Pathology slide set 3 Flashcards
What are the 3 hypersensitivity pneumonitis discussed
- Farmer’s lung
- Pigeon breeder’s lung or bird fancier’s disease
- Humidifier or air-conditioner lunger
What does a BAL show in hypersensitivity pneumonitis
- increased proinflammatory cytokines (IL-8 and MIP-1alpha)
- increased CD4 and CD8 T lymphocytes
Which sufactant dysfunction disorder is autosomal dominant?
surfactant protein C
besides lung involvement, what are the next most common organs involved in sarcoidosis
eyes and skin
Then spleen
then liver
then bone marrow (pharyngeal bones of hand and feet)
bilateral sarcoidosis of parotid, submaxillary, and sublingual glands
the uveoparotid involvement: MIKULICZ syndrome
the pathogensis of pneumonconioses depends on what 4 things
- amount of dust retained
- size, shape, and buoyancy of particles
- particle solubility
- additional effects of other irritants
as silicosis progresses, what happens to the nodules
become hard collagenous scars
what type of particles tend to persist in lung parenchyma for years and evoke fibrosing collagenous pneumoconioses
larger insoluble particles such as silicosis
What are the environmental factors that cause injury in idiopathic pulmonary fibrosis
- tobacco smoke
- occupational irritants
- viruses
- persistent gastric reflux
extensive scarring in advanced restrictive disease leads to what gross finding
honeycomb lung
What is the most innocuous coal induced pulmonary lesion in coal miners lung
Anthrocosis
epidemiology for Pulmonary Langerhans cells histiocytosis
young smokers
What do patients with desquamative interstitial pneumonia present with
- cough
- dyspnea
- clubbing
over weeks or months
if an infarction occurs with a PE then what can be concluded about the patient
cardiovascular compromise
small lamellar bodies with electron dense cores are diagnostic of what/
ABCA3 mutation
Describe the granulomas in sarcoidosis
small, noncaseating often with multinucleated giant cells
CD4/CD8 ratio in sarcoidosis
5:1 to 15:1 suggesting pathogenic involvement of CD4 helper T cells
What cytotoxic cancer therapy drugs causes pulmonary damage and fibrosis
bleomycin
what is usually the first manifestation of asbestos
dyspnea on exertion
HLAs involved in Goodpasture
-HLA-DRB1*1501 and 1502
general pulmonary function changes in patients with restrictive lung disease
reductions in
- diffusing capacity
- lung volume
- lung compliance
What cell function is impaired in sarcoidosis
dendritic
Adult patients with PAP present how?
cough and abundant sputum that is gelatinous
What is the only tissue available to biopsy for diagnosis of polyangiitis with Granulomatosis (Wegener granulomatosis)
Transbronchial lung biopsy
idiopathic pulmonary hypertension is most common in who?
women 20-40
What genes are thought to be linked to idiopathic pulmonary fibrosis (IPF)
TERT and TERC genes; encode telomerase
- increase secretion of MUC5B
- other rare forms have mutations in genes encoding components of surfactant
What surfactant dysfunction disorder presents in first few months of life with rapidly progressive respiratory failure followed by death
ABCA3
Tiny sheet of calcification occur in lymph nodes and seen radiographically as EGGSHELL calcification
silicosis
What is the most common crystalline that is implicated in silicosis
quartz
explain the pathogenesis of silicosis after the particles are phagocytized by macrophages
- activate inflammasome
- release of IL-1 and IL-18
Goodpasture syndrome shows antibodies to what
alpha3 chain of collagen IV
Laminated concretions composed of calcium and proteins (Schaumann bodies) and stellate inclusions (asteroid bodies)
Sarcoidosis
not pathognomonic. also found in TB
Standard care for PAP
whole lung Lavage and GM-CSF therapy in autoimmune version
characterized by intensely blackened scars from 1 to 10 cm. microscopically dense collagen and pigment. center of lesion is often NECROTIC
progressive massive fibrosis
complicated coal workers pneumonconiosis
histologic changes of hypersensitivity pneumonitis are characteristically centered where and what type of cells are rare
- bronchioles
- Eosinophils
Defect in GM-CSF or pulmonary macrophage dysfunction that results in accumulation of surfactant in the intra-alveolar and bronchiolar spaces
Pulmonary Alveolar Proteinosis (PAP)
Whats the median survival after diagnosis of IPF
3 years . . doesn’t respond well to treatment
Ferruginous bodies
Asbestos
What are the major categories of chronic interstitial lung disease
- Fibrosing
- Granulomatous
- Eosinophilic
- Smoking related
- other
if coal workers pneumoconiosis leads to progressive massive fibrosis then what are the consequences
- respiratory failure
- pulmonary HTN
- cor pulmonale
fibroblastic foci, honeycombing, hyaline membranes, granulomas are ABSENT
NIP
- intermittent, diffuse alveolar hemorrhage
- young children
- productive cough, hemoptysis and anemia
- similar to goodpasture but NOanti-basement membrane antibodies
Idiopathic pulmonary Hemosiderosis
immunologic reaction to inhaled organic antigens causing interstitial pneumonitis (lymphocytes, plasma cells and macrophages, NONcaseating granulomas, and interstitial fibrosis
hypersensitivity pneumonitis
What is asbestos marked by
diffuse pulmonary interstitial fibrosis with asbestos bodies . . . may lead to honeycomb lung
if a nodule in silicosis undergoes central softening and cavitation then what happened
superimposed TB or ischemia
What type of asbestos is most often used industrially
serpentine chrysotile
golden brown, fusiform or beaded rods with a translucent center and consist of fibers coated with an iron containing proteinaceous material
Asbestos bodies
age for IPF
over 50
autoimmune form of PAP has antibodies to what and found in what age group
- GM-CSF - impairs macrophage ability to catabolize surfactant
- adults and lacks familial predisposition
immature dendritic cell with grooved, indented nuclei and abundant cytoplasm
Langerhans cell
characterized by presence of pigmented intraluminal macrophages within first and second order RESPIRATORY BRONCHIOLES
Respiratory Bronchiolitis-Associated Interstitial
Lung Disease
What diseases can cause secondary PAP
- hemotopoietic disorders
- malignancies
- immunodeficiency disorders
- Lysinuric protein intolerance
- acute silicosis
Goodpasture gender
males and most are active smokers
in IPF when dense fibrosis causes destruction of alveolar architecture and formation of cystic spaces lines by hyperplastic type II pneumocytes or bronchiolar epitheilum
honeycomb FIBROSIS
Acute attacks of hypersensitivity show what?
RECURRING episodes of fever, dyspnea, cough, and leukocytosis
group of fibrous hydrated silicates known to cause interstitial and plueral fibrosis and lead to lung carcinoma and malignant mesothelioma
Asbestos related
- S100
- CD1a
- CD207
-NEGATIVE for CD68
Langerhans cell
time frame for radiation-induced pneumonitis
1-6 months after
What part of lung is more heavily involved in simply coal workers pneumoconiosis
upper lobes and upper zones of lower lobes
Alveoli filled with numerous macrophages with, some with phagocytosed surfactant . . former or current smoker
desquamative interstitial pneumonia
What are the 2 histological forms of nonspecific interstitial pneumonia (NIP)?
- cellular (inflammation)
- fibrosing (SAME AGE, fibrotic lesions)
what do a great majority of Sarcoidosis patients present with
insidious onset of respiratory abnormalities (shortness of breath, cough, chest pain, and hemoptysis) or of constitutional signs and symptomes (fever, fatigue, weight loss, anorexia, night sweats)
What are the 2 broad categories of restrictive lung disorders
- chronic interstitial and infiltrative disease
- chest wall disorders
epidemiology for desquamative interstitial pneumonia
- genders equal
- 30s-40s
Alveoli precipitate periodic acid-schiff positivity (GRANULAR AND PINK), and contain cholesterol clefts and surfactant proteins in this disorder
PAP
what gene does Hereditary PAP (extremely rare) involve and what age group
GM-CSF
neonates
Shipyard
asbestos
What do patients with COP presnet with
cough and dyspnea
prognosis for Asbestosis complicated by lung or pleural malignancy
Poor/Grim
nonneoplastic lung reaction to inhalation of mineral dusts, organic, or inorganic particulates and chemical fumes and vapors encountered in the workplace
Pneumonconioses
Silicosis is associated with increased susceptibility to what?
TB and double risk of lung cancer
what are the 2 types of asbestos diseases
Serpentine chrysotile and amphibole
does coal workers pneumoconiosis in absence of smoking predispose to cancer?
NO
microscopically, fibrosis is patchy, variable intensity and age with early lesions showing fibroblastic foci
-coexistence of BOTH early and late lesions
IPF
clinical symptoms of IPF
- increasing dyspnea on exertion
- dry cough
Late in course
- hypoxemia
- cyanosis
- clubbing
What are the T cell derived cytokines increased in sarcoidosis and what are they responsible for
IL-2: T-cell expansion
IFN-gamma: macrophage activation
characterized predominantly by inflammation and fibrosis of pulmonary interstitium
chronic interstitial pulmonary diseases
Genetic association with sarcoidosis
HLA-A1 and HLA-B8
central area of WHORLED collegen fiber with a more peripheral zone of dust-laden macrophages . . UPPER
-by polarized microscopy you see birefringence
silicosis
time frame for symptoms of asbestos
more commonly 20 to 30 years after first exposure. rarely fewer than 10
What are the systemic immunologic abnormalitie that are found in those with sarcoidosis
- anergy to common skin test antigens such as Candida or TB PPD
- polyclonal hypergammaglobulinemia
Does “smoky coat” (bituminous), domestic indoor use for cooking and heating increase risk for lung cancer
YES
describe the lung grossly in PAP
increase in size and weight
Plexiform lesion . . . a tuft of capillary formations is present, producing a network, or web, that spans the lumens of dilated thin-walled small arteries and may extend outside the vessel
pulmonary hypertension
Inflammatory cells in IPF?
lymphocytes admixed with few plasma cells, neutrophils, eosinophils, and mast cells
Treatment for COP
some recover spontaneously but most need oral steroids for 6 months or longer
female nonsmokers in 50s presents with dyspnea and cough of several months that gets better
NIP
histological pattern of fibrosis in idiopathic pulmonary fibrosis
usual interstitial pneumonia (UIP)
what symptoms are caused by the pleural plaques of asbestos
NONE
if acute radiation pneumonitis progresses to chronic, what is the result
fibrosis . . DAD
- atypia of hyperplastic type II cells and fibroblasts
- epithelial cell atypia and foam cells within vessel walls
Some cases of Pulmonary Langerhans cell histocytosis are a reactive inflammation while others, the langerhans cells have acaquired activating mutations in what?
Serine/Threonine Kinase BRAF
Where do 3/4 of infarctions from PE occur
lower lobes
Does coal workers pneumoconiosis increase susceptibility to TB?
NO
clinicopathologic syndrome marked by progressive interstitial fibrosis and respiratory failure
idiopathic pulmonary fibrosis (IPF)
chest radiographs for restrictive lung disease
bilateral lesions that take form of small nodules, irregular lines, or GROUND GLASS shadows
in coal workers lung disease, where do the macrophages with the carbon dust accumulate
along pulmonary lymphatic tissue; along bronchi and hilus
Where are pleural plaques developed most frequently
anterior and posterolateral aspects of the PARIETAL PLEURA and over domes of diaphragm
Symptoms of radiation induced pneumonitis that resolve with steroid therapy
- fever
- dyspnea out of proportion to volume of lung irradiated
- pleural effusion
- infiltrates
Surfactant protein B
LEAST COMMON
- autosomal recessive
- full term baby
- rapidly progressive respiratory distress shortly after birth
- death b/t 3 and 6 months
patients with PAP are at risk for what
-respirator failure and infection
What cytokines are increased in the local environment of sarcoidosis and favor recruitment of additional T cells and monocytes and contribute to formation of granulomas
IL-8
TNF
MIP-1alpha
Lines of Zahn
clot was formed in living person
What type of particles cause rapid onset lung damage
high solubility
presence of polypoid plugs of loose connective tissue (Masson bodies) within ALVEOLAR ducts, alveoli and often bronchioles.
all same age and lung architecture normal
NO INTERSTITIAL FIBROSIS OR HONEYCOMB LUNG
cryptogenic organizing Pneumonia (COP)
which asbestos is more flexible, curled and soluble and susceptibe to ciliary elevator
serpentine chrysotile
multiorgan granulomatous disorder of unknown cause
Sarcoidosis
difference b/t hypersensitivity pneumonitis and asthma
the former leads to pathologic changes that primarily involve the ALVEOLAR WALL
what cardiac arrythmic drug can cause significant pneumonitis
Amiodarone
Early stages of silicosis
tiny, barely palpable, discrete PALE to blackened nodules in HYLAR lymph nodes and UPPER zones of lungs
COP is most often seen as a response to what?
infections or inflammatory injury of the lungs
what type of asbestos is more pathogenic
amphibole . goes deep in lungs (stiff and straight)
What size particles are most pathogenic in pneumonconioses
1-5 micrometers
whats on CT with NIP?
bilateral symmetric predominantly lower lobe reticular opacities
difference between coal macules and coal nodules seen in simple coal workers pneumonconiosis
macules: (1-2 mm) carbon laden macrophages
nodules: also contain a delicate network of collagen fibers
general clinical findings in patients with restrictive lung disease
- dyspnea
- tachypnea
- END INSPIRATORY CRACKLES
- eventual cyanosis WITHOUT WHEEZING
Accumulation of dendritic cells (langerhan cells) to form nodules, along with fibroblasts, macrophages, and numerous EOSINOPHILS
Pulmonary Langerhans cell histiocytosis
What type of emphysema can coal workers pneumoconiosis give to?
centrilobular (centriacinar)
What does desquamative interstitial pneumonia respond to
steroid therapy
Goodpasture age
teens or 20s
SUBPLEURAL and INTERLOBULAR septal fibrosis preferentially in lower lobes
IPF
what part of the lung does asbestos affect
base first and sub pleurally
What type of hypersensitivity is hypersensitivity pneumonitis
type 4
pleural plaques
most common manifestation of ASBESTOS exposure, are well-circumscribed plaques of dense collagen that are often calcified
macrophages with abundant cytoplasm containing dusty brown pigment (SMOKERS MACROPHAGES) in airspaces
desquamative interstitial pneumonia
What is the cause of idiopthic pulmonary fibrosis (IPF) thought to be
unknown but thought to occur secondary to repeated injury to alveolar epithelial cells with a pro-fibrotic response in GENETICALLY susceptible people
What cytokines does BMPR2 bind
- TGF-beta
- BMP
- activin
- inhibin
What in the bronchoalveolar fluid is a marker of sardoidosis disease activity
TNF
What is thought to be the pathogenesis of sarcoidosis
disordered immune regulation in genetically predisposed individuals
relationship between asbestos and smoking and cancer
Synergy. Asbestos alone increases incidence 5 fold. with smoking 55 fold
What is involved in 90% of cases of sarcoidosis
bilateral hilar lymphadenopathy or lung involvement
What is mutated or dysfunctional in idiopathic pulmonary arterial hypertension
BMPR2
epidemiology of sarcoidosis
- younger adults less than 40
- 10x higher in blacks
- females more common
- highest rates in southest U.S.
- RARE in chinese and southest Asians
Abnormalities in lamellar bodies in type II pneumocytes
All 3 surfactant dysfunction disorders
epidemiology of repiratory bronchiolitis-associated interstitial Lung disease
- mild
- current smoker in 30s-40s
- ave. 30 pack year history
- crystalline, sand blasting, concrete cutting, stressed denim, jewelers
- African Americans higher risk
- slowly progressing nodular collagenous/fibrosing scars
Silicosis
What is the most frequently mutated gene in surfactant dysfunction disorder? heredity?
ABCA3 (AUTOSOMAL RECESSIVE)
