Salivary Gland Neoplasms - MU

• Salivary gland neoplasms are growths in the salivary glands
• Pleomorphic adenomas, oncocytomas, acinous cell tumors, mucoepidermoid tumors, and squamous cell carcinomas are types of salivary glands neoplasms

Cell of Origin

• Pleomorphic adenomas originate from intercalated duct cells and myoepithelial cells
• Oncocytic tumors originate from striated duct cells
• Acinous cell tumors originate from acinar cells
• Mucoepidermoid tumors and squamous cell carcinomas develop in excretory duct cells

Epidemiology

• 1.2% of all neoplasms are salivary gland neoplasms
• 5% of head and neck tumors are salivary gland neoplasms
• 85% of salivary gland neoplasms are benign
• 15% of salivary gland neoplasms are malignant
• Benign salivary gland neoplasms usually appear after the age of 40
• Malignant salivary gland neoplasms usually appear after the age of 60
• Salivary tumors are rare in children, and mostly malignant
  • 80% of parotid neoplasms are benign including (60% pleomorphic adenoma)
  • 20% of parotid neoplasms are malignant (mucoepidermoid carcinoma)
  • 50% of submandibular gland neoplasms are benign including (pleomorphic adenoma)
  • 50% of submandibular gland neoplasms are malignant (adenoid cystic carcinoma)
  • 10% of sublingual and minor salivary glands neoplasms are benign
  • 90% of sublingual and minor salivary glands neoplasms are malignant
• Salivary gland neoplasms may arise from the secretory tissue, the duct system, or from the stromal tissue (mainly lymphoid tissue)

The rule of 80

• 80% of parotid tumors are benign
• 80% of benign parotid tumors are pleomorphic adenomas
• 80% of parotid pleomorphic adenomas occur in the superficial lobe
• 80% of untreated pleomorphic adenomas remain benign

Types of salivary glands neoplasms

• Adenomas can be pleomorphic or monomorphic
  • Common examples include pleomorphic adenoma and adenolymphoma (Warthin's tumor)
• Carcinomas can be low grade or high grade
  • Common examples include acinic cell carcinoma, adenoid cystic carcinoma, low-grade and high-grade mucoepidermoid carcinoma, adenocarcinoma, and squamous cell carcinoma
• Non-epithelial tumors include hemangioma and lymphangioma
• Lymphomas can be primary or secondary
  • Common examples include Non-Hodgkin's lymphomas and lymphomas in Sjogren's syndrome
• Secondary tumors can be local or distant
  • Common examples include tumors of the head and neck especially skin and bronchus
• Unclassified tumors have no common examples
• Tumor-like lesions can be solid or cystic
  • Common examples include benign lymphoepithelial lesion, adenomatoid hyperplasia, and salivary gland cysts

Etiology

• Genetic factors include genetic loss of alleles of chromosomes
• Race: Eskimos are more prone for salivary neoplasm
• Infections include infective mumps and Epstein-Barr virus
• Chronic sialadenitis and recurrent inflammation may be a cause although unproven
• Radiation: More common in survivors of atomic bomb explosion, mucoepidermoid carcinoma is more common in these patients
• Smoking: Adenolymphoma of Warthin's shows 40% risk in smokers
• Sex: Benign tumors and many malignancies are common in females, Warthin's and some malignancies are common in males
• Environment and diet: Arctic-Eskimos show diet deficiency of vitamin A and develop a salivary tumors
• Industrial agents like nickel, cadmium, hair dyes, silica, and preservatives may increase the risk of salivary tumors

Benign Lesions: Pleomorphic Adenoma

• 75% of parotid & 50% of submandibular gland neoplasms are Pleomorphic Adenomas
• Distribution between males and females are equal in numbers
• Arises from epithelial, myoepithelial and stromal components
• Exhibits wide variations in cellular and architectural morphology
• The capsule may be incomplete with the extension of tumor tissue into the surroundings
• Grows slowly without infiltration of the facial nerve
• Tumor is called pleomorphic adenoma because of the presence of epithelial cells, myoepithelial cells, mucoid material, pseudocartilage and lymphoid tissue
• Long-standing (more than 10 years) pleomorphic adenoma rarely turns malignant

Warthin’s Tumor (Adenolymphoma)

• Is the second most common benign tumor of parotid gland
• Accounts for 2-10% of all parotid gland tumors
• Bilateral in 10% of cases
• May contain mucoid brown fluid in FNA
• Consists of an epithelial component of papillary fronds which demonstrate 2 layers of oncocytic epithelial cells and a lymphoid component
  • Cytoplasm stains deep pink and show granularity because abundance of mitochondria
  • Occasionally undergoes squamous metaplasia (May mistakenly diagnose SCCa on FNA)
  • Lymphoid tissue forms the core or papillary structures
• Both lymphoid and oncocytic epithelial elements must be present to diagnose Warthin's
• Electron microscopy shows a large number of mitochondria in the epithelial cells
• Oncocytes selectively incorporate technetium Tc 99m and appear as hot spots on a radionucleotide scan

Malignant Salivary Gland Tumors: Mucoepidermoid Carcinoma

• Is the most common malignant salivary tumor
• Usually affects the parotid
• Arises from the ductal epithelium
• Three grades are described: low, intermediate, and high-grade tumors
• The low-grade type is the most frequent variant and is known to affect children
• Usually does not invade the facial nerve
• Carries an excellent prognosis, with approximately 98.8% 5-year survival rate

Adenoid Cystic Carcinoma

• Is the commonest malignancy affecting the minor salivary glands
• Arises from ductal and myoepithelial cells
• Has a slow rate of growth
• May grow in different patterns: tubular, cribriform, and/or solid
• Great tendency for perineural invasion, thus it usually invades the facial nerve
• Has a high frequency of local and distant recurrence and poor long-term prognosis

Benign Neoplasms: Clinical Picture

• Sexually equal
• Usually manifests around 40 years
• Slowly growing
• Painless (Not infiltrating or compressing facial nerve)
• Single
• Usually in the parotid region
  • Usually arises from its tail
  • Spherical and in superficial lobe as an obvious mass
  • Arise from deep lobe and present as a parapharyngeal tumor in oropharynx (Dumble tumor)
• Variable Size
• Hemispherical Shape
• Smooth - Lobulated Surface
• Freely mobile Skin
• Facial nerve is free
• Masseter muscle is not attached
• Preservation of superficial temporal artery pulsation
• Special characteristics: Fills space between ramus of mandible & mastoid process, May raise lobule of ear, Becomes more prominent on contraction of masseter, Less prominent on opening of the mouth
• Firm (Never hard) Consistency
• Well-defined edge
• Not tender
• Freely mobile in all directions
• No enlargement Lymph nodes

Malignant Neoplasms: Clinical Picture

• Acinic cell carcinoma is more common in females but malignancy is more common in males rather than in females

• 50 years

• Rapidly growing
• Slowly growing in adenoid cystic carcinoma
• Painless or painful in adenoid cystic
• Single Number
• Usually in parotid region Site
• Variable (Rapidly growing) Size
• Irregular Shape
• Nodular or irregular Surface
• Not freely mobile (Attached to tumor) Skin
• Facial nerve is free or infiltrated
• Masseter muscle is not attached
• Superficial temporal artery pulsation → May be absent
• Special characteristics:
  • Fills space between ramus of mandible & mastoid process
  • May raise lobule of ear
  • Becomes more prominent on contraction of masseter
  • Less prominent on opening of the mouth
• Hard or Soft in acinic cell tumor Consistency
• Ill-defined Edges
• Slightly tender
• Enlarged - Hard - Painless - Early mobile and later fixed Lymph nodes
• The patient may give a history of a painless swelling that has been stationary for years and now starting to regrow (carcinoma ex pleomorphic adenoma)
• The swelling may be painful, with ear radiation, and intensification by mastication

Differential Diagnosis

• Salivary swellings of non-neoplastic origin includes:
  • Examples of inflammation, calcular obstruction, sialosis
  • The gland is usually diffusely enlarged with no definite lump
• Extra salivary swellings includes:
  • Subcutaneous lipoma
  • Lymph nodes
  • Mandibular and maxillary swellings
  • Hypertrophy of the masseter is bilateral in most cases

Spread of Neoplasm

• Direct spread can be intrinsic or extrinsic
  • Intrinsic spread is within the gland infiltrating facial nerve
  • Extrinsic spread is to the surroundings (skin, masseter, mandible & oral cavity)
• Lymphatic spread: To deep cervical L.N
• Blood spread: To lungs & bones
• Perineural invasion in adenoid cystic type explains high rate of recurrence

Complications

• Fungation
• Ulceration
• Infection
• Hemorrhage
• Fistula formation
• Nerve palsy
  • Facial palsy in parotid tumor
  • Hypoglossal & lingual nerves injury in submandibular tumor
• Disfigurement
• Distant metastases

Investigations

• Fine Needle Aspiration Cytology (FNAC)
  • To confirm the diagnosis and rule out malignancy
• CT Scan if the tumor is arising from the deep lobe
  • Helps to define the extra glandular spread and the extent of parapharyngeal disease, cervical lymph nodes and bony infiltration
• FNAC of the Lymph Nodes if lymph nodes are palpable in the neck in cases of malignancy of the parotid gland
• X-Ray of the Bones (Mandible and mastoid process)
  • To look for bony resorption, if malignancy is suspected
• MRI is a better investigation
  • Expensive, CT Scan and MRI lack specificity for differentiating between benign and malignant lesions
• Isotope Scan TCM 99 Pertechnetate
  • All salivary tumors give cold spots except Warthin's tumor gives hot spots
• Low growing parotid tumors should not be subjected to biopsy because of:
  • Injury to the facial nerve
  • Seeding of tumor cells in the subcutaneous plane which causes recurrence in about 40 - 50% of cases

Prognosis

• Poor in general
• Low grade mucoepidermoid, acinic cell tumor, epidermoid carcinoma, and adenoid cystic carcinoma have a favorable prognosis

Treatment

• Is only reliable form of treatment of salivary neoplasms
• Operation should be carried out by a surgeon with experience
• For parotid tumors, the patient should be warned against the possibility of accidental facial nerve injury, or intentional sacrifice if the lesion is malignant
• Even when the nerve is successfully preserved, patients commonly develop nerve weakness because of neurapraxia that recovers spontaneously a few months after the operation

Treatment of Benign Salivary Tumors

• Standard treatment in majority of cases because the majority are pleomorphic adenomas that arise in the part of the gland that is superficial to the facial nerve - All parotid tissue that is superficial to the facial nerve and its branches is excised, taking great care not to injure them - The operation ensures removal of the tumor and its tiny tissue extensions outside the defective capsule
• Simple enucleation is contraindicated because of high incidence of recurrence
• Total conservative parotidectomy for tumors of the deep lobe and dumbbell parotid tumor
• In case of accidental nerve injury repair it immediately by microsurgical techniques either by direct suturing or by a nerve graft taken from the great auricular or sural nerves
• For benign tumors of the submandibular, the operation is submandibular sialoadenectomy

Submandibular Sialoadenectomy Procedure-

  -An incision is made parallel to and 2 cm below the lower border of the mandible to ensure safety of the mandibular division of facial nerve
  - Two other nerves are at risk when dissecting the deep aspect of the gland, the lingual and the hypoglossal nerves. These should be preserved

Treatment of Malignant Salivary Tumors

• Confirmation of malignancy - a biopsy
• Excision of the tumor with safety margin is sufficient for low grade tumors (e.g., mucoepidermoid carcinoma) - Do superficial parotidectomy with preservation of the facial nerve for treatment of tumors of parotid gland
• Do total radical parotidectomy for high-grade tumors - entails total gland excision and block neck dissection if lymph nodes are involved
• Total radical parotidectomy includes removal of the superficial & deep lobes of the gland
• Facial nerve is preserved if not infiltrated
• Or sacrificing facial nerve & grafted using great auricular nerve or hypoglossal nerve
• Remove masseter & part of mandible if infiltrated

Carcinoma of Submandibular Gland

Is treated with total radical submandibular sialadenectomy with, if necessary, adjacent mandible & tongue in continuity.

Lymph nodes in malignant salivary tumor:

• Negative LNs receive elective neck dissection for high grade tumors
• Positive LNs receive block neck dissection
• Post-operative radiotherapy for high grade tumor with extra glandular extension or perineural spread

Inoperable tumors:

• Palliative resection as radiotherapy has minor role
• Unfortunately, most salivary neoplasms are relatively radio-resistant

Complications of Parotidectomy

• Recurrence Incomplete removal - multicentric - missed malignancy
• Flap necrosis: Avoid acute bending of the incision and to use gentle retraction
• Facial nerve palsy needs careful identification how? - Facial nerve is 1 cm deep and below the tip of the inferior portion of the cartilaginous canal (Conley's point) - By nerve stimulator - Inferomedial to tragal point - Deep to digastric muscle and tympanic plate - Nerve is just lateral to the styloid process - Tracing branch from distal to proximal (Hamilton-Bailey technique)
• Fluid collection treated with blood or seroma-perfect hemostasis and drain
• Fistula managed with salivary-duct ligation or tympanic neurectomy
• Sialadenectomy arises as a complication of parotid surgery
• Manifested by sweating and flushing of the preauricular skin during mastication
• Result of aberrant innervation of sweat glands by parasympathetic secretomotor fibers which were destined for the parotid
• Is treated by tympanic neurectomy which interrupts these parasympathetic fibers at the level of middle ear
• Also causes gustatory sweating

Pleomorphic Adenoma

• 70-80% Incidence
• More common in females
• Single Number
• Unilateral site
• Nodular, firm Clinical feature
• Pleomorphism Histology
• Cold spot 99mTc- Pertechnetate scan

Adenolymphoma (Warthin’s tumor)

• • 10% Incidence
• More common in males
• Sometimes multiple Number
• Bilateral site
• Smooth, soft cystic Clinical feature
• Double layer epithelium and lymphoid tissue
• Hot spot 99mTc- Pertechnetate scan
• Superficial parotidectomy Treatment

Submandibular Tumor

• uncommon
• 50% malignancy
• submandibular triange location
• small intracapsular involvement
• treated with excision-Submandibular surgery

Parotid Tumor

• Common
• 10-20% malignancy
• Parotid region Location
• Tonsillar shift, can also be felt in the lateral wall Deep lobe involvement

Surgical Treatment of malignant tumors

• Remove small intracapsular
• Small tumors: intracapsular submandibular Excision
• Large tumors: radical excision with or without sacrifice of 2 nerves (lingual & hypoglossal)
• Selective neck dissection (supra-omohyoid neck Dissection)
• Does not occur here
• Total conservative parotidectomy for malignant tumors
• Do selective neck dissection (lateral) levels II, III, IV & V lymph nodes

Differential Diagnosis of Swelling

• Parotid region
• Submandibular region and Lymph node, skin, muscle and vessel
• Gland=inflammatory, autoimmune and tumor
• Lymph node = Pre-auricular,
• Pre-auricular dermoid cyst

Inflammatory tumors:

1. Adamantinoma
2. Osteoma
3. others such as neurofibromnia
4. Haemangioma