Lung - Non-Tumor Pathology

Lobar bronchi are usually called secondary bronchi and segmental bronchi are called tertiary bronchi, except in Japan, where they are called first order and second order, respectively.

Bronchioles lack cartilage and submucosal glands

Right lung has 3 lobes, left lung has 2 lobes plus lingula

Right bronchus more vertical than left, thus aspirated material tends to enter right lung

Lung has double arterial supply - pulmonary and bronchial

Lungs are surrounded by visceral pleural membrane; inner chest cavity is lined by parietal pleural membrane; these membranes define the pleural space, which normally has minimal volume

Regional lymph nodes: paratracheal, pre- and retrotracheal, aortic, subcarinal, periesophageal, inferior pulmonary ligament, hilar, peribronchial, intrapulmonary

Normal histology

Lung parenchyma consists of airways (bronchi / bronchioles) and alveoli

Alveolar capillary basement membrane fuses with alveolar epithelium to form a single membrane for oxygen and carbon dioxide diffusion

Acinus / terminal respiratory unit contains 3-5 terminal bronchioles, alveolar ducts and alveoli

Alveoli are lined by respiratory epithelium (pseudostratified, columnar, ciliated)

Alveoli contain type I and II pneumocytes

Type I pneumocytes: 95%, flattened

Type II pneumocytes: 5%, produce surfactant (lamellar bodies on EM), involved in repair if type I destroyed

Bronchial-bronchiolaar epithelium contains goblet cells, neuroendocrine (Kultschitsky’s) cells, serous cells, basal cells, Clara cells and ciliated cells

Neuroendocrine cells: numerous in neonatal bronchial and bronchiolar epithelium; rare in adults except as clusters within epithelium of bronchi and bronchioles

Clara cells: increase towards terminal bronchiole; have secretory function; main progenitor cell after bronchiolar injury; have apical PAS+ diastase resistant secretory granules

Submucosal glands: contain serous and mucus cells with myoepithelial lining; may have oncocytic changes

Lymphatics: not present in alveolar walls

Pulmonary arteries: have internal and external elastic membrane, compared to a single elastic layer in pulmonary veins

Normal findings in alveoli: alveolar macrophages, corpora amylacea, blue bodies (calcium carbonate), megakaryocytes

Normal findings in interstitium: anthracotic pigment, scattered silica crystals

Pores of Kohn: perforations in alveolar walls; permit passage of bacteria and exudate between alveoli

Histologic findings of no clinical significance

Apical caps: zones of fibrosis with chronic inflammatory infiltrate in lung apices

Ectopic tissue: skeletal muscle, pancreas, adrenal cortex, neuroglia

Intrapulmonary lymph nodes

Metaplastic bone: age related finding in bronchial cartilage; associated with bone marrow elements; also rarely associated with alveolar exudate

Biopsy

For non-neoplastic lesions, clinical correlation is essential

Evaluating biopsies: alveolar space, alveolar septal membrane, conducting airways, pulmonary arteries, other vessels and lymphatics

Tips of lingula and right middle lobe typically show more fibrosis than elsewhere

Frozen section is recommended for open biopsies so (a) tissue arrives fresh, not in preservative, (b) pathologist can tell surgeon if specimen is adequate and representative

Elastic and trichrome stains are often helpful for non-neoplastic tissue

Patterns of injury for non-neoplastic disease

Source: Sternberg, S: Diagnostic Surgical Pathology (3rd Ed); Lippincott Williams & Wilkins, 1999

Interstitial inflammation/fibrosis: DIP, UIP, diffuse alveolar damage, Langerhans cell histiocytosis, asbestosis, amyloidosis, sarcoidosis, extrinsic allergic alveolitis

Intraalveolar reaction: DIP, pulmonary alveolar proteinosis, infection, extrinsic allergic alveolitis, chronic eosinophilic pneumonia

Small-airway disease: bronchiolitis obliterans, respiratory bronchiolitis, mycoplasma infection, viral infection, extrinsic allergic alveolitis, eosinophilic pneumonia

Large-airway disease: allergic bronchopulmonary aspergillosis, bronchocentric granulomatosis, TB, fungi, Wegener’s

Granulomatous vasculitis: Wegener’s, sarcoidosis, Churg-Strauss, bronchocentric granulomatosis, fungi, TB

Small vessel disease: primary pulmonary hypertension, thromboembolism, polyarteritis nodosa, veno-occlusive disease, Churg-Strauss syndrome

Hemorrhage: Goodpasture’s, SLE, immune complex glomerulonephritis, idiopathic pulmonary hemosiderosis, Wegener’s

Lymphoid infiltrates: lymphocytic interstitial pneumonia, lymphoma, lymphoid aggregates, extrinsic allergic alveolitis

Eosinophils: chronic eosinophilic pneumonia, Churg-Strauss syndrome, bronchocentric granulomatosis, Langerhans cell histiocytosis

Cystic disease/congenital anomalies

Cystic disease-general

Congenital or acquired:

Congenital: cysts, cystic adenomatoid malformation, lobar hyperinflation, sequestrations

Acquired: emphysema, healed abscess, honeycombing

Mixed: cystic fibrosis

Bronchial atresia

Portion of bronchial tree with normal branching pattern, but without any demonstrable connection to the central bronchial tree

Bronchopulmonary dysplasia

Complication of prematurity

Respiratory distress continues for months

Patients have limited pulmonary reserve, develop repeated infections, often have pulmonary hypertension and develop cor pulmonale

Micro: bronchiolar and interstitial fibrosis, compensatory emphysema of less damaged acini, inadequate alveolar development causes fewer but larger alveoli

Cystic adenomatoid malformation

Rare, 1 per 25,000 births

Variably sized cysts lined by “adenomatoid” columnar-type epithelium

Associated with stillbirth, neonatal distress and bronchial atresia; type I found in older children and adults

May represent a maturation defect

May develop with and be related to other congenital or acquired lung conditions, Archives 2002;126:934

Classification:

Type 0: 1-3%, small/firm lungs; formerly called acinar dysplasia; associated with other malformations, incompatible with life

Type I: 60-70%: large cysts up to 10 cm, lined by pseudostratified ciliated cells interspersed with mucus cells; may appear late; good prognosis since can resect; shows lepidic growth within cysts and adjacent lung, resembles bronchioalveolar carcinoma

Type II: 10-15%: small cysts up to 2 cm, resemble dilated bronchioles separated by normal alveoli; associated with other malformations; poor prognosis

Type III: 5%, solid gross appearance, excess bronchiolar structures separated by small air spaces with cuboidal epithelium resembling fetal lung; poor prognosis

Type IV: 15%, large cysts up to 10 cm, lined by flattened epithelium; good prognosis; similar to grade 1 pleuropulmonary blastoma although less cellular; sample generously to rule out blastoma

Treatment: lobectomy

References: AJSP 2003;27:1139

Cystic fibrosis

1 in 20 in US are carriers; most common mutation is #708 (seen in 70% with disease)

Mutations cause reduced chloride ion in secretions, thicker respiratory secretions, upper respiratory infections, late pancreatic insufficiency

Mutations also cause defective cilia and infertility

Meconium ileus seen in 5-10% of patients; also intussusception

Gross: emphysema, bronchiectasis, abscess, fibrosis

DD: Kartegeners (defective cilia syndrome)

Cystic fibrosis associated infections

Burkholderia cepacia: unique to cystic fibrosis, seen in 20% of patients; causes rapid deterioration of pulmonary status and death; transmitted person to person, has marked social impact as those infected are excluded from social functions (camps) and ineligible for transplant; treat with Chloramphenicol, trimethoprim-sulfamethoxazole

Pseudomonas aeruginosa: bacteria produces alginate, a capsular protein that mediates adherence; mucoid phenotype is unique to cystic fibrosis; bacteria is never eradicated from lung; treat with ceftazidime

Staphylococcus aureus: infection persists despite treatment

Stenotrophomonus maltophilia: aerobic gram negative rod, multidrug resistant, smells like onions; treat with trimethoprim-sulfamethoxazole, resistant to imipenim

Cysts

Abnormal detachment of a fragment of primitive foregut

Usually are bronchogenic cysts, adjacent to bronchi, may not connect with airways, filled with air/mucin; may become infected

Emphysema due to alpha-1-antitrypsin deficiency

Genetic deficiency

Alpha-1-antitrypsin (AAT) inhibits proteases, particularly elastase (which digests lung tissue), which is secreted by neutrophils during inflammation

PiMM: normal phenotype; 90% of population

PiZZ: associated with AAT deficiency; 80% develop symptomatic emphysema; occurs earlier and is more severe in smokers

Neutrophils are normally present in lung and alveolar space; when stimulated, neutrophils and macrophages increase in number and release elastase and oxygen free radicals, which causes emphysema unless counteracted by antiproteases such as AAT

Smokers have more neutrophils and macrophages in alveoli, tobacco use enhances release of elastase from neutrophils, enhances elastase activity, oxidants in tobacco smoke inhibit AAT

Hypoplasia

Lung weighs less than normal with fewer alveoli than expected for gestational age

Bilateral disease is fatal

Causes: oligohydramnios (renal agenesis, fetal membrane rupture), decreased intrathoracic space (renal cystic disease, diaphragmatic hernia), reduced breathing (anencephaly, musculoskeletal disorders)

Lobar hyperinflation

Also called congenital lobar emphysema

Infants or young children

Perhaps due to hypoplasia of bronchial cartilage; associated with other cardiopulmonary anomalies

Affects left or right upper lobe or right middle lobe

May cause severe compression of other pulmonary lobes

Not emphysema since no tissue destruction

Micro: massive distention of alveolar spaces but no tissue destruction

Mesenchymal cystic hamartoma

Multifocal, bilateral cysts < 1 cm lined by normal or metaplastic respiratory epithelium resting on a cambium layer of mesenchymal cells

Sequestrations (intralobar and extrapulmonary lobar)

Lobes or segments of lung without a normal connection to the airway system

Extrapulmonary sequestrations: external to lung, covered with separate pleural lining, may be anywhere in thorax or mediastinum; usually infants, abnormal masses, 90% on left side, 20% have other congenital anomalies; associated with polyhydramnios and edema

Intralobar sequestrations: within the lung, usually lower lobe, segment is supplied by a large artery from aorta, not invested with its own pleura, associated with infections, bronchiectasis, chronic inflammation, fibrosis

Blood supply is from aortic branches, NOT pulmonary arteries

Chronic obstructive pulmonary disease (COPD)

COPD-General

Also called chronic obstructive lung disease (COLD)

Major cause of bed defining disability in US

Major symptom is dyspnea (shortness of breath)

Usually due to cigarette smoking

Site of disease: bronchi-chronic bronchitis, bronchiectasis, asthma; bronchioles-bronchiolitis, acini-emphysema

Obstructive airway disease: increase in resistance to airflow due to obstruction at any level; includes emphysema, chronic bronchitis, bronchiectasis, asthma, tumor, foreign body; reduced maximal airflow rates (FEV1)

Restrictive airway disease: reduced expansion of lung parenchyma with decrease in total lung capacity; normal FEV1; due to chest wall disorders (polio, obesity, pleural disease, kyphoscoliosis), interstitial / infiltrative diseases (ARDS, dust diseases, interstitial fibrosis)

Asthma

Chronic relapsing inflammatory disorder characterized by hyperreactive airways, causing episodic, reversible bronchoconstriction

Usually associated with atopy, mediated by IgE

Has increased in Western hemisphere over past 30 years

Extrinsic: Type I hypersensitivity; either atopic (due to allergens), occupational or due to allergic bronchopulmonary aspergillosis

Intrinsic: nonimmune; due to aspirin ingestion, pneumonia, cold, stress, exercise

Status asthmaticus: unremitting attacks due to exposure to previously sensitized antigen; may be fatal

Gross: overdistended lungs, small areas of atelectasis, thick mucus plugs in proximal bronchi containing whorls of shed epithelium

Micro: Curschmann spirals, eosinophils contain Charcot-Leyden crystals (eosinophil membrane protein); increased mucosal goblet cells and submucosal glands, thickened basement membrane, bronchial smooth muscle hypertrophy, airway wall edema

DD: allergic bronchopulmonary aspergillosis, bronchocentric granulomatosis without the granulomatous inflammation

Atopic asthma

Begins in childhood, triggered by environmental allergens (dander, dust, pollen, food), often positive family history

Skin test causes wheel and flare reaction

Classic example of Type I IgE mediated hypersensitivity reaction

Initial sensitization affects T helper 2 cells, which release IL-4/5, which promote IgE release by B cells, mast cells and eosinophils

Reexposure to allergen leads to mediator release from mucosal mast cells

Acute/intermediate response is bronchoconstriction, edema, mucus secretion, hypotension

Late phase reaction, due to influx of other inflammatory cells, is release of major basic protein from eosinophils, which causes epithelial damage and airway constriction

Putative mediators: leukotrienes C4, D4, E4 and acetylcholine; minor mediators: histamine, prostaglandin D2

Associated with serum eosinophilia, sputum eosinophils

Occupational asthma

Due to repeated exposure to fumes, dusts, gases, chemicals, often in minute quantities

Drug induced asthma

Associated with aspirin use

Rare, associated with recurrent rhinitis and nasal polyps

Patients are sensitive to small doses of aspirin, get urticaria and asthma

May be due to direct effects of aspirin on cyclooxygenase pathway

Nonatopic asthma

Due to respiratory infection (rhinovirus, parainfluenza virus); usually not familial

Normal serum IgE, negative skin tests

Viral induced inflammation may lower threshold of subepithelial vagal receptors to irritants

Bronchiectasis

Chronic necrotizing infection of bronchi and bronchioles associated with permanent dilation of these airways

Diagnosis is based on presence of infection (stasis occurs in dilated bronchi) and obstruction

Symptoms: cough, fever, copious amounts of foul-smelling, purulent sputum

Causes: bronchial obstruction (localized bronchiectasis), congenital bronchiectasis, cystic fibrosis, intralobar sequestration of lung, immunodeficiency states, immotile cilia / Kartegeners syndrome, Young’s syndrome, necrotizing pneumonia (staphylococcus, tuberculosis)

Obstruction (due to tumor, foreign body, inspissated mucus) causes resorption of air distal to obstruction, atelectasis, intraluminal secretions

Nonobstructive bronchiectasis is due to pneumonia and atelectasis, which increase negative intrapleural pressure, which exerts an external force on bronchial walls, causing them to dilate; usually left sided affecting lower lobes

Cystic fibrosis: obstruction due to mucus plugs, infection is due to decreased ciliary clearance of bacteria

Kartegeners syndrome: autosomal recessive condition with variable penetrance, due to absent or irregular dynein arms of cilia, which causes defective bacterial clearance (bronchiectasis, sinusitis), defective cell motility during embryogenesis (situs inversus), immotile sperm (infertility)

Young’s syndrome: infertility caused by azoospermia, but without ultrastructural ciliary abnormalities

Gross: markedly distended peripheral bronchi, usually in lower lobes, can trace to pleural surface; bronchial walls irregularly thickened

Micro: chronic inflammation, ossification and ulceration of bronchial cartilage; variable inflammation and fibrosis of alveoli; thickened pleura

Chronic bronchitis

Diagnosis: persistent cough with sputum for 3 months in 2 consecutive years

More infections, purulent sputum, hypercapnia, hypoxia than emphysema; clinically called “blue bloaters”

May cause secondary pulmonary vascular hypertension, cor pulmonale, congestive heart failure; death due to respiratory acidosis and coma, congestive heart failure, pneumothorax

Simple chronic bronchitis: cough but no physiologic evidence of airway obstruction

Chronic asthmatic bronchitis: hyperreactive airways with intermittent bronchospasm and wheezing

Obstructive bronchitis: often have associated emphysema

Causes: 4-10x more common in smokers, also chronic irritation, infections

Tobacco interferes with ciliary action, directly damages airway epithelium, inhibits ability of white blood cells to clear bacteria; infections maintain but do not initiate chronic bronchitis

Reid index: ratio of thickness of mucus gland layer to thickness of wall between epithelium and cartilage; normal is 0.4, increased in chronic bronchitis

Gross: boggy mucosa with excessive mucinous secretions, pus

Micro: early-hypersecretion of mucus in large airways with hypertrophy of submucosal glands in tracheobronchial tree

later-increase in goblet cells in small airways causes excessive mucus production and airway obstruction; increased Reid index; variable dysplasia, squamous metaplasia, bronchiolitis obliterans

Emphysema

Abnormal permanent enlargement of air spaces distal to terminal bronchiole with wall destruction but without fibrosis

Differs from overinflation, which is not due to wall destruction (example: due to loss of opposite lung)

Acinar and airspace enlargement is usually due to tobacco related wall destruction

Centroacinar emphysema: 95% of emphysema cases, causes significant airflow obstruction, affects central part of acini, sparing distal alveoli; worse in upper lobes, particularly apices; walls are anthracotic with parabronchial inflammation; seen in heavy smokers, coal worker pneumoconiosis; clinically significant at age 40+ in smokers, although ventilatory deficits seen earlier

Panacinar (panlobular) emphysema: 5% of cases, causes significant airflow obstruction; acini uniformly enlarged from respiratory bronchiole to terminal alveoli; usually lower lungs; associated with alpha-1-antitrypsin deficiency; lungs usually voluminous

Paraseptal (distal acinar) emphysema: minor clinically; distal acini only affected, emphysema is next to pleura, near areas of fibrosis, scarring or atelectasis; multiple continuous airspaces are affected; may be source of spontaneous pneumothorax in young adults

Irregular emphysema: minor clinically; invariably associated with scarring, irregular involvement of acini

Compensatory emphysema: response to loss of lung elsewhere, such as post-lobectomy

Senile emphysema: due to age-related alterations in internal geometry of alveoli leading to larger alveolar ducts, smaller alveoli, but no loss of elastic tissue or destruction of lung substance

Obstructive emphysema: due to tumor, foreign body or congenital lobar overinflation (infants, perhaps due to hypoplasia of bronchial cartilage; associated with other cardiopulmonary anomalies); due to ball-valve effect with inhalation via collaterals (pores of Kohn, canals of Lambert); may compress normal lung, may be life-threatening

Bullous emphysema: any form that produces blebs > 1 cm; often subpleural, near apex, associated with tuberculosis scarring; may rupture and cause pneumothorax, hemorrhage; called placental transmogrification if it resembles chorionic villi

Interstitial emphysema: air into connective tissue stroma of lung, mediastinum or subcutaneous tissue; due to alveolar tears, chest wounds, coughing, whooping cough

Pathogenesis: alteration in balance between proteases and antiproteases

Clinical: no symptoms until 1/3 of functional capacity is lost; get shortness of breath, coughing, wheezing, weight loss; barrel chest; breath through pursed lips (pink-puffer), which causes slowing of forced expiration

May cause secondary pulmonary vascular hypertension, cor pulmonale, congestive heart failure, death due to respiratory acidosis and coma, pneumothorax

Best to assess based on morphometry, not lung function data, Mod Path 2003;16:1

Infections

General/pneumonia

Lung is #1 site for infections that cause lost workdays

Pneumonia is due to impairment of normal defense mechanisms or lowered host resistance

Normal defense mechanisms: nasal clearance (sneezing, blowing, swallowing), tracheobronchial clearance (mucociliary action), alveolar clearance (alveolar macrophages)

Impairment due to suppression of cough reflex (drugs, virus), injury to mucociliary apparatus (smoking, virus, Kartegeners syndrome), injury to macrophages (tobacco, alcohol, anoxia), pulmonary congestion/edema, accumulation of secretions (cystic fibrosis)

Note: viral pneumonia predisposes to bacterial pneumonia

Common agents: Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenza, Pseudomonas aeruginosa, coliforms

Complications: abscess, empyema, organization, sepsis, meningitis

Consolidation: exudative solidification of lung

Symptoms of pneumonia: shortness of breath, fever, productive cough, malaise, friction rub (if fibrinous pleuritis)

Bronchopneumonia

Patchy consolidation of the lung centered on bronchi

Micro: neutrophils in bronchi, bronchioles and adjacent alveolar spaces; lipid pneumonia if marked lipid laden macrophages

Lobar pneumonia

Affects entire lung but now rare due to antibiotics; associated with increased virulence of organism or increased host vulnerability (infants, elderly); may be due to extension of existing bronchiolitis or bronchitis

Micro: initially congestion with bacteria and few neutrophils; then red hepatization (grossly resembles liver) with massive congestion, neutrophils, fibrin; then gray hepatization with fibrinopurulent exudate and organization; then resolution with resorption of exudate

Abscess

Due to sinobronchial infections, dental sepsis, aspiration (due to alcoholism, coma, debilitation), primary bacterial infection (Staphylococcus aureus, Klebsiella pneumonia, Streptococcus pneumonia), fungi, bronchiectasis, post-transplant, septic emboli, neoplasia induced obstruction, idiopathic

Aspiration induced abscesses more common on right side (right sided bronchus is more vertical), usually single

Air fluid level present if there is communication with air passages

Symptoms: cough, fever, copious foul-smelling sputum, fever, chest pain, weight loss, clubbing of digits

10% of cases are associated with underlying carcinoma

May extend into pleural cavity, create septic emboli causing meningitis or brain abscess, serve as nidus for fungal overgrowth (Mucor, Aspergillus), spread elsewhere in lung

Treatment: lobectomy

Gross: thick fibrotic walls and surrounding pneumonia in chronic abscesses

Adenovirus pneumonia

Cold agglutinins present in 20%

Micro: epithelial cells contain smudged nuclei with bricklike intranuclear inclusions; also necrosis of bronchial and alveolar epithelium and acute inflammation

Neonatal adenovirus infection of lung

More typical findings in liver and adrenal glands than in lung

Micro: glassy nuclei; severe necrotizing bronchiolitis extending into ducts and airways

AIDS related pneumonia

Diagnose with bronchoalveolar lavage, transbronchial biopsy or open lung biopsy

Nonspecific features resemble DIP or lymphocytic interstitial pneumonia

Patients often have multiple infections

Open lung biopsies should routinely be stained for Pneumocystis, fungi, mycobacteria

Cavitary lesions: Staphylococcus, fungi (Candida, Aspergillus, Cryptococcus, Histoplasma, Blastomyces), Mycobacterium tuberculosis, Mycobacterium avium intracellulare, Rhodococcus equi

Patients also have infections from CMV, Pneumocystis carinii, toxoplasma, microsporidia

Associated with Kaposi’s sarcoma

Aspergillus

Occurs as secondary colonization of lung abscess, aspergilloma, allergic bronchopulmonary aspergillosis or invasive aspergillosis in immunocompromised

Associated with renal transplant recipients

Micro: dichotomous (into two nearly equal branches) branching, septate hyphae, often invade vessels

Allergic bronchopulmonary aspergillosis

Bronchocentric granulomas in asthmatics that contain numerous eosinophils, and noninvasive Aspergillus organisms or other fungi

Also thick mucus plugs

Over time, bronchi become dilated, causing bronchiectasis

Atypical mycobacteria

Associated with immunosuppression, chronic obstructive lung disease, prior TB, pneumoconiosis, bronchiectasis, lung carcinoma

Culture required for diagnosis

Positive stains: acid fast (bacilli are longer [20 microns], more coarsely beaded and more bent than M. tuberculosis bacilli)

Bacillary angiomatosis

Pseudoneoplastic vascular proliferation affecting lungs, bronchi, other sites

Treatment: antibiotics

Blastomyces

Grossly resembles tuberculosis

Micro: mixed acute and granulomatous inflammation caused by large budding yeasts, with broad based buds

Candida

Pseudohyphae and budding yeasts

CMV pneumonia

Usually immunocompromised patients

Associated with Pneumocystis and other infections

Xray: 2-4 cm peripheral nodules, miliary pattern, diffuse interstitial process

Micro: mononuclear infiltrate, edema and pneumocyte hyperplasia; enlarged cells have nuclear and basophilic cytoplasmic inclusions; hemorrhagic necrosis may be present; CMV usually infects endothelial and epithelial cells

Positive stains: PAS, GMS, CMV

Coccidiodes immitis

In Southwest US, Mexico, Central America and San Joaquin Valley (California) in soil

In vitro, may have hyphae which form arthrospores, very infectious, requires careful handling in lab

Gross: necrotic center surrounded by fibrous tissue with concentric lamination

Micro: granulomatous inflammation, large thick-walled spherules contain variable sized daughter cysts

Cryptococcus neoformans

Yeast found in pigeon droppings, may cause meningitis

Micro: somewhat pleomorphic round/oval 4-10 micron yeast, thick mucinous capsule stains bright red with mucicarmine; some are unencapsulated

Cryptosporidium

Dirofiliaria immitis

Dog heartworm; may infect humans as secondary end-stage host, particularly in southern coastal states in US

Adult worms die in right ventricle, embolize in pulmonary arterial circulation, evoke necrotizing granulomatous response with vasculitis in lung tissue

Rarely see dead worms

Usually self limited in humans, but may cause lung infarct

Case report of solitary pulmonary nodule in 15 year old girl who had contact with dogs, Archives 2002;126:227

Chest Xray: solitary peripheral pulmonary nodule

Micro: rounded infarct with coagulative necrosis, well demarcated from surrounding normal lung by epithelioid histiocytes and fibrous connective tissue; focal calcifications and lymphoid aggregates; necrotic nematode has homogenous cuticle without external ridges, longitudinal muscle layer just internal to cuticle and internal cuticular ridges

Eosinophilic pneumonia

General term that includes all lung disease associated with peripheral eosinophilia and eosinophilic inflammation of lung regardless of peripheral eosinophilia, but excluding Langerhans cell histiocytosis

Usually chronic (see below), but may have sudden onset

Causes: parasites (helminths, Dirofiliaria, filarial), fungi, bacteria, hypersensitivity pneumonitis, drug allergies, asthma, allergic bronchopulmonary aspergillosis, polyarteritis nodosa, rheumatoid arthritis, nephrotic syndrome, scleroderma, ulcerative colitis

Symptoms: fever, weight loss, shortness of breath

Xray: peripheral infiltrate

Micro: alveolar and interstitial infiltration by eosinophils, also plasma cells and histiocytes; may have Charcot-Leyden crystals; variable angiitis, granulomatosis, fibrosis, mucus plugging, bronchiolitis with necrosis

Hantavirus pneumonia

Severe pulmonary disease, often in Southwest US

Causes interstitial pneumonitis with mononuclear infiltrate, edema, focal hyaline membranes

Herpes simplex pneumonia

Gross: diffusely firm lungs with small yellow/red necrotic areas

Micro: interstitial pneumonia with necrosis of bronchial and alveolar epithelium and acute and chronic inflammatory infiltrate; occasional intranuclear viral inclusions present at edge of necrotic areas

Neonatal HSV pneumonia

More typical findings in liver or adrenal gland than in lung

Gross: normal

Micro: patchy necrosis; minimal inflammatory response; not bronchocentric

Histoplasma capsulatum

Gross: resembles tuberculosis, has “tree-bark” appearance

Micro: small budding yeasts, 3-5 microns, intracellular

Negative stains: acid-fast

Influenza pneumonia

Variable changes from mild acute lung injury to necrotizing pneumonia to BOOP-like changes

Legionella pneumophila / Legionnaires’ disease

Initial awareness after epidemic in Philadelphia, Pennsylvania (US) convention of American Legion

Retrospective review disclosed sporadic cases since early 1900’s

Caused by short, gram-negative bacillus

Hilar lymph nodes infected in 50% of cases at autopsy, 25% have spread to other organs

Causes: initially infected water cooling systems; also corticosteroids in renal transplant patients, any potable water supplies

Treatment: erythromycin, other antibiotics, although high mortality in immunocompromised

Micro: extensive bronchopneumonia with intra-alveolar neutrophils, macrophages, fibrin, often with leukocytoclastic neutrophilic infiltrate, small vessel vasculitis and necrosis

Positive stains: Dieterle silver stain

Malakoplakia

Very rare, usually in immunocompromised patients

70% of cases are due to Rhodococcus equi, an animal pathogen causing opportunistic infections

Treatment: antibiotics

Gross: nodular masses or infiltrates with cavitation

Micro: intraalveolar histiocytes with pink or foamy cytoplasm that fill and destroy alveoli, not interstitium; histiocytes contain PAS+ bacteria, also Michaelis-Gutmann bodies [round/oval structures, 5-20 microns, with laminated or targetoid appearance that stain deeply with H&E, iron and calcium stains]; also lymphocytes, plasma cells, neutrophils

DD: atypical mycobacteria (blue histiocytes, positive acid fast stain), Whipple’s disease, Gaucher’s disease

Measles

Micro: giant cells with viral inclusions; nuclei may contain single large Cowdry Type A inclusion

Mucor

Fungi common in patients with diabetes

Micro: large, non-septa hyphae with 90 degree angle branching and non-parallel walls

Mycobacterium avium-intracellulare

More common in AIDS patients with low CD4 counts or other immunosuppressed individuals

Micro: marked intraalveolar and parenchymal infiltration by foamy histiocytes or proteinaceous reaction

Positive stains: acid fast (high numbers of intracellular bacteria)

Mycoplasma pneumoniae pneumonia

Formerly called atypical pneumonia

Causes interstitial pneumonia (usually) or bronchopneumonia

Often asymptomatic

Diagnosis: cold agglutinins present in 50% of cases

Gross: red-blue, congested, patchy lungs, usually no pleuritis

Micro: bronchiolitis, interstitial and minimal intra-alveolar involvement with widened alveolar septa due to lymphoplasmacytic inflammatory cells; intra-alveolar proteinaceous material; neutrophilic infiltrate in bronchioles, bronchiolar metaplasia, lymphoplasmacytic infiltrate in bronchial wall, pneumocyte hyperplasia

DD of infectious interstitial pneumonia: respiratory syncytial virus, rhinovirus, rubeola, varicella, Chlamydia psittacosis, Coxiella burnetti (Q fever)

Nocardia

Opportunistic lung infection associated with transplantation, chemotherapy, immunosuppression, steroids

Gram stain: slender, slightly beaded, branching, filamentous bacilli

Micro: focal bronchopneumonia with microabscesses, ill-defined granulomas

Positive stains: acid fast

Organizing pneumonia

Pneumonia may resolve or organize

Organizing pneumonia may simulate malignancy due to radiographic shadows and clinical cough, hemoptysis and weight loss; usually due to Streptococcus pneumoniae or Haemophilus influenza

Gross: sharply outlined, firm area, with preservation of lung pattern; extends to thickened pleura

Micro: exudate of fibrin and neutrophils, necrotizing changes in bronchi, alveolar macrophages

DD: BOOP, inflammatory pseudotumor

Paragonimus kellicotti

Due to ingestion of raw or undercooked crayfish infected with trematode Paragonimus (lung fluke)

Case report of 35 year old North American man with recurrent pneumothorax and cavitary lesion, AJSP 2003;27:1157

Micro: non-necrotizing granulomas with giant cells containing eggs with operculum; also lymphocytes, plasma cells, eosinophils

Pneumocystis carinii pneumonia

Opportunistic fungus present in bronchoalveolar lavage (BAL), sputum or biopsy

Most common pneumonia in AIDS patients, who are at high risk if CD4 < 200 or if protein-calorie malnutrition

Causes diffuse or patchy pneumonia; may have coexisting CMV or other infections

Diagnosis: bronchoalveolar lavage and imprints have high sensitivity

Treatment: pentamidine, folic acid inhibitors, anti-HIV drugs

Micro: alveolar spaces filled with pink, foamy, amorphous material composed of proliferating fungi and cell debris; fungi are 4-6 microns, cup/boat shaped cysts; also mild inflammatory reaction with fibrin exudate, hyaline membranes

Positive stains: GMS, Warthin Starry, other silver stains, Gram-Weigert

DD: alveolar proteinosis (diffuse pulmonary opacification and intra-alveolar PAS-positive material and lipid; sputum contains gelatinous material; no inflammation; alveolar contents contain type II pneumocytes & necrotic alveolar macrophages)

DD: Goodpasture’s (necrotizing, hemorrhagic, interstitial pneumonitis; associated with rapidly proliferative glomerulonephritis, linear immunoglobulin deposits on basement membranes of alveolar septal walls; also intra-alveolar hemorrhage, septal thickening and hypertrophy, organization of blood in alveolar spaces)

DD: BOOP (bronchiolar and alveolar plugs of loose fibrous tissue)

Pseudomonas aeruginosa

Gram negative bacillus

Infants (below), patients with burns or on ventilators, immunocompromised, critically ill

Immunocompromised patients usually have paucicellular pattern below; immunocompetent have cellular pattern

Perivascular bacterial infiltration is somewhat specific for pseudomonas

Micro: necrotizing pneumonia with 2 patterns - paucicellular coagulative confluent bronchopneumonia with perivascular bacillary infiltration or cellular pneumonia without evidence of perivascular organisms

Infants

Rare (0.3% of neonatal ICU admissions); usually low birth weight (1.2% of low birth weight admissions)

Mortality 32-87% with death within 1-2 days

Diagnosis made by culture

Rapidly progressive course in immunosuppressed individuals, who often have paucicellular bronchopneumonia and bacteremia

More protracted course if immunocompetent, associated with cellular pneumonia

Micro: necrotizing pneumonia with 2 patterns - paucicellular coagulative confluent bronchopneumonia with perivascular bacillary infiltration or rarely a cellular pneumonia without evidence of perivascular organisms

References: Hum Path 2003;34:929

Respiratory syncytial virus (RSV)

Often in children under 2 years old, may cause death in infants 1-6 months

Micro: giant cells with round, pink, intracytoplasmic inclusions

Rhodococcus equi

May cause malakoplakia in AIDS patients

Case report of cavitary lesion in 15 year old girl with congenital AIDS, Archives 2003;127:e315.

“Rhodo” since salmon-pink pigment in culture

Treated with antibiotics, but mortality is 50% in AIDS patients, 20% in other immunocompromised, 10% in immunocompetent

Micro: epithelioid macrophages containing gram positive, partially acid fast coccobacilli organisms; may produce malakoplakia

SARS

Severe Acute Respiratory Syndrome

Caused by SARS-associated coronavirus, a new member of Coronaviridae

Outbreaks worldwide in 2002

Micro: diffuse alveolar damage (DAD) varying based on duration of illness; 10 or fewer days - acute phase DAD, airspace edema, bronchiolar fibrin, small airway injury; 11+ days - organizing phase DAD, type II pneumocyte hyperplasia and marked reactive atypia, squamous metaplasia, multinucleated giant cells, acute bronchopneumonia

Acute phase DAD: hyaline membranes lining alveolar walls, interstitial and airspace edema, interstitial infiltrates of inflammatory cells, and vascular congestion

Organizing-phase DAD: fibroblast proliferation in interstitium and air spaces

Small airway injury: loss of cilia, bronchiole epithelial denudation, deposition of fibrin within the lumen and on exposed basement membranes

References: Hum Path 2003;34:743

Serratia marcesens

Gram negative rod

Staphylococcus aureus

Syphilis

Case report of premature newborn with congenital syphilis, acute hyaline membrane disease and bilateral lung abscesses with spirochetes, Archives 2002;126:484

Toxoplasma gondii

Associated with AIDS, immunosuppression

Intracellular parasite that causes focal parenchymal necrosis, diffuse interstitial pneumonia

Micro: organisms present in histiocytes, alveolar lining cells, endothelial cells

Positive stains: GMS, Giemsa, Gram-Weigert

Tropical eosinophilia

Due to microfilaria of Wuchereria bancrofti, which circulate in pulmonary capillaries and cause immediate type of eosinophilic hypersensitivity reaction

Restricted to tropical regions

Micro: microfilaria within pulmonary capillaries with marked eosinophilic infiltrate

Tuberculosis (TB)

Due to Mycobacteria tuberculosis

Lung involvement is the major cause of morbidity/mortality

Cases increasing due to AIDS and emergence of multiple-drug resistant strains; AIDS patients may lack granulomas

Rarely involves skin, oropharynx, lymphoid tissue

Initial focus of infection is Ghon complex, consisting of parenchymal subpleural lesion, near upper/lower lobe interlobar fissure (apex has high oxygen tension) with enlarged caseous lymph nodes; lesions usually undergo fibrosis, calcification and cause no symptoms

Rarely (infants, children, immunocompromised), get progressive spread with cavitation, TB pneumonia, miliary TB

Treatment: prolonged multi-agent antibiotics

Surgery: pulmonary resection indicated for open cavity after 4-6 months of drug therapy, residual caseous disease, irreversible destructive lesion (bronchiectasis, bronchial stenosis), recurrent hemorrhage, unexpandable lobe with associated TB empyema, suspected tumor; surgical success rate (inactive disease) is 80% after 2-5 years

Gross: inflamed, fibrotic, nonfunctioning lung parenchyma, may have bronchial strictures, bronchiectasis, cavitation, thickened pleura

Micro: caseating granulomas; cavities show approximation of walls, granulation tissue, fibrosis, stellate scar; may have metaplastic bone formation

Secondary (reactivation) pulmonary TB

5-10% of cases of primary infection

Produces more damage than primary TB

Apical areas of consolidation with caseous necrosis in draining nodes

Usually get progressive fibrous encapsulation, which causes focal pleural adhesions, may contain anthracotic pigment

Tubercles coalesce over time, creating confluent area of consolidation

Diagnosis: appearance of bacteria with acid-fast stain, positive smears or cultures; 1 bacillus in a 1 cm3 granuloma indicates the presence of 2000 organisms

Micro: caseating granulomas with Langhans giant cells

Progressive pulmonary TB

Progression to cavitary disease, miliary TB or TB bronchopneumonia

Cavitary disease: drainage of caseous focus transforms it into a cavity, usually in apex and walled off; may spread to other parts of lung, producing endobronchial and endotracheal TB, laryngeal seeding, intestinal TB

Miliary TB: seeds bone marrow, liver, spleen, retina via blood or lymphatics; grossly see distinct, small, yellow-white areas of consolidation, central necrosis identifiable microscopically

TB bronchopneumonia: occurs in highly sensitized, highly susceptible people; also called “galloping consumption”; multi-agent treatment is effective unless resistant organisms, diabetes, AIDS, reactive amyloidosis

Tuberculomas

Due to reinfection; may rupture and cause widespread dissemination

Treatment: excision to rule out malignancy and destroy possible nidus for infectious spread

Gross: round, discrete, solitary, firm nodules, adjacent to pleura; may have concentric laminations, cavitation or calcification; may communicate with bronchus

Micro: persistent caseation surrounded by thick fibrous walls with Langhans giant cells, epithelioid histiocytes, lymphocytes; also subpleural fibrous thickening

Positive stains: acid-fast bacilli

Varicella zoster pneumonia

Associated with necrosis of bronchial and alveolar epithelium and acute inflammation

Granulomatous inflammation (non-infectious)

General

Rosai recommends culture and stains for fungi and Mycobacteria in every case

Other disorders with granulomas: fungi (Actinomyces, Aspergillus, Blastomyces, Coccidiodes, Cryptococcus, Histoplasma, Mucor, Sporotrichosis), eosinophilic pneumonia, bronchial chondromalacia, inhalation of talc (drug abusers), metal dust from occupational exposure (berylliosis), extrinsic allergic alveolitis, prior alveolar hemorrhage (cholesterol granulomas), lipogranulomas (with diabetes)

Allergic granulomatosis

Also called Churg-Strauss syndrome

Very rare

Systemic vasculitis resembling polyarteritis nodosa associated with asthma, peripheral eosinophilia, pulmonary involvement, fever

Rarely presents without pulmonary disease as fever of unknown origin

Treatment: steroids (effective, but patients may relapse)

Micro: lung and extrapulmonary sites (skin, heart, nervous system, GI) have prominent eosinophilic infiltrate, granulomatous reaction around necrotic foci with radially arranged histiocytes and pallisading giant cells near small arteries or arterioles, eosinophilic vasculitis; may have fibrin-rich edema, lymphocytes, sarcoid-like granulomas, focal fibrosis, eosinophilic microabscesses

DD: Wegener’s (also kidney involvement, no tissue or serum eosinophilia or asthma), rheumatoid nodules (no tissue or serum eosinophilia or asthma)

Bronchocentric granulomatosis

Granulomatous disease of lungs in which almost all granulomas are centered in bronchi or bronchioles, causing their destruction

Immunologic reaction related to chronic eosinophilic pneumonia and allergic bronchopulmonary aspergillosis

Usually adults, often with asthma history, limited to lungs, may be asymptomatic

Usually solitary lesions that appear on chest Xray as atelectasis or consolidation, not nodules

Favorable prognosis

Gross: viscous material in involved bronchi

Micro: large and medium bronchi infiltrated by neutrophils, eosinophils and necrotic debris surrounded by foreign body giant cells; fragmented elastic tissue (with elastic stain); also bronchiolitis obliterans; no fibrinoid necrosis of vessels

DD: Wegener’s (may also have bronchocentric granulomas), TB, fungi, cystic fibrosis, rheumatoid arthritis

Hyalinizing granuloma

Rare nodular lung lesion

Usually multiple, bilateral, cause unknown

Associated with sclerosing mediastinitis, retroperitoneal fibrosis, lymphoma

May be progressive but doesn’t cause death

Micro: central keloid-like collagen, arranged in whorls, surrounded by foreign body giant cells simulating nodular amyloidosis; may have plasma cells and lymphocytes between collagenous bands; usually no epithelioid granulomas, no necrosis

Negative stains: Congo red

Sarcoidosis

Multisystemic disease of unknown origin that involves lung in 90% of cases

Presents as perihilar node involvement, diffuse pulmonary disease, pulmonary interstitial fibrosis, localized bronchial stenosis, distal bronchiectasis and atelectasis

Usually 20-40 years, F > M, 90% are black, rare in Chinese, Southeast Asians

80% have elevated serum angiotensin-converting enzyme (not specific); polyclonal serum hypergammaglobulinemia is common

65% recover without further problems; 20% have permanent pulmonary loss; 3% die of pulmonary fibrosis, congestive heart failure

Best prognosis: hilar lymphadenopathy alone

Worst prognosis: pulmonary disease without adenopathy

Treatment: steroids for severe symptoms, advanced disease

A diagnosis of exclusion, since there are no specific criteria for disease; should culture and use special stains

Lungs: either no gross lesion or 1-2 cm nodules; often in bronchial submucosa, so biopsies are helpful

Lymph nodes: hilar or mediastinal lymph nodes involved in almost all cases, tonsils involved in 25% of cases; nodes are enlarged, may be calcified

Liver/spleen: microscopic involvement in 75% of cases, gross disease in 20%

Bone: Xray changes in 20%, usually small bones of hands and feet

Skin: involved in 30-50% with erythema nodosum; also mucus membranes

Eye: iritis or iridocyclitis in 20-50%

Micro: non-caseating epithelioid granulomas with tightly packed epithelioid cells, Langhans giant cells, lymphocytes (T cells), usually in interstitium adjacent to bronchioles and around and within vessel walls, pleura, connective tissue septa; may also be hyalinization, diffuse interstitial fibrosis, fibrinoid necrosis and fibrosis within granulomas, intra- and extracellular inclusions; pleural involvement in 10%

Schaumann bodies: laminated concretions of calcium and protein

Asteroid bodies: stellate inclusions within giant cells, in 60% of granulomas

Neither is specific for sarcoid (also seen in berylliosis)

DD: mycobacteria, fungi, berylliosis (need clinical history to differentiate), extrinsic allergic aspergillosis (loosely arranged epithelioid cells in granulomas)

Necrotizing sarcoid granulomatosis

May be localized or diffuse

Appears to be a variant of sarcoidosis

Usually women, often with mild or no symptoms

Excellent prognosis

Treatment: steroids and immunosuppressive drugs, surgery for localized lesions

Micro: extensive vascular noncaseating sarcoid-like granulomas invading pulmonary arteries and veins with diffuse necrosis of lung parenchyma

DD: tuberculosis, fungal infection

Wegener’s granulomatosis

Triad of necrotizing angiitis, aseptic necrosis of upper respiratory tract and lungs, focal glomerulonephritis

May also involve temporal artery, cutaneous small vessels and cause extrapulmonary masses

All ages, but most common with ages 45+

Rarely associated with diffuse pulmonary hemorrhage

Should order special stains and cultures to rule out TB and fungi

Labs: c-ANCA positive in 90% with active generalized disease and 60% with limited disease (diffuse cytoplasmic staining, directed against neutrophil serine proteinase 3); can monitor course of disease with titers

p-ANCA (perinuclear staining, directed against myeloperoxidase) usually negative, positive in microscopic polyarteritis, inflammatory bowel disease, crescentic glomerulonephritis

Other causes of positive c-ANCA or p-ANCA: connective tissue disorders, chronic hypersensitivity pneumonia, postinfectious bronchitis, ulcerative colitis related lung disease, Mod Path 2002;15:197

Chest Xray: waxing and waning of pulmonary infiltrates and nodules is relatively specific

Diagnosis: biopsy of upper airway or skin showing inflammatory change is helpful

Treatment: cyclophosphamide, trimethoprim-sulfamethoxazole

Gross: well circumscribed lesion with necrotic appearance

Micro: liquefactive or coagulative necrosis in lungs with profuse eosinophils, multinucleated giant cells as part of poorly formed granulomas surrounded by pallisading histiocytes and giant cells with central necrosis; destructive leukocytic angiitis of arteries and veins outside of the necrotic granuloma by neutrophils, plasma cells and eosinophils; scanty lymphocytes and plasma cells; bronchial wall is rarely involved; fulminant subtype has predominance of exudative changes; fibrous scar subtype has marked collagenous stroma; small vessel variant involves alveolar septal capillaries instead of large arteries or veins (resembles SLE)

DD pulmonary vasculitis: tuberculosis, fungi

Limited Wegener’s

Confined to lungs, no glomerulonephritis (or occurs many years later)

More protracted clinical course

Treatment: steroids, cytotoxic drugs

Gross: multiple, bilateral nodules, round or infarct-like, often in lower lobes

Micro: similar to classic type, but must have angiitis outside of granulomas and necrotic areas for diagnosis

Other interstitial pneumonitis / fibrosis

General

Clinical information is usually necessary to properly interpret biopsy

Acute interstitial pneumonia

Also called Hamman-Rich syndrome

Rapidly progressive disease with no identifiable cause; death usually within 2 months

Young adults with influenza-like illness followed by shortness of breath

Micro: resembles diffuse alveolar damage with brisk interstitial fibroblastic proliferation

Amiodarone induced pulmonary toxicity

Case report of 68 year old man with amiodarone induced pulmonary toxicity, Archives 2002;126:745

Treatment: drug withdrawal or dose reduction

May have 50% mortality if diffuse alveolar damage present

Micro: intra-alveolar exudate of finely vacuolated foamy macrophages, also present within alveolar septa; may have diffuse alveolar damage or BOOP type changes

Cytology: finely vacuolated, foamy macrophages; variable neutrophils

EM: membrane-bound cytoplasmic lamellar inclusions due to drug accumulation in the lungs

Bronchiolitis obliterans-organizing pneumonia (BOOP)

Common response to infectious or inflammatory injury to lungs

Also associated with drugs, collagen vascular disease, graft versus host disease in bone marrow transplant patients

Cause cannot be determined from biopsy - requires clinical history

Acute onset with cough, shortness of breath, fever and malaise

Excellent prognosis; steroid resistance may lead to death

Treatment: steroids

Micro: patchy fibroblastic plugs in bronchioles (bronchiolitis obliterans) and alveoli (organizing pneumonia); plugs formed by spindled fibroblasts in pale-staining matrix, with serpiginous or elongated shape; also foamy macrophages, rare neutrophils, thickened alveolar septa

Low power: evenly spaced nodules or plugs of organizing connective tissue and inflammation that obliterates terminal airways

Bronchiolocentric interstitial pneumonitis

May resemble hypersensitivity pneumonitis

80% women, ages 40-50 years

Xray: interstitial and restrictive lung disease

Poor prognosis - 33% dead after mean 4 years

Similar pattern seen with rheumatoid arthritis, Sjogren’s syndrome, scleroderma, methotrexate, amiodarone (5-10% of patients)

Micro: centrilobular inflammation with peribronchiolar fibrosis and inflammation radiating into interstitium of distal acinus in a patchy fashion; inflammatory process begins at bronchovascular bundle, accompanied by centrilobular fibrosis and metaplasia; periphery of lobule shows relative sparing; no granulomas, no honeycomb change

DD: hypersensitivity pneumonitis (specific cause usually identifiable, less centrilobular fibrosis, usually has granulomas), nonspecific interstitial pneumonia (by definition excludes bronchiolocentric interstitial injury)

References: Mod Path 2002;15:1148

Chronic eosinophilic pneumonia

Reaction to drugs, Aspergillus or other fungi

Prolonged febrile illness with cough, weight loss, generalized fatigue

Associated with chronic asthma, peripheral eosinophilia

Xray: patchy infiltrates in peripheral lungs with central sparing

Treatment: steroids cause complete resolution

Gross: consolidation, mucus plugs in distal bronchi or bronchioles

Micro: patchy intraalveolar edema, interstitial inflammation with giant cells, eosinophils, chronic inflammatory cells; mucus plugs composed of inflammatory cells and cellular debris; often bronchiolitis obliterans; blood vessel infiltration by inflammatory cells is common, but no vascular necrosis

DD: DIP (if extensive intraalveolar macrophages), Langerhans cell histiocytosis (interstitial infiltrate, Langerhans cells), extrinsic allergic alveolitis (less edema, more interstitial inflammation), parasites, fungal allergies

Chronic pneumonitis of infancy

Rare

Micro: marked alveolar thickening, alveolar pneumocyte hyperplasia, alveolar exudate

Desquamative interstitial pneumonitis (DIP)

Usually adults with insidious onset of shortness of breath, progressing to respiratory insufficiency; also cough, cyanosis, clubbing

Cause unknown

Mean survival 12 years, mortality 28%

90% are current or past cigarette smokers

Associated with collagen vascular disease, positive ANA (similar to UIP)

Xray: bilateral, lower lobe, ground glass infiltrates

Treatment: steroids (respond better than UIP)

Micro: diffuse collections of intraalveolar macrophages containing lipid and PAS+ granules (originally thought to be desquamated pneumocytes); type II pneumocyte hyperplasia, acute and chronic inflammatory cells; may be focal interstitial fibrosis; no necrosis, no hyaline membranes, no fibrin

Positive stains (macrophages): PAS after diastase, iron

EM: type II pneumocytes contain lamellar bodies (surfact