Difference between revisions of "Colorectal tumours"

From Libre Pathology
Jump to navigation Jump to search
Line 76: Line 76:
**MSH2 and MSH6 are lost together.
**MSH2 and MSH6 are lost together.
**Lost in nuclei of tumour.
**Lost in nuclei of tumour.
*MSH2 mutation (IHC stain -ve) is often associated with a germline mutation,<ref name=pmid16216036>{{cite journal |author=Mangold E, Pagenstecher C, Friedl W, ''et al.'' |title=Tumours from MSH2 mutation carriers show loss of MSH2 expression but many tumours from MLH1 mutation carriers exhibit weak positive MLH1 staining |journal=J. Pathol. |volume=207 |issue=4 |pages=385–95 |year=2005 |month=December |pmid=16216036 |doi=10.1002/path.1858 |url=}}</ref> while mutation in MLH1 are usually sporatic.<ref>A. Pollett. 2010.</ref>
*MSH2 mutations (IHC stain -ve) - often associated with a germline mutation,<ref name=pmid16216036>{{cite journal |author=Mangold E, Pagenstecher C, Friedl W, ''et al.'' |title=Tumours from MSH2 mutation carriers show loss of MSH2 expression but many tumours from MLH1 mutation carriers exhibit weak positive MLH1 staining |journal=J. Pathol. |volume=207 |issue=4 |pages=385–95 |year=2005 |month=December |pmid=16216036 |doi=10.1002/path.1858 |url=}}</ref> while mutations in MLH1 are usually sporatic.<ref>A. Pollett. 2010.</ref>
*PMS2 mutation (IHC stain -ve) is often associated with a germline mutation.<ref name=pmid20205264>{{cite journal |author=Vaughn CP, Robles J, Swensen JJ, ''et al.'' |title=Clinical analysis of PMS2: mutation detection and avoidance of pseudogenes |journal=Hum. Mutat. |volume=31 |issue=5 |pages=588–93 |year=2010 |month=May |pmid=20205264 |doi=10.1002/humu.21230 |url=}}</ref>
*PMS2 mutations (IHC stain -ve) - often associated with a germline mutation.<ref name=pmid20205264>{{cite journal |author=Vaughn CP, Robles J, Swensen JJ, ''et al.'' |title=Clinical analysis of PMS2: mutation detection and avoidance of pseudogenes |journal=Hum. Mutat. |volume=31 |issue=5 |pages=588–93 |year=2010 |month=May |pmid=20205264 |doi=10.1002/humu.21230 |url=}}</ref>


===Other ancillary studies===
===Other ancillary studies===

Revision as of 06:05, 19 November 2010

Colorectal tumours are very common. They are the bread and butter of GI pathology. Non-tumour colon is dealt with in the colon article.

An introduction to gastrointestinal pathology is in the gastrointestinal pathology article. The precursor lesion of colorectal carcinoma (CRC) is, typical, an adenomatous polyp. Polyps are discussed in the intestinal polyps article.

Classification

Other tumours - many (incomplete list):[2]

  • Mucinous carcinoma.
  • Adenosquamous carcinoma.
  • Signet-ring carcinoma.
  • Squamous carcinoma.
  • Neuroendocrine neoplasms (carcinoid tumours).
  • Lipoma.
  • Leiomyoma.
  • Gastrointestinal stromal tumour (GIST) - dealt with in a separate article.
  • Angiosarcoma.
  • Lymphoma (Non-Hodgkin's lymphoma).

Grading

  • "Adenocarcinoma in situ" and "high-grade dysplasia" is used interchangeably by many in the colon and rectum.
    • Splitting hairs - adenocarcinoma in situ is invasion into the lamina propria, high-grade dysplasia does not have lamina propria invasion. Ergo, the difference (in my opinion) amounts to seeing a desmoplastic stroma (adenocarcinoma) or not seeing one (dysplasia).

Grading of tumours:

  • Tis - in situ (intramucosal).
  • T1 - into submucosa (through mucularis mucosae).
    • This is different than elsewhere, e.g. in the small bowel tumour cells in the lamina propria is defined as T1. The rationale for the T1 definition in CRC is that no lymphatics are present in the mucosa, ergo no risk of distant spread.
  • T2 - into muscularis propria.
  • T3 - into fat beyond musclaris propria.
  • T4 - into something else.

Nodes:

  • N0 - no positive nodes.
  • N1 - 1-3 positive nodes.
  • N2 - 4+ positive nodes.

Staging of colorectal cancer

Simple version

Tumour/node grade for stage:[3]

  • Stage I - T1 or T2 N0 M0.
  • Stage II - T3 or T4 N0 M0.
  • Stage III - Tx N1 or N2 M0.
  • Stage IV - Tx Nx M1.

Complex version

Detailed tumour/node grade for stage:[4]

  • Stage I - T1 or T2.
  • Stage IIA - T3.
  • Stage IIB - T4.
  • Stage IIIA - T1 N1 or T2 N1.
  • Stage IIIB - T3 N1 or T4 N1.
  • Stage IIIC - Tx N2.
  • Stage IV - Tx Nx M1.

Pathogenesis

Overview

Colorectal carcinoma is thought to arise from one of two pathways:[5][6]

  1. APC (adenomatous polyposis coli) gene mutation pathway, AKA classic adenoma-carcinoma pathway.
  2. Serrated pathway, AKA mutator pathway, mismatch repair pathway.

Mismatch repair pathway

    • Associated with microsatellite instability (MSI).
    • Common associated gene mutations:
      1. MLH1.
      2. PMS2.
      3. MSH2.
      4. MSH6.
    • Less common gene mutations:
      1. PMS1.
      2. MLH3.
      3. MSH3.

Notes:

  • IHC interpretation:
    • MLH1 and PMS2 are lost together.
    • MSH2 and MSH6 are lost together.
    • Lost in nuclei of tumour.
  • MSH2 mutations (IHC stain -ve) - often associated with a germline mutation,[7] while mutations in MLH1 are usually sporatic.[8]
  • PMS2 mutations (IHC stain -ve) - often associated with a germline mutation.[9]

Other ancillary studies

  • BRAF V600E missense mutation found in ~10% CRC.[10]
  • KRAS mutation status.

BRAF V600E mutation

Features:[10]

  • Independently assoc. with BRAF V600E:
    • Usually older (>70 years old).
    • Female gender
    • Right-sided tumour location.
  • Worse prognosis - in the context of metastatic disease.

KRAS mutation

Features:[11][12]

  • Patient must have wild type KRAS to get drugs; KRAS mutation predicts resistance to cetuximab (Erbitux) and panitumumab (Vectibix).
    • Cetuximab and panitumumab are EGFR inhibitors.

MSI cancers

General

Features:[13]

  • Prognosis: slightly better than other CRC without MSI.
  • Treatment implication: different response to chemotherapy.

MSI classification

MSI associated cancers can be classified into:[14][15]

  • MSI-H >= 30% of loci have abnormality.
  • MSI-L <30% of loci have abnormality.

Gross

Features:[13]

  • Location: left-sided predominance.

Microscopic

Features:[13]

  • Lymphocytic infiltrate.
  • Pushing border.[16]
  • Histomorphology:
    • Poorly differentiated.
    • Mucinous.
    • Signet ring.
    • Medullary.[17]

Syndromes

  • Lynch syndrome AKA hereditary non-polyposis colorectal cancer syndrome (HNPCC).
  • Familial polyposis coli (FPC).

See also

References

  1. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 864. ISBN 0-7216-0187-1.
  2. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 198. ISBN 978-0781765275.
  3. ↑ TN 2006 GS27.
  4. ↑ http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_colon_and_rectum_cancer_staged.asp
  5. ↑ Goldstein NS (January 2006). "Serrated pathway and APC (conventional)-type colorectal polyps: molecular-morphologic correlations, genetic pathways, and implications for classification". Am. J. Clin. Pathol. 125 (1): 146–53. PMID 16483003.
  6. ↑ Rüschoff J, Aust D, Hartmann A (2007). "[Colorectal serrated adenoma: diagnostic criteria and clinical implications]" (in German). Verh Dtsch Ges Pathol 91: 119–25. PMID 18314605.
  7. ↑ Mangold E, Pagenstecher C, Friedl W, et al. (December 2005). "Tumours from MSH2 mutation carriers show loss of MSH2 expression but many tumours from MLH1 mutation carriers exhibit weak positive MLH1 staining". J. Pathol. 207 (4): 385–95. doi:10.1002/path.1858. PMID 16216036.
  8. ↑ A. Pollett. 2010.
  9. ↑ Vaughn CP, Robles J, Swensen JJ, et al. (May 2010). "Clinical analysis of PMS2: mutation detection and avoidance of pseudogenes". Hum. Mutat. 31 (5): 588–93. doi:10.1002/humu.21230. PMID 20205264.
  10. ↑ 10.0 10.1 Tie J, Gibbs P, Lipton L, et al. (July 2010). "Optimizing targeted therapeutic development: Analysis of a colorectal cancer patient population with the BRAF(V600E) mutation". Int J Cancer. doi:10.1002/ijc.25555. PMID 20635392.
  11. ↑ Dunn EF, Iida M, Myers RA, et al. (October 2010). "Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab". Oncogene. doi:10.1038/onc.2010.430. PMID 20956938.
  12. ↑ Di Nicolantonio F, Martini M, Molinari F, et al. (December 2008). "Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer". J. Clin. Oncol. 26 (35): 5705–12. doi:10.1200/JCO.2008.18.0786. PMID 19001320.
  13. ↑ 13.0 13.1 13.2 Boland CR, Goel A (June 2010). "Microsatellite instability in colorectal cancer". Gastroenterology 138 (6): 2073–2087.e3. doi:10.1053/j.gastro.2009.12.064. PMID 20420947.
  14. ↑ Lawes DA, Pearson T, Sengupta S, Boulos PB (August 2005). "The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers". Br. J. Cancer 93 (4): 472–7. doi:10.1038/sj.bjc.6602708. PMC 2361590. PMID 16106253. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361590/.
  15. ↑ Guidoboni M, Gafà R, Viel A, et al. (July 2001). "Microsatellite instability and high content of activated cytotoxic lymphocytes identify colon cancer patients with a favorable prognosis". Am. J. Pathol. 159 (1): 297–304. PMC 1850401. PMID 11438476. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1850401/.
  16. ↑ AP. 18 October 2010.
  17. ↑ Truta B, Chen YY, Blanco AM, et al. (2008). "Tumor histology helps to identify Lynch syndrome among colorectal cancer patients". Fam. Cancer 7 (3): 267–74. doi:10.1007/s10689-008-9186-8. PMID 18283560.
Retrieved from "https://librepathology.org/w/index.php?title=Colorectal_tumours&oldid=2817"