lymph node metastasis
Of the 616 head and neck ACC patients, 62 cases were confirmed to have cervical lymph nodes metastases, with an incidence of almost 10%. Metastasis was reported at the time of surgery in 38 cases and after primary surgery in the remaining 24 cases. Lesions involving the base of tongue, mobile tongue and mouth floor were the three primary sites that reported the highest incidences of cervical lymph nodes metastasis, with incidences of 19.2%, 17.6% and 15.3%, respectively ( Fig. 1 ).
Clinicopathological variables affecting lymph node metastasis
Clinicopathological parameters such as primary tumour site and peri-tumoral lymphovascular invasion were significantly associated with cervical lymph node metastasis. Other factors, including age, sex, tumour size and growth pattern, were found to have no relation to cervical lymph node metastasis ( Table 2 ). Although statistically insignificant ( P = 0.06), patients with perinueral invasion may have a high tendency for cervical lymph node metastasis.
| Clinicopathologic characteristic | Lymph node status | P -value (chi-square) | |
|---|---|---|---|
| Positive (+) | Negative (−) | ||
| Age (year) | P = 0.18 | ||
| ≤50 | 26 | 282 | |
| >50 | 36 | 272 | |
| Sex | P = 0.08 | ||
| Male | 37 | 265 | |
| Female | 25 | 289 | |
| Tumour size | P = 0.60 | ||
| ≤3 cm | 45 | 419 | |
| >3 cm | 17 | 135 | |
| Tumour location | P = 0.0026 | ||
| Tongue–mouth floor complex | 22 | 106 | |
| Other sites | 40 | 448 | |
| Histological grade | P = 0.17 | ||
| 1 (without solid) | 33 | 345 | |
| 2 and 3 (with solid) | 29 | 209 | |
| Perinueral invasion | P = 0.06 | ||
| Yes | 40 | 288 | |
| No | 22 | 266 | |
| Lymphovascular invasion | P = 0.012 | ||
| Yes | 19 | 97 | |
| No | 43 | 457 | |
Region and pattern of affected lymph nodes
Of the 62 cases, cervical lymph node metastasis was reported in only one region in almost 60% (46/62) of cases. For the remaining 16 patients, cervical lymph node metastasis was reported in two or more regions. Level Ib and II regions were the most frequently involved, with a reported incidence of 27 (43.5%) and 37 (59.6%) cases, respectively. Level III and IV regions were affected only in 14 cases (22.5%) ( Fig. 2 ).
Based on the combined analysis of clinical investigation, CT/MRI features as well as histopathological features, the majority of the cases exhibited a classic ‘tunnel-style’ metastasis (i.e. along lymphatic or vascular channels) from the original site to regional lymph nodes ( Figs 3 and 4 ). In tumours involving the submandibular gland, metastastic lymph nodes were mostly involved by direct extension of the primary tumour ( Fig. 5 ).
