Resp. Pathology - 5 - SRS Flashcards
What are the seven broad categories of infiltrative/restrictive diseases?
- Idiopathic pulmonary fibrosis
- Cryptogenic Organizing Pneumonia
- Environmental Interstitial Lung Diseases
- Sarcoidosis
- Surfactant Disorders
- Pulmonary Eosinophilia
What are the six causes of environmental interstitial lung disease he highlighted?
- Coal
- Silica
- Asbestos
- Drugs
- Hypersensitivity Pneumonitis
- Tobacco
What pattern do infiltrative diseases have on x-ray?
Reticulonodular or ground glass
What are the four common clinical signs for restrictive lung diseases?
- dyspnea
- tachypnea
- cyanosis
- end-inspiratory crackles
what is the end stage of these fibrosing disorders?
Honeycomb lung
What are the major categories of chronic interstitial lung disease?
- Fibrosing
- Granulomatous
- Smoking related
- Other…
What are the fibrosing diseases?
3 bolded
4 non-bolded
- Usual interstitial pneumonia (idiopathic pulmonary fibrosis)*
- Nonspecific interstitial pneumonia*
- Cryptogenic organizing pneumonia*
- Connective tissue disease-associated
- Pneumoconioses
- Drug reactions
- Radiation pneumonitis
What are the etiologies for:
- Usual interstitial pneumonia (idiopathic pulmonary fibrosis)*
- Nonspecific interstitial pneumonia*
- Cryptogenic organizing pneumonia*
Unknown
What are the granulomatous interstitial lung diseases?
1 bolded
1 bolded AND italicized
1 plain font
(3 total)
- Sarcoidosis*
- Hypersensitivity pneumonitis
- Eosinophilic (eosinophilic pneumonias)*
What are the two smoking-related interstitial lung diseases?
- Desquamative interstitial pneumonia
- Respiratory bronchiolitis-associated interstitial lung disease
What are the three interstitial lung diseases that fall into the “other” category?
- Pulmonary Langerhans cell histiocytosis
- Pulmonary alveolar proteinosis *
- Lymphoid interstitial pneumonia *
What is another term for the idiopathic pulmonary fibrosis?
Usual interstitial pneumonia
What pattern is shown on this x-ray?
Reticular pattern (or knot? Nut? pattern… couldn’t understand what he said)
The biopsy attached shows early phase usual interstitial pneumonia, with mononuclear infiltrates and fibrotic thickening of the interstitium.
What cells are being slaughtered here and what cells are taking their place?
What is causing the pathology in this condition?
- • Type I pneumocyte death, type II hyperplasia
- Pathology occurs as a result of:
- TH2 lymphocytes,
- cytokines,
- macrophages,
- fibroblast/myofibroblast proliferation (TGF-β1 driven),
- collagen deposition
What gene mutations predispose one to development of idiopathic pulmonary fibrosis?
TERT and TERC
There is some evidence the activated fibroblasts in idiopathic pulmonary fibrosis exhibit signaling abnormalities in a particular pathway that leads to synthesis and deposition of collagen leading to interstitial fibrosis and eventual respiratory failure. What pathway is this?
PI3K/AKT pathway
When epithelium is injured it releases TGF-B which not only stimulates fibroblasts and myofibroblasts to deposit collagen, it also inhibits what inhibitor of collagen production?
Caveolin in fibroblasts
Idiopathic pulmonary fibrosis is an insidious, upredictable disease that typically strikes in middle age. (>50). The patient may complain of dyspnea, dry cough, hypoxemia with cyanosis and have digital clubbing.
What is the median survival?
3 years
The repeated cycles of alveolitis in idiopathic pulmonary fibrosis lead to healing/scarring and patchy interstitial fibrosis.
What part of the lung is typically involved?
What is the treatment for this condition?
Predominantly the subpleural/interlobar and lower lobe
Lung transplant. (does not respond well to anti-inflammatory agents)
This image shows fibrosis of the subpleural region which is typical of the changes seen in?
Usual interstitial pneumonia
This image of usual interstitial pneumonia show fibrolastic foci with fibers running parrallel to the surface and bluish myxoid extracellular matrix.
What is shown on the left side of the image?
Honeycombing - associated with the end stages of this disease
What is shown here?
Honeycomb lung
What will the lesions in idiopathic pulmonary fibrosis look like as far as age and progression?
Variable age and progression
Patient presents with dyspnea and cough of several months duration, is middle age and a non-smoker. You biopsy the lung at the lingula and get lucky. The lesions you find are all at the same stage of progresion with lymphocytes and some plasma cells. There is mild patchy or diffuse interstitial fibrosis present. What is the disease this patient likely has?
Do you expect to see honeycombing or fibroblastic foci?
Nonspecific interstitial pneumonia
Do not see fibroblastic foci or honeycombing. If you do, then it may have to be reclassified d/t progression.
You see a patient with cryptogenic organizing pneumonia for a check up. Being the sweet doc that you are, you this disease has what two specific characteristics?
The patient expresses concerns about their lung turning into some kind of cereal lung. What do you tell them?
- All connective tissue is of the same age
- No interstitial fibrosis
Since no fibrosis, does not progress to honeycomb lung. Reassure the patient this will not happen.
You obtain the following biopsy from a patient with cough and dyspnea. What is indicated by the green and blue arrows respectively?
What disease are these findings indicative of?
What is the treatment?
Cryptogenic Organizing Pneumonia (COP)= Bronchiolitis Obliterans Organizing Pneumonia (BOOP)
Green arrow = Masson Bodies
Blue Arrow = Obliterated bronchiole
Treat with oral steroids for 6 or more months
Cryptogenic Organizing Pneumonia (COP) is of unknown etiology by definition but organizing pneumonias can be a reaction to what two other events?
- Infection
- Inflammatory process
What are the examples of collagen vascular disorder related autoimmune interstitial lung diseases?
6
- •Rheumatoid arthritis (30-40% abnormal PFT Caplan syndrome - combination of rheumatoid arthritis and pneumoconiosis
- •Scleroderma (systemic sclerosis)
- •Systemic lupus erythematosus
- •Sjӧgren syndrome
- •Polymyositis/dermatomyositis
- •Mixed connective tissue disorder
Your patient presents with evidence of lung disease, you biopsy the lung and find the two particulalry significant samples attached to this card. What are the findings you see here and what do they point to this patient having?
Image at left: Follicular bronchiolitis - parabronchiolar lymphoid follicles seen here indicate a likely autoimmune process.
Image at right: a rheumatoid nodule - granuloma form surrounding necrotic tissue.
These two things combine to strongly suggest Rheumatoid Arthritis
Environmentally related lung diseases are inhalation related but can have a genetic predisposition to developing disease. What particles are dangerous?
- 1-5 micron size are most dangerous
- size, shape and buoyancy play a role - an example of shape is asbestos, shaped like a thin spear.
- soluble/cytotoxics
- concomitant irritants
What is pneumoconiosis?
originally limited to mineral dust inhalation but now all inclusive of pretty much anything you breath at work
What are the mineral dusts that cause pneumoconiosis?
(4 bold and likely on exams, three extra)
- Coal dust
- Silica
- Asbestos
- beryllium
- iron oxide
- barium sulfate
- tin oxide
What diseases does coal dust cause? 4
- Anthracosis
- Macules
- Progressive massive fibrosis
- Caplan syndrome
What diseases does silica inhalation lead to? 2
Silicosis
Caplan syndrome
What professions are at risk for silicosis? 4 examples
- metal casting (foundry)
- sandblasting
- rock mining
- stone cutting
What are 5 diseases asbestos has been shown to cause?
- Asbestosis
- Pleural plaques
- Caplan syndrome
- Mesothelioma
- Carcinoma of the lung, larynx, stomach, colon
What are some exposure risks for asbestos?
- mining
- milling
- fabrication
- installation/removal of insulation
Workers in fabrication and mining can be exposed to berylium, what are three diseases they are at risk for?
- Acute berylliosis
- beryllium granulomatosis
- lung carcinoma
Is a patient that has been exposed to asbestos more likely to develop mesothelioma or carcinoma of the lung?
Much more likely to develop carcinoma of the lung
What are the organic dusts that induce hypersensitivity pneumonitis?
Will you see eosinophilia in these hypersensitivies?
- Moldy hay - Farmer’s lung
- Bagasse - Bagassosis
- Bird droppings - Bird breeders lung
NO EOSINOPHILIA - NOT A TYPE I hypersensitivity
Someone working in the Rum business might contract what disease?
Bagassosis
What are the three stages of the disease this sample represents?
- Asymptomatic anthracosis
- Simple coal worker’s pneumoconiosis (benign - no problems breathing)
- Complicated CWP
What are the characteristics of complicated CWP?
Progressive massive fibrosis
- scars >2 cm
- pulmonary dysfunction
- pulmonary HTN
- cor pulmonale
What percent of cases of CWP progress to complicated CWP with PMF?
Less than 10%
Classify these anthracosed lungs!
Left to right
- Asymptomatic anthracosis
- CWP
- CWP with PMF
Your patient who is at the end of their career as a sandblaster complains of SOB, cough, and feeling tired. You biopsy the lung and find the attached samples.
What does this patient have?
What should you tell the patient they are at increased risk for?
Silicosis - note the polarizing illuminated bits of silica showing up on the right and the presence of fibrosis and granulomas in the image on the left.
These patients are at increased risk for:
- Carcinogenesis (2x risk)
- Tuberculosis
What is the process by which the damage occurs in silicosis
- Silica is inhaled
- Macros eat the silica
- Silica kills macros
- Dead macos dump the ingested silica along with TNF
- TNF stimulates fibroblasts to fibrose
- A new macro eats the dumped silica and the process repeats
What caused the finding shown on this radiograph?
Silicosis of a lymph node
What are some diseases caused by asbestos?
- Pleural effusion
- Pleural Plaque or diffuse pleural fibrosis
- Asbestosis
- Lung cancer
- Laryngeal cancer
- mesothelioma
- ovarian and colon carcinoma
Asbestos can increase lung cancer risk by 5x, what is the risk increase if that patient takes up smoking?
55x when combined with smoking
Which of these types of asbestos is the one that causes mesothelioma?
What are the two types shown here?
The one on the right shows amphiboles, which is the only causative type of asbestos that causes mesothelioma.
The one on the left is serpentine chrysotile
What is shown in this image?
Asbestos (iron/ferruginous) body - Asbestos covered by a protenaceous material that contains iron.
HEADS UP THE IMAGE AT RIGHT WIGGLED
What is shown here?
What is the stain used to identify these?
Asbestos bodies
Prussian blue stain
If you sample the mesothelium of a patient who has mesothelioma will you see these?
NO, these will only be in the lung tissue.
This patient was exposed to asbestos and has pleural plaques. Will you find asbestos bodies in pleural plaques?
NOPE
What is shown here?
What has this patient been exposed to?
Pleural plaques
- on x-ray will look like masses
- MRI/CT can visualize the calcified plaques well
What are the pulmonary consequences that can arise due to these drugs?
- Bleomycin
- Methotrexate
- Amiodarone
- Nitrofurantoin
- Aspirin
- β-Antagonists
- ACE inhibitors
- Bleomycin - pneumonitis and fibrosis
- Methotrexate - hypersensitivity pneumonitis
- Amiodarone - pneumonitis and fibrosis
- Nitrofurantoin - hypersensitivity pneumonitis
- Aspirin - bronchospasm
- β-Antagonists - bronchospasm
- ACE inhibitors - cough
Radiation can cause pneumonitis either acutely or chronically. What do each look like on x-ray?
Acute: alveolitis or hypersensitivy pneumonitis with pleural effusions and infiltrates on x-ray within 6 months of radiation.
Chronic - pulmonary fibrosis (looks like diffuse alveolar damage)
Extrinsic allergic alveolits or hypersensitivity pneumonitis can be caused by…
- Occupational
- Pets/hobbies
- Environmental
•Medications/
iatrogenic
•Dietary
What are three examples he pointed out in particular?
•Farmer’s lung
(actinomyces in hay)
•Bird fancier’s lung
(reaction to sera, feces)
•Humidifier lung
(thermophilic bacteria)
Patient presents complaining of fever, cough, dyspnea. CBC shows leukocytosis. When asking in the history about potential exposures it turns out the patient trains carrier pigeons for a hobby. (We’ll all be thankful for his efforts when society crumbles and electricity becomes a thing of legend)
You take a lung biopsy and find the attached image. At what level of the lungs is this disease process occuring?
What is shown in the image that is classic of this disease?
Hypersensitivity pneumonitis occurs at the level of the alveolus.
Image shows noncaseating granulomas (type IV), typically found in the distal lung.
Farmer’s lung arises due to exposure to moldy hay. What organisms cause this?
- Micropolyspora faeni
- Actinomyces
Bagossosis is associated with exposure to moldy pressed sugar cane (bagasse). What organism is the causative agent/antigen?
Thermophilic actinomycetes
What are the three interstitial lung diseases (only an interstitial pattern on xray, not truly interstitial) associated with cigarette smoking?
- Desquamative interstitial pneumonia (D.I.P.)
- Respiratory bronchiolitis associated interstitial lung disease (R.B.I.L.D.)
- +/- Pulmonary Langerhans cell histiocytosis (Eosinophilic granuloma) (aka histiocytosis X)
Patient with SOB and dyspnea presents to your office. You do a biopsy and find the attached image depicting large collections of smoker’s macrophages. What level of fibrosis is present? Will this progress to honeycomb lung?
What is the treatment?
Desquamative interstitial pneumonia
- minimal fibrosis, so no progression to honeycomb lung
- steroids and cessation of smoking
Is DIP restrictive or obstructive?
He told us to figure out if desquamative interstitial pneumonia was restrictive or obstructive. I’d say restrictive based on the following…
- He presented it in a presentation on restrictive diseases
- a cursory internet search
Patient with a 30 pack year history of smoking and CC of dyspnea and cough. You find the attached histology in the bronchioles. What is the condition and what are the two key findings?
Respiratory bronchiolitis-associated interstitial lung disease (RBILD)
- •Pigmented smokers’ macrophages in bronchioles
- • Peribronchiolar fibrosis
This EM finding was obtained from a cell taken from a patient with general lung complaints. What cell did this come from?
What is the name for the thing shown here?
What condition has this person’s smoking habit lead to?
This is a Birbeck granule, and is found in Langerhan’s cells.
This person has developed Pulmonary Langerhans cell histiocytosis
THIS PICTURE WIGGLED
With the patient who has pulmonary langerhans cell histiocytosis, what are you likely to be able to perform immunohistochemistry for?
3
CD1a
S-100
CD207 (Langerin) - nearly pathognomonic for langerhan’s cells
What light microscopic finding can indicate that a macrophage is possibly a Langerhans cell?
A cleft in the macrophage nucleus. Then you should do either EM or immunohistochem to prove the dx.
You’ve excluded all other diagnoses with histology, and can see non-caseating granulomas on x-ray. What can you say this patient may have?
Sarcoidosis
Sarcoidosis can occur almost anwyere including the CNS. Where do they most commonly occur?
Pulmonary>eye>skin
also spleen and liver
From more to less favorable outcomes rank the following for sarcoidosis.
Hilar LN
LN + infiltrates
Lung parenchymal disease
- Hilar LN
- LN + infiltrates
- Lung parenchymal disease
What conditions can you see elevated levels of angiotensin converting enzyme?
Sarcoidosis
Leprosy
This image was from a transbronchial biopsy from a patient in whom you spotted large nodules and lines on x-ray.
What is this?
Sarcoidosis lung with patchy appearance, LN involvement
WIGGLED
The patient with this biopsy came from demonstrated anergy to PPD and/or Candida antigens.
What is the diagnosis?
Indicative of sarcoidosis.
Image shows a sarcoidosis lymph node.
Wiggled
While not pathognomonic, this image shows what “body” that is associated with sarcoidosis?
Asteroid body
(must be presented with a clinical description to make dx)
While not pathognomonic, this image shows what “body” that is associated with sarcoidosis?
Schaumann body
Pulmonary alveolar proteinosis is uncommon. What is the typical clinical presentation?
Cough and sputum with gelatinous chunks
(blech)
What are the histologic and radiographic findings in pulmonary alveolar proteinosis?
- X-ray: bilateral patchy distribution
- Histo: accumulation of acellular surfactant in the intra-alveolar and bronchiolar spaces
What are the three classes of pulmonary alveolar proteinosis
- Autoimmune (acquired)
- Secondary
- Hereditary (congenital)
Autoimmune pulmonary alveolar proteinosis has a variable course.
What are the antibodies against?
Transplant may be indicated for these patients. How does that work out for them?
- Ab to GM-CSF (defective phagocytosis of surfactant)
- Recurs after transplantation
Hereditary pulmonary alveolar proteinosis is rare and involved genes for GM-CSF signaling. What is the outcome of this condition?
FATAL
What are the treatments for autoimmune and congenital pulmonary alveolar proteinosis?
- Pulmonary lavage and GM-CSF therapy in autoimmune
- Transplant in congenital
What are the attached findings associated with?
Pulmonary alveolar proteinosis
Histo: alveol filled with a dense, amorphous, protein-lipid granular precipitate, while the alveolar walls are normal.
Acute Pulmonary eosiniphilia is an eosinophilic pneumonia with respiratory failure. For most cases, the etiology is unknown
What are some secondary causes of this?
- parasitic, fungal, and bacterial infections
- tropical eosinophilia (microfilariae)
- hypersensitivity pneumonitis
- allergic bronchopulmonary aspergillosis
- drug allergies
- asthma
- vasculitis
What is Löeffler syndrome?
What is one specifically noteable cause?
Transient acute pulmonary eosinophilia from any cause. (Pretty much can use Löeffler syndrome and pulmonary eosiniphilia interchangeably)
One cause he highlighted was eosinophilic leukemia.
