Subject: Pathology Topic: Head and Neck 1 Lecturer: Dr.

Pascual Date of Lecture: July 26, 2011 Transcriptionist: Mopster Editor: TelsioPao Pages: 9

Oral Soft Tissue y Inflammatory/reactive lesions: Non neoplastic. Usually a response to chronic irritation, ie ill fitting dentures, braces or dental caries o Fibrous proliferative lesions o Aphthous ulcers (canker sores) o Glossitis y Infections y Tumors and pre cancerous lesions Inflammatory/reactive lesions y Fibrous proliferative lesions o Irritation fibroma: see diagram below  61% of proliferative lesions  Primarily occurs in the buccal mucosa along the bite line at the gingivodental margin  Consists of a nodular mass of fibrous tissue with few inflammatory cells covered by squamous mucosa  Grossly, lesion is smooth. Takes on color of local tissue. Erosions may be present.

Histologically: overlying epithelium is eroded and proliferation of capillary sized blood vessels surrounded by inflammatory cells

Pyogenic granuloma: see diagram below  12% of proliferative lesions  Similar to capillary hemangioma  Regresses spontaneously, particularly after pregnancy or undergo fibrosis  May develop into a peripheral ossifying fibroma  Vascular lesion, so reddish hue  Common in lower lip  Pedunculated, highly vascular, bright red lesion occurring in the gingival of children, young adults, and commonly, pregnant women (pregnancy tumor)

Peripheral ossifying fibroma  22% of proliferative lesions  Reactive growth of gingival (red, ulcerated, nodular lesions) with unknown etiology  Some arise as result of maturation of long standing pyogenic granuloma, others do not; may be mistaken clinically for pyogenic granulomas  Peak incidence: young females o Peripheral giant cell granuloma (Giant Cell Epulis)  5% of proliferative lesions  Similar to pyogenic granuloma but is more bluish purple in color  Lesion protrudes from gingival at sites of chronic inflammation  Covered by gingival mucosa but may be ulcerated  Histologically: aggregates of multinucleated, foreign body type giant cells separated by a fibrovascular stroma. Note: Dr. Pascual said that the frequency of the above lesions is, in descending order: y Irritation fibroma y Pyogenic granuloma y Peripheral giant cell granuloma y Peripheral ossifying fibroma However, the percentages above were taken from the book. So, use your judgment should this question appear on the exam. y Canker Sores, aka Aphthous Ulcers: see diagram below o Etiology unknown, but some say may be stress related o

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Common superficial, painful, often recurrent ulcerations of the oral mucosa Lesions appear as single or multiple Shallow, hyperemic ulcer with thin rim of exudates and rimmed by a narrow zone of erythema

Glossitis : see diagram below o Inflammation of tongue o Beefy red tongue encountered in certain deficiency states (Vitamin B12, niacin, pyridoxine, riboflavin deficiency, iron deficiency anemia) o Plummer Vinson Syndrome/Paterson Kelly Syndrome  Triad: glossitis, esophageal webs, iron deficiency anemia. o Atrophy of papillae thinning of mucosa exposure of underlying vasculature beefy red tongue o Glossitis with ulcerative lesions (sometimes along the lateral borders of the tongue), may also be seen with jagged carious teeth, ill fitting dentures, and rarely, with syphilis, inhalation burns, or ingestion of corrosive chemicals

Blisters and vesicles around mucosal orifices (lips, nose)  Formed by intercellular edema and ballooning degeneration of epidermal cells o Gingivostomatitis  Usually encountered in children; HSV1  Vesicular eruption extending from the tongue to the retropharynx associated with cervical lymphadenopathy o Recurrent herpetic stomatitis  Occurs either at the site of the primary inoculation or in adjacent mucosal areas that are associated with the same ganglion  Take the form of groups of small (1 to 3 mm) vesicles in the lips, hard palate, nasal orifices Oral candidiasis (Thrush) o Most common fungal infection in the oral cavity o Candida albicans o Factors that increase likelihood of infection:  Immune status  Strain of C. albicans present  Composition of individual s flora o 3 clinical forms:  Pseudomembrane: can be scraped off to reveal a hyperemic base  Erythematosus  Hyperplastic o Common in:  Diabetes mellitus  Bone marrow or organ transplant  Neutropenia  Chemotherapy induced immunosuppression  AIDS  Use of broad spectrum antibiotics

Infections y Herpes Simplex virus infections o Commonly HSV1 but may also be caused by HSV2 o Morphology: vesicle filled with serous fluid rupture painful ulcer o Findings on Tzanck smear:  multinucleated giant cells  intranuclear inclusions  intercellular edema (acantholysis) o Cold sores

Tumors and pre cancerous lesions y Smoking is the most common antecedent y Leukoplakia: see 4 diagrams below o A white patch or plaque that cannot be scraped off (which differentiates it from oral thrush) and cannot be characterized clinically or pathologically as any other disease o All leukoplakias must be considered precancerous o May occur anywhere in the oral cavity (favored locations: buccal mucosa, floor of the mouth, ventral surface of tongue, gingival, palate) o Morphology:  Solitary, or multiple, with indistinct or sharply demarcated borders  May be slightly thickened and smooth or wrinkled and fissured or

may appear as raised, sometimes corrugated, verrucous plaques Histologically: hyperkeratosis acanthotic, orderly or markedly dysplastic mucosal epithelium

Intense subepithelial inflammatory reaction with vascular dilatation red appearance

Erythroplakia: see both diagrams below o Less common but more ominous than leukoplakia, incurring a higher risk of malignant transformation o Red: intense subepithelial inflammation with vascular dilatation o Markedly dysplastic epithelium, velvety, sometimes eroded area o May be slightly depressed or blend in with surrounding area. o Histologically:  Superficial erosions with dysplasia, carcinoma in situ, or already developed carcinoma

Speckled leukoerythroplakia o Intermediate forms with the characteristics of both leukoplakia and erythroplakia Squamous Cell Carcinoma o 95% of head and neck cancers are SCC, most commonly in the oral cavity o HNSCC: aggressive  Multiple primary tumors: field cancerization  Risk factors  Smoked tobacco  Alcohol  HPV oncogenic variants  Family history of head and neck cancer  Actinic radiation: exposure to UV radiation  Pipe smoking  Betel chewing  Chronic irritation o Molecular biology  Genetic alteration have been identified and related to morphologic changes in epithelium:  Inactivation of P16 gene hyperplasia/hyperkeratos is  Mutation of p53 dysplasia  Alterations and deletions at 4q, 6p, 8p, 11q, 13q, 14q frank malignancy o SCC of the Oral Cavity  Sites: floor of mouth, ventral surface of tongue, lower lip, soft palate, gingival  May invade the underlying stroma without going through full thickness CIS stage 3

Differentiation depends on degree of keratinization, but does not correlate with behavior  Tends to infiltrate locally before distant metastasis  Spread and metastasis:  Tends to infiltrate locally before distant metastasis  Metastasis is primarily by lymphatic route:  Cervical lymph nodes  Favored distant sites:  Mediastinal lymph nodes  Lungs  Liver  Bones Prognostic determinants:  Location: best prognosis lower lip (5 year SR = 90%) b/c of earlier detection due to its obvious visibility (as opposed to, say, the back of the tongue).  Stage: depth of invasion, lymph node involvement, metastasis  Grade  Desmoplastic reaction: in the lip, florid desmoplasia is a marker of aggressive behavior  Tissue eosinophilia (favorable factor)  Loss of H antigen (precursor antigen in RBC s which helps determine blood type) invasiveness and distant spread  Overexpression of p21 gene favorable prognosis in tongue cancer  Amplification of 3q26-3 locus poor prognosis

Mixed inflammatory infiltrates: Neutrophils, lymphocytes, and plasma cell Nasal polyps: see 2 diagrams below o Focal protrusions of the nasal mucosa secondary to recurrent attacks of rhinitis o 3 -4 cm; edematous mucosa; hyperplastic or cystic mucous glands o Histologically:  Polypoid structures lined by respiratory epithelium  Inflammatory infiltrates: Neutrophils, eosinophils, plasma cells, occasionally lymphocytes

--------------------------------------------------------------------Upper Airways: nose, sinuses, pharynx, larynx Inflammation: o Infectious Rhinitis: o Infectious rhinitis (common cold)  Adenovirus, echovirus, rhinovirus  Thickened, edematous and red mucosa o Allergic rhinitis (hay fever)  Type I hypersensitivity reaction  Edema, redness, mucus reaction  Eosinophils are prominent in the inflammatory reaction o Chronic rhinitis  Results from repeated attacks of acute rhinitis with development of bacterial invasion  Superficial desquamation or ulceration

Sinusitis o Most commonly preceded by acute or chronic rhinitis o Occasionally, is an extension of periapical infection (maxillary sinusitis) o Inflammatory edema of the mucosa impairs drainage of the sinus  if suppurative exudates empyema of the sinus  Accumulation of mucus secretion and cystic formation mucocele  May spread to the orbit and other bony structures dural vein sinus thrombosis Pharyngitis/tonsillitis o Usually after or part of a viral URTI o Etiology: rhinovirus, echovirus, adenovirus, - hemolytic streptococcus o Reddening to slight edema of the nasopharynx o Enlarged, reddened (follicular) tonsils (due to reactive lymphoid hyperplasia) Laryngitis o Most common disease in the larynx o Causes:  Part of a generalized URTI  Heavy exposure to tobacco smoke

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Part of a systemic disease (TB, diphtheria) In children (whose larynx are small), severe edema and inflammation cause obstruction  laryngeoepiglottitis (H. influenza, - hemolytic Strep)  laryngotracheobronchitis (croup) inspiratory stridor

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Tumors y Nasopharyngeal angiofibroma o Very vascular o Almost exclusively in adolescent males o Despite its benign nature, may cause serious clinical problems because of its tendency to bleed profusely during surgery y Sinonasal papilloma: see diagram below o Lined by squamous or columnar epithelium o HPV type 6 and 11 o 3 forms:  Septal (most common)  Inverted: benign but locally aggressive (no desmoplasia) can invade the orbit or rarely, develop into carcinoma. Called inverted because it seems to be growing inward instead of outward.  Cylindrical  Figure below: inverted type

Multiple in children juvenile laryngeal papillomatosis Etiology: HPV type 6 and 11 Morphology:  Soft, raspberry like excresences, <1 cm in diameter  Finger like projections with a central fibrovascular core  Covered with orderly stratified squamous epithelium If located at the edge of the vocal cord ulceration hemoptysis

Reactive nodules (vocal cord nodules and polyps) o Etiologic factors  Heavy smoking  Great strain on voice (singers) can lead to change in character of voice or lead to progressive hoarseness o Smooth, rounded, sessile or pedunculated excrescences o Covered by squamous epithelium (keratotic , hyperplastic, or slightly dysplastic) o Loose myxoid CT core o Vocal cord polyps tend to be unilateral o Vocal cord nodules tend to be bilateral Squamous papilloma: see diagram below o Arise on true vocal cords o Single in adults

Olfactory neuroblastoma (esthesioneuroblastoma) o From neuroendocrine cells in the olfactory mucosa o Has neurosecretory granules o Highly malignant; metastasizes widely Nasopharyngeal carcinoma o Distinctive geographic distribution:  Africa: children  Southern China: adults o Close anatomic relationship to lymphoid tissue o Associated with EBV infection o Etiologic factors:  Heredity  Age  EBV infection o Histologic types:  Keratinizing squamous cell carcinoma  Least radiosensitive  Non keratinizing squamous cell carcinoma  Undifferentiated carcinoma  Has abundant lymphocytes  Most radiosensitive  Most commonly associated with EBV o Present as masses in the nasopharynx (or tonsils, posterior tongue, or upper airways) o Histologically: nest of larger cells surrounded by lymphocytes (see diagram below)

Laryngeal carcinoma: see diagrams below o Spectrum of hyperplasia dysplasiacarcinoma is seen o Risk factors: tobacco, alcohol o Clinical manifestations: persistent hoarseness leading to pain, dysphagia, hemoptysis o 95% of these cases are of the squamous cell carcinoma type o Smooth, white, or reddened focal thickenings o Verrucous or ulcerated, white to pink or gray lesions o 60% are confined to the larynx (intrinsic); if outside the larynx extrinsic

From remnants of branchial arches or from developmental salivary gland inclusions within cervical lymph nodes o 2 5 cm; lined by stratified squamous or pseudostratified columnar epithelium underlain by intense lymphoid aggregates Thyroglossal duct cyst o 1 4 cm; lined by stratified squamous epithelium (if near the tongue) or by pseudostratified columnar epithelium (if it is lower) o Within the cyst wall are lymphoid aggregates and remnants of thyroid tissue Carotid body tumor (paraganglioma) o Refers to extra adrenal tumors arising from paraganglia o Develop in 2 general locations:  Paravertebral paraganglia: with sympathetic connections; 50% elaborate catecholamines chromaffin positive  Aorticopulmonary chain (including carotid bodies, etc)  Parasympathetic connections  Infrequently release catecholamines nonchromaffin paraganglioma  Sense oxygen and CO2 tensions within adjacent vessels chemodectoma  Red pink to brown; <6cm; close to or encloses the bifurcation of the common carotid artery  Nests (zellballen) of polygonal chief cells  Histologically benign but metastasizes; 50% are fatal because of infiltrative growth  Diagrams below: Note appearance of Zellballen o

--------------------------------------------------------------------Neck y Branchial cyst

--------------------------------------------------------------------Salivary glands Inflammation y Sialadenitis o Etiology: traumatic, viral, bacterial or autoimmune (Sjogren s) o Types:  Acute suppurative sialdenitis: bacterial  Viral sialadenitis:  CMV, paramyxoviruses, EBV, parainfluenza virus, influenza virus (mumps)  Granulomatous sialadenitis  Often due to response to freed ductal contents in obstructive sialadenopathy  Infectious in some  Chronic sclerosing sialadenitis (submandibular gland)  Plasmacytic and lymphocytic periductal infiltrates  Eventually a thick fibrous capsule encloses the salivary ducts y Sialolithiasis: see diagram below o 2 forms of lithiasis in the head and neck  Angiolithiasis: less common; more often in oral or perioral soft tissue  Sialolithiasis: exclusively in the salivary gland  May occur in any gland but more often the submandibular gland because of the more torturous course of its duct and its more mucinous nature ductal obstruction glandular swelling after meals  Histologically:  Dilated ducts often with squamous metaplasia  Variable acinar destruction chronic inflammation and fibrosis

tissue capsule and no lining epithelium  Most common sites: lips (80%)  Ranula: refers to mucocele arising from damaged duct of the sublingual gland (plunging ranula) Retention mucocele  Salivary glands  Lined by epithelium (flat, cuboidal, or stratified)

Cysts: mucocele: see both diagrams below o Extravasation Mucocele most common (85%)  Obstruction or rupture of salivary gland cause the saliva to leak into the surrounding stroma mucous filled pseudocysts with connective

Tumors y 65 80% occur in the parotid (10% in submandibular) y Likelihood of malignancy is inversely proportional to the size of the gland. Ie, the smaller the gland the larger the likelihood of malignancy. y Malignant: 15 30% of tumors in the parotid; 40%... y F>M y Pleomorphic adenoma (mixed tumor): see diagrams below o Most common neoplasm of the salivary gland o 60% are in the parotid o Painless, slowly growing mass o Derived from ductal (or epithelial) cells and myoepithelail cells o Recall: mixed tumor is more than one tissue derived from 1 germ layer o Carcinoma ex pleomorphic adenoma is malignant counterpart o Gross:  Rounded and well demarcated  Encapsulated except in areas where the capsule is not fully developed with tongue like protrusions into the surrounding glandular

parenchyma, so tumor is likely to recur if it is not removed entirely. Histologically:  Epithelial elements  Mesenchyme like myxoid tissue  Chondroid or rarely, bony islands

Warthins tumor (papillary cystadenoma lymphomatosum): see diagrams below o 2nd most common salivary gland tumor o Almost always seen in the parotid gland o Benign o M>F; 5th 7th decades of life o 10% are multifocal; 10% are bilateral o Gross:  Round to oval  2 5 cm  Encapsulated  Pale grey surface with narrow cystic or cleft like spaces filled with mucinous or serous fluid o Histologically:  Papillary excrescences papillary  Cystic spaces are lined by double lining of cells/ polypoid projections cystadenoma  Surface layer of columnar cells (toward lumen) resting on a layer of cuboidal to polygonal cells  Beneath this is dense reactive lymphoid stroma lymphomatosum

Mucoepidermoid carcinoma o Most common primary malignant tumor of the salivary gland o Occurs mainly in the parotid gland (60 70%) but accounts for a large fraction of salivary gland tumors in other glands, especially minor glands o Low grade tumors:  Locally invasive  Rarely metastasize o High grade tumors:  Invasive; difficult to excise  High recurrence rate  Spreads to distant sites o Gross:  Up to 8 cm  No distinct capsule  Infiltrative at margins  Pale gray white parenchyma with small, mucin containing cysts o Histologically:  Squamous, mucous and intermediate cells in cords, sheets or cystic structures (see below)

Ear y Otitis media o Mostly in infants o Serous to suppurative exudates o Acute: bacterial/viral (Strep. Pneumonia, H. influenza, Moraxella catarrhalis) o Chronic: Pseudomonas aeruginosa, Staph. aureus, fungal o Can perforate eardrums o Can penetrate cranial vault cerebritis, abscess Cholesteatoma o Associated with chronic otitis media o 1 4 cm cystic lesion lined by keratinizing squamous cell epithelium or metaplastic mucus secreting epithelium and filled with amorphous debris and/or cholesterol spicules o Foul smelling o Etiology:  Chronic inflammation and perforation of the eardrum ingrowth of squamous epithelium (or metaplasia of the secretory epithelial lining of the middle ear) formation of squamous cell nest that eventually becomes cystic  Progressive enlargement erode into ossicles, labyrinth, adjacent bone, surrounding soft tissue, sometimes producing visible neck mass Otosclerosis o Abnormal bone deposition in the middle ear about the rim of the oval window (into which the footplate of the stapes fits) o Usually beings in early decades of life o In most instances, familial following autosomal dominant transmission o Uncoupling of normal bone resorption and bone formation o Slowly progressive marked hearing loss Tumors: rare o Pinna  Basal cell carcinoma  Squamous cell carcinoma o Elderly males  Exposure to actinic radiation

Other: o Adenoid cystic carcinoma: see diagrams below  50% are found in the minor salivary glands (especially palate)  Recurrent; invades perineural space and can be painful as a result  Small compact and dark tumor cells in cribriform pattern

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Actinic cell carcinoma  Histo: similar to serous glands In general o 65 80% of salivary gland neoplasms occur in the parotid o The likelihood of a salivary gland tumor being malignant is more or less inversely proportional to the size of the gland o The most common neoplasm of the salivary gland: pleomorphic adenoma o The most common primary malignant: mucoepidermoid carcinoma o 2nd most common neoplasm: Warthin s tumor o Neoplasm that is likely to invade perineural space: Adenoid cystic carcinoma

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The Lord is loving and merciful, slow to become angry and full of constant love. Psalm 145:

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