Lung tumours

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Lung tumours comes to pathology to get diagnosed. This article basically deals with core biopsies. 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.

Management of primary lung cancer

Management is currently determined by categorization into:

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

Microscopic features overview

Adenocarcinoma

  • Glands or cytoplasm with mucin.

Squamous cell carcinoma

  • Distinct cell borders with intercellular bridges.
  • Eosinophilic cytoplasm.

Small cell carcinoma

  • Very cellular.
  • Large NC ratio - very small amount of cytoplasm.
  • Cells fragile - they tend to look "smudged" (Azzopardi phenomenon).

IHC

There is a great review paper by Jagirdar.[4]

Small cell carcinoma

  • CD56 +ve - sensitive.[5]
  • CK7 -ve, CK20 -ve.

Note:

  • CD56 - cytoplasmic.[6]

Squamous cell carcinoma

  • CK7 -ve, CK20 -ve.
  • HMWK +ve.
  • Usually TTF-1 -ve.[7]

Primary vs. secondary

  • TTF-1 is considered useful.[4]
    • 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:

Primary adenocarcinoma

General

Treatment:

  • Lung adenocarcinoma may be treated with EGFR inhibitors (e.g. gefitinib (Iressa), erlotinib (Tarceva)).[9]

Patients that receive EGFR inhibitors classically are:[10]

  • Non-smokers.
  • Female.
  • Asian. (???)

Microscopic

Features:

  • Nuclear atypia.
  • Eccentrically placed nuclei.
  • Abundant cytoplasm - classically with mucin vacuoles.

Negatives:

  • Lack of intercellular bridges.

Patterns:[11]

  • Lepidic.
  • Acinar.
  • Papillary.
  • Solid.

Classification

Extent:[11]

  • Adenocarcinoma in situ (AIS).
  • Minimally invasive adenocarcinoma (MIA).
    • Have lepidic growth (AIS), upto 5 mm of invasion.
    • Usually nonmucinous.

Subtypes of invasive adenocarcinoma:

  • Micropapillary
  • Mucinous.
  • Colloid.
  • Fetal.
  • Enteric.

Neuroendocrine tumours

Overview

Classification

The grouping can be divided into four types:[14]

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

Cytologic features

Cytologic features useful for differentiation:

  • Small cell carcinoma: necrosis, scant cytoplasm, mitoses.
  • Typical carcinoid: often more cytoplasm, no necrosis, low mitotic rate (MIB-1: scant staining).
  • Atypical carcinoid: higher mitotic rate/MIB-1 than typical carcinoid,[15] no necrosis.

Notes:[14]

  • 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.

Mesothelioma

Locations

  • Lung.
  • Primary peritoneal.

Epidemiology

  • Associated with asbestos exposure.

Microscopy

  • Ferruginous body (AKA asbestos body).[16]
    • Made of asbestos fiber.
    • Looks like a (twirling) baton.

Images:

IHC

  • Several panel exists - no agreed upon best panel.[17]
    • Usually two carcinoma markers + two mesothelial markers.

Panel:[17]

  • Mesothelial markers:
    • Calretin.
    • WT-1.
    • D2-40.
    • CK5/6.
  • Carcinoma markers:
    • CEA.
    • TTF-1.

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 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.
  5. ↑ 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.
  6. ↑ URL: http://jcp.bmjjournals.com/content/58/9/978.full. Accessed: 11 February 2010.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ Sun Y, Ren Y, Fang Z, et al. (October 2010). "Lung adenocarcinoma from East Asian never-smokers is a disease largely defined by targetable oncogenic mutant kinases". J. Clin. Oncol. 28 (30): 4616–20. doi:10.1200/JCO.2010.29.6038. PMID 20855837.
  10. ↑ Job B, Bernheim A, Beau-Faller M, et al. (2010). "Genomic Aberrations in Lung Adenocarcinoma in Never Smokers". PLoS One 5 (12): e15145. doi:10.1371/journal.pone.0015145. PMC 2997777. PMID 21151896. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997777/.
  11. ↑ 11.0 11.1 Travis WD, Brambilla E, Noguchi M, et al. (February 2011). "International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma". J Thorac Oncol 6 (2): 244–85. doi:10.1097/JTO.0b013e318206a221. PMID 21252716.
  12. ↑ URL: http://emedicine.medscape.com/article/426400-overview. Accessed on: 20 January 2010.
  13. ↑ 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.
  14. ↑ 14.0 14.1 URL: http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_is_lung_carcinoid_tumor_56.asp. Accessed on: 16 February 2011.
  15. ↑ WG. February 2010.
  16. ↑ http://medical-dictionary.thefreedictionary.com/asbestos+body
  17. ↑ 17.0 17.1 Marchevsky AM (March 2008). "Application of immunohistochemistry to the diagnosis of malignant mesothelioma". Arch. Pathol. Lab. Med. 132 (3): 397-401. PMID 18318582. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=397.
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