Journal of Gastrointestinal Surgery

, Volume 16, Issue 2, pp 411–414

Turcot Syndrome: A Case Report in an Unsuspected Setting

Authors

  • Hyuk Jun Chung
    • Department of Surgery, Seoul St May’s HospitalThe Catholic University of Korea
  • Seong Taek Oh
    • Department of Surgery, Seoul St May’s HospitalThe Catholic University of Korea
  • Jun Gi Kim
    • Department of Surgery, Seoul St May’s HospitalThe Catholic University of Korea
    • Department of Surgery, Seoul St May’s HospitalThe Catholic University of Korea
Case Report

DOI: 10.1007/s11605-011-1698-0

Cite this article as:
Chung, H.J., Oh, S.T., Kim, J.G. et al. J Gastrointest Surg (2012) 16: 411. doi:10.1007/s11605-011-1698-0

Introduction

Turcot syndrome (TS) is a rare hereditary disorder named after Dr. Jacques Turcot who first reported it in 1959.1 The primary clinical feature of TS is the concurrent presence of multiple colorectal adenomas or carcinomas and primary tumors of the central nervous system. The mode of transmission for TS may be either autosomal dominant or autosomal recessive.2,3 To date, TS has been subdivided clinically and genetically into two subtypes.4,5 TS type 1 has mutations in one of the mismatch repair (MMR) genes (MSH2, MSH6, MLH1, PMS1, and PMS2) that are usually found in hereditary nonpolyposis colorectal cancer (HNPCC) and is associated with glioblastoma. TS type 2 has a germline mutation of the adenomatous polyposis coli (APC) gene that is usually found in familial adenomatous polyposis and is associated with anaplastic astrocytoma, ependymoma, or medulloblastoma.4,5

We report the case of a TS type 1 female patient who had survived exceptionally long with glioblastoma multiforme (GBM) and who had experienced an unusually long gap between the initial diagnosis of GBM and colon cancer.

Case Report

A 25-year-old female presented with a pelvic mass as an outpatient to the Department of Gynecology. The patient complained of dyspepsia and discomfort of the lower abdomen. Her physical examination revealed a large palpable mass in the lower abdomen. Pelvic magnetic resonance image (MRI) revealed 10.3 × 16.9 cm on the right, 14.6 × 9.7 cm on the left in size, bilateral multicystic borderline ovarian cystadenoma, or cystadenocarcinoma with left hydronephrosis (Fig. 1). Preoperative cancer antigen 125 was elevated at 281.1 U/mL (Ref range, <35 U/mL) and carcinoembryonic antigen was normal at 1.86 ng/mL (Ref range, <3.5 ng/mL). At 13 years of age, she had been diagnosed with right parietotemporal glioblastoma multiforme (GBM) that was treated with resection, radiation therapy, and four cycles of procarbazine/chloroethylcyclohexylnitrosourea/vincristine adjuvant chemotherapy. She underwent an operation by a gynecological surgeon in which a total hysterectomy and bilateral salpingo-oophorectomy were performed. During the operation, gynecological surgeon noticed sigmoid colon mass and consulted with a colorectal surgeon. A frozen biopsy of the ovarian masses showed metastatic adenocarcinoma consistent with the pathology of a Krukenberg tumor. She underwent anterior resection and no other lesions were found during the operation (Fig. 2). The result of the pathologic examination was moderately differentiated adenocarcinoma in sigmoid colon with regional lymph node invasion (1/21) and bilateral ovary metastasis (T3N1aM1a). The lengths of proximal and distal resection margins were 9 and 5 cm, respectively. The resection margins were free from carcinoma. Her family history was suggestive of HNPCC (Fig. 3). Her mother had ascending colon cancer at age 45 years and cervical cancer with brain metastasis at age 52 years. Her aunt had a small colonic polyp. The patient had experienced sigmoid colon cancer at 25 years. Anti-MLH1 immunohistochemistry showed lack of MLH1 expression in tumoral cells. A genetic study identified a mutation of the MLH1 gene (1721T>C). She underwent colonoscopic examination 1 month after operation and cancers of ascending colon and hepatic flexure and several polyps were found. Brain MRI showed no recurrence of GBM. She underwent total colectomy and ileorectal anastomosis (Fig. 4). Her family members were advised to undergo genetic testing, screening colonoscopy, and imaging studies of the brain. She is undergoing FOLFOX chemotherapy and follow-up studies document no recurrence nor metastases.
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Fig. 1

An initial MRI shows multicystic borderline bilateral ovarian cystadenoma or cystadenocarcinoma. Superior 10.3 × 16.9-cm-sized mass (a-1, a-2) is connected with left uterine cornus and an inferior 14.6 × 9.7-cm-sized mass (b-1, b-2) is connected with the right uterine cornus

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Fig. 2

Resected specimen by initial AR

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Fig. 3

The patient’s pedigree. Tumors and age at onset are reported. Black symbols indicate HNPCC-related tumors. Co colon cancer, Cx cervix cancer, Br met brain metastasis, Po colonic polyp, GBM glioblastoma multiforme

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Fig. 4

Resected specimen by total colectomy. It shows cancers of the ascending colon and the hepatic flexure

Discussion

Since Dr. Turcot reported the first TS case, fewer than 200 patients have been identified with the syndrome, although many cases have not documented genetic analyses.6 TS type 2 consists of two thirds of all TS cases7 and most of TS type 2 patients harbor the germline APC gene mutation.8 TS type 1 account one third of TS cases and shows MMR gene mutations, commonly involving MSH2, MLH1.4,5 For CNS tumor, TS type 1 shows GBM and TS type 2 consists of mainly medulloblastoma. Our patient showed GBM and colon cancer with a mutation of the MLH1 gene (1721T>C). The patient case described herein was consistent with TS type 1.

Seventy percent of patients with Turcot syndrome present with intestinal cancer and develop the CNS manifestations within 5 years; the mean age range of disease onset is in the second and third decades.5,9 However, if brain tumors appear first, colonic polyps tend to become symptomatic within 1 year.1012 Our patient had an unusual 12-year gap between the initial diagnosis of GBM and developing colon cancers. This length of survival following the diagnosis of GBM is exceptional. In a review of 100 patients with TS, the average survival of GBM patients was estimated at 27 months post diagnosis, much longer than the typical 12 months in sporadic GBM patients.5 In the previous study by Hamilton et al., the length of survival for four patients with glioblastoma was over 3 years.4 Among these patients, two developed GBM first. Recently, Sarin et al. reported on a TS type-2 patient who had an unusual 22-year gap between the initial diagnosis of medulloblastoma and colon cancer.13 Although the reported cases of TS-associated brain tumor have often been associated with enhanced survival time, however the reason remains in question.

In our case, the patient had two large lower abdominal masses that were suspected bilateral multicystic borderline ovarian cystadenoma or cystadenocarcinoma by MRI. During operation, gynecologist found sigmoid colon cancer and referred to colorectal surgeon. We checked the entire abdominal cavity, including the colon and the rectum; no other lesions were found. However, there was the possibility that cancers of the ascending colon and hepatic flexure were ignored because a mechanical bowel preparation had not been done. Those cancers were found on colonoscopic examination 1 month after the operation. It is not clear whether or not they existed at the first operation time. This case demonstrates the limitation of imaging studies and the importance of colonoscopic examination in diagnosing large pelvic masses. If there is no result of colonoscopic examination, we should consider doing a perioperative colonoscopic examination.

In conclusion, our case demonstrates that colonoscopic examination is important in the evaluation of pelvic masses to rule out a colonic neoplasia. In this case, the gynecologist should have suspected TS and performed a preoperative colonoscopy. Suspicion and awareness of Turcot syndrome enable physicians to diagnose and to treat it properly. When a colorectal tumor is encountered without the use of colonoscopy, one should perform postoperative follow-up with colonoscopy in the short term. If possible, intraoperative colonoscopic examination may help with proper treatment of the patient.

Copyright information

© The Society for Surgery of the Alimentary Tract 2011