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. Interstitial lung disease is dealt with in the diffuse lung diseases article.

Infectious pneumonia

Includes:

Diffuse lung diseases

These are also known as idiopathic interstitial pneumonias.

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:[2]

  • Antigen TH2 lymphocyte -> IgE B-cell -> mast cell IgE Fc -> leukotrienes + other mediators -> bronchospasm, edema, leukocyte recruitment -> airway remodeling.

Gross

  • Lung over-inflation.
  • Mucous plugs.
  • Focal resorption atelectasis,[3] i.e. collapse.

Microscopic

Features:[4]

  • 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.[5]

Emphysema

General

Pathologic classification

Based on morphology:[7]

  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.[8]

Notes:

  • Bleb = (small) vesicle.[9]
  • Bulla = large vesicle.[10]

Microscopic

Features:[8]

  • 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:[11]

  • 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:[12]

Note:

  • BOOP is used as a synonym for organizing pneumonia which has the long differential diagnosis above.[12]
    • Confusingly, it may be used to refer to the idiopathic form of organizing pneumonia, now generally known as cryptogenic organizing pneumonia (COP).
      • In other words, strictly speaking, BOOP is not the same as COP; idiopathic BOOP is COP.

Microscopic

Features:[13]

  • Distal airway disease -- airways plugged with organizing exudate ("Masson bodies").
    • "Organized exudate" = fluffy light-staining paucicellular regions with stellate cells (fibroblasts & immature connective tissue).

Images:

Constrictive bronchiolitis

  • AKA bronchiolitis obliterans, AKA obliterative broncholitis,[15] AKA bronchiolitis obliterans syndrome (BOS).[16]

General

  • Not the same as (idiopathic) bronchiolitis obliterans organizing pneumonia (BOOP) - in short:
    • BOOP: clogs the airway, has Masson bodies, treated with steroids - good prognosis.
    • Constrictive bronchiolitis: fibrosis around airways, crappy prognosis.
  • No good treatment.
  • Progressive.

Etiology/associations:[15]

  • Post-infectious.
    • Viral.
    • Mycoplasma.
  • Post-lung transplant.[17]
  • Post-hematopoietic stem cell transplantation
    • Associated with GVHD.[17]
  • Connective tissue disease, mostly rheumatoid arthritis.
  • Ulcerative colitis.
  • Drugs - penicillamine.
  • Toxins.
  • Idiopathic.

Microscopic

Features:[15]

  1. Bronchiolitis - mononuclear and neutrophilic.
    • May be minimal late in the disease.
  2. Fibrosis - submucosal and peribronchiolar.
    • Can be patchy.

Notes:

  • Bronchioles = noncartilagenous airways usu. < 2 mm in diameter.[15]

Images:

Stains

  • Elastic trichrome - useful for delineation of obliterated bronchioles.


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]

Note:

Causes of upper lung fibrosis FASSTEN:[22]

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.).[23][24]

Patterns of fibrosis:

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

Disease with fibrosis

There are many of 'em.

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

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:[28]

  • 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.[28]
  • Definition - reactive lymphoid cells.

Gross/radiology

  • Has nodules radiographically.

Microscopic

Features:[28]

  • Reactive lymphoid nodules.

Notes:[29]

  • 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

Desquamative interstitial pneumonia

Pulmonary Langerhans cell histiocytosis

  • AKA eosinophilic granuloma of the lung.

General

Subtypes:[30]

  • Cellular form.
  • Fibrotic form.

One form usually predominates.

Radiology

  • Upper lung zones.

Microscopic

Features:[31]

  • 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+.[31]

Granulomatous lung disease

See: Granulomas for an introduction to the general topic.

Most common:

  • Infectious - mycobacterial and fungal.[32]

Noninfectious causes:[32]

  • 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.[33]

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.[34]
  • 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.[35]
  • Progesterone-receptor positive stromal cells.[36]

Epidemiology

  • Female in 40s.[37]
  • Considered benign; excision is curative.
    • Rare case reports of metastases.

Gross

  • Peripheral, solitary.
  • Well-circumscribed.

Microscopic

Features:[37]

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

DDx:[38]

IHC

Features:[35]

  • 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.[39]

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:[42]

  • 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.[43]

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:[43]

  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:[44]

  • 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:[46]

Severity

Eosinophilic pneumonia

Specific entities:[47]

  • 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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  2. Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 370-2. ISBN 978-1416054542.
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