Difference between revisions of "Colorectal carcinoma"

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*[[Intestine with tumor]]
 
*[[Intestine with tumor]]
 
*[[Colorectal polyp]]
 
*[[Colorectal polyp]]
 +
{{Comprehensiveness}}
  
 
==Microscopic evaluation==
 
==Microscopic evaluation==
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===Subtyping===
 
===Subtyping===
 
[[File:Pie chart of colorectal carcinoma etiologies.svg|thumb|300px|Relative incidences of subtypes of colorectal carcinomas.]]
 
[[File:Pie chart of colorectal carcinoma etiologies.svg|thumb|300px|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.
+
{{Moderate-begin}}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.{{Moderate-end}}
 
<gallery mode=packed heights=350>
 
<gallery mode=packed heights=350>
 
File:Micrograph of serrated adenocarcinoma, mucinous carcinoma, signet ring carcinoma and medullary carcinoma.jpg|H&E stained sections: <br>'''(A) Serrated adenocarcinoma''': epithelial serrations or tufts (thick blue arrow), abundant eosinophilic or clear cytoplasm, vesicular basal nuclei with preserved polarity.<br>'''(B) Mucinous carcinoma:''' Presence of extracellular mucin (>50%) associated with ribbons or tubular structures of neoplastic epithelium.<br>'''(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).<br>'''(D) Medullary carcinoma:''' Neoplastic cells with syncytial appearance (thick yellow arrow) and eosinophilic cytoplasm associated with abundant peritumoral and intratumoral lymphocytes.<ref name=Remo2019>Initially copied from: {{cite journal|last1=Remo|first1=Andrea|last2=Fassan|first2=Matteo|last3=Vanoli|first3=Alessandro|last4=Bonetti|first4=Luca Reggiani|last5=Barresi|first5=Valeria|last6=Tatangelo|first6=Fabiana|last7=Gafà|first7=Roberta|last8=Giordano|first8=Guido|last9=Pancione|first9=Massimo|last10=Grillo|first10=Federica|last11=Mastracci|first11=Luca|title=Morphology and Molecular Features of Rare Colorectal Carcinoma Histotypes|journal=Cancers|volume=11|issue=7|year=2019|pages=1036|issn=2072-6694|doi=10.3390/cancers11071036}} [https://creativecommons.org/licenses/by/4.0/ Attribution 4.0 International (CC BY 4.0) license]</ref>
 
File:Micrograph of serrated adenocarcinoma, mucinous carcinoma, signet ring carcinoma and medullary carcinoma.jpg|H&E stained sections: <br>'''(A) Serrated adenocarcinoma''': epithelial serrations or tufts (thick blue arrow), abundant eosinophilic or clear cytoplasm, vesicular basal nuclei with preserved polarity.<br>'''(B) Mucinous carcinoma:''' Presence of extracellular mucin (>50%) associated with ribbons or tubular structures of neoplastic epithelium.<br>'''(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).<br>'''(D) Medullary carcinoma:''' Neoplastic cells with syncytial appearance (thick yellow arrow) and eosinophilic cytoplasm associated with abundant peritumoral and intratumoral lymphocytes.<ref name=Remo2019>Initially copied from: {{cite journal|last1=Remo|first1=Andrea|last2=Fassan|first2=Matteo|last3=Vanoli|first3=Alessandro|last4=Bonetti|first4=Luca Reggiani|last5=Barresi|first5=Valeria|last6=Tatangelo|first6=Fabiana|last7=Gafà|first7=Roberta|last8=Giordano|first8=Guido|last9=Pancione|first9=Massimo|last10=Grillo|first10=Federica|last11=Mastracci|first11=Luca|title=Morphology and Molecular Features of Rare Colorectal Carcinoma Histotypes|journal=Cancers|volume=11|issue=7|year=2019|pages=1036|issn=2072-6694|doi=10.3390/cancers11071036}} [https://creativecommons.org/licenses/by/4.0/ Attribution 4.0 International (CC BY 4.0) license]</ref>
 
File:Micrograph of lymphoepitelioma-like carcinoma, cribiform comedo-type carcinoma, micropapillary carcinoma and low grade tubulo-glandular carcinoma.jpg|H&E stained sections:<br>'''(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.<br>'''(B) Cribiform comedo-type carcinoma''': Cribriform gland (yellow arrow) with central necrosis comedo-like (yellow asterisk).<br>'''(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.<br>'''(D) Low grade tubulo-glandular carcinoma''': Very well-differentiated invasive glands with uniform circular or tubular profiles (blue arrow) with bland cytologic atypia.<ref name=Remo2019/>
 
File:Micrograph of lymphoepitelioma-like carcinoma, cribiform comedo-type carcinoma, micropapillary carcinoma and low grade tubulo-glandular carcinoma.jpg|H&E stained sections:<br>'''(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.<br>'''(B) Cribiform comedo-type carcinoma''': Cribriform gland (yellow arrow) with central necrosis comedo-like (yellow asterisk).<br>'''(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.<br>'''(D) Low grade tubulo-glandular carcinoma''': Very well-differentiated invasive glands with uniform circular or tubular profiles (blue arrow) with bland cytologic atypia.<ref name=Remo2019/>
File:Micrograph of villous carcinoma, squamous carcinoma, clear cell carcinoma and hepatoid carcinoma.jpg|H&E stained sections:<br>'''(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. Scale bar 400 micron.<br>'''(B) Squamous carcinoma''': morphologically similar to other squamous cell carcinomas occurring in other organs with possible keratinization. Scale bar 200 micron.<br>'''(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. Scale bar 50 micron.<br>'''(D) Hepatoid carcinoma:''' large polygonal-shaped cells, with granular eosinophilic cytoplasm, prominent nucleoli and trabecular and pseudo-acinar growth pattern similar to hepatocarcinoma.<ref name=Remo2019/>
+
File:Micrograph of villous carcinoma, squamous carcinoma, clear cell carcinoma and hepatoid carcinoma.jpg|H&E stained sections:<br>'''(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.<br>'''(B) Squamous carcinoma''': morphologically similar to other squamous cell carcinomas occurring in other organs with possible keratinization.<br>'''(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.<br>'''(D) Hepatoid carcinoma:''' large polygonal-shaped cells, with granular eosinophilic cytoplasm, prominent nucleoli and trabecular and pseudo-acinar growth pattern similar to hepatocarcinoma.<ref name=Remo2019/>
File:Micrograph of colorectal choriocarcinoma, rhabdoid colorectal carcinoma, carcinoma with osseous metaplasia and undifferentiated carcinoma.jpg|H&E stained sections<br>'''(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).<br>'''(B) Rhabdoid colorectal carcinoma:''' rhabdoid cells characterized by a large, eccentrically located nuclei, prominent nucleoli (red arrow) and abundant eosinophilic cytoplasm. Scale bar 100 micron.<br>'''(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.<br>'''(D) Undifferentiated carcinoma:''' sheets of undifferentiated cells showing a variable grade of pleomorphism with no gland formation, mucin production or other line of differentiation.<ref name=Remo2019/>
+
File:Micrograph of colorectal choriocarcinoma, rhabdoid colorectal carcinoma, carcinoma with osseous metaplasia and undifferentiated carcinoma.jpg|H&E stained sections<br>'''(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).<br>'''(B) Rhabdoid colorectal carcinoma:''' rhabdoid cells characterized by a large, eccentrically located nuclei, prominent nucleoli (red arrow) and abundant eosinophilic cytoplasm. <br>'''(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.<br>'''(D) Undifferentiated carcinoma:''' sheets of undifferentiated cells showing a variable grade of pleomorphism with no gland formation, mucin production or other line of differentiation.<ref name=Remo2019/>
 
</gallery>
 
</gallery>
  
 
===Differential diagnosis===
 
===Differential diagnosis===
 
{{Colorectal adenoma versus adenocarcinoma}}
 
{{Colorectal adenoma versus adenocarcinoma}}
 +
 +
===Grading===
 +
Conventional adenocarcinoma may be graded as follows<ref>:{{cite journal |vauthors=Fleming M, Ravula S, Tatishchev SF, Wang HL |title=Colorectal carcinoma: Pathologic aspects |journal=J Gastrointest Oncol |volume=3 |issue=3 |pages=153–73 |date=September 2012 |pmid=22943008 |pmc=3418538 |doi=10.3978/j.issn.2078-6891.2012.030 |url=}}</ref>
 +
{|class="wikitable" style="text-align: center;"
 +
|+ Gland forming volume or surface
 +
|-
 +
| >95% || 50-95% || <50%
 +
|-
 +
| Well differentiated  || Moderately differentiated || Low or poorly differentiated
 +
|-
 +
|colspan=2| Low grade || High grade
 +
|}
 +
<gallery mode=packed heights=220>
 +
File:Micrograph of moderately differentiated colorectal carcinoma.jpg|Moderately differentiated colorectal carcinoma
 +
File:Micrograph of moderately-to-poorly differentiated colorectal carcinoma.jpg|Moderately-to-poorly differentiated colorectal carcinoma
 +
</gallery>
  
 
===Staging===
 
===Staging===
 
Determine depth of growth and/or infiltration. Preferably stage by the AJCC or TNM system:
 
Determine depth of growth and/or infiltration. Preferably stage by the AJCC or TNM system:
 
{{Colorectal cancer staging }}
 
{{Colorectal cancer staging }}
 +
{{Evaluation of tumors}}
 +
 +
===Mismatch repair gene testing===
 +
[[File:Immunohistochemistry of indeterminate expression of MSH-6.jpg|thumb|Indeterminate expression of MSH-6.]]
 +
{{Moderate-begin}}Perform immunohistochemistry for MLH-1, PMS-2, MSH-2 and MSH-6. They are generally scored as:<ref name="SarodeRobinson2019">{{cite journal|last1=Sarode|first1=Venetia R.|last2=Robinson|first2=Linda|title=Screening for Lynch Syndrome by Immunohistochemistry of Mismatch Repair Proteins: Significance of Indeterminate Result and Correlation With Mutational Studies|journal=Archives of Pathology & Laboratory Medicine|volume=143|issue=10|year=2019|pages=1225–1233|issn=0003-9985|doi=10.5858/arpa.2018-0201-OA}}</ref>
 +
*0% nuclear expression in carcinoma cells: "Loss of expression"
 +
*More than 0% but less than 10%: "Indeterminate"
 +
*At least 10%: Retained expression"{{Moderate-end}}
 +
 
===Reporting===
 
===Reporting===
Report at least:
+
Include:
 
*Size of tumor
 
*Size of tumor
*Tumor type, where subtyping of adenocarcinoma is not mandatory
+
*Tumor type {{Moderate-begin}}and subtype where applicable{{Moderate-end}}
 +
*{{Moderate-begin}}Grade{{Moderate-end}}
 
*Stage, at least including T.
 
*Stage, at least including T.
 
*Significant stricture of the lumen if present
 
*Significant stricture of the lumen if present
 +
*If tested: Intact versus loss of expression of mismatch repair genes.
 
Example:
 
Example:
 
{|class="wikitable"
 
{|class="wikitable"
| 7 cm large stricturing adenocarcinoma. Stage T3.
+
| 7 cm large {{Moderate-begin}}moderately differentiated{{Moderate-end}} 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
 
|}
 
|}
 
{{Reporting}}
 
{{Reporting}}
 
{{Bottom}}
 
{{Bottom}}

Revision as of 17:56, 24 May 2021

Author: Mikael Häggström [note 1]

Gross evaluation

Depending on presentation:

Comprehensiveness

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.

Subtyping

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

edit
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]

Gland forming volume or surface
>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:

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

Indeterminate expression of MSH-6.

(Perform immunohistochemistry for MLH-1, PMS-2, MSH-2 and MSH-6. They are generally scored as:[7]

  • 0% nuclear expression in carcinoma cells: "Loss of expression"
  • More than 0% but less than 10%: "Indeterminate"
  • At least 10%: Retained expression")

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.
  • 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


Notes

  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

References

  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. 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:10.3322/caac.21388. ISSN 00079235. 
  7. 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. 

Image sources