Medical lung diseases

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The medical lung diseases are a huge topic. Most pathologists have little to do with 'em. They are the domain of respirology. An introduction to lung pathology is in the lung article, along with a general approach.

Acute infectious pneumonia

This is seen by pathologists in autopsy from time-to-time.

Radiologic correlate

  • Air space disease.

Gross pathology

  • Consolidation (the lung parenchyma is firm) - best appreciated by running a finger over the cut surface of the lung with a small-to-moderate amount of pressure.

Microscopy

Features:

  • Alveoli packed with PMNs.
  • +/-Clusters of bacteria - small dots or rods.

Image: Normal alveoli & pneumonia (WC).

Asthma

General

  • The bread and butter of respirology.
  • May be associated with atopy (allergies), medications (e.g. NSAIDs), occupational exposures.[1]

Pathogenesis

  • T-cell response TH2 dominant.

Sequence:[1]

  • Antigen + mast cell -> IgE --> leukotriene -> bronchospasm, edema, leukocyte recruitment -> airway remodelling.

Gross

  • Lung over-inflation.
  • Mucous plugs.
  • Focal resorption atelectasis,[2] i.e. collapse.

Microscopic

Features:[3]

  • Edema.
  • Mucous (plugs).
  • +/-Smooth muscle hypertrophy.
  • +/-Inflammation - especially with eosinophils.
  • +/-Charcot-Leyden crystals (formed from eosinophil granules -- breakdown product).
    • Sharp edge, diamond shaped, intense pink.

Images:

Notes:

  • Leyden in Charcot-Leyden is also seen written as Leiden.
  • Pulmonary cytopathology: Curschmann's spirals - spiral-shaped mucous plugs.[4]

Emphysema

General

  • Usually due to smoking.
  • May be associated with alpha-1 antitrypsin deficiency.
  • Often lumped together with chronic bronchitis and called chronic obstructive pulmonary disease (COPD).[5]

Pathologic classification

Based on morphology:[6]

  1. Centriacinar (centrilobular) - associated with heavy smoking.
  2. Panacinar (panlobular) - associated with alpha-1 antitrypsin deficiency.
  3. Distal (paraseptal) acinar - associated with spontaneous pneumothorax.
  4. Irregular - usu. insignificant.
  • Q. Why does smoking lead to centriacinar emphysema?
  • A. The bad stuff from smoking gets enters the acinus at the centre; ergo, this is the location of the most damage.

Gross

  • Holes (blebs, bullae), usually upper lung field predominant.
  • Lungs may overlap the heart.[7]

Notes:

  • Bleb = (small) vesicle.[8]
  • Bulla = large vesicle.[9]

Microscopic

Features:[7]

  • Large alveoli.
  • Thin septa (no interstitial thickening).

Image:

Chronic bronchitis

General

  • Often seen together with emphysema with which it is lumped together with in the term COPD.
  • It's a clinical diagnosis - criteria:[1]
    • Cough with sputum for thee months in at least two consecutive years.
    • No other cause identified.

Clinical:[1]

  • Blue bloater (carbon dioxide retainers)
  • Develop cor pulmonale.

Microscopic

Features:[1]

  • Mucous gland hypertrophy + mucinous secretions in airway.
  • Goblet cell metaplasia.
  • Bronchiolar inflammation and fibrosis.

Pulmonary edema

General

  • Seen in a number of conditions, e.g. congestive heart failure.

Microscopic

Features:[10]

  • Dilated capillaries.
  • Blood in airspace.
  • Plasma proteins in airspace - light pink acellular junk.
  • +/-Hemosiderin-laden macrophages (heart failure cells).

Organizing pneumonia

General

  • Multiple causes, e.g. transplant rejection, infection.

Clinical diagnoses:

  • Transplant rejection.
  • Cryptogenic organizing pneumonia (COP).
    • AKA bronchiolitis obliterans organizing pneumonia (BOOP).

Microscopic

Features:[11]

  • Distal airway disease -- airways plugged with organizing exudate.
    • "Organized exudate" = fluffy light-staining paucicellular regions with stellate cells (fibroblasts?).

Obliterative broncholitis

General

  • AKA bronchiolitis obliterans.
  • Not the same as Bronchiolitis obliterans organizing pneumonia (BOOP).

Idiopathic interstitial pneumonia

  • Often abbreviated IIP, is a term used for a type of diffuse lung disease.
    • Diffuse lung disease is also known as interstitial lung disease.
      • Diffuse lung disease is probably a better term... as some diseases lumped into this category have involvement of the alveoli, i.e. are not interstitial.

Histologic classification of IIP

Idiopathic interstitial pneumonia can be subclassified based on histologic appearance into the following patterns:[15][16]

Histology Clinical Correlates Associations
Desquamative interstitial pneumonia (DIP) DIP Smoking
Diffuse alveolar damage (DAD) ARDS, AIP, TRALI ARDS: trauma, infection; TRALI: blood transfusion; AIP: viral (???)
Nonspecific interstitial pneumonia (NSIP) NSIP ???
Respiratory bronchiolitis RB-ILD Smoking
Usual interstitial pneumonia (UIP) CVD, IPF, drug toxicity, pneumoconiosis Allergen (hypersensitivity pneumonitis), idiopathic, autoimmune
Organizing pneumonia Cryptogenic organizing pneumonia autoimmune (???)
Lymphoid interstitial pneumonia (LIP) LIP Viral/autoimmune

ARDS = adult respiratory distress syndrome, AIP = acute interstitial pneumonia, TRALI = transfusion related acute lung injury, CVD = collagen vascular disease, IPF = idiopathic pulmonary fibrosis.


Notes:

  • Usual interstitial pneumonia is the most common type of ILD.[17]

Fibrosis

Histomorphological classification

  1. Hyaline membranes - glassy pink material lining airways & alveoli.
  2. Microscopic honeycombing - "holes" in the lung.
  3. Bronchiolization - ciliated (respiratory) epithelium in distal airway.
  4. Uniform alveolar septal thickening - septae look similar at low power.
  5. Peripheral lobular fibrosis - septae thickening peripheral, HRCT shows: irregular peripheral reticular opacities.[18]
    • Reticular = net-like.[19]
  6. Siderophages in alveoli - macrophages with hemosiderin the alveoli.
  7. Fibrinous pleuritis - peripheral only (based on imaging).
  8. Granulomata, non-necrotizing.
  9. Abundance of vacuolated cells.
  10. Chronic inflammation.
  11. Bronchiolocentric scarring - fibrosis concentrated around airway/assoc. with airway.

Radiologic/gross pathologic DDx by location

Causes of lower lung fibrosis BAD RASH:[20]

  • Brochiolitis obliterans with organizing pneumonia (BOOP).
  • Asbestosis.
  • Drugs (nitrofurantoin, hydralazine, isoniazid (INH), amiodarone).
  • Rheumatologic disease.
  • Aspiration.
  • Scleroderma.
  • Hamman-Rich syndrome (really should be -- interstital pulmonary fibrosis).

Causes of upper lung fibrosis FASSTEN:[21]

  • Farmer's lung.
  • Ankylosing spondylitis.
  • Sarcoidosis.
  • Silicosis.
  • Tuberculosis (miliary).
  • Eosinophilic granuloma.
  • Neurofibromatosis.

Prognosis

  • The pattern and severity of fibrosis seems to be the most important factors prognostically - more important than the underlying cause (ILD, CVD, drug reaction etc.).[22][23]

Patterns of fibrosis:

  • "Linear" - follows alveolar walls, no architectural distortion.
  • UIP-like (honeycombing).

Disease with fibrosis

There are many of 'em.

Diffuse alveolar damage

General

  • Abbreviated DAD.

DAD is the histologic correlate of:

  • Adult respiratory distress syndrome (ARDS).
  • Acute interstitial pneumonia (AIP).
  • Transfusion related acute lung injury (TRALI).

Microscopic

Features:[24]

  • Early:
    • Hyaline membrane: debris (pink crap) lines the alveolar spaces.
  • Intermediate:
    • Macrophage proliferation.
  • Late:
    • Interstitial inflammation.
    • Fibrosis.

Image: Diffuse alveolar damage (WC).

Usual interstitial pneumonia

General

  • It is sometimes used incorrectly as a synoym for idiopathic pulmonary fibrosis.
  • Cannot be diagnosed via bronchoscopic or transbronchial biopsy.[25]

Epidemiology

  • Disease of the old - rare in under 50 years old.[26]
  • Dismal prognosis - mean survival after diagnosis ~ 2.8 years.[22]

Differential diagnosis

UIP is seen in:[27]

  • Idiopathic pulmonary fibrosis.
  • Asbestosis - one ought to see ferruginous bodies.
  • Chronic hypersensitivity pneumonitis (extrinsic allergic alveolitis).
  • Collagen vascular disease.
  • Chronic drug toxicity.[28]

Radiologic

  • Honeycombing - multiple defects that obliterate the normal lung architecture - multiple spherical voids in the lung parenchyma; radiologically these are seen as lucencies.[29]
    • Usually subplural, i.e. peripheral lung.
    • Classically lower lobe predominant.
    • Associated with interstitial thickening. (???)

Note:

  • Cysts - have thin walls (think of emphysema, lymphangioleiomyomatosis et cetera).
    • Cysts may be isolated/not close to a neighbour.
    • Medcyclopaedia defines it as: thin-walled, well-demarcated and >1 cm.[30]

Microscopic

Features:[31]

  • Fibroblast foci:
    • "Crescent-shaped bulge" of fibroblasts -- a rounded projection of spindle cells into the airspace.
    • Location: in the areas of transisition between active inflammation and old inflammation.[32]
    • Note: Technically, fibroblast foci are composed of myofibroblasts.[33]
  • Interstitial inflammation,
  • Microscopic honeycombing,
    • Typically peripheral - cysts lined by ciliated epithelium.
  • Spatial heterogeneity - patchy lesional distribution (areas of abnormal and normal lung may appear beside one another).
  • Temporal heterogeneity - lesions of differing age side-by-side.[34]

Notes:

  • Disease worse distant from large airways: lower lung field predominance, typically worse at periphery of lobule and lung.[35]
  • Heterogeneity of inflammation: airspace macrophages & inflammation minimal in honeycombed foci.

Asbestosis

General

  • Important to diagnose... asbestosis = compensation.

Microscopic

  • Histologic appearance as for UIP -- plus ferruginous bodies.
    • Segmented twirling batton with long slender fibre within.

Image(s):

Non-specific interstitial pneumonia

  • Abbreviated NSIP.
  • Better prognosis than UIP.
  • Some radiologists and pathologists don't believe in this entity.

Gross/Radiology

  • No honeycombing.
  • Fibrosis usually lower lung zone.
  • Patchy ground glass.

Microscopic

  • Fibrosis:
    • May be uniform.
    • "Linear fibrosis" has a good prognosis - should be mentioned in the report.
      • Linear fibrosis = fibrosis that follows alveolar walls + no architectural distortion.
  • +/-Lymphoid nodules - assoc. with collagen vascular disease.

Notes:

  • Like UIP... also temporally and spatially heterogeneous.
  • Inflammation in NSIP usually more prominent than in UIP.
  • No honeycombing - key difference between UIP and NSIP.

DDx

  • Collagen vascular disease.
  • Drug reaction.
  • Hypersensitivity pneumonitis (extrinic allergic alveolitis).

Hypersensitivity pneumonitis

  • AKA extrinsic allergic alveolitis
  • Exposure to stuffs... e.g. moldy hay - Farmer's lung, atypical mycobacteria - hot tub lung.
  • Upper lung predominant disease (???).

Microscopic

Features:

  • Lesions have centrilobular prominence - important feature. [36]
    • Allergens enter lung through airway which has a centrilobular location.
  • Granulomata (not typically seen in UIP) - important feature.[36]
  • Chronic interstitial inflammation consisting primarily of lymphocytes.
  • Interstitial fibrosis.
  • Air space involvement (alveolitis).

Images:

Lymphocytic lesions of the lung

Diagnosis Key histologic feature Radiology Other diagnostic
Lymphocytic interstitial pneumonia interstitial lymphoid cells, usu. no nodules interstitial pattern
Follicular bronchiolitis/bronchitis lymphoid cell around bronchioles / bronchus, normal parenchyma interstitial pattern
Nodular lymphoid hyperplasia abundant lymphoid cells in nodules nodules /interstitial pattern stains to exclude lymphoma; germinal centres do not exclude lymphoma
Lymphoma (BALToma) abundant lymphoid cells usu. in nodules nodules / interstitial pattern may require stains to prove, germinal centres may be present

Lymphocytic interstitial pneumonia

General

Gross

  • Location: basilar predominance.
  • Increased interstitial markings.

Microscopic

Features:[39]

  • Small mature lymphocytes (usually B cells).[40]
  • Plasma cells.
  • +/-Lymphoid follicles.

Negatives:

  • No Vasculitis.
  • No necrosis.

Image: LIP (scielo.br).

DDx:

  • Lymphoma.
  • Follicular bronchitis/bronchiolitis.
  • Nodular lymphoid hyperplasia.
    • This is determined in part by radiology; it has nodules radiographically.

Follicular bronchitis/bronchiolitis

General

Gross/radiology

  • No distinct nodule or mass.
  • Classically: increased reticular marking, i.e. interstitial pattern.

Images: Intersitial pattern - radiographs (ucsf.edu).

Microscopic

Features:[43]

  • Peribronchiolar/peribronchial lymphoid nodules with:
    • Reactive germinal centres.
      • Lack of these should raise suspicion for lymphoma.
    • Plasma cells.
  • +/-Lymphoid nodules in the interlobular septa.

Notes:

  • Lung parenchyma distant from nodule = normal; no lymphocytic infiltrate.

DDx:

Nodular lymphoid hyperplasia

General

  • AKA pseudolymphoma - a term some dislike.[43]
  • Definition - reactive lymphoid cells.

Gross/radiology

  • Has nodules radiographically.

Microscopic

Features:[43]

  • Reactive lymphoid nodules.

Notes:[44]

  • Presence of germinal centres do not exclude lymphoma - may still be a BALToma.
    • BALT = bronchial/bronchus associated lymphoid tissue.

DDx:

Smoking associated disease

  • RB = respiratory bronchiolitis.
  • RBILD = respiratory bronchiolitis interstitial lung disease.
  • DIP = desquamative interstitial pneumonia.
  • Eosinophilic granuloma (of lung) - AKA pulmonary langerhans cell histiocytosis.

All of the above are assoc. with smoking. RBILD & DIP are considered by many to be on a continuum, i.e. RBILD is early DIP.

Respiratory bronchiolitis

  • Diagnosis is based on clinical criteria.

Microscopic

Features:

  • Inflammation.
  • No interstitial lung disease, i.e. no fibrosis.

Respiratory bronchiolitis interstitial lung disease

  • Abbreviated RBILD.

General

  • May be an early version of DIP.

Microscopic

Features:[45]

  • Brown pigmented airspace macrophages - smoker's macrophages.
  • Inflammation of the terminal bronchioles.

Note:

  • The histologic features of RBILD may be present peri-tumoural.

Desquamative interstitial pneumonia

  • Abbreviated DIP.

General

  • Thought to be advanced RBILD.

Microscopic

Features:

  • Brown pigmented airspace macrophages - smoker's macrophages.
  • Architecture preserved; "linear fibrosis".

Notes:

  • Some fields of view may be indistinguishable from RBILD.
  • Amiodarone toxicity, fibrotic NSIP - may appear similar.

Pulmonary Langerhans cell histiocytosis

  • AKA eosinophilic granuloma of lung.

General

Subtypes:[46]

  • Cellular form.
  • Fibrotic form.

One form usually predominates.

Radiology

  • Upper lung zones.

Microscopic

Features:[47]

  • Cellular peribronchiolar nodules with:
    • Langerhans cells - key feature:
      • Pale staining nucleus (H&E) with nuclear infolding - "crumpled tissue paper" appearance.
    • +/-Smoker's macrophages (brown pigmented airspace macrophages).
    • +/-Eosinophilia (may be rare) - significantly narrow DDx.
    • Chronic inflammatory cells (lymphocytes). (???)

IHC

  • Langerhans cells: S100+ and CD1a+.[47]

Granulomatous lung disease

See: Granulomas for an introduction to the general topic.

Most common:

  • Infectious - mycobacterial and fungal.[48]

Noninfectious causes:[48]

  • Aspiration pneumonia.
  • Hypersensitivity pneumonitis.
  • Hot tub lung.
  • Talc granulomatosis.
  • Sarcoidosis.
  • Wegener granulomatosis.

Sarcoidosis

General

  • Diagnosis of exclusion - infection must be excluded.
  • Radiologic differential diagnosis includes carcinomatosis.[49]

Microscopic

Features:

  • Granulomata, well-formed, non-necrotizing.
    • Negative for microorganisms with special stains (PAS-D, GMS, AFB).
    • Granulomata - interstitial location.

Image(s):

Pulmonary talcosis

General

  • Associated with herion use.[50]
  • X-ray findings similar to asbestosis.

Microscopic

Features:

  • Granulomas with foreign material.
    • Foreign material often polarizes.

Images:

Miscellaneous diseases

Pneumocytoma

General

  • Previously known as sclerosing hemangioma.
  • AKA sclerosing hemangioma.
  • Derived from type 2 pneumocyte.[51]
  • Progesterone-receptor positive stromal cells.[52]

Epidemiology

  • Female in 40s.[53]
  • Considered benign; excision is curative.
    • Rare case reports of metastases.

Gross

  • Peripheral, solitary.
  • Well-circumscribed.

Microscopy

Features:[53]

  • Mixed cell population.
  • Variable architecture:
    • Papillary.
    • Sclerotic.
    • Solid.
    • Hemorrhagic.
  • +/-Granulomas.

DDx:[54]

  • Papillary adenoma.
  • Neuroendocrine tumour (carcinoid).

IHC

Features:[51]

  • TTF-1 +ve.
  • HNF-3 alpha +ve.
  • HNF-3 beta +ve.

Lymphangioleiomyomatosis

  • Abbreviated LAM.
  • AKA lymphangiomyomatosis.

General

  • Clinical: dyspnea, recurrent pneumothorax.
  • May be an indication for lung transplantation.
  • Non-neoplastic muscle proliferation vs. tumour that can metastasize.[55]

Notes:

Epidemiology

Radiology

  • Bullae/thin walled cysts - distributed in all lung fields.
  • Lymphadenopathy.

Radiologic DDx (of cysts):

  • Eosinophilic granuloma (assoc. with smoking).
  • Interstitial pulmonary fibrosis (UIP).
  • Emphysema.

Microscopic

Features:[58]

  • Spindle cells with small nuclei + larger epithelioid cells with clear cytoplasm and round nuclei.
  • Cyst formation.
  • Thick arterial walls.

Images:

IHC

  • HMB-45 +ve.
  • ER +ve.
  • PR +ve.
  • SMA +ve.

Pulmonary alveolar proteinosis

  • Abbreviated PAP.

General

  • Associated with smoking - particularily in men.[59]

Pathophysiology:

  • GM-CSF (granulocyte-macrophage colony stimulating factor) signaling in macrophages/lack of GM-CSF.
    • GM-CSF is required by alveolar macrophages to clear surfactant.

Classification:[59]

  1. Congenital:
      • Abnormal surfactant.
      • GM-CSF receptor defect.
  2. Secondary:
    • Infections.
    • Haematologic malignancy.
  3. Acquired:
    • Dusts - interfere with macrophage function.

Clinical:

  • Dyspnea & cough - gradual onset.

Radiology

Microscopic

Features:

  • Crap in the alveoli:
  • "Dense bodies" - dead macrophages ("Chatter" in the alveoli).
    • Edema - has pink stuff in the alveoli like PAP but no dense bodies.

DDx - may mimic:[60]

  • Edema.
  • Pneumocystis - exudates foamy & vacuolated.
  • Pulmonary hemorrhage (acute). (???)

Images:

Images of DDx:

Drug reactions

  • Effects are often non-specific.

Website: http://www.pneumotox.com

Pulmonary hypertension

General classification:

  • Primary, i.e. primary pulmonary hypertension, or
  • Secondary, e.g. due to congenital heart disease (like ventricular septal defect), interstitial pulmonary fibrosis.

Non-secondary pulmonary hypertension

Causes:[62]

  • Primary pulmonary hypertension.
  • Pulmonary embolic disease (thromboembolism, and non-thrombotic embolism).
  • Pulmonary capillary haemangiomatosis (PCH).
  • Pulmonary veno-occlusive disease (PVOD).

Severity

Eosinophilic pneumonia

Specific entities:[63]

  • Churg-Strauss syndrome.
  • Acute eosinophilic pneumonia.
  • Chronic eosinophilic pneumonia.
  • Eosinophilic granuloma (pulmonary histiocytosis X, Langerhans cell granulomatosis).

Entities which may have eosinophilia as prominent feature:

  • AIDS.
  • Lymphoma.
  • Collagen vascular disease.

Churg-Strauss syndrome

Microscopic

Features:

Lung transplant pathology

This subspecialty is dealt with in its own article.

See also

References

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