Difference between revisions of "Small cell carcinoma of the lung"

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{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Image      = Lung_small_cell_carcinoma_%281%29_by_core_needle_biopsy.jpg
| Width      =
| Caption    = Lung small cell carcinoma. [[H&E stain]].
| Synonyms  =
| Micro      = stippled chromatin, high [[NC ratio]] with scant basophilic cytoplasm, typically small cells (~2x [[RBC]] diameter), +/-nuclear moulding, nuclei with smudgy appearance ([[Azzopardi phenomenon]]), necrosis, [[mitoses]]
| Subtypes  = large cell neuroendocrine carcinoma (LCNEC)
| LMDDx      = poorly differentiated [[adenocarcinoma of the lung]], [[atypical carcinoid]], [[lung carcinoid]], metastatic [[small cell carcinoma]], [[lymphoma]], other [[small round blue cell tumours]]
| Stains    =
| IHC        = chromogranin +ve, synaptophysin +ve, CD56 +ve, NSE +ve, TTF-1 +ve, Ki-67 (>50%)
| EM        =
| Molecular  =
| IF        =
| Gross      =
| Grossing  =
| Staging    = [[lung cancer staging]]
| Site      = [[lung]] - see ''[[lung tumours]]''
| Assdx      =
| Syndromes  =
| Clinicalhx = [[smoking]] - usually a long history, heavy
| Signs      = +/-hemoptysis
| Symptoms  =
| Prevalence = not common
| Bloodwork  =
| Rads      = lung mass, usu. central location
| Endoscopy  =
| Prognosis  = poor
| Other      =
| ClinDDx    = other lung tumours ([[squamous cell carcinoma of the lung]]), metastatic tumours
| Tx        = medical (chemotherapy)
}}
'''Small cell carcinoma of the lung''', also '''small cell lung carcinoma''' (abbreviated '''SCLC''')<ref name=pmid20943645/> is an aggressive [[malignant]] [[Lung tumours|tumour of the lung]]. It is strongly associated with [[smoking]].
'''Small cell carcinoma of the lung''', also '''small cell lung carcinoma''' (abbreviated '''SCLC''')<ref name=pmid20943645/> is an aggressive [[malignant]] [[Lung tumours|tumour of the lung]]. It is strongly associated with [[smoking]].
Small cell carcinoma in general is dealt with in the ''[[small cell carcinoma]]'' article.


==General==
==General==
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*[[typical carcinoid|Carcinoid]].
*[[typical carcinoid|Carcinoid]].
*[[atypical carcinoid|Atypical carcinoid]].
*[[atypical carcinoid|Atypical carcinoid]].
*Small cell carinoma/large cell neuroendocrine carcinoma.
*Small cell carinoma/[[large cell neuroendocrine carcinoma]] (LCNEC).


Precursor lesion - uncommonly seen:
Precursor lesion - uncommonly seen:
*Pulmonary neuroendocrine cell hyperplasia.<ref name=pmid20943645>{{Cite journal  | last1 = Travis | first1 = WD. | title = Advances in neuroendocrine lung tumors. | journal = Ann Oncol | volume = 21 Suppl 7 | issue =  | pages = vii65-71 | month = Oct | year = 2010 | doi = 10.1093/annonc/mdq380 | PMID = 20943645 }}</ref>
*Pulmonary neuroendocrine cell hyperplasia.<ref name=pmid20943645>{{Cite journal  | last1 = Travis | first1 = WD. | title = Advances in neuroendocrine lung tumors. | journal = Ann Oncol | volume = 21 Suppl 7 | issue =  | pages = vii65-71 | month = Oct | year = 2010 | doi = 10.1093/annonc/mdq380 | PMID = 20943645 }}</ref>
Clinical:
*+/-Hemoptysis.


==Gross==
==Gross==
*Central location (close to large airways) - typical.
*Central location (close to large airways) - typical.
*[[Necrosis]].
*[[Necrosis]].
===Images===
<gallery>
Image:Small cell carcinoma (3931938372).jpg| Small cell carcinoma of the lung - centre of image. (WC/Rosen)
</gallery>


==Microscopic==
==Microscopic==
Line 25: Line 67:
*Typically small cells ~2x RBC diameter.
*Typically small cells ~2x RBC diameter.
*+/-Nuclear moulding.
*+/-Nuclear moulding.
*Necrosis.
*Nuclei with a smudgy appearance ([[Azzopardi phenomenon]]).
*[[Necrosis]].
*Mitoses.
*Mitoses.


Notes:
Notes:
*There should be no nucleolus.
*There should be no [[nucleolus]].


DDx:
DDx:
*Poorly differentiated [[adenocarcinoma of the lung]].
*Metastatic [[small cell carcinoma]].
*Metastatic [[small cell carcinoma]].
*[[Lymphoma]].
*[[Lymphoma]].
*[[Atypical carcinoid]].
*[[Atypical carcinoid]].
*[[Squamous cell carcinoma of the lung|Basaloid squamous cell carcinoma of the lung]].<ref>{{Cite journal  | last1 = Maleki | first1 = Z. | title = Diagnostic issues with cytopathologic interpretation of lung neoplasms displaying high-grade basaloid or neuroendocrine morphology. | journal = Diagn Cytopathol | volume = 39 | issue = 3 | pages = 159-67 | month = Mar | year = 2011 | doi = 10.1002/dc.21351 | PMID = 21319315 }}</ref>
*[[Non-small cell carcinoma of the lung]].
*Other [[small round blue cell tumours]].
*Other [[small round blue cell tumours]].
===Subtypes===
*Large cell neuroendocrine carcinoma (LCNEC).
*Large cell neuroendocrine carcinoma (LCNEC).
===Grading===
As per CAP protocol (version 3.4.0.0):<ref name=cap_protocol>CAP Lung protocol. Version: 3.4.0.0. URL: [http://www.cap.org/ShowProperty?nodePath=/UCMCon/Contribution%20Folders/WebContent/pdf/cp-lung-16protocol-3400.pdf http://www.cap.org/ShowProperty?nodePath=/UCMCon/Contribution%20Folders/WebContent/pdf/cp-lung-16protocol-3400.pdf]. Accessed on: March 23, 2016.</ref>
*G4 = undifferentiated - used for small cell carcinoma and large cell carcinoma.


===Images===
===Images===
Line 43: Line 95:
Image:Lung_small_cell_carcinoma_%281%29_by_core_needle_biopsy.jpg | SCLC - high mag. (WC)
Image:Lung_small_cell_carcinoma_%281%29_by_core_needle_biopsy.jpg | SCLC - high mag. (WC)
</gallery>
</gallery>
==IHC==
==IHC==
*Synaptophysin +ve.
*Synaptophysin +ve.
**May be very weak.
**May be very weak.
*TTF-1 +ve (15 of 16 cases).<ref name=pmid16138374>{{Cite journal  | last1 = Wu | first1 = M. | last2 = Szporn | first2 = AH. | last3 = Zhang | first3 = D. | last4 = Wasserman | first4 = P. | last5 = Gan | first5 = L. | last6 = Miller | first6 = L. | last7 = Burstein | first7 = DE. | title = Cytology applications of p63 and TTF-1 immunostaining in differential diagnosis of lung cancers. | journal = Diagn Cytopathol | volume = 33 | issue = 4 | pages = 223-7 | month = Oct | year = 2005 | doi = 10.1002/dc.20337 | PMID = 16138374 }}</ref>
*[[TTF-1]] +ve  
**Misch ''et al.'' reported: 82.8% positive (183 +ve of 221 cases).<ref name=pmid25889870>{{Cite journal  | last1 = Misch | first1 = D. | last2 = Blum | first2 = T. | last3 = Boch | first3 = C. | last4 = Weiss | first4 = T. | last5 = Crolow | first5 = C. | last6 = Griff | first6 = S. | last7 = Mairinger | first7 = T. | last8 = Bauer | first8 = TT. | last9 = Kollmeier | first9 = J. | title = Value of thyroid transcription factor (TTF)-1 for diagnosis and prognosis of patients with locally advanced or metastatic small cell lung cancer. | journal = Diagn Pathol | volume = 10 | issue =  | pages = 21 | month = Apr | year = 2015 | doi = 10.1186/s13000-015-0250-z | PMID = 25889870 }}</ref>
**Wu ''et al.'' reported: 15 positive of 16 cases.<ref name=pmid16138374>{{Cite journal  | last1 = Wu | first1 = M. | last2 = Szporn | first2 = AH. | last3 = Zhang | first3 = D. | last4 = Wasserman | first4 = P. | last5 = Gan | first5 = L. | last6 = Miller | first6 = L. | last7 = Burstein | first7 = DE. | title = Cytology applications of p63 and TTF-1 immunostaining in differential diagnosis of lung cancers. | journal = Diagn Cytopathol | volume = 33 | issue = 4 | pages = 223-7 | month = Oct | year = 2005 | doi = 10.1002/dc.20337 | PMID = 16138374 }}</ref>
*CK7 -ve.<ref name=pmid10874668>{{Cite journal  | last1 = Gyure | first1 = KA. | last2 = Morrison | first2 = AL. | title = Cytokeratin 7 and 20 expression in choroid plexus tumors: utility in differentiating these neoplasms from metastatic carcinomas. | journal = Mod Pathol | volume = 13 | issue = 6 | pages = 638-43 | month = Jun | year = 2000 | doi = 10.1038/modpathol.3880111 | PMID = 10874668 }}</ref>
*[[CK20]] -ve.<ref name=pmid10874668/>
*Ki-67 ~80% (>50% proposed as criteria for ''large cell neuroendocrine carcinoma''<ref name=pmid25318848>{{Cite journal  | last1 = Liu | first1 = SZ. | last2 = Staats | first2 = PN. | last3 = Goicochea | first3 = L. | last4 = Alexiev | first4 = BA. | last5 = Shah | first5 = N. | last6 = Dixon | first6 = R. | last7 = Burke | first7 = AP. | title = Automated quantification of Ki-67 proliferative index of excised neuroendocrine tumors of the lung. | journal = Diagn Pathol | volume = 9 | issue =  | pages = 174 | month =  | year = 2014 | doi = 10.1186/s13000-014-0174-z | PMID = 25318848 }}</ref>).
**Useful for separating from ''atypical carcinoid'' and ''typical carcinoid''.
 
Others:
*[[p63]] +ve in ~75-80% of the cases.<ref name=pmid15551738>{{Cite journal  | last1 = Au | first1 = NH. | last2 = Gown | first2 = AM. | last3 = Cheang | first3 = M. | last4 = Huntsman | first4 = D. | last5 = Yorida | first5 = E. | last6 = Elliott | first6 = WM. | last7 = Flint | first7 = J. | last8 = English | first8 = J. | last9 = Gilks | first9 = CB. | title = P63 expression in lung carcinoma: a tissue microarray study of 408 cases. | journal = Appl Immunohistochem Mol Morphol | volume = 12 | issue = 3 | pages = 240-7 | month = Sep | year = 2004 | doi =  | PMID = 15551738 }}</ref>


==Sign out==
==Sign out==
===Biopsy===
<pre>
Lung, Left Lower Lobe, Core Biopsy:
- SMALL CELL CARCINOMA.
</pre>
====Possible LCNEC====
<pre>
Lung, Left Lower Lobe, Core Biopsy:
- NON–SMALL CELL CARCINOMA WITH NEUROENDOCRINE (NE) MORPHOLOGY AND POSITIVE NE MARKERS, POSSIBLE LARGE CELL NEUROENDOCRINE CARCINOMA (LCNEC).
</pre>
Note:
*The above is the wording recommended by 2011 ATS/ERS/IASLC panel.<ref>{{cite journal |authors=Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger K, Yatabe Y, Ishikawa Y, Wistuba I, Flieder DB, Franklin W, Gazdar A, Hasleton PS, Henderson DW, Kerr KM, Petersen I, Roggli V, Thunnissen E, Tsao M |title=Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification |journal=Arch Pathol Lab Med |volume=137 |issue=5 |pages=668–84 |date=May 2013 |pmid=22970842 |pmc=4509741 |doi=10.5858/arpa.2012-0263-RA |url=}}</ref>
====Block letters====
<pre>
<pre>
LOWER LOBE OF LUNG, LEFT, CORE BIOPSY:
LOWER LOBE OF LUNG, LEFT, CORE BIOPSY:
- SMALL CELL CARCINOMA.
- SMALL CELL CARCINOMA.
</pre>
</pre>
===Resection===
<pre>
Left Lower Lobe, Lobectomy:
    - LARGE CELL NEUROENDOCRINE CARCINOMA.
    -- Margins clear.   
    - Two lymph nodes NEGATIVE for malignancy (0/2).
    - Please see synoptic report.
Comment:
The tumour stains as follows:
POSITIVE: CD56, synaptophysin, p63 (scattered).
NEGATIVE: chromogranin A, CK5/6, TTF-1, napsin A.
</pre>
====Micro====
The sections show large cells epithelioid cells (~3-4x the size of a lymphocyte) with salt and pepper chromatin, scant basophilic cytoplasm, and focally streaming.  Mitotic activity is brisk and multifocal zonal necrosis is present.


==See also==
==See also==

Latest revision as of 21:53, 10 December 2021

Small cell carcinoma of the lung
Diagnosis in short

Lung small cell carcinoma. H&E stain.
LM stippled chromatin, high NC ratio with scant basophilic cytoplasm, typically small cells (~2x RBC diameter), +/-nuclear moulding, nuclei with smudgy appearance (Azzopardi phenomenon), necrosis, mitoses
Subtypes large cell neuroendocrine carcinoma (LCNEC)
LM DDx poorly differentiated adenocarcinoma of the lung, atypical carcinoid, lung carcinoid, metastatic small cell carcinoma, lymphoma, other small round blue cell tumours
IHC chromogranin +ve, synaptophysin +ve, CD56 +ve, NSE +ve, TTF-1 +ve, Ki-67 (>50%)
Staging lung cancer staging
Site lung - see lung tumours
Clinical history smoking - usually a long history, heavy
Signs +/-hemoptysis
Prevalence not common
Radiology lung mass, usu. central location
Prognosis poor
Clin. DDx other lung tumours (squamous cell carcinoma of the lung), metastatic tumours
Treatment medical (chemotherapy)

Small cell carcinoma of the lung, also small cell lung carcinoma (abbreviated SCLC)[1] is an aggressive malignant tumour of the lung. It is strongly associated with smoking.

Small cell carcinoma in general is dealt with in the small cell carcinoma article.

General

  • Strong association with smoking.
  • Typically treated with chemotherapy.
  • Poor prognosis.

On a spectrum of lesions (benign to malignant):[1]

Precursor lesion - uncommonly seen:

  • Pulmonary neuroendocrine cell hyperplasia.[1]

Clinical:

  • +/-Hemoptysis.

Gross

  • Central location (close to large airways) - typical.
  • Necrosis.

Images

  • Small cell carcinoma of the lung - centre of image. (WC/Rosen)

Microscopic

Features:

  • Stippled chromatin.
  • High NC ratio, scant basophilic cytoplasm.
  • Typically small cells ~2x RBC diameter.
  • +/-Nuclear moulding.
  • Nuclei with a smudgy appearance (Azzopardi phenomenon).
  • Necrosis.
  • Mitoses.

Notes:

DDx:

Subtypes

  • Large cell neuroendocrine carcinoma (LCNEC).

Grading

As per CAP protocol (version 3.4.0.0):[3]

  • G4 = undifferentiated - used for small cell carcinoma and large cell carcinoma.

Images

  • SCLC - low mag. (WC)

  • SCLC - high mag. (WC)

IHC

  • Synaptophysin +ve.
    • May be very weak.
  • TTF-1 +ve
    • Misch et al. reported: 82.8% positive (183 +ve of 221 cases).[4]
    • Wu et al. reported: 15 positive of 16 cases.[5]
  • CK7 -ve.[6]
  • CK20 -ve.[6]
  • Ki-67 ~80% (>50% proposed as criteria for large cell neuroendocrine carcinoma[7]).
    • Useful for separating from atypical carcinoid and typical carcinoid.

Others:

  • p63 +ve in ~75-80% of the cases.[8]

Sign out

Biopsy

Lung, Left Lower Lobe, Core Biopsy:
- SMALL CELL CARCINOMA.

Possible LCNEC

Lung, Left Lower Lobe, Core Biopsy:
- NON–SMALL CELL CARCINOMA WITH NEUROENDOCRINE (NE) MORPHOLOGY AND POSITIVE NE MARKERS, POSSIBLE LARGE CELL NEUROENDOCRINE CARCINOMA (LCNEC).

Note:

  • The above is the wording recommended by 2011 ATS/ERS/IASLC panel.[9]

Block letters

LOWER LOBE OF LUNG, LEFT, CORE BIOPSY:
- SMALL CELL CARCINOMA.

Resection

Left Lower Lobe, Lobectomy:
     - LARGE CELL NEUROENDOCRINE CARCINOMA.
     -- Margins clear.     
     - Two lymph nodes NEGATIVE for malignancy (0/2).
     - Please see synoptic report.

Comment: 
The tumour stains as follows:
POSITIVE: CD56, synaptophysin, p63 (scattered).
NEGATIVE: chromogranin A, CK5/6, TTF-1, napsin A.

Micro

The sections show large cells epithelioid cells (~3-4x the size of a lymphocyte) with salt and pepper chromatin, scant basophilic cytoplasm, and focally streaming. Mitotic activity is brisk and multifocal zonal necrosis is present.

See also

References

  1. ↑ 1.0 1.1 1.2 Travis, WD. (Oct 2010). "Advances in neuroendocrine lung tumors.". Ann Oncol 21 Suppl 7: vii65-71. doi:10.1093/annonc/mdq380. PMID 20943645.
  2. ↑ Maleki, Z. (Mar 2011). "Diagnostic issues with cytopathologic interpretation of lung neoplasms displaying high-grade basaloid or neuroendocrine morphology.". Diagn Cytopathol 39 (3): 159-67. doi:10.1002/dc.21351. PMID 21319315.
  3. ↑ CAP Lung protocol. Version: 3.4.0.0. URL: http://www.cap.org/ShowProperty?nodePath=/UCMCon/Contribution%20Folders/WebContent/pdf/cp-lung-16protocol-3400.pdf. Accessed on: March 23, 2016.
  4. ↑ Misch, D.; Blum, T.; Boch, C.; Weiss, T.; Crolow, C.; Griff, S.; Mairinger, T.; Bauer, TT. et al. (Apr 2015). "Value of thyroid transcription factor (TTF)-1 for diagnosis and prognosis of patients with locally advanced or metastatic small cell lung cancer.". Diagn Pathol 10: 21. doi:10.1186/s13000-015-0250-z. PMID 25889870.
  5. ↑ Wu, M.; Szporn, AH.; Zhang, D.; Wasserman, P.; Gan, L.; Miller, L.; Burstein, DE. (Oct 2005). "Cytology applications of p63 and TTF-1 immunostaining in differential diagnosis of lung cancers.". Diagn Cytopathol 33 (4): 223-7. doi:10.1002/dc.20337. PMID 16138374.
  6. ↑ 6.0 6.1 Gyure, KA.; Morrison, AL. (Jun 2000). "Cytokeratin 7 and 20 expression in choroid plexus tumors: utility in differentiating these neoplasms from metastatic carcinomas.". Mod Pathol 13 (6): 638-43. doi:10.1038/modpathol.3880111. PMID 10874668.
  7. ↑ Liu, SZ.; Staats, PN.; Goicochea, L.; Alexiev, BA.; Shah, N.; Dixon, R.; Burke, AP. (2014). "Automated quantification of Ki-67 proliferative index of excised neuroendocrine tumors of the lung.". Diagn Pathol 9: 174. doi:10.1186/s13000-014-0174-z. PMID 25318848.
  8. ↑ Au, NH.; Gown, AM.; Cheang, M.; Huntsman, D.; Yorida, E.; Elliott, WM.; Flint, J.; English, J. et al. (Sep 2004). "P63 expression in lung carcinoma: a tissue microarray study of 408 cases.". Appl Immunohistochem Mol Morphol 12 (3): 240-7. PMID 15551738.
  9. ↑ Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger K, Yatabe Y, Ishikawa Y, Wistuba I, Flieder DB, Franklin W, Gazdar A, Hasleton PS, Henderson DW, Kerr KM, Petersen I, Roggli V, Thunnissen E, Tsao M (May 2013). "Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification". Arch Pathol Lab Med 137 (5): 668–84. doi:10.5858/arpa.2012-0263-RA. PMC 4509741. PMID 22970842. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509741/.
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