Difference between revisions of "Medical lung diseases"

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==Sarcoidosis==
==Sarcoidosis==
{{Main|Sarcoidosis}}
===General===
===General===
*Diagnosis of exclusion - infection must be excluded.
*Diagnosis of exclusion - infection must be excluded.

Revision as of 17:37, 29 September 2010

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.

This article includes a discussion about pulmonary hypertension, which may arise due to congenital heart disease.

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 from normal region to abnormal region.

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.
  • Associated with atopy.
  • Mast cells thought to play an important role.

Microscopic

Features:[1]

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

Images:

Notes:

  • Leyden in Charcot-Leyden is also seen written as Leiden.

Emphysema

General

  • Usually due to smoking.
  • May be associated with alpha-1 antitrypsin deficiency.

Gross

  • Holes, usually upper lung field predominant.

Microscopic

Features:

  • Large alveoli.
  • No interstitial thickening.

Image: Emphysema (WC).

Pulmonary edema

General

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

Microscopic

Features:[2]

  • 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:[3]

  • 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:[7][8]

Histology Clinical Correlates Associations
Desquamative interstitial pneumonia (DIP) DIP Smoking
Diffuse alveolar damage (DAD) ARDS, AIP, TRALI ARDS: trauma, infection; TRALI: blood transfusion; AIP: ???
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.[9]

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.[10]
    • Reticular = net-like.[11]
  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:[12]

  • 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:[13]

  • 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.).[14][15]

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:[16]

  • 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.[17]

Epidemiology

  • Disease of the old - rare in under 50 years old.[18]
  • Dismal prognosis - mean survival after diagnosis ~ 2.8 years.[14]

Differential diagnosis

UIP is seen in:[19]

  • Idiopathic pulmonary fibrosis.
  • Asbestosis - one ought to see ferruginous bodies.
  • Chronic hypersensitivity pneumonitis (extrinsic allergic alveolitis).
  • Collagen vascular disease.
  • Chronic drug toxicity.[20]

Radiologic

  • Honeycombing - multiple defects that obliterate the normal lung architecture - multiple spherical voids in the lung parenchyma; radiologically these are seen as lucencies.[21]
    • 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.[22]

Histology

Features:[23]

  • 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.[24]
    • Note: Technically, fibroblast foci are composed of myofibroblasts.[25]
  • 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.[26]

Notes:

  • Disease worse distant from large airways: lower lung field predominance, typically worse at periphery of lobule and lung.[27]
  • 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. [28]
    • Allergens enter lung through airway which has a centrilobular location.
  • Granulomata (not typically seen in UIP) - important feature.[28]
  • Chronic interstitial inflammation consisting primarily of lymphocytes.
  • Interstitial fibrosis.
  • Air space involvement (alveolitis).

Images:

Lymphocytic interstitial pneumonia

General

  • Often abbreviated LIP.
  • Associated with autoimmune disorders (rheumatoid arthritis, pernicious anemia, Sjoegren syndrome).[29]
  • Associated with viral infections (HIV, EBV, human T-cell leukemia virus (HTLV) type 1).

Gross

  • Basilar predominance.

Microscopic

Features:[30]

  • Small mature lymphocytes.
  • Plasma cells.
  • +/-Lymphoid follicles.

Negatives:

  • No Vasculitis.
  • No necrosis.

Image: LIP (scielo.br).

Smoking assoc. 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.

RBILD

General

  • Respiratory bronchiolitis interstitial lung disease.

Histology

Features:[31]

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

Note:

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

DIP

  • Desquamative interstitial pneumonia.
  • Thought to be advanced RBILD.

Histology

  • 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

General

  • AKA eosinophilic granuloma of lung.
  • Associated with smoking.[32]
  • Not assoc. with systemic diseases of Langerhans cells (AKA Hand-Schueller-Christian disease).

Subtypes:[32]

  • Cellular form.
  • Fibrotic form.

One form usually predominates.

Radiology

  • Upper lung zones.

Histology

Features:[33]

  • 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+.[33]

Granulomatous lung disease

Most common:

  • Infectious - mycobacterial and fungal.[34]

Noninfectious causes:[34]

  • 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.[35]

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.[36]
  • 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.[37]
  • Progesterone-receptor positive stromal cells.[38]

Epidemiology

  • Female in 40s.[39]
  • Considered benign; excision is curative.
    • Rare case reports of metastases.

Gross

  • Peripheral, solitary.
  • Well-circumscribed.

Microscopy

Features:[39]

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

DDx:[40]

  • Papillary adenoma.
  • Neuroendocrine tumour (carcinoid).

IHC

Features:[37]

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

Lymphangioleiomyomatosis

General

  • Abbreviated LAM.
  • Clinical: dyspnea, recurrent pneumothorax.
  • May be an indication for lung transplantation.
  • Non-neoplastic muscle proliferation vs. tumour that can metastasize.[41]

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.

Histology

Features:[44]

  • 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.
  • Associated with smoking - particularily in men.[45]

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:[45]

  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

Histology

  • Crap in 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:

  • Edema.
  • Pneumocystis.

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:[46]

  • 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:[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

Features GAFE:

  • Granulomata.
  • Asthma.
  • Fever.
  • Eosinophilia.

General

  • AKA allergic granulomatous angiitis.[48]
  • Small vessel vasculitis.
  • Similar to Wegener's granulomatosis (classically c-ANCA +ve) and microscopic polyangiitis (a form of polyarteritis nodosa).[49]

Lung transplant pathology

Main article: Lung transplant pathology

This subspecialty is dealt with in its own article.

See also

References

  1. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 108. ISBN 978-1416002741.
  2. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 102. ISBN 978-1416002741.
  3. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 110. ISBN 978-1416002741.
  4. ↑ Nicholson AG (November 2002). "Classification of idiopathic interstitial pneumonias: making sense of the alphabet soup". Histopathology 41 (5): 381-91. PMID 12405906. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0309-0167&date=2002&volume=41&issue=5&spage=381.
  5. ↑ Flaherty KR, King TE, Raghu G, et al (October 2004). "Idiopathic interstitial pneumonia: what is the effect of a multidisciplinary approach to diagnosis?". Am. J. Respir. Crit. Care Med. 170 (8): 904-10. doi:10.1164/rccm.200402-147OC. PMID 15256390. http://ajrccm.atsjournals.org/cgi/pmidlookup?view=long&pmid=15256390.
  6. ↑ Kim DS, Collard HR, King TE (June 2006). "Classification and natural history of the idiopathic interstitial pneumonias". Proc Am Thorac Soc 3 (4): 285-92. doi:10.1513/pats.200601-005TK. PMID 16738191. http://pats.atsjournals.org/cgi/pmidlookup?view=long&pmid=16738191.
  7. ↑ Leslie KO, Wick MR. Practical Pulmonary Pathology: A Diagnostic Approach. Elsevier Inc. 2005. ISBN 978-0-443-06631-3.
  8. ↑ "American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001". Am. J. Respir. Crit. Care Med. 165 (2): 277-304. January 2002. PMID 11790668. http://ajrccm.atsjournals.org/cgi/pmidlookup?view=long&pmid=11790668.
  9. ↑ Visscher DW, Myers JL (June 2006). "Histologic spectrum of idiopathic interstitial pneumonias". Proc Am Thorac Soc 3 (4): 322-9. doi:10.1513/pats.200602-019TK. PMID 16738196. http://pats.atsjournals.org/cgi/pmidlookup?view=long&pmid=16738196.
  10. ↑ http://www.rsna.org/Publications/rsnanews/may06/jrnl_may06.cfm
  11. ↑ http://dictionary.reference.com/browse/reticular
  12. ↑ TN05 R13.
  13. ↑ TN05 R13.
  14. ↑ 14.0 14.1 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.
  15. ↑ AC UBC S.425.
  16. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 103. ISBN 978-1416002741.
  17. ↑ Leslie, Kevin O.; Wick, Mark R. (2004). Practical Pulmonary Pathology: A Diagnostic Approach (1st ed.). Churchill Livingstone. pp. 186. ISBN 978-0443066313.
  18. ↑ AC UBC S.102.
  19. ↑ Wick, Mark R.; Leslie, Kevin (2005). Practical pulmonary pathology: a diagnostic approach. Edinburgh: Churchill Livingstone. ISBN 0-443-06631-0. OCLC 156861539.
  20. ↑ Rossi SE, Erasmus JJ, McAdams HP, Sporn TA, Goodman PC (2000). "Pulmonary drug toxicity: radiologic and pathologic manifestations". Radiographics : a review publication of the Radiological Society of North America, Inc 20 (5): 1245-59. PMID 10992015.
  21. ↑ http://www.medcyclopaedia.com/library/topics/volume_v_1/h/honeycombing.aspx
  22. ↑ http://www.medcyclopaedia.com/library/topics/volume_v_1/l/lung_cyst.aspx
  23. ↑ Leslie, Kevin O.; Wick, Mark R. (2004). Practical Pulmonary Pathology: A Diagnostic Approach (1st ed.). Churchill Livingstone. pp. 186-9. ISBN 978-0443066313.
  24. ↑ http://www.epler.com/IPFWhat%27sIPFDiseaseInformation2.htm
  25. ↑ Leslie, Kevin O.; Wick, Mark R. (2004). Practical Pulmonary Pathology: A Diagnostic Approach (1st ed.). Churchill Livingstone. pp. 189. ISBN 978-0443066313.
  26. ↑ H. 8 July, 2009.
  27. ↑ AC UBC S.103.
  28. ↑ 28.0 28.1 PMID 16061708.
  29. ↑ URL: http://emedicine.medscape.com/article/299643-overview. Accessed on: 2 June 2010.
  30. ↑ URL: http://emedicine.medscape.com/article/299643-diagnosis. Accessed on: 2 June 2010.
  31. ↑ Leslie, Kevin O.; Wick, Mark R. (2004). Practical Pulmonary Pathology: A Diagnostic Approach (1st ed.). Churchill Livingstone. pp. 197-8. ISBN 978-0443066313.
  32. ↑ 32.0 32.1 Leslie, Kevin O.; Wick, Mark R. (2004). Practical Pulmonary Pathology: A Diagnostic Approach (1st ed.). Churchill Livingstone. pp. 234. ISBN 978-0443066313.
  33. ↑ 33.0 33.1 Leslie, Kevin O.; Wick, Mark R. (2004). Practical Pulmonary Pathology: A Diagnostic Approach (1st ed.). Churchill Livingstone. pp. 237. ISBN 978-0443066313.
  34. ↑ 34.0 34.1 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.
  35. ↑ URL: http://www.radiologyassistant.nl/en/46b480a6e4bdc. Accessed on: 23 May 2010.
  36. ↑ 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/.
  37. ↑ 37.0 37.1 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.
  38. ↑ 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.
  39. ↑ 39.0 39.1 Keylock, JB.; Galvin, JR.; Franks, TJ. (May 2009). "Sclerosing hemangioma of the lung.". Arch Pathol Lab Med 133 (5): 820-5. PMID 19415961.
  40. ↑ URL: http://www.med.muni.cz/biomedjournal/pdf/2004/01/37_42.pdf. Accessed on: 17 June 2010.
  41. ↑ 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.
  42. ↑ 42.0 42.1 http://emedicine.medscape.com/article/299545-overview
  43. ↑ 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.
  44. ↑ http://emedicine.medscape.com/article/299545-diagnosis
  45. ↑ 45.0 45.1 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.
  46. ↑ Bush A (December 2000). "Pulmonary hypertensive diseases". Paediatr Respir Rev 1 (4): 361-7. doi:10.1053/prrv.2000.0077. PMID 16263465.
  47. ↑ http://emedicine.medscape.com/article/301070-overview
  48. ↑ http://emedicine.medscape.com/article/333492-overview
  49. ↑ http://emedicine.medscape.com/article/334024-overview

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