Abstract
Purpose
The purpose of the current study was to evaluate the frequency rates of tumour recurrences and rates of metastases in patients with surgical removal of malignant salivary gland tumours throughout 5 years of follow-up after initial therapy, and determine which salivary gland and histological diagnosis are the major contributors for the occurrence.
Methods
Between 2005 and 2017, 74 patients underwent surgical removal of localized malignant cancers of the salivary glands. Data were analysed retrospectively from our tertiary hospital database. The demographic characteristics (age and gender) were obtained from the patients’ records. Pearson’s χ-square test and logistic regression were used to analyse the data with p < 0.05 as statistically significant.
Results
Malignant salivary gland tumours were mostly diagnosed at parotid gland in 51.4% of cases, thus majority of patients underwent surgical extirpation (37.8% of cases) of tumour removal. Adenocarcinoma was the most common form of malignancy (19 patients, 25.6%), followed by adenoid cystic carcinoma (13 patients 17.6%) and mucoepidermoid carcinoma (11 patients, 14.9%). Postoperative complications; namely tumour recurrences were detected in 8 patients (10.8%) throughout 5 years of follow-up after initial therapy. Metastases were observed in 6 patients (8.1%), and facial nerve paralyses were diagnosed in 19 (25.7%) of all patients and with no specific risk factors, that could have contributed to the occurrence of nerve damage.
Conclusions
A significant proportion of patients who are presumed to be cured of their disease through 5 years after initial treatment for salivary gland cancer will be found to develop late disease recurrences or metastases.
1
Introduction
Malignant salivary gland tumours (MSGTs) are uncommon neoplasms that account for 3–5% of all head and neck cancers and have unpredictable clinical course by frequent metastases, which often occur years after diagnosis [ ]. Although much has been learned regarding the biologic behaviour of these tumours and the propensity for late recurrences over the last decades, questions persist and according to our knowledge only scarce data exist addressing these issues.
For instance, histology of the tumours is varied ( Table 1 ), with adenoid cystic carcinoma as the most common form of malignancy with regional recurrence occurring years later [ ]. Moreover, Ladeinde et al. [ ] reported that MSGTs represented 60.8% of all salivary gland tumours, while benign tumours accounted for 40.2% of their cases. Although, there are many studies [ , ], which have examined the demography of benign salivary gland tumours, studies examining MSGTs are rare [ , ].
| N = 74 | |
|---|---|
| Gender | |
| M/F | 44/30 |
| Age [years] | 59.2 ± 17.3 |
| Salivary gland | |
| Parotid | 38 (51.4%) |
| Buccal | 4 (5.4%) |
| Submandibular | 12 (16.2%) |
| (Sub)lingual | 6 (8.1%) |
| Palate | 14 (18.9%) |
| Operation | |
| Superficial parotidectomy | 7 (9.5%) |
| Total parotidectomy | 20 (27.0%) |
| Surgical excision | 19 (25.7%) |
| Surgical extirpation | 28 (37.8%) |
| Histological diagnosis | |
| Acinic cell carcinoma | 6 (8.1%) |
| Adenocarcinoma | 16 (21.6%) |
| Adenoid cystic carcinoma | 13 (17.6%) |
| Lymphoma | 6 (8.1%) |
| Squamous Cell Carcinoma | 10 (13.5%) |
| Mucoepidermoid Carcinoma | 11 (14.9%) |
| Salivary duct Carcinoma | 3 (4.1%) |
| Melanoma | 1 (1.4%) |
| Others a | 8 (10.8%) |
| Tumour recurrence | 8 (10.8%) |
| Metastasis | 6 (8.1%) |
| Facial nerve injury | 19 (25.7%) |
a Carcinoma ex adenoma pleomorphe, clear cell carcinoma, carcinoma metastaticum.
General management guides for such tumours are available, but they vary from centre to centre [ , ] so the management of carcinomas are still discussable. The treatment of MSGTs is often challenging, mainly due to unpredictable and varied biologic behaviour and their prolonged risk of recurrence [ ]. Although a surgery with or without postoperative radiotherapy results in effective disease control for many patients, disease recurrence, in the form of both regional recurrence and distant metastasis, has been reported to occur approximately 20 years after the completion of treatment [ , ].
Furthermore, the aetiology of MSGTs is still unknown. High or prolonged doses of radiation to the head and neck have been shown to be risk factors in previous studies [ ]. Reports from several studies have shown that a history of prior cancer, especially those related with ultraviolet radiation, immunosuppression and Epstein-Barr virus were found to be associated with an increased occurrence of MSGTs [ ].
The aim of our study was to evaluate the frequency rates of tumour recurrences and rates of metastases in patients with surgical removal of malignant salivary gland tumours, throughout 5 years of follow-up after initial therapy, and determine which salivary gland and histological diagnosis are the most frequent contributors for the occurrence.
2
Materials and methods
2.1
Study design
Study was designed as a 12-year retrospective analysis of patients who underwent different surgical procedures of removal of MSGTs from our tertiary Department of Maxillofacial Surgery in Clinical University Centre of Kosovo between the years 2005–2017. The research has been conducted in full accordance with the Declaration of Helsinki on medical protocols and ethics and was approved by the Institutional ethical review board at Medical faculty in Prishtina. Patients did not need to give the consent of participation since all data were obtained from our archive database.
2.2
Patients’ data
Data were collected from the electronic archive database of patients, who were treated at our department. All cases of MSGTs were included, that were resected at our institute during 2005 and 2017 time period. The patients who were selected for analysis underwent superficial/total parotidectomy, extirpation, excision or biopsy of different salivary glands resection. Excision of tumours was done for minor salivary gland tumours located in palate region. Extirpation was performed for tumours located at superficial parotid lobe and which were encapsulated. From the sublingual and submandibular regions gland tumours were resected together with the salivary gland, thus we performed extirpation of salivary gland together with the tumour. We included patients of all ages (children and adults), who underwent surgery for removal of MSGTs, and were followed up for 5 years after initial therapy. In total, 74 cases were selected for analysis.
The diagnosis of tumours was established pre-operatively in all cases by histology. The specimens were reviewed by a blind and experienced histo-pathologist. The following pre-operative demographic and clinical data were included: age and sex of patients, location of the tumour and type of surgical procedure. Postoperative complications such as tumour recurrence, metastasis or facial paralysis were prospectively recorded in follow-up visits through 5 years.
2.3
Statistical analysis
Statistical Package of Social Sciences SPSS 21 (IBM, New York, USA) was used for statistical analyses. Quantitative variable (patients’ age) was expressed as mean ± standard deviation, was normally distributed and compared by the independent t -test. Qualitative variables were compared by Pearson’s chi square test according to the type of variable. The main outcome parameters were diagnosis of metastasis and tumour recurrence. Odds ratios as predictive values for probability of tumour recurrence and metastasis were calculated by univariate and multivariate logistic regression. Statistical significance for all tests was set at p < 0.05.
3
Results
Between 2005 and 2017, MSGTs were removed from 74 patients. Basic characteristics of patients with MSGTs are presented in Table 1 . Tumours were diagnosed in 44 males and 30 females with approximate male-to-female ratio 1.5:1. Mean age at presentation was 59.2 ± 17.3 years.
MSGTs were mostly diagnosed at parotid gland in 51.4% of cases. Therefore, majority of patients underwent surgical extirpation (37.8% of cases), one quarter underwent total parotidectomy and surgical excision, respectively. Adenocarcinoma was the most common form of malignancy (16 patients, 21.6%), followed by adenoid cystic carcinoma (13 patients, 17.6%) and mucoepidermoid carcinoma (11 patients, 14.9%) ( Table 1 ).
Post-operative complications in aspect of tumour recurrences were detected in 8 patients (10.8%) throughout 5 years of follow-up after initial therapy. Metastases were observed in 6 patients (8.1%), and facial nerve paralyses were diagnosed in 19 (25.7%) out of all examined patients.
According to the gender, males were older than females, but the difference was not statistically significant ( Table 2 ). Distribution of tumour anatomical locations varied between the genders (p < 0.001). Most males accounted tumours at parotid gland (70.5% of male cases). Meanwhile, most females accounted tumours at palate region (40.0% of female cases). There were no differences in the type of MSGTs, tumour recurrence rates and metastases rates between the genders.
| Male (N = 44) | Female (N = 30) | p-value | |
|---|---|---|---|
| Age [years] | 61.5 ± 17.3 | 55.8 ± 17.0 | 0.173 |
| Salivary gland | <0.001 | ||
| Parotid | 31 (70.5%) | 7 (23.3%) | |
| Buccal | 1 (2.3%) | 3 (10.0%) | |
| Submandibular | 7 (15.9%) | 5 (16.7%) | |
| (Sub)lingual | 3 (6.8%) | 3 (10.0%) | |
| Palate | 2 (4.5%) | 12 (40.0%) | |
| Operation | 0.006 | ||
| Superficial parotidectomy | 6 (13.6%) | 1 (3.3%) | |
| Total parotidectomy | 17 (38.6%) | 3 (10.0%) | |
| Surgical excision | 6 (13.6%) | 13 (43.3%) | |
| Surgical extirpation | 15 (34.1%) | 13 (43.3%) | |
| Histological diagnosis | 0.856 | ||
| Acinic cell carcinoma | 3 (6.8%) | 3 (10.0%) | |
| Adenocarcinoma | 9 (20.5%) | 7 (23.3%) | |
| Adenoid cystic carcinoma | 6 (13.6%) | 7 (23.3%) | |
| Lymphoma | 4 (9.1%) | 2 (6.7%) | |
| Squamous Cell Carcinoma | 8 (18.2%) | 2 (6.7%) | |
| Mucoepidermoid carcinoma | 6 (13.6%) | 5 (16.7%) | |
| Salivary duct carcinoma | 2 (4.5%) | 1 (3.3%) | |
| Melanoma | 1 (2.3%) | 0 | |
| Others a | 5 (11.4%) | 3 (10.0%) | |
| Tumour recurrence | 4 (9.1%) | 4 (13.3%) | 0.564 |
| Metastasis | 5 (11.4%) | 1 (3.3%) | 0.214 |
a Carcinoma ex adenoma pleomorphe, clear cell carcinoma, carcinoma metastaticum, cylindroma.
Tumour recurrences were detected in 8 cases. No risk factors were identified as potential contributor to the tumour recurrence by univariate and multivariate regression ( Table 3 ). Although highest recurrence rates were detected in females, at (sub)lingual and palate region, after superficial parotidectomy or surgical excision and adenoid cystic carcinoma, no associations were statistically confirmed.
| Tumour recurrence | ||||||
|---|---|---|---|---|---|---|
| No(N = 66) | Yes(N = 8) | Recurrence rates | B value | OR (95% CI) | p-value | |
| Age | 58.6 ± 17.6 | 63.6 ± 15.6 | / | 0.019 | 1.019 (0.971–1.070) b | 0.447 |
| Gender M/F | 40/26 | 4/4 | 9.1%/13.3% | −0.431 | 0.650 (0.149–2.830) b | 0.564 |
| Salivary gland | 0.105 | 1.110 (0.771–1.733) b | 0.917 | |||
| Parotid | 34 (51.5%) | 4 (50.0%) | 10.5% | |||
| Buccal | 4 (6.1%) | 0 | / | |||
| Submandibular | 11 (16.7%) | 1 (12.5%) | 8.3% | |||
| (Sub)lingual | 5 (7.6%) | 1 (12.5%) | 16.7% | |||
| Palate | 12 (18.2%) | 2 (25.0%) | 14.3% | |||
| Operation | −0.054 | 0.948 (0.569–1.578) b | 0.885 | |||
| Superficial parotidectomy | 6 (9.1%) | 1 (12.5%) | 14.3% | |||
| Total parotidectomy | 18 (27.3%) | 2 (25.0%) | 10.0% | |||
| Biopsy | 3 (4.5%) | 0 | / | |||
| Surgical excision | 16 (24.2%) | 3 (37.5%) | 15.8% | |||
| Surgical extirpation | 23 (34.8%) | 2 (25.0%) | 8.0% | |||
| Histological diagnosis | 0.015 | 1.015 (0.748–1.378) b | 0.922 | |||
| Acinic cell carcinoma | 6 (9.1%) | 0 | / | |||
| Adenocarcinoma | 15 (22.7%) | 1 (12.5%) | 6.3% | |||
| Adenoid cystic carcinoma | 10 (15.2%) | 3 (37.5%) | 23.1% | |||
| Lymphoma | 6 (9.1%) | 0 | / | |||
| Squamous cell carcinoma | 7 (10.6%) | 3 (37.5%) | 30.0% | |||
| Mucoepidermoid carcinoma | 11 (16.7%) | 0 | / | |||
| Salivary duct carcinoma | 3 (4.5%) | 0 | / | |||
| Melanoma | 1 (1.5%) | 0 | / | |||
| Others a | 7 (10.6%) | 1 (12.5%) | 12.5% | |||
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