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Sessile Serrated Polyp / Adenoma

Definition

  • Cytologically bland lesion of the large intestine composed of serrated glands with architectural disturbances of the deep crypts

Alternate/Historical Names

  • Serrated adenoma
  • Serrated adenoma type I
  • Serrated polyp with abnormal proliferation
  • Note: many gastroenterologists use the term "serrated polyp" to mean "sessile serrated adenoma/polyp
    • Be cautious about using this as a descriptive term even though hyperplastic polyps are serrated too

Covered separately

Background

  • Sessile serrated adenoma (SSA) and sessile serrated polyp (SSP) are equivalent terms
    • SSP appeals to those who note that the lesion lacks neoplastic cytologic features
    • SSA appeals to those who note the genetic abnormalities and association with carcinoma
  • Although not generally used as diagnostic criteria, characteristic location and genotypic abnormalities linking SSA/P to sporadic MSI high colorectal carcinoma (serrated carcinoma pathway) are the main justifications for defining this as a separate lesion from usual hyperplastic polyp

Diagnostic Criteria

  • Architectural disturbances of the bases of crypts is required
    • Marked dilation of crypts with flattened, horizontal bases
      • “L, inverted T, hockey stick or boot” shaped crypt bases
      • Moderate dilation without flattening is suggestive but not diagnostic
    • How many abnormal crypts are required for the diagnosis is currently in a state of flux
      • The WHO requires at least three adjacent abnormal crypts to make the diagnosis
      • A recent consensus conference recommends that a single abnormal crypt be sufficient for the diagnosis of SSA (Rex 2012)
  • The majority of crypts lack the uniform pattern of prolferative bases with regular maturation towards the surface
    • Serration is variably present throughout gland length
      • Usually exaggerated serration
      • Apical cytoplasm typically filled with microvesicular mucin
        • Goblet cells not conspicuous
    • Mature mucinous cells at base of crypts
    • May form serrations at base
    • Proliferative zone frequently displaced from base
      • Patchy proliferative zones can be seen at all levels
    • Crypt compartmentalization aberration (CCA) (Torlakovic 2008)
      • Abnormalities of location of proliferative and mature compartments within the length of the crypt
        • Encompasses most of the above criteria
      • May be visualized with Ki67 and CK20 stains
  • Lacks the architectural complexity of tubular adenomas
    • Most crypts extend from lumen to muscularis mucosae
  • Significant nuclear dysplasia is not a feature of pure sessile serrated adenoma
    • Nuclear stratification and loss of polarity are not seen
    • Nuclei may be mildly atypical with open chromatin and distinct nucleoli
    • Presence of dysplasia in a lesion with hyperplastic features suggests either
      • Traditional serrated adenoma if present throughout (see Differential Diagnosis at left), or
      • Sessile serrated adenoma with dysplasia if focal (see below)
  • Usually large (≥1 cm) sessile right sided lesions
    • Using strictly the histologic criteria above (and even genetic studies), many small left sided lesions could be considered sessile serrated adenoma
      • As sporadic MSI high colorectal carcinomas are unusual in the left colon, this has led to the suggestion that SSA/P should only be diagnosed on right sided lesions ≥1 cm in size (Chung)
      • We suggest that lesions that are left sided and <1cm should be designated hyperplastic polyp unless they unequivocally and fully fulfill all the criteria above for SSA/P
    • Left sided lesions should raise the possibility of hyperplastic polyp or traditional serrated adenoma
  • In our experience, nearly all serrated lesions >0.5 cm proximal to the splenic flexure are SSA
  • There is poor interobserver agreement in the recognition and diagnosis of SSA by both endoscopists and pathologists (Hetzel 2010)
    • The criteria for the recognition of SSP/A can be expected to be refined in the future
  • "Indeterminate polyp (SSA vs HP)" is used for serrated polyps with indeterminate or mixed features, for example:
    • 90% of crypts are straight and narrow but one crypt is dilated and flattened
    • Several of the crypts are moderately dilated but none are markedly dilated with flattening
    • A <0.5 cm rectosigmoid polyp with one dilated, flattened crypt base
    • A >1 cm right sided serrated polyp with only one margnally dilated and flattened gland
    • Any poorly oriented specimen in which the bases of the crypts cannot be well evaluated
      • (Rectosigmoid serrated polyps <0.5 cm are usually considered to be HPs even if the bases are not well seen as long as there is no clear dilation present)
  • Sessile serrated adenoma may be associated with dysplasia or carcinoma
    • Discrete foci of dysplasia or carcinoma may develop
      • Dysplastic foci resemble classic tubular adenomas
        • Many were historically called mixed hyperplastic-adenomatous polyps
          • Polyps representing a true "collision" of a hyperplastic and an adenomatous polyp, especially in the right colon, must be rare
        • May show usual low grade dysplasia or high grade dysplasia
        • Carcinomas are frequently invasive into submucosa even when small
    • Dysplastic and carcinomatous foci may be MSI high
      • About half of studied cases show loss of MLH1 and PMS2
    • Adjacent SSA lacks both cytologic dysplasia and MSI
    • Clinical and morphologic evidence suggests that the development of dysplasia may herald rapid development of carcinoma (Sheridan 2006)
  • Serrated polyposis (hyperplastic polyposis) (covered separately)
    • Any of the following:
      • ≥20 serrated polyps, any kind or size, anywhere in colorectum
        • Some investigators prefer ≥30
      • ≥5 serrated polyps proximal to sigmoid
        • ≥2 of which are ≥1 cm
      • Any serrated polyp proximal to sigmoid in a first degree relative of a patient with serrated polyposis
    • It is now apparent that many of the polyps of this entity are SSA
  • SSP/A and hyperplastic polyps may be associated with perineurioma or prominent submucosal fat
    • No clinical significance

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

Original posting/last update : 1/31/10, 7/15/11, 11/11/11, 6/11/12, 3/20/13, 8/19/13

Supplemental studies

Immunohistology

  • We do not use stains for the identification of SSA/P
  • B- Catenin (nuclear staining)
    • 41%  of SSA, 0% in HP
  • CDX2
    • Labels crypt bases in SSAs, and extends to crypt surface in HPs
  • MUC6 positive
    • At least focal staining of basal crypts in 100% of cases
    • Most staining seen in straight, regular crypts
    • Occasional staining in horizontal or dilated bases of crypts
    • Only rare staining in branched or basally serrated crypts
    • (Based on one report so far by Owens 2008, but Gibson 2011 finds considerable overlap with hyperplastic polyps)

      Ki67 CK20
    Normal mucosa Limited to basal ¼ Limited to surface
    Hyperplastic polyp Expanded to basal 1/3-1/2 Expanded to luminal 1/2-2/3
    SSA Patches of staining at all levels Patches of staining at all levels
    TSA Mainly localized to ectopic crypts Irregular staining of luminal surface
    Usual adenoma High overall Random
    (based on Torlakovic 2008)
  • Clear cell variant reported to be positive for hepatocyte nuclear factor-1Beta but sensitivity and specificity do not appear to be useful for diagnosis

Genetic analysis

  • Genotype  is not useful for diagnosis but supportive of separate pathways for TSA and SSA
      Traditional Serrated Adenoma Sessile Serrated Polyp / Adenoma
    KRAS Majority (~80%) Minority (~0-10%)
    BRAF Minority (~20%) Majority (~75%)
    p53 Infrequent Infrequent
    APC Infrequent Infrequent
    MSI Can lead to MSI-L or MSS Serrated adenocarcinoma (SAca) Can lead to MSI-H or L SAca
    CpG island methylator phenotype (CIMP) Primarily MGMT involvement in SAca Primarily MLH1 involvement in SAca
    (based on Makinen 2007 and O’Brien 2006)
  • Genotype suggests SSA may be a precursor of sporadic MSI high colorectal carcinomas (serrated carcinoma pathway)
    • BRAF mutations and DNA hypermethylation in both
    • Large (≥1 cm) SSA share marked predominance of right colon location with sporadic MSI high carcinomas
    • Same genotype is frequent in small left sided lesions demonstrating some but not all of the histologic features of SSA
      • This suggests that size ≥1 cm and right side location should be required for the diagnosis to maintain its relevance to the serrated carcinoma pathway

Differential Diagnosis

Hyperplastic Polyp Sessile Serrated Polyp / Adenoma
≥90% of bases of crypts straight, regular, narrow, frequently pointed, no dilated flattened bases 1 to 3 crypts required with basal dilation and flattening, bases boot or inverted T shaped, <90% of bases are narrow
Proliferative zone reliably restricted to base Bases contain mature mucous cells
Serrations and CK20+ maturation limited to luminal 2/3 of crypt Serrations and CK20+ patches of maturation can be seen at all levels
Predominantly left sided and small Predominantly right sided and frequently ≥1 cm
Polyps with mixed or intermediate features are designated indeterminate (e.g. between 50-90% narrow crypts and/or <3 flat crypt bases)

 

Traditional Serrated Adenoma Sessile Serrated Polyp / Adenoma
Cytologic dysplasia throughout Cytologic dysplasia, if present, is a focal lesion
Multiple short crypts, right angled, not reaching the muscularis mucosae Basal dilation and flattening, boot or inverted T shaped, but overall, crypts are vertically arranged and span entire thickness of mucosa
Serration predominantly due to multiple adjacent ectopic crypts Serration predominantly due to exaggerated apical cytoplasm
Proliferation (Ki67) largely restricted to ectopic crypts Patches of proliferation can be seen at all levels
Predominantly polypoid and left sided Sessile and predominantly right sided

 

Usual Colorectal Adenoma Sessile Serrated Polyp / Adenoma
Cytologic dysplasia throughout Cytologic dysplasia, if present, is a focal lesion
Typically complex architecture Basal dilation and flattening, boot or inverted T shaped, but overall, crypts are vertically arranged and not complex
Lacks serrations Prominent serrations

Clinical

  • Primarily occur in adults
    • Age range of patients with SSA and foci of dysplasia or carcinoma 54-87 years
  • May be the principal source of sporadic MSI high adenocarcinomas
    • They share DNA hypermethylation and BRAF mutations
  • Complete removal is recommended if possible, especially for:
    • Lesions >1 cm
    • Lesions with focal dysplasia
  • Following resection, patients are typically followed up in a similar manner as those with a usual type tubular adenoma (Huang 2011, Snover 2011)
      Number and Size Surveillance Interval
      <3 polyps, all <1 cm 5 years
      ≥3 polyps or any one ≥1 cm 3 years
    • If dysplasia is present, polyp must be completely removed
      • May require both colonoscopic and pathologic evaluation
      • May require immediate repeat endoscopy to assess adequacy
      • Surveillance colonoscopy in 1 to 3 years
    • Above intervals may be shortened in cases with family history or arising < age 50
  • See serrated adenomatous polyposis if numerous

Bibliography

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