1 30 Pathology ت سنيم أبو دلو 10/111/2015 ه دى محمد د.
*Slides are included, if you want to check few extra photos refer to them The oral cavity ANATOMY - It is the orifice to digestive & respiratory tracts - It has a diverse microflora, over 300 species - Parts of oral cavity: lips, labial mucosa, bucccal mucosa, alveolar mucosa, gingiva, terminal sulcus, soft palate mucosa, tonsillar area in the oropharengeal area, dorsal tongue, ventral tongue and the floor of mouth. -All these sites have specific or general diseases - Most common diseases of oral cavity are: (not discussed in the lecture) dental carries periodontal diseases [peri + odous, tooth] -diseases of tissues supporting the teeth which are; Periodontal ligament, Gingiva and Alveolar bone 1 P a g e
HISTOLOGY -The oral cavity is lined by stratified squamous epithelium which is: Keratinized in dorsum of the tongue papillae, the gingiva and the hard palate. It is called the functional mucosa or mastecatory mucosa due to its function; it provides friction for mastication. Non-keratinized found in the remaining parts of the oral cavity. -It has minor salivary gland tissue. -Sebaceous glands (Fordyce spots): Present in 70-80% of population but they are nonfunctional. They result from migration during fetal life. They present on the buccal mucosa mainly and vermilion border of the lip as small yellowish granules. -Lymphoid tissue: In addition to palatine tonsils and lingual tonsils, sometimes (not in all people) accessory lymphoid tissue present in the floor of the mouth. 2 P a g e
Diseases of oral cavity Diseases of salivary glands Congenital anomalies orofacial cleft macroglossia branchial cleft cysts Inflammatory & infectious lesions aphthous ulcers herpatic stomatits fungal infection AIDS Pre-malignant lesions leukoplakia erythroplakia Tumors SCC Inflammation Viral sialadenitis Bacterial sialadenitis Autoimmune sialadenitis Tumors Benign Pleomorhpic adnoma (mixed tumor) Warthin s tumor Malignant Pleomorphic adenoma Mucoepidermoid carcinoma Adenoid cystic carcinoma Mickulicz s syndrome [These diagrams are your guideline throughout the lecture] 3 P a g e
Diseases of oral cavity OROFACIAL CLEFTS -Relatively common lesion; about 1 to 2 per 1000 births in the developed world develop this lesion. -It occurs due to failure of palatal processes and facial processes to combine, which can be caused by: genetic factors (mostly) environmental factors like stress, drugs, etc syndrome related - Types of orofacial clefts: Combined cleft lip and cleft palate (usually cleft lip /+ cleft palate) most common type. Isolated cleft palate transverse facial cleft or oblique lateral facial cleft rare conditions -Associated with many difficulties. In the past, these infants used to die but nowadays they do successive surgery to treat it. They don t use the surgery right away because it results in scarring early in life but there is a team approach in the treatment involving: surgical, speech, dental and psychological therapies. 4 P a g e
MACROGLOSSIA -Definition: enlargement of the tongue -Occurs due to: vascular tumors (e.g. lymphangioma or hemangioma) amyloidosis associated with Down s syndrome functional causes: like when someone loses his teeth and then the tongue has all the space to expand. In some cases, the tissue is normal but there is enlargement in the tongue, since the tongue is a muscle and it can get hypertrophied. -Microglossia = small tongue APHTHOUS ULCERS (CANKER SORES) -Extremely common, up to 40% of population. - Single or multiple shallow fibrin-coated painful ulcers of oral mucosa, usually <1 cm which may coalesce. - Characteristically, they take the form of round, superficial erosions, covered with grey-white exudates and having erythmatous rim. -It is an autoimmune disease but the exact cause is unknown. It might be due to hypersensitivity reaction of viral or bacterial infection. - Triggered by: stress, fever, menstruation, pregnancy, certain foods and may be familial. - some people get them recurrently and called recurrent aphthous stomatitis (RAS) [stoma: mouth] 5 P a g e
-Related to some syndromes: malabsorption syndrome with inflammatory bowel disease behcet syndrome: due to immune complexes that cause vasculitis resulting in skin lesions -Types: minor apthous ulcer => - 1or 2 superficial ulcers, really painful, limited within few days - most common type Herpetiform aphthous ulcers => -small, up to 100 ulcers major aphthous ulcer => - really big and deep ulcers -take several weeks to heal -we manage these ulcers but we can t cure them. If there is an underlying cause we do CBC, blood test, vit. D deficiency scan and iron deficiency scan. but in some people we never know the cause. -self limited disease, managed by steroids 6 P a g e
HERPETIC STOMATITIS -Caused by HSV: HSV 1 affects the oral cavity but also could be affected by HSV 2 HSV 2 affects the genitalia -person to person transmission -most cases of herpetic infections are subclinical (asymptomatic). Only 5% are symptomatic. - In primary infection: * whether symptomatic or asymptomatic, the virus enters the body and travels through the sensory nerve into certain areas of the trigeminal nerve ganglion and it stays in a dormant (asleep) state. *Usually occurs during childhood and may affect the adults. * When symptomatic (pain & fever) you get vesicles on the labial mucosa - In recurrent infection: *due to: fever, sun or cold exposure,urti(upper respiratory tract infections) * occurs in the form of herpes labialis or herpetic lesions on the orofacial area represented by cold sores or fever blisters. * some people never recur the infection but others do whenever their immune system gets compromised *Recurrence occurs in limited area and may lead to shingles 7 P a g e
HISTOLOGY important in diagnosis -The infected cells (Tzanc cells) become ballooned and develop intranuclear inclusion bodies can be seen by electromicroscope. -Adjacent cells fuse to form giant cells FEATURES Vesicular lesion Edema degeneration of epidermis PROGNOSIS - in immunecompetent host => it is subsided within 7-10 days with systemc antiviral agents, supportive therapy, antipyratics and fluid intake. it goes away and recurrence may occurs in the future. -in immunocompromised host => As a person with HIV infection the recurrent infection is much more diffused. It becomes chronic infection. Sometimes the patient gets intraoral lesions - not only limited to the lipand ulcers in palatal or gingival mucosa resulting in gingivostomatitis or in worst cases it may reach the brain resulting in encephalitis. 8 P a g e
FUNGAL INFECTIONS - Candida albicans -which is part of normal flora- is the most commonly implicated organism in oral candidiasis. About (30-40%) of population carry this fungus. - Oral candidiasis also known as (moniliasis, thrush) is an opportunistic infection. -People who get this infection are usually immunocompromised not necessarily systemically but may be local immune suppression. For example, people who wear denture for long hours without maintaining hygiene or disinfecting them during night they are likely to get atrophy. - Pseudomembranous is a type of candidiasis that invade the superficial layer of epithelium resulting in necrotic epithelium depris. - It is characterized * by Soft white cheese-like plaques of pseudomembranous slough that can be easily wiped away * Minimal- marked ulceration with inflammatory exudate and fungal microorganisms (pseudohyphae) * Yeast is the inactive form when it starts to proliferate it gives rise to pseudohyphae -It is common with: At extremes of age (ie, children and the elderly) Diabetes mellitus Anemia Immunodeficiencies & debilitating diseases Under antibiotic or glucocorticoid Rx especially the broad spectrum antibiotics. 9 P a g e
ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) HIV infection is associated with different lesions in the oral cavity: Pseudomembranous Candidiasis Herpetic vesicles Kaposi s sarcoma: multifocal vascular tumor, present in 25% of AIDS patients; HSV8 Hairy leukoplakia: white patches with hairy surface on the lateral aspect of the tongue: *caused by EBV (which also can cause nasopharyngeal carcinoma) EPV is a part of hepris family * rare, but seen mainly in AIDS *histology shows acanthosis, hyperkeratotic ridges on the lateral borded of the tongue. This lesion by itself is benign and not exclusively related to AIDS. It might be found in other immuonocomromised patients because it is related to EPV 10 P a g e
PRE-MALIGNANT LESIONS OF THE ORAL CAVITY LEUKOPLAKIA=white patch -A clinical term not a histopathological term used to describe a whitish well-defined mucosal patch or plaque caused by epidermal thickening or hyperkeratosis with any degree of dysplasia and sometimes it could be malignant. -We have to exclude all possibilities for other white lesions in the mouth clinically and microscopy in order to diagnose as leukoplakia (the premalignant). like candidiasis (easily scratched), hairy leukoplakia (on the lateral aspect of the tongue) and lichen planus. -It is idiopathic but seen more frequently in: * Older men; associated with tobacco * Chronic friction (dentures) * Irritant foods * HPV link * alcohol -Microscopically, they vary from hyperkeratosis and acanthosis without dysplasia to mild to severe dysplasia or CIS(carcinoma in situ). Only histological examination distinguishes these changes. Benign hyper-keratinisation Severe dysplasia 11 P a g e
-3-6% transform into squamous cell carcinoma -We worry more if it is thick and has red areas at the floor and ventral of the mouth it is a sign of lack of differentiation and the malignant transformation is higher in these areas. -Proliferative verrucous leukoplakia( PVL) is an uncommon form of progressive multifocal leukoplakia with a high rate of malignant transformation (very thick) ERYTHROPLAKIA =red patch -Red velvety areas (atrophic areas) which may remain level with or slightly depressed in relation to surrounding mucosa - Hyperkeratosis is less frequent; red color is due to intense inflammation and vascular congestion -Microscopically, many of them are dysplastic and some are malignant -Have higher risk (50%) of malignant transformation (the risk corresponds to the degree of atypia) -95% are dysplastic in microscopic appearance -Erythroleukoplakia(speckled leukoplakia): mixture of erythroplakia and leukoplakia. -We do a biopsy from different areas because lesions could appear differently to exclude other causes 12 P a g e
SQUAMOUS CELL CARCINOMA -most common oral cancer; represent 90% of oral cavity malignancies (3% of all malignant tumors) - most common sites: Lip > ant. floor of mouth > tongue > palate -tendency to occur in males above the age of 40 - Etiological factors: Tobacco; Strongest factor, whether smoker or smokeless and it has synergistic effect if combined with alcohol Chronic fungal infection; Chronic candidiasis especially in heavy smokers can cause candidan leukoplakia which is different from pseudomembranous, it has higher transformation rate than regular leukoplakia HPV Sun exposure (radiation); affects the external part of the lip resulting in Actinic cheilitis which is a variant of Actinic keratosis which occurs in fairskinned people and we should be worried about malignant transformation Protracted irritation (e.g. dentures); weakly associated - Different manifestations: Leukoplakia Ulcer Mucosal thickening and swelling of the tongue -The histopathology varies from well differentiated with keratin formation to poorly differentiated and even undifferentiated 13 P a g e
- An example of ulcer in posterior mandible in the molar area and presented with enlarged LNs of mandible and then it spreads to cervical LNs and then to the rest of the body -the prognosis depends location (e.g. lip), grade, clinical stage: *50% lead to death in 5 years *overall 5 YS survival without L.N mets is 40% after chemo & radio * 20% with L.N mets -this diagram represents the transformation from normal tissue to SCC but it is not a rule; not all SCC arise from pre-existing pre-malignant lesion. Some arises de novo. Note: the doctor did not mention the molecular transformation. It s up to you. 14 P a g e
Salivary glands diseases -They affect the major salivary glands which are parotid, sublingual and submandibular. VIRAL SIALADENITIS Sialadenitis: inflammation of salivary glands -Most common cause is a paramyxovirus known as mumps. -Nowadays the incidence has decreased because of vaccination but outbreaks occur when the vaccine is not working or when people decline to get vaccinated -Painful infection which usually affects the parotid gland 70% bilateral parotid; 20% unilateral; 10% other salivary glands or glandular tissue -Spread by respiratory droplets during the incubation period -Usually self limited, but may lead to severe complications, which are commoner in adults: Pancreatitis Orchitis: inflammation of one or both of the testicles. usually unilateral; rarely leads to infertility CNS inflammation: rare but serious 15 P a g e
AUTOIMMUNE SIALADENITIS -Connective tissue disease that cause bilateral parotid enlargement in 50% of cases. 90% are middle age females. - Sjögren s syndrome: inflammation of salivary glands, mucussecreting glands of nasal mucosa and lacrimal glands. There is an attack on the parenchyma of these glands by lymphocytes. -Primary or secondary: Primary Sjögren s syndrome => when it is limited to salivary and lacrimal glands Secondary Sjögren s syndrome (60%) => when it is related to other autoimmune diseases such as RA, SLE, polymyositis -In severe cases this parenchymal damage results in: Xerostomia: dryness of the mouth Xerophthalmia: dryness of the eyes keratoconjunctivitis sicca: inflammation in the cornea and conjunctiva due to dryness -Histology: Lymphocytic infiltration, replacement of parenchymal tissue and fibrosis -serology: RF(rheumatoid factor) ANAs (antinuclear antibodies) anti-ribonucleoprotein Ro/SSA and La/SSB which are specific for SS(Sjögren s syndrome). -High risk to develop lymphomas in more than 20 40% of patients -Managed by immunosuppressive agents 16 P a g e
SIALOLITHIASIS & NONSPECIFIC SIALADENITIS -Under normal conditions the flow of saliva though the parotid duct prevents bacteria from ascending the duct to cause infection. -so ascending parotitis[inflammation of parotid] is due ductal obstruction that decrease saliva secretion and therefore increase the tendency of infection. -The obstruction results from: mainly from stone formation (sialolithiasis) major surgery (anesthesia cause decrease in secretions) dehydration (no saliva = no prevention) long-term phenothiazines Rx -Ductal dilatation, periductal inflammation, secondary bacterial invasion & suppuration -Pathogenesis: impacted food debris & edema around orifice following injury - ascending parotitis is less common than submandibular sialdenitis which has more recurrence and more associated with sialolithiasis. -An excisional biopsy of the submandibular gland is done to limit the recurrence of saldenitis but it cannot be applied to parotid gland because of facial nerve involvement. -Usually unilateral 17 P a g e
SALIVERAY GLANDS TUMORS -Relatively uncommon; 2% of tumors in humans -80% of tumors occur in parotid gland -Equal M:F ratio; affects all ages but certain tumors occur in [6th - 7th decade] -Most of these neoplasms are benign: 70-80% of parotid tumors ( because pleomorphic adenoma is the most common tumor and it is benign that s why benign tumors of parotid are more than malignant ones) 50% of submaxillary tumors -A mass in the parotid gland is presented as mass at the angle of the mandible. -Wide histologic variations -Benign: pleomorphic adenoma, Warthin s tumor -Malignant: carcinoma ex-pleomorphic adenoma, mucoepidermoid carcinoma, adenoid cystic carcinoma PLEOMORPHIC ADENOMA -Most common benign tumor (65-80%) of the salivary glands and most common tumor affecting the parotid gland but also it can affect the minor glands especially on the posterior palate -Slowly growing tumor, well-demarcated, usually not fully encapsulated which can explain the relatively high recurrence rate -Pleomorphic: because it has dual origin from epithelial and myoepithelial elements and may be arranged in duct-like structures, sheets and different other forms. 18 P a g e
-AKA: mixed tumor: Cells of origin produce variable background stroma that may be mucoid or cartilaginous. those make the appearance of myxochondroid (mixed) -This myxochondroid appearance is imported by aminoglycans which are jelly like material and when you try to excise the tumor lobular outgrowths fragment, giving a chance for the tumor to recur up to 10%. -Malignant transformation: 15% in parotid, 40% in submandibular gland WARTHIN S TUMOR -ANA: Papillary cystadenoma lymphomatosum -Pathology: (cystadenoma) composed of cystic spaces (Papillary) lined by 2 layers of tall columnar cells that project like papilla (lymphomatosum) overlying abundant dense lymphoid stroma -Benign slowly growing tumors -5-10% of all parotid tumors; extremely rare in other salivary glands -Histogenesis: vestigial embryonic remnants of branchial cleft origin? -Rx: cured by surgical excision normally does not recur. 19 P a g e
MICKULICZ S SYNDROME - Combination of salivary and lacrimal glands enlargement with xerostomia -May be due to many causes: Sarcoidosis Leukemia/lymphoma Sjögren s syndrome -It describes a clinical presentation; it is not a pathological diagnosis. -Therefore, many recent textbooks have abandoned this term since it is confusing. THE END (Get busy studying or get busy dying).. both lead to same way :P -medicine redemption Thanks to everyone who was ready to help doing this sheet Done by: Tasneem Abu-dalo 20 P a g e