for
SALIVARY GLAND DISORDERS
Developed for the
Aerospace Medical
Association
by their
constituent organization
American Society of
Aerospace Medicine Specialists
Overview: There are three major
salivary glands: parotid, submandibular, and sublingual. They collectively serve to secrete saliva
through a ductal system. Saliva from the
parotid is released adjacent to the maxillary molars through Stenson’s
duct. Saliva from the submandibular
gland (and portions of the sublingual gland) empty into the floor of the mouth
via Wharton’s duct, whose orifice lies adjacent to the lingual frenulum. Additionally, there are numerous minor
salivary glands scattered throughout the oral cavity and generally named based
on co-location to various anatomic structures (e.g. labial, buccal, etc). The saliva released from these salivary
structures is a protein-rich hypotonic fluid, whose release is controlled by
sympathetic and parasympathetic stimulation.
Pharmacologic agents with positive muscarinic activity (agonists) will
result in increased saliva output. Any
condition (or treatment) which diminishes salivary production, leading to a
condition known as xerostomia (dry mouth), can contribute to a variety of oral
conditions (e.g. increased risk of dental caries) and systemic
complications. The leading cause of
xerostomia is pharmacological agents such as anticholinergics, tricyclic
antidepressants, neuroleptics, and monoamine oxidase inhibitors. Previous exposure to radiation to the head
and neck and systemic diseases such as Sjögren’s syndrome, sarcoidosis, and
amyloidosis also cause xerostomia. Individuals
with xerostomia complain of dry mouth and throat and associated difficulty with
mastication and swallowing. More severe
cases will have difficulty with speech.
Non-tumor
salivary gland disorders can be divided into inflammatory and trauma. Traumatic enlargement of salivary glands can
result from either penetrating or blunt trauma, as well as that resulting from
radiation therapy. Injuries to salivary
glands are uncommon, with penetrating trauma the primary cause. Penetrating trauma is best managed with
surgical exploration and repair as indicated.
The formation of hematomas, seromas, etc, from blunt trauma can be
managed by observation and/or needle aspiration or drainage as necessary. Injuries that cause disruption to the
submandibular and parotid glands have a higher likelihood of associated
vascular and skeletal injury. Mucoceles
(known as ranulas if they involve the floor of the mouth) of the extravasation
type usually result from trauma to minor salivary gland excretory ducts and
caused by the accumulation of saliva into the surrounding tissue. They frequently present (following trauma) as
painless smooth swellings with a bluish hue.
The treatment of choice is surgical marsupialization. (Occasionally the associated salivary gland
is removed to prevent recurrence). Necrotizing
sialometaplasia is a benign condition which typically affects the palate and
other sites containing salivary glands.
The etiology is believed to be secondary to local trauma or focal
vascular compromise which results in necrosis.
This condition should be observed, and usually heals spontaneously in
6-10 weeks. The challenge,
however, is that it tends to mimic malignancy both grossly in appearance and
microscopically; often leading to an erroneous diagnosis and subsequent
unnecessary and potentially extensive surgical excision. Secondary damage following radiation therapy
is generally managed with supportive measures.
Inflammatory
disorders include viral infections, bacterial infections, granulomatous, and
noninfectious. Viral infections (e.g.
mumps, human immune virus, and cytomegalovirus) are generally managed with
supportive and symptomatic care. Acute suppurative
sialadenitis is a bacterial infection of the salivary gland; the parotid is the
most common. It usually is associated
with medically debilitated and post surgical individuals. It is caused by retrograde bacterial
contamination of the salivary gland; due to stasis of saliva, dehydration or
significant hemorrhage. All of the
bacterial conditions require anti-microbial therapy, hydration, culture, and
possible incision and drainage (particularly for those associated with abscess
formation).
Sialolithiasis,
stones or calculi in the salivary gland typically present with acute, painful,
and swollen major salivary gland (pain being proportional to the degree of
ductal obstruction and/or the presence of secondary infection). Acute episodes are frequently precipitated by
eating or the anticipation. Entrapment
of salivary fluid within the encapsulated gland generates the pain. As such, the involved gland is typically
enlarged and tender to palpation.
Complications from sialoliths include fistula formation, acute
sialadenitis, stricture, mucus retention cyst (obstructive sialadenitis) and
ductal dilatation. The submandibular
gland is the most common site for sialoliths to occur (80-90%), with 5-15% in
the parotid gland, and the remaining 2-5% in the sublingual gland. The high frequency of submandibular
involvement is believed to be secondary to the torturous course of Wharton’s
duct, higher levels of calcium and phosphate, and the relative dependent
position of the gland, thus facilitating stasis and stone formation. The actual etiology of sialolith formation
remains a mystery (however, gout can cause salivary stones of uric acid),
despite many suspected contributing factors such as inflammation, irregular
duct system, irritants, medications, and salivary organic material acting as a
nidus for subsequent calcification.
Recurrence rate is approximately 20%.
Stones are primarily crystalline in nature composed of mostly hydroxyapatite
(calcium phosphate and carbon, with trace amounts of magnesium, potassium
chloride and ammonium). Approximately
half of parotid gland stones, and roughly 20% of submandibular stones are
poorly calcified and therefore radiolucent.
Gout and nephrolithiasis have been associated with sialolithiasis. An occlusal view plain radiograph will
identify most radiopaque submandibular stones, and an anteroposterior facial
view will facilitate parotid stone identification. CT is approximately ten-fold more sensitive
in the detection of sialoliths than is plain-film imaging. Acute management is generally supportive such
as remaining well hydrated, tart candy (e.g. lemon drops) to promote salivary
flow, moist heat to gland, massage the gland, pain control, and antibiotics, if
infection suspected. Surgical
intervention is required in pronounced cases; however, lithotripsy has become
increasingly popular as a noninvasive treatment option. Ultrasound for stone detection, followed by
extracorporeal lithotripsy may also be performed.
Granulomatous
disease is managed according to etiology, often with long-term chemotherapeutic
agents (e.g. anti-tuberculin medications for mycobacterium, and/or surgical
excision for atypical mycobacterium).
Sarcoid is generally managed symptomatically. Autoimmune/noninfectious conditions include
benign lymphoepithelial disease and Sjögren’s syndrome; both which are managed
medically and symptomatically. Sjögren’s
syndrome consists of a constellation of complaints which include xerostomia,
dry eyes (sicca), dry nasal mucosa or vaginal mucosa. Miscellaneous chronic salivary gland
conditions include systemic diagnoses of allergies, cystic fibrosis, and drug
induced. Tissue samples are often
required for definitive diagnosis, particularly when a systemic condition such
as Sjögren’s syndrome or amyloidosis is suspected; in which case a minor
salivary gland (e.g. labial) is sampled for histologic examination. When tissue is required from a major salivary
gland, fine-needle aspiration is the method of choice. Certain serologic studies (e.g., ANA, RF,
ESR, immunoglobulins, etc) are helpful in the diagnosis of many systemic
conditions (Sjögren’s syndrome), as is the elevation of amylase isoenzymes (so
as to differentiate between pancreatic and salivary sources).
Siladenosis
is when both parotid glands may be diffusely enlarged, soft and nontender, and
not associated with salivary hypofunction.
This occurs at age 20-60 years and gender nonspecific. Biopsy shows enlarged acinar cells (twice
normal) with cytoplasm packed with granules.
The exact cause is unknown, but inappropriate autonomic nervous system
stimuli is suspected; approximately half the individuals with this disorder
have endocrine disorders such as diabetes, nutritional disorders or have taken
drugs such as guanethidine, thioridazine or isoprenaline. No treatment is usually necessary, although
partial parotidectomy may be used for cosmetic reasons.
Tumors
of the salivary glands typically present as asymptomatic masses. Benign salivary gland tumors include the
following: mixed tumor (pleomorphic adenoma), monomorphic adenomas (basal cell
adenomas, canalicular adenomas, myoepithelioma, oncocytic tumors, and sebaceous
adenomas), and ductal papillomas (inverted ductal papillomas, sialadenoma
papilliferum, and intraductal papilloma).
These tumors may arise from any of the major or minor salivary glands,
with the vast majority arising from epithelial originated tissue. The frequency of gland involvement/percent
malignant is as follows: 65% parotid/25%
malignant, 10% submandibular/40% malignant, <1 % sublingual/90% malignant
and 25% minor salivary gland/50% malignant.
Generally, the smaller the salivary gland of origin, the more likely it
is malignant. There are two major classification
systems for salivary gland pathology, one from the World Health Organization
and the other from Armed Forces Institute of Pathology (AFIP). Both of these systems are very detailed and
differ somewhat in their malignant tumor classifications.
The
mixed tumor (pleomorphic adenoma) is the most common tumor of the salivary
glands; the vast majority (85%) arising in the parotid gland. Submandibular involvement accounts for
approximately 8% of cases and the remaining 7% are distributed amongst the
minor salivary glands. These tumors
account for 50% of all minor salivary gland lesions. Mixed tumors tend to present between the
fourth and sixth decades, with a slight predilection for males. They are most commonly located on the palate,
followed by upper lip and buccal mucosa.
Treatment is simple surgical excision, by means of a superficial
parotidectomy (with facial nerve preservation).
Lesions involving the palate typically require adjacent bone
removal. Failure to completely remove
mixed tumors in major salivary glands frequently results in recurrence. Additionally, 25% of these lesions undergo
malignant transformation over a period of many years.
Most
monomorphic adenomas are rare and exhibit benign growth characteristics. Approximately 70% of basal cell adenomas
occur within the parotid gland.
Canalicular adenomas, however, occur almost exclusively within the oral
cavity, frequently on the upper lip.
Again, treatment consists of simple surgical excision with narrow clear
margins. Myoepitheliomas most commonly
arise from the parotid gland, and while epithelial in origin, they appear more
as smooth muscle. Treatment is the same
as for mixed tumors. Oncocytomas are
rare lesions which typically arise from the parotid gland, with superficial parotidectomy
being the treatment of choice. Warthin’s
tumor (papillary cystadenoma lymphomatosum) arises mostly from the parotid
gland and has been linked to tobacco use.
Sebaceous adenomas are rare lesions, occurring most commonly in the
submandibular and parotid glands.
Parotidectomy or local excision is the treatment of choice. Ductal papillomas are rare lesions which
arise from the ductal structures of the salivary gland involved.
Malignant
neoplasms of the salivary glands typically exhibit the following properties:
rapid growth, ulceration, fixed, associated facial palsy, lack of
encapsulation, and metastasis. As
opposed to the benign lesions discussed above, which are generally curative
with simple local excision, these lesions require wider resection and
frequently follow-up radiation therapy.
In general, salivary gland neoplasms respond poorly to chemotherapy and
usually are used for palliation. A
malignancy which presents with pain often indicates nerve involvement, and as
such, a poorer prognosis. Documenting
facial nerve function is particularly important, as associated facial paralysis
is a harbinger of malignancy; as are multiple palpable masses, fixed mass, and
the presence of adjacent lymphadenopathy.
Malignant
salivary gland tumors are a heterogeneous group of tumors with a great
diversity in histologic appearance and biologic behavior. The American Joint Committee on Cancer (AJCC)
TNM staging system is used for parotid, submandibular and sublingual
glands. Tumors arising from the smaller
salivary glands are classified and staged based on site of origin. T categories are based on size and extension
of the tumor; N categories are based on lymph node involvement; and M is based
on presence or absence of distant metastasis.
The following tumors are considered low-grade lesions: mucoepidermoid
carcinoma, polymorphous low-grade adenocarcinoma, acinic cell carcinoma, clear
cell carcinoma, and basal cell adenocarcinoma.
Low-grade lesions typically have an excellent prognosis. Mucoepidermoid carcinoma is unique in that it
is the most common salivary gland malignancy with growth properties ranging
from low-grade to very high-grade. They
are also the most common salivary gland malignancy in children. Most arise from the parotid gland. The most common intraoral site is the
palate. The following tumors demonstrate
intermediate-grade malignancy: mucoepidermoid carcinoma, epimyoepithelial
carcinoma, and sebaceous adenocarcinoma.
High-grade malignancies include mucoepidermoid carcinoma, adenoid cystic
carcinoma, carcinoma ex-mixed tumor, salivary duct carcinoma, squamous cell
carcinoma, and oncocytic adenocarcinoma.
Five-year survival rate for various malignant
tumors range from mucoepidermoid (75-95%); adenoid cystic (40-80%);
adenocarcinoma (20-75%); malignant mixed tumor (35-75%); and squamous cell
carcinoma (25-60%).
A
variety of imaging techniques are utilized to diagnose salivary gland
disorders, including plain-film radiography, sialography, ultrasonography
(U/S), radionucleotide imaging, magnetic resonance imaging (MRI), and computed
tomography (CT). Standard dental imaging
is often sufficient in the initial evaluation of local pain and swelling of the
salivary gland, particularly those associated with larger radiopaque
sialoliths. Sialography (via retrograde
instillation of contrast material) provides a clear image of the ductal system,
and will readily identify obstructions from stones and strictures; and is the
imaging modality of choice in the initial evaluation of acute pain and swelling
of a single salivary gland. Sialography
can be performed for the evaluation of submandibular and parotid glands, but
should not be performed if infection is suspected due to increased risk of
additional irritation and the potential for gland and/or duct rupture. Neoplastic lesions are best imaged with CT or
MRI. Adjacent bony destruction, often
associated with malignant lesions, may be evident on initial plain films in
some cases. These modalities most
accurately detail gland pathology, surrounding structures, and the proximity to,
or actual involvement of the facial nerve.
U/S is particularly useful in the identification of more superficial
lesions in the submandibular and parotid glands, and is especially useful in
differentiating between intra- and extraglandular masses and determining
whether the lesion is solid or cystic in nature; with benign lesions typically
appearing as solid, and well-circumscribed hypoechoic intraglandular
masses. U/S is also well suited for
identifying abscess formations and sialoliths.
Radionucleotide imaging typically involves scintigraphy with technetium
99m (Tc99m) pertechnetate, and is the only modality capable of providing
information regarding the salivary glands’ functional capability (as evidenced
by abnormal gland uptake and/or excretion).
Also Tc99m is useful in assessing tumors; both Wharthin’s and oncoytomas
light up strongly.
Aeromedical Concerns:
Most
salivary gland disorders would generally not be considered to pose an immediate
risk to flight; at least relative to the risk for sudden incapacitation in
flight from a known or yet to be diagnosed condition. Certainly a salivary stone may cause pain
during flight (especially following a meal) but this does not generally produce
incapacitating levels of discomfort such as that frequently associated with
renal stones. As such, most aeromedical
concerns relate to the identification of conditions which might interfere with
wear of the oxygen mask, or generally impair function, or require acute medical
intervention (e.g. antibiotic, anti-inflammatory, etc.).
Medical Work-up and
Waiver Consideration: Recurrent calculi of the salivary glands or ducts, and
salivary fistulas are disqualifying for all flying classes in the
military. Furthermore, any anatomic or
functional anomaly of head or neck structures, which interfere with normal speech,
ventilation of the middle ear, breathing, mastication, swallowing, or wear of
aviation or other military equipment is disqualifying. Specifically, xerostomia (dry mouth) from
whatever cause, if significant enough to interfere with mastication and swallowing
would be grounds for disqualification, as would any condition which interferes
with the wear of the aviator oxygen mask (as might occur with certain
conditions involving swelling of the parotid and/or submandibular glands). The cockpit environment of low
humidity also can exacerbate xerostomia.
Of course, malignancies of any sort are disqualifying for continued
flying duty. Benign tumors are
considered disqualifying only if they interfere with the function or ability to
wear required life support equipment or if they are likely to enlarge or be
subjected to trauma during routine military service or have high malignant
transformation potential. Chronic
systemic conditions which may involve salivary gland structures (or function)
are addressed under the specific condition identified (e.g., Sjögren’s
syndrome, diabetes mellitus, and sarcoidosis).
The
aeromedical summary for waiver of recurrent
salivary stones or fistula should
include:
A.
History, physical (thorough head and neck examination), medical
evaluation and treatment for all episodes; to include complete description of
presenting symptoms.
B.
Reference to all laboratory and imaging studies obtained.
C.
Otolaryngology/oral-maxillary consultation; with specific reference to
likelihood of recurrence.
D.
Statement regarding ability to speak clearly and to adequately fit
aviator oxygen mask and other required life support equipment.
The
aeromedical summary for an initial waiver for impaired speech or mastication or other condition which precludes wear
of life support equipment should include:
A.
History, physical, medical evaluation and treatment; to include complete
description of presenting symptoms.
B.
Reference to all laboratory and imaging studies obtained.
C.
Operative notes, if applicable.
D.
Histology report, if applicable.
E. Otolaryngology/oral-maxillary consultation;
with specific reference to likelihood of recurrence and/or malignant
transformation and need for on-going surveillance.
F.
Statement regarding ability to speak clearly and to adequately fit
aviator oxygen mask and other required life support equipment.
The
aeromedical summary for a waiver for a benign
tumor should include:
A.
History, physical, medical evaluation and treatment; to include complete
description of presenting symptoms and any residual symptoms after treatment.
B.
Reference to all laboratory and imaging studies obtained.
C.
Operative notes (initial waiver only).
D.
Histology report (initial waiver only).
(For rare cell types, an AFIP report required.)
E. Otolaryngology/oral-maxillary consultation;
with specific reference to likelihood of recurrence and/or malignant
transformation and need for on-going surveillance.
F.
Statement regarding ability to speak clearly and to adequately fit
aviator oxygen mask and other required life support equipment.
The
aeromedical summary for a waiver for a malignant
tumor should include:
A.
History, physical, medical evaluation and treatment; to include complete
description of presenting symptoms any residual symptoms after treatment.
B.
Reference to all laboratory and imaging studies obtained.
C.
Operative notes (initial waiver only).
D.
Histology report (to include AFIP report) (initial waiver only).
E.
Medical evaluation board summary recommendations (initial waiver only).
F.
Otolaryngology/oral-maxillary and oncology consultation; with specific
reference to likelihood of local recurrence or metastasis and detailed
description of recommended surveillance regiment.
G.
Statement regarding ability to speak clearly and to adequately fit
aviator oxygen mask and other required life support equipment
List
of Relevant ICD9 Codes Associated with Salivary Gland Disorders
|
ICD9 Code |
Non-neoplasm
Salivary Gland Conditions |
|
527.5 |
Sialolithiasis |
|
527.6 |
Mucucoele |
|
527.7 |
Disturbance
of salivary secretion, to include hyposecretion, ptyalism, sialorrhea, and
xerostomia |
|
527.8 |
Other
specified diseases of the salivary glands (benign lymphoepithelial lesions, sialectasia, sialosis, stenosis
of the salivary duct, stricture of the salivary duct) |
|
710.2 |
Sicca
syndrome (Sjögren’s syndrome, keratoconjunctivitis sicca) |
|
750.23 |
Atresia, salivary gland |
|
750.24 |
Congenital
fistula of the salivary gland |
|
ICD9 Code |
Salivary Gland
Neoplasms |
|
142.0 |
Parotid
gland, malignant neoplasms |
|
142.1 |
Submandibular
gland, malignant neoplasms |
|
142.2 |
Sublingual
gland, malignant neoplasms |
|
142.8 |
Other
major salivary glands, malignant neoplasms |
|
142.9 |
Salivary
gland, unspecified, malignant neoplasms |
|
210.2 |
Major
salivary glands, benign neoplasm |
|
230.0 |
Lip,
oral cavity, and pharynx, carcinoma in situ |
|
235.0 |
Major
salivary gland, neoplasm of uncertain behavior |
Aeromedical Disposition (military):
Military
guidance (Air Force Instruction 48-123, Army Regulation 40-501, and Navy
Aeromedical Reference and Waiver Guide) have very few specific references to
salivary gland disorders. Non-recurrent
conditions and/or benign lesions which have been excised without functional
deformities or impairment are favorably considered for all waiver categories. Recurrent calculi of the salivary glands or
ducts, and salivary fistulas are specifically referenced as disqualifying. Malignancies of any sort are disqualifying
for continued flying duty. Benign tumors
are considered disqualifying only if they interfere with the function or the
wear of equipment, or are likely to enlarge or be subjected to trauma during
military service or show malignant potential.
Chronic systemic conditions which may involve salivary gland structures
(or function) are addressed under the specific condition identified (e.g.,
Sjögren’s syndrome, diabetes mellitus, sarcoidosis). As suggested above, the challenge for the
provider is often making the diagnosis of a chronic systemic condition, which
just happens to manifest itself with symptoms involving the salivary gland or
related structures.
More
generally, any anatomic or functional anomaly of head or neck structures, which
interfere with normal speech, ventilation of the middle ear, breathing,
mastication, swallowing, or wear of aviation or other life support equipment is
grounds for disqualification.
Specifically, xerostomia (dry mouth) from whatever cause, if significant
enough to interfere with mastication and swallowing would be grounds for
disqualification, as would any condition which interferes with the wear of the
aviator oxygen mask (as might occur with certain conditions involving swelling
of the parotid and/or submandibular glands).
Malignant lesions would not be favorably considered for waiver on any
initial flying physical. Unless of a
temporary nature (i.e., currently and permanently resolved), any condition
which results in impaired speech or mastication or precludes the wear of
required life support equipment (such as the aviator oxygen mask) would not be
considered for waiver.
Aeromedical
Disposition (civilian): Similarly considering
the issues addressed above relative to military flight, the current AME
guidance does not list salivary gland disorders as disqualifying in and of
themselves; except for of course, those associated with malignancies. Additionally, the FAA utilizes a pathology
code system rather than the ICD9 coding system utilized by the military. As such, a query of the FAA database does not
provide comparable data with respect numbers of cases submitted.
Waiver Experience
(military): A recent ICD9 and
diagnosis text query of the Aeromedical Information and Waiver Tracking System
(AIMWTS) database was accomplished. A
total of three entries were identified for flying personnel: (1) benign mixed
parotid tumor in a 33 year old male loadmaster (Indefinite Class III waiver was
granted following successful local excision), (2) submandibular sialoadenitis and sialolithiasis in a 31 year old senior
pilot (Flying Class II waiver granted following surgery to remove stone), and
(3) Mucoepidermoid carcinoma of the right palate (Flying Class I/IA waiver
denied). Due to the relative infrequency
of salivary gland disorders in the flying population, a conservative case-by-case
approach to waiver consideration is reasonable.
Any salivary gland disorder presenting in a younger patient (such as
with any initial flight physical) are in and of themselves quite unusual cases.
Waiver Experience
(civilian): Under pathology code
259 (diseases of the mouth, parotid gland, tongue, neurosarcoma,
mandible, and jaw) the follow numbers of examinations have been certified
within the past three years: First Class, 84; Second Class, 75; and Third
Class, 212. For pathology code 261
(disease of the pharynx) the following cases have been certified within the
past three years: First Class, 50; Second Class, 36; Third Class, 47. Lastly, for pathology code 269 (other throat
pathology, tonsil cancer): First Class, 50; Second Class, 39; and Third Class,
108.
References:
1.
Arrieta AJ, McCaffrey TV. Chapter 58 – Inflammatory disorders of the
salivary glands. In Cummings C, ed. Otolaryngology: Head and Neck Surgery, 4th
ed. Mosby. 2005
2.
Battaglia S, Kern R, Kies
M. Salivary Gland Tumors: UpToDate: http://www.uptodate.com/; version 15.3;
June 13, 2007.
3.
Cappaccio P, Ottaviani F, Manzo R, et al.
Extracorporeal lithotripsy for salivary calculi: a long-term clinical
experience. Larygoscope. Jun 2004; 114: 1069-107.
4.
Daniels T. Chapter 451: Diseases of the Mouth and Salivary Glands. In: Goldman,
ed. Cecil Medicine. 23rd ed.
5.
FAA, Guide for Aviation Medical Examiners (version V). Retrieved 29 February
2008 from: http://www.faa.gov/about/office_org/headquarters_offices/avs/offices/aam/ame/guide/media/guide06.pdf.
6.
Fazio SB, Deschler DG. Salivary Gland Stones:
UpToDate: http://www.uptodate.com/; version 15.3;
November 30, 2006.
7. Ferri F, Wachtel T. Instant Diagnosis and Treatment. In: Ferri F, ed. Ferri's Clinical
Advisor 2007. 9th ed:
Mosby; 2007.
8.
Fox R, Creamer P, Moschella S. Clinical
Manifestations of Sjogren's syndrome: Exocrine gland
disease: UpToDate: http://www.uptodate.com/;
version 15.3; May 9, 2007.
9.
Johns MM. Salivary Gland Neoplasms: emedicine:
http://www.emedicine.com/ent/topic679.htm; 2007.
10.
Regezi. Chapter 8: Salivary Gland Diseases. In: Regezi, ed. Oral
Pathology: Clinical Pathological Correlations. 4th ed: Saunders; 2003.
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July 22, 2008