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Adenoma and Adenocarcinoma of the Small Intestine

Definition

  • Benign and malignant epithelial neoplasms arising in the ampulla of Vater, duodenum, jejunum or ileum

Covered separately:

  • Endocrine neoplasms of the duodenum (including proximal jejunum) and ileum
  • Small cell (undifferentiated) carcinoma of the GI tract

Diagnostic Criteria

  • Adenomas and adenocarcinomas of the small intestine are rare
    • Approximately half occur in the duodenum
      • Many of these are ampullary
    • Metastases are more common than primary carcinomas
  • Many adenomas and carcinomas are associated with defined syndromes and diseases (see full descriptions)
  • Same histologic features as colorectal adenomas and adenocarcinomas
    • Rare mixed types have been reported
      • Adenosquamous
      • Tripartite (endocrine, squamous and adenocarcinoma)
  • Also rarely reported in the duodenum
    • Hyperplastic polyp
    • Serrated adenoma

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

    Original posting/updates : 11/29/09, 8/21/10, 2/12/11

Supplemental studies

Immunohistology

  Small Intestine Adenocarcinoma Small Intestine Normal Mucosa
MUC1 52-82% Negative vs basal staining
MUC5AC 28-54% Negative, but goblets and gastric metaplasia positive

 

  Small Intestine Adenocarcinoma Colorectal Adenocarcinoma
Racemase 5% 62%
CK7 100% 5-10%
CK20 67% 95%
Small intestinal mucin antigen (SIMA) 50% 94%
Villin 67% 98%
CDX2 60% 70-98%

Differential Diagnosis

  • Principal differential is from colorectal adenocarcinoma
    • Because of the rarity of small intestinal carcinomas, most questionable cases should be considered colorectal
      • Reports from Chen and Zhang suggest that immunohistologic stains may be useful:
        Favors Small Intestine

        Favors Large Intestine

         

        Racemase positive

        CK7 positive

        CK7 negative

        CK20 negative

         

        SIMA negative

         

        Villin negative

         

        CDX2 negative

         

        Note that the opposite result is not always discriminatory; see Special Studies for complete staining results
  • Misplaced glands in a Peutz-Jeghers polyp must always be ruled out, especially in a young patient or a cytologically bland tumor
    Peutz-Jeghers Polyp with Misplaced Glands Small Intestinal Adenocarcinoma
    Overlying typical hamartomatous polyp Overlying adenoma may be present
    Usually cytologically bland Usually cytologically malignant
    Glands may permeate muscle but no desmoplastic response Desmoplastic response usually present
    Lamina propria may be retained around entrapped glands No retained lamina propria around infiltrating glands
    Glands frequently have a mixed population of cell types - mucus, goblet, paneth cells Monomorphic population
  • Expression of MUC1 or MUC5AC has been suggested as favoring carcinoma over normal small intestinal mucosa (Zhang 2007)
    • One report, however, describes basal staining of normal mucosa with MUC1 (Matsubayashi)
    • MUC5AC stains normal goblet cells and gastric metaplasia
    • Ultimately, the diagnosis of carcinoma must be made on morphologic grounds
      • Positivity may suggest rebiopsy in a marginal specimen
    • See Special Studies for complete staining results

Grading / Staging

Grading

  • WHO accepts grading simply as Low vs. High grade
  • CAP protocol requires well, moderately, poorly differentiated and undifferentiated designations
    • Low grade ≥50% gland forming
      • Well differentiated
        • >95% gland forming
      • Moderately differentiated
        • 50-95% gland forming
    • High grade <50% gland forming
      • Poorly differentiated
        • 5-49% gland forming
        • Signet ring (>50% of cells signet ring)
      • Undifferentiated
        • <5% gland forming

Staging

  • Use TNM staging:
    • Ampulla and peri-ampullary is different from rest of small intestine including duodenum
      Tis Carcinoma in situ (no lamina propria invasion)
      T1 Confined to ampulla and sphincter of Oddi
      T2 Invasion of duodenal wall
      T3 Invasion of pancreas
      T4 Peripancreatic soft tissue or other organs/structures
      Size of tumor is not included in TNM but is predictive
      • <2.5 cm has 85% 5 year survival
      • ≥2.5 cm has 20% 5 year survival
    • Small intestine other than ampulla:
      Tis Carcinoma in situ (no lamina propria invasion)
      T1 Lamina propria or submucosal invasion
      T2 Invasion of muscularis propria
      T3 Through muscularis propria ≤2 cm into subserosa, mesentery or retroperitoneum
      T4 Invasion >2 cm, serosal perforation, or into other organs/tissues including pancreas
  • For ampulla, regional nodes include:
    • Superior and inferior to head and body of pancreas
    • Anterior and posterior pancreaticoduodenal
    • Proximal and superior mesenteric
    • Pyloric, pancreaticoduodenal, common bile duct or pericholedochal
    • Hepatic artery nodes, infrapyloric, subpyloric
    • Celiac, retroperitoneal, and lateral aortic
  • Miscellaneous TNM issues
    • 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 number of primary lesions e.g. pT3(m)
    • Post-neoadjuvant therapy excision specimens
      • TNM as usual but add prefix, e.g. ypT1
      • Pools of mucin without epithelial cells are counted as negative at both the primary site and in lymph nodes
    • 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

Bibliography

  • Hamilton SR, Aaltonen LA eds. Pathology and genetics of tumours of the digestive system. World Health Organization classification of tumours, Vol. 2. Lyon: IARC Press 2000.
  • Chen ZM, Wang HL. Alteration of cytokeratin 7 and cytokeratin 20 expression profile is uniquely associated with tumorigenesis of primary adenocarcinoma of the small intestine. Am J Surg Pathol. 2004 Oct;28(10):1352-9.
  • Zhang MQ, Lin F, Hui P, Chen ZM, Ritter JH, Wang HL. Expression of mucins, SIMA, villin, and CDX2 in small-intestinal adenocarcinoma. Am J Clin Pathol. 2007 Nov;128(5):808-16.
  • Chen ZM, Ritter JH, Wang HL. Differential expression of alpha-methylacyl coenzyme A racemase in adenocarcinomas of the small and large intestines. Am J Surg Pathol. 2005 Jul;29(7):890-6.
  • Gürbüz Y, Klöppel G. Differentiation pathways in duodenal and ampullary carcinomas: a comparative study on mucin and trefoil peptide expression, including gastric and colon carcinomas. Virchows Arch. 2004 Jun;444(6):536-41.
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  • Matsubayashi H, Watanabe H, Yamaguchi T, Ajioka Y, Nishikura K, Kijima H, Saito T. Differences in mucus and K-ras mutation in relation to phenotypes of tumors of the papilla of vater. Cancer. 1999 Aug 15;86(4):596-607.
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  • Roche HJ, Carr NJ, Laing H, Bateman AC. Hyperplastic polyps of the duodenum: an unusual histological finding. J Clin Pathol. 2006 Dec;59(12):1305-6.
  • Rubio CA. Serrated adenoma of the duodenum. J Clin Pathol. 2004 Nov;57(11):1219-21.
  • Chang HK, Yu E, Kim J, Bae YK, Jang KT, Jung ES, Yoon GS, Kim JM, Oh YH, Bae HI, Kim GI, Jung SJ, Gu MJ, Kim JY, Jang KY, Jun SY, Eom DW, Kwon KW, Kang GH, Park JB, Hong S, Lee JS, Park JY, Hong SM; Korean Small Intestinal Cancer Study Group. Adenocarcinoma of the small intestine: a multi-institutional study of 197 surgically resected cases. Hum Pathol. 2010 Aug;41(8):1087-96
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