Difference between revisions of "Diffuse lung diseases"

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'''Diffuse lung diseases''', abbreviated '''DLD''', are a group of uncommon pathologies, also known as '''idiopathic interstitial pneumonias''', abbreviated '''IIPs'''. They are a subgroup of the [[medical lung diseases]].   
'''Diffuse lung diseases''', abbreviated '''DLD''', are a group of uncommon pathologies, also known as '''idiopathic interstitial [[pneumonia]]s''', abbreviated '''IIPs''', and '''interstitial lung disease''', abbreviated '''ILD'''.  
 
They are a subgroup of the [[medical lung diseases]].   
 
Diffuse lung disease is the preferred term, as some diseases lumped into this group have involvement of the alveoli, i.e. are not interstitial. Also, some DLDs are not considered idiopathic, e.g. [[DIP]] is caused by [[smoking]].


An introduction to pulmonary pathology is found in the ''[[pulmonary pathology]]'' article.
An introduction to pulmonary pathology is found in the ''[[pulmonary pathology]]'' article.


*Often [[abbreviated]] '''IIP''', is a term used for a type of diffuse lung disease.
=Overview=
**Diffuse lung disease is also known as ''interstitial lung disease''.  
==Specimens==
***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.
*Diffuse lung disease is best assessed on an open biopsy.
**These procedure are quite invasive; thus, not infrequently clinicians will try a transbrochial biopsy that ends-up providing in useful information.
 
===Sign out===
<pre>
LUNG, LEFT, TRANSBRONCHIAL BIOPSY:
- SMALL FRAGMENTS OF LUNG PARENCHYMA WITHOUT SIGNIFICANT CHANGES, SEE MICROSCOPIC
  DESCRIPTION AND COMMENT.


=Overview - histologic classification=
COMMENT:
The clinical findings are noted. The size and type of biopsy significantly limit the
interpretation.  Suspected diffuse lung disease (interstitial lung disease)
is best assessed on an open lung biopsy.
</pre>
====Micro====
The sections show small fragments of lung parenchyma. A very small amount of anthracotic
pigment is present. Interstitial fibrosis is not apparent. No granulomata are identified.
No nuclear atypia is identified. Air-space macrophages show minimal pigmentation and are
not present in large numbers. No significant airspace or interstitial inflammation is
identified.
 
==Histologic classification==
*Can be complex,<ref name="pmid12405906">{{cite journal |author=Nicholson AG |title=Classification of idiopathic interstitial pneumonias: making sense of the alphabet soup |journal=Histopathology |volume=41 |issue=5 |pages=381-91 |year=2002 |month=November |pmid=12405906 |doi= |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0309-0167&date=2002&volume=41&issue=5&spage=381}}</ref> and the combined efforts of [[clinician]]s, [[radiologist]]s, and [[pathologist]]s can help in the generation of a more specific diagnosis.<ref name="pmid15256390">{{cite journal |author=Flaherty KR, King TE, Raghu G, ''et al'' |title=Idiopathic interstitial pneumonia: what is the effect of a multidisciplinary approach to diagnosis? |journal=Am. J. Respir. Crit. Care Med. |volume=170 |issue=8 |pages=904-10 |year=2004 |month=October |pmid=15256390 |doi=10.1164/rccm.200402-147OC |url=http://ajrccm.atsjournals.org/cgi/pmidlookup?view=long&pmid=15256390}}</ref><ref name="pmid16738191">{{cite journal |author=Kim DS, Collard HR, King TE |title=Classification and natural history of the idiopathic interstitial pneumonias |journal=Proc Am Thorac Soc |volume=3 |issue=4 |pages=285-92 |year=2006 |month=June |pmid=16738191 |doi=10.1513/pats.200601-005TK |url=http://pats.atsjournals.org/cgi/pmidlookup?view=long&pmid=16738191}}</ref>
*Can be complex,<ref name="pmid12405906">{{cite journal |author=Nicholson AG |title=Classification of idiopathic interstitial pneumonias: making sense of the alphabet soup |journal=Histopathology |volume=41 |issue=5 |pages=381-91 |year=2002 |month=November |pmid=12405906 |doi= |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0309-0167&date=2002&volume=41&issue=5&spage=381}}</ref> and the combined efforts of [[clinician]]s, [[radiologist]]s, and [[pathologist]]s can help in the generation of a more specific diagnosis.<ref name="pmid15256390">{{cite journal |author=Flaherty KR, King TE, Raghu G, ''et al'' |title=Idiopathic interstitial pneumonia: what is the effect of a multidisciplinary approach to diagnosis? |journal=Am. J. Respir. Crit. Care Med. |volume=170 |issue=8 |pages=904-10 |year=2004 |month=October |pmid=15256390 |doi=10.1164/rccm.200402-147OC |url=http://ajrccm.atsjournals.org/cgi/pmidlookup?view=long&pmid=15256390}}</ref><ref name="pmid16738191">{{cite journal |author=Kim DS, Collard HR, King TE |title=Classification and natural history of the idiopathic interstitial pneumonias |journal=Proc Am Thorac Soc |volume=3 |issue=4 |pages=285-92 |year=2006 |month=June |pmid=16738191 |doi=10.1513/pats.200601-005TK |url=http://pats.atsjournals.org/cgi/pmidlookup?view=long&pmid=16738191}}</ref>


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| [[Desquamative interstitial pneumonia]] (DIP)
| [[Desquamative interstitial pneumonia]] (DIP)
| DIP
| DIP
| Smoking
| [[smoking]]
|-
|-
| [[Diffuse alveolar damage]] (DAD)
| [[Diffuse alveolar damage]] (DAD)
Line 32: Line 56:
| [[Respiratory bronchiolitis]]  
| [[Respiratory bronchiolitis]]  
| [[Respiratory bronchiolitis-associated interstitial lung disease|RB-ILD]]
| [[Respiratory bronchiolitis-associated interstitial lung disease|RB-ILD]]
| Smoking
| smoking
|-
|-
| [[Usual interstitial pneumonia]] (UIP)
| [[Usual interstitial pneumonia]] (UIP)
| [[collagen vascular disease|CVD]], [[idiopathic pulmonary fibrosis|IPF]], [[drug toxicity]], [[pneumoconiosis]]
| [[collagen vascular disease|CVD]], [[idiopathic pulmonary fibrosis|IPF]], [[drug toxicity]], [[pneumoconiosis]]
| Allergen (hypersensitivity pneumonitis), idiopathic, autoimmune
| allergen (hypersensitivity pneumonitis), idiopathic, autoimmune
|-
|-
| [[Organizing pneumonia]]
| [[Organizing pneumonia]]
Line 42: Line 66:
| autoimmune (???)
| autoimmune (???)
|-
|-
| [[Lymphoid interstitial pneumonia]] (LIP)
| [[Lymphocytic interstitial pneumonia]] (LIP)
| LIP
| LIP
| Viral/autoimmune
| 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.
ARDS = adult respiratory distress syndrome, AIP = acute interstitial pneumonia, TRALI = transfusion related acute lung injury, CVD = [[collagen vascular disease]], IPF = idiopathic pulmonary fibrosis.
 


Notes:
Notes:
*''Usual interstitial pneumonia'' is the most common type of ILD.<ref name="pmid16738196">{{cite journal |author=Visscher DW, Myers JL |title=Histologic spectrum of idiopathic interstitial pneumonias |journal=Proc Am Thorac Soc |volume=3 |issue=4 |pages=322-9 |year=2006 |month=June |pmid=16738196 |doi=10.1513/pats.200602-019TK |url=http://pats.atsjournals.org/cgi/pmidlookup?view=long&pmid=16738196}}</ref>
*''Usual interstitial pneumonia'' is the most common type of ILD.<ref name="pmid16738196">{{cite journal |author=Visscher DW, Myers JL |title=Histologic spectrum of idiopathic interstitial pneumonias |journal=Proc Am Thorac Soc |volume=3 |issue=4 |pages=322-9 |year=2006 |month=June |pmid=16738196 |doi=10.1513/pats.200602-019TK |url=http://pats.atsjournals.org/cgi/pmidlookup?view=long&pmid=16738196}}</ref>
==Gross pathologic DDx by location==
Causes of upper lung fibrosis ''FASSTEN'':<ref name=Ref_TN2005_R13>{{Ref TN2005| R13}}</ref>
*[[Farmer's lung]].
*[[Ankylosing spondylitis]].
*[[Sarcoidosis]].
*[[Silicosis]].
*[[Tuberculosis]] (miliary).
*[[Eosinophilic granuloma]].
*[[Neurofibromatosis]].
Causes of lower lung fibrosis ''BAD RASH'':<ref name=Ref_TN2005_R13>{{Ref TN2005| R13}}</ref>
*[[Bronchiolitis obliterans organizing pneumonia]] (BOOP).
*[[Asbestosis]].
*Drugs (nitrofurantoin, hydralazine, isoniazid (INH), amiodarone).
*[[Rheumatologic disease]].
*[[aspiration pneumonia|Aspiration]].
*[[Scleroderma]].
*Hamman-Rich syndrome (really should be -- ''[[idiopathic pulmonary fibrosis]]'').
Note:
*''Hamman-Rich syndrome'' is another name for [[acute interstitial pneumonia]].<ref name=Ref_WMSP90>{{Ref WMSP|90}}</ref>


=Specific diseases/pattterns=
=Specific diseases/pattterns=
Line 56: Line 101:
==Diffuse alveolar damage==
==Diffuse alveolar damage==
*Abbreviated ''DAD''.
*Abbreviated ''DAD''.
===General===
{{Main|Diffuse alveolar damage}}
DAD is the histologic correlate of:
*Adult respiratory distress syndrome (ARDS).
*Acute interstitial pneumonia (AIP).
*Transfusion related acute lung injury (TRALI).
 
===Microscopic===
Features:<ref name=Ref_Klatt103>{{Ref Klatt|103}}</ref>
*Early:
**Hyaline membrane: debris (pink crap) lines the alveolar spaces.
*Intermediate:
**Macrophage proliferation.
*Late:
**Interstitial inflammation.
**Fibrosis.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Hyaline_membranes_-_intermed_mag.jpg DAD - intermed. mag. (WC)].
*[http://en.wikipedia.org/wiki/File:Hyaline_membranes_-_very_high_mag.jpg DAD - very high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:ARDS.jpg DAD (WC)].


==Usual interstitial pneumonia==
==Usual interstitial pneumonia==
*Abbreviated ''UIP''.
*Abbreviated ''UIP''.
===General===
{{Main|Usual interstitial pneumonia}}
*It is sometimes used incorrectly as a synoym for ''idiopathic pulmonary fibrosis''.
*Cannot be diagnosed via bronchoscopic or transbronchial biopsy.<ref name=Ref_PPP186>{{Ref PPP|186}}</ref>
 
====Epidemiology====
*Disease of the old - rare in under 50 years old.<ref>AC UBC S.102.</ref>
*Dismal prognosis - mean survival after diagnosis ~ 2.8 years.<ref name=pmid9445300>{{Cite journal  | last1 = Bjoraker | first1 = JA. | last2 = Ryu | first2 = JH. | last3 = Edwin | first3 = MK. | last4 = Myers | first4 = JL. | last5 = Tazelaar | first5 = HD. | last6 = Schroeder | first6 = DR. | last7 = Offord | first7 = KP. | title = Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. | journal = Am J Respir Crit Care Med | volume = 157 | issue = 1 | pages = 199-203 | month = Jan | year = 1998 | doi =  | PMID = 9445300 }}</ref>
 
====Differential diagnosis====
UIP is seen in:<ref name=leslie>{{cite book |author=Wick, Mark R.; Leslie, Kevin |title=Practical pulmonary pathology: a diagnostic approach |publisher=Churchill Livingstone |location=Edinburgh |year=2005 |pages= |isbn=0-443-06631-0 |oclc= 156861539|doi= |accessdate=}}</ref>
*Idiopathic pulmonary fibrosis.
*Asbestosis - one ought to see ''ferruginous bodies''.
*Chronic hypersensitivity pneumonitis (extrinsic allergic alveolitis).
*Collagen vascular disease - includes [[systemic lupus erythematousus]], [[rheumatoid arthritis]], [[scleroderma]].<ref>{{Ref PCPBoD8|374}}</ref>
*Chronic drug toxicity.<ref>{{cite journal |author=Rossi SE, Erasmus JJ, McAdams HP, Sporn TA, Goodman PC |title=Pulmonary drug toxicity: radiologic and pathologic manifestations |journal=Radiographics : a review publication of the Radiological Society of North America, Inc |volume=20 |issue=5 |pages=1245-59 |year=2000 |pmid=10992015 |doi=}}</ref>
 
===Radiology===
*Honeycombing - ''multiple'' defects that obliterate the normal lung architecture - multiple spherical voids in the lung parenchyma; radiologically these are seen as lucencies.<ref>[http://www.medcyclopaedia.com/library/topics/volume_v_1/h/honeycombing.aspx http://www.medcyclopaedia.com/library/topics/volume_v_1/h/honeycombing.aspx]</ref>
**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.<ref>[http://www.medcyclopaedia.com/library/topics/volume_v_1/l/lung_cyst.aspx http://www.medcyclopaedia.com/library/topics/volume_v_1/l/lung_cyst.aspx]</ref>
 
===Microscopic===
Features:<ref name=Ref_PPP186-9>{{Ref PPP|186-9}}</ref>
*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.<ref>[http://www.epler.com/IPFWhat%27sIPFDiseaseInformation2.htm http://www.epler.com/IPFWhat%27sIPFDiseaseInformation2.htm]</ref>
**Note: Technically, ''fibroblast foci'' are composed of myofibroblasts.<ref name=Ref_PPP189>{{Ref PPP|189}}</ref>
*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.<ref>H. 8 July, 2009.</ref>
 
Notes:
*Disease worse distant from large airways: lower lung field predominance, typically worse at periphery of lobule and lung.<ref>A. Churg. UBC S.103.</ref>
*Heterogeneity of inflammation: airspace macrophages & inflammation minimal in honeycombed foci.


==Asbestosis==
==Asbestosis==
===General===
{{Main|Asbestosis}}
*Important to diagnose... asbestosis = compensation.
 
===Microscopic===
*Histologic appearance as for UIP -- plus ''ferruginous bodies''.
**Segmented twirling batton with long slender fibre within.
 
Image(s):
*[http://commons.wikimedia.org/wiki/File:Ferruginous_body.jpg Ferruginous bodies (WC)].
*[http://commons.wikimedia.org/wiki/File:Asbestosis_high_mag.jpg Asbestosis (WC)].


==Non-specific interstitial pneumonia==
==Non-specific interstitial pneumonia==
*Abbreviated ''NSIP''.
*Abbreviated ''NSIP''.
*Better prognosis than UIP.
{{Main|Non-specific interstitial pneumonia}}
*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===
==Organizing pneumonia==
*Collagen vascular disease.
{{Main|Organizing pneumonia}}
*Drug reaction.
*Hypersensitivity pneumonitis (extrinic allergic alveolitis).


==Hypersensitivity pneumonitis==
==Hypersensitivity pneumonitis==
*AKA ''extrinsic allergic alveolitis''
*AKA ''extrinsic allergic alveolitis''
*Exposure to stuffs... e.g. moldy hay - ''Farmer's lung'', atypical mycobacteria - ''hot tub lung''.
{{Main|Hypersensitivity pneumonitis}}
*Upper lung predominant disease (???).


===Microscopic===
==Lymphocytic interstitial pneumonia==
Features:
*Often abbreviated '''''LIP'''''.
* Lesions have centrilobular prominence - '''important feature'''. <ref name=pmid16061708/>
{{Main|Lymphocytic interstitial pneumonia}}
** Allergens enter lung through airway which has a centrilobular location.
* [[Granulomata]] (not typically seen in UIP) - '''important feature'''.<ref name=pmid16061708>PMID 16061708.</ref>
* Chronic interstitial inflammation consisting primarily of lymphocytes.
* Interstitial fibrosis.
* Air space involvement (alveolitis).


Images:
==Respiratory bronchiolitis-interstitial lung disease==
*[http://commons.wikimedia.org/wiki/File:Hypersensitivity_pneumonitis_intermed_mag.jpg Hypersensitivity pneumonitis - intermed. mag. (WC)].
*Abbreviated ''RB-ILD'' or ''RBILD''.
*[http://commons.wikimedia.org/wiki/File:Hypersensitivity_pneumonitis_high_mag.jpg Hypersensitivity pneumonitis - high mag. (WC)].
*[[AKA]] ''respiratory bronchiolitis-associated interstitial lung disease''.
{{Main|Respiratory bronchiolitis-interstitial lung disease}}


==Desquamative interstitial pneumonia==
*Abbreviated ''DIP''.
{{Main|Desquamative interstitial pneumonia}}


=See also=
=See also=

Latest revision as of 03:37, 18 April 2016

Diffuse lung diseases, abbreviated DLD, are a group of uncommon pathologies, also known as idiopathic interstitial pneumonias, abbreviated IIPs, and interstitial lung disease, abbreviated ILD.

They are a subgroup of the medical lung diseases.

Diffuse lung disease is the preferred term, as some diseases lumped into this group have involvement of the alveoli, i.e. are not interstitial. Also, some DLDs are not considered idiopathic, e.g. DIP is caused by smoking.

An introduction to pulmonary pathology is found in the pulmonary pathology article.

Overview

Specimens

  • Diffuse lung disease is best assessed on an open biopsy.
    • These procedure are quite invasive; thus, not infrequently clinicians will try a transbrochial biopsy that ends-up providing in useful information.

Sign out

LUNG, LEFT, TRANSBRONCHIAL BIOPSY:
- SMALL FRAGMENTS OF LUNG PARENCHYMA WITHOUT SIGNIFICANT CHANGES, SEE MICROSCOPIC
  DESCRIPTION AND COMMENT.

COMMENT:
The clinical findings are noted. The size and type of biopsy significantly limit the 
interpretation.  Suspected diffuse lung disease (interstitial lung disease) 
is best assessed on an open lung biopsy.

Micro

The sections show small fragments of lung parenchyma. A very small amount of anthracotic pigment is present. Interstitial fibrosis is not apparent. No granulomata are identified. No nuclear atypia is identified. Air-space macrophages show minimal pigmentation and are not present in large numbers. No significant airspace or interstitial inflammation is identified.

Histologic classification

Idiopathic interstitial pneumonia can be subclassified based on histologic appearance into the following patterns:[4][5]

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 (???)
Lymphocytic 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.[6]

Gross pathologic DDx by location

Causes of upper lung fibrosis FASSTEN:[7]

Causes of lower lung fibrosis BAD RASH:[7]

Note:

Specific diseases/pattterns

Diffuse alveolar damage

  • Abbreviated DAD.
Main article: Diffuse alveolar damage

Usual interstitial pneumonia

  • Abbreviated UIP.
Main article: Usual interstitial pneumonia

Asbestosis

Main article: Asbestosis

Non-specific interstitial pneumonia

  • Abbreviated NSIP.
Main article: Non-specific interstitial pneumonia

Organizing pneumonia

Main article: Organizing pneumonia

Hypersensitivity pneumonitis

  • AKA extrinsic allergic alveolitis
Main article: Hypersensitivity pneumonitis

Lymphocytic interstitial pneumonia

  • Often abbreviated LIP.
Main article: Lymphocytic interstitial pneumonia

Respiratory bronchiolitis-interstitial lung disease

  • Abbreviated RB-ILD or RBILD.
  • AKA respiratory bronchiolitis-associated interstitial lung disease.
Main article: Respiratory bronchiolitis-interstitial lung disease

Desquamative interstitial pneumonia

  • Abbreviated DIP.
Main article: Desquamative interstitial pneumonia

See also

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ Leslie KO, Wick MR. Practical Pulmonary Pathology: A Diagnostic Approach. Elsevier Inc. 2005. ISBN 978-0-443-06631-3.
  5. ↑ "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.
  6. ↑ 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.
  7. ↑ 7.0 7.1 Yeung, J.C.; Leonard, Blair J. N. (2005). The Toronto Notes 2005 - Review for the MCCQE and Comprehensive Medical Reference (2005 ed.). The Toronto Notes Inc. for Medical Students Inc.. pp. R13. ISBN 978-0968592854.
  8. ↑ 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.
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