Lung Flashcards
1
Q
Diagnosis, name of finding, etiology
A
- Small cell carcinoma
- Azzopardi effect
- Tumor DNA debris deposition in vessel wall
2
Q
A
3
Q
What is the pathogenesis of hypersensitivity pneumonitis?
A
- Triggered by immunologic reaction to inhaled organic antigens or simple chemicals
- Combination of immune complex (type 3) and T-cell mediated (type 4) hypersensitiviy reaction
4
Q
List 5 pathogens that cause hypersensitivity pneumonitis
A
- Farmer’s lung (Saccharopolyspora rectivirgula), moldy hay
- Sugarcane workers lung (Thermoactinomyces saccharai)
- Maple bark workers (Cryptostroma corticale)
- Bird keeper’s lung (from bird droppings)
- Fungi from stagnant water in air conditioners, swimming pools, central heating vents
5
Q
Describe the clinical presentation of hypersensitivity pneumonitis at different stages
A
Acute: occurs in previously sensitized individuals, abrupt fever, chills, cough, dyspnea, subsiding over hours/days
Subacute: incidious over days/weeks, cough and dyspnea
Chronic: insidious, dry cough, fatigue, malaise, s/s of airway obstruction, PFT show restrictive pattern
6
Q
Describe the pathology of hypersensitivity pneumonitis at different stages
A
Acute: neutrophilic infiltrate in alveoli and respiratory bronchioles, diffuse alveolar damage
Subacute: lymphocytic interstitial infiltrate, poorly formed granulomas, focal organizing pneumonia (fibroblastic polyps/plugs), eosinophils and neutrophils NOT PROMINENT
Chronic: cellular chronic bronchiolitis with peribronchial interstitial mononuclear cell infiltrate, poorly formed nonnecrotizing granulomas, focal organizing pneumonia (fibroblastic plugs), eosinophils scant or absent, intersitial fibrosis
7
Q
List the three most consistent and diagnostic histologic features of hypersensitivity pneumonitis
A
- A temporally uniform chronic interstitial pneumonia with peribronchial accentuation
- non-necrotizing granulomas (poorly formed)
- foci of organizing changes (fibroblastic plugs)
8
Q
List 3 findings in a BAL from a patient with hypersensitiviy pneumonitis
A
- Marked lymphocytosis (often >50%), with CD3+, CD8+, CD56+, CD57+, CD10-
- decreased CD4+/CD8+ ratio
- Increased numbers of mast cells >1%
9
Q
List 4 variants of squamous cell carcinoma in the lung
A
- Papillary
- Clear cell
- Small cell
- Basaloid
10
Q
What is combined small cell carcinoma?
A
- Admixture of small cell carcinoma wiht any type of non-small cell carcinoma components
- For combined, need at least 10% of the component
11
Q
List the subtypes of adenocarcinoma
A
HIstologic subtypes: mixed (most common), lepidic, acinar, papillary, solid (solid with mucin production >5 mucin + cells in each of 2 hpf)
12
Q
List the variants of adenocarcinoma
A
- Fetal adenocarcinoma
- Invasive mucinous
- colloid (previous mucinous cyastadenoma)
- enteric (looksl like colorectal)
rare variants: hepatoid, adenomatoid, endometrioid-like, warthin-like
13
Q
List 5 variants of large cell carcinoma
A
- Large cell neuroendocrine carcinoma
- Basaloid carcinoma
- Lymphoepithelioma-like carcinoma
- Clear cell carcinoma
- Large cell carcinoma with rhabdoid phenotype
14
Q
What are the diagnostic criteria of adenosquamous carcinoma?
A
admixture of adeno and squamous cell carcinoma components
each component at least 10%
15
Q
How do you distinguish pleomorphic carcinoma from carcinosarcoma?
A
- Pleomorphic carcinoma composed of any type of non-small cell carcinoma containing spindle cells and/or giant cells, or a carcinoma consisting only of spindle and giant cells, with a spindle/giant cell component >10% of tumor
- Carcinosarcoma composed of an admixture of carcinoma and sarcoma with differentiated sarcomatous elements such as malignant cartilage, bone or skeletal muscle
16
Q
List 3 salivary gland tumors of the lung
A
- Mucoepidermoid carcinoma
- Adenoid cystic carcinoma
- Epithelial-myoepithelial carcinoma
17
Q
Describe the diagnostic criteria of adenocarcinoma in situ of the lung
A
- Pure lepidic pattern
- Smaller than 3 cm
- No invasion into stroma (previously bronchioalveolar carcinoma)
18
Q
Describe the diagnostic criteria of minimally invasive carcinoma (MIA)
A
- Includes the diagnostic criteria of adenocarcinoma in situ (i.e. 3cm max, lipidic pattern, no LVI, no pleural invasion, no necrosis etc)
- Invasion <0.5 cm
19
Q
List 5 subtypes of invasive adenocarcinoma
A
- Lepidic predominant (non-mucinous, predominant lepidic, >0.5cm)
- Acinar predominant
- Papillary predominant
- Micropapillary predominant
- Solid predominant with mucin production (>5 mucin producing cells in 2 HPFS)
20
Q
What qualifies for invasion in lung carcinoma?
A
- Histologic pattern other than lepidic
- Myofibroblastic stroma associated with invasive tumor cells
- tumor invading lymphatics, blood vessels or pleura
- presence of tumor cell necrosis
21
Q
LIst 4 variants of invasive adenocarcinoma of the lung
A
- Mucinous
- COlloid
- fetal
- enteric (can have same morphology/IHC as colorectal, must show >50% of this differentiation
22
Q
List 3 pre-invasive lesions of the lung and their diagnostic criteria
A
- squamous cell dysplasia/squamous cell carcinoma in-situ (increased NC ratio, hyperchromasia and coarse chromatin, disorientation and loss of maturation, nuclear angulations, folding, pleomorphism; all changes upto full thickness of epithelium)
- Atypical adenomatous hyperplasia (lepidic pattern,<0.5cm)
- adenocarcinoma in-situ (AIS); pure lepidic pattern, no LVI/pleural inv/necrosis, <3cm
- Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (widespread proliferation of pulmonary neuroendocrine cells, confined to bronchial/bronchioalr epithelium, absence of inflammatory/fibrous lesions, accompanying tumorlets or carcinoid)
23
Q
List the spectrum of neuroendocrine tumors
A
- typical carcinoid
- atypical carcinoid
- large cell neuroendocrine carcinoma
- small cell carcinoma
24
Q
Describe the diagnostic criteria for each group of pulmonary endocrine tumors
A
Typical carcinoid: mitoses
Atypical carcinoid: mitoses 2-10/10HPF and or foci of tumor cells
Large cell neuroendocrine carcinoma: neuroendocrine morphology, mitoses >11/10 HPF, large zones of necrosis, neuroendocrine differentiation on IHC
Small cell carcinoma: size lest than 3x lymphocyte, scant cytoplasm/naked nuclei with molding, hyperchromatic nuclei, finely granular chromatin, nucleoli absent, increaed mitotic figures AVERAGING >60/10HPF, prominent crush artefact/Azzopardi effect, tumor cell necrosis
25
List 3 commonly used IHC markers for neuroendocrine tumors
- chromogranin
- synaptophysin
- CD56
26
What are the features of neuroendocrine tumors on EM?
Neurosecretory granules (dense core granules)
Low grade lesions have many, high grade have fewer
27
What are the diagnostic criteria for neuroendocrine cell hyperplasia, tumorlet, carcinoid
Neuroendocrine cell hyperplasia: proliferation of neuroendocrine cells confined to the epithelium of airways without penetration of basement membrane
Tumorlet: proliferation of neuroendocrine cells extending through basement membrane, less than 5mm in size
Carcinoid: nodular lesion of neuroendocrine cells \>5mm
28
List 8 important parameters for pathology reports of lung cancer
Histologic type
Pathologic staging
Tumor size
extent (eg. involving visceral pleura, main bronchus, chest wall, mediastinum)
resection margins
lymph node status
lymphatic and vascular invasion
29
List 3 IHC stains used to diagnose Squamous cell carcinoma of lung
- High molecular weight keratin (34BE12, CK5/6) +
- p63 +
- TTF-1 negative
30
List 3 IHC stains used to diagnose adenocarcinoma of the lung
- TTF-1 (75% +)
- CK7+
- p63 neg
- Napsin A +
31
List 5 immunostains positive in small cell carcinoma of the lung
- TTF-1
- chromogranin
- synaptophysin
- AE1/AE3 (perinuclear dot)
- CD56
32
List 3 subtypes of malignant mesothelioma
- Epithelioid
- Sarcomatoid
- Biphasic
33
List 2 stains that can be used to differentiate benign from malignant mesothelial cells
Bening: EMA neg, Desmin +
Malignant: EMA +, Desmin -
34
Describe cytologic features of malignant mesothelioma
- Cellular specimen, with epithelioid cells
- sheets/cluster/3d morulae/papillae usually \>12 cells per cluster
- +/- psammoma bodies
- Maintain mesothelial features including villi, windows, dense biphasic cytoplasm
- lack atypia seen in carcinoma
- no 2nd population of cells
35
List IHC stain panel used to differentiate malignant mesothelioma from bronchogenic adenocarcinoma
Positive in mesothelioma: calretinin, CK5/6, WT1, D240
Positive in adenoca: CEA, TTF-1, MOC31, B72.3, LeuM1 (CD15)
36
List 2 EM findings of malignant mesothelioma
- Branched bushy microvilli
- Tonofilaments surrounding nucleus
37
What is the clinical definition of chronic bronchitis?
- Persistent cough with sputum production for at least 3 months in 2 consequtive years, in absence of other identifiable causes
38
Describe pathogenesis of chronic bronchitis
- Long-standing irritation by inhaled substances (tobacco, environmental dust) results in hypersecretion of mucous in large airways with hypertrophy of submucosal glands
- Proteases released from neutrophils and MMPs are stumulatory
- Marked increase in goblet cells in small airways leading to obstruction
- Cigarette smoke interferes with ciliary action of respiratory epitheliumk, damaging airway epithelium and inhibiting leukocytes ability to clear bacteria
39
List 4 pathogenic factors in chronic bronchitis
- Cigarette smoking
- Environmental causes
- Chronic irritation/inflammation
- Infections
40
List 4 microscopic features of chronic bronchitis
- Chronic inflammation of the airways-lymphocytic
- Mucous gland hyperplasia of the trachea/bronchi
- Reid index \>0.4- ratio of thickness of mucous gland layer to thickness of wall between BM of bronchial epithelium and perichondrium of bronchial cartilage
- Marked narrowing of bronchioles-caused by mucous plugging, inflammation, fibrosis
41
Define emphysema
- Abnormal and permanent enlargement of airspaces distal to terminal bronchiole with destruction of walls
42
Describe the pathogenesis of emphysema
- Imbalance of proteases and their inhibitors leads to destruction of lung tissue
- Inflammatory cells, mediators and oxidative stress
- Cigarette smoking is cause of centriacinar emphysems
- alpha-1-antitrypsin is associated with panacinar emphysema
43
List 4 common types of emphysema and define each type
Centriacinar: distension/destruction involving proximal portionor respiratory bronchioles
Panacinar: distension and destruction of entire acinus, causing diffuse/bilateral lung involvmenet
Paraseptal: distension/destruction involving distal alveolar duct/alveoli in subpleural/paraseptal
Irregular: irregular airspace enlargement/destruction associated with a scar
44
List 4 causes of emphysema
- Cigarette smoking (centriacinar)
- Chronic inflamamtion
- A-1-antitrypsin-panacinar
- scarring-irregular emphysema
- IV drug abuse, Marfan
45
Define granuloma
- Focus of chronic inflammation consisting of a microscopic aggregation of macrophages surrounded by a colar of mononuclear leukocytes
- Macrophages often tranformed into epithelioid cells, which often fuse to form multinucleate giant cells
- Giant cells may have haphazard nuclei (FB type) or peripherally located (Langhans-type)
46
Give 5 examples of non-necrotizing granulomas
- Sarcoidosis
- Berylliosis
- Sarcoid reaction
- Hypersensitivity pneumonitis
- Foreign body granuloma
47
List 4 examples of necrotizing granulomas
- TB/atypical mycobacteriosis
- Mycoses (histoplasmosis, cryptococcus, blastomycosis, coccidiomycosis)
- Syphilis
- Necrotizing sarcoid granulomatosis
48
List 3 granulomas accompagnied by necrotizing bronchiolitis
- Tuberculosis/atypical mycobacteriosios
- mycoses
- bronchocentric granulomatosis (allergic bronchopulmonary fungal disease, Wegener's, rheumatoid arthritis)
49
list 5 examples of granulomas with vasculitis in the lung
- Infection
- Wegeners
- Churg-Strauss
- Sarcoidosis
- Necrotizing sarcoid granulomatosis
50
What are 2 synonyms for pulmonary eosinophilic granuloma
Langerhan's cell histiocytosis, Histiocytosis X
51
Describe the clinical features of pulmonary eosinophilic granuloma
- Adults with smoking history
- Variable presentation from asymptomatic to rapidly progressive dyspnea, cough, chest pain, fatigue, pneumothorax (25%)
- Extrapulmonary involvement in 10-15%
- Can occur in children as isolated lesion or multisystem
- No increase in peripheral eosinophils on CBC!!!
52
What are the radiologic features of eosinophilic granuloma in the lung?
- XR: intersitial process with predilection for mid/upper lobes sparing costophrenic angles
- CT: small nodules/cystic spaces with upper/mid lung patchy distribution
53
List 4 microscopic features of pulmonary eosinophilic granuloma
- Multiple nodular lesions centered on bronchioles with a stellate border
- Langerhans cells with moderate eosinophilic cytoplasm, indistinct cell borders, bean shaped nuclei, prominent nuclear grooves
- Variable numbers of eos
- spectrum of disease from cellular infiltrate to stellate fibrotic tissue
54
List 4 positive IHC stains in eosinophilic granuloma
- S100
- CD1a
- Vimentin
- CD68
55
List 2 common extrapulmonary organs involved with eosinophilic granuloma
- Bone
- Lymph nodes
56
What is the diagnostic ultrastructural finding of pulmonary eosinophilic granuloma?
Birbeck granule
57
Describe the etiology and pathogenesis of CF
- CF gene on chromosome 7 encodes CFTR (cystic fibrosis transmembrane regulator)
- CFTR expressed in epithelial cells in lung, GI tract, etc.
- Mutations result in inability to secrete salt (and H20) with excessive reabsorption of salt and water leading to dessication of luminal secretions
- Mucous plugging and decreaed clearance predispose to bacterial growth
58
Describe the clinical features of CF in lungs, GI tract and other organs
- Lungs: wheezing, chronic cough, recurrent infections, hemoptysis
GI: meconium ileus, steatorrhea, malapsorption, rectal prolapse, biliary cirrhosis, portal HTN, hypoproteinemia, vitamin deficiency, recurrent pancreatitis
- GU: infertility
- Upper respiratory: nasal polyps, pansinusitis
- Failure to thrive
59
List 8 pathologic findings of CF in lungs
- Acute and chronic bronchitis, bronchiolitis, pneumonia
- Purulent mucous plugging
- Bronchiectasis and bronchostenosis
- Constrictive bronchiolitis and peribronchiolar scarring
- Abcess
- Atelectasis
- Emphysema
- Interstitial inflammatory infiltrate/fibrosis
60
List 3 gross findings in CF lungs
- Bronchiectasis and purulent airway mucous
- Atelectasis and pneumonic consolidation
- Emphysematous changes with bullae formation
61
LIst 5 extrapulmonary manifestations of CF
- Sinusitis
- nasal polyps
- pancreatitis
- biliary cirrhosis
- acrodermatitis
62
What 2 microorganisms cause lung infections in CF
- S. aureus
- H. influenzae
63
What are 2 synonyms for Kartagener's
immotile cilia, ciliary dyskinesia
64
What is the normal ultrastructure of cilia?
- 3-6 microns in length, main body formed by central pair with 9 peripheral doublets of microtubules
- Each doublet has complete tubula with attached 3/4circles of B subfiber
- 2 rows of denein arms from a subfiber protrude towards b subfiber of adjacent doublet, and one raidal spoke extends towards central pair
65
List 4 common presentations of Kartagener's
- Bronchiectasis
- Situs inversus
- Sinusitis
- Infertility
66
List the ultrastructural findings of cilia in Kartagener's
- Absent/shortened dynein arms
- Absence of radial spokes
- Absence/transposition/disarrangement of microtubules
- Presence of compound cilia and ciliary disorientation
67
What specimens are submitted for evaluation of respiratory cilia?
- Brush or scrape specimens from nose/airways
- EM to assess ciliary structure
68
Define diffuse alveolar damage
- Histologic pattern of acute lung injury
- presents as acute respiratory distress syndrome
- Hyaline membrane formation and or organizing interstitial changes are present
- diffuse means diffusely involving alveolus, may have pathcy distribution in lung
69
List at least 10 causes of diffuse alveolar damage
- Infection
- Shock
- Trauma (lung contusion, head injury)
- Inhalational injury (smoke, corrosive chemical)
- aspiration of gastric contents
- drugs
- metabolic disorders (uremia, pancreatitis)
- radiation
- DIC
- idiopathic AKA ACUTE INTERSTITIAL PNEUMONIA
- burngs, near drowning, venous air embolism, IV contrast, high altitute
70
What are the radiologic findings in DAD by stage?
12-24hrs: decreased lung volume
\>24 hrs: patchy airspace consolidation, then confluent/diffuse involvement rapidly progressing
resolving: gradual replacement of consolidated areas by ground glass and then reticular opacities
71
List the main histologic features and stages of diffuse alveolar damage
Acute/exudative phase: pulmonary congestion, interstitial/alveolar edema with fibrin deposition, alveolar wall damage, hyaline membrane formation
Organizing/proliferative phase: type 2 pneumoncyte proliferation, interstitial fibroblast proliferation with edematous stroma, fibrotic thickening of alveolar septa
Fibrotic/chronic phase: intersitial fibrosis, honeycomb changes
72
Describe the pathogenesis of DAD
- Lung injury by imbalance of pro-inflammatory and anti-inflammatory mediators, leading to pro-inflammatory state
- Activated neutrophils release a variety of mediators (proteases, oxidants, platelet activating factor, leukotrienes)
- Results in damage to alveolar capillary membrane with endothelial injury, followed by increased vascular permeability, widespread surfactant abnormality
- Endothelial injury also causes microthrombi
- Hyaline membranes result from inspissation of protein-rich edema fluid and debris of dead alveolar cells
- Balance between destructive/protective factors determines degree of tissue injury
73
List 8 causes of organizing pneumonia
- Idiopathic
- Collagen vascular disease
- Drug reaction
- Infection (viral, bacterial, HIV, PCP)
- Hypersensitivity pneumonitis
- Radiation
- Hemorrahge
- Non-specific reaction to adjacent tumor, abcess, infarct etc.
74
Describe the clinical features of organizing pneumonia
- Acute/subacute onset, 40-60 yrs
- Non-productive cough, SOB
- Fever, malaise, fatigue, weight loss
- Restrictive pattern on PFTs
75
List 4 microscopic features of organizing pneumonia
- Organizing fibrosis with fibroblastic plugs in distal airspaces including bronchioles, alveolar ducts, alveoli
- Uniform temporal appearance and patchy distribution
- Mild interstitial chronic inflammation
- Preservation of lung architecture
76
What is UIP?
- Idiopathic histologic pattern of interstitial lung disease (IPF)
- similar pattern seen in collagen vascular disease, drug reaction
77
Describe the clinical features of UIP
- 50-70 yrs, M\>F
- Insidious onset dyspnea, non-productive cough, digital clubbing
- Slowly progressive with poor prognosis
- Constitutional symptoms uncommon
78
List 3 common causes of a UIP pattern
- Idiopathic
- collagen vascular disease
- drug reaction
- others; radiation, pneumoconioses (asbestos)
79
What are the main histologic features of UIP?
Patchy lung involvement with peripheral/paraseptal predominance and preserved normal alveolar architecture
- Temporally variegated appearance
- Dense collagen fibrosis, fibroblastic foci, honeycomb change
- Interstiial inflammation, smooth muscle proliferation, focal alveolar macrophage accumulation, lymphoid aggregates
80
Describe the clinical presentation of lymphangioleiomyomatosis
- Sporadic or with TSC
- young women of reproductive age, 20-40
- caucasians
- dyspnea, cough, chest pain
- complications include spontaneous pneumothorax, hemoptysis, chylothorax, chyloperitoneu, chyluria, chylopericardium
81
Describe 2 radiologic features of lymphangioleiyomyomatosis
- cystic, evenly distributed lung lesions
- diffuse reticular infiltrates with hyperinflation
82
List 4 disorders in same family as lymphangioleiyomyomatosis
- Tuberous sclerosus
- micronodular pneumocyte hyperlasia
- angiomyolipoma
- clear cell tumor of lung
- pecoma
83
List 2 main histologic features of lymphangioleiomyomatosis
- Variable sized cystic spaces lined by plaques or nodular aggregates of smooth-muscle-like spindle cells
- Spindle cells admixed with more rounded epithelioid cells (perivascular epithelioid cells)
84
List 4 IHC stains helpful to make diagnosis of lymphangioleiyomyomatosis
- HMB45+
Desmin+
- actin +
ER+
85
List some etiologies of Diffuse Alveolar Damage
- Infections (viruses, mycoplasma, other)
- inhaled toxins (oxygen, smoke)
- Drugs (amiodarone, chemo drugs)
- Shock (traumatic, cardiogenic)
- Sepsis (any organism)
- Misc (radiation, burns, cardiopulmonary bypass)
- Pancreatitis
- SLE
86
Name 5 processes that may demonstrate an organizing pneumonia-like pattern
- Idiopathic BOOP
- collagen vascular disease
- toxins
- organizing infection
- proximity fo space occupying lesion (neoplasm, abcess, granuloma)
- Distal to bronchiectasis
- Acute infection
87
List the pulmonary manifestations of the following connective tissue diseases:
- Rheumatoid arthritis, SLE, Scleroderma, Polymyositis and dermatomyositis, Sjogren
RA: non-specific pleuritis, necrobiotic nodules, intersitial pneumonia/fibrosis, vasculitis, pulmonary hypertension
SLE: chronic interstitial pneumonia, DAD, intraalveolar hemorrhage, vasculitis, pulmonary hypertension
Scleroderma: interstitial fibrosis (UIP like), NSIP like, pulmonary HTN
Polymyositis/dermatomyositis: interstitial fibrosis, organizing pneumonia
Sjogren: lymphocytic inflammation of tracheobronchial glands, peribronchiolar lymphocytic inflammation, lymphoid hyperplasia, lymphomas (MALT)
88
List 6 pulmonary manifestations of drug reactions
- Chronic interstitial pneumonia
- diffuse alveolar damage
- organizing pneumonia
- Obliterative bronchiolitis
- eosinophilic pneumonia
- pulmonary hemorrahge
- pulmonary edema
- pulmonary veno-occlusive disease
- large and small vessel vasculitis
89
List 4 etiologies implicated in hypersensitivity pneumonitis
- Thermophilic actinomyces
- Molds
- Animal proteins
- drugs (methotrexate, amiodarone)
90
Tracheal lesion, diagnosis?
glomus tumor
91
List 6 disorders associated with asbestos exposure
- asbestosis
- benign asbestos effusion
- hyaline pleural plaques
- rounded atelectasis
- lung carcinoma
- malignant mesothelioma
92
What are the methods to quantify asbestos burden in the lungs?
- Quantifying asbestos bodies in tissue sections by H&E or Prussian blue stain (2/cm2)
- COunting asbestos bodies in lung tissue digest preparations with a light microscope
- COunting uncoated asbestos fibers in lung digest preparations with phase microsope
COunting uncoated asbestos fibers by EM
93
What are the diagnostic criteria for asbestosis?
Presence of pulmonary interstitial fibrosis with or without associated visceral pleural fibrosis
Presence of asbestos bodies
94
Pulmonary Hypertension what is the current clinical classification of pulmonary hypertension?
1. Pulmonary arterial hypertension
2. Pulmonary hypertension due to left heart disease
3. Pulmonary hypertension due to lung disease/hypoxia
4. Chronic pulmonary thromboembolic hypertension
5. Pulmonary hypertension with unclear/multifactorial mechanisms
95
Pulmonary hypertension: For Pulmonary arterial hypertension, give 8 causes
- Idiopathic
- Heritable
- Drug and toxin induced
- Pulmonary veno-occlusive disease +/- capillary hemangiomatosis
- Other associations: connective tissue disease, HIV, portal HTN, systemic/pulmonary shunts, schistosomiasis, chornic hemolytic anemia
96
Pulmonary hypertension due to left heart disease; give 3 mechanisms within the heart
- Valvular disease
- Systolic dysfunction
- Diastolic dysfunction
97
Pulmonary hypertension due to intrinsic lung disease: give 5 examples
- COPD
- Interstitial lung disease
- sleep apnea
- chronic exposure to high altitude
- bronchopulmonary dysplasia
98
List 5 histologic changes of primary pulmonary arterial hypertension
- Medial hypertrophy and muscularization of arterioles
- Cellular proliferation of intima/concentric intimal fibrosis
- Angiomatoid lesions
- Plexiform lesions
- Fibrinoid necrosis
99
PUlonary hypertension: In what setting is the Heath and Edwards grading system useful?
- Designed to assess severity of pulmonary hypertension in the setting of congenital heart disease, has 6 grades (encompasses all histologic features)
- grade 1: medial thickening of medial arteries
- grade 2: cellular intimal proliferation limited to small muscular arteries
- grade 3: medial hypertrophy and concentric intimal fibrosis
- grade 4: progressive generalized arterial dilatation with plexiform lesions
- grade 5: prominent pleiform lesions and angiomatoid lesions
- grade 6: necrotizing arteritis
100
What are the characteristic histologic changes in pulmonary veno-occlusive disease (chronic)?
- Pulmonary veins/venules:
* obstructive intimal fibrosis
* recanalization and septal formation
* scarcity of recent thrombi
* medial hypertrophy and arterilization
- pulmonary arteries:
* intimal fibrosis, often with recent thrombi
* sometimes medial hypertrophy
- lung tissue:
* prominent hemosiderosis, focal congestion, interstitial fibrosis
101
What are three types of pulmonary aspergillosis?
- Colonization of aspergillus to form fungus ball
- hypersensitivity reaction
- invasive aspergillosis
102
List 5 examples of hypersensitivity reaction related to aspergillosis
- Allergic bronchopulmonary aspergillosis
- Bronchocentric granulomatosis
- Mucoid impaction
- Hypersensitivity pneumonitis
- Eosinophilic pneumonia
103
List 5 clinical manifestations related to invasive aspergillosis
- Acute invasive aspergillosis
- Chronic necrotizing aspergillosis
- Necrotizing pseudomembranous tracheobronchitis
- Empyema
- Bronchopleural fistula
104
What is the pathogenesis of silicosis?
- Silica particles are inhaled and deposited in lung tissue
- Particles damage lung tissue via direct cytotoxicity, or by production of oxidants and other mediators to cause fibrosis
105
List 5 disorders/pathologic changes associated with silica exposure
- Acute siliocoproteinosis
- Nodular silicosis
- Silicotuberculosis
- Rheumatoid pneumoconioses
- Mixed dust fibrosis, diffuse interstitial fibrosis, pleural fibrosis
106
What is the characteristic history of silicosis?
- Early/cellular stage: aggregation of dust-filled macrophages distributed along lymphatic routes (around bronchovascular bundles/pleura/sepate)
- Silicotic nodules formed of nodular dense collagen, may become hyalinized/calcified
- Polarized light shows weakly birefringent silica particles in nodules an in macrophages
- Progresses to massive fibrosis and diffuse interstitial fibrosis
107
What are the pathologic criteria of silicosis?
Silicotic nodules or progressive massive fibrosis associated with silica exposure
\*\*\* CHANGES HAVE TO BE IN LUNG AND NOT ONLY IN LYMPH NODES!!
108
What is sarcoidosis?
- Multiorgan disease of non-necrotizing granulomatous inflammatio
- unknown etiology
109
What demographics are common in sarcoidosis?
- Young adults (30-40)
- Female gender predominant
- African americans, Swedes, Danish
110
List 4 histologic findings of sarcoidosis in lungs
- Well-formed, non-necrotizing granulomas, may be confluent and hyalinized
- DIstribution of granulomas along lymphatic route-allong bronchovascular bundles and pleura/septa
- vasculitis
- inclusions: Schaumann bodies, asteroid bodies, birefringent calcium carbonate/oxylate
111
List 5 ddx of sarcoidosis
- fungal infection
- mycobacterial infection
- hypersensitivity pneumonitis
- berylliosis and other inhaled substances such as talc, aluminum
- sarcoidal reaction: malignancies, vasculitis, collagen vascular diseae
112
List 5 most common extrapulmonary sites for sarcoidosis
- Lymph nodes
- Liver
- Spleen
- skin
- heart
113
Pulmonary edema: what is the classification
- Hemodynamic pulmonary edema
- Microvascular injury (alveolar injury)
- Undertermined origin
114
List 8 causes of pulmonary edema
- Increased hydrostatic pressure
* Left sided heart failure
* volume overload
* pulmonary vein obstruction
- Decreased oncotic pressure
* Hypoalbuminemia
* Nephrotic syndrome
* liver disease
-Others
* infections (pneumonia, sepsis)
* inhaled gases
* liquid aspiration (near drowning)
* drugs/chemicals
* shock/trauma
* radiation
115
List 4 histologic changes in pulmonary edema
- Alveolar capillaries engorged
- Alveolar spaces filled with homogenous or fine granular pink material
- Hemosiderin laden-macrophages "heart failure cells"
- long standing congestion leads to fibrosis/thickening of alveolar walls
116
What is the etiology of acute interstitial pneumonia, and what is common in the clinical presentation?
- Idiopathic disorder
- Clinical presentation:
* prodromal illnes like viral URTI
* onset acute respiratory failure
* cough/dyspnea
* profound hypoxemia
117
What are the histologic findings in acute interstitial pneumonia?
- Similar to DAD
- Exudative phase: hyaline membranes, pulmonary edema, alveolar wall damage, endothelial injury, inflammatory exudates
- organizing phase: interstitial fibroblast proliferation, type 2 pneumocyte proliferation, endothelial injury with intimal fibroproliferation and medial hypertrophy
118
List 4 types of asthma
- Extrinsic (atopy)
- Intrinsic
- Occupational
- Other: drug related, obstructed, persistent
119
List 5 histologic findings of asthma
- Thickening of bronchial/bronchiolar basement membranes and subbasement membrane fibrosis
- Increase in size of submucosal glands
- Goblet cell metaplasia
- Hypertrohpy and hyperplasia of bronchial wall smooth muscle
- Mucous plugs with many eosinophils
120
What are Charcot-Leyden crystals and Cushmann spirals?
- Charcot-Leyden crystals are slender, rhomboid, organogphilic structures derived from breakdwon of eosinophil cell granules
- Curschman spirals: coiled/corkscrew shaped casts of bronchioles formed by insipated mucous (don't mean anything)
121
Briefly describe the lymph node stations in the chest
Supraclavicular zone: station 1 (includes low cervical/supraclavicular)
Upper zone:
* Station 2: upper paratracheal
* Station 3: retrotracheal
* Station 4: lower paratracheal
AP zone:
* Station 5: subaortic
* Station 6: paraaortic
Subcarinal zone:
* Station 7: subcarinal
Lower zone:
* Station 8: paraesophageal (below carina)
* Station 9: pulmonary ligament
Hilar:
* Staion 10: hilar
* Station 11: interlobar
Peripheral zone:
* Station 12: lobar
* Station 13: segmental
* Station 14: subsegmental
122
Describe the T categories for lung carcinomas
- T0: no primary
- TS: carcinoma in Situ
- T1 \<3cm, not invading pleura, not in main bronchus
* T1a: \<2cm
* T1b: \>2 but \<3cm
- T2: \>3 cm but \<7
* OR in main bronchus and small
* OR small but invades pleura
* OR obstructive pneumonitis in hilar region
* T2a: between 3 and 5 cm
* T2b: \>5 but less than 7 cm
- T3: tumor \>7cm
* OR: invadies parietal chest wall, diagphragm, phrenic nerve, mediastinal pleura
* OR: in main bronchus, \<2cm from carina
* OR: associated with entire-lung atelectasis
* OR: multiple tumor nodules in same lobe
- T4: Any size but inades mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, carina OR multiple noduels in different lobe IPSILATERAL
123
What is the N category in lung ca?
N0=no nodes
N1=mets in ipsilateral peribronchial/hilar nodes or intrapulmonary nodes, including direct extension (stations 10-14)
N2=mets in ipsilateral mediastinal or subcarinal lymph nodes (stations 2-9)
N3=mets in contralateral 1-2, or ipsilateral 1
124
What is the M staging in lung ca?
- M1a: separate tumor nodules in contralateral lung, tumor with pleural nodules, or malignant pleural effusion
- M1b: distant mets
125
What is pulmonary blastoma?
- Biphasic tumor containing primitive epithelial component and primitive mesenchymal stroma
126
What are the characteristic histologic features of pulmonary blastoma?
- Biphasic pattern
- Primitive epithelial component presents as malignant gland growing in tubules that resemble fetal bronchioles
- Tubules and glans lined by pseudostratified, non-ciliated columnar cells with subnuclear/supranuclear vacuoles giving endometrioid appearance
- Primitive epithelial component is embedded in sarcomatous mesenchyma with embryonic appearance, with small oval and spindle cells in a myxoid stroma. Foci of rhabdomyosarcoma, chondrosarcoma or osteosarcoma may be present
127
What is the IHC profile of pulmonary blastoma?
- Primitive epithelial component: cytokeratins, EMA, CEA, may show some staining with chromogranin, synaptophsyin, calcitonin
- primitive stromal component: vimentin/muscle specific actin, MAYBE desmin if muscle, S100 if cartilage
128
What are 4 groups of disorders predisposing patients to cor pulmonale? List 2 disorders in each group
- Pulmonary parenchymal disorders: COPD, diffuse interstitial lung disease
- Pulmonary vascular disease: massive PE, exacerbation of chronic cor pulmonale
- Disorders affecting chest wall movement: sleep apnea, neuromuscular
- Disorders inducing pulmonary arterial constriction: hypoxemia, chronic altitude
129
What are 2 acute causes of cor pulmonale (rv failure)?
- Massive PE
- exacerbation of chronic cor pulmonale
130
List 2 autopsy findings in the heart in cor pulmonale
- Dilatation of right ventricle
- Right ventricular hypertrophy
131
How can you differentiate primary from metastatic adenocarcinoma in the lung based on clinical, imaging and microscopic findings?
- Primary: hx smoking, spiculated edge, usually solitary lesion. Possible in-situ component (lepidic). IHC should show TTF-1/Napsin A/CK7+/CK20- for adenocarcinoma
- Mets: hx primary tumor elsewhere, smooth edge, often multiple. Similar morphology to primary. Panel depends on met: CK7/CK20/ER/PR/PSA/PAP/PLAP to figure out primary. Note TTF-1 positive in thyroid too
132
What is the significance of TTF-1 staining in lung cancer?
- positive in 75% of bronchogenic adenocarcinoma
- positive in majority of small cells
- variablly positive in large cell
- negative in SCC and salivary type adenocarcinomas
- may be negative in low-grade neuroendocrine tumors
133
What's the rationale for doing FS on lung lesions?
- establish cancer diagnosis prior to further sx
- evaluate resection margins
- determine nature of multiple nodular lesions
- confirm/rule out metastasis prior to further sx
134
In a chest wall mass with poorly formed neoplastic glands in a desmoplastic stroma, what would be ddx and how would you work up an adenocarcinoma of unknown primary?
Ddx: metastatic adenocarcinoma, malignant epithelioid mesothelioma, primary lung with extension to cheset wall, metastatic germ cell
Work-up: check clinical history, pmhx, family hx, review radiology
review slides from previous bx specimens if previous primary
IHC panel (standard AE1/AE3, CK7, CK20, CDX2, TTF1, PSA/PAP, etc.)
135
How can you differentiate mesothelioma from lung adenocarcinoma using gross, micro and IHC?
- Mesothelioma:
* pleural based, diffuse, often with pleural effusion.
* Micro: biphasic, sarcomatoid, low-grade cytology
* IHC: calretinin, CK5/6, WT1, D240 positive
* histochemistry: alcian blue may be+
- Adenocarcinoma:
* lung based, single mass, usually no effusion
* micro: only epithelioid, high-grade cytology
* IHC: CEA, MOC31, B72.3, BerEP4, CD15 positive, PAS
136
What is ddx of granuloma in lung
- Infecton (fungal, TB, atypical mycobacterium)
- Sarcoid
- Hypersensitivity pneumonitis
- Reactions to inhaled substances
- Berylliosis
- Necrotizing sarcoid granuloma
- Sarcoid-like rx to malignancies, vasculitis
137
How do you work up a granuloma?
- Clinical hx including symptoms, medical history, drugs, radiology, travel hx, etc.
- Determine whether necrotizing/non-necrotizing
- Determine distribution: sarcoid/berylliosis in lymphatic distribution vs. TB @ superior portion of lower lobe vs. hypersensitivity near small airways
- Perform special stains and send for PCR for infections (TB and fungus)
- If acid fast identified, treat as critical value and notify public health and lab supervisor, also inform all exposed individuals
138
What are some important items on clinical history for work-up of a pulmonary granuloma?
- Medical hx: any other lesions, drug,s vasculitis, collagen vascular disease, immune status
- TB exposure hx
- Travel hx
- Living conditions (hot tub, bird fancier...)
- Onset of disease and treatment to date
139
What ancillary studies should be ordered when working up a granuloma?
- PAS/PASD and GMS for fungi
- ZN or other acid-fat stain such as Fite, for acid fast bacilli + PCR
- Gram stain for bacteria
140
What do you do if TB is suspected on FS?
- Take universal precautions!
- use N95 mask
- inform surgeon/OR staff immediately
- request surgeon to take tissue for culture
- take some tissue for culture
- decontaminate equipment, workstation surface, cryostat
- after FS keep specimen in formalin for min 48-72 hrs to ensure full fixation
- report to lab supervisor
- inform occ health and public health if confirmed TB
141
What is the ddx of metastatic melanoma on pleural bx?
- metastatic carcinoma
- metastatic/primary sarcoma
- malignant lymphoma
- malignant mesothelioma
- desmoplastic small round cell tumor
- others
142
List 4 IHC stains used in the undifferentiated tumor
S100
AE1/AE3
LCA
VImentin
143
Patient with diffuse lung infiltrate, micro shows diffuse interstitial inflammation with numerous, obvious fungal elements
What type of fungi most likely?
What history is relevant?
What special stains help detect fungi?
- If immunosuppressed: pneumocystis jirovecci
- relevant history: immune status, travel hx, cancer hx, chemo/rads, history of BMT
- stains? PAS/D, GMS
144
List 8 fungi that affect lung, and morphologic features
Candida:
* oval, yeast like, 2-6um, pseudohypal forms
Aspergillus:
* septate hyphae, 3-6um, acute angle (45) branching
Zygomycetes:
* Broad hypahe, 5-25um, irregular or right angle branching
Histoplasma:
* Yeast-like, single buds, 2-4um
Cryptococcus:
* yeast, 4-6um, single buds, mucin halo
Blastomyces:
* yeast, 8-15um, single bud with broad base and multiple nuclei
COccidioides:
* matures spherules, 30-200um, refractile wall
Pneumocystis:
* round, 5-7um, prominent groove, tiny central dot, foamy exudate
145
How do you handle a wedge biopsy for non-neoplastic lung disease?
- request fresh tissue be sent immediately to lab from OR
- take small piece for culture
- measure
- inject formalin into tissue
- submerge tissue in formali n x 1hr
- slice perpendicular to surface to obtain largest plane
- plasse tisue into cassettes and back into formalin
- routine processing
- universal precautions
146
What is the ddx of geographic necrosis, granulomatous inflammation and vasculitis in the lung?
- Wegner granulomatosis
- Infection
- Necrotizing sarcoid
- CHurg-Strauss
- Bronchocentric granulomatosis (i.e. allergic bronchopulonary aspergillosis)
- Rheumatoid arthritis
147
Define ANCAs
- ANCA: antineutrophil cytoplasmic antibodies, a heterogenous group of ABs directed against neutrophil granules, lysosomes, endothelial cells
- Can be classicied as cyoplasmic (c-ANCA) or perinuclear (p-ANCA)
- Can be clasfied based on target antigens: anti-proteinase 3 (c-ANCA) and antimyeloperoxidase (p-ANCA)
148
Define positive predictive value
- the number of true positives, divided by sum of true positives and false positives, value representing the proportion of subjects with a positive test who actually have the disease
149
What is the significance of positive ANCA tests?
- Not specific, but c-ANCA antiproteinase 3 typical in Wegner's and p-ANCA antimyeloperoxidase in Churg-strauss/microsopic polyangiitis
- ANCAS are useful diagnostic markers for vasculitides, might reflect degree of inflamamtion
- ANCA can directly activate neutrophils and may stimulate neutrophils to release ROS and proteolytic enzymes
150
If Wegner is suspected, what would you advise the clinican?
- Check hx and presentation, esp. for nasal lesions, kidney, and other organ
- check renal function
- test ANCA status
- review radiology
- eliminate other ddx
151
Other than lung, what other organs are involved in wegners?
- systemic, but head and neck, upper and lower respiratory tract, kidneys most common
- others: joints, skin, pericardium, CNS, PNS
152
What is CMV?
- Herpes virus, dsDNA, replicates in host nucleus, enveloped virus
153
What are pathologic patterns of CMV pneumonia?
- CMV inclusions associated with minimal inflammation or lung injury
- Diffuse interstitial pneumonia
- Miliary pattern
- Hemorrhagic pneumonia
154
How do you diagnose CMV pneumonia?
- Based on culture or evaluation of lung biopsies/BAL
155
What other types of infections are caused by CMV?
- congenital/perinatal infections
- infectoius mononucleosis
- hepatitis
- opportunistic infections in HIV, transplant
- immunodeficiencies
- postransfusion rxns
- infection in those on chemo/steroids
156
Wedge lung bx shows organizing pneumonia with small amount of eosinophilic alveolar exudate. What is ddx?
- organizing pneumonia
- infection
- acute interstitial pneumonia/diffuse alveolar damage
- usual interstitial pneumonia
- non-specific interstitial pneumonia
- hypersensitivity pneumonitis
- others: drugs, collagen vascular
157
What are primary and seconary types of organizing pneumonia?
Primary: cryptogenic organizing pneumonia
Seconary: infectoin, collagen vascular diseae, drug reaction, non-specific rxn near neoplasm/infarct, aspiration, radiation, hemorrhage, wegners, cocaine, MDS
158
How can you differentiate organizing pneumonia from usual interstitial pneumonia?
OP:
* 40-50s, 1-6 mo duration, response to steroids, good prognosis
* patchy distribution, uniform temporality, absent fibroblastic foci in scars, fibroblastic plugs in alveoli, no dense fibrosis or honeycombing
UIP:
* older 60s, insidious onset 1-3yrs, no response to steroids, poor prognosis
* patchy, peripheral, lower lobes, heterogenous temporality, fibroblastic foci+fibrous scarring, dense fibrosis, honeycombing
159
What is the clinical behaviour of cryptogenic organizing pneumonia?
- mimics community-acquried pneumonia
- onset in 40s-50s
- acute/subacute course
- main symptoms cough/dyspnea
- no specific lab test
- PFTs show restrictive defect
160
Describe the common tumors and tumor like lesions of the mediastinum
Superior mediastinum:
* thymoma/thymic cyst
* malignant lymphoma
* thyroid lesions
* parathyroid lesions
Anterior mediastinum:
* thymoma/thymic cyst
* germ cell tumors
* thyroid lesions
* parathyroid lesions
* lymphoma
* paraganglioma
* lymphangioma
* hemangioma
* lipoma
Middle mediastinum:
* pericardial cyst
* bronchogenic cyst
* lymphoma
Posterior mediastinum:
* neurogenic tumors (neurilemmoam, neurofibroma, ganglioneuroma, ganglioneuroblastoma, schwannaoma, paraganglioma)
* gastroenteric cyst
161
What is the classification of epithelial tumors of thymus?
Thymoma:
* A (spindle cell)
* AB (mixed)
* B1 (lymphocyte rich, cortical)
* B2 (cortical)
* B3 (well-diff.thymic carcinoma)
Thymic carcinoma
* Squamous cell carcinoma
* Basaloid carcinoma
* Mucoepidermoid
* lymphoepithelioma-like
* sarcomatoid
* clear cell
* adenocarcinoma
* t (15;19) translocation
* neuroendocrine
* undiff
Combined thymic-epithelial tumors
162
WHat features should be mentioned in the report of a thymoma, regardless of type?
- Encapsulation
- Minimally invasive
- Widely invasive
- With implants
- With lymph node mets
- With distant mets
163
How does smoking induce tissue damage in the lung?
- tobacco smoke generates reactive oxygen species, triggering IL-8, TNF and causing tissue damage, also inactivates antiproteases
- also neutrophils release neutrophil elastase, and because of inhibition of antiproteases=more damage
