Colorectal carcinoma
Author:
Mikael Häggström [note 1]
Contents
Gross evaluation
Depending on presentation:
Comprehensiveness
On this resource, the following formatting is used for comprehensiveness:
- Minimal depth
- (Moderate depth)
- ((Comprehensive))
Microscopic evaluation
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.
Subtyping
(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.)
H&E stained sections:
(A) Serrated adenocarcinoma: epithelial serrations or tufts (thick blue arrow), abundant eosinophilic or clear cytoplasm, vesicular basal nuclei with preserved polarity.
(B) Mucinous carcinoma: Presence of extracellular mucin (>50%) associated with ribbons or tubular structures of neoplastic epithelium.
(C) Signet ring carcinoma: More than 50% of signet cells with infiltrative growth pattern (thin red arrow) or floating in large pools of mucin (thick red arrow).
(D) Medullary carcinoma: Neoplastic cells with syncytial appearance (thick yellow arrow) and eosinophilic cytoplasm associated with abundant peritumoral and intratumoral lymphocytes.[3]H&E stained sections:
(A)Lymphoepitelioma-like carcinoma: Poorly differentiated cells (red arrow) arranged in solid nests, tubules and trabeculae with poorly demarcated, infiltrative margins; intratumoral lymphoid infiltrate is extremely abundant.
(B) Cribiform comedo-type carcinoma: Cribriform gland (yellow arrow) with central necrosis comedo-like (yellow asterisk).
(C) Micropapillary carcinoma: Small, tight round to oval cohesive clusters of neoplastic cells (>5 cells) floating in clear spaces (double circle red-black), without endothelial lining and with no evidence of inflammatory cells.
(D) Low grade tubulo-glandular carcinoma: Very well-differentiated invasive glands with uniform circular or tubular profiles (blue arrow) with bland cytologic atypia.[3]H&E stained sections:
(A) Villous carcinoma: invasive carcinoma with villous features consisting of usually intraglandular papillary projections (yellow arrow) associated with an expansile growth pattern, at the deep portions of the tumor.
(B) Squamous carcinoma: morphologically similar to other squamous cell carcinomas occurring in other organs with possible keratinization.
(C) Clear cell carcinoma: clear cell cytoplasm identified in polygonal cells with a central nucleus, columnar cells with an eccentric nucleus (red arrow) and/or round/oval cells with abundant cytoplasm and inconspicuous marginally located nucleus similar to lipocytes or lipoblasts.
(D) Hepatoid carcinoma: large polygonal-shaped cells, with granular eosinophilic cytoplasm, prominent nucleoli and trabecular and pseudo-acinar growth pattern similar to hepatocarcinoma.[3]H&E stained sections
(A) Colorectal choriocarcinoma: biphasic solid nests and trabeculae of mononucleated cells with clear cytoplasm (thin yellow arrow) and pleomorphic cells with abundant vacuolated or eosinophilic cytoplasm and single or multiple vescicular nuclei with conspicuous nucleoli (thick yellow arrow).
(B) Rhabdoid colorectal carcinoma: rhabdoid cells characterized by a large, eccentrically located nuclei, prominent nucleoli (red arrow) and abundant eosinophilic cytoplasm.
(C) Carcinoma with osseous metaplasia: osseous metaplasia (blue arrow) is recognized in conventional CRC as foci of bone formation in the stroma, with calcification, osteoid matrix, osteoclasts and osteoblasts.
(D) Undifferentiated carcinoma: sheets of undifferentiated cells showing a variable grade of pleomorphism with no gland formation, mucin production or other line of differentiation.[3]
Differential diagnosis

-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]
Grading
Conventional adenocarcinoma may be graded as follows[5]
>95% | 50-95% | <50% |
Well differentiated | Moderately differentiated | Low or poorly differentiated |
Low grade | High grade |
Staging
Determine depth of growth and/or infiltration. Preferably stage by the AJCC or TNM system:
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 |
|
|
Stage III-B |
|
|
Stage III-C |
|
|
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]
Reporting
Include:
- 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.
Example:
7 cm large (moderately differentiated) stricturing adenocarcinoma. Stage T3.
|
See also: General notes on reporting
Notes
- ↑ 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
References
- ↑ 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
- ↑ 2.0 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: . ISSN 1083-3668.
- ↑ 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: . ISSN 2072-6694. Attribution 4.0 International (CC BY 4.0) license
- ↑ Robert V Rouse. Colorectal Adenoma Containing Invasive Adenocarcinoma. Stanford University School of Medicine.
- ↑ :"Colorectal carcinoma: Pathologic aspects ". J Gastrointest Oncol 3 (3): 153–73. September 2012. doi: . PMID 22943008.
- ↑ 6.0 6.1 6.2 . Colorectal Cancer: Stages. Cancer.net (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: . ISSN 00079235. - ↑ 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: . 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: . 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: . PMID 34680502. PMC: 8533409. Archived from the original. . - ↑ Chen W, Frankel WL (2019). "A practical guide to biomarkers for the evaluation of colorectal cancer.
". Mod Pathol 32 (Suppl 1): 1-15. doi: . 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 - ↑ Practice at Danbury Hospital, Danbury, Connecticut, New England.
- ↑ Practice at Danbury Hospital, Danbury, Connecticut, New England.
Image sources