Thyroid cancer in Gardner's syndrome: Case report and review of literature.

Gardner's syndrome is a variant of familial adenomatous polyposis. A multitude of extra-colonic manifestations including various endocrine tumors have been associated with this syndrome, the commonest of which is thyroid cancer. Majority of the patients with thyroid cancer and Gardner's syndrome are females. Here we describe a male patient with Gardner's syndrome who subsequently developed thyroid cancer.

Introduction

Following the original description of Gardner’s syndrome consisting of a classic triad of colonic polyps, osteomas and soft tissue tumors, various other extraintestinal manifestations and endocrine tumors have been reported to be associated with Gardner’s syndrome, thyroid cancer being the most common. Here we report one such case and briefly review the literature.

Case Report

A 40-year-old gentleman with no previous medical or family history was referred to our hospital with a diagnosis of adenocarcinoma of the rectum. At our institute, a colonoscopic evaluation revealed multiple polyps scattered throughout the colon. He underwent panproctocolectomy with ileostomy. The histology showed tubulovillous and adenomatous polys in caecum, colon and rectum with a moderately differentiated adenocarcinoma of rectum. All lymph nodes were negative [Figure 1]. Fifteen months later, he had a swelling around the stoma site. CT scan showed a 9.5x5.6x7.5 cm peritoneal mass at the site of ileostomy with multiple smaller similar lesions throughout the abdomen. The tumor was excised (R1 resection) with reconstruction of the abdominal wall, histologically showing it to be a desmoid tumor The patient was given weekly systemic therapy with vinblastine, methotrexate and tamoxifen (methotrexate 30 mg/m2 weekly intravenously, vinblastine 6 mg/m2 weekly intravenously and tamoxifen 20 mg/m2 twice a day orally daily) for 6 cycles. Six months later (21 months following the diagnosis of colon carcinoma), CT scan showed a partial response of the desmoid tumors. A new thyroid nodule was detected at a screening ultrasound of the neck. FNAC confirmed the diagnosis to be papillary carcinoma of thyroid [Figure 2]. Total thyroidectomy was done which revealed a well-differentiated papillary carcinoma of the thyroid. The patient is currently on maintenance doses of thyroxine and is continued on tamoxifen. . Almost 3 years since the initial detection of Gardner’s syndrome, the patient continues to remain stable.

Figure 1

(a) Section from one of the multiple polyps in the surgical specimen shows features of a villous adenoma with moderate dysplasia. H and E stain, ×20 magnification, (b) Section from the tumor in the rectum shows invasive adenocarcinoma. Tumor is seen invading into the muscularis propria in this field. H and E stain, ×10 magnification

Figure 2

Papillary thyroid cancer - tumor with papillary configuration, showing prominent Orphan Annie eye nuclei, nuclear overlapping and grooves ((a) - at ×200 magnification and (b) – at ×400 magnification). The lower magnification picture shows bluish deposits (Psammomatous calcification)

Discussion

Familial adenomatous polyposis (FAP) is a syndrome caused by mutations in the adenomatous polyposis coli (APC) gene. The gene is located on chromosome 5q21. The normal gene protein is a classic tumor suppressor protein. Mutations of the APC gene are inherited in an autosomal dominant fashion. The disease is characterized by hundreds to thousands of colonic adenomas developing at a young age which almost invariably turn malignant if left untreated. Gardner’s syndrome is a clinical variant of FAP. It is characterized by the association of FAP with the characteristic triad of desmoids tumors, osteomas and epidermoid cysts. Mutations in another gene, MUTYH can also lead to a phenotype similar to FAP but have lesser number of polyps (the attenuated FAP phenotype).

The association of thyroid cancer with Gardner’s syndrome/FAP was first reported in 1949 by Crail. In 1968, independent reports by Smith and Camiel pointed out that there could be an association between thyroid cancer and Gardner’s syndrome. We reviewed the cases of thyroid cancer occurring in association with Gardner’s syndrome/FAP reported in English literature. The details of these cases are summarized in Table 1. Associated manifestations, in addition to colonic and thyroid cancer, are listed in Table 2. The vast majority of the cases occur in females, forming 86% of cases. Most patients present in the second or third decade of life. Colonic manifestations were seen earlier than thyroid cancer in nearly 65% patients. Most colonic cancers are well differentiated and the chances of local or systemic recurrence are rare if total procto-colectomy is carried out (<10%). Most thyroid cancers are also well differentiated and papillary cancer is the most commonly associated. An element of papillary cancer is found in 87% of the cases. Isolated follicular carcinoma is rare and found in only about 9% cases. Only one case of medullary carcinoma has so far been reported (case no 24; confirmed on. Immunohistochemistry with anti-calcitonin being strongly positive). Additionally, multicentric thyroid cancer is much more common in these patients as compared to the sporadically occurring thyroid cancer. No recurrence of thyroid cancer was seen if total thyroidectomy was performed. Metastasis from thyroid cancer was found in only one case, this patient had vertebral metastasis which showed a thyroid origin on biopsy (Case no 6). Although multiple osteomas are associated with Gardner’s syndrome, none of these patients had multiple osteomas. Solitary osteoma was seen in <15% of patients. Among the dental abnormalities, supernumerary teeth were the commonest. Desmoid tumors, although common in Gardner’s syndrome in general, were found be present in <15% of patients with thyroid cancer and Gardner’s syndrome. Epidermoid inclusion cysts, retinal pigmentation, gastric fundic polyps, small intestinal polyps and carcinoma of ampulla of Vater are some of the other important reported associations. Gastric adenomyoma and uterine leiomyomas were found in one patient each.

Table 1

Details of cases of thyroid cancer occuring in association of Gardner’s syndrome/fap

Table 2

Extra colonic manifestations associated with Gardner’s syndrome

Our patient had colonic polyps and adenocarcinomas as his presenting manifestation, as is seen in nearly 65% cases. His colonic malignancy was a moderately differentiated adenocarcinoma, as is seen in most patients with FAP/Gardner’s syndrome [Figures 1 and 2]. His thyroid cancer was well-differentiated papillary carcinoma; more than 85% cases of thyroid cancer occurring in association with Gardner’s syndrome have an element of papillary histology. To the best of our knowledge, our patient is the only male patient reported in the English literature with thyroid cancer and Gardner’s syndrome who had multiple desmoid tumors associated with his syndrome.

Conclusions

Thyroid cancer may occur in patients with FAP/Gardner’s syndrome and has a prevalence of around 0.6% in patients with FAP/Gardner’s syndrome.[24] This amounts to a more than 150-fold increased risk as compared to the general population.[25] All patients diagnosed with Gardner’s syndrome/FAP should be screened periodically by ultrasound for the early detection of thyroid cancer. Additionally, all young patients with thyroid cancer should be examined clinically for other manifestations of Gardner’s syndrome and a meticulous family history should be taken. Total proctocolectomy should be offered to all patients because of the nearly 100% risk of developing a colonic carcinoma in untreated cases. When thyroid nodules are detected, total thyroidectomy should be done as partial thyroidectomy carries a risk of recurrent thyroid cancer in this patient group.