Stanford School of Medicine

Surgical Pathology Criteria

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Adenocarcinoma of the Colon and Rectum


  • Adenocarcinoma arising in the colon or rectum

Alternate/Historical Names

  • For high grade intramucosal neoplasia
    • Carcinoma in situ
    • High grade dysplasia
    • High grade intraepithelial neoplasia
    • High grade intramucosal neoplasia
    • Intramucosal carcinoma

Covered Separately

Diagnostic Criteria

  • See Grading/Staging at left for additional critical criteria applicable to problematic situations
  • High grade intramucosal neoplasia (high grade dysplasia) requires any one of three criteria below:
    • Cribriform architecture
      • Back to back gland lumens without intervening stroma
        • Should clearly be a manifestation of total loss of polarity by atypical cells
      • Frequently, well differentiated mucin producing cells will pile up in adenomas, forming lumens, technically appearing cribriform
        • Nuclei show regular basal orientation
        • Nuclei typically not markedly enlarged
        • This should not be considered evidence of high grade dysplasia
    • Severe cytologic atypia
      • This is unusual in the absence of cribriform architecture, but can occur
    • Invasion with a desmoplastic response confined to the lamina propria including muscularis mucosae
  • Invasive adenocarcinoma requires invasion through the muscularis mucosae at least into the submucosa
    • Varying degrees of gland formation (see Grading at left)
      • Typically lined by tall columnar cells
    • Frequent desmoplastic response
    • Dirty necrosis commonly seen
      • Extensive central necrosis composed of granular eosinophilic karyorrhectic debris
      • Frequent surrounding garland of cribriform glands
  • Special types of carcinoma are covered separately
    • Adenosquamous
      • Both glandular and squamous components are malignant
    • Medullary
      • Pushing border, many intraepithelial lymphocytes
    • Mucinous
      • >50% composed of mucin
    • Poorly differentiated endocrine
      • Both small cell and large cell with endocrine differentiation
    • Signet ring
      • >50% signet ring cells
    • Squamous
    • Undifferentiated
      • 0% gland formation
  • The following features are suggestive of microsatellite instability and/or hereditary non-polyposis colorectal carcinoma syndrome (HNPCC) but may also be seen in a subset of sporadic adenocarcinomas
    • Intraepithelial lymphocytes, ≥3 per HPF
    • Crohn-like response at edge of carcinoma
      • Lymphoid aggregates / follicles with or without germinal centers not associated with a lymph node
    • Mucinous or signet ring carcinoma component
    • Medullary carcinoma
    • Less specific criteria
      • Right side location
      • High grade histology
      • Lack of dirty necrosis
    • Sporadic carcinomas with these features are frequently MSI high
      • Such carcinomas share essentially all histologic features with HNPCC tumors
      • May be present in 15% of colorectal adenocarcinomas
      • Familial and sporadic cases share some other clinical features
        • Better prognosis than non-MSI carcinomas
        • Decreased response to 5-FU therapy
        • Right sided predominance
  • Circumferential / radial margin applies to rectum and non-peritonealized surfaces of colon
    • It does not apply to peritoneal surface
    • See Grading/Staging for details
  • Following features may have prognostic value but have not been sufficiently validated
    • Tumor border configuration
      • Expansile – smooth and pushing
      • Infiltrative
        • Limit of carcinoma not definable on naked eye exam of slide
        • Inability to resolve carcinoma from host response on naked eye exam of slide
        • Streaming dissection / permeation of muscularis propria without desmoplastic response
        • Dissection of pericolic fat by single cells, cords or clusters of cells
        • Perineural invasion
    • Budding
      • Based on high power examination of edge of carcinoma
      • Detached clusters ≤5 cells each embedded in desmoplastic stroma
      • May become spindled (epithelial-mesenchymal transition)
      • More often seen in MSI carcinomas associated with HNPCC and with MSS carcinomas but not with sporadic MSI carcinomas

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 1/31/10, 7/15/11, 11/12/11

Supplemental studies


Results for colorectal adenocarcinoma NOS
p63 Negative
CK5/6 5%
CDX2 75-98%
CK7 5-10%
CK20 95

Genetic analysis

Differential Diagnosis

Metastatic adenocarcinoma of unknown type

  • Tall columnar cells with prominent dirty necrosis should suggest colorectal primary
  • Immunohistochemistry can be quite useful:

CK7 and CK20 expression in carcinomas

CK7+20+ CK7-20+
Ovary mucinous 90% Colorectal adeno 80%
Transitional cell 65% Merkel cell 70%
Pancreas adeno 65% Gastric adeno 35%
Cholangio 65%  
Gastric adeno 40%  
Excluded tumors 5% or less Carcinoid; Germ cell; Esoph squam; Head/neck squam; Hepato-cellular; Lung small cell & squam; Ovary non-mucinous; Renal adeno Excluded tumors 5% or less Breast; Carcinoid lung; Cholangio; Esoph squam; Germ cell; Lung all types; Hepato-cellular; Ovary; Pancreas adeno; Renal adeno; Transitional cell; Uterus endometrioid
CK7+20- CK7-20-
Ovary non-mucinous 100% Adrenal 100%
Thyroid (all 3 types) 100% Seminoma & Yolk Sac 95%
Breast 90% Prostate 85%
Lung adeno 90% Hepatocellular 80%
Uterus endometrioid 85% Renal adeno 80%
Embryonal 80% Carcinoid intestinal & lung 80%
Mesothelioma 65% Lung small cell & squam 75%
Transitional cell 35% Esoph squam 70%
Pancreas adeno 30% Head/neck squam 70%
Cholangio 30% Mesothelioma 35%
Excluded tumors 5% or less Colorectal adeno; Ovary mucinous; Yolk Sac; Seminoma Excluded tumors 5% or less Breast; Cholangio; Lung adeno; Ovary; Pancreas adeno
  • Derived from Chu PG, Weiss LM. Histopathology 2002, 40:403-439 and other sources

    Adenocarcinoma Type CDX2 Staining
    Colorectal 70-98%
    Small intestine 60%
    Stomach 60-70%
    Endocervix 30%
    Ovary primary mucinous 40-70%
    Uterus 10-15%
    Bile duct 13-25%
    Lung 0-12%
    Pancreas 0-32%
    Liver 0%
    Breast 0%


    Colorectal Adenoma Containing Invasive Adenocarcinoma Colorectal Adenoma with Benign Misplacement of Glands / Pseudoinvasion
    Usually significant architectural and/or cytologic atypia Usually lacks significant architectural and/or cytologic atypia (high grade dysplasia may be misplaced occasionally but is typically accompanied by bland adenoma tissue)
    Desmoplastic stroma Inflammatory or fibrotic stroma
    Infiltrates through muscularis mucosae Frequently demonstrable continuity with surface through a gap in the muscularis mucosae
    Hemosiderin restricted to head of polyp Hemosiderin common in stalk stroma
    Glands not accompanied by lamina propria Glands may be accompanied by lamina propria
    Usually infiltrative, non-circumscribed Frequently circumscribed
    May occur throughout the colorectum Virtually restricted to left colon
    Collagen type IV weak, discontinuous Collagen type IV strong, continuous around epithelial nests
    E cadherin markedly decreased staining compared to overlying adenoma E cadherin same intensity as overlying adenoma (high grade dysplasia may show decrease)


    Mucosal Prolapse / Cloacogenic Polyp (Localized Colitis Cystica Profunda) Invasive Colorectal Adenocarcinoma
    No surface carcinoma component Surface component usually present
    No high grade nuclear atypia High grade nuclear atypia usually present
    No cribriform glands or complex architecture Complex architecture with cribriform glands frequent
    No desmoplastic stromal response Desmoplastic stromal response
    Lamina propria may accompany displaced glands No lamina propria accompanying invasive glands
    Mean age 35 years Occurs in older patients


    Colorectal Medullary Carcinoma Colorectal Poorly Differentiated Carcinoma NOS
    Lacks any gland formation At least 5% gland formation
    Uniform small to medium sized nuclei Pleomorphic large nuclei
    Uniformly prominent nucleoli Variable nucleoli
    Pushing border Infiltrative border
    Prominent lymphoid infiltrate in virtually all cases Lymphoid infiltrate variable


    Colorectal Medullary Carcinoma Colorectal Undifferentiated Carcinoma NOS
    Lacks any gland formation May have <5% gland formation
    Uniform small to medium sized nuclei Pleomorphic large nuclei
    Uniformly prominent nucleoli Variable nucleoli
    Pushing border Infiltrative border
    Prominent lymphoid infiltrate in virtually all cases Lymphoid infiltrate variable

    Grading / Staging


    • Grading based on worst area
      • Leading front of invasion excluded from grading
    • It is acceptable to grade simply as Low vs. High grade
      • Applies only adenocarcinoma NOS
        • See special types for relevant grading criteria (mucinous, signet ring, medullary, squamous)
      • Low grade ≥50% gland forming
        • Well differentiated
          • >95% gland forming
        • Moderately differentiated
          • 50-95% gland forming
        • Any MSI-H carcinoma
      • High grade <50% gland forming
        • Poorly differentiated
          • 0-49% gland forming
      • Use TNM staging
      • Problematic issues in T staging (see also miscellaneous issues below)
        • Tis
          • Includes high grade intraepithelial dysplasia and intramucosal carcinoma
          • Includes invasion into but not through muscularis mucosae
        • T3 (invasion through muscularis propria into subserosa or pericolic and perirectal tissues)
          • Absence of smooth muscle between advancing edge of carcinoma and the surrounding soft tissue counts as pT3
          • A nodule of carcinoma in the pericolic fat that lacks continuity with intramural invasive carcinoma should be considered as a Tumor Deposit (see lymph nodes below)
            • Such a nodule does not constitute evidence of T3
        • T4a (tumor penetrates visceral peritoneum)
          • Any of the following 3 criteria qualify
            • Carcinoma at surface with mesothelial inflammation/hyperplasia or ulceration
            • Free carcinoma cells on surface with underlying ulceration of peritoneum
            • Positive cytology scrape preparation taken from the serosal surface
          • Proposed but not widely accepted
            • Mesothelial inflammatory/hyperplastic response with carcinoma cells close to surface
        • T4b (invasion of other organs or structures)
          • Longitudinal spread to adjacent bowel sites (e.g. terminal ileum) is not pT4a
            • Direct invasion through the bowel wall into another GI site does qualify
        • Multiple simultaneous carcinomas
          • Includes those diagnosed within 2 months
          • Includes Tis lesions
          • TNM should be reported for the lesion with the highest T score
          • Add (m) or (2) etc. to indicate multiple or number of primary lesions e.g. pT3(m)
        • Margin evaluation
          • Proximal and distal margins
            • Histologic evaluation optional if grossly >5 cm
          • Circumferential / radial margin applies to rectum and non-peritonealized surfaces of colon
            • Does not apply to peritoneal surface
            • In colon with a mesentery
              • Mesenteric margin is the radial margin
              • It is not applicable if the carcinoma is anti-mesenteric
                • When grossing in, the location relevant to the mesentery should be noted
            • When applicable, the distance should be given
        • For rectal resections, the mesorectal tissue should be evaluated for the following
          • Surface of resection
            • Intact surface
            • Defects >5 mm but not extending to muscularis propria
            • Defects in surface extending to muscularis propria
          • Bulk of mesorectal tissue should be noted
      • Problematic issues in N staging (see also miscellaneous issues below)
        • Direct invasion of a node by the carcinoma counts as nodal involvement
        • Only regional draining nodes count for N staging
          • Nodes draining other bowel areas count towards M staging
          • If the primary spreads longitudinally to an adjacent bowel area, nodes draining that area count towards N staging
        • Involvement only of afferent lymphatics in a node counts as pL1, not as pN1
        • Nodules in the extra-tumoral soft tissue, discontinuous from intramural carcinoma:
          • (If there is any evidence of residual lymph node, they should be considered nodal metastases)
          • They should be recorded as Tumor Deposits (pTD)
            • They are not counted as nodes
            • They do not constitute evidence of pT3
          • If no lymph nodes are involved by carcinoma, these tumor deposits qualify for pN1c
            • If nodes are involved, they are not designated pN1c and have no impact on TNM
            • pN1c affects the overall Stage Group in the same manner as pN1a and b
            • This applies only to deposits within the lymphatic drainage of the tumor
          • Thus Tumor Deposits function as nodal metastases in staging when they are needed, but do not contribute to your node count
          • Circumscribed vs. stellate contour is no longer a criterion
        • Isolated tumor cells (ITC) in lymph nodes
          • Defined as either:
            • Detectable only by special techniques, or
            • If identified on H&E, ≤0.2 mm each cluster, even if multiple
          • Defined as negative for TNM purposes but indicate as appropriate if present:
            • pN0(i+) = morphologic or immunohistologic ITC present
            • pN0(m+) = molecular evidence of ITC
          • Report should state number of nodes with ITC and that the biologic significance is presently unknown
          • Routine use of special studies for detection of ITC is not currently recommended
          • Clusters of cells ≥0.2 mm but <2 mm are considered micrometastases and designated as positive for TNM
      • Problematic issues in M staging (see also miscellaneous issues below)
        • Isolated tumor cells (ITC) in distant organs (e.g. bone marrow)
          • Same definitions and recommendations as above for lymph nodes
        • The following all count as pM1
          • Involvement restricted to lymphatics in a distant organ
          • Involvement of non-regional lymph nodes
          • Involvement of peritoneal surface away from the leading edge of the tumor
          • Involvement of peritoneal surface of other intra-abdominal structures and organs
          • Peritoneal fluid positivity
        • Lateral spread or mucosal skip lesions in adjacent bowel sites does not count as pM1
        • Absence of carcinoma in any examined site does not constitute pM0
          • A 0 designation is only applicable to autopsies and is recorded as aM0
      • Miscellaneous issues
        • Post-neoadjuvant therapy excision specimens
          • TNM as usual but add prefix, e.g. ypT1
          • Size is based on dimensions of residual viable tumor, not the scar or mucin pools
          • Pools of mucin without epithelial cells are counted as negative at both the primary site and in lymph nodes (Shia 2011)
        • Residual tumor in patient at end of surgical excision
          • Either distant or at positive surgical margin
            • Positive margin generally is interpreted as indication of residual neoplasm but should be discussed with surgeon
            • Designate as R1 if microscopic
            • Designate as R2 if macroscopic
        • Recurrences
          • Coded as rpT1 etc.
          • Use usual TNM guidelines as for primary
          • Label recurrence as located in proximal segment of anastomosis, except when that is ileum following a right colon resection



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