Colon

Carcinoma

Serrated adenocarcinoma (SAC)


Editorial Board Member: Debra L. Zynger, M.D.
Deputy Editor-in-Chief: Catherine E. Hagen, M.D.
David Hernandez Gonzalo, M.D.
Michael Feely, D.O.

Last author update: 21 January 2022
Last staff update: 21 January 2022

Copyright: 2019-2023, PathologyOutlines.com, Inc.

PubMed Search: Serrated adenocarcinoma[TIAB]

David Hernandez Gonzalo, M.D.
Michael Feely, D.O.
Page views in 2022: 2,281
Page views in 2023 to date: 176
Cite this page: Hernandez Gonzalo D, Feely M. Serrated adenocarcinoma (SAC). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colontumorserratedadeno.html. Accessed February 3rd, 2023.
Definition / general
  • Morphologic variant first recognized in the fourth edition of WHO; accounts for approximately 9.1% of all colorectal carcinomas (Hum Pathol 2010;41:1359)
Essential features
  • Likely arises from malignant transformation of some sessile serrated polyps and traditional serrated adenomas (Mod Pathol 2019;32:1390)
  • Can be diagnosed on histologic grounds alone without having to resort to recognition of residual serrated lesion
  • Considered an end point carcinoma of the so called serrated pathway that can be reliably identified by morphologic features
  • Most carcinomas arising from serrated precursors do not represent serrated adenocarcinomas (Mod Pathol 2019;32:1390)
ICD coding
  • ICD-O: 8213/3 - serrated adenocarcinoma
Epidemiology
Sites
  • More often proximal colon than conventional carcinoma, only in men (this association is not observed in women) (Hum Pathol 2010;41:1359)
Clinical features
  • More frequently with lymph node metastases (51.8%) than conventional carcinomas (39.9%) (Hum Pathol 2010;41:1359)
  • Node positive serrated adenocarcinomas have worse survival than node positive conventional carcinomas; left sided ones have the worst prognosis (Hum Pathol 2010;41:1359)
  • Synchronous carcinomas are more often found in serrated adenocarcinoma than in conventional carcinoma (12.9% versus 3%) (Hum Pathol 2010;41:1359)
  • Frequently encountered in more advanced stages than conventional carcinomas
  • Less favorable 5 year survival than conventional carcinoma (especially left sided) (Hum Pathol 2010;41:1359)
Diagnosis
  • Generally discovered on colonoscopy and confirmed on biopsy
Prognostic factors
Case reports
Treatment
  • Surgical excision, with adjuvant chemotherapy for advanced / metastatic cases
  • No treatment related differences between serrated adenocarcinoma and conventional carcinoma
  • Treatment based on whether they are microsatellite stable or microsatellite instable (PD1 inhibitors but not 5FU are potential therapies if instable) and BRAF / KRAS / NRAS status (EGFR inhibitors not an option if any are mutated)
Clinical images

Contributed by David Hernandez Gonzalo, M.D. and Michael Feely, D.O.

Colonoscopy

Microscopic (histologic) description
  • Sawtoothed epithelial serrations
  • Abundant clear or eosinophilic cytoplasm
  • Vesicular nuclei with chromatin condensation at the nuclear envelope
  • Absence of necrosis or < 10% of the total surface area
  • Mucin production (cell balls and papillary rods in mucinous areas of tumor)
  • A serrated polyp with or without dysplasia can sometimes be seen around its edges (Histopathology 2007;50:131)
Microscopic (histologic) images

Contributed by David Hernandez Gonzalo, M.D. and Michael Feely, D.O.

Precursor lesions

Adjacent epithelium

Tumor and depth

Architectural changes

Cytologic changes

Positive stains
Molecular / cytogenetics description
  • KRAS mutations (45%)
  • BRAF mutations (33%)
  • Microsatellite instable - high (18.9%)
  • Microsatellite stable or microsatellite instable - low (81.1%) (Histopathology 2011;58:679)
Sample pathology report
  • Colon, transverse, resection:
    • Invasive serrated adenocarcinoma (see synoptic report)
    • 54 lymph nodes, negative for carcinoma (0/54)
Differential diagnosis
Board review style question #1

Which of the following is true about this variant of colorectal adenocarcinoma?

  1. Diagnosis requires the presence of a serrated polyp adjacent to the serrated adenocarcinoma
  2. Extensive necrosis is usually present
  3. Most carcinomas arising from serrated precursors have this morphology
  4. This variant accounts for approximately 9.1% of all colorectal carcinomas
Board review style answer #1
D. Serrated adenocarcinoma accounts for approximately 9.1% of all colorectal carcinomas. A precursor serrated lesion is not always identified (A). There is no or little necrosis (< 10%) in serrated adenocarcinoma (B). Most carcinomas arising from serrated polyps have a microsatellite instable - high histology (such as medullary, mucinous, signet ring cells, lack of dirty necrosis, tumor infiltrating lymphocytes) (C).

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Reference: Serrated adenocarcinoma
Board review style question #2
Which of the following is true regarding the molecular aspect of serrated adenocarcinoma?

  1. Chemotherapy regimens are currently different for serrated adenocarcinoma compared to conventional adenocarcinoma
  2. GNAS mutant serrated adenocarcinoma has a better prognosis
  3. KRAS or BRAF mutations are present in over 75% of cases
  4. Most serrated adenocarcinomas are microsatellite instable - high
Board review style answer #2
C. Mutually exclusive mutations in KRAS or BRAF are present in over 75% of cases. There are no treatment related differences between serrated adenocarcinoma and conventional carcinoma (A). GNAS mutant serrated adenocarcinoma appears to be related to a poor prognosis and advanced stage (B). Microsatellite instability - high is only seen in 18.9% of serrated adenocarcinoma cases (D). Remember, in general, a serrated pathway can lead to microsatellite instable - high, microsatellite instable - low or microsatellite stable cancer.

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Reference: Serrated adenocarcinoma
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