ORIGINAL ARTICLE

RARE INVOLVEMENT OF SUBMANDIBULAR GLAND BY ORAL

SQUAMOUS CELL CARCINOMA
Tseng-Cheng Chen, MD,1 Wu-Chia Lo, MD,1 Jenq-Yuh Ko, MD, PhD,1
Pei-Jen Lou, MD, PhD,1 Tsung-Lin Yang, MD,1,2 Cheng-Ping Wang, MD1,2,3
1
Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College
of Medicine, Taipei, Taiwan. E-mail: wangcp@ntu.edu.tw
2
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan
University, Taipei, Taiwan
3
Department of Otolaryngology, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan

Accepted 2 October 2008

Published online 9 April 2009 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.21039

Keywords: submandibular gland; oral cancer; xerostomia; neck

Abstract: Background. The true involvement of the sub-
dissection; saliva
mandibular gland in primary oral cancer seems quite

uncommon.
Methods. We retrospectively reviewed the pathologic
records of 342 patients with oral squamous cell carcinoma who
underwent wide excision of primary oral cancer and simultane-
ous neck dissection from January 2000 to December 2003.
Results. Of the 383 submandibular glands, only 7 (1.8%)
exhibited tumor involvement. Of them, 5 glands were involved
by direct extension from the primary tumor. One gland showed
local invasion from an adjacent involved lymph node in level I
and 1 was from intraglandular lymph node metastasis. All of
these 6 tumors with submandibular gland involvement were T4
disease (p ¼ .0003) and the neck nodal status on each was
more than N2b (p < .0001).
Conclusion. The patients with early-stage oral squamous
cell carcinoma with preoperative N0 neck may be candidates
for preservation of the submandibular gland. V C 2009 Wiley
Periodicals, Inc. Head Neck 31: 877–881, 2009
Correspondence to: C.-P. Wang
Contract grant sponsor: National Science Council of the Republic of
China; Contract grant number: NSC 96-2314-B-002-075-MY2.
V
C 2009 Wiley Periodicals, Inc.
The
current treatment for oral cancer is wide
excision of the primary tumor and simultaneous
neck dissection of various types such as selec-
tive or radical neck dissection, depending on the
extent of neck involvement. Because the sub-
mandibular gland is located in level Ib, with 6
groups of lymph nodes around/within the gland,
and it is close to primary oral tumors,1 the
submandibular gland is usually removed regard-
less of the type of neck dissection performed.
Because the submandibular glands are responsi-
ble for about 70% to 90% of unstimulated sali-
vary volume,2,3 especially at night, removal of
the submandibular gland as part of the neck
dissection causes xerostomia of some degree,
even though the patient does not receive postop-
erative radiotherapy.2 However, the limited data
available in the literature4,5 indicate that true
involvement of the submandibular gland in pri-
mary oral cancer is quite uncommon. Therefore,
the submandibular gland might be innocent and

Involvement of Submandibular Gland by Oral Cancer HEAD & NECK—DOI 10.1002/hed July 2009 877
might be considered for preservation in surgical
treatment of oral cancer to prevent xerostomia,
especially when postoperative radiotherapy is
not instituted. In this article, we want to answer
the first basic question about the incidence of
submandibular gland involvement by oral squa-
mous cell carcinoma and then try to identify
clinical risk factors that may predict submandib-
ular gland involvement.
PATIENTS AND METHODS
This retrospective study reviewed the pathologic
records of patients with oral squamous cell car-
cinoma who underwent wide excision of primary
oral cancer and simultaneous neck dissection at
the National Taiwan University Hospital from
January 2000 to December 2003. The inclusion
criteria for the study were (1) histopathologi-
cally confirmed squamous cell carcinoma, (2)
primary site located in the oral cavity, and (3)
no previous treatment for head and neck
tumors. The exclusion criteria included patients
with a previous history of other head and neck
cancer, previous irradiation in the head and
neck regions, a proven distant metastasis at
presentation, or nonsquamous cell oral cancer.
All surgical specimens including the primary
tumor and the neck were submitted to the
department of the pathology for permanent histo-
pathological examination. The submandibular
glands were routinely examined grossly and
microscopically. Grossly, the submandibular
glands were dissected out from the adjacent
lymph nodes and neck tissue. When the adjacent
lymph nodes were easily dissected from the gland
and did not harbor malignant cells microscopi-
cally and the primary oral tumor was far from
the gland grossly, several sections by 5 mm along
the longest axis of the gland were microscopically
examined. When the adjacent lymph nodes har-
bored malignancy microscopically or any gross
adhesions between adjacent tissue and the gland
were noted, the submandibular gland nearby the
involved lymph nodes and the adhesion regions
were microscopically examined in detail.
The incidence of pathologic involvement of
the submandibular gland by oral squamous cell
carcinoma was calculated. In addition, potential
risk factors such as sex, age, T classification,
and N classification were evaluated. The TNM
status of each tumor was reclassified according
878 Involvement of Submandibular Gland by Oral Cancer
to the 2002 criteria of the American Joint Com-
mittee on Cancer.6
All statistical analyses were performed using
SPSS software for Windows, version 12.0 (SPSS,
Chicago, IL). Associations between submandibu-
lar gland metastasis and several clinical factors
were assessed using Fisher exact test. Statisti-
cal significance was set as p < .05.
RESULTS
The pathology reports of 342 patients were
reviewed, including 302 men and 40 women,
with a mean age of 50 years (range, 20–90
years). Primary sites of oral cancers included
the buccal mucosa (n ¼ 143, 41.81%), tongue
(n ¼ 121, 35.38%), retromolar trigone area (n ¼
22, 6.43%), alveolar ridge (n ¼ 20, 5.85%), floor
of the mouth (n ¼ 17, 4.97%), hard palate (n ¼
14, 4.09%), and lip (n ¼ 5, 1.46%). Of these
patients, 301 underwent unilateral neck dissec-
tion including excision of the ipsilateral sub-
mandibular gland and 41 patients underwent
bilateral neck dissection with excision of bilat-
eral submandibular glands, thus 383 subman-
dibular glands were available for pathologic
examination. Of the 383 submandibular glands,
7 (1.8%) exhibited tumor involvement, including
5 tumors with ipsilateral gland involvement and
1 with bilateral submandibular gland involve-
ment. Four primary tumors were buccal cancer,
with mandible extension in 3 and extension to
the floor of the mouth in 1; and 2 primary
tumors were gingival cancer, with extension of
the floor of the mouth in 1. Five submandibular
glands were involved by direct extension from
the primary tumor. One submandibular gland
showed local invasion from an adjacent involved
lymph node in level I and 1 was involved due to
intraglandular lymph node metastasis (Table 1).
All of these 6 tumors with submandibular gland
involvement were T4 disease (p ¼ .0003) and
the neck nodal status in each was more than
N2b (p < .0001) (Table 2). Three of the patients
died of the disease within 6 months after treat-
ment due to locoregional recurrence. Two pa-
tients have been alive for about 3 years and 1
patient has been alive for more than 6 years af-
ter definitive treatment.
DISCUSSION
From this series with 383 submandibular
glands examined, there was no case with
HEAD & NECK—DOI 10.1002/hed July 2009
 Table 1. Patterns of submandibular gland invasion by oral
dence of cancer of the floor of the mouth because
squamous cell carcinoma. of different chewing habits of the betel nut in
this country. Despite this, all buccal cancers
No. of except 1 involving the submandibular gland
submandibular gland
clinically extended to either the alveolar ridge
Incidence of invasion or the floor of the mouth. Interestingly, contra-
Ipsilateral submandibular 6/342 (1.75%)
lateral submandibular gland involvement from
gland
Contralateral submandibular 1/41 (2.43%) head and neck cancer has not been previously
gland reported in the literature.4 In this series, there
Direct invasion from primary 5 was 1 locally advanced buccal cancer directly
tumor and bilaterally invading the submandibular
Buccal cancer 4 1=4
glands. Actually, this tumor was so huge that
contralateral
gland the ipsilateral parotid and sublingual glands
Mouth floor involved 2 were involved simultaneously.
Alveolar ridge involved 3 In view of the mechanism of the invasion,
Gingival cancer (mouth floor 1 most of the submandibular glands were directly
involved)
invaded by the primary tumor, which is in ac-
Invasion from metastatic 2
lymph node cordance with Spiegel’s series4; only 2 glands
Gingival cancer 1 Adjacent were invaded by the metastatic lymph node
lymph node in this series. Interestingly, 1 of them showed
Buccal cancer (alveolar ridge 1 Intraglandular local invasion from a metastatic intraglandular
involved) lymph node
lymph node of the submandibular gland, which
is against the comment of Spiegel’s series.4 This
finding proved the opinions of Bartels7 and
submandibular gland involvement in T1-T3 or DiNardo,1 who noted the existence of lymph
N0-N2a disease. Although all cases with sub- nodes within the submandibular gland and
mandibular gland involvement were T4 and believed that they account for 1 mechanism of
N2b-N3, the incidence of submandibular gland tumor involvement of the gland although it is
involvement was only 6.67% in T4 disease and rare.
8.22% in N2b-N3 disease. Therefore, subman- What does this rare occurrence of subman-
dibular gland involvement in oral squamous cell dibular gland involvement by oral squamous cell
carcinoma carcinoma imply in clinical practice? Because
is quite uncommon, especially in early stages. saliva enhances taste, speech, and swallowing
This is in accordance with previous reports.4,5 and facilitates irrigation and lubrication of the
From an anatomical viewpoint, the floor of the oral cavity, salivary gland dysfunction impairs
mouth, lower alveolar ridge, and tongue are the mastication, deglution, and gustatory functions,
nearest to the submandibular gland. Theoreti- and results in dental caries and dry, painful
cally, oral cancer involving these parts has the
greatest chance of directly invading the ipsilat-
eral submandibular gland. In Spiegel’s series,4 Table 2. Clinical factors predicting submandibular
all of the 9 involved submandibular glands, gland invasion.
either invaded from the primary tumor directly Variables Positive submandibular gland p value
or from the involved lymph node, were from
Age NS
ipsilateral cancers of the floor of the mouth,

45 y 1/110 (0.90%)
alveolar ridge, and tongue. In this series, there >45 y 5/232 (2.15%)
was no tongue cancer or cancer of the floor of Sex NS
the mouth involving the submandibular gland Male 4/302 (1.3%)
even though tongue cancer accounted for one Female 2/40 (5%)
T classification .0003
third of our cases. Unlike previous reports,4 buc-
T1þT2þT3 0/252 (0%)
cal cancer was the most common oral cancer T4 6/90 (6.67%)
involving the submandibular gland, followed by N classification <.0001
cancer of the alveolar ridge in this series. This
N2a 0/269 (0%)
may be due to a higher incidence of locally N2b 6/73 (8.22%)
advanced buccal cancer and much lower inci- Abbreviation: NS, not significant.

Involvement of Submandibular Gland by Oral Cancer HEAD & NECK—DOI 10.1002/hed July 2009 879
ulcerative oral mucosa.2,4,8 Among the major
salivary glands, the submandibular gland
produces about 70% to 90% of unstimulated sali-
vary volume, especially during sleep.2,3 There-
fore, about one third of submandibular-gland
resection patients reported xerostomia and
impaired quality of life, particularly complaining
of nocturnal xerostomia.2 Although there are
many therapies for xerostomia including syn-
thetic saliva, gustatory stimulants, autologous
saliva storage, acupuncture, electrostimulation,
and various medi- cations, none of them can
adequately improve quality of life, and some are
associated with side effects.4,9 If the lymph
nodes around the submandibular gland can be
removed with preservation of the functional
gland, xerostomia and complications associated
with saliva deficiency will be avoided, especially
in early-stage oral cancers without expected
postoperative radiotherapy. Given the findings
of the present series, because T4 tumors posi-
tively predicted submandibular gland invasion
and no T1-3N0 tumors involved the submandib-
ular gland, patients with oral cancer at T1-
T3N0 might be candidates for preservation of
the submandibular gland during neck dissection
for xerostomia prevention if section margin of
the primary tumor is adequate. From the expe-
riences of neck dissection for head and neck can-
cers and simple excision of the submandibular
gland for other benign gland diseases, it is not
difficult to dissect the adjacent tissue and lymph
nodes from the submandibular gland without
presence of the tumor nearby. The 4 groups of
the lymph nodes around the submandibular
gland including preglandular, postglandular,
prevascular, and postvascular groups, which are
the more consistent and draining nodes of the
oral cancer, are easily dissected from the gland.1
It is somewhat difficult to dissect the deep group
located between the gland and the mylohyoid
muscle with preservation of the gland, but may
be still doable by means of submandibular gland
transfer technique.10 It is really impossible to
dissect the intraglandular lymph nodes with
preservation of the gland, but fortunately, this
group is rarely present and involved by cancer.1
When any suspicious lymph node metastasis or
close contact between tumor and the gland was
noted during neck dissection, the gland must be
oncologically removed. Despite it is technically
doable, this still needs further evaluation for
feasibility and the potential risk for locoregional
recurrence before this conservative approach is
880 Involvement of Submandibular Gland by Oral Cancer
instituted. Although no submandibular gland
invasion was noted in N1-N2a tumors in our
review, preservation of the submandibular gland
is not suitable for the patients with the preoper-
ative presence of positive cervical lymph node
even though the positive nodes were located out-
side of the level I as most of these patients
might require postoperative adjuvant radiother-
apy, which further leads to dysfunction of the
remaining submandibular gland.
Clark’s series11 found that sublingual gland
invasion was not an adverse prognostic factor
for local recurrence or survival. To date, no
studies have addressed the prognostic value of
submandibular gland invasion.4 This is not
evaluable in this present series because of the
small sample size. Although 3 patients died of
disease within 6 months after treatment,
aggressive treatment for this subgroup of oral
cancer is still valuable because the other 3
patients in this series have lived disease-free for
more than 3 years.
CONCLUSION
Submandibular gland involvement by oral squa-
mous cell carcinoma is quite rare, especially in
the early stages. Locoregionally advanced T4 or
N2b-N3 tumors positively predict the presence
of submandibular gland invasion, especially in
cases of buccal cancer and cancer of the alveolar
ridge in this series. The patients with early-
stage oral squamous cell carcinoma with preop-
erative N0 neck might be candidates for preser-
vation of the submandibular gland during neck
dissection. Further prospective study is needed
to demonstrate the findings from this retrospec-
tive study.
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