Small intestine & ampulla
Carcinoma
Adenocarcinoma-small intestine


Minor changes: 16 February 2021

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PubMed Search: adenocarcinoma small intestine [title] pathology review[ptyp]

See also: Ampullary adenocarcinoma

Krutika S. Patel, M.B.B.S., M.D.
Annika L. Windon, M.D.
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Cite this page: Patel KS, Windon AL. Adenocarcinoma-small intestine. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/smallboweladenocarcinoma.html. Accessed March 9th, 2021.
Definition / general
  • Nonampullary primary malignant epithelial neoplasm of the small intestine showing glandular differentiation
Essential features
  • Small bowel adenocarcinomas are histologically very similar to colorectal adenocarcinomas, with complex glandular formations
  • Gross identification of the tumor epicenter is essential in duodenal tumors that involve the ampulla to exclude a primary ampullary adenocarcinoma or extension from pancreatic or bile duct malignancies
  • Adenocarcinomas can arise in a variety of inflammatory, autoimmune and familial conditions
ICD coding
  • ICD-O: 8140/3 - Adenocarcinoma, NOS
  • ICD-10:
    • C17.0 - Malignant neoplasm of duodenum
    • C17.1 - Malignant neoplasm of jejunum
    • C17.2 - Malignant neoplasm of ileum
    • C17.3 - Meckel diverticulum, malignant
    • C17.8 - Malignant neoplasm of overlapping sites of small intestine
    • C17.9 - Malignant neoplasm of small intestine, unspecified
  • ICD-11: 2B80.20 - Adenocarcinoma of small intestine, site unspecified
Epidemiology
Sites
  • Most common locations include the periampullary region of the duodenum (50 - 64%) followed by the jejunum (18 - 20%) and finally the ileum (15%) (Ann Surg 2009;249:63, Cancer 1999;86:2693)
  • Patients with Crohn's disease have adenocarcinomas in a predominantly ileal location
Etiology
Clinical features
  • Patients are typically asymptomatic or exhibit nonspecific symptoms in the early stages of disease
  • Some symptoms include abdominal pain, anemia, GI bleeding, weight loss, nausea and vomiting
  • Intestinal obstruction may develop in ileal and jejunal cancers as the disease progresses, necessitating surgical intervention (Cancer 2004;101:518)
Diagnosis
  • Initial workup for primarily duodenal adenocarcinomas includes esophagogastroduodenoscopy (EGD) with endoscopic ultrasound (EUS) and biopsy for diagnosis and staging (J Natl Compr Canc Netw 2019;17:1109)
  • CT or MRI can be used to evaluate local tumor invasion and assess for metastatic disease
  • Balloon assisted and video capsule endoscopy allow for a detailed examination of entire small bowel if nonobstructed (J Natl Compr Canc Netw 2019;17:1109)
Laboratory
Radiology description
  • Distal adenocarcinomas may manifest as annular narrowing with abrupt concentric or irregular overhanging edges, a discrete tumor mass or an ulcerative lesion, while duodenal adenocarcinomas tend to be papillary or polypoid on CT scan (Radiographics 1998;18:379)
Radiology images

Images hosted on other servers:

Infiltrating duodenal mass with luminal narrowing

Large bulky mass of distal small bowel

Thickening of ileum with Crohn's and adenocarcinoma

Prognostic factors
Case reports
Treatment
  • Surgery is the mainstay of treatment with regional lymph node removal for stage I - III disease (J Natl Compr Canc Netw 2019;17:1109)
    • Segmental resection is usually performed for jejunal, ileal and some duodenal primaries; pancreaticoduodenectomy may be indicted for some duodenal tumors that invade the pancreas or ampulla
  • Adjuvant chemotherapy and radiation have mixed, limited results and are still being evaluated
Clinical images

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Suspicious growth with jejunal stricture

Near obstructing mass distal to duodenal bulb

Irregular and ulcerated jejunal lesion (capsule endoscopy)

Gross description
  • A substantial number of duodenal adenocarcinomas show plaque-like growth but they can also present with polypoid growth in approximately 33% of cases (Mod Pathol 2017;30:255)
  • Jejunal and ileal adenocarcinomas present as large, annular, constricting apple core lesions with circumferential bowel wall involvement (Cancer 1975;36:1876)
  • Gross appearance can also be influenced by background mucosa in adenocarcinomas that arise in inflammatory conditions (Crohn's disease), polyposis syndromes or intestinal duplications (Virchows Arch 2018;473:265)
  • Frequent serosal involvement or extension into other organs is not uncommon
Gross images

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Jejunal
submucosal tumor
with overlying
normal mucosa

Jejunal tumor invading adherent transverse colon

Ileal tumor with ulceration

Frozen section description
  • Intraoperative consultation (gross or microscopic) may be requested to evaluate margin status for pancreaticoduodenectomy or segmental resection specimens
  • In patients undergoing surgery for inflammatory bowel disease, intraoperative findings concerning for malignancy (i.e. abscess formation, strictures, fistula tracts, perforation) may prompt a frozen section analysis
  • Microscopic features compatible with malignancy include complex glandular architecture, invasion, desmoplastic reaction, cellular and nuclear pleomorphism, loss of epithelial polarity and luminal necrosis
Frozen section images

Contributed by Krutika S. Patel, M.B.B.S., M.D. and Annika L. Windon, M.D.

Invasive jejunal adenocarcinoma

Microscopic (histologic) description
  • Adenocarcinomas, not otherwise specified, are characterized by columnar epithelial cells with elongated, pseudostratified nuclei forming complex glandular architecture with nuclear pleomorphism, loss of epithelial polarity and luminal dirty necrosis
  • Additional histologic characterizations include mucinous adenocarcinoma (> 50% mucin), poorly cohesive cell carcinoma (with or without signet ring cells), medullary carcinoma, adenosquamous carcinoma (squamous and adenocarcinoma components), undifferentiated carcinoma or mixed neuroendocrine nonneuroendocrine neoplasm (MiNEN)
  • Signet ring cell / poorly differentiated carcinomas, presenting as late stage disease, are more common in Crohn's disease than as de novo small intestinal carcinomas (Inflamm Bowel Dis 2005;11:828)
  • Lynch syndrome associated small intestinal adenocarcinomas show similar features to their colorectal counterparts; tumors often show a high number of intratumoral lymphocytes and Crohn's-like lymphoid reaction (Gastroenterology 2005;128:590)
  • Preexisting adenoma is present in the majority of proximal tumors but sometimes cannot be identified in large distal small intestinal adenocarcinomas due to tumor overgrowth
  • Determining a background of Crohn's disease can sometimes be difficult because the histologic characteristics of Crohn's disease such as transmural inflammation can be caused by the tumor; oftentimes patients present without an established diagnosis of inflammatory bowel disease (J Crohns Colitis 2014;8:19)
Microscopic (histologic) images

Contributed by Krutika S. Patel, M.B.B.S., M.D. and Annika L. Windon, M.D.

Well differentiated adenocarcinoma

Moderately and poorly differentiated adenocarcinoma

Mucinous adenocarcinoma


Higher stage carcinomas

Ileal adenocarcinoma arising in Crohn's disease


Signet ring adenocarcinoma

Adenocarcinoma arising in a tubulovillous adenoma

Lymphovascular invasion

Perineural invasion


Lymph node metastasis

Cytokeratin 7

Cytokeratin 20

Cytology description
  • Cytopathologic analysis (FNA or brushing) is rarely used in the small intestine, except for occasionally diagnosing duodenal tumors in the ampullary or pyloric region
  • Malignant cells are arranged in loose 3 dimensional clusters of crowded epithelial cells without goblet cells
  • Alternatively, many single atypical cells with mitoses, increased nuclear to cytoplasmic ratio and marked nuclear pleomorphism are present
  • Reference: J Gastrointest Oncol 2012;3:285
Cytology images

Images hosted on other servers:

Duodenal adenocarcinoma and normal mucosa

Positive stains
Negative stains
Molecular / cytogenetics description
  • 2 well defined molecular pathways are reported in small bowel adenocarcinomas, similar to colorectal adenocarcinoma tumorigenesis
  • First pathway includes APC, KRAS, TP53 (Int J Cancer 1997;70:390)
    • Prevalence of mutations in KRAS is similar between colorectal and small bowel adenocarcinomas, typically 30 - 60%
    • Prevalence of TP53 mutations is also comparable, 20 - 50%
    • Fewer than 20% of small bowel adenocarcinomas have mutations in APC, in contrast to 80% of colorectal carcinomas
  • Second pathway includes inactivation of mismatch repair (MMR) genes, either by germline mutations (Lynch syndrome) or promoter hypermethylation (sporadic), which occurs in up to 38.5% of small bowel adenocarcinomas (Clin Cancer Res 2020 Nov 16 [Epub ahead of print])
  • A number of other genetic alterations have been reported in small bowel adenocarcinomas, including mutations in CTNNB1, SMAD4, IDH1, CDH1, KIT, FGFR2, FLT3, NPM1, PTEN, MET, AKT, RET, ERBB2 (HER2), NOTCH1 and ERBB4 (Gut 2002;50:218, Scand J Gastroenterol 2004;39:748, Int J Cancer 1997;70:390, Am J Gastroenterol 2000;95:1576, Oncotarget 2015;6:20863)
Sample pathology report
  • Small bowel, duodenum, biopsy:
    • Invasive moderately differentiated adenocarcinoma arising in a tubular adenoma; lymphovascular invasion is present (see comment)
    • Comment: Mucosal colonization from an ampullary, biliary or pancreatic origin must be excluded. Clinical and radiographic correlation is recommended. Immunohistochemical testing for mismatch repair (MMR) proteins shows intact nuclear expression of MLH1, PMS2, MSH2, MSH6 in the tumor cells. Background nonneoplastic tissue / internal control shows intact nuclear expression. Based on these results, there is low probability of MSI-H (MSI = microsatellite instability; H = high).
Differential diagnosis
  • Metastatic adenocarcinoma (e.g. colon, breast, ovary, lung):
    • Presence of preexisting adenoma or dysplasia supports a small bowel primary
    • Immunohistochemistry is primarily used to exclude metastatic disease (CK7+, CK20- might be helpful to rule out metastatic colon adenocarcinomas)
  • Adenoma with high grade dysplasia:
    • Differentiating prolapse from invasion around ampulla can be challenging
    • Presence of desmoplasia and single cells supports invasion
  • Ectopic pancreas:
    • Presence of only ducts in a small biopsy specimen may be misinterpreted as neoplasm
  • Endometriosis:
    • Presence of endometrial stroma and ciliated epithelium helps to make this diagnosis
  • Ampullary adenocarcinoma:
    • Advanced duodenal carcinoma may extend to involve the ampulla but only those centered on or circumferentially surrounding the ampulla are regarded as ampullary carcinomas
    • Careful gross examination to assess the tumor epicenter helps in distinguishing ampullary / periampullary primary from duodenal primary
Board review style question #1

Which of the following syndromes is most associated with this tumor, arising in the small bowel?

  1. Budd-Chiari syndrome
  2. Cronkhite-Canada syndrome
  3. Hereditary mixed polyposis syndrome
  4. Juvenile polyposis syndrome
  5. Peutz-Jeghers syndrome
Board review style answer #1
E. Peutz-Jeghers syndrome. This image illustrates a well differentiated adenocarcinoma of the small bowel. Patients with Peutz-Jeghers syndrome have a 1.7 - 13% lifetime risk of developing small bowel adenocarcinoma. It arises most commonly in jejunum and ileum and can arise from hamartomatous or adenomatous polyps.

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Reference: Adenocarcinoma-small intestine
Board review style question #2
Which of the following statements is true regarding development of small bowel carcinoma in patients with Crohn's disease?

  1. Carcinoma that develops in Crohn's disease is usually seen in older individuals in their 80s
  2. Carcinoma that presents in Crohn's disease tends to present as early stage disease
  3. Carcinomas in Crohn's disease usually are well differentiated
  4. Risk of developing carcinoma is related to duration of disease
  5. There is no increased risk when compared to the general population
Board review style answer #2
D. Risk of developing carcinoma is related to duration of disease. The cumulative risk of small carcinoma increases after 10 years, with an absolute risk of 2.2% at 25 years in Crohn's disease. Risk increases with longstanding ileal inflammation, younger than average age of onset, previous immunosuppressant use, male sex, strictures and fistula formation. Signet ring cell / poorly differentiated carcinomas, presenting as late stage disease, are more common in Crohn's disease than as de novo small intestinal carcinomas.

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Reference: Adenocarcinoma-small intestine
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