LG 17 Pathology of the upper airways

The tongue is lined by [blank_start]keratinizing stratified squamous[blank_end] epithelium.

Buccal Mucosa and Gingiva is lined by [blank_start]non-keratinizing stratified squamous[blank_end] epithelium.

The tongue is comprised of [blank_start]skeletal[blank_end] muscle.

Oral Squamous Cell Carcinoma Clinical Presentation. Oral lesions: [blank_start]Erythroplakia, Mass, Ulcer[blank_end] Can be painful or painless Neck mass: [blank_start]Lymph node metastasis[blank_end] can be present at presentation Weight loss

Oral Squamous Cell Carcinoma has Two Major Types: [blank_start]Classic[blank_end] and [blank_start]HPV[blank_end] Associated

70% of oral squamous cell carcinoma associated with [blank_start]oncogenic[blank_end] HPV, usually [blank_start]HPV-16[blank_end]

Classic carcinogen induced oral squamous cell carcinoma: Is caused by [blank_start]Tobacco and alcohol[blank_end] Location: Ventral surface of tongue, floor of mouth, lower lip, soft palate, gingiva

HPV Associated oral squamous cell carcinoma: 70% of oral squamous cell carcinoma associated with oncogenic HPV, usually HPV-16 Location: Usually [blank_start]tonsils, base of tongue, pharynx[blank_end] Note: HPV associated oral squamous cell carcinoma has a [blank_start]better[blank_end] prognosis than classic tobacco and alcohol associated oral squamous cell carcinoma Miscellaneous Note: Other common sites for Squamous Cell Carcinoma are Cervix, Skin, Lung, Esophagus, Anus

In Normal Squamous Epithelium to Dysplasia to Squamous Cell Carcinoma you go from: Orderly maturation towards surface with Maturation: Means the cells are more plump at bottom and flatten out as they approach the surface. TO No [blank_start]maturation[blank_end]. Completely [blank_start]disordered[blank_end] growth. Invasive. [blank_start]Keratinization[blank_end] in all areas.

In Classic Oral Squamous Cell Carcinoma you have can have: [blank_start]p53[blank_end] mutations [blank_start]p63[blank_end] mutations [blank_start]Notch 1[blank_end] mutation

In HPV associated Oral Squamous Cell Carcinoma you can have: [blank_start]p16[blank_end] over-expression [blank_start]p53[blank_end] inactivation [blank_start]RB[blank_end] pathway inactivation

Leukoplakia [blank_start]White[blank_end] lesion may represent benign [blank_start]hyperkeratosis[blank_end] (thicker keratinized layer) or pre-cancerous lesion 5-25% of leukoplakia lesions are [blank_start]premalignant[blank_end]

Erythroplakia [blank_start]Red[blank_end] lesion, usually represents carcinoma in situ Up to [blank_start]90[blank_end]% can be carcinoma in situ

Oral Squamous Cell Carcinoma Prognosis: Dependent on [blank_start]location and stage[blank_end] Low stage: 65-75% 5 year survival Metastatic disease: 35% 5 year survival HPV associated cancer has [blank_start]better[blank_end] prognosis than classic tobacco/alcohol associated oral cancer

Sjogren Syndrome: Autoimmune Disease with Dry Mouth and Dry Eyes Clinical Features: Most common in [blank_start]women[blank_end] 50-60 years old [blank_start]Xerostomia[blank_end] (dry mouth): Difficulty swallowing, decreased taste, cracks and fissures in mouth [blank_start]Keratoconjunctivitis sicca[blank_end] (dry eyes): Blurring of vision, burning, itching [blank_start]Parotid gland[blank_end] enlargement secondary to inflammation; however, involves all major and minor salivary glands Note: [blank_start]Sicca[blank_end] means dry

Sjogren Syndrome: Auto-immune destruction of [blank_start]lacrimal and salivary[blank_end] glands 90% of patients have antibodies directed against two ribonucleoprotein antigens, [blank_start]SS-A[blank_end] (Ro) and [blank_start]SS-B[blank_end] (La) Pathogenesis: Aberrant [blank_start]T-cell and B-cell[blank_end] activation against salivary gland tissue in genetically susceptible patients Associations: Rheumatoid arthritis, synovitis, diffuse pulmonary fibrosis, peripheral neuropathy Therapy: [blank_start]Supportive[blank_end] Prognosis: Slowly progressive, evolves over decades, waxing and waning About 5% of patients develop [blank_start]lymphoma[blank_end] secondary to chronic B-cell activation

Sjogren Syndrome Pathology in Salivary Gland: Large numbers of [blank_start]lymphocytes[blank_end] attacking acinar cells Normal salivary gland has very few [blank_start]inflammatory[blank_end] cells The [blank_start]inflammation[blank_end] will cause [blank_start]acinar[blank_end] cell death and tissues will no longer produce saliva

Mucocele of minor salivary gland: Blockage of minor salivary gland duct causes leakage of [blank_start]saliva[blank_end] into surrounding tissues, which causes [blank_start]inflammatory[blank_end] response

Pleomorphic Adenoma: Benign tumor that shows epithelial, myoepithelial and [blank_start]mesenchymal[blank_end] tissues Most common location is [blank_start]parotid[blank_end] gland, less common in submandibular gland Wide age range, with two peaks one in childhood and one in 4th-6th decade [blank_start]PLAG1[blank_end] gene rearrangements: [blank_start]PLAG1[blank_end] is a transcription factor that [blank_start]upregulates[blank_end] expression of genes involved in cell growth

Warthin Tumor (Papillary Cystadenoma Lymphomatosum): Benign tumor composed of [blank_start]double[blank_end] layer of oncocytic epithelioid cells forming [blank_start]papillary[blank_end] and cystic structures, resting on reactive [blank_start]lymphoid[blank_end] stroma Occurs largely in [blank_start]Parotid[blank_end] gland Risk factors: [blank_start]Smoking[blank_end] 10% are bilateral, 10% are multifocal; multiple tumors may be synchronous or metachronous

[blank_start]Metachronous[blank_end]: Tumors occur at different points in time [blank_start]Synchronous[blank_end]: Tumors occur at same time

Mucoepidermoid Carcinoma: Malignant tumor composed of [blank_start]squamous[blank_end] cells and [blank_start]mucus[blank_end]-secreting cells forming solid and cystic patterns Occurs in both major and minor salivary glands Approximately half of tumors associated with t(11;19)(q21;p13) that creates [blank_start]MECT1[blank_end] and [blank_start]MAML2[blank_end] fusion Prognosis depends on histologic [blank_start]grade[blank_end] of tumor

Nasopharyngeal Carcinoma: Malignant tumor associated with [blank_start]EBV[blank_end] infection Also associated with high [blank_start]nitrosamine[blank_end] diet (preserved meats), smoking, chemical fumes Clinical presentation: Common in African children and southern Chinese adults (rare in US), may present with enlarged lymph node 3 histologic types: Keratinizing Squamous Cell Carcinoma Non-keratinizing Squamous Cell Carcinoma Undifferentiated/Basaloid Carcinoma Prognosis: Overall 5 year survival of 60%

Nasopharyngeal Carcinoma, Undifferentiated Type, Pathology: Large [blank_start]epithelial[blank_end] cells with round to ovoid nuclei with prominent nucleoli and moderate amounts cytoplasm [blank_start]Syncytium[blank_end] like clusters of cells Benign [blank_start]lymphocytes[blank_end] in background [blank_start]EBV[blank_end] positive by in situ hybridization

Nasopharyngeal Angiofibroma: Benign, highly vascular tumor that occurs almost exclusively in adolescent males due to [blank_start]testosterone[blank_end] dependent puberty induced growth Clinical presentation: [blank_start]Epistaxis[blank_end] (nose bleed) Avoid biopsy due to [blank_start]bleeding[blank_end] risk

Nasopharyngeal Angiofibroma Pathology: [blank_start]Fibroblasts[blank_end] produce fibrous (collagenous) stroma

Nasal Polyps: [blank_start]Inflammatory[blank_end] polyps of nasal mucosa Many etiologies: Allergy, Infection, Cystic fibrosis, Aspirin Intolerance, Familial Aspirin Intolerance: Tetrad of [blank_start]asthma[blank_end], nasal polyps, chronic hypertrophic [blank_start]eosinophilic[blank_end] sinusitis and aspirin intolerance

Nasal Polyp Pathology: Histology: Surface lined by [blank_start]respiratory[blank_end] epithelium with underlying stroma showing fibrous stroma and edema and mixed inflammation with [blank_start]eosinophils[blank_end], plasma cells, [blank_start]neutrophils[blank_end], lymphocytes