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:

Asthma

Cytopathology: Asthma in pulmonary cytopathology

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, pink on H&E.

Images:

Notes:

  • Leyden in Charcot-Leyden is also seen written as Leiden.
    • Finding associated with hypereosinophilia[5] - not pathognomonic for asthma.
  • Pulmonary cytopathology:
    • Curschmann's spirals = spiral-shaped mucous plugs.[6]
    • Creola bodies = clusters of (ciliated) bronchial epithelial cells.[7]

DDx:

  • Infection - fungal.

Stains

Features - crystals:

  • PAS-D -ve.
  • GMS -ve.

Sign out

BRONCHIAL CAST, RIGHT LOWER LOBE, REMOVAL:
- CHARCOT-LEYDEN CRYSTALS.
- CELLULAR DEBRIS WITH NEUTROPHILS AND ABUNDANT EOSINOPHILS.
- RESPIRATORY MUCOSA WITH PROMINENT SMOOTH MUSCLE.
- NEGATIVE FOR MALIGNANCY.

COMMENT:
GMS and PAS-D stains are negative for fungal organisms. The findings are non-specific; 
however, they would be compatible with asthma. Clinical and microbiological correlation 
is required.

Emphysema

Chronic obstructive pulmonary disease, abbreviated COPD, is dealt with in the emphysema article.

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]

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.

Gross

Features - autopsy:

  • Bubbles - when squeezed (due to surfactant).
  • Heavy.

Microscopic

Features:[8]

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

DDx:

Images:

Bronchiectasis

General

Gross

  • Large airways at the periphery of the lung.
  • Central airways larger than the adjacent arteries.
  • Typically focal.

Radiologic:

  • Central airways larger than the adjacent arteries.
  • Airway wall-thickening.[11]
  • "Tree-in-bud" abnormalities.

Images

www:

Microscopic

Features:

  • Dilated airways.
    • Airways larger than arteries.

Image

www:

Pulmonary hemorrhage

General

  • Many causes.

A few causes:

Pulmonary hemorrhage syndromes:[12]

Radiology

  • Airspace opacity.

Microscopic

Features:

DDx:

  • Decomposition.

Constrictive bronchiolitis

  • AKA bronchiolitis obliterans, AKA obliterative broncholitis,[13] AKA bronchiolitis obliterans syndrome (BOS).[14]

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:[13]

Microscopic

Features:[13]

  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.[13]

Images:

Stains

  • Elastic trichrome - useful for delineation of obliterated bronchioles.

Diffuse lung diseases

These are also known as idiopathic interstitial pneumonias.

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.[16]
    • Reticular = net-like.[17]
  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:[18]

Note:

Causes of upper lung fibrosis FASSTEN:[18]

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.).[20][21]

Patterns of fibrosis:

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

Disease with fibrosis

There are many of 'em.

Fibrosing pleuritis

General

  • Benign.

Microscopic

Features:[22]

  • Fibrosis.
    • Spindle cells.
    • Moderate cellularity.
  • No necrosis.

DDx:[23]

  • Mesothelioma, desmoplastic.
    • Mesothelioma should not be diagnosed on core biopsy.[22]

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:[27]

  • 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:

Pulmonary nodular lymphoid hyperplasia

  • AKA pseudolymphoma - a term some dislike.[27]

General

  • Definition - reactive lymphoid cells.

Gross/radiology

  • Has nodules radiographically.

Microscopic

Features:[27]

  • Reactive lymphoid nodules.

Notes:[28]

  • 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:[29]

  • Cellular form.
  • Fibrotic form.

One form usually predominates.

Radiology

  • Upper lung zones.

Microscopic

Features:[30]

  • 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). (???)

Images:

IHC

  • Langerhans cells: S100+ and CD1a+.[30]

Granulomatous lung disease

See: Granulomas for an introduction to the general topic.

Most common:

  • Infectious - mycobacterial and fungal.[31]

Noninfectious causes:[31]

  • 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.[32]

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

Microscopic

Features:

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

Images

www:

Miscellaneous diseases

Pneumoconioses

Pneumocytoma

  • AKA benign sclerosing pneumocytoma.[35]
  • Previously known as sclerosing hemangioma.

General

  • Derived from type 2 pneumocyte.[36]
  • Progesterone-receptor positive stromal cells.[37]

Epidemiology

  • Female in 40s.[38]
  • Considered benign; excision is curative.

Gross

  • Peripheral, solitary.
  • Well-circumscribed.

Microscopic

Features:[38]

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

DDx:[39]

Image:

IHC

Features:[41]

  • EMA +ve.
  • PR +ve.[37]

Negative stains:[41]

  • SMA -ve.
  • CEA -ve.
  • CD34 -ve.
  • S100 -ve.
  • Chromogranin A -ve.

Others:[36]

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

Lymphangioleiomyomatosis

  • Abbreviated LAM.
  • AKA lymphangiomyomatosis.

Pulmonary alveolar proteinosis

  • Abbreviated PAP.

Diffuse panbronchiolitis

  • Abbreviated DPB.

General

  • Rare lung disease predominantly found among asians.[42]
  • Has been likened to cystic fibrosis - but doesn't really share any features with it.

Gross

Features:[42]

  • Bronchiectasis.
  • Hyperinflation.
  • Small nodules (~2-3 mm) around the small airways.
  • Diffuse involvement of both lungs.

Microscopic

Features:[42]

  • Transmural inflammation of bronchioles - esp. respiratory bronchioles.
    • Lymphocytes, plasma cells, histiocytes.
  • Neutrophils within the airway.

Images:

Pulmonary amyloidosis

General

Microscopic

Features:

  • Interstitial cotton candy-like material - see amyloidosis.

DDx:

Images:

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:[44]

Severity

Eosinophilic pneumonia

Specific entities:[45]

  • 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:

Churg-Strauss syndrome

Microscopic

Features:

Eosinophilic pleural effusions

  • Definition: 10%+ eosinophils.[46]
  • Uncommon 5-16% of effusions.[47]

Causes - mnemonic I'M PAID:[47]

  • Infection, e.g. tuberculosis.
  • Malignancy - uncommon.
  • Pulmonary emboli.
  • Asbestos exposure.
  • Inflammatory diseases.
  • Drug reactions.

Lung transplant pathology

This subspecialty is dealt with in its own article.

See also

References

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