Other Lung Path

Question 1

Sarcoidosis

Answer 1

Multisystem disease of unknown etiology characterized by noncaseating granulomas in many tissues and organs
Bilateral hilar lymphadenopathy and/or lung involvement is the major presenting manifestation in most cases
Epidemiology
-Adults younger than 40
-Danish, Swedish, African Americans (10x)
-Higher prevalence even in non-smokers

Question 2

Sarcoidosis path

Answer 2

Disordered immune regulation in genetically predisposed individuals exposed to certain environmental agents
Process is driven by TH1 cells

Question 3

Sarcoidosis morphology

Answer 3

Noncaseating epithelioid granulomas
Many organs involved
-Lungs: involved at some point in 90% of patients; in 5-15% of patients granulomas are eventually replaced by diffuse interstitial fibrosis
-Hilar and paratracheal lymph nodes enlarged in 75-90%
-Skin, eye, lacrimal glands, salivary glands
-Spleen, liver, bone marrow

Question 4

Sarcoidosis clinical

Answer 4

Many individuals are entirely asymptomatic
In symptomatic cases,
-2/3 have respiratory symptoms (shortness of breath, dry cough, substernal discomfort) or constitutional symptoms (fever, fatigue, weight loss, anorexia, night sweats)
Unpredictable course
-Progressive chronicity or periods of activity and remission
-65-70% recover with minimal to no residual effects
-20% develop permanent lung dysfunction or visual impairment
-15-20% die from progressive pulmonary fibrosis and cor pulmonale

Question 5

Hypersensitivity Pneumonitis

Answer 5

Allergic alveolitis
Immunologically mediated inflammatory lung disease that primarily affects the alveoli
-Immune complex and delayed-type hypersensitivity reactions
-2/3 have interstitial noncaseating granulomas
Heightened sensitivity to inhaled antigens
-Most often an occupational disease

Question 6

Hypersensitivity Pneumonitis clinical

Answer 6

Acute reaction
-Fever, cough, dyspnea, constitutional complaints 4-8 hours after exposure
-Complete remission, if antigen exposure is terminated
Chronic disease
-Insidious onset of cough, dyspnea, malaise, weight loss
-If antigen is not removed, chronic interstitial disease develops without the acute exasperations on antigen re-exposure

Question 7

Pulmonary Eosinophilia

Answer 7

Entities characterized by an infiltration and activation of eosinophils
-Generally immunologic in origin, but poorly understood
Acute eosinophilic pneumonia with respiratory failure
-Rapid onset of fever, dyspnea, hypoxia, and diffuse pulmonary infiltrates
-Bronchioalveolar lavage fluid contains >25% eosinophils
-Prompt response to steroids

Question 8

Pulmonary Eosinophilia

Answer 8

Simple pulmonary eosinophilia (Löffler syndrome)

• Transient pulmonary lesions and blood eosinophilia
• Alveolar septal infiltrate of eosinophils
• Benign clinical course

Tropical eosinophilia
-Microfilariae infestation

Secondary eosinophilia
-Asthma, drug allergies, vasculitis

Idiopathic chronic eosinophilic pneumonia

• Aggregates of lymphocytes and eosinophils in alveolar septa and airspaces
• High fever, night sweats, dyspnea
• Disease of exclusion

Question 9

Smoking Related Interstitial Diseases

Answer 9

Desquamative interstitial pneumonia (DIP)

• Accumulation of large numbers of macrophages in the airspaces
• Good prognosis
• Excellent response to steroids and smoking cessation

Respiratory bronchiolitis
-Similar histology to DIP but centered on respiratory bronchioles

Clinical

• Gradual onset of dyspnea and dry cough
• Symptoms recede with smoking cessation

Question 10

Pulmonary Thromboembolism

Answer 10

95% arise from thrombi within the deep veins of the legs
Risk factors
Prolonged bedrest
Surgery
Severe trauma
Congestive heart failure
Around childbirth
High estrogen birth control pills
Disseminated cancer
Primary hypercoagulability disorders

Question 11

Pulmonary Thromboembolism

Answer 11

Pathophysiologic consequences depend upon the size of the embolus and the cardiopulmonary status of the patient
-Increase in pulmonary artery pressure from occlusion and possibly vasospasm
-Ischemia of down-stream lung tissue
-Hypoxia
Infarct of lung occurs in only about 10% of cases
-Depends on size of vessel occluded, status of bronchial circulation and cardiac function, ventilation of effected lung region
Thromboemboli may cause virtually instantaneous death

Question 12

Pulmonary Thromboembolism clinical course

Answer 12

Most emboli are clinically silent (60-80%)
-Embolus removed by fibrinolytic activity
-Lung viability is maintained
Sudden death, acute right-sided heart failure, or cardiovascular collapse (5%)
->60% of total pulmonary vasculature is obstructed
Obstruction of small to medium pulmonary branches (10-15%)
-Causes pulmonary infarction
Recurrent multiple emboli (<3%)
-Pulmonary hypertension, chronic right-sided heart failure, vascular sclerosis, worsening dyspnea
30% chance of having a second embolus after having a first

Question 13

Pulmonary Thromboembolism Non-thrombotic emboli

Answer 13

Air, fat, amniotic fluid, foreign body, bone marrow
Talc in intravenous drug users
-Interstitial and vascular complications

Question 14

Pulmonary Hypertension

Answer 14

Pulmonary hypertension occurs when mean pulmonary pressures reach ¼ systemic pressure
Most often a secondary disease
-Chronic obstructive or interstitial lung disease
*Reduction in alveolar capillaries results in increased resistance
-Recurrent pulmonary emboli
*Reduces functional cross-section of pulmonary vasculature
-Heart disease
*Mitral stenosis, congenital left to right shunt
Primary or idiopathic pulmonary hypertension
-Most cases are sporadic (6% familial form)

Question 15

Pulmonary Hypertension path

Answer 15

Pulmonary endothelial cell and/or smooth muscle dysfunction
In secondary pulmonary hypertension, endothelial cell dysfunction
-Reduced vasodilatory agents
-Increase vasoconstrictive mediators
-Induce replication of vascular smooth muscle and extracellular matrix elaboration

Question 16

Pulmonary Hypertension clinical

Answer 16

Secondary PH may develop at any age
-Accentuation of respiratory insufficiency and right-sided heart strain
Primary PH is almost always in young persons, more commonly women
-Fatigue, syncope (particularly on exercise), dyspnea on exertion, and sometimes chest pain
-Develop severe respiratory insufficiency and cyanosis
-Death usually results from right-sided heart failure
-Survival is 2-5 years from diagnosis

Question 17

Diffuse Alveolar Hemorrhage Syndromes

Answer 17

Immune related diseases that present with the triad of hemoptysis, anemia, and diffuse pulmonary infiltrates
Goodpasture syndrome
Idiopathic pulmonary hemosiderosis

Question 18

Goodpasture syndrome

Answer 18

• Proliferative, usually rapidly progressive, glomerulonephritis and hemorrhagic interstitial pneumonitis
• Caused by antibodies targeted against collagen IV
• 90% have detectable serum antibodies
• Diffuse alveolar hemorrhage
• Linear pattern of immunoglobulin deposition along alveolar septa
• Treat with plasmapheresis and immunosuppressives

Question 19

Idiopathic pulmonary hemosiderosis

Answer 19

Diffuse alveolar hemorrhage similar to Goodpasture syndrome but no renal involvement or anti-basement membrane antibodies
Mild to moderate course with periods of activity followed by prolonged remissions
Most cases are seen in children

Question 20

Pulmonary Angiitis and Granulomatosis

Answer 20

Wegner granulomatosis
>80% of WG patients develop upper respiratory or lung involvement
Lung lesions
-Necrotizing vasculitis and parenchymal necrotizing granulomatous inflammation
-Pulmonary vessels may show necrotizing granulomas but most often acute and chronic inflammation with fibrinoid necrosis

Question 21

Pulmonary Angiitis and Granulomatosis

Answer 21

Can have both upper respiratory and pulmonary symptoms
-Chronic sinusitis, epistaxis, nasal perforation
-Cough, hemoptysis, chest pain
Radiographically, multiple nodular densities (confluence of granulomas, some may cavitate)
While usually a multisystem disease, it may be restricted to the lung (“limited” WG)

Question 22

Lung Tumors

Answer 22

Common site for metastatic disease
Primary lung cancer is also common
Primary lung tumors
-Bronchial epithelium; carcinomas (95%)
-Others (5%)
*Bronchial carcinoids, mesenchymal malignancies, lymphomas, benign lesions
*Hamartoma is the most common benign lesion
Spherical, small (3-4 cm), often appear as “coin” lesions

Question 23

Carcinomas

Answer 23

1 cause of cancer related deaths in industrialized countries

-1/3 of cancer deaths in men in US
-Leading cause of cancer death in women since 1987
Causal link to cigarette smoking
Peak incidence: 50-70 years of age
At diagnosis,
-50% have distant metastatic disease
-25% have disease in regional lymph nodes
5 year survival rate
-All stages combined: 15%
-Localized to lung: 45%

Question 24

Carcinomas Four major histological types

Answer 24

Squamous cell carcinoma
Adenocarcinoma
Small-cell carcinoma
Large-cell carcinoma
Combination patterns exist
Adenocarcinoma is now the most common type
Adenocarcinomas are by far the most common type in women, lifetime non-smokers, and younger than 45 years of age

Question 25

For therapeutic purposes, lung carcinomas are divided into two broad groups

Answer 25

Small-cell lung cancer (SCLC) Non-small-cell lung cancer (NSCLC) Virtually all SCLC has metastasized at the time of diagnosis Not curable by surgery Treated by chemotherapy with or without radiation NSCLC respond poorly to chemotherapy and are better treated by surgery

Question 26

Genetic differences between SCLC and NSCLC

Answer 26

G1-S checkpoint is abrogated by different mechanisms SCLC has high frequency of RB gene mutations NSCLC commonly has inactivated p16/CDKN2A gene Activating KRAS and EGFR mutations occur in adenocarcinomas

Question 27

Carcinomas Etiology and pathogenesis

Answer 27

Arise by step-wise accumulation of genetic abnormalities that transform benign bronchial epithelium into neoplastic tissue Predictable sequence that parallels histologic progression -Inactivation of tumor suppressor genes on 3p is a very early event -p53 mutations and KRAS activation occurs late Subset of adenocarcinoma arising in non-smoking, Far-Eastern women has EGFR activation

Question 28

Carcinomas

Answer 28

There is an impressive body of evidence that cigarette smoking causes lung cancer -Squamous cell and small-cell carcinomas have the strongest association with tobacco exposure Other environmental influences are associated with an increased incidence of lung cancer -Miners of radioactive ores; asbestos workers; exposure to dusts containing arsenic, chromium, uranium, nickel, vinyl chloride, mustard gas

Question 29

Carcinomas morphology

Answer 29

Usually begin as small mucosal lesions May form intraluminal masses, invade the bronchial mucosa, or push into the lung parenchyma Large masses may undergo central necrosis, hemorrhage, or cavitation May extend to pleura and invade the pleural cavity, chest wall, or adjacent intrathoracic structures May spread by lymphatic or hematogenous routes

Question 30

Squamous Cell Carcinoma

Answer 30

M>F Closely correlated with smoking history Tend to arise centrally in major bronchi Spread to local hilar lymph nodes eventually Spreads outside the thorax later than other types Large tumors may have central necrosis and may cavitate Preneoplastic lesions are well characterized -Squamous metaplasia -Dysplasia -Carcinoma in situ

Question 31

Adenocarcinoma

Answer 31

More peripherally located Most common type in non-smokers and women Slower growing and form smaller masses Metastasize at an early stage Precursor lesion is thought to be atypical adenomatous hyperplasia Cell of origin is thought to be bronchioalveolar stem cells -Multipotential cells at the bronchioalveolar junction

Question 32

Bronchioloalveolar Carcinoma

Answer 32

Subtype of adenocarcinoma Key feature is growth along preexisting structures preservation of alveolar architecture

Question 33

Small-cell Carcinomas

Answer 33

Centrally located masses with extension into the parenchyma Early involvement of hilar and mediastinal lymph nodes Necrosis is always present and may be extensive Tumor cells are fragile Derived from neuroendocrine cells Associated with paraneoplastic syndromes

Question 34

Carcinomas clinical

Answer 34

Silent, insidious lesions -Often unresectable before they produce symptoms Chronic cough and expectoration may call attention to an early lesion Hoarseness, superior vena cava syndrome, effusions, persistent segmental atelectasis, pneumonitis all tend to appear with advanced lesions Often symptoms related to metastatic disease are the presenting symptoms -Brain, liver, bone

Question 35

carciomas clinical contin

Answer 35

Overall, NSCLC has a better prognosis than SCLC -NSCLC can be detected before metastasis or local spread *Surgical cure possible -SCLC has always spread at time of diagnosis *While very sensitive to chemotherapy, they always recur *Mean survival is 1 year 3-10% of people with lung cancer develop paraneoplastic syndromes -Hypercalcemia (SCC), Cushing syndrome, SIADH, neuromuscular syndromes, clubbing of fingers, hematologic manifestations (adenoca)

Question 36

Bronchial Carcinoids

Answer 36

Arise from neuroendocrine cells of the bronchial mucosa Appear at an early age (mean: 40 years) About 5% of all pulmonary neoplasms Often resectable and curable

Question 37

Bronchial Carcinoids growth pattern

Answer 37

Obstructing, polypoid, spherical intraluminal mass Mucosal plaque penetrating the bronchial wall and fanning out into the peribronchial tissue 5-15% have metastasized to hilar lymph nodes Distant metastasis is rare

Question 38

Bronchial Carcinoids Atypical carcinoids

Answer 38

More aggressive Higher rates of lymph node and distant metastasis p53 mutations in 20-40% of cases Typical carcinoid, atypical carcinoid, and small-cell carcinoma represent increasing histologic aggressiveness and malignant potential among pulmonary neuroendocrine neoplasms

Question 39

Bronchial Carcinoids Clinical

Answer 39

``` Most present with findings related to intraluminal growth -Cough, hemoptysis, infections Carcinoid syndrome is rare -Intermittent attacks of diarrhea, flushing, and cyanosis 10 year survival rates -Typical carcinoid: >85% -Atypical carcinoid: 35% -Small-cell carcinoma: 5% ```

Question 40

Pulmonary Infections

Answer 40

Pneumonia can be broadly defined as any infection in the lung Pneumonia is responsible for 1/6 of all deaths in the US -Epithelial surfaces are exposed to liters of contaminated air -Nasopharyngeal flora are regularly aspirated during sleep -Other lung diseases render the lung vulnerable

Question 41

Lung Defenses

Answer 41

Defects in innate or humoral immunity typically leads to infections with pyogenic bacteria Defects in cell-mediated immunity typically leads to infection with intracellular microbes, viruses, low virulence organisms Exogenous interferences -Cigarette smoking (mucociliary clearance, macrophage activity), alcohol (impaired reflexes, neutrophil mobilization and chemotaxis)

Question 42

Pneumonia

Answer 42

Clinically, may present as an acute, fulminant disease or as chronic disease with a protracted course Histologically -Fibrinopurulent exudate in acute bacterial pneumonias -Mononuclear interstitial infiltrates in viral and other atypical pneumonias -Granulomas and cavitation in some chronic pneumonias

Question 43

Acute bacterial pneumonias

Answer 43

Acute bacterial pneumonias present with one of two anatomic and radiographic patterns - Bronchopneumonia * Patchy distribution of inflammation that generally involves more than one lobe - Lobar * Part or all of a lobe is filled homogenously with an exudate * 90% are due to S. pneumoniae - Distinction can be blurry * Many organisms can present with either pattern * Confluent bronchopneumonia can be hard to distinguish from lobar pneumonia

Question 44

Community-Acquired Acute Pneumonias

Answer 44

Most are bacterial Frequently follows a viral upper respiratory tract infection Onset is usually abrupt with high fever, shaking chills, pleuritic chest pain, productive mucopurulent cough, sometimes hemoptysis S. pneumoniae (pneumococcus) is the most common cause

Question 45

Pneumoncoccal Pneumonia

Answer 45

Pneumococcal infections are more frequent in those with: -Underlying chronic disease like CHF, COPD, or diabetes -Congenital or acquired immunoglobulin defects -Decreased or absent splenic function Lobar or bronchopneumonia Lower or middle lobes are most frequently involved

Question 46

Before antibiotics, lobar pneumococcal pneumonia had 4 classic pathologic stages

Answer 46

Congestion Red hepatization Gray hepatization Resolution

Question 47

Congestion

Answer 47

Affected lobe is heavy, red, and boggy | Vascular congestion with proteinaceous fluid, scattered neutrophils, and many bacteria in the alveoli

Question 48

Red hepatization

Answer 48

A few days later Lung as a liver-like consistency Alveoli packed with neutrophils, red cells, and fibrin

Question 49

Gray hepatization

Answer 49

Lung is gray, dry, and firm (red cells have lysed) | Fibrinosuppurative exudate persists in the alveoli

Question 50

Resolution

Answer 50

Exudates are digested by enzymes producing a granular semi-fluid debris that is resorbed, ingested by macrophages, or coughed up Alternatively, exudates are organized by fibroblasts growing into them

Question 51

Pneumoncoccal Pneumonia complications

Answer 51

The pleural reaction may resolve or undergo organization leaving fibrous thickening or permanent adhesions Early antibiotic treatment alters this classic progression Complications -Abscess -Empyema -Organized areas of solid fibrosis -Bacteremic dissemination (meningitis, arthritis, infective endocarditis)

Question 52

Community-Acquired Acute Pneumonias

Answer 52

``` Haemophilus influenzae Moraxella catarrhalis Staphylococcus aureus Klebsiella pneumoniae Pseudomonas aeruginosa Legionella pneumophila ```

Question 53

Haemophilus influenzae

Answer 53

Most common bacterial cause of acute exacerbation of COPD in adults

Question 54

Moraxella catarrhalis

Answer 54

Second most common bacterial cause of acute exacerbation of COPD in adults

Question 55

Staphylococcus aureus

Answer 55

Post-viral secondary pneumonia Abscess and empyema IV drug use

Question 56

Klebsiella pneumoniae

Answer 56

Most frequent cause of gram-negative bacterial pneumonia Debilitated and malnourished persons (chronic alcoholics) Thick, gelatinous sputum

Question 57

Pseudomonas aeruginosa

Answer 57

Cystic fibrosis, neutropenic, burns, ventilators

Question 58

Legionella pneumophila

Answer 58

Cardiac, renal, immunologic, hematologic disease | Organ transplant recipients

Question 59

Community-Acquired Atypical Pneumonia

Answer 59

``` Acute febrile respiratory disease characterized by patchy inflammation in the lungs, largely confined to the alveolar septa and interstitium Moderate amounts of sputum, absence of consolidation, moderately elevated WBC, lack of alveolar exudates Causative organisms -Mycoplasma pneumoniae *Most common -Viruses *Influenza, RSV, adenovirus -Chlamydia pneumoniae ```

Question 60

Community-Acquired Atypical Pneumonia clinical

Answer 60

Acute, non-specific febrile illness -Fever, headache, malaise, and later, cough without sputum May have respiratory distress out of proportion to the physical and radiographic findings

Question 61

Nosocomial Pneumonia

Answer 61

Infections acquired in the course of a hospital stay Most common in persons with severe underlying disease, immunosuppression, prolonged antibiotic therapy, and on ventilators Organisms -Gram-negative rods *Enterobacteriaceae, Pseudomonas spp. -S. aureus usually MRSA

Question 62

Aspiration Pneumonia

Answer 62

Aspiration of gastric contents, typically while unconscious or vomiting Partly chemical, partly bacterial Aerobes and anaerobes Often necrotizing with a fulminant course Frequent cause of death in people predisposed to aspiration Abscess formation is a common complication

Question 63

Lung Abscess

Answer 63

An lung abscess is a localized area of suppurative necrosis within the pulmonary parenchyma, resulting in the formation of one or more large cavities Necrotizing pneumonia is a similar process resulting in multiple small cavities How -Aspiration of infective material -Aspiration of gastric contents -Complication of necrotizing pneumonia *S. aureus, S. pyogenes, K. pneumoniae, Pseudomonas ssp. *Mycotic infection and bronchiectasis -Bronchial obstruction *Especially by tumor -Septic embolism *Septic thrombophlebitis, infective endocarditis -Hematogenous spread of bacteria *Multiple abscesses

Question 64

Lung Abscess info

Answer 64

Anaerobic bacteria are present in almost all lung abscesses -1/3 to 2/3 of the time only anaerobes are present -Oral cavity organisms More common on the right side May rupture into airway or pleural cavity

Question 65

Lung Abscess clinical

Answer 65

Prominent cough that usually yields copious amounts of foul-smelling, purulent, or sanguineous sputum; occasionally hemoptysis Spiking fever and malaise are common Clubbing of fingers, weight loss, and anemia may occur Infective abscesses occur in 10-15% of persons with bronchogenic carcinoma Secondary amyloidosis may develop in chronic cases Antibiotics and surgical drainage, if needed Mortality rate: 10%

Question 66

Chronic Pneumonia

Answer 66

In the immunocompetent patient, chronic pneumonia is often a localized lesion that may or may not have regional lymph node involvement Typically granulomatous inflammation due to bacteria or fungi In the immunocompromised patient, there is often systemic dissemination and widespread disease Tuberculosis is the most important chronic pneumonia

Question 67

Chronic Pneumonia organisms

Answer 67

``` Mycobacterium tuberculosis Nontuberculous mycobacteria Histoplasma capsulatum Coccidioides immitis Blastomyces dermatitidis ```

Question 68

Pneumonia in the Immunocompromised Host

Answer 68

``` Cytomegalovirus pneumonitis Pneumocystis pneumonia Candida albicans Cryptococcus neoformans Invasive aspergillosis and zygomycosis (Rhizopus and Mucor) ```

Question 69

Cytomegalovirus pneumonitis

Answer 69

``` Most common groups -Recipients of organ transplants -Recipients of allogeneic bone marrow transplant -AIDS Viral pneumonia with foci of necrosis -Can progress to full-blown ARDS ```

Question 70

Pneumocystis pneumonia

Answer 70

Pneumocystis jiroveci Common infection in AIDS -Risk increases in proportion to decreasing CD4 count

Question 71

Candida albicans

Answer 71

Invasive candidiasis of the lung is most common in profoundly neutropenic acute leukemia patients Bilateral nodular infiltrates; mimics pneumocystis

Question 72

Cryptococcus neoformans

Answer 72

AIDS and hematolymphoid malignancies Localizes in the lungs then disseminates Minimal inflammation to granulomas depending on degree of immunodeficiency

Question 73

Invasive aspergillosis and zygomycosis (Rhizopus and Mucor)

Answer 73

Predilection for vascular invasion, causing vascular necrosis and infarction Hematolymphoid malignancies, allogeneic bone marrow transplant

Question 74

Pulmonary Disease and HIV

Answer 74

Not every infection is “opportunistic” -Think of “usual” pathogens too Not all pulmonary infiltrates are infections -Kaposi sarcoma, non-Hodgkin lymphoma, and primary lung cancer are all more common with HIV CD4 counts can help narrow the differential diagnosis ->200 cells/mm3: bacterial and tubercular more common -<50 cells/mm3 : CMV and MAI complex Multiple causes and atypical presentations