Head and Neck Final

PATHOLOGY HEAD AND NECK DR. INOCENCIO

Teeth and Supporting Structures

Teeth

- important fxns: mastication and proper speech. - firmly implanted in the jaw; surrounded by gingival mucosa - crown of the tooth projects into the mouth - covered by enamel, a hard, inert, acellular tissuehighly

mineralized tissue in the body. - enamel rests upon dentina specialized form of CT - makes up most of the remaining hard-tissue portion of the

tooth. - Cellular, contains numerous dentinal tubules, w/c contain

cytoplasmic extensions of odontoblasts. - pulp chamber is surrounded by dentin &consists of loose CT

stroma rich in nerve bundles, lymphatics, & capillaries. - in mammals, teeth attached to the alveolar ridge of the

jaws by the periodontal ligament, w/c provides a strong yet flexible attachment can withstand forces of mastication.

- The periodontal ligament attaches to the alveolar bone of the jaw on one side and to cementum, present on the roots of the teeth

- acts as a cement anchor periodontal ligament to the tooth.

CARIES (TOOTH DECAY)

- Dental cariescaused by focal degradation of the tooth structure

- one of the most common dses throughout the world - most common cause of tooth loss before age 35. - Carious lesions result of mineral dissolution of tooth

structure by acid metabolic end products from bacteria (present in oral cavity & capable of fermenting sugars.

- improved oral hygiene & fluoridation of the drinking water has become a standard practice.

- Fluoride incorporates into crystalline structure of enamel, forming fluoroapatite contributes to resistance to degradation by bacterial acids.

GINGIVITIS

- Gingiva squamous mucosa bet the teeth & around them. - Gingivitisinflamm of mucosa & assoc soft tissues. - result of a lack of proper oral hygiene accumulation of

dental plaque &calculus. - Dental plaquesticky, usually colorless, biofilm; builds in

bet &on surface of the teeth. - formed by a complex of oral bacteria, proteins from the

saliva, &desquamated epithelial cells. - If plaque continues to build mineralized to form calculus

(tartar). - Repeated erosions dental caries. - Plaque build-up beneath gumline gingivitis.

Chronic gingivitis is characterized by:

o gingival erythema, o edema, bleeding, changes in contour, o loss of soft-tissue adaptation to the teeth.

- Gingivitis occurs at any age;most prevalent & severe in

adolescence (ranging from 40%-60%),

- reversible disease; therapy primarily aimed at accumulation of plaque &calculus via brushing, flossing, and regular dental visits.

PERIODONTITIS

- Periodontitis inflammatory process that affects the supporting structures of the teeth: periodontal ligaments, alveolar bone, and cementum.

- periodontitis serious sequelae, including: - loss of attachment caused by complete destruction of the

periodontal ligament & alveolar bone. Loosening and eventual loss of teeth are possible.

- Devt of periodontal dse is now considered to be an independent process,

- reasons that are still unclear, assoc w/ a marked shift in the types and proportions of bacteria along the gingiva.

Pathogenesis: poor oral hygiene!

- facultative gram-positive organisms colonize healthy sites, while plaque within areas of active periodontitis contains anaerobic and microaerophilic gram-negative flora.

- 300 types of bacteria reside in oral cavity, adult periodontitis assoc primarily w/

Aggregatibacter (Actinobacillus) actinomycetemcomitans, Porphyromonas gingivalis Prevotella intermedia.

- periodontal dse- component of several different systemic diseases, including:

- acquired immunodeficiency syndrome (AIDS), leukemia, Crohn's disease, diabetes mellitus, Down syndrome, sarcoidosis, and syndromes associated with polymorphonuclear defects (Chdiak-Higashi syndrome, agranulocytosis, and cyclic neutropenia).

Inflammatory/Reactive Tumor-like Lesions

- tumor masses or ulcerationsreactive in nature & represent inflamm induced by irritation or by unknown mechanisms.

- All suspicious lesionsexamined by biopsy. - Reactive nodules of the oral cavity are fairly common and

microscopically diverse.

Most common fibrous proliferative lesions: o fibroma (61%), o peripheral ossifying fibroma (22%), pyogenic

granuloma (12%), o peripheral giant-cell granuloma (5%).

- Most common inflammatory/reactive ulcerations of the oral

cavity traumatic and aphthous ulcers. FIBROUS PROLIFERATIVE LESIONS

- Aka. irritation fibroma primarily occurs in the buccal mucosa along the bite line or @ gingivodental margin.

- Consists of a nodular mass of fibrous tissue, w/ few inflammatory cells, covered by squamous mucosa.

- TX: complete surgical excision.

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Fibroma. Smooth pink exophytic nodule on the buccal mucosa.

- Pyogenic granuloma highly vascular pedunculated lesion, usuoccurring in the gingiva of children, young adults, and, commonly, pregnant women (pregnancy tumor).

- Surface of lesion ulcerated &red to purple color. - some cases growth alarmingly rapid, raising the fear of a

malignant neoplasm. - Histologically: highly vascular proliferation that is similar to

granulation tissue. - form of capillary hemangioma - either regress, particularly after pregnancy, or undergo

fibrous maturation, may develop into peripheral ossifying fibroma.

- TX: complete surgical excision. - peripheral ossifying fibroma relatively common growth

of the gingiva . - considered to be reactive in nature rather - etiology of lesion is unknown. - arise as a result of maturation of a long-standing pyogenic

granuloma. - peak incidence in young &teenage females, - appear as red, ulcerated, and nodular lesions of the gingiva. - TX: Complete surgical excision down to the periosteum

(recurrence rate of 15% to 20%.)

Pyogenic granuloma. Erythematous, hemorrhagic, and exophytic mass arising from the gingival mucosa.

- peripheral giant cell granuloma relatively common lesion of the gingiva.

- generally covered by intact gingival mucosa, but may be ulcerated.

- clinical appearance of peripheral giant-cell granuloma : more bluish purple in color while the pyogenic granuloma is more bright red.

- Histologically: lesions are distinct.

- made up of a striking aggregation of multinucleate, foreign bodylike giant cells separated by a fibroangiomatous stroma.

- not encapsulated, lesions are well delimited and easily excised.

**should be differentiated from central giant-cell granulomas found w/in the maxilla /mandible & from histologically similar but frequently multiple brown tumors seen in hyperparathyroidism. APHOTHOUS ULCERS (CANKER SORES)

- extremely common superficial ulcerations of the oral mucosa - more common in the first two decades of life - extremely painful and often recurrent - lesions appear as single or multiple, shallow, hyperemic

ulcerations - covered by a thin exudate - rimmed by a narrow zone of erythema - underlying inflammatory infiltrate is at first largely

mononuclear - SECONDARY BACTERIAL INFECTION introduces numerous

neutrophils - lesions may spontaneously resolve in 7 to 10 days or

stubbornly persistent for weeks - Most ulcers are more painful than serious and require only

symptomatic treatment Recurrent apthous ulcers

- May be associated with celiac disease and inflammatory bowel disease

Aphthous ulcer. Single ulceration with an erythematous halo surrounding a yellowish fibrinopurulent membrane. GLOSSITIS

- implies inflammation of the tongue - sometimes applied to the beefy-red tongue encountered in

certain deficiency states - results from atrophy of the papillae of the tongue and

thinning of the mucosa o exposing the underlying vasculature

- atrophic changes do indeed lead to inflammation and even shallow ulcerations

- Such changes changes may be encountered in deficiencies of o vitamin B12 (pernicious anemia) o riboflavin o niacin o pyridoxine

- Similar alterations are sometimes encountered with sprue and iron-deficiency anemia

o complicated by deficiency in one of the B vitamins

PATHOLOGY HEAD AND NECK DR. INOCENCIO

- Plummer-Vinson or Paterson-Kelly syndrome - The combination of iron-deficiency anemia, glossitis, and esophageal dysphagia usually related to web

CHARACTERIZED BY

o ulcerative lesions sometimes along the lateral borders of the

tongue - May also be seen with

o Jagged carious teeth o ill-fitting dentures o **Rarely with

syphilis inhalation burns ingestion of corrosive chemicals

INFECTIONS

- oral mucosa is highly resistant to its indigenous flora - have many defenses including:

o competitive suppression of potential pathogens by organisms of low virulence

o elaboration of secretory IgA and other immunoglobulins

- submucosal collections of lymphocytes and plasma cells o antibacterial effects of saliva o irrigating effects of food and drink

- any lowering of these defenses sets the stage for oral infections

o immunodeficiency o disruption of the microbiologic balance by

antibacterial therapy HERPES SIMPLEX VIRUS INFECTIONS

- Most orofacial herpetic infections are caused by HERPES SIMPLEX VIRUS TYPE 1 (HSV-1)

- changes in sexual habits = increase in HSV-2 (genital herpes) has been observed in the oral cavity

- Primary HSV infection typically occurs in CHILDREN AGE 2 TO 4 YEARS

o often asymptomatic o does not cause significant morbidity

- 10 20% of the time = primary infection presents as acute herpetic gingivostomatitis

o abrupt onset of vesicles and ulcerations throughout the oral cavity

o ESPECIALLY in the gingiva - Lesions also accompanied by lymphadenopathy, fever,

anorexia, and irritability Morphology

- vesicles range from lesions of a few millimeters to large bullae

o at first filled with a clear, serous fluid o often rupture to yield extremely painful, red-

rimmed, shallow ulcerations Microscopic Examination

- intracellular and intercellular edema (acantholysis) - form clefts that may become transformed into macroscopic

vesicles

- Individual epidermal cells - Margins of vesicles or lying free within the fluid - sometimes develop eosinophilic intranuclear viral inclusions - several cells may fuse to produce giant cells - aka multinucleate polykaryons - demonstrated by the diagnostic Tzanck test - vesicles and shallow ulcers USUALLY SPONTANEOUSLY

CLEAR within 3 to 4 weeks - virus treks along the regional nerves - eventually becomes dormant in the local ganglia (eg

trigeminal)

- Usually in young adults, the virus becomes reactivated to produce the common but usually mild cold sore

- influences predisposing to activation are poorly understood BUT MAY include:

- Trauma - Allergies - exposure to ultraviolet light - upper respiratory tract infections - pregnancy - menstruation - immunosuppression - exposure to extremes of temperature - Recurrent herpetic stomatitis

o In contrast to acute gingivostomatitis o occurs either at the site of primary inoculation OR o adjacent mucosal areas that are associated with the

SAME GANGLION

- groups of small (13 mm) vesicles

- MOST COMMON LOCATIONS for recurrent lesions

o The lips (Herpes labialis) o nasal orifices o buccal mucosa o gingival o hard palate

- **resemble those already described in the primary infections much more limited in duration

- are milder - usually dry up in 4 to 6 days - heal within a week to 10 days

OTHER VIRAL INFECTIONS

- herpes zoster - Epstein-Barr virus (EBV; mononucleosis) - Cytomegalovirus - enterovirus (herpangina, hand-foot-and-mouth disease,

acute lymphonodular pharyngitis) - rubeola (measles)

ORAL CANDIDIASIS (THRUSH)

- By far the most common fungal infection in the oral cavity - Candida albicans

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o normal component of the oral flora in 50% of the population

o three factors that influence the likelihood of a clinical infection:

immune status of the individual the strain of C. albicans present the composition of an individual's oral

flora - three major clinical forms of oral candidiasis

o pseudo-membranous (thrush) MOST COMMON o erythematous o hyperplastic

- ** with several different variations within these groups - Pseudo-membranous form

o aka thrush o typically takes the form of a superficial, curdy, gray

to white inflammatory membrane - composed of matted organisms - enmeshed in a fibrinosuppurative exudates - reveal an underlying erythematous inflammatory base when

scraped off - causes mischief only in individuals who have some form of

IMMUNOSUPPRESSION

- patients with diabetes mellitus - organ or bone marrow transplant recipients - those with neutropenia - chemotherapy-induced immunosuppression - AIDS

o broad-spectrum antibiotics - eliminate or alter the normal bacterial flora of the mouth - also result in the development of oral candidiasis

DEEP FUNGAL INFECTIONS Such fungi include:

Histoplasmosis Blastomycosis Coccidioidomycosis Cryptococcosis Zygomycosis Aspergillosis

- Due to increasing number of patients who are

IMMUNOCOMPROMISED ORAL MANIFESATIONS OF SYSTEMIC DISEASES

Systemic Disease

Associated Oral Changes

INFECTIOUS DISEASES

Scarlet fever Fiery red tongue with prominent papillae (raspberry tongue); white-coated tongue through which hyperemic papillae project (strawberry tongue)

Measles Spotty enanthema in the oral cavity often precedes the skin rash; ulcerations on the buccal mucosa about Stensen duct produce Koplik spots

Infectious mononucleosis

Acute pharyngitis and tonsillitis that may cause coating with a gray-white exudative membrane; enlargement of lymph nodes in the neck, palatal petechiae

Diphtheria Characteristic dirty white, fibrinosuppurative, tough, inflammatory membrane over the tonsils and retropharynx

Human immunodeficiency virus

Predisposition to opportunistic oral infections, particularly herpesvirus, Candida, and other fungi; oral lesions of Kaposi sarcoma and hairy leukoplakia (described in text)

DERMATOLOGIC CONDITIONS[*]

Lichen planus Reticulate, lacelike, white keratotic lesions that rarely become bullous and ulcerated; seen in more than 50% of patients with cutaneous lichen planus; rarely, is the sole manifestation

Pemphigus Vesicles and bullae prone to rupture, leaving hyperemic erosions covered with exudates

Bullous pemphigoid

Oral lesions resemble macroscopically those of pemphigus but can be differentiated histologically

Erythema multiforme

Maculopapular, vesiculobullous eruption that sometimes follows an infection elsewhere, ingestion of drugs, development of cancer, or a collagen vascular disease; when it involves the lips and oral mucosa, it is referred to as Stevens-Johnson syndrome

HEMATOLOGIC DISORDERS

Pancytopenia (agranulocytosis, aplastic anemia)

Severe oral infections in the form of gingivitis, pharyngitis, tonsillitis; may extend to produce cellulitis of the neck (Ludwig angina)

Leukemia With depletion of functioning neutrophils, oral lesions may appear like those in pancytopenia

Monocytic leukemia

Leukemic infiltration and enlargement of the gingivae, often with accompanying periodontitis

MISCELLANEOUS

Melanotic pigmentation

May appear in Addison disease, hemochromatosis, fibrous dysplasia of bone (Albright syndrome), and Peutz-Jegher syndrome (gastrointestinal polyposis)

Phenytoin (Dilantin) ingestion

Striking fibrous enlargement of the gingivae

Pregnancy A friable, red, pyogenic granuloma protruding from the gingiva (pregnancy tumor)

PATHOLOGY HEAD AND NECK DR. INOCENCIO

Rendu-Osler-Weber syndrome

Autosomal dominant disorder with multiple congenital aneurysmal telangiectasias beneath mucosal surfaces of the oral cavity and lips

- MANY SYSTEMIC DISEASES are associated with oral lesions - not uncommon for oral lesions to be the FIRST SIGN of some

underlying systemic condition HAIRY LEUKOPLAKIA

- distinctive oral lesion that is usually seen in immunocompromised patients

- Approximately 80% of patients with hairy leukoplakia are INFECTED WITH THE HUMAN IMMUNODEFICIENCY VIRUS (HIV)

- 20% of lesions are seen in patients who are immunocompromised for other reasons (cancer therapy or transplant immunosuppression)

- takes the form of white, confluent patches of fluffy (hairy), hyperkeratotic thickenings, almost always situated on the LATERAL BORDER OF THE TONGUE

- Unlike thrush, the lesion cannot be scraped off Microscopic appearance:

- Consists of hyperparakeratosis and acanthosis with balloon cells in the upper spinous layer

- Sometimes there may be koilocytosis of the superficial, nucleated epidermal cells

o suggesting human papillomavirus (HPV) infection - EBV is present in most cells and is NOW ACCEPTED AS THE

CAUSE of the condition - Sometimes there is superimposed candidal infection

o Adds to the hairiness - In HIV-positive individuals, with hairy leukoplarkia,

symptoms of AIDS follow in 2 to 3 years Tumors and Precancerous Lesions

- Oral squamous cell carcinoma and its associated precancerous lesions

LEUKOPLAKIA AND ERYTHROPLAKIA

- early detection in populations at risk have been proposed to decrease the morbidity and mortality associated with oral cancer

- Leukoplakia- a white patch or plaque that cannot be scraped off and cannot be characterized clinically or pathologically as any other disease

o lesions that are present in the oral cavity for no apparent reason

o lichen planus and candidiasis are not leukoplakias o until it is proved otherwise via histologic

evaluation, all leukoplakias must be considered precancerous.

- Erythroplakia- red, velvety, possibly eroded area within the oral cavity that usually remains level with or may be slightly depressed in relation to the surrounding mucosa

o epithelium in such lesions tends to be markedly atypical, incurring a much higher risk of malignant transformation than that seen with leukoplakia

- Speckled leukoerythroplakia.- both leukoplakia and erythroplakia

Erythroplakia. A, Lesion of the maxillary gingiva. B, Red lesion of the mandibular alveolar ridge. Biopsy of both lesions revealed carcinoma in situ. Morphology:

- Leukoplakias- Oral cavity o Favored location: buccal mucosa, floor of the

mouth, ventral surface of the tongue, palate, and gingiva

o Appear as solitary or multiple white patches or plaques, often with sharply demarcated borders

o May be slightly thickened and smooth or wrinkled and fissured, or they may appear as raised, sometimes corrugated, verrucous plaques

Histologic examination

- they present a spectrum of epithelial changes ranging from hyperkeratosis overlying a thickened, acanthotic but orderly mucosal epithelium to lesions with markedly dysplastic changes sometimes merging into carcinoma in sit

Leukoplakia. Clinical appearance of leukoplakias is highly variable and can range from (A) smooth and thin with well-demarcated borders, (B) diffuse and thick, (C) irregular with a granular surface, to (D) diffuse and corrugated.

Histologic changes in erythroplakia only rarely consist of orderly epidermal maturation; virtually all (approximately 90%) disclose superficial erosions with dysplasia, carcinoma in situ, or already developed carcinoma in the surrounding margins SQUAMOUS CELL CARCINOMA

- Multifactorial - Chronic abusers of smoked tobacco and alcohol - Actinic radiation (sunlight) and, particularly, pipe smoking

are known predisposing influences for cancer of the lower lip Molecular Biology of Squamous Cell Carcinoma.

- Several genetic alterations, some definitively identified and some inferred from tumor-specific chromosomal alterations, have been found in HNSCC

HANSEL, CHINEE, JOAN 6

- The first change is the loss of chromosomal regions of 3p and 9p21

- Loss of heterozygosity (LOH) in conjunction with promoter hypermethylation at this locus results in the inactivation of the p16 gene, an inhibitor of cyclin-dependent kinase

- Subsequent LOH at 17p with mutation of the p53 tumor suppressor gene is associated with progression to dysplasia

- gross genomic alterations as well as deletions on 4q, 6p, 8p, 11q, 13q, and 14q may act as predictors of progression to malignancy

- amplification and overexpression of the cyclin D1 gene (located on chromosome 11q13), which constitutively activates cell cycle progression, is a common late event

Clinical, histologic, and molecular progression of oral cancer. A, The typical clinical progression of oral cancer. B, The histologic progression of squamous epithelium from normal, to hyperkeratosis, to mild/moderate dysplasia, to severe dysplasia, to cancer. C, The sites of the most common genetic alterations identified as important for cancer development. CIS, carcinoma in situ; SCC, squamous cell carcinoma. Morphology:

- Favored locations are the ventral surface of the tongue, floor of the mouth, lower lip, soft palate, and gingival

Schematic representation of the sites of origin of squamous cell carcinoma of the oral cavity, in numerical order of frequency.

Cancers of the oral cavity appear either as raised, firm, pearly plaques or as irregular, roughened, or verrucous areas of mucosal thickening, possibly mistaken for leukoplakia

Histologic examination, these cancers begin as dysplastic lesions, which may or may not progress to full-thickness dysplasia (carcinoma in situ) before invading the underlying connective tissue stroma

Squamous cell carcinomas range from well-differentiated keratinizing neoplasms to anaplastic, sometimes sarcomatoid, tumors, and from slowly to rapidly growing lesions

The favored sites of local metastasis are the cervical lymph nodes, while the most common sites of distant metastasis are mediastinal lymph nodes, lungs, liver, and bones. ODONTOGENIC CYSTS AND TUMORS

- Epithelial lined cysts are quite common in jaws

DENTIGEROUS CYST

- Originates around the crown of an unerupted tooth - Result of a degeneration of dental follicle - Radiographically unilocular lesions

- Most associated with impacted 3rd molar (wisdom) teeth

Histologically:

- lined by thin layer of stratified squamous epithelium - Very dense chronic inflammatory cell infiltrate in the

connective tissue stroma - Complete removal of the lesion is curative - incomplete excision: may result in recurrence or very rarely

into an ameloblastoma or squamous cell carcinoma

KERATOCYSTIC ODONTOGENIC TUMOR formerly known as Odontogenic Keratocyst (OKC)

- Locally aggressive and has a high rate of recurrence - Patients between 10-40 years old - Most common in males within posterior mandible - Presents as well defined unilocular or multilocular

radiolucencies

Histologically:

- cyst lining consists of a thin layer of parakeratinized or orthokeratinized stratified squamous epithelium with a prominent basal cell layer and corrugated appearance of the epithelial surfaces

- Treatment requires aggressive and complete removal - Recurrence rates 60% - Gorlin syndrome (nevoid basal cell carcinoma syndrome)

multiple OKC related to mutations in the tumor suppressor gene PTCH located in 9q22

PATHOLOGY HEAD AND NECK DR. INOCENCIO

PERIAPICAL CYST

- Inflammatory in origin - Found at the apex of teeth - Develop as long standing pulpitis, which may be caused by

advanced carious lesions or by trauma to the tooth - Inflammatory process may result in necrosis of pulpal tissue

which can transverse the length of the root and exit the apex of the tooth into the surrounding alveolar bone, giving rise to periapical abscess

- A lesion with granulation tissue may develop (periapical granulomas is not appropriatee because it does not show true granulomatous inflammation)

- Lesions persist as a result of bacteria - Removal of offending material and appropriate restoration of

the tooth or extraction ODONTOGENIC TUMORS

- Complex group of lesions with diverse histologic appearances and clinical behavior

- True neoplasm or hamartomas - Derived from odontogenic epithelium, ectomesenchyme or

both Two most common tumors: 1. Ameloblastoma arises from odontogenic epithelium and shows no ectomesenchymal differentiation. Mostly in jaw bone and required wide surgical resection to prevent recurrences Cystic, slow growing, locally invasive Most are indolent 2. Odontoma most common type, arises from epithelium but shows extensive deposition of enamel and dentin Probably hamartomas, cured by excision

UPPER AIRWAYS

(Nose, Pharynx, Larynx and their related structures) disorders are among the most common afflictions of humans, but overwhelming majority are more nuisances than threats NOSE

- Inflammatory diseases in the form of common cold- Most common disorders of the nose and its accessory sinuses

- most are viral in origin but often complicated by superimposed bacterial infections

INFLAMMATIONS INFECTIOUS RHINITIS

- Common cold - Caused by one or more viruses - Major offenders: adenoviruses, echoviruses, and

rhinoviruses - Profuse catarrhal discharge - Initial Acute stages: nasal mucosa is thickened, edematous

and red ;Nasal cavities are narrowed ;Turbinates are enlarges

- May produces concomitant pharyngotonsillitis - Secondary bacterial infections: enhances the inflammatory

reaction Produces mucopurulent or suppurative exudate

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ALLERGIC RHINITIS

- Hay fever - Hypersensitivity reactions to one of a large group of

allergens - Ig-E mediated immune reaction with an early and late

response phase - Marked mucosal edema - Redness - Mucus secretion, accompanied by leukocytic infiltration with

prominent eosinophils NASAL POLYPS

- recurrent attacks of rhinitis may eventually lead to focal protrusions of the mucosa producing nasal polyps

- may reach 3-4 cm in length

Histologically:

- edematous mucosa having a loose stroma, often harboring hyperplastic or cystic mucous glands, infiltrated with a variety of inflammatory cells, including neutrophils, eosinophils, and plasma cells with cluster of lymphocytes

- When multiple or large, may encroach on the airway and impair sinus drainage

- if with absence of bacterial infection: mucosal covering is intact; chronicity

- may cause ulceration or infection -

a. nasal polyps. Low-power magnification showing adenomatous masses lined by epithelium B. High power view, showing deem and eosinophil-rich inflammatory infiltrates CHRONIC RHINITIS

- Repeated attacks of acute rhinitis - Either microbial or allergic in origin with the eventual

development of superimposed bacterial infection - Deviated nasal septum or nasal polyps with impaired

drainage of secretion - Superficial desquamation or ulceration of

mucosal epithelium

- Variable inflammatory infiltrate of neutrophils, lymphocytes, and plasma cells

SINUSITIS

- Acute sinusitis: commonly preceded by acute/chronic rhinitis

- Maxillary sinusitis arises by extension of periapical infection through the bony floor of the sinus

- Offending agents: inhabitants of the oral cavity - Inflammatory reaction is non specific - Impairment of drainage of the sinus by inflammatory edema

of mucosa - Suppurative exudate producing empyema of the sinus - Obstruction of outflow most often from the frontal sinus

leads to accumulation of mucous secretions in the absence of direct bacterial invasion producing mucocele

- Component of Kartagener syndrome which also includes bronchiectasis and and situs inversus.

Chronic sinusitis:

- caused by fungi (e.g mucormycosis) especially in diabetics - Infection may spread into the orbit or penetrate the

surrounding bone to give rise to osteomyelitis or spread into the cranial vault, causing septic thrombophlebitis of a dural venous sinus

NECROTIZING LESIONS OF THE NOSE AND UPPER AIRWAYS May be produced by:

- Acute fungal infections (including mucormycosis particularly in diabetics and immunosuppressed)

- Wegener granulomatosis - Lymphoma of natural killer cells infected with EBV

previously known as Lethal midline granuloma or polymorphic reticulosis

o Ulceration and superimposed bacterial infection complicate the process

o Uncontrolled growth of lymphoma possibly with penetrating the cranial vault

o Tumor necrosis with secondary bacterial infection and blood borne dissemination of the infection

NASOPHARYNX INFLAMMATIONS PHARYNGITIS AND TONSILLITIS

- Multitudinous rhinoviruses, echoviruses and adenoviruses, respiratory syncytial viruses and various strains of influenza virus

- Reddening and slight edema of nasopharyngeal mucosa - Reactive enlargement of related lymphoid structures - Inflamed mucosa may be covered by an exudative membrane

(pseudomembrane) - Nasopalatine and palatine tonsils are often enlarged and

covered by exudate - Most common offenders: B hemolytic streptococci ;

sometimes Staphylococcus aureus - Follicular tonsillitis- typical appearance of an enlarged,

reddened tonsils (due to reactive typhoid hyperplasia)

PATHOLOGY HEAD AND NECK DR. INOCENCIO

dotted by pinpoints of exudates emanating from the tonsillar crypts

- Streptococcal sore throats may develop into rheumatic fever (late sequelae) and glomerulonephritis

TUMORS OF THE NOSE, SINUSES AND NASOPHARYNX

- Infrequent - Mesenchymal and epithelial neoplasm

NASOPHARYNGEAL ANGIOFIBROMA

- Highly vascular tumor - Occurs almost exclusively in adolescent males - Tendency to bleed profusely during surgery (death caused by

haemorrhage)

SINONASAL (SCHNEIDERIAN) PAPILLOMA

- Benign neoplasm - Arising from the sinonasal mucosa - Composed of squamous or columnar epithelium - HPV types 6 and 11 have been identified in the lesion

Three forms of lesions:

- Exophytic (most common) - Inverted (most important biologically) - Cylindrical

INVERTED PAPILLOMAS

- uniquely aggressive biologic behavior - Benign but locally aggressive neoplasm - Occurring in nose and paranasal sinuses - Papillomatous proliferation of squamous epithelium - Extends into the mucosa - High rate of recurrence - Serious complication of invasion of the orbit or cranial vault,

frank carcinoma may develop

Inverted papilloma. the masses of squamous epithelium are growing inward; hence the term inverted. OLFACTORY NEUROBLASTOMA (ESTHESIONEUROBLASTOMA)

- Uncommon, malignant tumors - Composed of small round cells, resembling neuroblasts - Form lobular nests encircled by vascularized connective

tissue - Most often arise superiorly and laterally in nose from the

neuroendocrine cells dispersed in the olfactory mucosa - Differential diagnosis: lymphoma, Ewing sarcoma, and

embryonal rhabdomyosarcoma - Cells are of neuroendocrine origin - Are primitive neuroectodermal tumors - Some reveal trisomy 8 - Exhibit membrane bound secretory granules - Express neuron specific enolase, synaptomhysin, CD56 and

chromogranin by immunohistochemistry (all look the same sa stain will be needed)

- many don not share the 11;22 translocation or fusion-gene products typical of ewing sarcoma (has rosette formation) of the bone and other primitive neuroectodermal tutors

- 5 year survival rate of 40-90% NUT MIDLINE CARCINOMA

- uncommon tumor that may occur in the nasopharynx, the salivary gland or in other midline structures in the thorax or abdomen

- can occur at any age - extremely aggressive and resistant to conventional therapy - most patient survive for less than a year - associated with translocations that create fusion genes

encoding chimeric proteins comprised of most of NUT, a chromatin regulator and a portion of a chromatin reader protein, usually BRD1

NASOPHARYNGEAL CARCINOMA

- Close anatomic relationship to lymphoid tissue and an association with EBV infection

Three patterns:

- Keratinizing squamous cell carcinoma (least radiosensitive) - Nonkeratinizing - Undifferentiated carcinomas (most radiosensitive)

- Abundant non neoplastic, lymphocytic infiltrates - Lymphoepithelioma

Three factors that affect the origin:

- Heredity - Age - Infection with EBV (EBNA-1 in tumor epithelial cells)

Other factors:

- Diets high in nitrosamines (fermented foods and salted fish) - Smoking - Chemical fumes

HANSEL, CHINEE, JOAN 10

- Primary Nasopharyngeal Ca often occult for long periods and present as metastases in cervical lymph nodes

Morphology Histologically:

- Keratinizing and nonkeratinizing squamous cell lesions resemble usual well differentiated and poorly differentiated squamous cell carcinoma arising from other locations

- Undifferentiated: large epithelial cells with oval or round vesicular nuclei, prominent nucleoli, and indistinct cell borders dispodes in syncytium-like array

- admixed with abundant, mature, normal appearing lymphocytes, predominantly T cells

Nasopharyngeal Carcinoma, undifferentiated type. The syncytium-like nests of epithelium are surrounded by lymphocytes LARYNX INFLAMMATIONS LARYNGITIS

- Sole manifestation of allergic, viral, bacterial or clinical insult - More commonly part of generalized URTI or result of heavy

exposure to environmental toxins (tobacco) - Occurs in association with gastroesophageal reflux due to

irritating effects of gastric content - Affected in systemic infections (TB or diphtheria) - Mucosal congestion, exudation or edema may

cause laryngeal obstruction - Heavy smokers: predisposes to squamous epithelial

mataplasia and sometimes carcinoma

LARYNGOEPIGLOTTITIS

- Caused by Haemophilus influenza or B hemolytic streptococci

- Infants and children with small airways - Sudden swelling of the epiglottis and vocal cords

CROUP

- Laryngotracheobronchitis in children - Inflammatory narrowing of the airway

REACTIVE NODULES (VOCAL CORD NODULES & POLYPS)

- Polyps or reactive nodules develop on the - vocal cords - Often in heavy smokers or singers (singers nodules) - Adult men are most often affected - Singers nodules - Bilateral lesion and polyps are unilateral - Smooth, rounded, sessile or pedunculated excrescences - Located usually on the true vocal cords - Covered by squamous epithelium that may become keratotic,

hyperplastic or dysplastic - Core of nodule is loose myxoid connective tissue that may be

fibrotic or punctuated by numerous vascular channels - When nodules impinge each other, mucosa may undergo

ulceration - Change in character of voice and often progressive

hoarseness - Virtually never give rise to cancers -

SQUAMOUS PAPILLOMA AND PAPILLOMATOSIS

- Benign neoplasm - Located on the true vocal cords - Soft, raspberry like excrescences rarely more than 1 cm in

diameter

Histologically: - papillomas are made up of multiple slender, finger like

projections supported by central fibrovascular cores and covered by an orderly stratified squamous epithelium

- When papillomas are on the free edge, trauma may lead to ulceration with hemoptysis

- Papillomas are usually single in adults; multiple in children - Lesions are caused by HPV types 6 and 11 - Do not become malignant but may recur - Juvenile laryngeal papillomatosis - Papillomas in children

- Benign comparison of a benign papilloma and an exophytic

carcinoma of the larynx to highlight their quite different appearances

CARCINOMA OF THE LARYNX

- Sequence of hyperplasia-dysplasia-carcinoma - Hyperplasia, dysplasia, carcinoma in situ to invasive

carcinoma - typically a squamous cell carcinoma seen in male chronic

smokers - those confined within the larynx proper are termed intrinsic,

whereas those that arise or extend outside the larynx are called extrinsic

- Epithelial changes vary from smooth, white or reddened focal thickenings, sometimes roughened by keratosis, to irregular verrucous or ulcerated white-pink lesions that are similar in appearance to carcinoma

- There are all gradations of epithelial hyperplasia of the true vocal cords, and the likelihood of the development of an overt carcinoma is directly proportional to the level of atypia when the lesion is first seen

- Orderly hyperplasias have almost no potential for malignant transformation

- Changes are often related to tobacco smoke The changes often regress after cessation of smoking

- Alcohol is also a risk factor

PATHOLOGY HEAD AND NECK DR. INOCENCIO

- Nutritional factors, exposure to asbestos, irradiation and infection with HPV may contribute to increased risks

- Persistent hoarseness - Tumors may produce pain, dysphagia, and hemoptysis - Vulnerable to secondary infection of the ulcerating lesion - Surgery, irradiation, combination therapy

Morphology

- 95 % are typical squamous tumors - Develops directly on the vocal cords but may arise above or

below, on the epiglottis or aryepiglottic folds or pyriform sinuses

- Intrinsic: confined within larynx - Extrinsic: outside the larynx - Begins as in situ lesions that later appear as pearly gray,

wrinkled plaques on the mucosal surface, ultimately - ulcerating and fun gating - Adjacent mucosa may demonstrate squamous cell

hyperplasia with foci or dysplasia or even carcinoma in situ

A. Larngeal Carcinoma, Note the large, ulcerated, fun gating lesion involving the vocal cord and pyriform sinus. B, Histologic appearance of laryngeal squamous cell carcinoma. note the atypical lining epithelium and invasive keratinising cancer cells in thesubmucosa

EARS

- Most common aural disorders in descending order of

frequency: - Acute and chronic otitis (most often middle ear and mastoid),

sometimes leading to cholesteatoma - symptomatic otosclerosis - aural polyps - labyrinthitis - carcinomas, largely of external ear - paragangliomas, found mostly in the middle ear

INFLAMMATORY LESIONS OTITIS MEDIA (ACUTE/CHRONIC)

- Inflammation of the ear - Occur mostly in infants and children - Viral in nature - Produce a serous exudate but may become suppurative with

superimposed bacterial infection - Most common offenders: Streptococcus, pneumonia, non

typeable H. influenza, Moraxella catarrhalis, Pseudomonas aeroginosa (chronic om), Staphylococcus aureus, or a fungus

- In diabetic person, is aggressive and spreads widely causing destructive necrotizing otitis media

CHRONIC OTITIS MEDIA

- Has potential to perforate the eardrum - Encroach on the ossicles or labyrinth - Spread into the mastoid space - Even penetrate into the cranial vault to produce a temporal

cerebritis or abscess - with serous accumulation, may rupture

CHOLESTEATOMAS

- Associated with chronic otitis media - Not neoplasms, nor do they always contain cholesterol - Cystic lesions 1-4 cm in diameter - Lined by keratinizing squamous epithelium or metaplastic

mucus- secreting epithelium - Filled with amorphous debris - Sometimes contain specules of cholesterol - Chronic inflammation and perforation of the eardrum with

ingrowth of squamous epithelium or metaplasia of secretory epithelial lining of the middle ear are responsible for formation of a squamous cell nest that become cystic

- Sometimes, the cyst ruptures, increasing the inflammatory reaction and inducing the formation of giant cells that enclose partially necrotic squames and other debris

- Can erode ossicles, labyrinth, adjacent bone or surrounding tissues

- Sometimes produce visible neck masses OTOSCLEROSIS

- Abnormal bone deposition in the middle ear about the rim of the oval window into which the footplate of the stapes fit

- Both ears are usually affected - First, there is fibrous ankylosis of the footplate followed by

bony overgrowth anchoring it into the oval window - degree of immobilization governs the severity of the hearing

loss - basis for osseous overgrowth appears to represent

Uncoupling of normal bone resorption and bone formation - Begins with bone resorption, followed by fibrosis and

vascularization of the temporal bone in the immediate vicinity of the oval window, in time replaced by dense new bone anchoring the footplate of the stapes

HANSEL, CHINEE, JOAN 12

- Usually begins in the early decades of life - May be familial autosomal dominant - May lead to marked hearing loss

TUMORS

- Epithelial and mesenchymal tumors external, middle, internal

- Basal cell or squamous cell carcinomas of the pinna (external ear)

- Tend to occur in elderly men - Associated with actinic radiation - Locally invasive but rarely spread

Squamous cell carcinomas within canal

- Middle aged to elderly women - Not associated with sun exposure - Beginning as papules that extend, crode and invade locally - May invade the cranial cavity or metastasize to regional

nodes

NECK

The following are uncommon but unique to the neck: Branchial Cyst (Cervical Lymphoepithelial Cyst)

- thought to arise from remnants of the second brachial arch and are most commonly observed in young adults between ages 20 and 40

- appear on the upper lateral aspect of the neck along sternocleidomastoid muscle

- cyst are well circumscribed, 2 to 5 cm in diameter, with fibrous walls usually lined by stratified squamous epithelium or pseudostratified columnar epithelium

- cyts wall typically contains lymphoid tissue with prominent germinal centers.

- contents of the cyst may be clear and watery or mucinous and may contain desqwuamated, granular cellular debris. benign cysts

- slowly progressive - readily excised

- upper lateral aspect of the neck along the

sternocleidomastoid muscle - arise from remnants of second branchial arch

Thyroglossal Duct Cyst

- 1 to 4 cm in diameter - lined by stratified squamous epithelium - near the base of the

tongue, or by pseudostratified columnar epithelium - lower locations

- Transitional patterns are also encountered - Possible of malignant transformation but rare! - Tx: excision

Paraganglioma (Carotid Body Tumor)

- most common location of the tumor is within the adrenal medulla, where they give rise to pheochromocytoma

- approximately 70% of estra- adrenal paragangliomas occur in the head and neck region

- pathogenesis is not fully understood - chiefly composed of nests (zellballen) of round to oval chief

calls (neuroectodermal in origin) that are surrounded by delicate vascular septae

- tumors cell contain abundant, clear or granular, eosinophilic cytoplasm and uniform, round to ovoid, sometimes vesicular nuclei

- slow-growing and painless masses - usually arise in the fifth and sixth decades of life - associated with the sympathetic and parasympathetic

nervous systems - can be seen throughout various regions of the body

- possible cause: succinate oxidoreductase, an enzyme involved in mitochondrial respiration

- microscopic features - remarkably uniform

2 locations of possible growth:

1. Paravertebral paraganglia - tumors have sympathetic connections chromaffin-positive - a stain that detects catecholamines

2. Paraganglia related to the great vessels of the head and neck, the so- called aorticopulmonary chain, including carotid bodies; aortic bodies; jugulotympanic ganglia; ganglion nodusom of the vagus nerve; and clustersw located about the oral cavity, nose, nasopharynx, larynx, and orbit. These are innervated by parasympathetic nervous sytem and release cathecholamines.

Morphology: Carotid body tumor:

PATHOLOGY HEAD AND NECK DR. INOCENCIO

- prototpye parasympathetic ganglioma - rarely exceeds 6cm in diameter - arises close to or envelops the bifurcation of the common

carotid artery - red-pink to brown - composed of nests (Zellballen) of round to oval chief cells

(neuroectodermal in origin) that are surrounded by delicate vascular septae

- abundant, clear or granular, eosinophilic cytoplasm - uniform, round to ovoid, sometimes vesicular, nuclei - little cellular pleomorphism, and scant mitoses - sustentacular cells - positive for S-100 protein - ** chief cells that stain in chromogranin, synaptophysin,

neuron-specific enolase, CD56, and CD57

FIGURE 16-14 Carotid body tumor. A, Low-power view showing tumor clusters separated by septa (Zellballen). B, High-power view of large, eosinophilic, slightly vacuolated tumor cells with elongated sustentacular cells in the septa

- may be familial - with autosomal dominant transmission - frequently recur after incomplete resection - benign but may metastasize to regional lymph nodes and

distant sites - **mitoses, pleomorphism, and even vascular invasion are not

reliable indicators**

SALIVARY GLANDS

- parotid, submandibular, and sublingual Xerostomia

- decreased saliva production - aka dry mouth - major feature of the autoimmune disorder Sjgren

syndrome - major complication of radiation therapy

drug-induced:

- anticholinergic - antidepressant/antipsychotic - diuretic, antihypertensive - sedative - muscle relaxant

- analgesic - antihistamine agents

Complications:

- increased rates of dental caries - candidiasis - difficulty in swallowing and speaking.

Inflammation (Sialadenitis)

- traumatic, viral, bacterial, or autoimmune - Mucoceles are the most common type of lesion - keratoconjunctivitis sicca dry eyes

Mumps

- most common form of viral sialadenitis - parotid glands are affected

Mucocele

- most common lesion of the salivary glands - results from the blockage or rupture of salivary gland duct,

with consequent leakage of saliva into the surrounding connective tissue stroma.

- most often found in lower lip and the result of trauma - typically seen in toddlers and young adults and elderly, ho

are more prone to falling histologically,

- has a cystlike space (filled with mucin and inflammatory cells)that is lined by inflammatory granulation tissue or by fibrous connective tissue

- Complete excision of the cyst with the minor salivary gland

lobule origin is required to avoid recurrence.

FIGURE 16-15 Mucocele. A, Fluctuant fluid-filled lesion on the lower lip subsequent to trauma. B, Cystlike cavity filled with mucinous material and lined by organizing granulation tissue

Ranula identical to mucocele in which duct of the sublingual gland has been damaged; can become extremely large and develop into a plunging ranula

HANSEL, CHINEE, JOAN 14

Sialolithiasis and Nonspecific Sialadenitis

- major salivary glands submandibular glands - usually secondary to ductal obstruction produced by stones

(sialolithiasis) - common etiology: S. aureus and Streptococcus viridians - unilateral involvement

Most common Salivary Gland Tumors Benign:

- Pleomorphic adenoma. i.e. Mixed Tumor - warthin Tumor (Papillary Cystadenoma Lymhpomatosum)

Malignant:

- all are adenocarcinoma - muciepidermoid carcinoma - adenoid cystic carcinoma

Neoplasms

- About 65% to 80% arise within the parotid, 10% in the submandibular gland, and the remainder in the minor salivary glands, including the sublingual glands

- The likelihood of a salivary gland tumor being malignant is more or less inversely proportional to the size of the gland.

- Adults, slight female predominance Warthin tumors

- Males - Benign - often appear in the fifth to seventh decades of life - Malignant ones later in life - no reliable criteria to differentiate benign from malignant

tumors. PLEOMORPHIC ADENOMA/MIXED BENIGNBENIGN TUMOR

- 60% of tumors in the parotid Dominant histologic feature:

- great heterogeneity - mixture of ductal (epithelial) and myoepithelial cells - Epithelial - myxoid, hyaline, chondroid (cartilaginous), and

even osseous tissue - Resembles ductal cells or myoepithelial cells - arranged in duct formations, acini, irregular tubules, strands,

or sheets of cells Morphology

- Pleomorphic adenomas rounded, well-demarcated masses (encapsulated)

- Palate capsule (not fully developed) - expansile growth produces protrusions into the surrounding

gland - enucleation of the tumor hazardous - cut surface gray-white with myxoid and blue translucent

areas of chondroid (cartilage-like) - epithelial resembling ductal cells or myoepithelial cells - arranged in acini, irregular tubules, strands, or sheets of

cells - typically dispersed within a mesenchyme-like background of

loose myxoid tissue containing islands of chondroid and, rarely, foci of bone

-

- lined by cuboidal to columnar cells with an underlying layer of deeply chromatic, small myoepithelial cells

- no difference in biologic behavior between the tumors composed largely of epithelial elements and those composed largely of seemingly mesenchymal elements

Clinical Features

- tumors: painless, slow-growing, mobile discrete masses within the parotid or submandibular areas or in the buccal cavity (image earlier)

- carcinoma ex pleomorphic adenoma or a malignant mixed tumor carcinoma arising in a pleomorphic adenoma

- cancer usually takes the form of an adenocarcinoma or undifferentiated carcinoma

WARTHIN TUMOR (PAPILLARY CYSTADENOMA LYMPHOMATOSUM)

- benign neoplasm

PATHOLOGY HEAD AND NECK DR. INOCENCIO

- second most common salivary gland neoplasm - arises almost exclusively in the parotid gland (the only tumor

virtually restricted to the parotid) - more commonly in MALES - Smokers have higher risk

Morphology

- round to oval, encapsulated masses, 2 to 5 cm in diameter - superficial parotid gland palpable - transaction: pale gray surface punctuated by narrow cystic

or cleftlike spaces filled with a mucinous or serous secretion microscopic:

- lined by a double layer of neoplastic epithelial cells resting on a dense lymphoid stroma sometimes bearing germinal centers

- spaces: narrowed by polypoid projections of the lymphoepithelial elements

- double layer of lining cells consists of a surface palisade of columnar cells having an abundant, finely granular, eosinophilic cytoplasm (oncocytic appearance) rests on a layer of cuboidal to polygonal cells

- Oncocytes epithelial cells stuffed with mitochondria - Secretory cells dispersed in the columnar cell layer

MUCOEPIDERMOID CARCINOMA Composed of:

- Squamous cells - Mucus-secreting cells - Intermediate cells

- 15% of ALL salivary gland tumors - 60-70% in the PAROTIDS - MECT1-MAML2 gene play a key role in the genesis of this

tumor, possibly by perturbing the notch and cAMP-dependent signaling pathways

- most common form of primary malignant tumor of the salivary glands

Morphology

- can grow as large as 8 cm in diameter - circumscribed but lack well-defined capsules (infiltrative at

the margins Transection:

- pale and gray-white

- contain small, mucin-containing cysts histologic pattern:

- cords, sheets, or cystic configurations of squamous, mucous, or intermediate cells

- hybrid cell types squamous features, with small to large mucus-filled vacuoles (highlighted with mucin stains)

- tumor cells regular and benign appearing OR highly anaplastic and unmistakably malignant

- subclassified: low, intermediate, or high grade

OTHER SALIVARY GLAND TUMORS ADENOID CYSTIC CARCINOMAS

- uncommon tumor - 50% cases minor salivary glands (palate) - (major) parotid and submandibular glands most common

locations Morphology Gross:

- small, poorly encapsulated, infiltrative, gray-pink lesions Histologic:

- composed of small cells having dark, compact nuclei and scant cytoplasm

- Cells disposed in tubular, solid, or cribriform patterns reminiscent of cylindromas arising in the adnexa of the skin

- Spaces: filled with a hyaline material thought to represent excess basement membrane

HANSEL, CHINEE, JOAN 16

ACINIC CELL TUMOR

- Composed of resembling serous acinar cells of salivary glands

- uncommon (2-3% of salivary gland tumors) - most arise in the parotids; remainder arise in the

submandibular glands - sometimes bilateral or multicentric

Gross:

- small, discrete lesions that may appear encapsulated Histologic:

- cells clear cytoplasm but the cells are sometimes solid and at other times vacuolated

- disposed in sheets or microcystic, glandular, follicular, or papillary patterns

- course of these neoplasms dependent on the level of pleomorphism

- recurrence after resection is uncommon _________________________________________________________________________________ END. Hansel, chinee, joan REFERENCES: 1. Kumar et al. 2010. Robbinsand Cotran Pathologic Basis of Disease. 8th ed. Pp. 3-42 2. DR. nocencios lecture 3. Trascription from Batch 2016