Small intestine cancer pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Qurrat-ul-ain Abid, M.D.[2], Parminder Dhingra, M.D. [3]

Overview

Adenocarcinoma is the most common sub-type of small intestine cancer. Second most common is carcinoid tumor. Adenocarcinomas may be polypoid, infiltrating or they appear as annular constricting lesions in small intestine. On gross pathology, napkin ring appearance or polypoidal fungatining mass are characteristic findings of small intestine cancer. Carcinoid tumors of the smalls intestine are mostly associated with malignant tumors of the other sites. Gastrointestinal stromal tumors (GISTs) are the most common benign tumors of the gastrointestinal (GI) tract. Small intestinal lymphomas are of low-grade on histology and arise from mucosal-associated lymphoid tissues (MALT).

Pathophysiology

  • Small intestinal cancers is a rare condition and information on its pathophysiologic mechanisms is limited.
  • Studies are being conducted to evaluate the association of small intestinal cancers with environmental risk factors.[1]
  • Pathophysiology of small intestinal cancers depends on the histological subtype.
  • Duodenal tumors are more common than the tumors of jejunum and illeum.[2]
  • Adenomas arises commonly in the proximal small intestine (duodenum) whereas lymphomas arises more distally (jejunum and ileum).[3]
  • Low susceptibility of the small intestine to malignant changes may be explained as follows:
    • Short exposure of the mucosa to carcinogens due to rapid transit of contents
    • Liquid nature of the contents and less mucosal irritation
    • Low bacterial load
    • High concentration of lymphoid tissue

Adenocarcinoma

  • Adenocarcinoma are most common neoplasm of small bowel.
  • Males are more predisposed to risk of having adenocarcinoma of small intestine.[4]
  • Adenocarcinoma of small intestine is more common in patients with colorectal cancer, suggesting a common pathogenetic mechanism.
  • Adenocarcinoma may develop from malignant changes in the polyps of small intestine.[5][6]
  • Long standing Crohn's disease is known as a risk factor of small intestine cancer.[7]
  • Certain hereditary conditions with intestinal polyps such as adenomatous polyposis coli (ACP) predisposes to adenocarcinoma of small intestine.
  • Adenocarcinoma are more common in duodenum.
  • Development of adenocarcinoma in duodenum may be explained by vigorous exposure of that part of intestine to different carcinogens, which gets diluted in the latter part of intestine.[8]

Carcinoid Tumors

Mucosa- associate lymphoid tissue Lymphoma (Non-Hodgkin)

  • Small intestinal lymphomas are of low-grade on histology and arise from mucosa-associated lymphoid tissues (MALT) present in ileum and jejunum.
  • Sometimes distinct clinicopathologic entities arise from these mucosal-associated lymphoid tissues (MALT), such as immunoproliferative small intestinal disease, primary intestinal T-cell lymphoma, and multiple lymphomatous polyposis.[12]
  • Lymphoma may be present as a primary tumor of small intestine or may be a part of some systemic disease.
  • After stomach, small intestine is the most common extra-nodal site of presentation of non-Hodgkin lymphomas and it represents 4% to 20% of all the non-Hodgkin lymphomas.
  • The diagnosis of small intestinal lymphoma can be made using following criteria:[13][14]

Small intestinal stromal tumors (GISTs)

  • GISTs are the most benign tumors of GIT and rarely have malignant potential.
  • They typically develop in older age.
  • Small intestinal GIST are second most common stromal tumors (20-25%) of GI tract only after stomach GISTs (60-70%). Colon and rectum GIST (5%) and esophageal GIST (<5%) forms the remaining.
  • One of the subset of intestinal stromal cell tumors is the gastrointestinal autonomic nerve tumors (GANTs). Stromal tumors may be differentiated from other tumors of small intestine by their cell specific markers.
  • GISTs express following stromal cell markers:[15]
    • 70% of GISTs are positive for CD34
    • 20–30% are positive for smooth muscle actin (SMA)
    • 10% are positive for S100 protein
    • <5% are positive for desmin

Genetics

Cancer of small intestine may arise sporadically or they may be associated with genetic diseases.

Adenocarcinoma:

Carcinoid Tumors:

Non-Hodgkin Lymphoma:

  • Lymphomas of small intestine have no established genetic predisposition.

Small intestinal stromal tumors (GISTs):

Associated Conditions

Some GIT disorders such as inflammatory diseases of GIT may predispose to malignancy. Some of the associations include:[22]

Adenocarcinoma:

  • Adenocarcinoma of the smalls intestine originate locally or may be associated with malignant tumors of other sites.
  • Rarely, it may develop malignant changes in polyps present in the small intestine.
  • Dietary factors, tobacco, and obesity may also play a role in malignant transformation.[23][24][25][26][27][28]

Carcinoid Tumors:

Non-Hodgkin Lymphoma:

Small intestinal stromal tumors (GISTs):

  • These tumors are associated with older age and are rare before the age 40 years[35][36][37]
  • They can be sporadic or inherited.

Gross Pathology

Tumor type Gross findings Gross pathology
Adenocarcinoma
Adenocarcinoma of the small intestine. Endoscopic image of adenocarcinoma of duodenum. Source: Wikimedia commons
Carcinoid Tumors
Carcinoid tumor of small intestine invading plica. circularisSource: Wikimedia commons
Multiple Carcinoid tumor of the small intestine Source: Wikimedia commons
Mucosa- associate lymphoid tissue Lymphoma (Non-Hodgkin)
Small intestinal stromal tumors(GISTs)
Gastrointestinal stromal tumor in the jejunum, endoscopic image.Wikimedia commons

Microscopic Pathology

Tumor type Microscopic Findings Microscopic pathology
Adenocarcinoma
Sample taken from duodenum biopsy reveals Adenocarcinoma of periampullary region, showing dysplastic changes.Source: Wikimedia Commons
Carcinoid Tumors
Typical histological appearance of neuroendocrine carcinoma, showing neuroednocrine tumor cells(bottom), Paneth cells(red cells at the base of the crypt) and intestinal villi.Source: Wikimedia Commons
Mucosa- associate lymphoid tissue Lymphoma (Non-Hodgkin)
Diffuse large B-cell lymphoma of the small intestine. Malignant large lymphoid cells infiltrating the smooth muscle layer of intestinal wall.Source: Wikimedia Commons
Diffuse large B-cell lymphoma arising in the small intestine (higher magnification). Notice the malignant lymphoid cells with prominent nucleoli.Source: Wikimedia Commons
Small intestinal stromal tumors(GISTs)
Spindle cell type of intestinal gastrointestinal stromal tumor(GIST) showing areas of myxoid changes , hemorrhage and necrosis and surrounding vessels.Source: Wikimedia Commons

References

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