Pulm Path Flashcards
LARGE AIRWAYS (trachea / bronchi)
pseudostratified, tall columnar, ciliated epithelium
goblet cells
basal cells
neuroendocrine cells
submucosal mucous glands
cartilage
SMALL AIRWAYS (bronchioles)
lack of cartilage
lack of submucosal glands
gradually thinner epithelium
gradually less mucous cells
non ciliated columnar clara cells (terminal bronchioles)
ALVEOLI
- capillary network
- fusion of BM of endothelium and epithelium - (gas-exchange areas)
- pores of Kohn (between alveoli)
- macrophages
- surfactant layer
- interstitium
Hypoplastic lung
A 15 year old girl presents to the emergency room coughing up blood. On CT scan there is a fluid-filled mass in her left lung. Surgical ressection reveals the following non-malignant structure. What is it and what are the complications?
Congenital cysts (pulmonary)
cystic spaces lined by bronchial type epithelium
contain mucinous secretions or air
anywhere in the lung
connection with airway may not be apparent
complications
- infection (abscess)
- rupture (hemorrhage, hemoptysis, pneumothorax)
A 37-week pregnant woman comes to her OB/GYN for a physical and ultrasound exam. On ultrasound the obstetrician notices a mass pressing on the fetus’ heart- there are no pathological findings while listening to the heart sounds, but she is concerned about malignancy or danger to heart function. The mass is removed via fetal surgery and the following histologic sample is recovered. What is the diagnosis and treatment?
Cystic adenomatoid malformation:
- Cystic structures resembling terminal bronchioles
- Different types based on the size of the cysts
- Within the first week to month of life
- Usually unilateral/one lobe
On physical exam of a 3-week-old infant, her pediatrician notices absent lung sounds in her right lower lobe. Percussion is dull (non-tympanic) and she is concerned about hepatomegaly or some other malignant process. Imaging is taken and the following abnormality is found. What is this condition?
- *Bronchopulmonary sequestration**= segment of lung tissue without connection to the airway system
- blood supply from aorta or its branches
- *Extralobar sequestration (image)**:
- most common in infants
- associated with other congenital anomalies
- outside the lung anywhere in the thorax or mediastinum.
Intralobar sequestration:
- most common in adults
- associated with recurrent infections
- within the lung parenchyma
A 50 year old man has an MI and suffers damage to the left side of his heart. While in the hospital he suddenly has trouble breathing and begins coughing up blood (hemoptsysis). On auscultation, there are diffuse crackles that are louder at the bases of his lungs. He soon experiences another MI and expires. On autopsy the following histologic sample is taken from his lung. What is his diagnosis?
Acute Pulmonary congestion and edema: accumulation of fluid in dependent basal regions of lower lobes
Causes of Hemodynamic Edema:
- Increase hydrostatic pressure (left-sided HF, volume overload, PV obstruction, etc.)
- Decrease oncotic pressure (hypoalbuminemia)
- Lymphatic obstruction
- *Histologic findings:**
- engorged capillaries
- granular pink precipitate in alveolar spaces
- microhemorrhages
- hemosiderin-laden macrophages (chronic)
- interstitial fibrosis (chronic)
Below: gross findings= heavy, wet lungs
A 92 year-old woman had a myocardial infarction 3 years ago and has been suffering from congestive heart failure. On auscultation there are diffuse, heavy, wet crackles heard throughout her lungs. At autopsy, the following histologic changes are found in her lungs. What occured and what types of changes are seen?
Chronic pulmonary hemodynamic congestion= due to heart failure–> blood backs up into lungs, eventually fills alveolar spaces
Histologic findings:Histologic findings:
- engorged capillaries
- granular pink precipitate in alveolar spaces
- microhemorrhages
- *- hemosiderin-laden macrophages
- interstitial fibrosis (chronic)**
A 50 year old chemical plant worker is brought into the Emergency room after passing out at work. His co-worker states he turned blue and appeared to have trouble breathing and then fell to the ground. After administration of oxygen and attempts to ressucitate the man, he eventually dies due to respiratory failure. The following histologic specimen is taken from his lungs. What may have caused these changes and what is the condition called?
Diffuse alveolar damage: early phase: Clinical manifestation of Adult respiratory distress syndrome (ARDS)
ARDS: more than 50% mortality, refractory to O2 administration
Causes:
- Infections
- Toxins
- Drugs
- Shock
- Radiation
Histo:
- Pattern of acute lung injury and repair, bilateral interstitial involvement
- edema, +/- hemorrhage
- fibrinous exudate
- hyaline membranes= pathognomic
- mild interstitial inflammation
- fibrin microthrombi
A 60 year old man is in the ICU recovering from exposure to radiation that caused damage to his lungs. A lung biopsy is taken on day 10- what type of changes are noted below and what was his condition?
Diffuse alveolar damage: repair (organizing) phase: following ARDS (adult respiratory distress syndrome), type II pneumocytes go through hyperplastic phase to repair lost Type I pneumocytes, see squamous metaplasia, interstitial/airspace fibroblastic proliferation
Below: fibroblastic proliferation within alveolar space to lay down collagen matrix (repair damage)- AKA organizing DAD
A 45 year old man is in the hospital for spinal surgery. He has been in the unit for one week recovering when he suddenly stops breathing, turns blue, and expires. On autopsy, the following is discovered. What happened and what caused this?
Saddle embolism (pulmonary embolism):
Symptoms:
- Chest pain
- tachypnea
- dyspnea
- hemoptysis
- unremarkable chest x-ray
Large emboli= saddle embolus–> sudden death due to cardiovascular collapse (repeated small emboli can have same effect as large emboli)
Pathology: pulmonary artery completely occluded by large embolus
- Most common source of emboli= deep venous thrombi (DVT)
- Other sourse: pelvic vein, foreign body, bone marrow, amniotic fluid, air emboli
- Predisposing factors= venous stasis, hypercoagulable state, endothelial injury
- Risk factors= immobilization, obesity, pregnancy, estrogenic OCP, hereditary clotting disorders
Incidence: General population= 1%; hospitalized= 30%
A 30 year old woman comes to her doctor after coughing up blood and experiencing some chest pain for the past day. She recently returned from a trip to California. Based on the histology below, what is her diagnosis, prognosis and treatment and what caused this condition?
Pulmonary embolism: Infarct due to middle-sized emboli
- *Causes**:
- Most common source of emboli= deep venous thrombi (DVT)
- Other sourse: pelvic vein, foreign body, bone marrow, amniotic fluid, air emboli
- Predisposing factors= venous stasis, hypercoagulable state, endothelial injury
- Risk factors= immobilization, obesity, pregnancy, estrogenic OCP, hereditary clotting disorders
Incidence: General population= 1%; hospitalized= 30%
Outcome of small pulmonary emboli (60-80% of all emboli)
- Usually asymptomatic, transient chest pain, hemoptysis
- Rarely: small infarctions (cardiac failure patients), chronic cor-pulmonale (multiple PE), pulmonary hypertension
Outcome of middle-size emboli (below):
- *PULMONARY INFARCTION**
- Hemorrhagic
- pleural-based
- wedged-shaped
- fibrinous exudate on pleural surface
- form contracted scar with resolution
- predominantly lower lobes
Hemorrhagic infarction due to dual blood supply (vs renal infarct–> whitens tissue b/c sole blood supply cut off)
- *Outcome**;
- Respiratory compromise
- ventilated segment not perfused
- Hemodynamic compromise
- increased resistance to pulmonary blood flow (vasoconstriction)
- Outcome depends on the size of embolus and adequacy of bronchial circulation
Prognosis: Two-thirds of PE not diagnosed, even when fatal
- Mortality rate reduced to 5-10% with treatment
Treatment:Improvement without treatment due to fibrinolysis and contraction of thrombus
- Treatment with fibrinolytic agents ASAP
- Early diagnostic tools: perfusion lung scan, pulmonary angiography
A 45 year old woman with a history of a clotting disorder has noticed progressive shortness of breath while trying to carry laundry up the stairs or while chasing her 8 year old around the house. On auscultation she has a low S2 over the left mid-clavicular line at the 3rd intercostal space. What is her diagnosis, what caused this, and what is her treatment?
Pulmonary hypertension= increased pulmonary vascular resistance leading to elevated pulmonary arterial pressure
Primary pulmonary hypertension:
- uncommon
- children and young women
- progression to severe respiratory insufficiency, cor-pulmonale, death
- pathogenesis unknown; dx of exclusion
- *Secondary pulmonary hypertension:** due to:
- chronic obstructive lung disease
- interstitial lung disease
- left-sided heart disease
- *- recurrent PE**
- *Histologic findings:**
- atherosclerosis, large elastic arteries
- concentric intimal fibrosis and medial hypertrophy, medium-sized arteries and small arterioles (Below)
- thrombotic arteriopathy (eccentric intimal fibrosis and recanalization)
- veno-occlusive disease (venous sclerosis and muscularization)
- *Treatment:** vasodilators, diuretics, oxygen therapy, exercise and eventual heart-lung transplantation
- Sildenafil/ Tadalafil (PDE5 inhibitor)
- Bosentan/ Ambriesentan= antiproliferative, vasodilatory
- Epoprostenol= Prostacyclin, antiproliferative, anti-aggregative
- Alternative treatment: Ca-channel blockers (nilfedipine, diltiazem), warfarin, O2 therapy
A 12 year old boy was brought to his pediatrician because of progressive shortness of breath. He said he started to get tired more quickly while playing soccer and now his mother states that he seems to have a hard time with less intensive exercise, even climbing a couple flights of stairs. She is worried he may have asthma. Upon auscultation, there is a loud S2 over his left mid-clavicular line at the 3rd intercostal space. Additionally there is some visible jugular venous distension. A lung biopsy is ordered and the following is found. What is his diagnosis, what caused this, and what is the treatment?
Primary pulmonary hypertension:
Pulmonary hypertension= increased pulmonary vascular resistance leading to elevated pulmonary arterial pressure
- *Epidemiology and prognosis:**
- uncommon
- children and young women
- progression to severe respiratory insufficiency, cor-pulmonale, death
- pathogenesis unknown; dx of exclusion
- *Treatment**: vasodilators, heart-lung transplantation
- Sildenafil/ Tadalafil (PDE5 inhibitor)
- Bosentan/ Ambriesentan= antiproliferative, vasodilatory
- Epoprostenol= Prostacyclin, antiproliferative, anti-aggregative
- Alternative treatment: Ca-channel blockers (nilfedipine, diltiazem), warfarin, O2 therapy
Histologic findings:
- plexogenic pulmonary arteriopathy (also seen in congenital heart disease with L-R shunt)
- atherosclerosis, large elastic arteries
- concentric intimal fibrosis and medial hypertrophy, medium-sized arteries and small arterioles (Below)
- thrombotic arteriopathy (eccentric intimal fibrosis and recanalization)
- veno-occlusive disease (venous sclerosis and muscularization)
Below is a histologic specimen from lung tissue of a smoker. He has been suffering from progressive shortness of breath- what types of changes have occurred?
- *Centriacinar emphysema**:
- Central/proximal acinus
- distal alveoli spared
- apical segments/upper lobes
- seen in smokers
- *Histo**: normal lung tissue with areas of dilated alveolar space
- pieces of alveolar wall not connected anywhere else (free-floating)
A 35 year old female smoker is being followed by her physician due to a new onset of hepatitis (hepatomegaly, jaundice). Additionally she reports increasing difficulty with breathing. Her breath sounds distant and there are slight crackles noted. Based on the histologic sample below, what is her diagnosis and underlying etiology? What is the treatment for this condition?
- *Panacinar emphysema**:
- all portions of acinus
- lower basal zones (seen in lower lobes)
- More homogenous distribution than centiacinar (scan below- Left= centriacinar, Right= panacinar)
- Make diagnosis based on location, not on histology alone (lower lobes)
Etiology:
- *- alpha-1-antitrypsin deficiency (PiZZ** or Pi null)
- *- worse in smokers**
Treatment: liver transplant cures alpha-1-antitrypsin deficiency
A 50-year-old man with a history of smoking two packs a day for the last 32 years (64 pack years) presents to the emergency room with a sudden onset of difficulty with breathing. He states that there was no trauma but he suddenly had tremendous chest pain and was unable to breathe. His EKG comes back normal. Upon auscultation of his lungs, you notice absent breath sounds on the left side and his heart souds are shifted to the left within his chest. What is his diagnosis and based on the histology below, what was the underlying cause of this?
Spontaneous pneumothorax due to paraseptal emphysema
- *Paraseptal emphysema**:
- Seen in distal acinus, proximal acini spared
- Adjacent to atelectasis/scarring
- Can cause spontaneous pneumothorax
- Close to septum, pleural space
Most common form of emphysema associated with spontaneous pneumothorax
- Small bubble in pleura with concomittant emphysema–> rupture–> pneumothorax
- *Theory behind emphysematous changes:** Protease-antiprotease hypothesis:
- Irritation (smoke particles)
- Activation of macrophages
- recruitment of neutrophils
- Release/enhancement of elastase
- Inactivation of alpha-1-antitrypsin
- Destruction of alveolar wall
- *Gross changes**: voluminous lung
- *Histo**: enlarged airspaces, thin alveolar walls, compressed septal capillaries, rupture of walls
A 75 year old man with a 50-year history of smoking a pack a day comes to his physician with increasing difficulty with breathing. The physician notices how he leans forward and purses his lips to breath. Upon percussion of the lungs, there is hyperresonance. Is there any treatment for the condition, based on the gross specimen below? Why is the patient having so much trouble breathing?
- *Bullous emphysema**: bullae (bubbles) form under surface of pleura (sub-pleural air accumulation)
- Less than 1 cm= blebs
- > 1 cm= bullae
Air bubble does NOT participate in gas exchange- actually inhibits gas exchange
Treatment: remove dead air space–> improve oxygenation (more space for functional lung tissue)
Pathophysiology of emphysema:
- decreased gas-exchange area (starts in distal airways–> moves toward larger airways)
- reduction of diffusion capacity
- small airway collapse (loss of support structures)
- airflow obstruction
- clinically apparent after reduction of 25% of lung volume
Symptoms of emphysema= “Pink puffer”
- exertional dyspnea
- minimal cough
- minimal sputum
- use accessory muscles
- asthenic wasting
- barrel chest
- pursed lips, paradoxical breathing (recruit ARM)
Signs of emphysema:
- hyperresonance
- depressed diaphragm
- increased static lung volume
- increase resistance to air flow
- minimal blood-gas exchange
A 65 year old man with a 40 year history of smoking comes to your office. You notice that he appears slightly cyanotic (bluish lips) and there is some swelling of his extremities. He is in your office due to a persistant cough after a cold that “just won’t go away”. On auscultation he has early crackles (large airway involvement). What is his diagnosis and what is the treatment?
Chronic bronchitis=“blue bloater”; persistant cough with sputum production for three months in at least 2 consecutive years
- *Symptoms**:
- Copious mucoid sputum
- hypercapnia, hypoxemia
- Cyanosis- vs emphysema (no prob with gas exchange, only decreased surface area)
- pulmonary hypertension, cor pulmonale (RHF)
- peripheral edema
- secondary bacterial infections
- episodes of asthma
- early inspiratory crackles
- *Treatment**:
- beta-2 agonists (bronchodilators)
- inhaled glucocorticoids (oral/IV for acute)
- Antibiotics (as needed, with acute onset)
- Inaled anticholinergic (spiriva)
- *Path**:
- Chronic irritation (due to tobacco smoke, pollution, allergies)
- Mucous gland hypertrophy/hypersecretion
- Bronchiolitis
- Secondary infections
- *Histo:**
- Hyperemia and edema of mucous membranes
- Mucinous secretions/casts filling airways
- Mucous glands hyperplasia (50% larger)
- Bronchial/bronchiolar mucous plugging
- Bronchial epithelium with squamous and goblet-cell metaplasia
- Inflammation and fibrosis
- Ciliated epithelium replaced by squamous epithelium
A 5-year old girl is taken to the physician by her mother for new onset shortness of breath. She also has watery eyes and persistant sneezing. The symptoms get worse when she goes outside to play with her dogs. Her mother says she has been giving her daughter children’s benedryl, but she started wheezing today and was having enough difficulty breathing that she considered taking her to the emergency room. The daughter currently appears to be in no acute distress and upon auscultation the physician does not hear any abnormal lung sounds. There are no obstructions in her mouth or throat. Based on a histologic sample from another person, what might this girl have and how can the physician test for it? What is the treatment?
Extrinsic (Atopic) Asthma: paroxysmal contraction of bronchial smooth muscle in response to various stimuli–> increased mucous secretion, reversible airway narrowing (obstructive lung disease)
Can be intrinsic or extrinsic, exacerbated by cold, stress, exercise
* NO NEED TO BIOPSY- diagnosis based on function tests, methacholine challenge testing
- *Clinical manifestations:**
- Acute dyspnea
- Wheezing (expiratory)
- Reversible (spontaneous or with therapy)
- Status asthmaticus= hypoxia, hypercapnia, acidosis, can be fatal
- *Treatment**:
- Acute= Beta-adrenergic agents (short acting), Anticholinergic agents (short acting), Oral prednisone (burst for flares)
- Chronic= inhaled glucocorticoids (kills eosinophils); alternatives (anti-leukotrienes, theophylline, cromylyn sodium)
- *Gross**:
- Overinflated lungs; patchy atelectasis; airways with mucous plugs
- *Histopathology:**
- Edema
- Inflammation with eosinophils (bronchitis-olitis)
- Hypertrophy of smooth muscle and mucous glands
- _Curschmann’s spirals (_whorled mucous plugs)
- Charcot-Leyden crystals (debris of eosin. Membranes)
A 35 year old woman with a history of cystic fibrosis presents to the emergency room after her husband noticed she seemed to have increased confusion and disorientation. Additionally she had a spiking fever. Her symptoms of CF had worsened over the past few days but she had not been able to get in to see her physician due to work. On auscultation, she had mid-inspiratory crackles. Based on a gross specimen below, what is her diagnosis?
Bronchiectasis: chronic necrotizing infection affecting bronchi and bronchioles–> leads to abnormal dilatation of airways. Basal segments most affected (worst drainage)
Clinical manifestations:
- Cough
- Mid-inspiratory crackles
- Fever
- Abundant purulent sputum
- Obstructive respiratory insufficiency
dyspnea/cyanosis
- Cor-pulmonale
- Metastatic brain abscesses - necrotizing infection moves to brain (first exclusion in brain abscess= bronchiectasis)
- Amyloidosis- amyloid deposition around vessels
- *Causes**:chronic necrotizing infection:
- Adenovirus, RSV infection
- Inherited: CF, dyskinetic ciliary syndrome (Kartagener syndrome), hypogammaglobulinemia- all states allow infection proliferation within air spaces
- Acquired: neurologic (swallowing, loss of cough reflex)
- *Histopath:**
- Dilatation of airways (normal airways narrow toward pleura)
- Severe necrotizing acute and chronic inflammation (bronchitis/bronchiolitis)
- Squamous metaplasia due to dilatation (reaction to environment)
- Fibrosis
- *- Abscesses- infection with necrosis**
Below: mucous material, debris fills dilated airway
CXR- Basilar idiopathic pulmonary fibrosis (IPF) with basilar infiltrate
CT: Nonspecific pulmonary fibrosis “Ground glass” appearance
A 65-year-old miner presented to his physician complaining of progressive, worsening dyspnea. He reported working in a foundry for 35 years. Based on the CXR below (compared to normal), what is his diagnosis?
Simple silicosis (chronic)
Caused by inhalation of crystalline silica (usually quartz)
- Occupational hazards: mining, quarrying, stonework foundries, abrasive, ceramic, lens polishing
- Characterized by progressive pulmonary nodules and fibrosis
CXR:
- Small nodules (1-3 mm diameter)
- Symmetric, bilateral upper lobes
- Calcified nodules (10-20%)
- Hilar lymph nodes with eggshell
- calcification
Clincal presentation:
- Acute: a few weeks to a few years after the initial exposure
- Chronic: 10 to 30 years after first exposure
- Accelerated: within 10 years of initial exposure
Dose and duration of exposure important
Symptoms variable (PFT)
Associations/complications:
- *- Progressive massive fibrosis (PMF)- below**= nodules coalesce into large masses (poor prognosis)
- Tuberculosis (2-30 fold increased incidence)
- Lung cancer (esp. in smokers)
Diagnosis:
- CXR: eggshell calcification
- Histo: nodular fibrosis, collagen whorls, birefringent silica particles
A 70-year old man dies of progressive lung disease. He was a ceramic factory worker for 45 years and a pack-a-day smoker for 50 years. He retired 5 years ago due to increasing dyspnea and eventually a diagnosis of lung cancer. Based on the histology below, what was the underlying condition that led to his cancer?
Silicosis: Causes lung cancer (increased risk in smokers)
Caused by inhalation of crystalline silica (usually quartz)
- Occupational hazards: mining, quarrying, stonework foundries, abrasive, ceramic, lens polishing
- Characterized by progressive pulmonary nodules and fibrosis
Clincal presentation:
- Acute: a few weeks to a few years after the initial exposure
- Chronic: 10 to 30 years after first exposure
- Accelerated: within 10 years of initial exposure
Dose and duration of exposure important
Symptoms variable (PFT)
Associations/complications:
- Progressive massive fibrosis (PMF)= nodules coalesce into large masses (poor prognosis)
- Tuberculosis (2-30 fold increased incidence)
- *- Lung cancer (esp. in smokers)**
Diagnosis:
- CXR: eggshell calcification
- Histo: nodular fibrosis, collagen whorls (front), birefringent silica particles (below)
A 70 year-old former ship-builders has developed progressive dyspnea on exertion. His physician orders a chest x-ray which reveals the following. What is his likely diagnosis and prognosis?
Asbestosis
“unquenchable disease”
Spectrum:
- Asbestos–> fibrosis (below)
- Pleural disease–> plaques and effusion
- Rounded atelectasis
- Malignancy: lung cancer, mesothelioma
Causes:
- Mining and milling of fibers, textiles, cement, insulation, shipbuilding; spouses clothes
Clinical presentation:
- 30-40 years post-exposure (pleural effusions 15 years post): dyspnea on exertion
Benign asbestos pleural effusion (BAPE)
- Esosinophilic, bloody, exudative
- Asymptomatic/dyspnea, chest pain, fever
- Spontaneous resolution
Complications of asbestos:
- Respiratory failure
- Malignancy: bronchogenic carcinoma (synergistic with tobacco), mesothelioma
- *Histo:**
- Granuloma with ferruginous bodies (below)
* No medical therapy for asbestos-related pulmonary disease
Below is a specimen from an 80 year-old former coal mine worker who passed away after an MI. His wife reported that he had a chronic cough, but he remained fairly active until his death. Based on the gross specimen below, what happened to his lungs?
Coal-workers pneumoconiosis:
Chronic inhalation of coal dust–> anthracosis
1. Simple CWP= small nodular opacities on chest imaging (asymptomatic)
- Coal macules (coal-dust laden macrophages, peribroncial)
- Cough
- Black sputum
- no dysfunction
- Complicatied CWP= progressive massive fibrosis (PMF) similar to silicosis (dyspnea, cough)
- Progressive severe fibrosis
- Nodules > 1 cm (dense collagen/black pigment)
- Respiratory insufficiency)
Anthracosis= accumulation of coal dust in lungs, pleura, lymph nodes
- No significant reaction
- Smokers/urban dwellers
A 40 year-old heroin user is found unresponsive in an alleyway. She is taken to the ER, where she is pronounced dead from an overdose. At autopsy, the following specimen is taken from her lungs. What changes are noted and what caused this?
Talcosis
Exposure to talc (Mg silicates: seen in mining, leather, rubber, paper)
- Diffuse foreign body granulomas with polarizable talc particles, fibrotic nodules, interstitial fibrosis
- Seen with IV drug abusers (cut heroin with talc)
A 45 year old woman presents to her physician for follow-up after completing radiation for a lymphoma 7 months ago. She reports some dyspnea with exertion which she thought may be related to her therapy, but it seems to have gotten worse lately and she has a persistant non-productive cough. On auscultation there are diffuse crackles in the bases of her lungs. What is her diagnosis and treatment?
Radiation-induced fibrosis:
Acute radiation pneumonitis (1-6 months post radiation)
- Fever, dyspnea, radiologic infiltrates
- DAD
- Responds to steroids
- *Chronic radiation pneumonitis
- Progresses to interstitial fibrosis**
- Treatment: supportive (not responsive to corticosteroids)
9 weeks post-lung transplant, a 45 year old man presents to his surgeon with a fever, shortness of breath and a persistant cough. The physician takes a CXr which reveals infiltrates in the new lung. A biopsy is taken that reveals the following- what is his diagnosis and treatment?
Post-transplant lymphocytic infiltrate
Due to:
- Infections
* *2. Acute rejection:
- Early weeks-months post-transplant
- Symptoms: fever, dyspnea, cough, CXR infiltrates
- Histo: perivascular, peribronchiolar mononuclear cell infiltrates
- Treatment: increase immunosuppression** - Chronic rejection:
- 6-12 months post-transplant
- Symptoms; dyspnea, cough
- Histo: bronchiolitis obliterans (destroyed bronchioles
- Treatment: none
- Accelerated pulmonary atherosclerosis
- Lymphoproliferative diseases
A 60 year old man with a collection of exotic birds presents to his physician because of progressive dyspnea and cough. On physical exam, he has diffuse upper lobe crackles. A biopsy of his lung reveals the following changes- what is his diagnosis and treatment?
Hypersensitivity pneumonitis: bronchiolitis obliterans organizing pneumonia (BOOP)
Extrinsic allergic alveolitis= cell-mediated reaction to inhaled antigens
Organic antigens:
- Bacteria, fungi (Farmer’s lung- Actinomyces)
- Humidifiers- thermophilic bacteria
- Indoor hot tubs
- Animal proteins (bird fancier’s lung)
Acute disease: dyspnea, chest pain, fevers, chills, productive cough
Chronic disease: insiduous, dyspnea, cough, fibrosis
Diagnosis: serm precipitins, pathology, history of exposure (presents like ILD)
Histo:
- Interstitial pneumonitis (non-specific interstitial pneumonia pattern)
- Non-caseating, poorly formed granulomas- below
- *- BOOP reaction (bronchiolitis obliterans organizing pneumonia)**
- May progress to severe interstitial fibrosis
Treatment: steroids (symptomatic), antigen avoidance
A 30-year old woman presents to her physician with a new onset of rashes on her shins. Additionally she has some joint pain and she states her eyes are pinker than normal. Based on these symptoms and the rash (below), what might her diagnosis be?
Sarcoidosis: erythema nodosum
Feature of Sarcoidosis=
- Acute, nodular and erythematous hypersensitivity reaction that involves the subcutaneous tissue of the shins (panniculitis)
- Often self-limited, resolving with mild residual hyperpigmentation.
- Typically in young women (18-34)
- May occur as drug reaction, manifestation of systemic disease, or idiopathic entity
- Biopsy non-diagnostic
Sarcoidosis:
Systemic disease of unknown etiology, affects lungs 90% of cases
- Prevalence 10-20/100,000 (AAs, N. Europeans)
- Most common ILD in USA
Presentation:
- Young adults (women)
- Asymptomatic, incidental chest x-ray finding
- Pulmonary symptoms
- Skin lesions
- Fever, arthralgia, skin (erythema nodosum), uveitis and mediastinal adenopathy (LOFGREN’S syndrome)
- Can involve multiple organs
Diagnosis:
- PFT: Restrictive and/or obstructive disease
- Pathognomonic pathology
- Hypercalcemia/hypercalciuria
Prognosis: 70% of stage 1 improve–> declines with staging
- 85% remission by 2 years
Treatment: Corticosteroid immune suppression with symptomatic/organ-involvement (cardiac, neurological, ocular)
A 50-year old African-American woman comes to her physician complaining of progressive shortness of breath. You notice some red areas on her skin. On auscultation of her lungs you hear diffuse apical crackles. Her pulmonary function tests reveal a low FVC, though her FEV1 seems to be normal (thus increased FEV1/FVC ratio). Based on the clinical findings and the CXR and CT below, what is her diagnosis and treatment?
Sarcoidosis
Systemic disease of unknown etiology, affects lungs 90% of cases
- Prevalence 10-20/100,000 (AAs, N. Europeans)
- Most common ILD in USA
Presentation:
- Young adults (women)
- Asymptomatic, incidental chest x-ray finding
- Pulmonary symptoms
- Skin lesions
- Fever, arthralgia, skin (erythema nodosum), uveitis and mediastinal adenopathy (LOFGREN’S syndrome)
- Can involve multiple organs
Diagnosis:
- PFT: Restrictive and/or obstructive disease
- Pathognomonic pathology
- Hypercalcemia/hypercalciuria
- ACE increased
Histo:
- Non-caseating granulomas
- epithelioid histiocytes
- multinucleated giant cells
- rim of lymphocytes / collagen fibrosis
- schaumann bodies (laminated calcified concretions)
- asteroid bodies (stellate inclusions within giant cells)
Prognosis: 70% of stage 1 improve–> declines with staging
- 85% remission by 2 years
Treatment: Corticosteroid immune suppression with symptomatic/organ-involvement (cardiac, neurological, ocular)
A 75 year-old man is admitted to the hospital due to progressive dyspnea causing cyanosis. He has a 45 pack-year history (he quit 10 years ago when his dyspnea started). On physical exam he has bibasilar crackles, a loud S2 over the pulmonic valve and clubbing in his fingers. Based on his symptoms and the histologic sample below, what is his diagnosis, treatment and prognosis?
Idiopathic pulmonary fibrosis:
- Chronic progressive fibrotic disease affecting older adults > 55 years, predominantly males
- Usually in ex-tobacco smokers
- Relentless course and high mortality
- Pathology is “usual interstitial pneumonia” or UIP.
Clinical presentation:
- Dyspnea (>90%)
- Non-productive cough (>70%)
- Bibasilar crackles (>85%)
- Clubbing (>25%)
- Progressive disease: pulmonary insufficiency/cor-pulmonale, cardiac failure (poor prognosis)
Pathophysiology:
Progressive interstitial fibrosis with hypoxemia
Unknown etiology
Autoantibodies common
Immune complexes (unknown antigens)
Histo:
Fibrosing and inflammatory process
Distribution is patchy, peripheral and with temporal heterogeneity
Interstitial and alveolar fibroblastic proliferation, smooth muscle proliferation, pneumocyte II hyperplasia with atypia (front)
Foci of end-stage honeycomb lung (below)
Patches of normal appearing lung
PFTs consistent with restriction
Diagnosis made by clinical picture, radiology and PFTs and confirmed by open lung biopsy
Prognosis: 50-70% mortality in 5 years
Treatment: lung transplant
A 30 year old woman with a history of SLE presents to her physician complaining of increasing dyspnea. On CXR there are diffuse lung changes and the following sample is obtained by lung biopsy. What is her diagnosis, prognosis and treatment?
Nonspecific interstitial pneumonia (NSIP)
Idiopathic interstitial pneumonitis
- Diffuse inflammation of the interstitium
- *- Younger patients**
- May progress to fibrosis
- Ground glass opacities on CT scans
- Associated with many diseases- connective tissue diseases, hypersensitivity
Prognosis: 10% mortality over 5 years
Treatment: corticosteroids
Histo:
- Histologic pattern of interstitial disease
- Cellular and Fibrosing subtypes
- Diffuse uniform changes in the lung
- Diverse etiologies (collagen vascular, hypersensitivity, drug reaction, infection)
- Prognosis better than UIP
A 60 year old man with a 45 pack-year history of smoking presents with difficulty breathing. On auscultation there are diffuse bilateral basaliar crackles. Based on his history and the histolofic specimen below, what is his diagnosis and treatment?
Desquamative interstitial pneumonitis:
form of Idiopathic interstitial pneumonitis
- Chronic lung inflammation characterized by interstitial inflammation and fibrosis and a__ccumulation of macrophages in alveolar spaces: lamellar bodies (surfactant) aggregation
- Occurs almost exclusively in current or former cigarette smokers
- Ground glass opacities on CT scans
- *Prognosis:**
- 5% mortality in 5 years
- Can progress to severe interstitial fibrosis
Treatment: smoking cessation
A 60-year old man with a 40-year history of smoking two packs a day comes to his doctor with a persistant cough. On physical exam he has bilateral crackles with distant lung sounds. The physician convinces her patient to quit smoking- after 3 months his symptoms have drastically improved. Based on the histologic specimen below, what was his diagnosis?
Respiratory bronchiolitis interstitial lung disease (RBILD): Syndrome of small airway inflammation and interstitial lung disease occurring in smokers
BOOP= bronchiolitis obliterans organizing pneumonia
Similar histologic change as in Diffuse interstitial pneumonitis (DIP) but more bronchiolocentric/patchy distribution
- Disease of cigarette smokers
BOOP= Common response to:
- infection
- inflammation
- toxins
- drugs
- collagen-vascular disease
Histo:
Loose fibrous plugs within bronchioles
Organizing pneumonia
Treatment: Smoking cessation
Biopsy from a middle-aged female smoker’s lung: note eosinophilic granulomas
Langerhans cell histiocytosis
Proliferation of Langerhans cells
Nodules of Langerhans cells and eosinophils (interstitial nodular scars with stellate shape)
Systemic vs localized
Association with cigarette smoking
EM: Birbeck granules
Immunoprofile: CD1a + , S-100 +
Most patients have good prognosis
- Mainly middle-aged women (cigarette smokers)
- Diffuse bilateral nodules (< 2 cm diameter) in upper lobes
A 35-year old woman begins to develop respiratory failure with cough and hemoptysis. Based on the gross specimen below, what is her diagnosis?
Lymphangioleiomyomatosis: Abnormal smooth muscle proliferation in lungs, lymph nodes, lymphatic ducts
Reproductive age women
Seen with tuberous sclerosis
Cystic spaces in the lung lined by abnormal smooth muscle (HMB-45 + , ER/PR +)
Progressive respiratory failure
A 40 year old man develops a parasitic infection. He develops a nagging cough and there are sounds of infiltrative pneumonia on exam. On his next exam the sounds are in a different lobe. Based on his previous diagnosis and the histology below, what is his diagnosis?
Eosinophilic pneumonia:
Eosinophilic infiltration in interstitial/ alveolar spaces
- Idiopathic: Chronic/Acute/Simple (Loeffler syndrome)
- Secondary: Infections (parasites/fungal)
- Drug-induced
- Immunological or Systemic: ABA/Churg-Strauss syndrome
A 50-year old man suffered from an acute respiratory viral illness 6 months ago and is currently being treated for renal failure. Now he has developed an interstitial pneumonia. Based on the histology below, what is his diagnosis?
Goodpasture syndrome–> acute pulmonary hemorrhage (below)
A 50 year old woman presents with glomerulonephritis as well as lesions on her nose. She has just noticed that when she coughs there is some blood. Based on the histologic specimen of her lung below, what is her diagnosis and treatment?
Wegener granulomatosis
Granulomatous vasculitis involving upper and lower respiratory tract and kidney
- Anti-neutrophilic cytoplasmic antibodies
- Vasculitis (hemoptysis), necrotic lung nodules, destructive lesions of nose and sinuses, glomerulonephritis
Diagnosis: C-ANCA autoantibody
Treatment: Steroids, immunosuppresive drugs
A 45 year old man presents to his phyisician with persistant asthma. A blood panel reveals elevated peripheral eosinophils. After ruling out a parasitic infection, a biopsy is performed. Based image below, what is the diagnosis and treatment?
Churg-Strauss syndrome: can cause diffuse pulmonary hemorrhage
Systemic vasculitis, often associated with Asthma
- *- Anti-neutrophilic cytoplasmic antibodies** (p-ANCA), peripheral eosinophilia
- Eosinophilic pneumonia, eosinophilic vasculitis
- Asthma, sinusitis
- Palpable purpura
- Peripheral neuropathy (poly/mononeuropathy)
- Heart, GI, kidney involvement (pauci-immune glomerulonephritis)
Treatment: Steroids
A 50 year old chemical plant worker comes to his physician with increasing complaints of a cough that is now productive along with worsening dyspnea. The sputum is chunky and gelatinous. A chest x-ray shows diffuse opacification of the lung fields. Based on the symptoms and the histology below, what is his diagnosis and treatment?
Pulmonary alveolar proteinosis:
Pathology:
- Impaired activity of alveolar macrophages with overproduction of surfactant (decreased GM-CSF)
- Association with exposure to irritants and recurrent RTI (fungi/Nocardia)
- Progressive respiratory insufficiency or resolution
Treatment: Repeated BALs (chelation)
Clinical presentation:
- Cough
- Sputum (chunks of gelatinous material)
- Progressive respiratory difficulty
- Diffuse pulmonary opacification on chest x-ray
Histopath:
- Alveolar spaces filled with dense, amorphous, PAS-positive, lipid containing, surfactant-like material
- Hyperplastic pneumocytes
- Focal necrosis
- No inflammation
Based on the gross pathology of the lung of a 90 year-old man who died in his sleep after being in a hospital for 3 days, what happened to his lung?
Bronchopneumonia:
CAUSES
staphylococci, streptococci, pneumococci, hemophilus influenza, pseudomonas, coliforms
GROSS
focal patchy palpable consolitation and suppuration
HISTOPATHOLOGIC
acute suppurative exudate in airspaces & airways
abscess (aggressive disease)
- Affects infants and old people
- complete resolution or fibrous scarring
- Interstitial pattern in some pediatric infections (E. coli & beta-hemolytic streptococci)
What type of histologic changes have occured in the lung specimen from a 75 year old woman with infectious pneumonia?
BOOP: organizing pneumonia
A 55 year old homeless man with a history of alcohol abuse is found on the street in a nearly comatose state. He is admitted to the hospital and started on antibiotics but succumbs to his infection. Based on his history and the gross specimen from his lung below, what was his diagnosis?
Lobar pneumonia:
CAUSES
pneumococci (most common), klebsiella, etc.
GROSS
diffuse consolidation of entire lobe (big portion of it)
HISTOPATHOLOGY
- congestion
- red hepatization (PMNs and RBCs)
- gray hepatization (fibrinopurulent exudate)
- resolution
Following a prolonged hospital stay, a 50 year old woman recieving chemotherapy is diagnosed with a pneumonia. Based on the histology below, what process has occured and what is the likely cause?
Lung abscess:
Focal suppurative inflammation with tissue necrosis
causes: staph / strept / gram negative sp. / anaerobes
complications: extension into pleural cavity, hemorrhage, septic embolization, sec. amyloidosis
- Septic embolization can go to brain!
A 50 year old woman refuses to be vaccinated against the flu “because it causes the flu”. Four weeks later she is admitted to the hospital due to flu-like symptoms and worsening dyspnea. Based on the histology below, what is her diagnosis and what complications could ensue?
Viral infection- interstitial pneumonitis
- Peribronchiolar and interstitial inflammation without consolidation (atypical pneumonia)
- patchy or diffuse
- interstitial edema and mononuclear (lymphs) infiltrate
- alveolar damage with acute inflammation and hyaline membranes
- *- may lead to ARDS**
histo: lymphocytic infiltrates in alveolar spaces, see hyaline membranes (below)
A 70-year old woman has a protracted bout of influenza and develops consolidated masses in her lungs on X-ray. Based on the sample below, what is occuring?
Viral infection: necrotizing bronchitis/bronchiolitis
Due to:
- Influenza virus
- adenovirus
- varicella
- Herpes simplex virus
Histo: Necrotizing infiltrate also includes neutrophils (like acute bacterial pneumonia–> but there’s consolidation with necrosis
What type of viral infection is evident in the slide below?
Cytomegalovirus
Histo: Large intranuclear inclusions with halo
What type of viral infection is evident in the slide below?
Herpes simplex virus
Histo: multinucleation, “ground glass” appearance; see halo (like CMV), but also multinucleation
What type of viral infection is evident in the slide below?
Adenovirus:
large nuclear inclusion (huge ratio of nucleus to cell)
What type of viral infection is evident in the cells below?
Measles: Giant cell with multiple inclusions within
Can resemble RSV
A 25 year-old otherwise healthy man presents to his physician saying he feels tired and run down and has been unable to complete any of his regular workouts. On auscultation of his lungs, there is muffled lung sounds. Additionally he is running a low-grade fever. Based on his presentation and the sample below, what is his diagnosis?
- *Mycoplasma pneumonia**
- Atypical pneumonia
- Tracheobronchitis
- peribronchial, peribronchiolar and interstitial mononuclear inflammation
- children & young adults
- Ureaplasma urealyticum perinatal pneumonia
Histo: see inflammation around airway
Other intracellular bacteria causing atypical pneumonia:
CHLAMYDIA
C. pneumonia (adults)
C. trachomatis (infants)
COXIELLA BURNETTI (Q fever pneumonia)
RICKETTSIAE (Rocky mountain spotted fever)
A 50 year old woman who recently traveled to Russia to work in an orphanage comes to her physician for her annual physical. Her PPD comes back positive. Based on the test and the histology below, what is her diagnosis?
Tuberculosis granuloma= chronic pneumonia
Chronic communicable infection
Caused by Mycobacterium tuberculosis
Aerogenic transmission
Debilitating or immunosuppressive conditions
Pulmonary involvement significant for morbidity and mortality
PPD test 2-4 weeks post infection (Type IV)
- No previous exposure to TB
- GHON COMPLEX (parenchymal subpleural lesion and caseous lymph node draining the focus
- Caseating granuloma with Acid Fast Bacilli
- Usually asymptomatic; with fibrosis and calcification of the lesion
- Old calcified lesions may contain infective organisms for decades
- Rarely progression with cavitation, TB pneumonia, or miliary TB
Histo:
- Epithelioid cells
- zone of fibroblasts and lymphocytes
- Langhans’ giant cells
- Central caseating necrosis- can be acellular due to complete necrosis within granuloma
What type of microbe is in the sputum below?
Tuberculosis granuloma= chronic pneumonia
Chronic communicable infection
Caused by Mycobacterium tuberculosis
Aerogenic transmission
Debilitating or immunosuppressive conditions
Pulmonary involvement significant for morbidity and mortality
PPD test 2-4 weeks post infection (Type IV)
- No previous exposure to TB
- GHON COMPLEX (parenchymal subpleural lesion and caseous lymph node draining the focus
- Caseating granuloma with Acid Fast Bacilli
- Usually asymptomatic; with fibrosis and calcification of the lesion
- Old calcified lesions may contain infective organisms for decades
- Rarely progression with cavitation, TB pneumonia, or miliary TB
Histo:
- Epithelioid cells
- zone of fibroblasts and lymphocytes
- Langhans’ giant cells
- Central caseating necrosis- can be acellular due to complete necrosis within granuloma
A 50 year old man from India goes to a clinic because of recent difficulty sleeping and a persistant hacking cough. He says he wakes up sweating at night and sometimes when he coughs there is blood. What is his diagnosis and how would this be confirmed?
Secondary pulmonary TB
Reactivation of old TB
Apices of lung (high oxygen pressure)
Often with symptoms (fever, night sweats,weight loss, productive cough, hemoptysis)
May progress to cavitary fibrocaseous TB, TB bronchopneumonia or miliary TB
Dx: Cultures
Prognosis: Variable
Cavitary lesion–> opens into airway system–> can then be exhaled/coughed out
Lymphohematogenous dissemination
- miliary TB (below) (foci of infection in many organs; eg. Liver, Bone marrow, spleen and kidneys- highly perfused organs)
- isolated organ TB (adrenals, kidneys, bone or female GU)
An ornothologist recently returned from the Ohio river valley with a persistant cough. Based on his travel and the sample below, what is his diagnosis?
Histoplasma capsulatum
Small yeast
Narrow-based bud
Multiply within macrophages
Dx: direct visualization & capsular Ag in body fluids and urine
Endemic in Ohio and Mississippi river valleys and Caribbean (bird/bat droppings)
Below: silver stain demonstrates presence of fungus (rule out TB)
A 40 year old woman spent 6 months in Arizona researching cactuses in the dessert. She has since developed a persistant cough. Based on her history and the sample below, what is her diagnosis?
Coccidiodes immitis
Thick-walled nonbudding large spherule with endospores
Like Histoplasmosis and TB may present as asymptomatic pulmonary disease (60%), progressive pulmonary disease, or miliary disease
Endemic in SW US
A man recently returned from a backpacking trip in Louisiana and Mississippi. Since returning he has had a nagging cough. Based on the sample below and his history, what is his diagnosis?
Blastomyces: broad-based budding
Round to oval thick-wall yeast
Broad-based bud
Similar pathology with histoplasmosis and coccidiomycosis
Endemic in central and SE US
A 45 year old woman undergoing chemotherapy develops a nagging cough. The following is cultured from her sputum. What is the diagnosis?
Candida albicans
Small yeast and pseudo-hyphae in tissue
Endogenous organism
Systemic dissemination commonly involves lung
Seen in immuno-suppressed patients (chemo, radiation, HIV)
A 45 year old man who is HIV positive comes to his physician with a new-onset cough, along with sneezing and wheezing. He states he was recently remodeling his basement. Based on his history and the sample below, what is his diagnosis?
Aspergillus spp.
Septae hyphae branching @ 45 degrees
Causes allergic bronchopulmonary aspergilosis
Aspergillomas (preexisting cavities)
Invasive infection in immunosuppressed patients
- Seen in basements, moisture-rich environments. Aerosolized–> inhalation
Histo: angioinvasive fungus: attacks vessels–> can cause hemorrhage
A 55 year old HIV-positive woman is in a car accident and has a chest CT that shows a mass in her lung. The tissue is biosied and the following is found. What is her diagnosis?
Cryptococcus neoformans
Small yeast
Thick mucoid capsule (mucicarmine positive)- sections easily Identified with stain
Cerebromeningeal dissemination from primary pulmonary focus
Harbored in GI tract of pigeons/birds
HIV infection: see “tumor” in lung
A 63 year old diabetic patient was recently diagnosed with leukemia. She develops an infection on her face that is not treatable with antibiotics and eventually needs to have surgery to ressect the areas of infection. Based on the histology below, what infection did she acquire?
- *Mucor**
- Broad irregular non-septae hyphae, 90 degrees brunching
- Nasal, pulmonary, and disseminated infections
- Diabetes / leukemia patients- devastating infections in nasal area–> have to ressect part of face/sinuses
A 34 year old man is currently being treated for an AIDS infection. While in the hospital he develops a productive cough with foamy sputum. A bronchoalveolar lavage is performed and the following is found. What is his diagnosis?
- *Pneumocystis carinii**
- Immunocompromised host (AIDS, chemo, radiation, organ transplant)
- Diffuse pulmonary infiltrates
- Foamy alveolar exudate containing proliferating organisms- seen in bronchoalveolar lavage
Histo: silver stain reveals PCP; ressembles alveolar proteinosis/pneumonia (foamy exudate and organism in alveolar space)
