Colorectal carcinoma

Author: Mikael Häggström

Gross evaluation

Depending on presentation:

• Intestine with tumor
• Colorectal polyp

Comprehensiveness

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

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

Microscopic evaluation

File:Colorectal adenocarcinoma, not otherwise specified.jpg

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
• Cribriform architecture, consisting of juxtaposed gland lumens without stroma in between, with loss of cell polarity. Rarely, they have foci of squamous differentiation (morules).

• 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.

• Invasive adenocarcinoma commonly displays:

• Varying degrees of gland formation with tall columnar cells.
• Frequenty desmoplasia.
• Dirty necrosis, consisting of extensive central necrosis with granular eosinophilic karyorrhectic cell detritus. It is located within the glandular lumina, or often with a garland of cribriform glands in their vicinity.

It may also show lymphovascular invasion.

• Desmoplastic reaction (*)
  Desmoplastic reaction (*)
• Dirty necrosis
  Dirty necrosis
• Lymphovascular invasion (lymphatic invasion pictured)
  Lymphovascular invasion (lymphatic invasion pictured)

Subtyping

File:Pie chart of colorectal carcinoma etiologies.svg

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.)

• 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) 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.
• 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)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.
• 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) 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.
• 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]
  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.

Differential diagnosis

File:Micrograph of villous adenoma with high-grade dysplasia.jpg

A colorectal tubular and ⁄or villous adenoma may also display high-grade dysplasia, so it is invasion that defined colorectal carcinoma. 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.

Grading

Conventional adenocarcinoma may be graded as follows

Gland forming volume or surface

>95%	50-95%	<50%
Well differentiated	Moderately differentiated	Low or poorly differentiated
Low grade		High grade

• Moderately differentiated colorectal carcinoma
  Moderately differentiated colorectal carcinoma
• Moderately-to-poorly differentiated colorectal carcinoma
  Moderately-to-poorly differentiated colorectal carcinoma

Staging

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

Colorectal cancer staging  

AJCC stage	TNM stage	TNM stage criteria
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

File:Immunohistochemistry of indeterminate expression of MSH-6.jpg

Indeterminate expression of MSH-6.

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

• 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

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