Adenoid cystic carcinoma is a tumour of glandular cells responsible for 10% of salivary gland neoplasms. It has a high rate of perineural spread but limited involvement of regional lymphatics even in late stage disease. Early survival is typically good (60–90%) although long term survival is poor with spread to distant sites in 40–60% of cases. The authors performed a retrospective review of clinical and pathological records for 24 patients managed by their institution over a 22-year period. The overall 5, 10 and 20-year survival rates in this study were 92%, 72% and 54%, respectively. Perineural invasion was seen in 63% and close or positive margins seen in 64% of all primary resection specimens although survival was not associated with any clinical factor other than the initial size of lesion. Most patients presented complaining of a lump, whilst a burning neuralgia-type pain was the second most common symptom. The study confirms the conclusion of previous studies that tumour size at diagnosis is the most important predictor of outcome.
Adenoid cystic carcinoma (ACC) is a tumour of mucous secreting glandular cells representing less than 1% of all malignant head and neck tumours . It is the fifth most common salivary gland malignancy and accounts for approximately 10% of all salivary gland neoplasms . Whilst over 70% of cases originate from within the salivary glands, up to 20% of cases arise within the airways and 9% at other sites including the skin, breast and lachrymal glands .
ACC most commonly arises within the minor salivary glands (31–60%) with the palate being the most frequently involved site in the oral cavity . Approximately 30–55% of ACC arises in the major glands , of which the parotid is the most common site of origin (25%) with ACC representing 2–5% of all parotid tumours .
Originally considered to be a benign tumour when it was first reported in 1856 , ACC is a slowly growing but aggressive, destructive and unpredictable malignant tumour . It is more commonly found in females and has a peak incidence in the fifth and sixth decades of life but may be found in a wide range of ages .
Compared with other epithelial head and neck tumours, ACC is known for its unusual predilection for perineural infiltration . Haematogenous spread to distant sites occurs in about 40–60% of patients, especially in late stage disease . In contrast to squamous cell carcinoma, local lymphatic spread to regional nodes is uncommon . The lungs are usually the first site of metastasis and bone involvement is common .
The clinical course of ACC is often protracted owing to its slow growth even with metastatic disease . Metastasis to bone is associated with rapid deterioration and disease progression as the response to chemotherapy is generally poor . Typically, 5-year survival rates are good (60–90%) but long term survival is reduced with 10-year survival rates of approximately 40–50% .
It is generally agreed that the most important factor for long term survival following treatment for ACC is the size and staging of the initial lesion . Tumours that are less than 4 cm tend to do well and are not affected by histological subtype . In contrast, tumours larger than 4 cm are more likely to develop distant metastases . Tumours of the maxillary antrum and posterior palate often fare poorly because of complex regional anatomy. These tumours often present at a locally advanced stage with extensive invasion of nerves and adjacent structures . The size of the tumour at initial presentation also has a significant effect on the patient’s quality of life. Patients with larger malignant oral tumours, particularly those requiring free flap reconstruction and those patients requiring radiotherapy, have been found to have reduced quality of life .
The treatment of ACC is based on the surgical removal of the tumour with margins of approximately 1–2 cm although this is not always possible, especially in the posterior maxilla . Lesions involving the palate and maxilla are excised en bloc by palatal fenestration, partial or total maxillectomy . Perineural invasion is responsible for frequent local recurrences (60–70%) and, despite aggressive local treatment, 40–60% of patients will develop systemic metastases . Positive surgical margins and major nerve involvement make local recurrence more likely . As a result, only small radically resected tumours have a good prognosis .
Adjuvant radiotherapy is commonly used in the management of ACC. For patients with small tumours there appears to be survival benefit compared with surgery alone but radiotherapy has also been shown to have a survival benefit for patients with tumours over 4 cm in size . Most tumours treated with standard photon based radiotherapy alone appear to recur with time although the use of fast neutron irradiation has been shown to be effective in treating patients even with gross residual disease .
The purpose of this study was retrospectively to assess the outcomes and factors affecting survival of patients referred with ACC arising from a minor salivary gland site in the maxillofacial region at a single institution.
A cohort of 24 cases managed between 1986 and 2008 was examined. It included 2 cases that underwent 2 episodes of treatment and 2 cases that were deemed inoperable at the time of presentation. Cases were identified from Royal Melbourne Hospital Pathology Service records as well as Head and Neck and Maxillofacial Unit databases. Follow-up information was obtained by case record review, return visits, or correspondence with other practitioners. For cases with follow-up information older than 12 months, mortality information was obtained from the Victorian Cancer Registry. Ethics approval was obtained from the Royal Melbourne Hospital Human Research Ethics Committee.
Data collected for analysis included age, gender, smoking status, alcohol consumption, time intervals, site of tumour, presentation details, clinical TNM stage, surgery performed, adjunctive treatments, histology and anatomical margins. All pathological specimens were assessed at the Royal Melbourne Hospital Department of Anatomical Pathology. All specimens had margins inked prior to blocking and sectioning. Specimens were assessed for tumour subtype, margin status and the presence of perineural, perilymphatic or perivascular spread. Margins were defined as being positive if tumour was detected at the resection margin or close if the tumour was within 5 mm of the resection margin. The histological subtype of each lesion was categorized into either solid tumours, cystic tumours (cribriform and tubular) or unspecified. Pathology reports for treatment of recurrence were not included in the analysis.
All data were entered into an Excel spreadsheet (Microsoft Corp., Seattle, WA, USA) and statistical analysis carried out using the Statview 5.0 statistical package (SAS, Cary, NC, USA). Kaplan–Meier analysis was used to assess univariate factors and disease free survival. Cox proportional hazard models were used for multivariate analysis. A p value of less than 0.05 was considered significant.
The cohort included 17 females (71%) and 7 males (29%) resulting in a female to male ratio of approximately 2.4:1. The mean and median age at presentation was 58 years (range 30–81 years).
No history of smoking was found in 14 cases (58%) whilst 10 (42%) had a positive history of past or current smoking. A history of heavy alcohol use was found in 13 cases (54%). Limited or no consumption was found in 11 cases (46%).
The median time to presentation for treatment was 3 months (range 1–52 months). In the three cases in which the presentation was delayed for over 48 months, two of the patients reported very slow growing tumours that had not increased appreciably in size whilst another patient was referred and investigated initially for trigeminal neuralgia.
A painless lump was the most common reason for presentation in 10 cases (42%) whilst a burning neuralgic-like pain was the second most common symptom seen in 7 cases (29%). Problems with denture fit were reported in 3 cases (12%) and in 2 cases, symptoms of intermittent submandibular swelling related to tumour infiltration of the submandibular duct and the floor of mouth were found. Ulceration and delayed healing were uncommon ( Table 1 ).
|Ill fitting denture||3||13|
|Salivary duct blockage||2||8|
Table 2 describes the primary site of tumour at presentation. The palate was the most common tumour site with 38% of tumours arising in the posterior palate and 4% arising within the soft palate.
|Base of tongue||3||13|
|Floor of mouth||2||8|
Metastases to ipsilateral regional lymph nodes were found at the time of presentation in 4 cases (17%) with a further one case having delayed cervical metastasis 2 years after initial treatment. All nodal metastases occurred in T3 and T4 tumours with 2 cases from base of tongue, 2 from the posterior palate and one from the floor of the mouth. There were no cases of distant metastasis at presentation.
Solid tumours were seen in 9 cases (38%) whilst cystic tumours were found in 13 cases (54%). Two cases were categorized as unspecified and were deemed inoperable at presentation.
15 cases (68%) showed evidence of perineural invasion whilst lymphovascular infiltration was seen in 5 cases (23%). Clear margins were seen in 8 cases (36%) whilst close or positive margins occurred in 14 cases (64%) ( Table 3 ). Perineural invasion was found in 11 (79%) of the 14 cases with close or positive margins compared with the 8 cases with clear margins in which only 4 (50%) showed perineural invasion. All patients who died of their disease had perineural invasion present in their primary resection specimen. This approached significance with log rank tests ( p = 0.085).
|Clear (>5 mm)||8||36|
|Close (<5 mm)||4||18|
Surgery was the primary treatment modality for all patients in this study except for the 2 cases deemed inoperable at presentation. Tables 4 and 5 describe the surgical approaches utilized and primary resections. Obturator reconstruction was performed in 12 (55%) of the cases receiving primary surgery whilst free-flap reconstruction, mainly utilising the radial forearm, was used in 10 cases (45%).
|Wide local excision||6||27|