1. DESEASES OF HEAD, NECK, EAR, NOSE and TRHOAT
Associate Professor
Dr. Alexey Podcheko
Spring 2015
The “realm” of “ENT”, or otolaryngology, includes diseases of the nose, nasal cavity, nasopharynx, oral cavity, oropharynx, larynx, laryngopharynx, “upper” airway, defined as airspaces leading ultimately into the lung, and all the structures in these spaces, such as the for pairs of nasal sinuses, auditory tubes, ears, nasolacrimal duct, tonsils, and salivary glands.
ENT docs do thyroid surgery too.

2. Topics:
1. oral cavity 2. upper airways, including the nose, pharynx, larynx, and nasal sinuses; 3. ears 4. neck 5. salivary glands

3. EVERYTHING that touches AIR (columnar) or FOOD (squamous) in the HEAD/NECK region
ORAL CAVITY
“UPPER” RESPIRATORY TRACT
EARS
NOSE
SALIVARY GLANDS
Because a tougher stratified squamous mucosa is needed when these spaces come into contact with particulate matter, or material other than air or water, this type of mucosa, no matter where it is in the ENT domain, behaves similarly to degenerative, inflammatory, and neoplastic influences. Similarly, upper “airway” mucosa, classically subject only to air contact, is pseudostratified ciliated columnar in histology, and behaves similarly to these three influences as well. Upper airway mucosa, however, often transforms into stratified squamous by a process called “squamous metaplasia” as a non specific response to a wide variety of injurious stimuli.

4. INTENDED LEARNING OUTCOMES
Understand the common disorders of the upper airway and upper digestive tract (i.e., head and neck) in the usual context of:
DEGENERATIVE,
INFLAMMATORY,
and
NEOPLASTIC
…deviations of normal anatomy and histology
Once again, amid the numerous brilliant adjectives one can place before the word “diseases”, from a solid anatomical point of view, the classifications of DEGENERATIVE, INFLAMMATORY, and NEOPLASTIC cover almost all basis, and is a good way to think of disease classifications of any organ or system.

5. ORAL CAVITY Common pathologic conditions of the oral cavity
TEETH/GINGIVA/ALVEOLAR BONE
INFLAMMATORY/”REACTIVE” LESIONS
INFECTIONS: HSV, VIRAL, FUNGI
LEUKOPLAKIA/”HAIRY” LEUKOPLAKIA
SQUAMOUS TUMORS: BEN/MALIG
ODONTOGENIC CYSTS/TUMORS
Common pathologic conditions of the oral cavity

7. Time frame of teething Incisors 10-15mo Bicuspids 15-18mo
Molars 18-24mo

8. Tooth Decay (Cavities, “Caries”)
Dental caries one of the most common diseases, is the most common cause of tooth loss before age 35
Result of mineral dissolution of tooth structure
“Processed” carbohydrates, i.e., sugars
Bacterial (Strep. Viridans: Strep. Mutans + Strep. Sanguis; Lactobacilli, Actinomycetes) acidic erosion of enamel due to ability to produce insoluble dextrans
Role of pH, spacing, brushing, Fl
Tartarplaquecalculus = bacteria, proteins, cells

9. Gram Positive cocci isolated from the blood of patient with bacteremia synthesize dextrans from glucose. The bacteria most likely contribute to which of the following pathological states?
A Glomerulonephritis
B. Sarcoidosis
C. Erythema nodosum
D. Migratory polyarthritis
E. Anterior uvetis
F. Dental Caries

10. Vindans streptococci, notably S. mutants and S
Vindans streptococci, notably S. mutants and S. sanguis, are normally present in the human mouth and are major contributors of tooth decay and the initiation of dental caries. The organisms also cause bacterial endocarditis. Viridans streptococci are adhere to the surface of tooth enamel and heart valves and multiply in those locations due to their ability to produce insoluble dextrans.

11. Find the “cavity”, i.e., caries, i.e., enamel erosion

12. GINGIVITIS
Gingiva - squamous mucosa in between the teeth and around them
Gingivitis is inflammation of the mucosa and the associated soft tissues.
Causes:
Bacteria: Actinobacilli, Porphyromona, Prevotella
Viruses: HSV1 and 2
Symptoms: erythema, edema, bleeding, changes in contour, and loss of soft-tissue adaptation and sores 12

13. Periodontitis
Definition: inflammatory process that affects the supporting structures of the teeth: periodontal ligaments, alveolar bone, and cementum
Causes: Bacteria, adult periodontitis is associated primarily with:
Actinobacillus actinomycetemcomitans,
Porphyromonas gingivalis
Prevotella intermedia
Affected structures: Gingiva, periodontal ligaments, bone, cementum

14. Periodontitis Component of several different systemic diseases:
1. AIDS
2. Leukemia
3. Crohn's disease
4. Diabetes mellitus
5. Down syndrome
6. Sarcoidosis,
7. Syndromes associated with polymorphonuclear defects (Chédiak-Higashi syndrome, agranulocytosis, and cyclic neutropenia)
Etiologic factor in several important systemic diseases:
1. infective endocarditis,
2. pulmonary and brain abscesses,
3. averse pregnancy outcomes (preeclampsia)

15. A 67-year-old male is hospitalized with low-grade fevers fatigue and a diastolic murmur at the left sternal border. Blood cultures reveal Gram positive cocci that are catalase-negative and able to grow in the presence of optocin. This patient’s medical history is most likely to reveal which of the following procedures in the past month?
A. Dental extraction
B. Skin biopsy
C. Sinus drainage
D. Nasal polypectomy
E. Cystoscopy

16. (Choice A) Dental extraction is associated with endocarditis caused by S. viridans, a Gram positive coccus. In most cases, S. viridans causes subacute bacterial endocarditis in already abnormal heart valves (e.g. congenital valvular abnormalities valves damaged by rheumatic fever.)

18. Inflammatory/Reactive Tumor-like Lesions
MC fibrous proliferative lesions of the oral cavity:
fibroma (61%)
reactive nodules of the oral cavity peripheral ossifying fibroma
pyogenic granuloma
peripheral giant-cell granuloma
gingival hyperplasia

19. Irritation fibroma
primarily occurs in the buccal mucosa along the bite line or at the gingivodental margin.
Morphology: nodular mass of fibrous tissue, with few inflammatory cells, covered by squamous mucosa.
Rx: Surgical excision
Smooth pink exophytic nodule on the buccal mucosa.

20. “Irritation” Fibroma
Often the terms “inflammatory” or “reactive” refers to this type of “fibroma”.

21. Peripheral ossifying fibroma
Growth of the gingiva that is considered to be reactive in nature rather than neoplastic.
Result of the maturation of a long-standing pyogenic granuloma
Rx: Surgical excision down to the periosteum (recurrence rate of 15% to 20%)

22. Pyogenic granuloma
Highly vascular pedunculated lesion on the gingiva (children, young adults, pregnant women (pregnancy tumor).
Growth can be rapid, raising the fear of a malignant neoplasm.
Histology: vascular proliferation that is similar to granulation tissue (capillary hemangioma?)
Regress with formation of peripheral ossifying fibroma.
Rx: surgical excision

23. PYOGENIC
GRANULOMA
Granuloma or neoplasm or granulation tissue? Who cares?
A pyogenic granuloma pops out like a “tumor” and is 100% indistinguishable from normal granulation tissue, and looks nice and pink and healthy like granulation tissue, i.e., organizing inflammation, too. The least thing it can be called is a granuloma, because it rarely has clusters of macrophages or giant cells. Would you expect a pyogenic granuloma to “blanch” and a fibroma NOT to “blanch”? Answer: YES

24. A 6-year-old boy presents with a painful sore in his mouth
A 6-year-old boy presents with a painful sore in his mouth. Physical examination reveals a small, elevated, and locally ulcerated red-purple gingival lesion. A soft red mass measuring 1 cm in diameter is surgically removed. Histologic examination discloses highly vascular granulation tissue, with marked acute and chronic inflammation. What is the most likely diagnosis?
(A) Acute necrotizing gingivitis
(B) Aphthous stomatitis
(C) Herpes labialis
(D) Pyogenic granuloma
(E) Tuberculosis

25. Peripheral giant cell granuloma
bluish purple tumor-like lesion
Histology: aggregation of multinucleate, foreign body–like giant cells separated by a fibroangiomatous stroma, not encapsulated
can cause resorption of alveolar bone
Rx: Surgical excision
Dif. diagnosis: central giant-cell granulomas of bones and “brown tumors” seen in hyperparathyroidism

26. Histology of peripheral giant cell granuloma reveals a dense infiltrate of histiocytes and multi-nucleated giant cells within the subepithelial fibrous stroma.

27. APHTHOUS ULCERS (CANKER SORES)
superficial ulcerations of the oral mucosa affect up to 40% of the population in the United States
Etiology: stress, fatigue, illness, injury from accidental biting, hormonal changes, menstruation, sudden weight loss, food allergies, and deficiencies in vitamin B12, iron, and folic acid , recurrent apthous ulcers may be associated with celiac disease and inflammatory bowel disease.
Clinic: extremely painful and often recurrent sores, tendency to be prevalent within certain families.
Morphology: Single or multiple, shallow, hyperemic ulcerations covered by a thin exudate and rimmed by a narrow zone of erythema
Histology: Mononuclear infiltrate
Prognosis: Spontaneously resolve in 7 to 10 days or be stubbornly persistent for weeks
Rx: local anesthetics

28. “Canker” sore = Aphthous ulcer
Obscure etiology, 40% of us have had them, painful, and you can bet there are inflammatory cells at the base. You know what they are. You’ve had them.
Things related to them include: stress, fatigue, illness, injury from accidental biting, hormonal changes, menstruation, sudden weight loss, food allergies, and deficiencies in vitamin B12, iron, and folic acid (wikipedia). Whenever a condition is associated with LOTS of things, like this, we call this an “obscure” etiology ;)

29. GLOSSITIS Inflammation of the tongue
atrophy of the papillae of the tongue and thinning of the mucosa, exposing the underlying vasculature
Atrophic Glossitis Causes: Deficiencies of vitamin B12 (pernicious anemia), riboflavin, niacin, or pyridoxine, sprue and iron-deficiency anemia.
Ulcerative Glossitis Causes: : jagged carious teeth, ill-fitting dentures, and, rarely, with syphilis, inhalation burns, or ingestion of corrosive chemicals
Clinic: Plummer-Vinson syndrome - combination of iron-deficiency anemia, glossitis, and esophageal dysphagia mostly in postmenopausal women

30. Glossitis: Bacterial or viral infections (including oral herpes simplex).
Mechanical irritation or injury from burns, rough edges of teeth or dental appliances, or other trauma
Exposure to irritants such as tobacco, alcohol, hot foods, or spices.
Allergic reaction to toothpaste, mouthwash, breath fresheners, dyes in candy, plastic in dentures or retainers, or certain blood-pressure medications (ACE inhibitors).
Disorders such as iron deficiency anemia, pernicious anemia and other B-vitamin deficiencies, oral lichen planus, erythema multiforme, aphthous ulcer, pemphigus vulgaris, syphilis, and others.
Occasionally, glossitis can be inherited. (Wikipedia)
If a “geographic” tongue mans only a part of the tongue is inflamed, i.e., “red”, then the tongue on the right has the geography of Maine or Illinois? Or India?

31. HERPES SIMPLEX VIRUS INFECTIONS
Mostly herpes simplex virus type 1 (HSV-1)
Enveloped double-stranded DNA virus
Primary HSV infection typically occurs in children age 2 to 4 years,
Forms:
acute herpetic gingivostomatitis – MOST Common form of primary infection
cold sores (Herpes labialis)
recurrent herpetic stomatitis

32. HERPES SIMPLEX VIRUS INFECTIONS
Herpetology is the study of creepy critters, reptiles and amphibians. Herpetic vesicles “creep” over mucosal surfaces.
Like CMV and V-Z viruses, the various herpes viruses (mainly type 1 and 2) are, amazingly, in the “herpes” family of viruses.
Early lesions crop up as vesicles, after a few days, these vesicles can be irritated, ulcerated, inflamed, and secondarily pustulated.
Classically type 1 was predominantly oral mucosa, and the slightly nastier type 2 was more genital, but nowadays, crossover is so common, who cares any more?
The virus recurs often for many years, triggered off by god-knows-what, and the newer antiviral agents have shown amazing efficacy in preventing recurrences.
Just about everybody had been exposed to herpes of some type.
HERPES SIMPLEX VIRUS INFECTIONS 32

33. HERPES SIMPLEX VIRUS INFECTIONS
Morphology:
Intracellular and intercellular edema (acantholysis) yielding clefts that may become transformed into macroscopic vesicles.
Cells have eosinophilic intranuclear viral inclusions,
multinucleate polykaryons
Tzanck test: microscopic examination of the vesicle fluid to find multinucleated polykarions

34. TZANCK SMEAR
The neat thing about a Tzanck smear is that you can do it easily in your office, just gently scrape a vesicle, smear it, stain it with just about anything, and look for much larger than usual squamous nuclei with inclusions. Most vesicles cause by herpes family viruses can have a POSITIVE Tzanck (pronounced “zank”) smear, or test.
Would you rule out herpes if the test was negative? Would you tend to be more likely to rule it in, if the smear was positive?
The neat thing about a Tzanck smear is that you can do it easily in your office, just gently scrape a vesicle, smear it, stain it with just about anything, and look for much larger than usual squamous nuclei with inclusions. Most vesicles caused by herpes family viruses can have a POSITIVE Tzanck (pronounced “zank”) smear, or test. 34

35. A 2-year-old male is brought to clinic with fever irritability, and decreased oral intake. Physical examination reveals swollen gums with ulcerative lesions and enlarged, tender cervical lymph nodes. Oral lesion scrapings demonstrate cells with intranuclear inclusions. Which of the following is most likely responsible for this patient’s disease?
A. Enveloped double-stranded DNA virus
B. Non-enveloped double-stranded DNA viru
C. Non-enveloped single-stranded DNA virus
D. Non-enveloped positive-sense RNA virus
E. Enveloped positive-sense RNA virus
F. Enveloped negative-sense RNA virus

36. A 5-year-old male is brought to the clinic with a several day history of fever, irritability and refusal to eat. Physical examination demonstrates painful gingival ulcers, swollen gums, and cervical lymphadenopathy. Microscopic examination of the oral ulcer base scrapings is shown on the slide below. This patient current situation is most likely represent:
A Primary infection
B. Virus reactivation
C. Latent infection
D. Abortive infect
E. Slow virus infection

37. ORAL CANDIDIASIS (THRUSH)
Candidiasis is by far the most common fungal infection in the oral cavity.
Factors:
(1) immune status of the individual;
(2) the strain of C. albicans present
(3) the composition of an individual's oral flora
(4) Abt therapy
(5) Underlying diseases (AIDS, Diabetes)
Major clinical forms of oral candidiasis:
Pseudo-membranous (thrush)
Erythematous
Hyperplastic,
Monilia, thrush-mouth, candida: they all mean the same thing. Look for a whitish oral film without much underlying inflammation (i.e., redness).
Common in babies, diabetics, immunocompromised people. Candida (almost always ablicans) always affects moist, usually non-keratinized, stratified squamous mucosa, i.e., mouth, vagina, moist genital skin areas. Everybody has it lying around waiting for an immunocompromised condition to occur.

38. White filmy patches NOT firmly attached to the underlying moist non-keratinized stratified squamous mucosa. Minimal redness. Candida is on all of us. It LOVES to proliferate on moist NON-keratinized stratifies squamous mucosae, especially in immune deficiency situations.

39. Finding the NON-septate hyphae (i. e
Finding the NON-septate hyphae (i.e., “pseudo”-hyphae) along with yeasts and budding yeasts in your simple office lab, is diagnostic. Almost any simple stain will show this. The “PAS” stain is best, because it imparts a bright red color to yeasts and pseuduhyphae

40. Oral Manifestations of Systemic Disease

41. Oral Manifestations of Systemic Disease

42. HAIRY LEUKOPLAKIA
Hairy leukoplakia - white patch or plaque that cannot be scraped off and cannot be characterized clinically or pathologically as any other disease, caused mostly by EBV infection
80% of patients with hairy leukoplakia are infected with the human immunodeficiency virus (HIV)!!!
Dif. diagnosis with Candidiasis - lesion cannot be scraped off.
Histology: Hyperparakeratosis and acanthosis with “balloon cells” in the upper spinous layer, koilocytosis of the superficial, nucleated epidermal cells,
Prognosis: In HIV-positive individuals, with hairy leukoplarkia, symptoms of AIDS follow in 2 to 3 years!

43. “Hairy” leukoplakia
LEUKOPLAKIA. This is defined as a dry flat “plaque” of, usually, the oral mucosa, due to ANY reason, many (most?) of which are NON-malignant, NON-dysplastic, and 100% reversible, but some of which are premalignant. Please understand “leukoplakia” is a clinical description, and NOT a specific clinical or pathological entity, and can range anywhere between hyperkeratosis/inflammation to carcinoma.

44. “Hairy” leukoplakia
“Hairy” leukoplakia however, is usually a sign of HIV.

45. Premalignant lesions in the oral cavity
Leukoplakia - a white patch or plaque that cannot be scraped off and cannot be characterized clinically or pathologically as any other disease
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
Speckled leukoerythroplakia :Erythro+Leukoplakia

46. Histologic progression of Leukoplakia into squamous cell carcinoma
EXTREMELY IMPORTANT concept in the insidious development of squamous cell carcinoma of ANY location, no matter what the genetics, molecular biology, or etiology is! UNDERSTAND THIS FOR THE REST OF YOUR LIFE!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
NORMAL DYSPLASIA CARCINOMA-IN-SITUINFILTRATING MALIGNANCY

47. Head and Neck are Squamous Cell Carcinomas (HNSCCs)
95% of cancers of the head and neck
overall long-term survival has remained at less than 50%
individual who is fortunate to live 5 years after the initial primary tumor has up to a 35% chance of developing at least one new primary tumor within that period of time
Etiology: Tabacco, Alcohol, actinic radiation (sunlight), pipe smoking, chewing of betel quid, mouthwash (25% alcohol)

48. Morphology of squamous cell carcinoma of the oral cavity
Favored locations:
1. ventral surface of the tongue
2. Floor of the mouth
3. Lower lip, soft palate, and gingiva

49. Does this look like more than a simple “plaque”
Does this look like more than a simple “plaque”? Like, perhaps, ulceration and induration under the ulcer bed.
This is a classic appearance of INFILTRATING or INFILTRATIVE SQUAMOUS CELL CARCINOMA of the mouth. Can there be any other type?
Where would you take the biopsy?
Morphology of squamous cell carcinoma of the oral cavity Raised, firm, pearly plaques or as irregular, roughened, or verrucous areas of mucosal thickening

50. Morphology of squamous cell carcinoma of the oral cavity
Well, moderate, poor.
These are the 3 types of differentiation of squamous cell cancer, no matter what the current trendy buzz words or grading letters/numbers are!!!
In “well” you can see “pearls”. This is a pearl above.
In “moderate”, you can usually see “intercellular bridges”, but not pearls.
In “poor” you usually have no real idea that it even looks squamous at all, and you have to rely on squamous or immunochemical markers, such as cytokeratin markers, or a whole host of others.
There are the 3 types of differentiation of squamous cell cancer: Well, moderate, poor.
In “well” you can see “pearls”. (pearl above).
In “moderate”, you can usually see “intercellular bridges”, but not pearls.
In “poor” you usually have no real idea that it even looks squamous at all, and you have to rely on squamous or immunochemical markers, such as cytokeratin markers, or a whole host of others.

51. WELL
MODERATE
POOR

52. ODONTOGENIC CYSTS
Definition: cyst like structures derived from epithelial linings or epithelial remnants in the jaw bone
Classification:
INFLAMMATORY CYSTS (e.g., Periapical “Radicular” - most common)
DEVELOPMENTAL CYSTS (DENTIGEROUS - most common)
As a rule of thumb, all cysts submitted by oral surgeons are benign. Many types often recur however. It is only a question of whether the cyst is “developmental”, i.e., an abnormal development, ultimately from embryology, or “inflammatory” in etiology.

53. Periapical cyst

54. Periapical cyst extremely common lesions found at the apex of teeth.
Result of long-standing pulpitis or periapical abscess.
Periapical inflammatory lesions persist as a result of the continued presence of bacteria or other offensive agents in the area

55. Dentigerous cyst
Def: Cyst that originates around the crown of an unerupted tooth and is thought to be the result of a degeneration of the dental follicle.
Xray: unilocular lesions and are most often associated with impacted third molar (wisdom) teeth.
Histology: they are lined by a thin layer of stratified squamous epithelium with chronic inflammatory cell infiltrate in the connective tissue stroma.
Rx: Excision
Complications: recurrence or, very rarely, neoplastic transformation into an ameloblastoma or a squamous cell carcinoma.

56. DENTIGEROUS
CYST
Classical histologic image of a dentigerous cyst.
lined by a thin layer of stratified squamous epithelium with chronic inflammatory cell infiltrate in the connective tissue stroma

57. Odontogenic keratocyst (OKC)
locally aggressive and has a high rate of recurrence
Most often diagnosed in patients between ages 10 and 40.
Males within the posterior mandible.
Xray: well-defined unilocular or multilocular radiolucencies
Histo: layer of parakeratinized or orthokeratinized stratified squamous epithelium with a prominent basal cell layer and a corrugated appearance of the epithelial surface.
Rx: Complete removal of the lesion

58. Odontogenic tumors
Odontoma- the most common type of odontogenic tumors (app. 70%), arises from epithelium but shows extensive depositions of enamel and dentin. Odontomas are probably hamartomas rather than true neoplasms and are cured by local excision.
Ameloblastoma (app. 30%) - from odontogenic epithelium. It is commonly cystic, slow growing, and locally invasive but has an indolent course in most cases

59. Circular sunburst opacity surrounded by a thin radiolucent border
Odontoma on x-ray?
Ameloblastoma on x-ray?
Circular sunburst opacity surrounded by a thin radiolucent border
Large expansile multilocular or soap-bubble radiolucency; favored location is posterior mandible

60. Histologic view of odontoma and ameloblastoma
Ameloblastoma: notice the stellate reticlulum and the row of ameloblasts with vacuoles (40x).
Odontoma consists of a mixture of hard substances, epithelial structures, and empty spaces formerly occupied by enamel matrix, 20x

61. Odontomas
Ameloblastomas