What is the pathophysiology of pediatric colorectal tumors?

Updated: Jun 06, 2020
  • Author: Jaime Shalkow, MD, FACS; Chief Editor: Cameron K Tebbi, MD  more...
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Colon cancer is triggered by a series of point mutations and genetic alterations that cause normal cells to transform into adenomas that progressively become dysplastic, resulting in carcinoma foci. [51] These mutations occur in a certain sequence that determines the clinical characteristics of the tumor.

CRC arises from the mucosal surface of the bowel, generally at a site of an adenomatous overgrowth or polyp. The tumor may penetrate the bowel wall and even perforate the serosa into the omental fat, lymph nodes, liver, ovaries, and other loops of bowel. Some lesions cause bowel obstruction. Synchronous lesions may be present, with the same or different histology and stages of development. Carcinoma in situ may occur in one or more polyps. Patients with synchronous primary tumors have the same prognosis as patients with single colon cancers. [52]

The epidermal growth factor receptor (EGFR) is abnormally expressed in CRC cells (72-82%). It promotes cell division, migration, and angiogenesis and inhibits apoptosis. [53] Thus, EGFR plays an important role in the pathogenesis of CRC. Its expression is associated with poor survival and increased risk of metastasis. Italiano et al demonstrated EGFR expression in CRC metastatic cells. [54]  Monoclonal antibodies and low molecular weight tyrosine kinase inhibitors may be useful in the therapeutic armamentarium for patients with CRC.

A rare "flat-type" colorectal tumor has been reported. This form tends to be more aggressive despite the small size of the tumor; it shows high-grade dysplasia and progresses rapidly to invasive cancer. Inactivation of p53 and 17p-LOH have been described in this tumor. [55] They are poorly differentiated and contain pools of mucin. Mucin-producing or signet ring adenocarcinoma is the predominant cell type; it occurs in 50% of pediatric cases compared with a 5% occurrence reported in adults. [56] These tumors may become huge. The differential diagnosis includes malignant carcinoid, leiomyosarcoma, malignant fibrous histiocytoma, and metastatic tumor from other sites.

In a series reported by La Quaglia et al, the interval from symptom onset to diagnosis was not a significant predictor of mortality; however, tumor grade was. [53]  Signet ring tumors, which are more common in children and adolescents than adults, behave more aggressively and are associated with earlier penetration of the bowel wall and extension along peritoneal surfaces, which suggests more aggressive tumor biology. The mucin absorbs water, swells, and invades tissues, thus promoting spread of malignant cells. Mucin also interferes with the mucopolysaccharide-coating immune recognition of carcinoma cells. [57] Children have a worse prognosis than adult patients who are at the same disease stage. [58]

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