METASTASIS TO THE SUBMANDIBULAR GLAND IN HEAD

AND NECK CARCINOMAS

Jeffrey H. Spiegel, MD, FACS,1 Agata K. Brys, MD,1 Amol Bhakti, MD,2 Mark I. Singer, MD, FACS2
1
Department of Otolaryngology – Head and Neck Surgery, Boston University School of Medicine, 88 East Newton
Street, D-616, Boston, MA 02118. E-mail: Jeffrey.Spiegel@bmc.org
2
Department of Otolaryngology – Head and Neck Surgery, University of California, San Francisco, California

Accepted 4 June 2004

Published online 30 September 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.20109

We demonstrated the submandibular gland to be involved only

Abstract: Background. The purpose of this retrospective
chart review was to determine whether and how the subman-
dibular gland is involved in metastases of squamous cell car-
cinoma of the head and neck.
Methods. We reviewed the records of all patients for whom
pathology specimens were available after neck dissection for
primary head and neck cancers at two institutions.
Results. One hundred sixty-nine patients were included in
the study, 27 underwent bilateral neck dissections, and 196
submandibular glands were resected and sent for pathology.
One hundred forty-four glands had normal histologic findings.
Normal or benign histologic changes were present in 187 glands.
Three submandibular glands showed invasion from a locally in-
volved lymph node, and six had direct extension from a primary
lesion. The primary lesions were all ipsilateral to the involved
gland and originated from cancers of the floor of the mouth, al-
veolar ridge, and tongue. No submandibular glands showed
pathologic evidence of metastases.
Conclusions. Because the submandibular gland has no in-
traparenchymal lymph nodes, its involvement in upper aerodi-
gestive tract carcinomas must be through extension from a
locally involved lymph node or the primary tumor. Previous work
has demonstrated that the submandibular gland can undergo
transplantation out of the neck with subsequent reimplantation,
as a possible means of protection from the effects of radiation.
Correspondence to: J. H. Spiegel
B 2004 Wiley Periodicals, Inc.
in cases of ipsilateral oral cavity tumors or metastasis to ip-
silateral level I lymph nodes. We conclude that it is oncologically
sound to consider transplantation and replantation of the con-
tralateral submandibular gland for patients with head and neck
squamous cell carcinoma when level I lymph nodes are unlikely
to be involved. A 2004 Wiley Periodicals, Inc. Head Neck 26:
1064 – 1068, 2004
Keywords: submandibular gland; head and neck carcinoma;
metastasis; xerostomia
Carcinomas of the head and neck affect 70,000
people every year in the United States. Treat-
ment often involves surgical excision of the af-
fected area followed by radiation therapy. Eighty
percent of patients with head and neck cancer in
the United States receive at least one course of
radiation as a component of their therapy.1 Ra-
diation therapy of the head and neck has sig-
nificant associated morbidity, including injury to
the major and minor salivary glands resulting in
xerostomia. Xerostomia as a radiation-induced
injury to the salivary glands was first described
by the French radiobiologist Jean Bergonie in
1911.2 Radiation treatment with as little as 35 Gy
causes permanent salivary dysfunction, and, de-
spite the availability of some newer pharmaceu-

1064 Submandibular Gland Metastasis HEAD & NECK December 2004

ticals that can maximize residual gland function,
so far no true recovery of salivary gland function
after radiation exposure has been reported.3
Saliva is important for everyday functions,
and its absence causes significant discomfort to
those affected.4 Saliva enhances taste, speech and
swallowing, facilitates irrigation and lubrication,
and protects the mucous membranes of the upper
digestive tract.5 It also has antimicrobial and
buffering properties that protect the teeth from
dental caries and chronic fungal infections and
enhances remineralization of tooth enamel.6 The
dental complications of radiation-induced xero-
stomia often lead patients to undergo complete
dental extractions. However, comfortable use of
prosthetic dentures or other dental appliances
after total extractions is hindered by the persis-
tent xerostomia.
Current therapy for xerostomia includes syn-
thetic saliva, gustatory stimulants, autologous sa-
liva storage, acupuncture, electrostimulation, and
various medications, although most patients
make do with frequent sips of water.7 – 9 None of
these treatments can adequately improve the pa-
tient’s quality of life, and some are associated with
significant side effects. For example, pilocarpine
hydrochloride, a widely used cholinergic antag-
onist, stimulates residual salivary gland tissue
not destroyed by radiation therapy, but its side
effects, including sweating, headache, rhinitis,
dizziness, and urinary frequency, make it an in-
tolerable treatment for many patients.
Attention has turned to prevention of xero-
stomia in patients undergoing radiation therapy.
Although shielding of the salivary glands is a
desirable method to preserve salivary function,
local shielding can compromise oncologic treat-
ment and is usually not effective. Surgical
options to preserve salivary gland function by
preventing damage to the submandibular gland
during radiation are being considered. Preserva-
tion of one submandibular gland is adequate to
prevent xerostomia.10
In 1982, Bourdin et al11 proposed that the
transposition of the contralateral submandibular
gland to the submental region can prevent xe-
rostomia after salivary gland irradiation during
radiotherapy for oropharyngeal cancer. The re-
searchers obtained good results in most cases
treated, with conserved salivary secretion as con-
firmed by scintigraphy, but they warn that this
method should be reserved for patients with oro-
pharyngeal cancer without lymph node metasta-
ses to the contralateral side.
Submandibular Gland Metastasis
More recently, Jha and Seikaly12 have shown
that submandibular gland transfer to the anterior
submental region allows for shielding of the gland
during radiation therapy and preventing xerosto-
mia. In other words, Jha and Seikaly demonstra-
ted that a single submandibular gland prevented
symptomatic xerostomia and that their patients
had a more mild radiotherapy course with less
mucositis and weight loss. This provides support
that a single gland may be adequate to prevent
xerostomia. Of course, by remaining pedicled, the
authors needed to be very careful in modifying
the radiation field to avoid the gland, and they
therefore limit the situations in which this
technique can be applied. Spiegel et al13 demon-
strated that it is possible to transplant the
submandibular gland to the groin area in rabbits
and to transfer it back to the neck area with the
gland maintaining its integrity and function.
They propose that this is a promising preventive
treatment for xerostomia in patients with head
and neck cancers about to undergo radiation
therapy. Although this work by Spiegel et al is
likely the first study to demonstrate that micro-
vascular transplantation and subsequent replan-
tation of the same organ is possible, certainly
many questions remain before this can be proven
as a successful technique in preventing postirra-
diation xerostomia. In this work, the rabbits did
not receive radiation to the neck before replan-
tation of the organ. Radiation treatments affect
blood vessels and nerves. Although there is large
clinical experience with successful microvascular
tissue reconstruction, including sensate flaps,
into radiated head and neck tissue, the particular
effect this may have on salivary gland replanta-
tion can be reasonably expected to be minimal but
is in reality unknown.
Another important question is whether this
procedure is oncologically sound in a patient with
a head and neck squamous cell carcinoma. That
is, does squamous cell carcinoma metastasize to
the submandibular gland? Clearly, it would be
unwise to transplant a potentially cancerous or-
gan. Metastatic spread of a neoplasm to the sal-
ivary glands is unusual, and if it occurs, the
parotid gland is more likely to be affected.14 It
has been postulated that unlike the parotid gland,
the submandibular gland is unlikely to be the
host tissue for metastases because of its lack of
lymph nodes or vessels.15 When the submandib-
ular gland is involved in metastatic cancer, it is
through hematogenous spread of cancers origi-
nating outside the head and neck.
HEAD & NECK December 2004 1065
 This study aims to determine whether and
how the submandibular gland is involved in
metastases of squamous cell carcinoma of the
head and neck.
METHODS
This retrospective study reviewed the records of
patients who underwent neck dissections for can-
cer at the Boston University and the University
of California San Francisco medical centers from
1996 to 2001. All patients who underwent dis-
section for primary head and neck lesions and for
whom pathology specimens were available were
included in the study.
We reviewed the pathology reports of 169
patients, including 103 men and 66 women, with
mean age of 63 years (range, 21 – 91 years). Of
the 169 patients, 27 had bilateral neck dissec-
tions, thus 196 submandibular glands were
available to examine. Primary tumors included
the tongue (n = 54), floor of the mouth (n = 25),
tonsillar fossa (n = 15), base of tongue (n = 15),
retromandibular trigone (n = 11), alveolar ridge
(n = 11), palate (n = 6), buccal mucosa (n = 6), lip
(n = 5), and the posterior pharynx (n = 2).
Twelve patients had primary tumors involving
multiple structures.
RESULTS
Of the 196 submandibular glands examined,
144 had no tumor involvement with completely
Table 1. Pathology of submandibular glands (SMG).
Histology Number of SMG
Normal
Malignant Changes:
Direct extension from primary tumor (all glands ipsilateral)
Floor of Mouth
Floor of Mouth and Alveolar Ridge
Floor of Mouth and Tongue
Local invasion from involved (all glands ipsilateral)
lymph node
Floor of Mouth
Tongue
Alveolar Ridge
Benign Changes:
Inflammation and changes consistent
with radiation therapy
Chronic Sialadenitis
Atrophy
Sialometaplasia
Oncocytosis
Total
1066 Submandibular Gland Metastasis
normal histologic findings. Three submandibular
glands showed local invasion from an involved
lymph node, and six had direct extension from
the primary lesion. All of these were from ipsi-
lateral cancers of the floor of the mouth, alveolar
ridge, and tongue (Table 1). Histologic exami-
nation of the remaining glands revealed inflam-
mation and changes consistent with radiation
therapy, chronic sialoadenitis, atrophy, sialometa-
plasia, and oncocytosis. No submandibular glands
showed pathologic evidence of metastases.
DISCUSSION
Metastasis to the submandibular gland occurs
more commonly through hematogenous spread of
cancers residing outside the head and neck. Ves-
secchia et al16 performed a review of the literature
that revealed more than 100 cases of metastases to
the submandibular gland. Most metastases arose
from primary tumors at distant sites, such as the
breast, lungs, or the genitourinary system. There
have been case reports of metastases to the sub-
mandibular gland from uterus leiomyosarcoma.17
Case reports of submandibular gland metastases
from the breast have been described by several
authors.18 – 21 Bilateral submandibular gland in-
volvement in a patient with advanced breast can-
cer has also been reported.22
In the 1970s, Evans and Cruickshank23 ob-
served that even with advanced carcinoma pre-
sent in the adjacent submandibular lymph areas,
it is unusual for the submandibular gland to be
involved. More recently, Junquera et al24 eval-
uated the involvement of the submandibular
gland in 31 patients with squamous cell carcinoma
of the floor of the mouth. Histopathologic exami-
nation identified cervical node metastasis in
144
34.1% of the ipsilateral neck dissections. Cervical
periglandular metastases were found in 31.7% of
4 neck dissections, but in no case was microscopic
1 affectation of the submandibular gland found.
1 Although periglandular metastases in carcinoma
of the floor of mouth are frequent, submandibular
1 gland involvement is unusual. Contralateral sub-
1 mandibular gland involvement from head and
1 neck carcinoma has not been reported.
Our own review of patients with head and
6
neck cancer who underwent neck dissection de-
20 monstrated that in no case did a squamous cell
14 carcinoma metastasize to the submandibular
1 gland. The submandibular gland was only in-
2 volved in cases in which the primary tumor was
196
in close proximity to the gland, or when meta-
HEAD & NECK December 2004
stasis to level I of the neck had occurred with
extension from a locally involved lymph node into
the submandibular gland. Clearly, it would be
unwise to dissect out for transplantation a sub-
mandibular gland that is ipsilateral to a tumor
of the floor of mouth or mandible, or one in
which metastasis to the submental region is
likely. However, in cancers in which contralateral
neck disease is not suspected, the submandibular
gland is very unlikely to be involved with car-
cinoma and would seem to be available to use for
a xerostomia prevention procedure.
Spiegel et al25 have been successful in trans-
planting the submandibular gland in rats and in
transplanting and replanting the submandibular
gland in rabbits.14 These methods can the-
oretically be applied to patients with head and
neck cancers who are going to undergo radiation
therapy. Removal of the submandibular gland
from the radiation field during treatment would
protect the gland from harm, and subsequent
reimplantation into the neck region could resolve
the patient’s xerostomia. Spiegel et al found that
the reimplanted rabbit gland both survived and
was functional; however, the volume of saliva from
the denervated gland was not calculated because
of limitations in the rabbit model. The size of the
submandibular ganglion should allow for reinner-
vation of the submandibular gland on reimplan-
tation in a human, although as with all neural
repairs, the degree to which this will be success-
ful or functional is not predictable. Before now,
the transplantation and replantation method of
xerostomia prevention has not been attempted
in humans because of the fear of transplanting
cancerous tissue to the distant site that would
be temporarily hosting the gland. This study dem-
onstrates that squamous cell carcinoma of the
head and neck is unlikely to metastasize to the
submandibular gland. Thus, we extrapolate that
submandibular gland transfer is a promising and
oncologically sound treatment alternative for xe-
rostomia prevention.
CONCLUSION
Because the submandibular gland has no intra-
parenchymal lymph nodes, its involvement in
upper aerodigestive tract carcinomas must be
through extension from a locally involved lymph
node or from distant metastases of a primary
tumor. Previous work has demonstrated that the
submandibular gland can undergo transplanta-
tion out of the neck with subsequent reimplanta-
Submandibular Gland Metastasis
tion, a technique protecting the salivary tissue
from the effects of radiation.
We demonstrated the submandibular gland to
be involved only in cases of ipsilateral oral cavity
tumors or metastasis to ipsilateral level I lymph
nodes. We conclude that it is oncologically sound
to consider transplantation and replantation of
the contralateral submandibular gland in pa-
tients with head and neck squamous cell carci-
noma when level I lymph nodes are unlikely to
be involved.
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