Colorectal carcinoma

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Author: Mikael Häggström [note 1]

Gross evaluation

Depending on presentation:


On this resource, the following formatting is used for comprehensiveness:

  • Minimal depth
  • (Moderate depth)
  • ((Comprehensive))

Microscopic evaluation

Colorectal adenocarcinoma, not otherwise specified

Microscopy criteria for colorectal adenocarcinoma

  • A lesion at least "high grade intramucosal neoplasia" (high grade dysplasia) has:
  • Severe cytologic atypia[1]
  • Cribriform architecture, consisting of juxtaposed gland lumens without stroma in between, with loss of cell polarity. Rarely, they have foci of squamous differentiation (morules).[1]
  • This should be distinguished from cases where piles of well-differentiated mucin-producing cells appear cribriform. In such piles, nuclei show regular polarity with apical mucin, and their nuclei are not markedly enlarged.[1]
  • Invasive adenocarcinoma commonly displays:
  • Varying degrees of gland formation with tall columnar cells.[1]
  • Frequenty desmoplasia.[1]
  • Dirty necrosis, consisting of extensive central necrosis with granular eosinophilic karyorrhectic cell detritus.[1][2] It is located within the glandular lumina,[2] or often with a garland of cribriform glands in their vicinity.[1]

It may also show lymphovascular invasion.


Relative incidences of subtypes of colorectal carcinomas.

(Determining the specific histopathologic subtype of colorectal adenocardinoma is not as important as its staging (see #Staging section below), and about half cases do not have any specific subtype. Still, it it customary to specify it where applicable.)

Differential diagnosis

A colorectal tubular and ⁄or villous adenoma may also display high-grade dysplasia, in this case seen mainly as loss of cell polarity as cells become more plump and haphazard than the elongated and parallel nuclei of surrounding low-grade dysplasia. Thus, colorectal carcinoma is defined by invasion. Other signs of high grade dysplasia:
-Substantial stratification
-Nuclear pleomorphism
-Atypical mitoses
-Increased nucleus to cytoplasm ratio
-Prominent nucleoli

Colorectal carcinoma (mainly adenocarcinoma) is distinguished from an adenoma (mainly tubular and ⁄or villous adenomas) mainly by invasion through the muscularis mucosae.[4]


Conventional adenocarcinoma may be graded as follows[5]

Gland forming volume or surface
>95% 50-95% <50%
Well differentiated Moderately differentiated Low or poorly differentiated
Low grade High grade


Determine depth of growth and/or infiltration. Preferably stage by the AJCC or TNM system:

Colorectal cancer staging   edit
AJCC stage[6] TNM stage[6] TNM stage criteria[6]
Stage 0 Tis N0 M0 Tis: Tumor confined to mucosa; cancer-in-situ
Stage I T1 N0 M0 T1: Tumor invades submucosa
T2 N0 M0 T2: Tumor invades muscularis propria
Stage II-A T3 N0 M0 T3: Tumor invades subserosa or beyond (without other organs involved)
Stage II-B T4a N0 M0 T4a: Tumor perforates the visceral peritoneum
Stage II-C T4b N0 M0 T4b: Tumor invades adjacent organs
Stage III-A
  • T1-2 N1 M0 or
  • T1, N2a, M0
  • N1: Tumor cells in 1 to 3 regional lymph nodes. T1 or T2.
  • N2a: Tumor cells in 4 to 6 regional lymph nodes. T1
Stage III-B
  • T3-4a, N1 M0 or
  • T2-3, N2a, M0 or
  • T1-2 N2b M0
  • N1: Tumor cells in 1 to 3 regional lymph nodes. T3 or T4
  • N2a: Tumor cells in 4 to 6 regional lymph nodes. T2 or T3
  • N2b: Tumor cells in 7 or more regional lymph nodes. T1 or 2
Stage III-C
  • T4a N2a M0 or
  • T3-4a N2b M0 or
  • T4b N1-2, M0
  • N2a: Tumor cells in 4 to 6 regional lymph nodes. T4a
  • N2b: Tumor cells in 7 or more regional lymph nodes. T3-4a
  • N1-2: Tumor cells in at least one regional lymph node. T4b
Stage IVa any T, any N, M1a M1a: Metastasis to 1 other part of the body beyond the colon, rectum or regional lymph nodes. Any T, any N.
Stage IVb any T, any N, M1b M1b: Metastasis to more than 1 other part of the body beyond the colon, rectum or regional lymph nodes. Any T, any N.
Stage IVc any T, any N, M1c M1c: Metastasis to the peritoneal surface. Any T, any N.
Further information: Evaluation of tumors

Mismatch repair gene testing

(Perform immunohistochemistry for the mismatch repair genes MLH-1, PMS-2, MSH-2 and MSH-6.) For these, scoring is as follows:[7]

Depending on the outcome, talk with a senior about what is the local procedure for further workup. Following is an example of an algorithm:[8]

BRAF V600E mutation and MLH1 promoter methylation can be ordered at the same time.[9]

Generally perform next generation sequencing if cancer is metastatic.[10]



  • Size of tumor
  • Tumor type (and subtype where applicable)
  • (Grade)
  • Stage, at least including T.
  • Significant stricture of the lumen if present
  • If tested: Intact versus loss of expression of mismatch repair genes.


7 cm large (moderately differentiated) stricturing adenocarcinoma. Stage T3.
  • MLH-1: Intact nuclear expression
  • PMS-2: Intact nuclear expression
  • MSH-2: Loss of nuclear expression
  • MSH-6: Loss of nuclear expression

  See also: General notes on reporting


  1. For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.

Main page


  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Robert V Rouse. Adenocarcinoma of the Colon and Rectum. Stanford University School of Medicine. Original posting/updates: 1/31/10, 7/15/11, 11/12/11
  2. 2.0 2.1 Li, Lianhuang; Jiang, Weizhong; Yang, Yinghong; Chen, Zhifen; Feng, Changyin; Li, Hongsheng; Guan, Guoxian; Chen, Jianxin (2014). "Identification of dirty necrosis in colorectal carcinoma based on multiphoton microscopy ". Journal of Biomedical Optics 19 (6): 066008. doi:10.1117/1.JBO.19.6.066008. ISSN 1083-3668. 
  3. 3.0 3.1 3.2 3.3 Initially copied from: Remo, Andrea; Fassan, Matteo; Vanoli, Alessandro; Bonetti, Luca Reggiani; Barresi, Valeria; Tatangelo, Fabiana; Gafà, Roberta; Giordano, Guido; et al. (2019). "Morphology and Molecular Features of Rare Colorectal Carcinoma Histotypes ". Cancers 11 (7): 1036. doi:10.3390/cancers11071036. ISSN 2072-6694.  Attribution 4.0 International (CC BY 4.0) license
  4. Robert V Rouse. Colorectal Adenoma Containing Invasive Adenocarcinoma. Stanford University School of Medicine.
  5. :"Colorectal carcinoma: Pathologic aspects ". J Gastrointest Oncol 3 (3): 153–73. September 2012. doi:10.3978/j.issn.2078-6891.2012.030. PMID 22943008. 
  6. 6.0 6.1 6.2 . Colorectal Cancer: Stages. (American Society of Clinical Oncology). Retrieved on 2019-09-26. Approved by the Cancer.Net Editorial Board, 11/2018. In turn citing:
    Amin, Mahul B.; Greene, Frederick L.; Edge, Stephen B.; Compton, Carolyn C.; Gershenwald, Jeffrey E.; Brookland, Robert K.; Meyer, Laura; Gress, Donna M.; et al. (2017). "The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging ". CA: A Cancer Journal for Clinicians 67 (2): 93–99. doi:10.3322/caac.21388. ISSN 00079235. 
  7. These cutoffs are used for both colorectal and endometrial cancers:
    - Sarode, Venetia R.; Robinson, Linda (2019). "Screening for Lynch Syndrome by Immunohistochemistry of Mismatch Repair Proteins: Significance of Indeterminate Result and Correlation With Mutational Studies ". Archives of Pathology & Laboratory Medicine 143 (10): 1225–1233. doi:10.5858/arpa.2018-0201-OA. ISSN 0003-9985. 
    - Sarode VR, Robinson L (2019). "Screening for Lynch Syndrome by Immunohistochemistry of Mismatch Repair Proteins: Significance of Indeterminate Result and Correlation With Mutational Studies. ". Arch Pathol Lab Med 143 (10): 1225-1233. doi:10.5858/arpa.2018-0201-OA. PMID 30917047. Archived from the original. . 
    - Lee JHS, Li JJX, Chow C, Chan RCK, Kwan JSH, Lau TS (2021). "Long-Term Survival and Clinicopathological Implications of DNA Mismatch Repair Status in Endometrioid Endometrial Cancers in Hong Kong Chinese Women. ". Biomedicines 9 (10). doi:10.3390/biomedicines9101385. PMID 34680502. PMC: 8533409. Archived from the original. . 
  8. Chen W, Frankel WL (2019). "A practical guide to biomarkers for the evaluation of colorectal cancer. ". Mod Pathol 32 (Suppl 1): 1-15. doi:10.1038/s41379-018-0136-1. PMID 30600322. Archived from the original. . 
    - This diagram is ineligible for copyright and is therefore in the public domain because it was published in the United States and consists of descriptions of pathology processes, without any significant artistic or poetic innovation. Further information: Patholines:Copyright
  9. Practice at Danbury Hospital, Danbury, Connecticut, New England.
  10. Practice at Danbury Hospital, Danbury, Connecticut, New England.

Image sources