Nasal Polyps and Nasopharyngeal Carcinoma

Nasal Polyps, inflammatory

• Focal protrusions of the nasal mucosa
• May result from recurrent attacks of rhinitis
• Usually affects those 30 years of age or older
• May reach 3-4 cm in size
• Usually multiple and bilateral and located in the nasal cavity
• Have a translucent, moist, or edematous cut surface
• Consist of respiratory epithelium, often with squamous metaplasia and edematous mucosa having loose stroma harboring hyperplastic or cystic mucous glands, with variety of inflammatory cells

Nasopharyngeal Carcinoma

• Age: (15-25 & 60-69 yrs)
• Has connections to EBV; its genome is in all nasopharyngeal carcinoma
• Presents with upper cervical lymphadenopathy due to lymph node metastasis or obstructive symptoms (nasal discharge or epistaxis)
• Extension to adjacent organs is common
• Histologically classified as: keratinizing squamous cell carcinoma, nonkeratinizing squamous cell carcinoma, and undifferentiated carcinoma

Undifferentiated carcinoma (lymphoepithelioma)

• The most common and closely linked to EBV
• Large epithelial cells with indistinct cell borders (syncytial growth) and prominent eosinophilic nucleoli
• Often includes of an influx of T lymphocytes
• EBV genomes can be detected in serum or tissue by in situ hybridization (ISH) or IHC
• The most radiosensitive, unlike keratinizing SCC

Vocal Cord Nodules and Polyps

• Usually located on the true vocal cords, more often in adults
• More often occurs in heavy smokers or singers (singer's nodes)
• Covered by squamous epithelium
• Core of the nodule is a loose myxoid connective tissue that may be variably fibrotic and may have numerous vascular channels
• Virtually never become cancerous

Laryngeal Papilloma or Squamous Papilloma

• Usually located on the true vocal cords as a soft excrescence
• Single in adults but often multiple in children and recurs after removal (juvenile laryngeal papillomatosis or recurrent respiratory papillomatosis (RRP))
• Caused by HPV types 6 and 11
• Cancerous transformation is rare
• Histologically, they have multiple fingerlike projections with central fibrovascular cores and covered by stratified squamous epithelium

Carcinoma of The Larynx

• Mostly occurs during the 6th decade

• More common in males than females (7:1)

• Presents as persistent hoarseness, dysphagia, and dysphonia

• Cases occur in smokers, and alcohol and asbestos exposure may also contribute

• HPV sequences are detected in about 15% of tumors which correlates to better prognosis

• The tumor grows directly on the vocal cords (glottic tumors) most common, or above the cords (supraglottic) or below the cords (subglottic)

• Grossly: Vary from white or reddened thickenings to irregular verrucous or ulcerated lesions

• The likelihood of the development of carcinoma is directly proportional to the grade of dysplasia when the lesion is first seen

• Histologically: 95% are squamous cell carcinomas and rarely, adenocarcinomas are seen

• About 90% of glottic tumors are confined to the larynx when diagnosed

• About one-third of supraglottic tumors metastasize to regional (cervical) lymph nodes

• Subglottic tumors remain clinically quiescent and present as advanced disease

• With treatment, many patients can be cured, but about one-third die of the disease (due to metastases and cachexia)

Lower Respiratory Tract Pathology

• The main bronchi give rise to smaller airways called bronchioles
• Bronchioles are distinct from bronchi due to lacking cartilage and submucosal glands within their walls
• Additional branching of the bronchioles leads to terminal bronchioles, the part of the lung distal to terminal bronchiole is called acinus
• The pulmonary acini are composed of respiratory bronchioles that proceed into alveolar ducts, which branch into the alveolar sac (formed of alveoli)
• A cluster of 3-5 terminal bronchioles, with each acinus, is called a lobule
• Alveolar walls (or alveolar septa) consist of the capillary endothelium and basement membrane, the pulmonary interstitium, and alveolar epithelium

Alveolar Epithelium

• Has flattened plate-like Type I pneumocytes
• Has rounded Type II pneumocytes that serve as a source of pulmonary surfactant and involved in the repair of pulmonary epithelium

Atelectasis

• Loss of lung volume from inadequate expansion of air spaces
• Results in the shunting of inadequately oxygenated blood from pulmonary arteries into veins, leading to a ventilation-perfusion imbalance and hypoxia
• Outcomes depend on cause, the size of the involved area, and the duration to start treatment
• Atelectasis (except when caused by contraction) is potentially reversible

Types of Atelectasis

• Resorption atelectasis occurs when obstruction prevents air from reaching distal airways, causing the air to become absorbed and alveolar collapse follows. The most common cause of bronchial obstruction is mucus or mucopurulent plug or aspiration of foreign bodies and tumors
• Compression atelectasis, sometimes called passive or relaxation, is associated with an accumulation of fluid, blood, or air within the pleural cavity, which collapses the adjacent lung. Possibly caused by an elevated diaphragm
• Contraction atelectasis (or cicatrization) occurs when local or generalized fibrotic changes affect the lung or pleura to hamper lung expansion, and is usually irreversible.
• Microatelectasis occurs due to loss of surfactant
• Gross morphology: Shrunken lung
• Microscopic morphology: Slit-like alveoli and congested septae

Acute Respiratory distress syndrome (ARDS)

• A severe form of acute lung injury
• Clinical syndrome caused by many conditions
• Characterized by: sudden and acute onset of severe dyspnea, severe arterial hypoxemia, hypercapnia, and cyanosis, possibly leading to life-threatening respiratory insufficiency
• Radiology: Diffuse bilateral alveolar infiltrate (GGO)
• Histologically: known as diffuse alveolar damage (DAD)
• Common causes are pneumonias and sepsis. Less common is aspiration of gastric contents and severe trauma with shock.
• The integrity of the alveolar-capillary membrane is compromised by endothelial or epithelial injury.
• This leads to increased vascular permeability, alveolar edema, loss of diffusion capacity, and surfactant abnormalities due to damage to type II pneumocytes.
• Neutrophils have an important role in the pathogenesis of ARDS

ARDS Cycle

• Release oxidants protease, platelets activating factor and leukotrienes is a key step
• Cause damage to alveolar epithelium and endothelium and maintain the inflammatory cascade
• Clotting cascades have a proinflammatory effect, and is also triggered in the ARDS cycle
• Destruction is opposed by endogenous antiproteases, anti-oxidants & anti-inflammatory cytokines
• Fibrogenesis occurs due to macrophage-derived fibrogenic factors
• In the acute/exudative phase the lungs are red, firm, airless, and heavy, along with capillary congestion.
• The most characteristic finding is the presence of hyaline membrane lining the distended alveolar ducts consisting of fibrin-rich edema fluid admixed with remnants of necrotic epithelial cells
• The organizing/proliferative phase shows marked proliferation of reactive type II pneumocytes trying to regenerate the alveolar lining, causing marked thickening of alveolar septa caused by the proliferation of interstitial cells and deposition of collagen
• Resolution is unusual, leading most often to intra-alveolar fibrosis (organizing pneumonia (OP))
• Fibrotic phase occurs weeks after the onset of ARDS

ARDS Clinical Course

• 85% of patients develop the clinical symptoms within 72 hours of the initiating insult
• Most patients who survive the acute insult recover normal respiratory function within 6 to 12 months
• But, the rest develop diffuse interstitial fibrosis, leading to chronic respiratory Insufficiency
• The predicting factors in ARDS are age, underlying bacteremia or sepsis, and development of underlying system failure such as cardiac, renal, or hepatic failure (multiorgan failure)