Lung tumours

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Lung tumours comes to pathology to get diagnosed.

A lung tumour (small cell carcinoma of the lung) - centre of image. (WC/Rosen)

This article deals with the surgical pathology (core biopsies, lung resections). Pulmonary cytopathology is dealt with in the pulmonary cytopathology article.

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

Lung tumours overview

Schematic overview of lung cancer (clinical)

 
 
 
 
 
 
 
 
Lung cancer
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Primary
 
 
 
 
 
 
 
Metastatic
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NSCLC
 
 
 
SCLC
 
 
 
 
 
 
 
 
 
 
 
  • NSCLC = non-small cell lung cancer.
  • SCLS = small cell lung cancer.

Basic pathologic approach to lung cancer

 
 
 
 
 
 
Lung cancer
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adenocarcinoma
 
Squamous
cell carcinoma
 
SCLC
 
LCLC
  • LCLC = large cell lung cancer.
  • SCLS = small cell lung cancer.

Notes:

  • Most lung cancer fits into one of the above categories.
  • All types may be metastatic. Pathologists usually don't have to sort this out, as the clinican often knows whether a given lesion is metastatic (when correlated with radiology).
  • Lung cancers may have a mixed morphology, e.g. SCLS may have squamous component.[1]
  • Categorization as non-small cell lung cancer (NSCLC) should be avoided, as treatment is now somewhat dependent on subcategorization.[2]

Major types (primary)

Mnemonic ASSL:

Epidemiology

  • Adenocarcinoma is the most common (primary lung cancer).[3]
  • Adenocarcinoma is the non-smoker tumour - SCLC and squamous are more strongly associated with smoking.

Distribution

  • Distribution - think about the location of letters in mnemonic ASSL.
    • Adenocarcinoma is usually periperal, i.e. smaller airways.
    • Squamous cell carcinoma and small cell carcinoma are typically central.

Margins in lung

Margin in pneumonectomy specimens include:

  • Vessels (artery, vein).
  • Airway (bronchus).
  • Soft tissue (lymphatics, fibrous tissue and lymph nodes).[4]

Notes:

  • The traditional teaching is there are only hollow structure margins (artery, vein, airway) - yet the bronchial margin has been divided into mucosal and extramucosal.[5]
  • Peribronchovascular soft tissue involvement is a poor prognosticator but not an independent predictor if considered within the TNM staging.[4]

Management of primary lung cancer

Management in the past was determined by categorization into:

  • Small cell cancer.
  • Non-small cell cancer (includes adenocarcinoma, squamous cell carcinoma, large cell carcinoma).

Microscopic features overview

Adenocarcinoma

Main article: Adenocarcinoma of the lung
  • Glands or cytoplasm with mucin.

Squamous cell carcinoma

Main article: Squamous cell carcinoma of the lung
  • Distinct cell borders with intercellular bridges.
  • Eosinophilic cytoplasm.

Small cell carcinoma

Main article: Small cell carcinoma of the lung

IHC

There is a great review paper by Jagirdar.[6]

Small cell carcinoma

Note:

  • CD56 - cytoplasmic.[8]

Squamous cell carcinoma

  • CK7 -ve, CK20 -ve.
  • HMWK +ve.
  • Usually TTF-1 -ve.[9]
  • p40 +ve.

Primary vs. secondary

  • TTF-1 is considered useful.[6]
    • 75% +ve adenocarcinoma
    • 11% +ve SSC
    • 50% +ve large cell carcinoma
    • 0% +ve mesothelioma
    • significant rates of +ve in some metastatic tumours -- see article by Jagirdar.

Note:

Neuroendocrine tumours

Main article: Neuroendocrine tumours

Overview

  • This is a group of tumours that has benign (e.g. carcinoid tumour of the lung) to malignant (e.g. small cell lung carcinoma) behaviour.[11]
  • They are thought to arise from pulmonary neuroendocrine cells.[12]

Classification

The grouping can be divided into four types:[13]

  • Small cell carcinoma.
  • Large cell neuroendocrine carcinoma.
  • Typical carcinoid.
  • Atypical carcinoid.

Notes:

Cytologic features

Cytologic features useful for differentiation:

  • Small cell carcinoma: necrosis, scant cytoplasm, mitoses.
  • Typical carcinoid: often more cytoplasm, no necrosis, low mitotic rate (MIB1: scant staining).
  • Atypical carcinoid: higher mitotic rate/MIB1 than typical carcinoid,[14] no necrosis.

Notes:[13]

  • Large cell and small cell tumours behave in a similar fashion; large cell can be considered a morphological variant of small cell.
  • 9/10 of carcinoids are typical and usually have a good prognosis, i.e. do not metastasize.
    • Central location (vis-a-vis peripheral location) tends favours typical carcinoid over atypical carcinoid.

Malignant tumours

Adenocarcinoma of the lung

  • AKA lung adenocarcinoma.
Main article: Adenocarcinoma of the lung

Bronchioloalveolar carcinoma

Abbreviated BAC.

The term is no longer used in the new classification;[15] it is now "adenocarcinoma in situ" - see lung adenocarcinoma.

Squamous cell carcinoma of the lung

Main article: Squamous cell carcinoma of the lung

Small cell carcinoma of the lung

  • AKA small cell lung carcinoma, abbreviated SCLC.[16]
Main article: Small cell carcinoma of the lung

Malignant mesothelioma

Should not be confused with benign multicystic mesothelioma and benign papillary mesothelioma.
Main article: Malignant mesothelioma

Poorly differentiated carcinoma

Sign out

Lung, Left Lower Lobe, Core Biopsy: 
- POORLY DIFFERENTIATED CARCINOMA, see comment. 

COMMENT: 
The tumour stains as follows: 
POSITIVE: EMA, AE1/AE3. 
NEGATIVE: TTF-1, chromogranin A, synaptophysin, CD56, CD45.

The morphology would be compatible with small cell carcinoma or basaloid 
squamous cell carcinoma.  

The neuroendocrine markers (chromogranin A, synaptophysin, CD56) and the squamoid 
markers available (p63, CK5/6) are negative; thus, the tumour is not further classified.

Lung metastasis

  • AKA pulmonary metastasis.
Main article: Lung metastasis

Malignant potential

Atypical alveolar hyperplasia

  • Abbreviated AAH.
  • AKA atypical adenomatous hyperplasia of the lung.[17]
Main article: Atypical adenomatous hyperplasia of the lung

Atypical carcinoid lung tumour

  • AKA atypical carcinoid tumour of the lung.

General

  • Approximately 20% of lung carcinoids.[18]

Microscopic

Features:[19]

  • Nests of cells.
    • Stippled chromatin.
    • Mild-to-moderate amount of cytoplasm.
  • No necrosis/focal necrosis.
  • Moderate mitotic rate (2-10/HPF - definition suffers from HPFitis).

DDx:

IHC

  • Ki-67 ~17% (range 10-26%).[20]

Note:

  • Typical carcinoid is considerably lower ~2% (range 0-7%) and large cell neuroendocrine considerable higher ~81% (range 63-92%).[20]

Solitary fibrous tumour of the pleura

Main article: Solitary fibrous tumour of the pleura

Benign tumours

Pulmonary carcinoid tumourlet

  • AKA carcinoid tumourlet.
Main article: Pulmonary carcinoid tumourlet

Typical carcinoid lung tumour

  • AKA carcinoid tumour of the lung.
  • AKA lung carcinoid.
Main article: Typical carcinoid lung tumour

Clear cell sugar tumour of the lung

  • AKA clear cell sugar tumour.
    • Abbreviated CCST.

General

Microscopic

Features:[21]

  • Sheets or trabeculae.
  • Irregular epithelioid cells with:
    • Focally clear cytoplasm.

Images:

IHC

  • HMB-45 +ve (nuclear & cytoplasmic).

See also

References

  1. ↑ Righi L, Volante M, Rapa I, Scagliotti GV, Papotti M (August 2007). "Neuro-endocrine tumours of the lung. A review of relevant pathological and molecular data". Virchows Arch. 451 Suppl 1: S51–9. doi:10.1007/s00428-007-0445-0. PMID 17684766.
  2. ↑ URL: http://www.nature.com/modpathol/journal/v21/n2s/full/3801018a.html. Accessed on: 8 September 2010.
  3. ↑ Lutschg JH (January 2009). "Lung cancer". N. Engl. J. Med. 360 (1): 87-8; author reply 88. doi:10.1056/NEJMc082208. PMID 19118313.
  4. ↑ 4.0 4.1 Sakai, Y.; Ohbayashi, C.; Kanomata, N.; Kajimoto, K.; Sakuma, T.; Maniwa, Y.; Nishio, W.; Tauchi, S. et al. (Jul 2011). "Significance of microscopic invasion into hilar peribronchovascular soft tissue in resection specimens of primary non-small cell lung cancer.". Lung Cancer 73 (1): 89-95. doi:10.1016/j.lungcan.2010.11.002. PMID 21129810.
  5. ↑ Kaiser, LR.; Fleshner, P.; Keller, S.; Martini, N. (Feb 1989). "Significance of extramucosal residual tumor at the bronchial resection margin.". Ann Thorac Surg 47 (2): 265-9. PMID 2537610.
  6. ↑ 6.0 6.1 Jagirdar J (March 2008). "Application of immunohistochemistry to the diagnosis of primary and metastatic carcinoma to the lung". Arch. Pathol. Lab. Med. 132 (3): 384-96. PMID 18318581. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=384.
  7. ↑ Hiroshima K, Iyoda A, Shida T, et al (October 2006). "Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis". Mod. Pathol. 19 (10): 1358-68. doi:10.1038/modpathol.3800659. PMID 16862075.
  8. ↑ URL: http://jcp.bmjjournals.com/content/58/9/978.full. Accessed: 11 February 2010.
  9. ↑ Al-Zahrani IH (July 2008). "The value of immunohistochemical expression of TTF-1, CK7 and CK20 in the diagnosis of primary and secondary lung carcinomas". Saudi Med J 29 (7): 957-61. PMID 18626520.
  10. ↑ Compérat E, Zhang F, Perrotin C, et al. (October 2005). "Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin". Mod. Pathol. 18 (10): 1371–6. doi:10.1038/modpathol.3800422. PMID 15861215. http://www.nature.com/modpathol/journal/v18/n10/full/3800422a.html.
  11. ↑ URL: http://emedicine.medscape.com/article/426400-overview. Accessed on: 20 January 2010.
  12. ↑ Chong S, Lee KS, Chung MJ, Han J, Kwon OJ, Kim TS (2006). "Neuroendocrine tumors of the lung: clinical, pathologic, and imaging findings". Radiographics 26 (1): 41–57; discussion 57–8. doi:10.1148/rg.261055057. PMID 16418242.
  13. ↑ 13.0 13.1 URL: http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_is_lung_carcinoid_tumor_56.asp. Accessed on: 16 February 2011.
  14. ↑ Geddie, W. February 2010.
  15. ↑ Travis, WD.; Brambilla, E.; Noguchi, M.; Nicholson, AG.; Geisinger, K.; Yatabe, Y.; Powell, CA.; Beer, D. et al. (Sep 2011). "International association for the study of lung cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary.". Proc Am Thorac Soc 8 (5): 381-5. doi:10.1513/pats.201107-042ST. PMID 21926387.
  16. ↑ Travis, WD. (Oct 2010). "Advances in neuroendocrine lung tumors.". Ann Oncol 21 Suppl 7: vii65-71. doi:10.1093/annonc/mdq380. PMID 20943645.
  17. ↑ Mori, M.; Rao, SK.; Popper, HH.; Cagle, PT.; Fraire, AE. (Feb 2001). "Atypical adenomatous hyperplasia of the lung: a probable forerunner in the development of adenocarcinoma of the lung.". Mod Pathol 14 (2): 72-84. doi:10.1038/modpathol.3880259. PMID 11235908.
  18. ↑ Naalsund, A.; Rostad, H.; Strøm, EH.; Lund, MB.; Strand, TE. (Apr 2011). "Carcinoid lung tumors--incidence, treatment and outcomes: a population-based study.". Eur J Cardiothorac Surg 39 (4): 565-9. doi:10.1016/j.ejcts.2010.08.036. PMID 20888248.
  19. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 115. ISBN 978-0781765275.
  20. ↑ 20.0 20.1 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.
  21. ↑ 21.0 21.1 21.2 Kim, WJ.; Kim, SR.; Choe, YH.; Lee, KY.; Park, SJ.; Lee, HB.; Chung, MJ.; Jin, GY. et al. (Dec 2008). "Clear cell "sugar" tumor of the lung: a well-enhanced mass with an early washout pattern on dynamic contrast-enhanced computed tomography.". J Korean Med Sci 23 (6): 1121-4. doi:10.3346/jkms.2008.23.6.1121. PMC 2610653. PMID 19119463. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2610653/.
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