Small cell carcinoma of the lung diagnostic study of choice: Difference between revisions

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__NOTOC__
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{{Small cell carcinoma of the lung}}
{{Small cell carcinoma of the lung}}
{{CMG}}; {{AE}}
{{CMG}}; {{AE}} {{SH}}{{Rim}}
== Overview ==
== Overview ==
The confirmation of the diagnosis of SCLC relies on the histopathological findings of the tumor [[biopsy]]. All patients with confirmed diagnosis of SCLC by [[histopathological]] findings should undergo a [[CT scan]] of the [[abdomen]] for staging purposes. [[Computed tomography|CT scan]] of the [[abdomen]] helps identify [[metastasis]] to organs, such as the [[liver]] or the [[adrenal glands]]. Staging schemes for small cell lung cancer (SCLC) have been developed by the Veterans Administration Lung Study Group (VALG), the American Joint Committee on Cancer (AJCC), and the National Comprehensive Cancer Network (NCCN).


== Diagnostic Study of Choice ==
== Diagnostic Study of Choice ==
==Microscopic Pathology==
===Biopsy===
* The confirmation of the diagnosis of SCLC relies on the histopathological findings of the tumor [[biopsy]].<ref name="NCCN">[http://www.nccn.org/professionals/physician_gls/f_guidelines_nojava.asp NCCN Clinical Practice Guidelines in Oncology. Small Cell Lung Cancer, version 2.2014] </ref>
* In SCLC, the [[Tumor cell|tumor cells]] are small and round, but they can sometimes be ovoid or spindle shaped.  They have a scant [[cytoplasm]] with a high [[mitotic]] count and a hyperchromatic [[nuclei]].  Nearly all SCLC are immunoreactive for [[keratin]], [[thyroid transcription factor 1]], and [[Epithelial cells|epithelial]] membrane [[antigen]]. [[Neuroendocrine]] and [[neural]] [[differentiation]] result in the expression of molecules like [[Dopamine beta-hydroxylase|dopa-decarboxylase]], [[calcitonin]], [[neuron-specific enolase]], [[chromogranin A]], [[CD56]] (also known as nucleosomal [[histone]] kinase 1 or [[neural]]-[[cell]] adhesion molecule), [[gastrin]]-releasing [[peptide]], and [[insulin-like growth factor 1]]. One or more markers of [[neuroendocrine]] differentiation can be found in approximately 75% of SCLC.<ref name="NCI">National Cancer Institute: PDQ® Small Cell Lung Cancer Treatment. Bethesda, MD: National Cancer Institute.  Available at: http://www.cancer.gov/cancertopics/pdq/treatment/small-cell-lung/healthprofessional.</ref>


In small cell lung cancer, the tumor cells are small and round, but they can sometimes be ovoid or spindle-shaped.  They have a scant [[cytoplasm]] with a high mitotic count and a hyperchromatic [[nuclei]].  Nearly all small cell lung cancer are immunoreactive for [[keratin]], [[thyroid transcription factor 1]], and epithelial membrane antigen.  Neuroendocrine and neural differentiation result in the expression of molecules like dopa decarboxylase, [[calcitonin]], neuron-specific [[enolase]], [[chromogranin A]], [[CD56]] (also known as nucleosomal histone kinase 1 or neural-cell adhesion molecule), gastrin-releasing peptide, and [[insulin-like growth factor 1]].  One or more markers of neuroendocrine differentiation can be found in approximately 75% of small cell lung cancer.<ref name="NCI">National Cancer Institute: PDQ® Small Cell Lung Cancer Treatment. Bethesda, MD: National Cancer Institute.  Available at: http://www.cancer.gov/cancertopics/pdq/treatment/small-cell-lung/healthprofessional.</ref>


{| class="wikitable"
{| class="wikitable"
|[[Image:Lung small cell carcinoma (1) by core needle biopsy.jpg|300px|thumb| Histopathologic image of small cell carcinoma of the lung. CT-guided core needle biopsy. H & E stain.By No machine-readable author provided. KGH assumed (based on copyright claims),via Wikimedia Commons <ref>href="http://www.gnu.org/copyleft/fdl.html">GFDL<nowiki></a></nowiki> or <nowiki><a href="http://creativecommons.org/licenses/by-sa/3.0/">CC-BY-SA-3.0</a></nowiki>], <nowiki><a href="https://commons.wikimedia.org/wiki/File%3ALung_small_cell_carcinoma_(1)_by_core_needle_biopsy.jpg"></nowiki></ref>]]  
|[[Image:Lung small cell carcinoma (1) by core needle biopsy.jpg|300px|thumb| Histopathologic image of small cell carcinoma of the lung. CT-guided core needle biopsy. H & E stain.By No machine-readable author provided. KGH assumed (based on copyright claims),via Wikimedia Commons <ref>href="http://www.gnu.org/copyleft/fdl.html">GFDL<nowiki></a></nowiki> or <nowiki><a href="http://creativecommons.org/licenses/by-sa/3.0/">CC-BY-SA-3.0</a></nowiki>], <nowiki><a href="https://commons.wikimedia.org/wiki/File%3ALung_small_cell_carcinoma_(1)_by_core_needle_biopsy.jpg"></nowiki></ref>]]
|[[Image:Lung small cell cancer 01.jpeg|300px|thumb| Micrograph of a small-cell carcinoma of the lung showing cells with nuclear moulding, minimal amount of cytoplasm and stippled chromatin. FNA specimen. Field stain.By No machine-readable author provided. KGH assumed (based on copyright claims), via Wikimedia Commons <ref>href="http://www.gnu.org/copyleft/fdl.html">GFDL ="http://creativecommons.org/licenses/by-sa/3.0/">CC-BY-SA-3.0], href="https://commons.wikimedia.org/wiki/File%3ALung_small_cell_carcinoma_(1)_by_core_needle_biopsy.jpg"></ref>]]
|[[Image:Lung small cell cancer 01.jpeg|300px|thumb| Micrograph of a small-cell carcinoma of the lung showing cells with nuclear moulding, minimal amount of cytoplasm and stippled chromatin. FNA specimen. Field stain.By No machine-readable author provided. KGH assumed (based on copyright claims), via Wikimedia Commons <ref>href="http://www.gnu.org/copyleft/fdl.html">GFDL ="http://creativecommons.org/licenses/by-sa/3.0/">CC-BY-SA-3.0], href="https://commons.wikimedia.org/wiki/File%3ALung_small_cell_carcinoma_(1)_by_core_needle_biopsy.jpg"></ref>]]
|- [[Image:Lung small cell cancer 03.jpeg|300px|thumb| Anaplastic (microcellular, oat cell) carcinoma from the lung., via Wikimedia Commons <ref>href="https://commons.wikimedia.org/wiki/File:Carcinoma_microcellulare_oatcell_carcinoma_or_anaplastic_carcinoma_(lung)H%26E_magn_200x.jpg</ref>]]
|- [[Image:Lung small cell cancer 03.jpeg|300px|thumb| Anaplastic (microcellular, oat cell) carcinoma from the lung., via Wikimedia Commons <ref>href="https://commons.wikimedia.org/wiki/File:Carcinoma_microcellulare_oatcell_carcinoma_or_anaplastic_carcinoma_(lung)H%26E_magn_200x.jpg</ref>]]
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===Overview===
Chest [[CT scan]], preferably with [[intravenous]] [[contrast]] administration, may be helpful in the [[diagnosis]] of small cell carcinoma. Findings on [[CT scan]] suggestive of small cell carcinoma include [[Hilum|hilar]] mass, [[mediastinal]] involvement, numerous [[lymphadenopathy]], direct infiltration of adjacent structures, [[necrosis]] and [[hemorrhage]]. Small cell carcinoma of the lung is the most common cause of [[SVC obstruction]], due to both compression/[[thrombosis]] and/or direct infiltration 2.  All patients with confirmed diagnosis of SCLC by [[histopathological]] findings should undergo a [[CT scan]] of the [[abdomen]] for staging purposes. [[Computed tomography|CT scan]] of the [[abdomen]] helps identify [[metastasis]] to organs, such as the [[liver]] or the [[adrenal glands]]. Brain imaging is also mandatory for staging; however, brain [[MRI]] is preferred over brain [[CT scan]] due to its superior [[sensitivity]] for the detection of brain [[metastasis]].  In addition, when limited stage small cell lung cancer is suspected, [[PET]] CT scan should be performed.


===CT===
===CT===
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*[[PET]] [[CT-scans|CT]] scan should be performed if limited stage small cell lung cancer is suspected.
*[[PET]] [[CT-scans|CT]] scan should be performed if limited stage small cell lung cancer is suspected.


==Microscopic Pathology==
===Staging===
The Veterans Administration Lung Study Group (VALG) staging, also known as VA staging, is an old staging system that has been previously used in most clinical trials.  Shown below is a table depicting the VA staging system which classifies SCLC into two stages.<ref name="pmid12234695">{{cite journal| author=Micke P, Faldum A, Metz T, Beeh KM, Bittinger F, Hengstler JG et al.| title=Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer--what limits limited disease? | journal=Lung Cancer | year= 2002 | volume= 37 | issue= 3 | pages= 271-6 | pmid=12234695 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12234695  }} </ref>
 
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=center |'''Stage'''||style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=center |'''Characteristics'''
|-
|style="font-size: 100; padding: 0 5px; background: #DCDCDC" align=left |'''Limited SCLC''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=left |
* Limited SCLC is characterized by the strict involvement of the ipsilateral lung.
|-
|style="font-size: 100; padding: 0 5px; background: #DCDCDC" align=left |'''Extensive SCLC''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=left |
* Extensive SCLC extends beyond the ipsilateral [[lung]] and may involve the contralateral lung, or can be associated with [[pleural effusion]], [[pericardial effusion]], or hematogenous spread.
|}
 
===AJCC and TNM Staging===
Shown below is a table summarizing the staging of lung cancer according to the American Joint Committee on Cancer (AJCC).  This staging scheme is the same for both SCLC and [[non small cell lung cancer]].<ref name="pmid18090577">{{cite journal| author=Shepherd FA, Crowley J, Van Houtte P, Postmus PE, Carney D, Chansky K et al.| title=The International Association for the Study of Lung Cancer lung cancer staging project: proposals regarding the clinical staging of small cell lung cancer in the forthcoming (seventh) edition of the tumor, node, metastasis classification for lung cancer. | journal=J Thorac Oncol | year= 2007 | volume= 2 | issue= 12 | pages= 1067-77 | pmid=18090577 | doi=10.1097/JTO.0b013e31815bdc0d | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18090577  }} </ref>
 
''For more information about the TNM staging, click '''[[lung cancer staging|here]]'''.''
 
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=center |'''Stage'''||style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=center |'''T'''||style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=center |'''N'''||style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=center |'''M'''
|-
|style="font-size: 100; padding: 0 5px; background: #DCDCDC" align=center |'''Occult carcinoma''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center|TX|| style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |N0|| style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |M0
|-
|style="font-size: 100; padding: 0 5px; background: #DCDCDC" align=center |'''Stage 0''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |Tis ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center | N0 || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |M0
|-
|style="font-size: 100; padding: 0 5px; background: #DCDCDC" align=center |'''Stage IA''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |T1 || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |N0 || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |M0
|-
|style="font-size: 100; padding: 0 5px; background: #DCDCDC" align=center |'''Stage IB''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |T2 || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |N0 ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center | M0
|-
|style="font-size: 100; padding: 0 5px; background: #DCDCDC" align=center |'''Stage IIA''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |T1 || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |N1 || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |M0
|-
|style="font-size: 100; padding: 0 5px; background: #DCDCDC" align=center rowspan="2"|'''Stage IIB''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |T2 || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |N1 ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center | M0
|-
|style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |T3 || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |N0 || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |M0
|-
|style="font-size: 100; padding: 0 5px; background: #DCDCDC" align=center rowspan="2" |'''Stage IIIA''' ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |T1, T2|| style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |N2 ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |M0
|-
|style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |T3|| style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |N1, N2 ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |M0
|-
|style="font-size: 100; padding: 0 5px; background: #DCDCDC" align=center rowspan="2"|'''Stage IIIB''' ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |Any T|| style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |N3 ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |M0
|-
|style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |T4 ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center|Any N ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |M0
|-
|style="font-size: 100; padding: 0 5px; background: #DCDCDC" align=center |'''Stage IV'''|| style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |Any T ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |Any N ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=center |M1
|}


In small cell lung cancer, the tumor cells are small and round, but they can sometimes be ovoid or spindle shaped.  They have a scant [[cytoplasm]] with a high mitotic count and a hyperchromatic [[nuclei]]Nearly all small cell lung cancer are immunoreactive for [[keratin]], [[thyroid transcription factor 1]], and epithelial membrane antigen.  Neuroendocrine and neural differentiation result in the expression of molecules like dopa decarboxylase, [[calcitonin]], neuron-specific [[enolase]], [[chromogranin A]], [[CD56]] (also known as nucleosomal histone kinase 1 or neural-cell adhesion molecule), gastrin-releasing peptide, and [[insulin-like growth factor 1]]One or more markers of neuroendocrine differentiation can be found in approximately 75% of small cell lung cancer.<ref name="NCI">National Cancer Institute: PDQ® Small Cell Lung Cancer Treatment. Bethesda, MD: National Cancer Institute.  Available at: http://www.cancer.gov/cancertopics/pdq/treatment/small-cell-lung/healthprofessional.</ref>
===NCCN Staging===
The National Comprehensive Cancer Network (NCCN) staging system combines the staging scheme of the AJCC and that of the VALGAlthough the AJCC staging scheme is newer than that of the VALG, clinicians commonly use the VALG staging system because it has been commonly referred to in clinical trialsShown below is a table depicting the NCNN staging which classifies SCLC into two stages.<ref name="NCCN">[http://www.nccn.org/professionals/physician_gls/f_guidelines_nojava.asp NCCN Clinical Practice Guidelines in Oncology. Small Cell Lung Cancer, version 2.2014] </ref>


{| class="wikitable"
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
|[[Image:Lung small cell carcinoma (1) by core needle biopsy.jpg|300px|thumb| Histopathologic image of small cell carcinoma of the lung. CT-guided core needle biopsy. H & E stain.By No machine-readable author provided. KGH assumed (based on copyright claims),via Wikimedia Commons <ref>href="http://www.gnu.org/copyleft/fdl.html">GFDL<nowiki></a></nowiki> or <nowiki><a href="http://creativecommons.org/licenses/by-sa/3.0/">CC-BY-SA-3.0</a></nowiki>], <nowiki><a href="https://commons.wikimedia.org/wiki/File%3ALung_small_cell_carcinoma_(1)_by_core_needle_biopsy.jpg"></nowiki></ref>]]  
|-
|[[Image:Lung small cell cancer 01.jpeg|300px|thumb| Micrograph of a small-cell carcinoma of the lung showing cells with nuclear moulding, minimal amount of cytoplasm and stippled chromatin. FNA specimen. Field stain.By No machine-readable author provided. KGH assumed (based on copyright claims), via Wikimedia Commons <ref>href="http://www.gnu.org/copyleft/fdl.html">GFDL ="http://creativecommons.org/licenses/by-sa/3.0/">CC-BY-SA-3.0], href="https://commons.wikimedia.org/wiki/File%3ALung_small_cell_carcinoma_(1)_by_core_needle_biopsy.jpg"></ref>]]
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=center |'''Stage'''||style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=center |'''Characteristics'''
|- [[Image:Lung small cell cancer 03.jpeg|300px|thumb| Anaplastic (microcellular, oat cell) carcinoma from the lung., via Wikimedia Commons <ref>href="https://commons.wikimedia.org/wiki/File:Carcinoma_microcellulare_oatcell_carcinoma_or_anaplastic_carcinoma_(lung)H%26E_magn_200x.jpg</ref>]]
|-
|
|style="font-size: 100; padding: 0 5px; background: #DCDCDC" align=left |'''Limited SCLC''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=left|
|
* Limited SCLC includes lung cancer cases of stage I, II, or III which can be treated with [[radiation therapy]].
* This stage does not include tumor [[Lung cancer staging#T:Primary Tumor|T3]] or [[Lung cancer staging#T:Primary Tumor|T4]] with multiple lung nodules, as well as tumor or [[lymph node]]s that are too large to fit in the radiation plan.
|-
|style="font-size: 100; padding: 0 5px; background: #DCDCDC" align=left |'''Extensive SCLC''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=left |
* Extensive SCLC includes all SCLC categorized as stage IV, '''or'''
* Tumor [[Lung cancer staging#T:Primary Tumor|T3]] or [[Lung cancer staging#T:Primary Tumor|T4]] with multiple lung nodules, '''or'''
* [[Tumor]] or [[lymph node]]s that are too large to fit in the radiation plan
|}
|}



Latest revision as of 22:32, 3 September 2019

Small Cell Carcinoma of the Lung Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dildar Hussain, MBBS [2]Rim Halaby, M.D. [3]

Overview

The confirmation of the diagnosis of SCLC relies on the histopathological findings of the tumor biopsy. All patients with confirmed diagnosis of SCLC by histopathological findings should undergo a CT scan of the abdomen for staging purposes. CT scan of the abdomen helps identify metastasis to organs, such as the liver or the adrenal glands. Staging schemes for small cell lung cancer (SCLC) have been developed by the Veterans Administration Lung Study Group (VALG), the American Joint Committee on Cancer (AJCC), and the National Comprehensive Cancer Network (NCCN).

Diagnostic Study of Choice

Biopsy


Histopathologic image of small cell carcinoma of the lung. CT-guided core needle biopsy. H & E stain.By No machine-readable author provided. KGH assumed (based on copyright claims),via Wikimedia Commons [3]
Micrograph of a small-cell carcinoma of the lung showing cells with nuclear moulding, minimal amount of cytoplasm and stippled chromatin. FNA specimen. Field stain.By No machine-readable author provided. KGH assumed (based on copyright claims), via Wikimedia Commons [4]

CT

Chest CT scan, preferably with intravenous contrast administration, may be helpful in the diagnosis of small cell carcinoma. Findings on CT scan suggestive of small cell carcinoma include:[1]

Staging

The Veterans Administration Lung Study Group (VALG) staging, also known as VA staging, is an old staging system that has been previously used in most clinical trials. Shown below is a table depicting the VA staging system which classifies SCLC into two stages.[6]

Stage Characteristics
Limited SCLC
  • Limited SCLC is characterized by the strict involvement of the ipsilateral lung.
Extensive SCLC

AJCC and TNM Staging

Shown below is a table summarizing the staging of lung cancer according to the American Joint Committee on Cancer (AJCC). This staging scheme is the same for both SCLC and non small cell lung cancer.[7]

For more information about the TNM staging, click here.

Stage T N M
Occult carcinoma TX N0 M0
Stage 0 Tis N0 M0
Stage IA T1 N0 M0
Stage IB T2 N0 M0
Stage IIA T1 N1 M0
Stage IIB T2 N1 M0
T3 N0 M0
Stage IIIA T1, T2 N2 M0
T3 N1, N2 M0
Stage IIIB Any T N3 M0
T4 Any N M0
Stage IV Any T Any N M1

NCCN Staging

The National Comprehensive Cancer Network (NCCN) staging system combines the staging scheme of the AJCC and that of the VALG. Although the AJCC staging scheme is newer than that of the VALG, clinicians commonly use the VALG staging system because it has been commonly referred to in clinical trials. Shown below is a table depicting the NCNN staging which classifies SCLC into two stages.[1]

Stage Characteristics
Limited SCLC
  • Limited SCLC includes lung cancer cases of stage I, II, or III which can be treated with radiation therapy.
  • This stage does not include tumor T3 or T4 with multiple lung nodules, as well as tumor or lymph nodes that are too large to fit in the radiation plan.
Extensive SCLC
  • Extensive SCLC includes all SCLC categorized as stage IV, or
  • Tumor T3 or T4 with multiple lung nodules, or
  • Tumor or lymph nodes that are too large to fit in the radiation plan

References

  1. 1.0 1.1 1.2 NCCN Clinical Practice Guidelines in Oncology. Small Cell Lung Cancer, version 2.2014
  2. National Cancer Institute: PDQ® Small Cell Lung Cancer Treatment. Bethesda, MD: National Cancer Institute. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/small-cell-lung/healthprofessional.
  3. href="http://www.gnu.org/copyleft/fdl.html">GFDL</a> or <a href="http://creativecommons.org/licenses/by-sa/3.0/">CC-BY-SA-3.0</a>], <a href="https://commons.wikimedia.org/wiki/File%3ALung_small_cell_carcinoma_(1)_by_core_needle_biopsy.jpg">
  4. href="http://www.gnu.org/copyleft/fdl.html">GFDL ="http://creativecommons.org/licenses/by-sa/3.0/">CC-BY-SA-3.0], href="https://commons.wikimedia.org/wiki/File%3ALung_small_cell_carcinoma_(1)_by_core_needle_biopsy.jpg">
  5. href="https://commons.wikimedia.org/wiki/File:Carcinoma_microcellulare_oatcell_carcinoma_or_anaplastic_carcinoma_(lung)H%26E_magn_200x.jpg
  6. Micke P, Faldum A, Metz T, Beeh KM, Bittinger F, Hengstler JG; et al. (2002). "Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer--what limits limited disease?". Lung Cancer. 37 (3): 271–6. PMID 12234695.
  7. Shepherd FA, Crowley J, Van Houtte P, Postmus PE, Carney D, Chansky K; et al. (2007). "The International Association for the Study of Lung Cancer lung cancer staging project: proposals regarding the clinical staging of small cell lung cancer in the forthcoming (seventh) edition of the tumor, node, metastasis classification for lung cancer". J Thorac Oncol. 2 (12): 1067–77. doi:10.1097/JTO.0b013e31815bdc0d. PMID 18090577.


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