Salivary Gland

Introduction

  • Three large, paired major glands
    • Parotid
    • Submandibular
    • Sublingual
  • Smaller, minor glands
    • Throughout the lamina propria of the upper aerodigestive tract
    • ~ 600-1000
    • Most in oral cavity
      • 50% in hard palate
  • Salivary gland function is produce saliva
    • 60% is produced by Parotid
  • Each gland is composed of acini of mucinous or serous cells
    • Myoepithelial cells surround the acinar cells
  • Salivary ducts within each gland:
    • Intercalated
    • Striated
    • Excretory

Anatomy

Parotid

  • The anatomic isocenter is at the axial level at C2/C3
  • Superficial to and partly behind the ramus of the mandible
  • Covers the masseter muscle
    • Posterior part of the muscle
  • Fills the space between the ramus of the mandible and the anterior border of the sternocleidomastoid muscle
  • Two lobes:
    • Superficial
    • Deep
    • One or more isthmi connects these two lobes
      • Facial nerve is wrapped through these isthmi
      • Facial n. enters the deep surface of the gland as a single trunk —> passing posterolateral to the styloid process
        • —> usually leaves the gland as five or more branches from ant, up and lower border of Parotid
        • Facial n. is superficial to the main blood vessels that traverse the gland
  • Lymphatics:
    • Facial LN
    • Downward along the retromandibular vein
      • —> Superficial LN along the outer surface of the SCM —> deep cervical chain
    • LN from parietal region of the scalp —> parotid nodes in front of the ear and partly to the retroauricular nodes in back of the ear, which, in turn, drain into upper deep cervical nodes

Submandibular Gland

  • Has a superficial and deep portion
  • Fills the triangle between the two bellies of the digastric and the lower border of the mandible
  • On the lower surface of the mylohyoid and behind it
  • Against the lateral surface of hypoglossus
  • Inferior surface is adjacent to the submandibular LN
  • Between the lingual nerve above and the hypoglossal nerve below
  • Wharton's ducts
  • Drain into the sublingual caruncles (caruncula sublingualis) on either side of the lingual frenulum along with the major sublingual duct (Bartholin).
  • LN
    • Submandibular
    • Two LN posteriorly fo the facial a.
      • —> anterior subdigastric nodes of the internal jugular chain(IJC)

Sublingual Gland

  • Smallest
  • Sup border —> floor of the mouth
  • Inf border —> Mylohyoid m.
  • Lat border —> Mandible
  • Med border —> Genioglossus m.
  • Rare for Ca
  • LN
    • Submandibular
    • Submental (rare)
    • IJC

Epidemiology

  • Rare
    • 0.4% of all ca
    • < 5% of head and neck cmaliga
  • White > other ethnicities
    • However mucoepidermoid carcinoma & adenoid cystic carcinoma are equal
Location Percentage of Salivary Gland Ca Proportion of malignant tumours (vs all masses)
Parotid 70% 25%
Submandibular 10% 40%
Minor Salivary 20% 65%
  • Benign tumour —> F>M
  • Malignant —> F=M
  • Benign —> younger (45 yrs)
  • Malignant —> (55 yrs)
  • All salivary neoplasm in children are malignant

Epidemiologic difference between genders:

Gender More common Paths
Male Squamous Cell Ca, AdenoCa, Salivary Duct Ca
Female Acinic Cell Ca, Adenoid Cystic Ca
  • Most common nonsquamous salivary gland cancers:
    • Males:
      • Mucoepidermoid ca
      • Adenocarcinoma
    • Females:
      • Mucoepidermoid
      • Acinic cell
      • Adenoid cystic ca

Etiologic factors:

  • Nutritional deficiencies
    • Eskimos in Arctic —> Low Vit A & C
  • Exposure to ionizing radiation
    • Maybe more in Minor Salivary Gland
  • UV light exposure
  • Genetic predisposition
  • History of previous cancer of the skin of the face
  • Occupational exposure
    • Hair dresser
    • Beauty Salon
  • Viral (EBV)
  • Alcohol use
  • Hair dye use
  • Higher educational
  • Smoking and Alcohol usually are NOT considered related
    • Smoking >80 might be!!!

Women (if younger than 35) with salivary gland cancer may have a 2.5 elevated breast cancer risk

Natural History

Local invasion

  • Parotid:
    • 20% fixed
    • 10% Skin invasion
    • 25% Facial Palsy
    • Invasion to External auditory canal
      • drainage from ipsilateral ear
    • Parapharyngeal space invasion
      • Involvement of Pterygoid m. ==> Trismus

Lymph Node Involvement

  • Histology
    • SCC, Undiff Ca & Salivary duct Ca > Mucoepidermoid cancer > Acinic cell, Adenoid cystic carcinoma, ex-pleomorph adenoma
  • Chance of contralateral LN(+) is very low (non-existent)
Tscore+Histology Score Parotid Submandibular Oral Cavity Other
2 <5% 0% <5% 0%
3 10% 30% 10% 30%
4 25% 60% 20% 50%
5 30% 60% cell-content cell-content
6 35% 60% cell-content cell-content

T1 = 1, T2 = 2, T3-4 = 3;
acinic/adenoid cystic/carcinoma ex pleomorphic adenoma = 1, mucoepidermoid = 2, squamous/undifferentiated = 3

Distant Metastases

  • Lung
  • Bone
  • Occasionally to the liver
  • Overall:
    • At presentation:3%
    • After 10yr: 30%
  • Common:
    • Adenoid cystic
      • Maybe a late event with no local recurrence
      • @ 10yr —> 40%
      • Survival 5yr after DM —> 40%
      • Survival 10yr after DM —> 10%
    • Salivary duct
    • Squamous cell
    • Undifferentiated carcinomas

Molecular Biology

  • Mucoepidermoid Ca
    • t(11;19)(q21;p13)
      • Associated with better DFS and OS
    • CDKN2A(p16) Mutation
      • ==> increase invasiveness
  • Adenoid cystic Ca
    • t(6:9)
      • ==> MYB-NFIB fusion oncoprotein
    • c-KIT/CD117 mutation


Neoneurogenesis in Salivary Gland tumours
* Perineural invasion
* Adenoid cystic ca

  • Mutual(دوطرفه) neurotropic interaction with cancer cells and neurons
  • Release of various paracrine growth factors
    • Brain-Derived Neurotrophic Factor (BDNF)
    • Nerve Growth Factor (NGF)
      • NGF receptor —> Tyrosine Kinase A (TrkA)
  • Neurotropin staining —> positive in adenoid cystic carcinomas

Pathology

Path.png
Risk%20Factors.png
  • The best prognosis is seen for acinic cell and (low-grade) mucoepidermoid cancer.
  • The worst for un-differentiated and squamous cell cancer.

Clinical Presentation

  • Painless, rapidly enlarging mass
    • Benign —> for years
      • Remember that 3/4 of Parotid mass are benign
    • Malignant —> 3-6

Malignant:

  • Pain (10-20%)
  • Facial Involvement (30%)
  • Involvement of deeper structures (masseter, temporal, and pterygoid muscles)
  • Base of skull invasion (rare)
    • Pain and paralysis of various cranial nerves

Signs more common in malignant mass vs benign:

  • Rapid growth rate
  • Pain
  • Facial nerve palsy
  • Childhood occurrence
  • Skin involvement
  • Cervical adenopathy

Diagnostic Work-Up

  • History
    • Ask about pain
    • change in facial grimace
    • Peripheral Facial m. Palsy
  • Physical Exam
    • Full oral cavity exam
      • Inspection
        • Hard palate ( minor salivary )
          • Posterior triangle —> Verify lesser and greater palatine foramina involvement
            • Palatine nerves ( branch of Maxillary n. )
            • Important specially in adenoid cystic
      • Bimanual exam
    • Cranial Nerve complete exam
    • Regional adenopathy
  • Investigation:
    • ALWAYS start with biopsy to confirm diagnosis
      • FNA
    • Blood work
      • CBC
      • KFT
      • LFT
    • CT
    • MRI
      • T1-weighted images are excellent to assess the margins, deep extent, and patterns of infiltration because the (fatty) background of the gland is hyperintensive
      • T2-weighted
        • Benign tumors are hyperintensive
        • Malignant tumors are intermediate or low intensivity
      • Sensitivity: 87%
      • Specificity: 94%
      • Verify Perineural invasion of adenoid cystic carcinoma

Staging

Staging.png