I



PATHOLOGY OF THE MOUTH AND SALIVARY GLANDS

Lecture Objectives

At the end of the lecture, the student should be able to:

1. Outline the causes of the main inflammatory lesions of the mouth and pharynx – stomatitis, pharyngitis and tonsillitis.

2. Discuss the pathologic features of benign and malignant epithelial tumours of the mouth.

3. Describe the premalignant epithelial lesions of the oral cavity.

4. List other/non-epithelial tumours that can involve the mouth.

5. Outline the causes of inflammation of the salivary glands (sialadenitis)

6. Name the main benign & malignant tumours of the salivary glands and discuss the pathology of each.

PATHOLOGY OF THE MOUTH AND PHARYNX

1) Inflammation

◆ Stomatitis

➢ This refers to generalized inflammation of the oral mucosa

➢ A variety of lesion types may be seen including vesicobullous lesions (VB) and ulcers (U). Some agents e.g. Candida sp. produce characteristic lesions.

CAUSES OF STOMATITIS

|Class of agent |Example |Type of lesion |

|Virus |Herpes simplex |VB/U |

| |Varicella |VB/U |

| |Coxsackie, type A |VB/U |

|Fungus |Candida albicans |Thrush/U |

|Bacteria |Vincent’s disease |U |

|Autoimmune |Pemphigus |VB |

| |Bullous pemphigoid |VB |

| |SLE |U |

|Other/unknown |Erythema multiforme |VB |

| |Lichen planus |U |

| |Aphthous stomatitis |U |

❑ Candidiasis

➢ Usually attributable to infection with C. albicans but other species can be causative

➢ Risk factors include immunosuppression, altered oral microflora (e.g. broad-spectrum antibiotics), denture use and endocrine disorders e.g. poorly controlled diabetes mellitus

➢ There are numerous manifestations of oral candidiasis and some of the main ones are outlined:

Thrush: “pseudomembranous candidiasis”—loosely adherent white pseudomembrane (fungi,

inflammatory cells, debris, fibrin and bacteria) overlies inflamed mucosa

Angular stomatitis: infection in deep grooves of the lips

Candidal leukoplakia: tightly adherent membrane—?associated with heavy cigarette smoking

Chronic mucocutaneous candidiasis: skin, nails and other mucous membranes involved; many variants including familial, sporadic and those assoc. with various endocrine and chronic disorders

❑ Vincent’s disease (Acute necrotizing ulcerative gingivitis)

➢ Incompletely understood but factors such as emotional stress and smoking may suppress immune system and predispose to infection by commensal organisms such as Bacteroides sp.

➢ Characterized by gingival necrosis, ulceration and pseudomembrane formation

❑ Aphthous stomatitis ( Recurrent aphthous ulcers)

➢ Condition characterized by recurrent shallow ulcers (aphthae); may be single or multiple

➢ 10 to 20% of individuals affected—the most common disease of the oral mucosa; women>men; 10 to 30 yr.

➢ Seen in healthy people; occasionally assoc. with certain diseases e.g. Crohn’s

➢ Cause still unknown—? Trauma/stress/food products/nutritional deficiency/hormones

➢ Aphthae last 1 to 3 weeks, subsequent episodes vary in frequency and the condition eventually spontaneously disappears in most people

( Acquired immunodeficiency syndrome

➢ Oral lesions are prominent, often early features in HIV-related diseases

➢ Refractory candidiasis e.g. thrush is often the first manifestation

➢ Specific oral lesion of HIV is hairy leukoplakia—bilateral, soft, white, hairy excrescences on the lateral margins of the tongue: squamous hyperplasia that appears to be induced by EBV ? in assoc. with Candida or HPV.

Oral Manifestations of AIDS

|Secondary infections | |

|Fungal |Candidiasis |

| |Histoplasmosis |

| |Cryptococcosis |

|Bacterial |Increased risk of dental caries and periodontitis |

| |Acute necrotizing ulcerative gingivitis |

| |Mycobacterial infection |

| |(such as M. tuberculosis, M. avium-intracellulare) |

| |Gram-negative bacteria (such as Klebsiella pneumoniae) |

|Viral |Herpetic stomatitis |

| |Cytomegalovirus |

| |Hairy leukoplakia |

| |Herpes zoster |

| |HPV (condyloma acuminatum) |

|Tumours |Kaposi’s sarcoma |

| |Squamous cell carcinoma |

| |Non-Hodgkin’s lymphoma |

|Miscellaneous |Recurrent aphthous ulcers |

| |Delayed wound healing |

| |Xerostomia |

( Pharyngitis

➢ Very common condition; seen especially in children and caused mainly by viruses

➢ Approx. 15 to 20% of all pharyngeal infections are caused by beta-hemolytic streptococci—children between 5 and 15 years of age are most susceptible

➢ Important complications of beta-hemolytic strep pharyngitis are rheumatic fever and poststreptococcal glomerulonephritis

➢ Other forms of bacterial pharyngitis include diphtheria (pharynx and tonsils covered by adherent membrane) and gonorrhea (lesions often ulcerative)

➢ Noninfectious causes of pharyngitis include allergies, pollutants and smoking

( Tonsillitis

➢ Seen also predominantly in children and causative agents similar to pharyngitis

➢ The inflamed tonsils are usually covered by a yellow-white exudate

➢ The adenoids may also be affected and associated hyperplasia of these organs may cause blockage of the eustachian tube and otitis media

➢ Inadequately treated tonsillitis may result in tonsillar ulceration and peritonsillar abscess

2) Tumours

a) Benign epithelial proliferations

( Squamous papilloma

➢ Most common oral neoplasm—believed to be caused by HPV

➢ Painless exophytic mass with warty surface, usually < 1 cm and may be single

or multiple; preferred sites are the palate, tongue, gingivae and lips

b) Premalignant lesions

( Leukoplakia

➢ Clinical term for a white patch occurring on the surface of a mucous membrane

➢ In the mouth, the term is used to include only those white patches or plaques that will not rub off, and that are not caused by another oral disease

➢ Has been associated with tobacco smoking and alcohol abuse

➢ Most common in fifth to seventh decade; M>F

➢ Lesions may be localized or diffuse; vary from faintly translucent areas to thick fissured, indurated lesions

➢ 6% lesions will have carcinoma; additional 4% will undergo malignant transformation

( Erythroplakia (erythroplasia of Queyrat)

➢ Initially described as syphilitic lesion of the glans penis—then recognized to also occur on vulva and oral mucosa in patients who are not syphilitic

➢ Sixth to seventh decades; M=F

➢ Defined as bright red velvety plaques not due to any other condition (e.g.gingivitis, candidiasis, hemangioma); unlike leukoplakia, almost all lesions will prove to be squamous dysplasia or carcinoma on biopsy

c) Malignant epithelial proliferations

( Squamous cell carcinoma

➢ Account for majority of intraoral cancers; tobacco use and alcohol abuse implicated as causative factors; role of viruses (e.g. HPV,EBV) being investigated

➢ Predominantly affects males > 50 yr.

➢ Can present as mucosal ulcer, exophytic growth, endophytic growth, leukoplakia, erythroplakia or painless lymphadenopathy

➢ Commonest sites of involvement are the tongue, lip and floor of mouth

➢ Spread primarily by local extension and lymphatic dissemination; distant sites of involvement include lungs, bone and liver

➢ 5year survival rates are 75% for localized disease, 41% for regional cases and18% for cases with distant metastases

d) Nonepithelial tumours and tumour-like lesions

❖ Cysts of the gingiva, mucosa and jaw

❖ Benign soft tissue lesions (e.g. pyogenic granuloma, fibroma, schwannoma)

❖ Malignant soft tissue lesions (e.g. rhabdomyosarcoma)

❖ Lymphomas

❖ Odontogenic tumors (e.g. ameloblastoma)

❖ Tumours of the jaw (e.g. fibrous dysplasia, giant cell tumours, bone and cartilaginous tumours)

II. PATHOLOGY OF THE SALIVARY GLANDS

1) Obstructive Disorders

( Mucocele

➢ Most common of the obstructive disorders; results from trauma to minor salivary glands with extravasation and pooling of mucus in surrounding tissues

➢ Seen mainly in young persons; the lips are the favoured site

➢ Usually appear as small, fluctuant masses—large mucoceles of the floor of the

mouth are known as ranulas; these may extend into the neck

( Sialolithiasis

➢ This is the formation of stones (calculi) in the ducts of salivary glands

➢ The stones result from the calcification of an intraluminal nidus e.g. dried

secretions or cellular debris—they are composed mainly of calcium phosphate

➢ Inflammation of the salivary duct and stasis of saliva have been suggested as

predisposing factors—the submandibular duct is the most common site

➢ Peak incidence in the fourth and fifth decades

➢ The stones vary in size, surface texture and colour

➢ Recurrent infection of affected glands (secondary to obstruction) is common

2) Inflammation (Sialadenitis)

➢ Can be caused mechanical, physical, infectious and immunologic factors:

( Mechanical

➢ Mechanical obstruction of salivary ducts can be intraluminal (e.g. stones) or

extraluminal (e.g. tumours)

➢ It leads to chronic and recurrent sialadenitis that can result in partial or

complete destruction of the affected gland

( Physical

➢ Physical causes of sialadenitis include radiation e.g. administered during

treatment of head and neck cancers

➢ Initial acute inflammation is followed by chronic sialadenitis and fibrosis

◆ Infectious

❑ Acute suppurative sialadenitis

➢ Usually caused by Staphylococcus aureus and group A streptococci that enter salivary ducts from the oral cavity: reduced or absent salivation thought to predispose

➢ Ductal epithelium and acini are destroyed by invading inflammatory cells and microabscesses may form

❑ Viral sialadenitis

➢ Several viruses can cause sialadenitis including paramyxovirus (the mumps virus), coxsackieviruses A and B, influenza viruses and cytomegalovirus—of these mumps is the most common to involve the glands

❑ HIV-associated cysts of the parotid

➢ HIV infection can cause lymphadenopathy of intraparotid lymph nodes

➢ There is marked lymphoid hyperplasia which can be accompanied by the formation of keratin-filled cysts (salivary duct epithelium undergoes metaplastic change)

➢ Unilateral or bilateral enlargement of the parotids can result

❑ Tuberculosis

➢ Tuberculosis may involve intraparotid and paraparotid lymph nodes; infection of these nodes may originate from a tuberculous focus in the mouth or pharynx, or result from dissemination of pulmonary TB

➢ Can present as painless mass/masses mimicking a tumour

➢ Histologic examination will reveal the typical caseating granulomas and the findings can be confirmed with cultures and special stains

◆ Immunologic

❑ Sjogren’s syndrome

➢ Autoimmune disease characterized by the progressive lymphocytic infiltration and destruction of exocrine glands, particularly the salivary and lacrimal glands

➢ Clinical hallmarks are keratoconjunctivitis sicca, xerostomia, and rheumatoid arthritis; may also be assoc. with other autoimmune disesases e.g. SLE

➢ 90% patients are female; average age at diagnosis is 50 yr.

➢ Firm, diffuse, painless enlargement of the salivary glands, which is usually but not always bilateral, is the typical presentation

➢ Histologic hallmark is a lymphocytic sialadenitis—lymphoid follicles may be presentThese patients are at increased risk for non-Hodgkins lymphoma

3) Benign Tumours

( Pleomorphic Adenoma (Benign mixed tumour)

➢ Most common salivary gland tumour overall

➢ Accounts for 60 – 70% of parotid tumours, 40 – 60% of submandibular tumours, and 40 – 70% of minor salivary gland tumours

➢ Peak incidence between 30 and 50 years; female to male ratio 3:1

➢ Slowly-growing painless, firm masses—in the parotid, most occur in the superficial lobe

➢ A variety of growth patterns may be seen histologically—the basic components are epithelium, myoepithelium and stroma .

➢ Recurrence may occur if the tumour is inadequately excised.

( Warthin’s tumour (Papillary cystadenoma lymphomatosum)

➢ Slow-growing benign tumour that arises almost exclusively in the parotid

➢ 5 – 6% of parotid tumours; peak incidence 40 – 70 years; male to female ratio is 5:1.

➢ It is proposed that the tumour develops from parotid ductal epithelium present in lymph nodes within the gland.

➢ Most tumours measure 2-3 cm at diagnosis; tumours are bilateral in 7% of patients

➢ The histology is distinctive and pathognomonic—epithelial-lined cystic spaces showing papillary projections are present in a lymphoid stroma.

➢ As with pleomorphic adenomas, recurrence may occur if the tumour is incompletely removed.

4) Malignant Tumours

➢ Malignant salivary gland tumours are less common than benign ones; ratio of benign to malignant approximately 4:1

➢ The most common tumours are mucoepidermoid carcinoma, adenoid cystic carcinoma, acinic cell carcinoma and malignant mixed tumours.

( Mucoepidermoid carcinoma

➢ Most common malignant salivary gland tumour; accounts for 2-10% of major salivary gland tumours and 10-40% of minor salivary gland tumours

➢ Most common in 35-65 year age group; however, it can affect children and adolescents

➢ They are slowly growing firm masses that are often clinically indistinguishable from the more common pleomorphic adenoma, and range in size from 1-4 cm.

➢ Histologically these tumours are composed of epidermoid cells, mucus-secreting cells and intermediate cells; classified as low, intermediate and high-grade

➢ The histologic grade is directly related to prognosis—survival rate in patients with low-grade tumours is 90-100%; intermediate and high-grade tumours tend to show local invasion, recurrence, and metastases, with survival rates of 40-60%.

( Adenoid Cystic Carcinoma

➢ Account for 3-10% of salivary gland tumours— more common in minor salivary glands

➢ Twenty-five percent arise in major salivary glands, most commonly the submandibular

➢ May arise at any age, but occur most frequently in the 4th to 6th decades

➢ Patients with tumours in the major glands commonly present with a painful mass. Those in the minor glands can also produce respiratory obstruction

➢ Usually form well-defined masses, but histologically are seen to infiltrate surrounding tissues

➢ Perineural invasion is characteristic of this neoplasm, and this feature seems to account for the poor long-term outcome in patients with this tumour.

➢ Metastasis can occur to cervical lymph nodes or distant sites e.g. lung, bone, liver, brain

➢ 5-year survival rates as high as 70% have been reported, but rate declines to 5-15% at 20 years.

( Acinic Cell Carcinoma

➢ Relatively uncommon tumour; accounts for 2-3% of salivary gland tumours.

➢ Most often involves the parotid; most common malignant tumour involving >one salivary gland

➢ Most common in the 5th decade

➢ Range in size from 2-4 cm; most are solid, though cystic change can occur.

➢ These carcinomas are regarded as low-grade tumours—regional metastasis occurs in 5-10% of patients, but distant metastasis is rare. Five and 10-year survival rates have been reported as 82% and 68% respectively

NB. The following link can provide you with additional information and images for this topic:



SESHIRLEY/Oct 2005

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