Clinical and Genetic Characteristics of Pediatric Colorectal Cancer

ABSTRACT Background Compared to colorectal cancer (CRC) in adults, CRC in children is extremely rare. Although its incidence has increased recently, there is a lack of clinical research on the disease. Inherited cancer susceptibility syndromes (ICSS), a group of disorders in which patients are predisposed to susceptibility to a wide range of tumors as a result of pathogenic mutations in genes in their germ line, are an important cause of CRC in children. Delayed diagnosis due to atypical clinical presentation, as well as limited awareness of ICSS among doctors, contributes to poor outcomes in juvenile CRC patients. Therefore, improving clinicians’ understanding of the diagnosis and treatment of the disease is crucial to enhancing children's prognosis with CRC. Methods Clinical data and laboratory reports were collected from eight pediatric patients diagnosed with CRC at the Children's Hospital of Nanjing Medical University between 2020 and 2023. The clinical and genetic characteristics of these patients were evaluated and compared with other patients with early‐onset CRC in the literature. Results A total of 8 children with CRC were enrolled in the study, including 5 male and 3 female children, with a median age of 140 (73–177) months. The main clinical manifestations were unexplained abdominal pain, abdominal distension, vomiting, and hematochezia. Three cases of intestinal obstruction and two cases of intestinal intussusception occurred among the patients. All eight children underwent surgical treatment, including one case of snare resection of rectal polyp, five cases of subtotal colectomy, and two cases of radical resection of CRC. One case of radical resection of CRC utilized laparoscopic and colonoscopic combined resection guided by indocyanine green (ICG) fluorescence navigation system. Postoperative combination of pathological pictures and immunohistochemical (IHC) staining results confirmed high‐grade squamous intraepithelial lesion (HSIL) in Case 1, and mucinous adenocarcinoma in the remaining seven cases. Out of eight pediatric patients with CRC, except for Case 1 and Case 7, who did not undergo chemotherapy, the remaining six patients all received postoperative chemotherapy; among them, the patients in Cases 1, 6, 7, and 8 achieved complete remission, whereas the patients in Cases 2 and 4 died due to postoperative recurrence and distant metastasis, the patient in Case 3 is still undergoing chemotherapy, and the patient in Case 5 was lost to follow‐up after surgery. The results of the genetic test report showed that two children had ICSS caused by mismatch gene repair system defects (deficient MMR, dMMR); in Case 3, the child's genetic test results showed heterozygous mutation of MSH2 in the MMR gene, with high microsatellite instability (MSI‐H), and the results of the methylation test of the MLH1 gene were negative, which, combined with the family history of heterozygous mutation of the MSH2 gene, ruled out sporadic CRC and led to the diagnosis of Lynch syndrome (LS); Case 8 genetic testing showed two heterozygous mutations in the MMR gene PMS2 with microsatellite stabilization (MSS), and a diagnosis of constitutional mismatch repair deficiency (CMMRD) was considered. Conclusion Pediatric CRC is confronted with delayed diagnosis and poor clinical prognosis, mainly due to nonspecific clinical presentation and the low index of suspicion among clinicians. Early detection and diagnosis is the fundamental guarantee to improve the prognosis of pediatric CRC patients, and pediatric surgeons enhance the understanding of pediatric CRC and standardize the surgery as much as possible.