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

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:

Neuroendocrine tumours

Overview

Classification

The grouping can be divided into four types:[11]

  • 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,[12] no necrosis.

Notes:[11]

  • 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.

Specific types

Lung adenocarcinoma

General

Treatment:

  • Lung adenocarcinoma may be treated with EGFR inhibitors (e.g. gefitinib (Iressa), erlotinib (Tarceva)).[13]

Patients that receive EGFR inhibitors classically are:[14]

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

Microscopic

Features:

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

Negatives:

  • Lack of intercellular bridges.

Patterns:[15]

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

Classification

Classification based on extent:[15]

  1. Adenocarcinoma in situ (AIS) - previously known as BAC.
    • Subtypes: nonmucinous, mucinous, mixed mucinous/nonmucinous.
  2. Minimally invasive adenocarcinoma (MIA).
    • Lepidic growth with upto 5 mm of invasion.
    • Subtypes: nonmucinous (most common), mucinous, mixed mucinous/nonmucinous.
  3. Invasive adenocarcinoma:
    • Subtypes: micropapillary, mucinous (previously mucinous BAC, colloid, fetal, enteric.

Pulmonary carcinoid tumourlet

  • AKA carcinoid tumourlet.

General

Microscopic

Features:

  • Nests of cells - classic pattern.
    • Salt and pepper chromatin - key feature.
  • Size criterion: <= 4 mm.[17]

DDx:

Images:

Typical carcinoid lung tumour

  • AKA carcinoid tumour of the lung.

General

  • Approximately 80% of lung carcinoids.[18]

Microscopic

Features:

  • Nests of cells.
    • Stippled chromatin.
    • Moderate cytoplasm.
  • No necrosis.
  • Low mitotic rate.

DDx:

IHC

  • MIB-1 scant staining.

Atypical carcinoid lung tumour

  • AKA carcinoid tumour of the lung.

General

  • Approximately 20% of lung carcinoids.[18]

Microscopic

Features:

  • Nests of cells.
    • Stippled chromatin.
    • Mild-to-moderate amount of cytoplasm.
  • No necrosis.
  • Moderate mitotic rate.

DDx:

IHC

  • MIB-1 moderate staining.

Malignant mesothelioma

  • AKA mesothelioma.

General

  • Prognosis sucks.

Locations:

  • Lung.
  • Primary peritoneal.

Epidemiology:

  • Strong association with asbestos exposure.

Conditions associated with asbestos exposure (mnemonic PALM):[19]

Possible association with asbestos exposure:

Microscopic

Features:

  • +/-Ferruginous body (AKA asbestos body) - diagnostic.[21]
    • Made of asbestos fiber.
    • Looks like a (twirling) baton.
  • +/-Atypical glands formed from epithelial cells.

Image:

IHC

  • Several panel exists - no agreed upon best panel.[22]
    • Usually two carcinoma markers + two mesothelial markers.

Panel:[22]

  • Mesothelial markers:
    • Calretinin.
    • WT-1.
    • D2-40.
    • CK5/6.
  • Carcinoma markers:
    • CEA (monoclonal and polyclonal).
    • TTF-1.
    • Ber-EP4.
    • MOC-31.

Solitary fibrous tumour of the pleura

See also: Solitary fibrous tumour.

General

  • Common.
  • Benign.
  • Elderly.

Gross/radiology

  • Chest wall.

Microscopic

Features:

  • Spindle cells.
  • Ropy collagen.

Image:

IHC

  • CD34 +ve.

Bronchioloalveolar carcinoma

  • Abbreviated BAC.

The term is no longer used in the new classification.[23]

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. ↑ URL: http://emedicine.medscape.com/article/426400-overview. Accessed on: 20 January 2010.
  10. ↑ 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.
  11. ↑ 11.0 11.1 URL: http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_is_lung_carcinoid_tumor_56.asp. Accessed on: 16 February 2011.
  12. ↑ WG. February 2010.
  13. ↑ 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.
  14. ↑ 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/.
  15. ↑ 15.0 15.1 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.
  16. ↑ Bennett, GL.; Chew, FS. (Mar 1994). "Pulmonary carcinoid tumorlets.". AJR Am J Roentgenol 162 (3): 568. PMID 8109497.
  17. ↑ URL: http://pathhsw5m54.ucsf.edu/case7/image75.html. Accessed on: 23 January 2012.
  18. ↑ 18.0 18.1 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. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 375. ISBN 978-1416054542.
  20. ↑ Reid, A.; Heyworth, J.; de Klerk, N.; Musk, AW. (Nov 2009). "Asbestos exposure and gestational trophoblastic disease: a hypothesis.". Cancer Epidemiol Biomarkers Prev 18 (11): 2895-8. doi:10.1158/1055-9965.EPI-09-0731. PMID 19900938.
  21. ↑ URL: http://medical-dictionary.thefreedictionary.com/asbestos+body. Accessed on: 4 November 2011.
  22. ↑ 22.0 22.1 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.
  23. ↑ 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.
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