A case of early onset adenocarcinoma associated with colorectal polyposis with an unknown germline mutation – Surgical Case Reports

An 8-year-old girl was admitted with a 4-year history of occasional bloody stools. Colonoscopy revealed profuse colorectal polyposis (Fig. 1). Pathological assessment confirmed well-differentiated adenocarcinoma in adenoma in 4/14 resected adenomatous polyps. The histological diagnosis was intramucosal adenocarcinoma (pTis) in adenoma. Upper gastrointestinal endoscopy and contrast computed tomography (CT) showed no extra-colorectal lesions associated with FAP and no metastatic lesions. There was no family history of colorectal polyposis. Colonoscopies confirmed that neither her parents nor her younger brother had colorectal polyposis.

Endoscopic view of profuse polyposis at the colon (A) and rectum (B)

Surgical procedure

Laparoscopy-assisted proctocolectomy was performed in the lithotomy position by a simultaneous abdominal and anal approach.

Abdominal approach: An umbilical incision was made, and mesentery from the terminal ileum to the sigmoid colon was dissected just proximal to the marginal vessels (D1 lymph node resection). The mesentery from the sigmoid colon to the rectum below the peritoneal reflection was laparoscopically dissected. After the transection of sigmoid colon with a linear cutting stapler, the colon from cecum to sigmoid was extracted from the umbilical incision.

Anal approach: To completely resect the rectal mucosa, excision was commenced just distal to the dentate line (Fig. 2A). Endorectal resection of the mucosa and submucosa was performed as in a Soave endorectal pull-through procedure for Hirschsprung’s disease (Fig. 2B). After the mucosal resection up to the peritoneal reflection level, an inverted muscular cuff was cut circumferentially. After the remaining sigmoid colon and rectum was extracted from the anus, the terminal ileum was pulled through the muscular cuff and anastomosed to the anal canal. Operative time was 264 min, blood loss was 55 mL, and there were no operative complications.

Surgical procedure for complete resection of rectal mucosa. A Excision was commenced just distal to the dentate line. B Transanal rectal mucosectomy was performed as in a Soave procedure for Hirschsprung’s disease

Histopathological findings

Tubular adenomas were found in the entire colon and well-differentiated tubular adenocarcinomas (tub1) (Fig. 3A, B) were detected in four sections of the rectum. All the carcinomas were classified as pTis (M) as well as in the polypectomy specimen. Histopathology revealed multiple adenomatous polyps and scattered highly atypical or adenocarcinoma components in the adenomatous polyps and the non-polypoid mucosal lesions (Fig. 3C). Stratified squamous epithelium covered the entire circumference of the distal resection margin (Fig. 3D). No metastases were observed in the peri-colorectal lymph nodes.

Histopathological findings of resected colorectum.. Staining of hematoxylin and eosin A and p53 B in a resected specimen with a magnification of × 200 showed well-differentiated tubular adenocarcinomas. C Strongly positive p53 staining which was expressed on highly atypical or adenocarcinoma components was also scattered in the non-polypoid mucosal lesions. D Distal resection margin was covered with stratified squamous epithelium (arrow)

Genetic analysis

After genetic counseling, the patient and her parents underwent genetic testing. Polymerase chain reaction (PCR)-direct sequencing of the entire coding region and the exon–intron junctions, and real-time PCR of DNA extracted from blood cells, revealed no mutations of either APC or MUTYH. No deletions or duplications of APC, MUTYH and GREM1 genes were found using multiplex ligation-dependent probe amplification (MLPA) (SALSA MLPA probemix P043-E1; MRC, Amsterdam, The Netherlands). No translocation or inversion of these genes was confirmed by G-banding analysis. Although next-generation target resequencing using a panel of 94 cancer related genes (TruSight cancer panel, Illumina Japan, Tokyo, Japan) was performed to explore the hereditary component associated with polyposis syndromes including APC, MUTYH, BMPRA1, SMAD4 and PTEN genes, no mutations were detected. Multi-gene panel sequencing using MHCRCv3 to detect hereditary colorectal cancer-related genes, including MLH1, PMS2, MSH2, MSH6, EPCAM, MSH3, MBD4, APC, MUTYH, NTHL1, POLD1, POLE, and TP53 was conducted, using the method described by Makabe et al. [6]. Trio-whole exome sequencing was performed using SureSelect Clinical Research Exome (Agilent Technologies Japan, Ltd.). However, no candidate pathogenic variants were detected in de novo dominant or autosomal recessive model, nor pathogenic variants on highly scored-polyposis related genes in GeneCards website. Somatic mutation of APC was not detected in 4 polyps by loss of heterozygosity analysis at a single nucleotide polymorphism in intron 14 (rs1217729675).

Postoperative clinical course

Complete resection was achieved, so no additional adjuvant chemotherapy was administered. Surveillance endoscopy and contrast CT were performed yearly for detection of extra-colorectal lesions and residual rectal carcinoma. The patient has remained disease-free for 5 years. Currently, the patient is on loperamide and passes stool 5 times/day without any soiling.