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

Main article: Pneumonia

Includes:

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) emphysema - associated with heavy smoking.
  2. Panacinar (panlobular) emphysema - associated with alpha-1 antitrypsin deficiency.
  3. Distal (paraseptal) acinar emphysema - associated with spontaneous pneumothorax.
  4. Irregular emphysema - 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).

DDx:

Image:

Bronchiectasis

General

Gross

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

Microscopic

Features:

  • Airways larger than arteries.

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]

  • Post-infectious.
    • Viral.
    • Mycoplasma.
  • Post-lung transplant.[15]
  • Post-hematopoietic stem cell transplantation
    • Associated with GVHD.[15]
  • Connective tissue disease, mostly rheumatoid arthritis.
  • Ulcerative colitis.
  • Drugs - penicillamine.
  • Toxins.
  • Idiopathic.

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

Main article: 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:[20]

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.).[21][22]

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:[23]

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

DDx:[24]

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

Main article: 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

Main article: Smoking
  • 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

Main article: Respiratory bronchiolitis interstitial lung disease

Desquamative interstitial pneumonia

Main article: 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). (???)

Images:

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

Main article: 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]
  • Seen in drug users that inject pills intended to be taken PO.[35]
  • X-ray findings similar to asbestosis.

Microscopic

Features:

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

Images:

Miscellaneous diseases

Pneumoconioses

Main article: Pneumoconioses

Pneumocytoma

General

  • Previously known as sclerosing hemangioma.
  • AKA sclerosing hemangioma.
  • 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]

IHC

Features:[36]

  • 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.[40]

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:[43]

  • 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.[44]

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:[44]

  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:[45]

Images:

Images of DDx:

Diffuse panbronchiolitis

  • Abbreviated DPB.

General

  • Rare lung disease predominantly found among asians.[47]
  • Has been likened to cystic fibrosis - but doesn't really share any features with it.

Gross

Features:[47]

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

Microscopic

Features:[47]

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

Images:

Drug reactions

  • Effects are often non-specific.

Website: http://www.pneumotox.com

Pulmonary hypertension

Main article: 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

Main article: Pulmonary hypertension

Causes:[48]

Severity

Eosinophilic pneumonia

Specific entities:[49]

  • 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

Main article: Churg-Strauss syndrome

Microscopic

Features:

Lung transplant pathology

Main article: Lung transplant pathology

This subspecialty is dealt with in its own article.

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 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. ISBN 978-1416054542.
  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.
  3. ↑ 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. 363. ISBN 978-1416054542.
  4. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 108. ISBN 978-1416002741.
  5. ↑ Cenci M, Giovagnoli MR, Alderisio M, Vecchione A (November 1998). "Curschmann's spirals in sputum of subjects exposed daily to urban environmental pollution". Diagn. Cytopathol. 19 (5): 349–51. PMID 9812228.
  6. ↑ 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. 368. ISBN 978-1416054542.
  7. ↑ 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. 368. ISBN 978-1416054542.
  8. ↑ 8.0 8.1 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. 369. ISBN 978-1416054542.
  9. ↑ URL: http://dictionary.reference.com/browse/bleb. Accessed on: 3 August 2011.
  10. ↑ URL: http://dictionary.reference.com/browse/bulla. Accessed on: 3 August 2011.
  11. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 102. ISBN 978-1416002741.
  12. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 745. ISBN 0-7216-0187-1.
  13. ↑ 13.0 13.1 13.2 13.3 Visscher, DW.; Myers, JL. (2006). "Bronchiolitis: the pathologist's perspective.". Proc Am Thorac Soc 3 (1): 41-7. doi:10.1513/pats.200512-124JH. PMID 16493150. http://pats.atsjournals.org/cgi/content/full/3/1/41.
  14. ↑ Sato, M.; Keshavjee, S. (2008). "Bronchiolitis obliterans syndrome: alloimmune-dependent and -independent injury with aberrant tissue remodeling.". Semin Thorac Cardiovasc Surg 20 (2): 173-82. doi:10.1053/j.semtcvs.2008.05.002. PMID 18707652.
  15. ↑ 15.0 15.1 Chien, JW.; Duncan, S.; Williams, KM.; Pavletic, SZ. (Jan 2010). "Bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation-an increasingly recognized manifestation of chronic graft-versus-host disease.". Biol Blood Marrow Transplant 16 (1 Suppl): S106-14. doi:10.1016/j.bbmt.2009.11.002. PMID 19896545.
  16. ↑ http://www.rsna.org/Publications/rsnanews/may06/jrnl_may06.cfm
  17. ↑ http://dictionary.reference.com/browse/reticular
  18. ↑ TN05 R13.
  19. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 90. ISBN 978-0781765275.
  20. ↑ TN05 R13.
  21. ↑ Bjoraker JA, Ryu JH, Edwin MK, et al. (January 1998). "Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis". Am. J. Respir. Crit. Care Med. 157 (1): 199-203. PMID 9445300. http://ajrccm.atsjournals.org/cgi/content/full/157/1/199.
  22. ↑ AC UBC S.425.
  23. ↑ 23.0 23.1 URL: http://www.ultrapath.org/oldsite/uscap/uscap05/meso1.html. Accessed on: 20 February 2012.
  24. ↑ Corson, JM. (Nov 2004). "Pathology of mesothelioma.". Thorac Surg Clin 14 (4): 447-60. doi:10.1016/j.thorsurg.2004.06.007. PMID 15559051.
  25. ↑ Nicholson AG (August 2001). "Lymphocytic interstitial pneumonia and other lymphoproliferative disorders in the lung". Semin Respir Crit Care Med 22 (4): 409–22. doi:10.1055/s-2001-17384. PMID 16088689.
  26. ↑ Aerni MR, Vassallo R, Myers JL, Lindell RM, Ryu JH (February 2008). "Follicular bronchiolitis in surgical lung biopsies: clinical implications in 12 patients". Respir Med 102 (2): 307–12. doi:10.1016/j.rmed.2007.07.032. PMID 17997299.
  27. ↑ Kinane BT, Mansell AL, Zwerdling RG, Lapey A, Shannon DC (October 1993). "Follicular bronchitis in the pediatric population". Chest 104 (4): 1183–6. PMID 8404188.
  28. ↑ 28.0 28.1 28.2 AFIP atlas of nontumour pathology. 2002. Vo. 2. P.277. ISBN 1-881041-79-4.
  29. ↑ AFIP atlas of nontumour pathology. 2002. Vo. 2. P.281. ISBN 1-881041-79-4.
  30. ↑ 30.0 30.1 Leslie, Kevin O.; Wick, Mark R. (2004). Practical Pulmonary Pathology: A Diagnostic Approach (1st ed.). Churchill Livingstone. pp. 234. ISBN 978-0443066313.
  31. ↑ 31.0 31.1 Leslie, Kevin O.; Wick, Mark R. (2004). Practical Pulmonary Pathology: A Diagnostic Approach (1st ed.). Churchill Livingstone. pp. 237. ISBN 978-0443066313.
  32. ↑ 32.0 32.1 Mukhopadhyay S, Gal AA (May 2010). "Granulomatous lung disease: an approach to the differential diagnosis". Arch. Pathol. Lab. Med. 134 (5): 667–90. PMID 20441499.
  33. ↑ URL: http://www.radiologyassistant.nl/en/46b480a6e4bdc. Accessed on: 23 May 2010.
  34. ↑ Davis, LL. (Dec 1983). "Pulmonary "mainline" granulomatosis: talcosis secondary to intravenous heroin abuse with characteristic x-ray findings of asbestosis.". J Natl Med Assoc 75 (12): 1225–8. PMC 2561715. PMID 6655726. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2561715/.
  35. ↑ Marchiori, E.; Lourenço, S.; Gasparetto, TD.; Zanetti, G.; Mano, CM.; Nobre, LF. (Apr 2010). "Pulmonary talcosis: imaging findings.". Lung 188 (2): 165-71. doi:10.1007/s00408-010-9230-y. PMID 20155272.
  36. ↑ 36.0 36.1 Yamazaki, K. (Jul 2004). "Type-II pneumocyte differentiation in pulmonary sclerosing hemangioma: ultrastructural differentiation and immunohistochemical distribution of lineage-specific transcription factors (TTF-1, HNF-3 alpha, and HNF-3 beta) and surfactant proteins.". Virchows Arch 445 (1): 45-53. doi:10.1007/s00428-004-1023-3. PMID 15138814.
  37. ↑ Einsfelder, BM.; Müller, KM. (Sep 2005). "["Pneumocytoma" or "sclerosing hemangioma": histogenetic aspects of a rare tumor of the lung]". Pathologe 26 (5): 367-77. doi:10.1007/s00292-005-0751-8. PMID 15731902.
  38. ↑ 38.0 38.1 Keylock, JB.; Galvin, JR.; Franks, TJ. (May 2009). "Sclerosing hemangioma of the lung.". Arch Pathol Lab Med 133 (5): 820-5. PMID 19415961.
  39. ↑ URL: http://www.med.muni.cz/biomedjournal/pdf/2004/01/37_42.pdf. Accessed on: 17 June 2010.
  40. ↑ Taveira-DaSilva, AM.; Pacheco-Rodriguez, G.; Moss, J. (Mar 2010). "The natural history of lymphangioleiomyomatosis: markers of severity, rate of progression and prognosis.". Lymphat Res Biol 8 (1): 9-19. doi:10.1089/lrb.2009.0024. PMID 20235883.
  41. ↑ 41.0 41.1 http://emedicine.medscape.com/article/299545-overview
  42. ↑ Schiavina, M.; Di Scioscio, V.; Contini, P.; Cavazza, A.; Fabiani, A.; Barberis, M.; Bini, A.; Altimari, A. et al. (Jul 2007). "Pulmonary lymphangioleiomyomatosis in a karyotypically normal man without tuberous sclerosis complex.". Am J Respir Crit Care Med 176 (1): 96-8. doi:10.1164/rccm.200610-1408CR. PMID 17431222.
  43. ↑ http://emedicine.medscape.com/article/299545-diagnosis
  44. ↑ 44.0 44.1 Trapnell BC, Whitsett JA, Nakata K (December 2003). "Pulmonary alveolar proteinosis". N. Engl. J. Med. 349 (26): 2527-39. doi:10.1056/NEJMra023226. PMID 14695413. http://content.nejm.org/cgi/content/extract/349/26/2527.
  45. ↑ Leslie, Kevin O.; Wick, Mark R. (2004). Practical Pulmonary Pathology: A Diagnostic Approach (1st ed.). Churchill Livingstone. pp. 248. ISBN 978-0443066313.
  46. ↑ Leslie KO (May 2009). "My approach to interstitial lung disease using clinical, radiological and histopathological patterns". J. Clin. Pathol. 62 (5): 387–401. doi:10.1136/jcp.2008.059782. PMC 2668105. PMID 19398592. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668105/.
  47. ↑ 47.0 47.1 47.2 Poletti, V.; Casoni, G.; Chilosi, M.; Zompatori, M. (Oct 2006). "Diffuse panbronchiolitis.". Eur Respir J 28 (4): 862-71. doi:10.1183/09031936.06.00131805. PMID 17012632.
  48. ↑ Bush A (December 2000). "Pulmonary hypertensive diseases". Paediatr Respir Rev 1 (4): 361-7. doi:10.1053/prrv.2000.0077. PMID 16263465.
  49. ↑ http://emedicine.medscape.com/article/301070-overview

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