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Flashcards in Pulmonary TBL Path Deck (318):
1

The definition of pneumonia?

The definition of pneumonia is inflammation of lung.

2

Infectious pneumonia can be due to?

Bacteria, fungi, viruses or parasites of various kinds.

3

Non-infectious pneumonia can be due to?

Autoimmunity, toxins, injury or idiopathic causes.

4

Almost all acute bacterial pneumonias are due to?

Aspiration of saliva containing the pathogen

5

Term “aspiration pneumonia” is used only for those due to?

Aspiration of gastroesophageal contents or food misrouted from the oropharynx.

6

“Infiltrate” is the term for a radiologic manifestation of?

Pneumonia or edema or hemorrhage (pus, or water, or blood).

7

“Consolidation” refers to manifestations of?

Alveoli filled with blood, pus or water on physical examination or radiology, again not specific for pneumonia.

8

Most types of pneumonia start with?

Acute inflammation, with neutrophilic infiltration.

9

Most types of acute inflammation go on to a subacute phase with?

Macrophages replacing neutrophils (garbage collectors replacing first responders) starting about day 3 of the pneumonia.

10

Individual types of pneumonia tend to be either?

Alveolar or interstitial (involving either airspaces or inter-alveolar septa), and necrotizing or non-necrotizing.

11

Alveolar non-necrotizing acute bacterial pneumonia is commonly due to?

Streptococcus pneumoniae (pneumococcus), but can also be due to Legionella species, Mycoplasma species and many other bacterial species.

12

Alveolar necrotizing acute bacterial pneumonia is caused by?

Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella species and other bacterial species.

13

Definition: Pneumococcal pneumonia

It is lung parenchymal infection by Streptococcus pneumoniae (pneumococcus) (aerotolerant anaerobic Gram-positive diplococcus).

14

Epidemiology: Pneumococcal pneumonia:

Very common and is community-acquired. Pneumococcal pneumonia is more common in older adults and more common in men, but has no racial predilection. Risk factors for getting it include smoking, chronic obstructive pulmonary disease, preceding viral respiratory infection (especially influenza), alcohol use, crack cocaine use, homelessness, splenectomy (including the “autosplenectomy” of sickle cell disease), defective humeral (B-cell) immunity, multiple myeloma, transplantation, lupus, incarceration, pregnancy, and other conditions.

15

Pathogenesis: Pneumococcus

Transient normal flora, colonizing the nasopharynx of 50% of individuals at any one time, acquired by aerosol inhalation, attaching to respiratory epithelial cells via platelet activating factor receptor. Secrete pneumolysin, a potent cytotoxin that binds to cholesterol in membranes and forms lethal pores in erythrocytes and leukocytes.

16

Gross pathology: Pneumococcal lobar pneumonia untreated has 4 phases:

(1) day 1: congestion with exudation of serous and frothy, blood-tinged fluid into alveoli
(2) days 2-3: red hepatization with drier, granular, dark red consolidation resembling liver
(3) days 4-7: grey hepatization with continuing consolidation, but color change to grey
(4) day 8 and following: slimy yellowish exudate, resolution without scarring

17

Microscopic pathology: Pneumococcal pneumonia is characteristically:

An acute non-necrotizing alveolitis, which stops at lobar septa because is non-necrotizing.

18

Pneumococcal pneumonia phases:

Phase (1): engorged septal capillaries, with a few erythrocytes, edema fluid and bacteria in alveoli
Phase (2): continuing congestion, extravasation of red cells and numerous neutrophils and abundant fibrin in alveoli, infection spreading through pores of Kohn into adjacent alveoli
Phase (3): degenerating dead cells (neutrophils, erythrocytes, sloughed pneumocytes and bacteria) in the alveoli, fibrin nets extending through pores of Kohn, foamy macrophages replace neutrophils

19

Pneumococcal pneumonia Symptoms:

Classic (in young people): sudden single severe shaking chill (rigor), followed by sustained high fever and cough productive of blood-tinged “rusty” sputum +/- pleuritic chest pain. Much more common (in heavy drinking heavy smoking older adults): Also common (in elderly): become confused, tired and cold, with no fever or cough.

20

Pneumococcal pneumonia Signs:

Low fever (typically 102-103 F), near or low tachycardia (HR 90-110/min), mild tachypnea (RR 20-24/min), pulmonary crackles (“rales”, old term for them), bronchial or tubular breath sounds (100%, in theory), dullness to percussion (50%).

21

Pneumococcal pneumonia Diagnosis:

Chest x-ray: lobar alveolar consolidation with air bronchograms (rare), segmental or subsegmental alveolar infiltrates without air bronchograms (common). Blood testing: leukocytosis (5% leukopenia [bad prognosis]), bandemia, elevated lactate dehydrogenase (LDH), elevated bilirubin (occasionally, not above 4 mg/dl), blood culture positive in <25%. Gram stain: diagnostic if patient not already treated (pairs of lancet-shaped organisms, flattened at their point of contact and pointed at the other end, with a capsule). Culture: commonly false negative. Urine antigen test: rapid, 70-80% sensitive, 80-100% specific.

22

Pneumococcal pneumonia Treatment:

Almost any beta-lactam antibiotic.

23

Pneumococcal pneumonia Prognosis:

Excellent (usually).

24

Staphylococcus aureus pneumonia. Definition:

Lung parenchymal infection by Staphylococcus aureus.

25

Staphylococcus aureus pneumonia
Epidemiology:

Common, community- or hospital-acquired (28% of hospital-acquired) [much smaller percent of community-acquired].

26

Staphylococcus aureus pneumonia
Demographics:

No age, sex or race predilection. Risk factors: S. aureus skin infection, nursing home residence, recent hospitalization, endotracheal intubation for mechanical ventilation.

27

Staphylococcus aureus pneumonia
Pathogenesis:

Commonly follows viral respiratory infection, especially influenza. Virulence factors include exotoxins (e.g. leukocidins, hemolysins), protein A (binds to TNF receptor 1 and opens path for invasion between epithelial cells) and resistance to many commonly used antibiotics in methicillin-resistant strains.

28

Staphylococcus aureus pneumonia
Gross pathology:

Heavy plum-colored lungs, which exude bloody fluid on sectioning and develop numerous small abscesses, which enlarge (and in children can be thin-walled “pneumatoceles”). Commonly with pleuritis and empyema.

29

Staphylococcus aureus pneumonia
Microscopic pathology:

Acute necrotizing bronchitis, bronchiolitis and alveolitis, with abundant neutrophils, fibrin and edema fluid; the edema fluid can condense into hyaline membranes. Hemorrhage usually present and commonly prominent. Abscesses very commonly present and may rapidly enlarge.

30

Staphylococcus aureus pneumonia
Symptoms:

Cough (commonly productive of purulent sputum only late in the course), dyspnea, fever, chills, confusion.

31

Staphylococcus aureus pneumonia
Signs:

Fever, tachycardia, hypotension, tachypnea, pulmonary crackles.

32

Staphylococcus aureus pneumonia
Diagnosis:

Chest x-ray: bronchopneumonic (alveolar) infiltrates +/- abscesses, pleural effusions. Blood testing: leukocytosis. Gram stain: Gram-positive cocci in clusters. Culture: aerobic, not fastidious. Specific diagnosis: not always easy because positive sputum culture can represent only colonization.

33

Staphylococcus aureus pneumonia
Treatment:

Oxacillin (or another beta-lactam) for methicillin-sensitive; vancomycin (or linezolid) for methicillin-resistant.

34

Staphylococcus aureus pneumonia
Prognosis:

Up to 50% mortality, even if treated.

35

IMPORTANT CONCEPT 3: Staph. aureus pneumonia is much worse than?

Pneumococcal pneumonia, probably because it is necrotizing and abscessing.

36

Legionella pneumonia
Definition:

Lung parenchyma infection by Legionella species (fastidious Gram-negative bacilli)

37

Legionella pneumonia
Epidemiology:

Relatively common, community- or hospital-acquired (2-9% of community-acquired, similar % of hospital-acquired), 90% L. pneumophila.

38

Legionella pneumonia
Demographics:

No age, sex or race predilection. Risk factors: smoking, COPD, transplant, not neutropenia, hematological malignancy or HIV infection

39

Legionella pneumonia
Pathogenesis:

Habitat: water, esp. warm water (25-42 degrees) in water heaters, shower heads, air conditioners, etc. Can hide inside amoebae. Once inhaled or aspirated, attach to respiratory epithelial cells and macrophages by flagellae and pili. After phagocytosis, evade intracellular destruction by inhibiting phagosome-lysosome fusion (two genes involved: dot [defective organelle trafficking] and icm [intracellular multiplication]). Never transmitted person-to-person

40

Legionella pneumonia
Gross pathology:

Bulging firm rubbery areas of consolidation

41

Legionella pneumonia
Microscopic pathology:

Acute non-necrotizing alveolitis, with early infiltration by numerous macrophages (unusual in acute pneumonia).

42

Legionella pneumonia
Symptoms:

Cough (dry or productive of mucoid sputum), high fever, chills, rigors, dyspnea, headache, diarrhea, confusion, myalgia, chest pain. Gastrointestinal symptoms, especially diarrhea, suggests Legionella.

43

Legionella pneumonia
Signs:

Fever virtually always, relative bradycardia (esp. in elderly), pulmonary crackles. Neurological signs, especially confusion, suggests Legionella

44

Legionella pneumonia
Diagnosis:

Chest x-ray: initially patchy unilobar bronchopneumonic (alveolar) infiltrate that progresses, + (in 50%) pleural effusion. Blood testing: leukocytosis, thrombocytopenia, hyponatremia, azotemia, liver dysfunction. Hyponatremia (sodium <130 ) suggests Legionella. Other: hematuria, proteinuria. Gram stain usually false negative. Culture requires buffered charcoal yeast extract agar (ideally supplemented with antibiotics and dyes). Urine antigen test for L. pneumophila rapid, sensitive, specific and cheap.

45

Legionella pneumonia
Treatment:

Newer macrolide antibiotics (especially azithromycin) or respiratory tract quinolones (especially levofloxacin). Prevention of hospital-acquired: copper-silver ionization units in hot water storage tanks.

46

Legionella pneumonia
Prognosis:

16-30% mortality untreated, if community-acquired, 50% mortality untreated, if hospital-acquired, <5% mortality if treated early and patient is immunocompetent, but 75% can have persistent fatigue and 66% persistent neurological symptoms more than a year later.

47

IMPORTANT CONCEPT 4: Acute pneumonia with diarrhea, confusion or hyponatremia suggests?

That Legionella may be the cause.

48

Pseudomonas aeruginosa pneumonia
Definition:

Lung parenchymal infection by Pseudomonas aeruginosa (Gram-negative bacilli)
.

49

Pseudomonas aeruginosa pneumonia
Epidemiology:

Common, hospital-acquired (18% of hospital-acquired).

50

Pseudomonas aeruginosa pneumonia
Demographics:

No age, sex or race predilection. Risk factors: intubation, neutropenia.

51

Pseudomonas aeruginosa pneumonia
Pathogenesis:

Habitat: water, transmitted from water. Once inhaled or aspirated, attach to respiratory epithelial cells; colonization generally precedes infection.

52

Pseudomonas aeruginosa pneumonia
Virulence factors

Include resistance to many commonly used antibiotics, ability to form a biofilm, many enzymes (particularly elastase) and many exotoxins

53

Pseudomonas aeruginosa pneumonia
Gross pathology:

Firm red areas of hemorrhagic consolidation +/- yellow areas of consolidation with a rim of hemorrhage (target lesions [not at all specific for Pseudomonas]).

54

Pseudomonas aeruginosa pneumonia
Microscopic pathology:

Acute necrotizing alveolitis, with groups of long thin, almost filamentous bacilli invading blood vessels from the adventitia (“Pseudomonas vasculitis” [misnomer because is most common with neutropenia and hence no –itis]) with associated hemorrhage and infarction.

55

Pseudomonas aeruginosa pneumonia
Symptoms:

Cough productive of purulent sputum, dyspnea, fever, chills, confusion.

56

Pseudomonas aeruginosa pneumonia
Signs:

Fever, tachycardia, hypotension, tachypnea, pulmonary crackles.

57

Pseudomonas aeruginosa pneumonia
Diagnosis:

Chest x-ray: diffusely distributed bilateral bronchopneumonic (alveolar) infiltrates +/- nodular lesions, small abscesses, pleural effusions. Blood testing: leukocytosis (unless neutropenia predisposed to Pseudomonas infection). Gram stain: long thin Gram-negative bacilli with pointed ends. Culture: aerobic, with characteristic sweet grape-like odor, green pigment resembling bronze.

58

Pseudomonas aeruginosa pneumonia
Specific diagnosis:

Difficult because positive sputum culture commonly represents only colonization.

59

Pseudomonas aeruginosa pneumonia
Treatment:

Combination of an antipseudomonal beta-lactam and antipseudomonal quinolone (or antipseudomonal beta-lactam and an aminoglycoside) [or an antipseudomonal quinolone and an aminoglycoside].

60

Pseudomonas aeruginosa pneumonia
Prognosis:

Up to 87% mortality, even if treated, but mortality attributable to the pneumonia is as low as 32%.

61

IMPORTANT CONCEPT 5: Pseudomonas pneumonia is much worse than?

Pneumococcal pneumonia mostly because it hits patients already hospitalized with some other bad disease.

62

Mycoplasma pneumoniae: Mycoplasma pneumonia.
Definition:

Lower respiratory tract infection by Mycoplasma pneumoniae

63

Mycoplasma pneumoniae: Mycoplasma pneumonia.
Epidemiology:

Common, community-acquired, more common in fall and winter. 1% of Americans get Mycoplasma pneumoniae infection per year, usually children and young adults, but 95% get only upper respiratory tract infection and 5% pneumonia. Mycoplasma pneumoniae is one of the most common causes of “atypical pneumonia” (as opposed to typical pneumonia, which is more severe), also called “walking pneumonia”. 20% of pneumonia in middle school and high school students and 50% of pneumonia in college students, 25% of pneumonia in non-hospitalized patients and 5% of pneumonia requiring hospitalization

64

Mycoplasma pneumoniae: Mycoplasma pneumonia.
Pathogenesis:

Smallest of free-living organisms, fastidious short or filamentous bacilli lacking a cell wall and invisible on Gram stain. Transmitted person-to-person by infected respiratory droplets during close contact, attach to respiratory epithelial cells by adherence proteins and cause illness that is largely immune-mediated, with an incubation period of 2-3 weeks.

65

Mycoplasma pneumoniae: Mycoplasma pneumonia.
Gross pathology:

Minimal

66

Mycoplasma pneumoniae: Mycoplasma pneumonia.
Microscopic pathology:

Lymphoplasmacytic bronchiolitis with mucosal ulceration and fibrinopurulent exudate in the lumen, then lymphoplasmacytic interstitial pneumonitis extending out from the bronchiolitis, associated with alveolar type 2 pneumocyte hyperplasia.

67

Mycoplasma pneumoniae: Mycoplasma pneumonia.
Symptoms:

Insidious onset of malaise, headache, anorexia, low-grade fever and chills, then (in 75-100%) a persistent incessant intractable dry cough (may get a little productive), +/- sore throat, +/- ear pain.

68

Mycoplasma pneumoniae: Mycoplasma pneumonia.
Signs:

All plus or minus: wheezing, scattered pulmonary rales, paranasal sinus tenderness, pharyngeal mucosal erythema, tympanic membrane erythema, mild cervical lymphadenopathy, erythematous maculopapular skin rash (that may go on to Stevens-Johnson syndrome).

69

Mycoplasma pneumoniae: Mycoplasma pneumonia.
Diagnosis:

Chest x-ray: patchy areas of airspace consolidation or reticulonodular infiltrate + (in 20%) pleural effusion, unilateral or bilateral, areas of consolidation more common in lower lobes. Blood testing: cold agglutinins (titer >1:64) in 60% (with hemolysis, usually mild). White blood cell count is normal in 75-90%. Other: may get cardiac arrhythmias and heart failure, may get meningitis or encephalitis.

70

Mycoplasma pneumoniae: Mycoplasma pneumonia.
Specific diagnosis:

Difficult and rare: serology (ideally requires acute and then convalescent titer 2-3 weeks later with a four-fold rise), PCR on throat specimen (sensitivity 92% and specificity 98% in one study, but sensitivity 48% in first 21 days of symptoms and 29% after that in another study).

71

Mycoplasma pneumoniae: Mycoplasma pneumonia.
Treatment:

Azithromycin or levofloxacin (or doxycycline) [or erythromycin] {or moxifloxacin}
Prognosis: vast majority recover without sequelae.

72

IMPORTANT CONCEPT 6: Mycoplasma pneumonia is the prototype?

Atypical pneumonia and walking pneumonia because it is not that bad.

73

Tuberculosis: Mycobacterium tuberculosis
Definition:

Mycobacterium tuberculosis infection

74

Tuberculosis: Mycobacterium tuberculosis
Epidemiology:

Uncommon, incidence in the US in 2010 was 3.6/100,000, 10% associated with HIV infection (especially among injection drug users, the homeless, prisoners and alcoholics), seasonal (peak in the spring and trough in the fall), more common in the elderly, more common in men, 83% in racial and ethnic minority groups (especially foreign-born [incidence 25.8/100,000 in Asians, 9.3/100,000 in blacks, 8.4/100,000 in Hispanics, 1.1/100,000 in whites]).

75

Tuberculosis: Mycobacterium tuberculosis
Pathogenesis:

Contagious, spread by the productive cough of heavily infected patients, four outcomes after inhalation (1) immediate clearance (2) primary disease (3) latent disease (4) reactivation disease.

76

Tuberculosis: Mycobacterium tuberculosis
Gross pathology:

Caseating granulomas (first one in primary infection usually 1 to 1.5 cm, grey-white, with central necrosis resembling cheese, called Ghon focus, if combined with hilar lymph nodal involvement [common], called Ghon complex), sometimes partly acute necrotizing pneumonia, sometimes with empyema, sometimes large cavitary lesions, rarely diffusely disseminated small foci of infection resembling millet seeds (miliary disease).

77

Tuberculosis: Mycobacterium tuberculosis
Microscopic pathology:

Necrotizing granulomas with epithelioid histiocytes, multinucleated giant cells (commonly Langhans type [with nuclei arranged in a peripheral semicircle or ring]), a collar of surrounding lymphocytes and very few organisms (dark red beaded bacilli on acid-fast stain), sometimes neutrophilic necrotizing pneumonia (usually with some mixture of granulomatous inflammation), necrosis with minimal inflammation with miliary disease.

78

Tuberculosis: Mycobacterium tuberculosis
Symptoms:

Insidious onset of anorexia, fatigue, weight loss, chills, fever, night sweats and a mild cough productive of mucopurulent sputum +/- mild hemoptysis, but may be asymptomatic or masked by concomitant chronic bronchitis

79

Tuberculosis: Mycobacterium tuberculosis
Signs:

Usually none, but may have post-tussive pulmonary rales or tubular breath sounds over a large lesion or amphoric (distant hollow) breath sounds over a cavity

80

Tuberculosis: Mycobacterium tuberculosis
Diagnosis:

Chest x-ray shows patchy or nodular infiltrate in apical- or subapical posterior areas of upper lobes or superior segment of a lower lobe in early chronic tuberculosis (most suggestive of TB if bilateral or cavitary), or small, nodular, sharply defined lesions (granulomas, increased density with caseation) or scarring, atelectasis, mass lesions or large cavities. Pneumonia associated with hilar adenopathy should always suggest primary tuberculosis.

81

Tuberculosis: Mycobacterium tuberculosis
Diagnosis: Besides CXR.

Usually not too difficult and made by radiology and sputum acid-fast stain and culture. Positive sputum smear indicates infectivity. Bronchoalveolar lavage or transbronchial biopsy can yield the diagnosis. Culture takes 4-8 weeks; positive requires PCR confirmation. Nucleic acid amplification tests for sputum (trade names Gen-Probe MTD and E-MTD and Amplicor) can be performed in remote sites and yield confirmation of the diagnosis in 2-7 hours and are being hotly researched.

82

Tuberculosis: Mycobacterium tuberculosis
Treatment:

In HIV-negative patients without isoniazid-resistant tuberculosis: 4 drugs (isoniazid, rifampin, pyrazinamide and ethambutol) for 2 months, followed by 2 drugs (isoniazid and rifampin) for 4 months.

83

Tuberculosis: Mycobacterium tuberculosis
Prognosis:

Good (usually).

84

IMPORTANT CONCEPT 7: .You might be punished for missing the diagnosis of tuberculosis in your patient?

By getting it from your patient.

85

Histoplasmosis
Definition:

Infection by Histoplasma species fungi (which mimic Mycobacterium tuberculosis [“TB wannabe”])

86

Histoplasmosis
Epidemiology:

Common (estimated half a million new infections per year in US), 75% asymptomatic, but can be severe with heavy exposure and disseminated with reactivation of latent infection in patients with acquired immunodeficiency syndrome or immunosuppressive therapy for transplantation. Histoplasmosis is hyperendemic in the Mississippi and Ohio river valleys. Histoplasma grows particularly well in soil enriched with chicken or bat feces, so areas around chicken coops and bat caves can be sites of heavy exposure.

87

Histoplasmosis
Pathogenesis:

Inhalation of airborne spores, whose small size allows them to get to alveoli, where macrophages phagocytose them, but do not kill them unless activated by sensitized T lymphocytes in a cytokine pathway involving tumor necrosis factor and interferon-gamma. Cellular immunity develops after 10-14 days after exposure. Infection becomes latent in old granulomas in the lungs or lymph nodes.

88

Histoplasmosis
Gross pathology:

Tan nodules, masses or areas of consolidation that develop caseous necrosis, may cavitate, and eventually become white, fibrotic and calcified, may have pulmonary hilar or mediastinal lymphadenopathy or pleural effusion

89

Histoplasmosis
Microscopic pathology:

Small 2-5 micron oval basophilic yeast forms with narrow-based budding and often in clusters (sometimes within macrophages). Tissue reaction ranges from none (in the most immunocompromised patients) to vigorous necrotizing granulomatous inflammation with lots of epithelioid histiocytes, multinucleated giant cells and surrounding lymphocytes (in the least immune-compromised patients); initial tissue reaction before cellular immunity has developed is neutrophilic.

90

Histoplasmosis
Symptoms:

Fever, chills, headache, myalgia, anorexia, cough and substernal chest pain (worse with deep inspiration) 2-4 weeks after exposure, concomitant coryza (runny nose) and/or sore throat go against the diagnosis of histoplasmosis, symptoms usually resolve without treatment in several weeks.

91

Histoplasmosis
Signs:

Fever, (uncommon: pulmonary crackles).

92

Histoplasmosis
Diagnosis:

Radiology detects histoplasmosis; chest x-ray typically shows nodules or masses (+/- cavitation) or patchy infiltrates, commonly with hilar or mediastinal lymphadenopathy, but may show reticulonodular infiltrates or miliary disease. Calcification is very common, but takes months to develop in children and years in adults. Diagnosis is made by biopsy, culture and antigen test: biopsy can yield definite diagnosis, culture takes up to 6 weeks and may be false negative, antigen can be detected in bronchoalveolar lavage, serum and urine, but can be cross-reaction due to blastomycosis or coccidioidomycosis.

93

Histoplasmosis
Treatment:

Itraconazole for mild-moderate disease, amphotericin for severe disease.

94

Histoplasmosis
Prognosis:

7.5% mortality if bad enough to require hospitalization (not too often).

95

IMPORTANT CONCEPT 8: Histoplasmosis mimics and is prevalent?

Tuberculosis and is prevalent in the Ohio and Mississippi river valleys.

96

Aspergillus pneumonia
Definition:

Lung parenchymal infection by Aspergillus (must be distinguished from colonization [of a cavity, for instance, producing a non-invasive fungus ball called an aspergilloma] and an allergic disease [allergic bronchopulmonary aspergillosis].

97

Aspergillus pneumonia
Epidemiology:

Aspergillus is ubiquitous, but invasive Aspergillus pneumonia is uncommon, primarily in patients with severe and prolonged neutropenia, immunosuppressive therapy or high dose corticosteroid therapy.

98

Aspergillus pneumonia
Pathogenesis:

Inhalation of airborne conidia, whose small size allows them to get to alveoli, where they germinate into hyphae and invade, especially blood vessels

99

Aspergillus pneumonia
Gross pathology:

Nodules, commonly with surrounding hemorrhage (may resemble a target, “target lesion”) and associated infarction, or patchy tan-red-brown consolidation, commonly without purulence because patient neutropenic, or masses, or peribronchial consolidation, or any combination of these

100

Aspergillus pneumonia
Microscopic pathology:

Necrosis, hemorrhage and (if patient has neutrophils) acute inflammation with regular septate hyphae, 3-6 microns in width, with dichotomous branching (two equal size branches) at acute angles (classically 45 degrees), progressive branching (the branches branch), frequently in radiating or parallel array.
Aspergillum = fruiting body producing conidia (resembling Roman Catholic holy water sprinkler in action), rarely seen, only in well aerated sites.

101

Aspergillus pneumonia
Symptoms:

Classic triad (in neutropenic patients): fever, pleuritic chest pain and hemoptysis, but these patients frequently have fever without symptoms localizing to the lungs. May have cough or dyspnea.

102

Aspergillus pneumonia
Signs:

Fever, tachycardia, tachypnea, pulmonary crackles or rhonchi.

103

Aspergillus pneumonia
Diagnosis:

Radiology detects Aspergillus pneumonia; chest x-ray is insensitive, but computed tomography typically shows nodules (+/- cavitation) or (second most common) patchy or segmental consolidation, or (third most common) peribronchial infiltrates (+/- tree-in-bud patterns), nodules most commonly small (subcentimeter), with surrounding ground glass infiltrates (halo sign) representing surrounding hemorrhage. Diagnosis is difficult, sought by biopsy, culture and serum test for galactomannan

104

Aspergillus pneumonia
Treatment:

Voriconazole.

105

Aspergillus pneumonia
Prognosis:

Poor (only 20% survival in the past, but getting a little better).

106

IMPORTANT CONCEPT 9: Aspergillus pneumonia needs distinguishing from?

Mere colonization (e.g. aspergilloma) and allergic bronchopulmonary aspergillosis.

107

Cryptococcal pneumonia
Definition:

Lung parenchymal infection by Cryptococcus species fungi. Important to note that cryptococcal pneumonia is a much less common and much less threatening infection than cryptococcal meningitis, but pneumonia is the second most common type of infection (65-94% of immunocompromised patients with cryptococcal pneumonia have meningitis).

108

Cryptococcal pneumonia
Epidemiology:

Uncommon, vast majority in patients with acquired immunodeficiency syndrome, prolonged corticosteroid therapy, transplantation, malignancy or sarcoidosis, more common in African Americans, very uncommon in children (even those with acquired immunodeficiency syndrome).

109

Cryptococcal pneumonia
Pathogenesis:

Inhalation of airborne spores, whose small size allows them to get to alveoli, where they multiply and resist phagocytosis with their large capsule. Cryptococcus grows particularly well in pigeon feces (and less notoriously chicken feces). Infection becomes latent in old granulomas in the lungs or lymph nodes.

110

Cryptococcal pneumonia
Gross pathology:

Soft, tan-grey nodules or masses (“cryptococcomas”) that may have a slimy cut surface and may cavitate, but are not hemorrhagic or calcified, or consolidation (that may even be lobar), may have pulmonary hilar or mediastinal lymphadenopathy or pleural effusion.

111

Cryptococcal pneumonia
Microscopic pathology:

Translucent or faintly basophilic yeast forms with narrow-based budding surrounded by a large clear space (yeast forms usually 4-10 microns, but full range is 2-20 microns and they are more variable in size than other pathogenic yeast forms) [clear space can be up to 5 X diameter of the yeast forms]{the more severe the infection, the more budding, and vice-versa}. Tissue reaction ranges from none (in the most immunocompromised patients) to vigorous mixed suppurative and granulomatous inflammation (in the least immunocompromised patients).

112

Cryptococcal pneumonia
Symptoms:

Fever (up to 94% of immunocompromised patients), productive cough (up to 71%), dyspnea (up to 50%), headache (41%), hemoptysis, chest pain, malaise, night sweats and weight loss, (less common: skin rash, gastrointestinal complaints).

113

Cryptococcal pneumonia
Signs:

Fever, tachycardia, tachypnea, (uncommon: pulmonary rales), [rare: upper body edema and plethora due to superior vena cava obstruction].

114

Cryptococcal pneumonia
Diagnosis:

Chest x-ray or computed tomography typically shows nodules or masses (+/- cavitation) or consolidation, but occasionally interstitial infiltrates.Diagnosis is made by biopsy, culture and antigen test: biopsy can yield definite diagnosis, but pathologist must notice the unstained or faintly stained yeast forms; silver stains show the yeast forms well and mucicarmine stain (or Fontana-Masson stain for capsule-deficient organisms) makes a definitive diagnosis even without culture. Culture48 hours and positive culture yields a diagnosis of infection without biopsy.

115

Cryptococcal pneumonia
Treatment:

Fluconazole (or voriconazole).

116

Cryptococcal pneumonia
Prognosis:

Not too bad for the pneumonia unless also have meningitis.

117

IMPORTANT CONCEPT 10: Serum cryptococcal antigen test can?

Frequently nail a specific diagnosis of cryptococcosis.

118

Pneumocystis jirovecii pneumonia.
Definition:

Lung parenchymal infection by Pneumocystis jirovecii (fungus long thought to be a protozoan, name changed from Pneumocystis carinii in 2001)

119

Pneumocystis jirovecii pneumonia.
Epidemiology:

Uncommon opportunistic infection in patients with deficient cell-mediated immunity (AIDS, lymphoma, leukemia, immunosuppression, etc.)

120

Pneumocystis jirovecii pneumonia.
Pathogenesis:

Basically unknown.

121

Pneumocystis jirovecii pneumonia.
Gross pathology:

Heavy, diffusely consolidated, tan lungs.

122

Pneumocystis jirovecii pneumonia.
Microscopic pathology:

Foamy eosinophilic, sparsely cellular, centro-alveolar “honeycomb” exudate +/- lymphoplasmacytic interstitial pneumonia.

123

Pneumocystis jirovecii pneumonia.
Symptoms:

In AIDS patients: insidious onset of progressive dyspnea (95%), cough (95%, non-productive in 70%) and fever. Other symptoms: fatigue, chills, chest pain and weight loss, but 7% asymptomatic. In patients without HIV infection, Pneumocystis pneumonia typically presents as fulminant respiratory failure associated with fever and dry cough.

124

Pneumocystis jirovecii pneumonia.
Signs:

In AIDS patients: fever (84%), tachypnea (62%), pulmonary crackles and rhonchi (<50%), but chest examination normal in 50%.

125

Pneumocystis jirovecii pneumonia.
Diagnosis:

Chest x-ray: diffuse bilateral hazy interstitial infiltrates which become dense alveolar infiltrates (most common), but normal in 25% of AIDS patients. High-resolution computed tomography: patchy or nodular ground-glass attenuation (100% sensitive, 89% specific). Blood tests: elevated lactate dehydrogenase level (90%). Pulmonary function tests: decreased diffusing capacity (most). Specific diagnosis: demonstration of the bug in induced sputum smear, bronchioalveolar lavage, aspirate or biopsy, with (1) immunostains [usual method], (2) cyst stains such as Grocott (Gomori) methenamine silver, or (3) trophozoite stains such as Giemsa stain, but not culture (since Pneumocystis does not grow in culture).

126

Pneumocystis jirovecii pneumonia.
Treatment:

Trimethoprim-sulfamethoxazole (usually).

127

Pneumocystis jirovecii pneumonia.
Prognosis:

93% survival in AIDS patients, up from 79% before highly active antiretroviral therapy and prophylaxis.

128

IMPORTANT CONCEPT 11: Pneumocystis pneumonia is the prototype subacute or chronic interstitial pneumonia in?

An immunocompromised patient.

129

Chronic Pneumonia and Viral Pneumonia.
Chronic pneumonias tend to be?

Fungal, mycobacterial, toxic, autoimmune or idiopathic (basically, anything but bacterial [not counting mycobacteria, who act more like fungi anyway]).

130

Chronic Pneumonia and Viral Pneumonia.
Chronic pneumonias tend to be?

Interstitial or nodular or both.

131

Chronic Pneumonia and Viral Pneumonia.
Chronic pneumonias tend to be

Chronic and nodular.

132

Chronic Pneumonia and Viral Pneumonia.
Causes of interstitial chronic pneumonia include?

Pneumocystis jirovecii, sarcoidosis and toxoplasmosis.

133

Chronic Pneumonia and Viral Pneumonia.
Causes of nodular chronic pneumonia include?

Tuberculosis, histoplasmosis, aspergillosis, cryptococcosis, coccidioidomycosis and blastomycosis.

134

Chronic Pneumonia and Viral Pneumonia.
Viral pneumonias tend to be?

Interstitial.

135

Chronic Pneumonia and Viral Pneumonia.
Influenza virus and respiratory syncytial virus (RSV) are?

The most common causes of viral pneumonia.

136

Chronic Pneumonia and Viral Pneumonia.
Cytomegalovirus (CMV) causes?

Interstitial pneumonias in immunocompromised patients.

137

Chronic Pneumonia and Viral Pneumonia.
Herpes simplex virus (HSV) causes

Nodular pneumonia in immunocompromised patients.

138

Lung Cancer in General.
Definition:

Lung cancer is a malignant epithelial neoplasm of lung; lymphomas and sarcomas originating in lung are rare and usually not included.

139

Lung Cancer in General.
Epidemiology:

Most frequently diagnosed major cancer and most common cause of cancer death worldwide. 228,000 new cases in the United States estimated for 2013, 52% in men and 48% in women, 160,000 deaths estimated for 2013 (more than breast, prostate and colon cancer combined [the next three most commonly fatal cancers]). More common & more fatal in black males, less common & less fatal in Asians and Hispanics. Risk Factors: 85% in active or former smokers. 3,400 cases/year attributable to second hand smoking. Non-smoking asbestos workers 5 x higher risk. Non-smoking uranium miners 4 x higher risk.

140

Lung Cancer in General.
Pathogenesis:

Multiple mutations in DNA over many years, common in EGFR/HER1, K-RAS, ALK, Myc, Rb, p16INK4a, p53 and FHIT. Initiation most commonly by smoking. Promotion by smoking, dietary and environmental factors. 85% due to smoking (>20 carcinogens in tobacco smoke). 4% due to radon (odorless colorless radioactive gas emitted from soil into the air).

141

Lung Cancer in General.
Pathology: 3 major types:

Adenocarcinoma 40% of cases
Squamous cell 20%
Small cell 15%,

142

Lung Cancer in General.
Pathology:
Adenocarcinoma

Adenocarcinomas are becoming more common all the time, more commonly peripheral, more common in women, in Asians and in never smokers.

143

Lung Cancer in General.
Pathology:
Squamous cell carcinomas

Squamous cell carcinomas becoming less common, more commonly central, more commonly cavitate, cause post-obstructive pneumonia and hypercalcemia.

144

Lung Cancer in General.
Pathology:
Small cell

Small cell more commonly metastatic at presentation (>67%), more commonly central, more commonly associated with paraneoplastic syndrome of inappropriate antidiuretic hormone, Cushing syndrome or Eaton-Lambert syndrome.

145

Lung Cancer in General.
Symptoms:

Most commonly present between ages 40 and 70, especially 60-70. Usually have symptoms for several months. Cough (60%, more common with squamous or small cell because central), dyspnea (50%), weight loss (40%), hemoptysis (30%), chest pain (20%, usually dull and persistent), hoarseness (10%), wheezing, fever, fatigue.

146

Lung Cancer in General.
Signs:

Usually none.

147

Lung Cancer in General.
Diagnosis:

Step 1 (discovery): most cases discovered by radiology. Screening 55-80-year-olds with 30 or more pack-years smoking picks up some while still curable.
Step 2 (actionable diagnosis): biopsy. Fine needle aspiration or other cytology rarely provides enough tissue for all the testing now needed.

148

Lung Cancer in General.
Treatment:

Surgery for non-small cell carcinoma if early enough stage. 2-agent chemotherapy for non-small cell carcinoma if higher stage (carboplatin plus docetaxel [or various alternatives]). Chemotherapy for small cell carcinoma. Targeted therapy: erlotinib for mutated EGFR, crizotinib for mutated ALK.

149

Lung Cancer in General.
Prognosis:

Overall 5-year survival 17%.

150

IMPORTANT CONCEPT 12: The 3 major types of lung cancer are?

Adenocarcinoma, squamous cell carcinoma and small cell carcinoma cancer and there are important differences among them.

151

Specific Types of Lung Cancer.
Adenocarcinoma of lung (lung primary adenocarcinoma).
Definition:

Malignant epithelial tumor of lung with glandular features such as making glands or mucin.

152

Specific Types of Lung Cancer.
Adenocarcinoma of lung (lung primary adenocarcinoma).
Epidemiology:

Increasingly common type of lung cancer, has become the most common type (over 40% of the total), esp. in women, young patients, east Asians and non-smokers. In the US in 2013, probably a little over 50% of women with lung cancer have adenocarcinoma (compared to more like 40% of men). In the US in 2013, probably about 60% of patients under age 40 with lung cancer have adenocarcinoma (compared to more like 40% of those over 40). In the US in 2013, probably about 55% of Asian patients with lung cancer have adenocarcinoma (compared to more like 40% for non-Asians). In the US in 2013, probably about 70% of never smokers with lung cancer have adenocarcinoma (compared with 50% of former smokers and 40% of current smokers).

153

Specific Types of Lung Cancer.
Adenocarcinoma of lung (lung primary adenocarcinoma).
Pathogenesis: General

77% due to smoking (vs. 94% of the other types), increase in adenocarcinoma partly attributed to the introduction of filter cigarettes, the filter removing larger particles from tobacco smoke, thus reducing deposition in larger airways, but smokers have to inhale more deeply to receive the same amount of nicotine, increasing particle deposition in small airways. Introduction of low tar cigarettes may have changed mix of carcinogens and peripheral cells transformed into malignant may be different types. Other causes: radon gas from the ground (4%), passive smoking (1.5%), air pollution (1.5%), radiation, asbestos.

154

Specific Types of Lung Cancer.
Adenocarcinoma of lung (lung primary adenocarcinoma).
Pathogenesis: At the molecular level:

An epidermal growth factor receptor (EGFR)-dependent pathway in never-smokers and a Kirsten rat sarcoma oncogene (KRAS)-dependent signaling pathway in smokers. KRAS mutation in 20-30% (conferring resistance to tyrosine kinase inhibitor erlotinib [Tarceva]), EGFR mutation in 10-15% (conferring responsiveness to gefitinib and erlotinib), EML4-ALK translocation fusion oncogene leading to the expression of the N-terminal half of EML4 fused with the intracellular kinase domain of ALK resulting in potent oncogenic activity in 3% (conferring responsiveness to ALK inhibitor crizotinib [Xalkori]), p53 tumor suppressor gene in 60-75%.
Other genes often mutated or amplified: c-MET, NKX2-1, LKB1, PIK3CA, and BRAF.

155

Specific Types of Lung Cancer.
Adenocarcinoma of lung (lung primary adenocarcinoma).
Gross pathology:

> 87% peripheral, often subpleural, most < 4 cm, solitary, solid, firm, gritty, grey-tan, lobulated or spiculated, may have grey glistening slimy cut surface (if mucinous), may have associated scar (desmoplastic reaction), may have puckering of pleural surface, may have hemorrhage or necrosis, may infiltrate pleura (mimicking mesothelioma)

156

Specific Types of Lung Cancer.
Adenocarcinoma of lung (lung primary adenocarcinoma).
Microscopic pathology:

5 patterns: acinar (making glands, with desmoplastic reaction, the most common type by far), papillary, micropapillary (rare, bad prognosis), solid (also bad prognosis), and lepidic (spreading within alveoli [commonly in a single cell layer] without invading {adenocarcinoma in situ}, good prognosis), occasionally need immunostains to prove it is lung primary or not poorly differentiated squamous cell type

157

Specific Types of Lung Cancer.
Adenocarcinoma of lung (lung primary adenocarcinoma).
Symptoms:

Usually have symptoms for several months: cough (50%), weight loss (40%), hemoptysis (25%), dyspnea (25%), chest pain (20%, usually dull and persistent), malaise, fatigue, wheezing, fever, bone pain, dysphagia; (only 10% asymptomatic), distant metastases may yield first manifestations

158

Specific Types of Lung Cancer.
Adenocarcinoma of lung (lung primary adenocarcinoma).
Signs:

Usually none

159

Specific Types of Lung Cancer.
Adenocarcinoma of lung (lung primary adenocarcinoma).
Diagnosis:

Radiology (detects it), biopsy (or cytology) needed for actionable diagnosis

160

Specific Types of Lung Cancer.
Adenocarcinoma of lung (lung primary adenocarcinoma).
Treatment:

Surgical resection (option only for early stage), erlotinib (if have EGFR mutation), and in inoperable cases pemetrexed (Alimta, antifolate metabolite inhibitor of thymidylate synthetase, inhibiting the formation of precursor purine and pyrimidine nucleotides, preventing the formation of DNA and RNA) and anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab (Avastin)

161

Specific Types of Lung Cancer.
Adenocarcinoma of lung (lung primary adenocarcinoma).
Prognosis:

Determined by stage (early stage live about 20 months on average, late stage about 13 months), tyrosine kinase inhibition adds about 5 months and ALK inhibition similar postponement.

162

IMPORTANT CONCEPT 13: Adenocarcinoma is the most common type of?

Lung cancer and the type most likely to be responsive to targeted therapy.

163

Specific Types of Lung Cancer.
Adenocarcinoma in situ of lung.
Definition:

Non-invasive adenocarcinoma of lung characterized by non-destructive growth along intact alveolar septa (called lepidic growth), name changed from bronchioloalveolar carcinoma in 2011

164

Specific Types of Lung Cancer.
Adenocarcinoma in situ of lung.
Epidemiology:

<5% of lung cancers, up to 63% are in women, slightly older average age (67) than lung cancer patients overall, 67% in smokers and 33% in non-smokers

165

Specific Types of Lung Cancer.
Adenocarcinoma in situ of lung.
Pathogenesis: Two Types:

(mucinous and non-mucinous) may have different pathogenesis

166

Specific Types of Lung Cancer.
Adenocarcinoma in situ of lung.
Pathogenesis:
Non-mucinous

Non-mucinous directly evolving from the terminal respiratory unit cells (type II pneumocytes and Clara cells), predominating in smokers, presenting more frequently as a radiologic ground-glass opacity, and frequently harboring epidermal growth factor receptor (EGFR) mutation, believed to be the driver of its malignant proces

167

Specific Types of Lung Cancer.
Adenocarcinoma in situ of lung.
Pathogenesis:
Mucinous

Mucinous type derived from metaplasia of bronchiolar epithelium, presenting more frequently as a pneumonia-type radiologic infiltrate, rarely demonstrating EGFR mutations, and much more frequently harboring and driven by a KRAS mutation
Multifocal nodules in 25% of cases may be from tumor spread via airways (tumor cells carried up by mucociliary ladder and then aspirated into other bronchi [“aerogenous spread”]) or may be just separate primaries arising at same time (synchronous) or later (metachronous), former mechanism suggested by fact that most multifocal nodular cases are mucinous type and latter mechanism suggested by studies showing different patterns of mutations in different nodules.
Single nodules are more commonly non-mucinous. Non-mucinous type more commonly goes through stepwise progression with precursor atypical adenomatous hyperplasia (comparable to atypical hyperplasia in breast or adenoma in colon).

168

Specific Types of Lung Cancer.
Adenocarcinoma in situ of lung.
Gross pathology:

Single nodule (25%), multifocal nodules (25%) or pneumonia-like area of consolidation, usually peripheral, tan to ivory, nodules usually small (<2 cm), may have slimy grey surface (mucinous type).

169

Specific Types of Lung Cancer.
Adenocarcinoma in situ of lung.
Microscopic pathology:

Spreads by replacing alveolar lining, commonly in a single cell layer, 2 types: mucinous (20% of them, probably derived from respiratory goblet cells, commonly CK20 positive and TTF-1 negative, usually KRAS positive and EGFR negative) and non-mucinous (80%, with features of either Clara cells or type II pneumocytes, usually TTF-1 positive and CK20 negative, usually KRAS negative and “commonly” EGFR positive).

170

Specific Types of Lung Cancer.
Adenocarcinoma in situ of lung.
Symptoms:

Majority have none, but some have cough, dyspnea and weight loss and in many symptomatic cases the symptoms mimic pneumonia with productive cough and fever; a rare few have bronchorrhea (producing up to 100 ml/day of watery sputum [with advanced mucinous type])

171

Specific Types of Lung Cancer.
Adenocarcinoma in situ of lung.
Signs:

Usually none

172

Specific Types of Lung Cancer.
Adenocarcinoma in situ of lung.
Diagnosis:

Discovered by radiology (nodules may have ground-glass character), but biopsy (or cytology) needed for actionable diagnosis

173

Specific Types of Lung Cancer.
Adenocarcinoma in situ of lung.
Treatment:

Surgical resection and in inoperable cases, erlotinib (EGFR tyrosine kinase inhibitor) for EGFR positive tumors (typically non-mucinous), crizotinib for ALK positive tumors (rare in the US), and cytotoxic chemotherapy with paclitaxel (Taxol, a taxane, antimicrotubule agent mitotic inhibitor) for EGFR negative tumors (typically mucinous)

174

Specific Types of Lung Cancer.
Adenocarcinoma in situ of lung.
Prognosis:

About 25% have single nodules that are cured by surgical removal, overall 5-year survival about 15% (similar to lung cancer in general), better prognosis of non-mucinous and single nodule types balanced out by poorer prognosis of mucinous, multifocal and pneumonia-like types.

175

IMPORTANT CONCEPT 14: Adenocarcinoma in situ can be?

A single small nodule curable by surgery, or multiple nodules, or a consolidation mimicking pneumonia.

176

Specific Types of Lung Cancer.
Squamous cell carcinoma of lung.
Definition:

Lung primary malignant epithelial neoplasm with keratinization and/or intercellular bridges.

177

Specific Types of Lung Cancer.
Squamous cell carcinoma of lung.
Epidemiology:

20% of lung cancers (decreasing proportion), 94% in smokers, more common in men, more common in older adults, more common in African Americans, less common in Asians.

178

Specific Types of Lung Cancer.
Squamous cell carcinoma of lung.
Pathogenesis:

Squamous metaplasia of bronchial mucosa and cumulative mutations in genes controlling cell proliferation caused by carcinogens in cigarette smoke, the type of lung cancer most likely to cause hypercalcemia due to the production of a substance resembling parathyroid hormone (an exception to the general principle that small cell neuroendocrine carcinoma is the type of lung cancer most likely to cause a paraneoplastic syndrome)

179

Specific Types of Lung Cancer.
Squamous cell carcinoma of lung.
Gross pathology:

Most commonly central, 2/3 arising from main, lobar, segmental or subsegmental bronchi, 1/3 arising from smaller peripheral bronchi, usually endobronchial and smaller than other types of lung cancer because it causes obstructive symptoms, firm or soft, white or grey, the type of lung cancer most likely to cavitate, commonly metastatic to local lymph nodes at initial presentation, commonly associated with post-obstructive pneumonia, abscess, bronchiectasis, mucus plugging and atelectasis

180

Specific Types of Lung Cancer.
Squamous cell carcinoma of lung.
Microscopic pathology:

Cohesive sheets, nests or cords of large cells with moderate smooth eosinophilic cytoplasm, intercellular bridges and/or keratinization (may form keratin pearls)
Symptoms: cough, hemoptysis, wheezing, dyspnea, weakness, weight loss, chest pain, fatigue, anorexia, dysphagia.

181

Specific Types of Lung Cancer.
Squamous cell carcinoma of lung.
Signs:

Usually none

182

Specific Types of Lung Cancer.
Squamous cell carcinoma of lung.
Diagnosis:

Majority can be diagnosed by H&E stained biopsy, but sometimes must be differentiated from poorly differentiated adenocarcinoma (100% p40 positive [new stain, later data will not be as good], near 100% p63 positive, 75-95% CK5/6 positive, 15% CK7 positive, 0-3% TTF-1 positive [as opposed to lung primary adenocarcinoma 0-3% p40 positive, 15-30% p63 positive, 0-3% CK5/6 positive, near 100% CK7 positive, 75-85% TTF-1 positive])

183

Specific Types of Lung Cancer.
Squamous cell carcinoma of lung.
Treatment:

Surgical resection (optimum), radiation or chemotherapy (very suboptimal), NOT bevacizumab (trade name Avastin, antibody to vascular endothelial growth factor [VEGF] because it was associated with hemorrhages from squamous cell carcinomas, some fatal), pemetrexed does not work well

184

Specific Types of Lung Cancer.
Squamous cell carcinoma of lung.
Prognosis:

Poor (only 15% of patients survive 5 years, with treatment).

185

.IMPORTANT CONCEPT 15: .Squamous cell carcinoma tends to be?

Central, endobronchial, cavitating, and to bleed causing hemoptysis.

186

Specific Types of Lung Cancer.
Small cell carcinoma of lung.
Definition:

Lung primary malignant epithelial neuroendocrine neoplasm composed of “small” cells.

187

Specific Types of Lung Cancer.
Small cell carcinoma of lung.
Epidemiology:

15% of lung cancers (decreasing proportion), 99% in smokers (usually heavy smokers), more common in men, more common in older adults (typically age 65-70, but one-third over 70).

188

Specific Types of Lung Cancer.
Small cell carcinoma of lung.
Pathogenesis:

Cumulative mutations in genes controlling cell proliferation caused by carcinogens in cigarette smoke (RASSF1 [>90%], RB1 [>90%], telomerase [>90%], bcl-2 [80%], FHIT [80%], p53 [75%]), the most aggressive (rapidly growing and rapidly metastasizing) type of lung cancer and the type most likely to cause a paraneoplastic syndrome.

189

Specific Types of Lung Cancer.
Small cell carcinoma of lung.
Gross pathology:

Typically (>90%) central (“hilar”), parabronchial (alongside bronchi without an endobronchial mass), soft, off-white (or tan or grey), mass with multifocal necrosis and metastatic tumor in lymph nodes and commonly liver, bones, brain, adrenals, typically bulky tumor already metastatic at initial presentation.

190

Specific Types of Lung Cancer.
Small cell carcinoma of lung.
Microscopic pathology:

“small” cells (3 times the size of a resting lymphocyte, only small among carcinoma cells) with round-to-oval shape, scant cytoplasm, finely granular (“salt and pepper”) nuclear chromatin, absent or inconspicuous nucleoli, frequent nuclear molding, many mitoses, usually in diffuse sheets, but sometimes nests, streams, ribbons, rosettes or palisades, with extensive necrosis, frequent crush artifact (in small biopsies, a feature shared with lymphocytic infiltrates).

191

Specific Types of Lung Cancer.
Small cell carcinoma of lung.
Symptoms:

Weight loss (46%), cough (45%), dyspnea (37%), weakness (34%), hemoptysis (27%), chest pain (27%), wheezing, fatigue, anorexia, dysphagia
Signs: Facial, cervical and arm edema, plethora and venous engorgement (superior vena cava syndrome, Pemberton's sign = development of facial flushing, distended neck and head veins, inspiratory stridor and elevation of jugular venous pressure upon raising both of the patient's arms above his/her head simultaneously, as high as possible)

192

Specific Types of Lung Cancer.
Small cell carcinoma of lung.
Diagnosis:

Vast majority can be diagnosed by H&E stained biopsy, but sometimes must be differentiated from lymphocytic bronchitis or lymphoma (only 50% CK7 positive, but most pancytokeratin positive) or poorly differentiated adenocarcinoma (80% TTF-1 positive, 90% CD56 positive [poor specificity], 75% synaptophysin positive [controversial], 50% chromogranin positive [maybe much less], 10% negative for all 3 neuroendocrine markers), up to 15% have hyponatremia due to syndrome of inappropriate antidiuretic hormone, up to 5% have Cushing syndrome (obesity [truncal], moon facies, decreased libido, facial plethora, thin skin, hirsuitism, hypertension, diabetes, depression, easy bruising, etc.), up to 3% have Eaton-Lambert syndrome (mimicking myasthenia gravis, due to autoantibodies against P/Q type voltage-gated calcium channels)

193

Specific Types of Lung Cancer.
Small cell carcinoma of lung.
Treatment:

Combination chemotherapy (with platinum-containing alkylating agents that mess up DNA by creating cross-links: cisplatin or carboplatin [second generation, less toxic]) plus etoposide (topoisomerase inhibitor that forms a complex with DNA and the enzyme [which normally aids in DNA unwinding], preventing re-ligation of DNA strands, causing them to break) generally with radiation therapy as well.

194

Specific Types of Lung Cancer.
Small cell carcinoma of lung.
Prognosis:

Poor, untreated live about 3 months (average), treated about 12 months (average, typically respond to therapy, but have untreatable relapse in about 8 months, then die in 4 months [average]).

195

IMPORTANT CONCEPT 16: Small cell carcinoma is usually?

Metastatic at presentation, responsive to chemotherapy and rapidly fatal despite being responsive.

196

Pulmonary Metastases.
Definition:

Malignant neoplasms in the lungs originating from primary tumors in other organs.

197

Pulmonary Metastases.
Epidemiology:

Common, more common than lung primary tumors.

198

Pulmonary Metastases.
Pathogenesis:

Lungs = organs that get the most metastases because (1) receive entire right heart blood flow with every heartbeat.
(2) have densest capillary bed in the body.
(3) have the first capillary bed met by venous return from every other organ.
(4) have the first capillary bed met by lymphatic drainage after it is dumped into superior vena cava from thoracic duct.
(5) this capillary bed offers uniquely high oxygen.

199

Pulmonary Metastases.
Primary sites of lung metastases:

(in approximate order of frequency): breast, colon, stomach, pancreas, kidney, skin (melanoma), prostate, liver, thyroid, adrenal, genital organs.

200

Pulmonary Metastases.
Sarcomas

Tend to metastasize to lungs because they tend to spread by vein (hematogenously) rather than by lymphatic channels (characteristic of carcinomas)

201

Pulmonary Metastases.
Gross pathology:

Metastases usually multiple and frequently numerous, only 3-9% solitary (30-40% of these from colon), tend to be smaller than lung primary tumors, usually <3 cm, tend to be rounder than primary tumors, more evenly contoured, more commonly peripheral, less commonly endobronchial, more rapidly growing, larger “cannonball” metastases more commonly from breast, kidney or sarcoma, metastases less likely to cavitate (4% vs. 9% of lung primaries, but most likely squamous cell in either)

202

Pulmonary Metastases.
Lymphangitic Carcinomatosis:

Metastatic disease can fill lymphatics and infiltrate interstitium without creating mass lesions (6-8% of pulmonary metastatic disease, esp. breast cancer and melanoma)

203

Pulmonary Metastases.
Microscopic pathology:

Adenocarcinoma (by far), immunohistochemical workup for lung primary adenocarcinoma vs. metastasis: first: CK7 and CK20, second: CDX2 and TTF-1, third: numerous ever evolving panels of immunostains

204

Pulmonary Metastases.
Immunostains: Lung primary

Usually CK7 and TTF-1 positive and CK20 and CDX2 negative

205

Pulmonary Metastases.
Immunostains: Colon primary

Usually CK20 and CDX2 positive and CK7 and TTF-1 negative.

206

Pulmonary Metastases.
Immunostains: Breast primary

Usually CK7 positive and CK20, CDX2 and TTF-1 negative,.

207

Pulmonary Metastases.
Immunostains: Stomach and Pancreas

Sometimes CK7 and CK20 positive, but more variable than colon or breast, kidney usually negative for all 4.

208

Pulmonary Metastases.
Symptoms:

(mostly attributable to primary or overall tumor burden): anorexia, weight loss, malaise, fatigue, chest pain, abdominal pain.

209

Pulmonary Metastases.
Signs:

Usually none specifically of the lung metastases

210

Pulmonary Metastases.
Diagnosis:

Radiology detects them, but fungal, mycobacterial and autoimmune diseases have radiological appearances extremely similar to pulmonary metastases; biopsy or cytology is essential for diagnosis and immunohistochemical study is commonly necessary to determine the site of the primary.

211

Pulmonary Metastases.
Treatment:

Cytotoxic chemotherapy (regimen depending on primary site), targeted therapy (e.g. cetuximab [Erbitux] for colon primary unless have KRAS mutation), {hospice}.

212

Pulmonary Metastases.
Prognosis:

Poor

213

IMPORTANT CONCEPT 17: Pulmonary metastases are more?

Common than lung primaries, usually multiple and most commonly from (in approximate order of frequency): breast, colon, stomach, pancreas, kidney, skin (melanoma), prostate, liver or thyroid.

214

Pulmonary Embolism.
Pulmonary thromboembolism
Definition:

Thrombi in the lungs that have traveled there from elsewhere in the body.

215

Pulmonary Embolism.
Pulmonary thromboembolism
Epidemiology:

Common, more common in older adults and in blacks > whites > Asians, sole or major contributing cause of death for 10% of patients dying acutely in hospitals.

216

Pulmonary Embolism.
Pulmonary thromboembolism
Risk factors:

Smoking, immobilization, malignancy, surgery, central venous instrumentation, long-haul travel, trauma, thrombophilia, obesity, oral contraceptives, pregnancy.

217

Pulmonary Embolism.
Pulmonary thromboembolism
Pathogenesis:

Deep venous thrombosis (due to Virchow’s triad of factors: endothelial injury, abnormal blood flow and hypercoagulability); endothelial injury due to blood vessel rupture or puncture, inflammatory states or toxins (smoking), abnormal blood flow including both stasis and turbulence, hypercoagulable states = congenital or acquired, including blood in contact with plastic or metal.

218

Pulmonary Embolism.
Pulmonary thromboembolism
Many pulmonary thromboemboli are from?

DVT in the legs (thigh, not calf), but more and more are from thrombi around long term central venous catheters, especially peripherally inserted central venous catheters (“PICC lines”) in the arms.

219

Pulmonary Embolism.
Pulmonary thromboembolism
Small emboli

Do not cause infarction because of the dual blood supply of the lungs

220

Pulmonary Embolism.
Pulmonary thromboembolism
Intermediate size emboli

(combined with poor bronchial circulation) cause infarcts (10%).

221

Pulmonary Embolism.
Pulmonary thromboembolism
Large emboli

Ones can obstruct the pulmonary trunk (“saddle embolus” hanging down over the heart like saddlebags), causing acute cor pulmonale and sometimes sudden death.

222

Pulmonary Embolism.
Pulmonary thromboembolism
Gross pathology:

Thromboemboli tend to be firm, variegated (mixture of purple, red, pink, tan, brown or grey), sometimes with alternating light and dark layers (lines of Zahn), tubular, branched and crammed into pulmonary arteries like coiled snakes (features differentiating them from postmortem clot).
Older thromboemboli are organized into arterial wall by fibroblast infiltration and conversion to fibrous tissue (may leave a fibrous band in the lumen)
Pulmonary infarcts tend to be subpleural, wedge-shaped and hemorrhagic.

223

Pulmonary Embolism.
Pulmonary thromboembolism
Microscopic pathology:

Thromboemboli have a variable mixture of all the elements of blood (red cells, platelets, fibrin) with condensation of the fibrin over time.

224

Pulmonary Embolism.
Pulmonary thromboembolism
Symptoms:

Dyspnea (73%), pleuritic chest pain (44%), leg pain (44%), leg swelling (41%), cough (34%), orthopnea (28%), wheezing (21%)

225

Pulmonary Embolism.
Pulmonary thromboembolism
Signs:

Tachypnea (54%), tachycardia (24%), pulmonary rales (18%), decreased breath sounds (17%), loud pulmonic component of second heart sound (15%), jugular venous distension (14%)

226

Pulmonary Embolism.
Pulmonary thromboembolism
Diagnosis:

Clinical impression 85% sensitivity and 51% sensitivity, common findings: leukocytosis, elevated erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST), arterial hypoxemia, hypocarbia and respiratory alkalosis, elevated B-type natriuretic peptide (BNP) and troponin (both +/-), chest x-ray abnormalities (88%) cardiomegaly, atelectasis, pulmonary infiltrates, pleural effusions (all nonspecific) focal oligemia (Westermark sign) or peripheral wedged-shaped opacity (Hampton hump) specific, but rare, EKG abnormalities (70%) sinus tachycardia, nonspecific ST-segment and T-wave changes, atrial fibrillation, supraventricular tachycardia, right bundle branch block or right ventricular strain pattern more specific, but rare
Spiral computed tomography with intravenous contrast 83% sensitivity and 96% specificity.

227

Pulmonary Embolism.
Pulmonary thromboembolism
Treatment:

Anticoagulation (subcutaneous low molecular weight heparin [enoxaparin, dalteparin, etc.] or subcutaneous fondaparinux or intravenous unfractionated heparin or subcutaneous unfractionated heparin followed by oral warfarin or oral dabigatran or oral rivaroxaban) +/- thrombolytic therapy.

228

Pulmonary Embolism.
Pulmonary thromboembolism
Prognosis:

30% fatal untreated, as low as 3% treated

229

IMPORTANT CONCEPT 18: Pulmonary thromboembolism is?

A common treatable, sometimes preventable condition with multiple causes, presenting most commonly with dyspnea.

230

Fat embolism
Definition:

Globules of fat traveling in the vascular circulation

231

Fat embolism
Fat embolism syndrome:

Hypoxemia, neurological impairment and petechial rash 1-3 days after trauma.

232

Fat embolism
Epidemiology:

Uncommon, most fat embolism is clinically silent, but the syndrome complicates 3% of single long bone fractures and 33% of bilateral femoral fractures (actually more common with closed fractures).

233

Fat embolism
Pathogenesis:

Most commonly from long bone fractures, but also orthopedic surgery and sickle cell bone crises, liposuction, burns, pancreatitis, osteomyelitis, etc.
1-3 day delay between trauma and syndrome could be due to metabolism of fat creating toxic intermediaries (including free fatty acids) and inflammatory response creating C-reactive protein that agglutinates lipids (or breakdown of necrotic fat.
Fat globules filtered out in the pulmonary capillary bed, if too numerous, cause respiratory failure, then later, if get through lungs (collaterals?, reforming after capillary bed?), clog cerebral capillaries, then later, can get to skin and clog capillaries there, rupturing them and causing petechiae (typically on head, neck and anterior chest)[but skin rash occurs in <50% of patients with syndrome]

234

Fat embolism
Gross pathology:

None

235

Fat embolism
Microscopic pathology:

Rounded cleared spaces in blood, which must be differentiated from air bubbles (oil-red-O stain of fresh tissue or freshly frozen tissue [or electron microscopy with osmium tetroxide of fixed tissue {not as good}]).

236

Fat embolism
Symptoms:

Dyspnea, confusion

237

Fat embolism
Signs:

Tachypnea, confusion, decreased level of consciousness.

238

Fat embolism
Diagnosis of exclusion:

History and physical in the right context, supporting findings: arterial hypoxemia, global cerebral dysfunction, petechial skin rash

239

Fat embolism
Treatment:

Supportive care (mechanical ventilation).

240

Fat embolism
Prognosis:

85-95% recovery without sequelae, 5-15% mortality for the syndrome.

241

Air embolism
Definition:

Mass(es) of air (or gas) present and traveling in the vascular circulation.

242

Air embolism
Epidemiology:

Uncommon

243

Air embolism
Pathogenesis:

Hole in blood vessel open to air at higher pressure than the blood (or formation of gas within the blood), usually occurs in 1 of 4 ways: vascular catheterization, surgery, trauma or barotrauma, disconnection or breakage of vascular catheter connections (60-90% of the vascular catheter type), upright positioning of patient during vascular catheter insertion or removal, failure to occlude needle hub or catheter during insertion or removal, deep inspiration during insertion or removal, persistent catheter tract following removal, surgery with surgical opening higher than the heart (especially brain surgery in sitting position or back surgery in prone position), traumatic blood vessel rupture (especially chest wall injury), mechanical ventilation at high pressure with blood vessel rupture in the lungs, rapid ascent during underwater diving (causing nitrogen gas bubbles to form), etc.

244

Air embolism
Gross pathology:

Can make blood bubbly or frothy, can see or feel bubbles if big enough and involved blood vessels visible or palpable.

245

Air embolism
Microscopic pathology:

Rounded cleared spaces in blood, which must be differentiated from fat globules dissolved out in tissue processing (oil-red-O stain of fresh tissue or freshly frozen tissue [or electron microscopy with osmium tetroxide of fixed tissue {not as good}])

246

Air embolism
Symptoms:

Dyspnea (near universal), sense of impending doom, lightheadedness or dizziness

247

Air embolism
Signs:

Gasp or cough when bolus enters pulmonary circulation, sucking sound, mill wheel heart murmur (churning sound heard throughout cardiac cycle), tachypnea, tachycardia, hypotension, pulmonary crackles, wheezing, change in mental status, focal neurological deficits, crepitus over superficial blood vessels, livedo recticularis, elevated jugular venous pressure.

248

Air embolism
Diagnosis of exclusion:

Supporting findings: arterial hypoxemia and hypercarbia, thrombocytopenia, elevated creatine phosphokinase, sinus tachycardia, peaked p-waves (right heart strain pattern) on EKG, nonspecific ST-segment and T-wave changes or ischemic changes on EKG, but computed tomography or echocardiography or even chest x-ray can be diagnostic of really large air emboli.

249

Air embolism
Treatment:

Left lateral decubitus positioning (Durant’s maneuver), cardiac massage, hyperbaric oxygen, supportive care (mechanical ventilation, vasopressor support, volume resuscitation)

250

Air embolism
Prognosis:

Generally, more than 100 ml needed to have a clinical effect, but 300-500 ml introduced at a rate of 100 ml/second is fatal (can be attained through a 14-gauge needle with a pressure gradient of 5 cm H2O); overall 30% mortality, down to 21% with hyperbaric oxygen, but 25% have moderate-severe neurological sequelae

251

Acute Lung Injury
Definition:

Non-cardiogenic pulmonary damage manifested by edema with an inflammatory and fibrosing response, = diffuse alveolar damage.

252

Acute Lung Injury
If due to shock or some other process affecting all of both lungs?

Then corresponds to acute respiratory distress syndrome (ARDS), a condition of arterial hypoxemia and bilateral radiographic opacities without evidence of left atrial hypertension.

253

Acute Lung Injury
Epidemiology:

Common (estimated 190,000 adult cases in US in 1999), but decreasing (maybe 100,000 cases/year in 2013, but hard data hard to find).

254

Acute Lung Injury
Pathogenesis:

Causes: lung infection, sepsis, shock, oxygen, collagen vascular disease, vasculitis, heat, burn, radiation, blood transfusion, amiodarone, methotrexate, idiopathic, etc., etc., etc., etc.

255

Acute Lung Injury
Starts with?

Edema, initially interstitial, then alveolar, sometimes with hemorrhage (when the injury kills capillary endothelial cells as well as pneumocytes) due to dysregulated inflammation (inappropriate accumulation and activity of leukocytes and platelets, uncontrolled activation of coagulation pathways, and altered permeability of alveolar endothelial and epithelial barriers

256

Acute Lung Injury
Pathogenesis:
Endogenous molecules

(danger-associated molecular patterns [DAMPs]) to pattern recognition receptors such as the Toll-like receptors on the lung epithelium and alveolar macrophages, and by innate immune effector mechanisms, such as formation of neutrophil extracellular traps (lattices of chromatin and antimicrobial factors that capture pathogens but also injure endothelium) and histone release by neutrophils.

257

Acute Lung Injury
Increased permeability of microvascular barriers?

Resulting in extravascular accumulation of protein-rich edema fluid = the central early pathophysiologic mechanism, due to disruption of the pulmonary microvascular endothelial barrier function maintained by vascular endothelial cadherin (VE-cadherin), an adherens junction protein.

258

Acute Lung Injury
The dysregulated inflammation is mediated by excess pro-inflammatory cytokines including?

IL-1, TNF and IL-8 (from alveolar macrophages) recruiting neutrophils into alveoli, activating them and loosening endothelial junctions, inadequately counteracted by anti-inflammatory cytokines such as IL-10 and anti-proteases and anti-oxidants, followed by excess fibrogenic cytokines such as TGF-beta and PDGF.

259

Acute Lung Injury
Gross pathology:

Heavy, dark red, airless, edematous (early) then progressively lighter color and denser consistency until firm and white with fibrosis (late).

260

Acute Lung Injury
Microscopic pathology:

3 phases (exudative, proliferative, fibrotic):

261

Acute Lung Injury
Microscopic pathology:
Exudative phase:

Exudative phase (days 1-4 or so) has edema (peaking around 24 hours, dissipating over next 2 days) with condensation into hyaline membranes of dense, sparsely cellular, pink, eosinophilic, proteinaceous, surfactant-rich material around the periphery of alveoli (peaking around day 3, dissipating over next 4 days), congestion (+/- hemorrhage) and neutrophils. Alveolar hyaline membranes = the histologic hallmark of the exudative phase.

262

Acute Lung Injury
Microscopic pathology:
Proliferative phase

Proliferative phase (next few weeks) has chronic interstitial inflammation (lymphocytes and macrophages, peaking around day 7), type 2 pneumocyte hyperplasia, and fibroplasia (proliferating fibroblasts).

263

Acute Lung Injury
Microscopic pathology:
Fibrosis phase

Fibrosis = interstitial and progressive for several months.

264

Acute Lung Injury
Semi-specific findings:

Lipid-laden foamy macrophage common with amiodarone toxicity, arteriolar and venular injury (+/- thrombosis) and fibrosis common with radiation

265

Acute Lung Injury
Symptoms:

Rapidly worsening dyspnea (+ symptoms of the cause, often more prominent), within 6-72 hours of inciting event (shock, toxin, whatever).

266

Acute Lung Injury
Signs:

Respiratory distress (tachypnea, tachycardia, diaphoresis, and use of accessory muscles of respiration), diffuse bilateral pulmonary crackles, +/- cough, +/- chest pain.

267

Acute Lung Injury
Diagnosis:

Progressive bilateral alveolar infiltrates on radiology and arterial hypoxemia with ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2) over 200 mmHg, with cardiac causes ruled out by echocardiography, B-type natriuretic peptide level or cardiac catheterization, etc.

268

Acute Lung Injury
Treatment:

Mechanical ventilation, but with lung-protective ventilation (lower tidal volumes [+/- lower airway pressures]). Fluid-conservative resuscitation. Numerous other interventions.

269

Acute Lung Injury
Prognosis:

Mortality of ARDS has decreased from around 50% to about 20%

270

IMPORTANT CONCEPT 19: Acute lung injury is a common condition with a myriad of causes?

Presenting with rapidly progressive dyspnea and bilateral pulmonary infiltrates superimposed on the manifestations of the cause.

271

Non-infectious Interstitial Lung Disease.
Radiation pneumonitis.
Definition:

A form of acute lung injury, typically occurring 1 to 2 months after radiation.

272

Non-infectious Interstitial Lung Disease.
Radiation pneumonitis.
Patients present:

With dyspnea, cough, pleuritic chest pain, fever and x-ray infiltrates.

273

Non-infectious Interstitial Lung Disease.
Radiation pneumonitis.
Microscopic pathology:

Atypical type 2 pneumocyte hyperplasia and blood vessel injury are features of this, which are added to all the other histopathologic features of acute lung injury. Late radiation pneumonitis can demonstrate residual hemosiderin from earlier bleeding, interstitial lymphocytes from ongoing chronic inflammation, active fibroblasts and early interstitial fibrosis, commonly most severe around small blood vessels, which are particularly vulnerable to radiation injury.

274

Non-infectious Interstitial Lung Disease.
Usual Interstitial Pneumonia(UIP) / Idiopathic Pulmonary Fibrosis (IPF).
Definition:

Prototype chronic, slowly progressive, fibrosing inflammatory disease of the lungs involving predominantly the septa between airspaces.
[Usual interstitial pneumonia is what pathologists usually see on the slides from the lungs of patients with what clinicians call idiopathic pulmonary fibrosis, although other lung diseases can also give rise to this pathologic pattern and some add the term “idiopathic” in front of “UIP” when correlated with IPF.]

275

Non-infectious Interstitial Lung Disease.
Usual Interstitial Pneumonia(UIP) / Idiopathic Pulmonary Fibrosis (IPF).
Epidemiology:

Uncommon, typically in late middle-aged patients (in their 50s or 60s), twice as common in men, with no racial or geographic predilection, majority smokers.

276

Non-infectious Interstitial Lung Disease.
Usual Interstitial Pneumonia(UIP) / Idiopathic Pulmonary Fibrosis (IPF).
Pathogenesis:

An enigma, really, but the leading theories involve recurring acute lung injury in small foci due to aspiration of gastric acid and pepsin, imbalance of oxidative-antioxidant systems, autoimmune attack or viral infection, causing an abnormal fibrosing repair response. Acute exacerbations with acute lung injury superimposed on UIP are common.

277

Non-infectious Interstitial Lung Disease.
Usual Interstitial Pneumonia(UIP) / Idiopathic Pulmonary Fibrosis (IPF).
Gross pathology:

Fibrosis without large discrete scars, making the lung firmer and more grey than normal, worse in the periphery (especially subpleural) and in the lower lobes, giving the visceral pleural surface a nodularity similar to cirrhosis of the liver, culminating in honeycomb lung.

278

Non-infectious Interstitial Lung Disease.
Usual Interstitial Pneumonia(UIP) / Idiopathic Pulmonary Fibrosis (IPF).
Microscopic pathology:

Strikingly non-uniform patchy interstitial inflammation, repair response (fibroblast foci of immature fibrosis bulging into alveoli from interstitium = hallmark) and fibrosis, with temporal heterogeneity (simultaneous presence of early, intermediate and late fibrosing lesions).

279

Non-infectious Interstitial Lung Disease.
Usual Interstitial Pneumonia(UIP) / Idiopathic Pulmonary Fibrosis (IPF).
Symptoms:

Insidious onset of dyspnea, commonly with a dry cough.

280

Non-infectious Interstitial Lung Disease.
Usual Interstitial Pneumonia(UIP) / Idiopathic Pulmonary Fibrosis (IPF).
Signs:

Dry inspiratory (“Velcro”) pulmonary crackles at the bases, +/- clubbing of fingers.

281

Non-infectious Interstitial Lung Disease.
Usual Interstitial Pneumonia(UIP) / Idiopathic Pulmonary Fibrosis (IPF).
Diagnosis:

Radiology: asymmetric bilateral irregular reticular (or reticulonodular) opacities at the bases and periphery, +/- ground-glass change (not too much), traction bronchiectasis, honeycomb change (late, initially subpleural, worst = cystic). Pulmonary function tests: restrictive pattern.

282

Non-infectious Interstitial Lung Disease.
Usual Interstitial Pneumonia(UIP) / Idiopathic Pulmonary Fibrosis (IPF).
Definitive diagnosis:

Open lung biopsy (if clinical and radiologic features are not sufficient for diagnosis).

283

Non-infectious Interstitial Lung Disease.
Usual Interstitial Pneumonia(UIP) / Idiopathic Pulmonary Fibrosis (IPF).
Treatment:

Transplantation Corticosteroids + immunosuppressive drugs + interferon-gamma = all proven not to work.

284

Non-infectious Interstitial Lung Disease.
Usual Interstitial Pneumonia(UIP) / Idiopathic Pulmonary Fibrosis (IPF).
Prognosis:

Bad. Typically die of respiratory failure 2-3 years following diagnosis. Important to differentiate UIP from cryptogenic organizing pneumonia (“COP”) and nonspecific interstitial pneumonia (“NSIP”), which do respond to steroid therapy.

285

IMPORTANT CONCEPT 20: Usual interstitial pneumonia is an?

Idiopathic chronic fibrosing lung disease that presents in late middle-aged male smokers with the insidious onset of dyspnea, commonly with a dry cough.

286

Non-infectious interstitial lung disease in general.
In general: acute/chronic? specific/idiopathic?

Chronic and Idiopathic.

287

Non-infectious interstitial lung disease in general.
Current categories of interstitial lung disease

Include usual interstitial pneumonia, cryptogenic organizing pneumonia, nonspecific interstitial pneumonia and interstitial lung disease associated with autoimmune collagen vascular disease (among many other categories).

288

Non-infectious interstitial lung disease in general.
Cryptogenic organizing pneumonia (“COP”)
Define:

The new name for bronchiolitis obliterans - organizing pneumonia (“BOOP”). Organizing pneumonia is commonly from necrotizing infection (not cryptogenic).

289

Non-infectious interstitial lung disease in general.
Cryptogenic organizing pneumonia
Etiology/Demographics:

Rare idiopathic subacute fibrosing lung disease, typically occurring in late middle aged patients (average age 55), equally frequently in men and women, the majority non-smokers.

290

Non-infectious interstitial lung disease in general.
Cryptogenic organizing pneumonia
Gross Pathology:

Organizing pneumonia is granulation tissue in alveoli (airspaces) and the histologic hallmark is plugs of fibrosing granulation tissue in the alveoli (and alveolar ducts). These are called Masson bodies.

291

Non-infectious interstitial lung disease in general.
Cryptogenic organizing pneumonia
Presentation:

The patients present with cough, which is sometimes productive of mucus and dyspnea. They may have intermittent fever, chills, night sweats, myalgias and even weight loss. They have dry inspiratory crackles.

292

Non-infectious interstitial lung disease in general.
Cryptogenic organizing pneumonia
Diagnosis:

Radiographs show bilateral opacities that are less dense than acute bacterial pneumonia or tumor and referred to as “ground glass”. There may be air bronchograms, pleural-based areas of more dense opacity and other findings.

293

Non-infectious interstitial lung disease in general.
Cryptogenic organizing pneumonia
Treatment:

The really important thing about COP is that it usually responds to steroid therapy and has a much better prognosis than UIP.

294

Non-infectious interstitial lung disease in general.
Nonspecific interstitial pneumonia (“NSIP”)
Define:

As the term is officially used since 2002 gets a prize for idiotic terminology because it is used to denote a SPECIFIC entity. This specific entity called nonspecific specifically differs from UIP in being rare, being much more common in women (usually middle-aged), the majority never smokers.

295

Non-infectious interstitial lung disease in general.
Nonspecific interstitial pneumonia (“NSIP”)
Disease:

The disease is temporally homogeneous. It can be more inflammatory than fibrotic (“cellular” type) or more fibrotic than inflammatory (“fibrotic” type, presumably later and more advanced), but all areas of involvement will be at the same stage and it less patchy than UIP.

296

Non-infectious interstitial lung disease in general.
Nonspecific interstitial pneumonia (“NSIP”)
Presentation:

The patients present with the usual dyspnea and cough. Radiographs show bilateral ground glass opacities.

297

Non-infectious interstitial lung disease in general.
Nonspecific interstitial pneumonia (“NSIP”)
Treatment/Prognosis:

The really important thing about NSIP is that it usually responds to steroid therapy and has a much better prognosis than UIP.

298

IMPORTANT CONCEPT 21: Cryptogenic organizing pneumonia and nonspecific interstitial pneumonia need distinguished from?

Usual interstitial pneumonia because they respond to steroid therapy and usual interstitial pneumonia does not.

299

Pneumothorax.
Definition:

Air in the pleural space between lung and chest wall

300

Pneumothorax.
Epidemiology:

Uncommon, typically in tall thin young male smokers in their 20s (spontaneous type) or older adult smokers with chronic obstructive pulmonary disease (secondary type), but also occurs in cystic fibrosis, Marfan syndrome, pneumocystosis, trauma, high pressure mechanical ventilation, subclavian (or jugular) central venous catheter insertion “misadventures”, tuberculosis and (rare) thoracic endometriosis

301

Pneumothorax.
Pathogenesis:

Rupture of subpleural bleb, allowing air at positive pressure into pleural space, which has negative pressure during inspiration, causing some degree of atelectasis (lung collapse).

302

Pneumothorax.
Tension pneumothorax:

One-way valve effect allowing air into, but not out of pleural space, so that it attains high pressure, typically causing total collapse of lung (rare, 1% of pneumothoraces)

303

Pneumothorax.
Gross pathology:

Atelectasis, rupture rarely big enough to see, air may audibly rush out with opening tension pneumothorax

304

Pneumothorax.
Microscopic pathology:

Atelectasis.

305

Pneumothorax.
Symptoms:

Sudden onset of dyspnea and chest pain on the side of the pneumothorax.

306

Pneumothorax.
Signs:

Diminished breath sounds, hyperresonant percussion and decreased chest excursion on the affected side, may have subcutaneous emphysema.

307

Pneumothorax.
Diagnosis:

Chest x-ray: white visceral pleural line (may be hard to differentiate from fibrous rim of emphysematous bulla), commonly have hypoxemia (but that’s not specific).

308

Pneumothorax.
Treatment:

100% oxygen (greatly speeds resorption), needle aspiration (if large or symptomatic), chest tube insertion (if patient clinically unstable), pleurodesis (if bad, to prevent recurrence).

309

Pneumothorax.
Prognosis:

Good (but recurrence common, esp. if patient continues to smoke).

310

Pneumonia:
Define:

Inflammation of lung.

311

Aspiration pneumonia:
Define:

Acute bacterial pneumonias due to large volume aspiration of gastroesophageal contents or food misrouted from the oropharynx.

312

Pulmonary infiltrate:
Define:

Radiologic manifestation of pneumonia or edema or hemorrhage (blood, pus or water in the lung).

313

Consolidation:
Define:

Manifestations of alveoli filled with blood, pus or water on physical examination or radiology.

314

Acute Bacterial Pneumonia Types

A. Pneumococcus
B. Staphylococcus aureus
C. Legionella
D. Pseudomonas
E. Mycoplasma

315

Fungal and Mycobacterial Pneumonia Types

A. Tuberculosis
B. Histoplasmosis
C. Aspergillosis
D. Cryptococcosis
E. Pneumocystis pneumonia

316

Specific Types of Lung Cancer:

A. Adenocarcinoma
B. Adenocarcinoma in situ
C. Squamous cell carcinoma
D. Small cell carcinoma

317

Pulmonary Embolism Types:

A. Thromboembolism
B. Fat embolism
C. Air embolism

318

Non-infectious Interstitial Lung Disease Types:

A. Radiation pneumonitis
B. Usual interstitial pneumonia
C. Non-infectious interstitial lung disease in general