ONLINE EXCLUSIVE
Submandibular salivary gland
tumors: Clinical course and outcome
of a 20-year multicenter study
Aviram Mizrachi, MD; Gideon Bachar, MD; Yaron Unger, MD; Ohad Hilly, MD;
Dan M. Fliss, MD; Thomas Shpitzer, MD
Abstract
The purpose of this retrospective chart review study was to
review the nature and clinical course of benign and malignant
submandibular gland tumors at 2 major university-affiliated
tertiary medical centers. All patients who underwent
submandibular salivary gland excision between 1990 and 2010
were included. Clinical and disease-related data were collected
from the medical charts. One hundred ninety-three patients
were identified, of whom 108 (56%) had non-neoplastic
disorders (sialolithiasis and sialadenitis). The remaining 85
patients (44%) had a submandibular salivary gland tumor.
The most common benign neoplasm was pleomorphic
adenoma (53 patients). Twenty tumors (24%) were malignant:
adenoid cystic carcinoma in 11 patients, mucoepidermoid
carcinoma in 6 patients, and adenocarcinoma in 3 patients.
Recurrence was noted in 7 patients with submandibular gland
malignancy and in 2 patients with pleomorphic adenoma.
The 5-year disease-free survival rate was 63%. Tumors of the
submandibular gland are infrequently malignant. Recurrent
submandibular salivary gland pleomorphic adenoma is rare
compared with recurrences in the parotid gland.
From the Department of Otorhinolaryngology–Head and Neck Surgery,
Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel
(Dr. Mizrachi, Dr. Bachar, Dr. Hilly, and Dr. Shpitzer); and the
Department of Otorhinolaryngology–Head and Neck Surgery,
Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (Dr. Unger and
Dr. Fliss).
Corresponding author: Aviram Mizrachi, MD, Department of
Otorhinolaryngology–Head and Neck Surgery, Rabin Medical
Center. Petah Tikva, Israel 49100. Email: aviramguy@hotmail.com
Volume 96, Number 3
Introduction
Salivary gland tumors are rare, comprising 10% of all
head and neck neoplasms.1 Among submandibular
salivary gland tumors, the proportion of malignancies
approaches 50%, which is a higher proportion than in
the parotid gland.2,3 The predominant types of salivary
gland malignancies are mucoepidermoid carcinoma,
adenoid cystic carcinoma, and adenocarcinoma.4
The diagnosis of submandibular gland neoplasms is
made by ultrasonography, computed tomography, or
magnetic resonance imaging together with fine-needle
aspiration biopsy. In some cases, the submandibular
gland is excised for diagnostic purposes.5 Excision of the
submandibular gland is the treatment of choice for both
neoplastic and non-neoplastic disorders that cannot
be controlled with conservative (medical) measures.
The surgical approach may be cervical, intraoral, or
endoscopic.6 Prompt treatment of submandibular gland
malignancies is important because of their relatively
aggressive behavior and the proximity of the gland to
adjacent vital structures.7
Given the high incidence of aggressive variants and the
high rate of locoregional recurrence of submandibular
gland malignancies, researchers have suggested that
adjuvant radiation should be considered in advanced
disease and in high-risk patients to improve locoregional
control.8,9 These findings also have been supported by
those from recent large studies.10,11 Nodal disease, tumor
stage, and perineural invasion have been found to be the
most important predictors of outcome that significantly
decrease the rate of survival.12-14 Other predictive factors
reported to date are patient age, tumor histopathologic
type, facial nerve involvement, extraglandular tumor
extension, and tumor grade.15
The purpose of the present study was to review the
nature and clinical course of submandibular salivary
gland tumors.
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 MIZRACHI, BACHAR, UNGER, HILLY, FLISS, SHPITZER
Patients and methods
The registry of two major tertiary university-affiliated
hospitals was reviewed for all patients who underwent
submandibular gland excision from 1990 to 2010. The
findings were then cross-referenced with a head and
neck surgical oncology registry.
Inclusion and exclusion criteria. Patients with newly
diagnosed, previously untreated, and pathologically
confirmed disease were included in the study. Exclusion
criteria were patient refusal of treatment, missing data,
and follow-up of less than 1 year.
Evaluation. In all cases, the pathologic assessment
was performed by a head and neck pathologist. Tumors
were staged at the time of diagnosis according to the
American Joint Committee on Cancer (TNM) classi-
fication system for the given time period. For purposes
of the study, the following data were collected from the
medical charts: patient age and sex, clinical parame-
ters, pathology studies, treatment, complications, and
follow-up.
Statistical analysis. Differences in mean continuous
variables between groups were analyzed by the Student
t test and differences in categorical variables by the
Fisher exact test. Rates of disease-specific survival
and disease-free survival, calculated from the date
of diagnosis to the date of death or recurrence or last
follow-up, were analyzed by the Kaplan-Meier method.
The study was approved by the Institutional Review
Board.
Results
Clinical and demographic features. A total of 193
patients underwent submandibular gland excision
during the study period; 108 (56%) had a non-neo-
plastic disorder (sialolithiasis or chronic sialadenitis).
The remaining 85 (44%) had a submandibular tumor.
Characteristics of the 85 patients with submandibular
tumors are presented in table 1.
Table 1. Clinical and demographic characteristics
of 85 patients with submandibular gland tumors
Age, yr (range) 57.4 (15-88)
Benign subgroup 55.4 (22-87)
Malignant subgroup 60.5 (15-88)
Sex, n (%)
Men 40 (47%)
Women 45 (53%)
Smoking history, n (%) 7 (8.2%)
Use of alcohol, n (%) 2 (2.4%)
Immunosupressed, n (%) 2 (2.4%)
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Pathology. Sixty-five patients (76%) had a benign
tumor and 20 (24%) had a malignant tumor. Mean
age of these respective subgroups was 55.4 years and
60.5 years. The most common benign neoplasm was
pleomorphic adenoma (n = 53), followed by benign
lymphoepithelial lesion (n = 8) and oncocytoma (n =
4). The malignant tumors consisted of adenoid cystic
carcinoma (n = 11), mucoepidermoid carcinoma (n =
6), and adenocarcinoma (n = 3). Pathologic distribution
is presented in table 2.
Table 2. Distribution of different pathologies in 85
patients with submandibular gland tumors
Histologic type n (%)
Pleomorphic adenoma 53 (62.4)
Benign lymphoepithelial lesion 8 (9.4)
Oncocytoma 4 (4.7)
Adenoid cystic carcinoma 11 (12.9)
Mucoepidermoid carcinoma 6 (7.1)
Adenocarcinoma not otherwise
3 (3.5)
specified
Five patients with malignant tumors had clinical and/
or radiographic evidence of regional nodal metastases
at presentation. The mean duration of follow-up was
6.5 years (range: 2 to 20 years).
Treatment. Patients with malignant tumors under-
went concomitant ipsilateral selective neck dissection
at levels 1 to 3. Modified radical neck dissection was
performed in 1 patient. In 1 patient with a high-grade
mucoepidermoid carcinoma, a marginal mandibulec-
tomy was required to completely excise the tumor. Four
patients (4.7%) had transient marginal mandibular
nerve paresis after surgery. There were no cases of
postoperative surgical wound infection.
Seventeen patients with malignant disease were
treated with adjuvant radiation, and 1 patient with high-
grade mucoepidermoid carcinoma received adjuvant
chemoradiotherapy.
Recurrence and survival. Recurrence was docu-
mented in 2 of the 53 patients (3.8%) with pleomorphic
adenoma and in 7 of the 20 patients (35%) with ma-
lignant tumors. In the group with malignant tumors,
regional recurrence was diagnosed in 5 patients and
distant recurrence in 2. The mean time to recurrence
from surgery was 9 months (range: 6 to 13 months).
The disease-free survival rate at 5 years was 63%. Five
patients were alive with disease at their last follow-up.
Three patients died of the disease and 1 died of other
causes. The 5-year overall survival rate was 52%. In 15
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 SUBMANDIBULAR SALIVARY GLAND TUMORS: CLINICAL COURSE AND OUTCOME OF A 20-YEAR MULTICENTER STUDY
of the 20 patients with malignant tumors, perineural
and/or lymphovascular invasion was noted but did not
correlate with recurrence or survival.
Discussion
In the present study, 24% of all submandibular neo-
plasms treated over a 20-year period were malignant,
which is a much lower proportion than previously re-
ported1-3 and resembles the frequency of malignant tu-
mors in the parotid gland.
Malignant neoplasms were associated with a relatively
high recurrence rate, with a 5-year disease-free survival
rate of 63% following surgery and radiation. A recent
retrospective study of 74 malignant submandibular
gland tumors reported a lower local recurrence rate in
patients treated by surgery and radiation than by surgery
alone.16 Although the difference was not statistically
significant, the authors speculated that radiotherapy
was probably beneficial.
Among patients with benign tumors, only 2 patients
with a pleomorphic adenoma had a recurrence and were
treated with additional surgery. These data suggest a low
recurrence rate for benign submandibular tumors as
opposed to the rate of recurrence in the parotid gland,
but we were unable to find precise data in the medical
literature to support these findings. One study report-
ed a higher rate of recurrence of benign neoplasms in
the parotid gland compared with the submandibular
gland.2 To explain this difference, we speculate that the
submandibular gland is more amenable to complete
excision than is the parotid because there is no need to
resect tissue adjacent to the facial nerve during surgery.
Moreover, the surgical difficulty of complete resection
of deep lobe parotid tumors does not exist in the sub-
mandibular gland.
Evaluation of the neck is essential in all cases of
submandibular malignancy. Mallik et al recommended
elective neck dissection for patients with all stages of
malignant submandibular tumors except T1.17 In our
study, all but 1 patient with a malignant submandibular
tumor underwent neck dissection. Given the tendency
for locoregional recurrence of malignant submandibular
tumors, we believe that comprehensive resection should
be performed for all but low-grade mucoepidermoid
tumors.
Overall 5-year survival in our cohort was 52%. This
rate is in accordance with that found in other studies.18
Pinkston and Cole found that the incidence rate for
both benign and malignant submandibular tumors
increases until age 70 and then declines.18 Crabtree and
Yarington noted that younger patients tend to have be-
nign tumors rather than malignancies.19 However, our
study yielded no correlation between age and tumor
incidence. Previous reports have shown that several
Volume 96, Number 3
histopathologic features may predict poor outcome,
including a cystic component of less than 20%, 4 or
more mitotic figures per 10 high-power fields, neural
involvement, necrosis, and anaplasia.18-20
Interestingly, for tumors of equal histopathologic
grade, the prognosis appeared to be better if the tumor
was located in the parotid gland than in the subman-
dibular gland.21 In a large study on salivary gland
tumors, Goode et al concluded that age, tumor size,
and preoperative symptoms affected patient outcome.12
In the present study, perineural and lymphovascular
invasion did not correlate with either recurrence or
survival.
In conclusion, our study shows that malignant disease
is infrequent in tumors of the submandibular salivary
gland. Patients with submandibular gland pleomorphic
adenoma have a low risk of recurrence compared with
that of the parotid gland.
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