Metastasis of colon cancer to medullary thyroid carcinoma: a case report.

Metastasis to the primary thyroid carcinoma is extremely rare. We report here a case of colonic adenocarcinoma metastasis to medullary thyroid carcinoma in a 53-yr old man with a history of colon cancer. He showed a nodular lesion, suggesting malignancy in the thyroid gland, in a follow-up examination after colon cancer surgery. Fine needle aspiration biopsy (FNAB) of the thyroid gland showed tumor cell clusters, which was suspected to be medullary thyroid carcinoma (MTC). The patient underwent a total thyroidectomy. Using several specific immunohistochemical stains, the patient was diagnosed with colonic adenocarcinoma metastasis to MTC. To the best of our knowledge, the present patient is the first case of colonic adenocarcinoma metastasizing to MTC. Although tumor-tumor metastasis to primary thyroid carcinoma is very rare, we still should consider metastasis to the thyroid gland, when a patient with a history of other malignancy presents with a new thyroid finding.

INTRODUCTION

Although the prevalence of metastases to the thyroid gland is variable in previous reports, metastasis to the thyroid gland is known to be an uncommon condition. Moreover, metastasis to primary thyroid carcinoma is extremely rare. Fourteen cases of metastatic tumor to the primary thyroid carcinoma have been reported previously in the literature. The majority of reported primary thyroid carcinomas were papillary thyroid carcinoma (PTC), including follicular variant papillary thyroid carcinoma (FVPTC) (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11). To our knowledge, there has been no reported case of a tumor metastasizing to medullary thyroid carcinoma (MTC). We report a case of tumor-to-tumor metastasis involving metastatic colonic adenocarcinoma and medullary thyroid carcinoma.

CASE DESCRIPTION

A 53-yr old man underwent an anterior resection of his cancerous sigmoid colon and adjuvant chemotherapy on November 14, 2005. About one year after surgery, a fluorine-18-fluorodeoxyglucose-positron emission tomography integrated with computed tomography (18F-FDG PET/CT) scan showed focal hypermetabolism in the right lobe of the thyroid gland (standardized uptake value, [SUV] 4) and pulmonary nodules in the right lung, suggesting hematogenous metastatic lesions. He received chemotherapy as palliative treatment. Two years later, a PET scan still revealed a nodule, showing focal activity in the thyroid gland (SUV 2.5) (Fig. 1A). A thyroid gland ultrasonography showed a marked hypoechoic solid nodule with a lobulated margin and inner microcalcification in the right mid pole, suggesting malignancy (Fig. 1B). The patient underwent ultrasound-guided fine needle aspiration biopsy (FNAB) of the thyroid nodule. FNAB showed tumor cell clusters, which were suspected to be MTC. Serum calcitonin and carcinoembryonic antigen (CEA) levels were mildly elevated (17.3 pg/mL (reference range: 0-10 pg/mL) for calcitonin; 29.31 ng/mL (reference range: 0-4.7 ng/mL) for CEA. Thyroid stimulating hormone was 2.47 µIU/mL (0.25-4.0 µIU/mL), thyroglobulin antigens were 9.96 ng/mL (0-35 ng/mL), antithyroglobulin antibodies were 0.19 IU/mL 0-0.3 IU/mL). The serum level of intact parathyroid hormone was 40.83 pg/mL (15-65 pg/mL). The 24-hr urine cortisol/metanephrine/cathecholamin levels were within the normal range. Rearranged during transfection (RET) proto-oncogene mutations were not detected. Subsequently, the patient underwent a total thyroidectomy and bilateral central neck dissection.

Fig. 1

PET scan and Ultrasound finding. (A) PET scan shows focal hypermetabolism in the right lobe of thyroid gland (SUV 2.5). (B) Ultrasonography shows marked hypoechoic solid nodule with lobulated margin with inner microcalcification, measured 1.6×1.0×2.5 cm (2.42 cm3), in right mid pole.

On gross examination, the capsule of the right lobe of thyroid was intact, smooth, and the surface was irregularly bosselated. The cut sections revealed a well-circumscribed, round gray-tan nodular mass, measuring 1.5×1.2 cm. There is an ill defined white solid mass with central irregular yellow necrosis, measuring 0.8×0.7 cm in the gray-tan nodular mass (Fig. 2A). Histological examination revealed metastatic colonic adenocarcinoma in MTC (Fig. 2). An immunohistochemical stain of CEA and caudal type homeobox protein CDX-2 showed a strong, diffuse positivity in colonic adenocarcinoma. In contrast, the medullary thyroid cancer cells were positive for chromogranin-A and calcitonin and negative for the colonic adenocarcinoma marker. Results of immunohistochemical stain of tumor cells are described in Table 1. There was no regional lymph node metastasis.

Fig. 2

Histopathologic and immunohistochemical staining findings of thyroid lesion. (A) Gross findings reveal a well circumscribed round gray-tan nodular mass with an ill defined white solid portion and central irregular yellow necrosis (arrow). (B) Microscopic findings show a medullary carcinoma which is composed of nests or sheets of round or spindle tumor cells and acellular eosinophilic stroma (center), and colonic adenocarcinoma with glandular differentiation (right) in the normal thyroid parenchyme (left), (H&E stain, ×40). (C) Immunohistochemical staining for chromogranin A reveals positive staining in medullary carcinoma (brown) and negative staining in colonic adenocarcinoma (×40). (D) Immunohistochemical staining for calcitonin shows diffuse strong cytoplasmic positivity (brown) in the tumor cell of medullary component (×100). (E) Immunohistochemical staining for CDX2 shows a strong positive nuclear staining (brown) in colonic adenocarcinoma (×200).

Table 1

Results of immunohistochemical stain

MTC, medullary thyroid carcinoma; TTF-1, Thyroid Transcription Factor-1; CEA, carcinoembryonic antigen; CDX2, caudal type homeobox 2.

After thyroidectomy, the patient continued palliative chemotherapy for the colon cancer and supportive care. One year later, he died from dyspnea due to the aggravation of pulmonary metastases.

DISCUSSION

While the coincident occurrence of multiple primary malignant tumors in the same host is not unusual, tumor-to-tumor metastasis is a rare phenomenon. Berent (12) first documented this phenomenon in 1902. Campbell et al. (13), proposed criteria for the diagnosis of tumor-to-tumor metastasis; 1) the presence of more than one primary malignant tumor must be proved, 2) the recipient tumor must be a true neoplasm, and 3) the donor malignant tumor must be a true metastasis, with established growth and invasion in the tumor. Direct contiguous growth of one tumor into another adjacent tumor (collision tumor), embolism of tumor cells, and metastasis to leukemic nodes are not defined as metastases. Our case satisfies the Campbell's criteria.

Previous studies reported the prevalence of metastases to the thyroid gland varied greatly (14, 15, 16, 17). However, the previous studies included preexisting or coexisting thyroid conditions, such as benign thyroid diseases (goiter and adenoma), and primary thyroid neoplasms. Cases involving metastasis to primary thyroid carcinoma only, have a prevalence rate estimated to be less than 1%, and only 14 cases have been reported in the literature (Table 2). Rosai (3) reported the first documented case of metastatic breast carcinoma to a papillary thyroid carcinoma (PTC) in 1992. The most commonly reported non-thyroid malignancies to metastasize to the thyroid gland are renal cell carcinoma and lung cancer (18). Colorectal carcinoma was an uncommon donor, accounting for only two of the cases (2, 4).

Table 2

Tumor-to-tumor metastases to a primary thyroid malignancy

FVPTC, follicular variant of papillary thyroid carcinoma; PTC, papillary thyroid carcinoma; FTC, follicular thyroid carcinoma; MTC, medullary thyroid carcinoma.

Willis (19) proposed a hypothesis for why the thyroid gland receives few metastatic deposits despite its rich blood supply. According to the Willis hypothesis, fast arterial flow through the thyroid and the high oxygen saturation and iodine content of the thyroid gland prevent of metastatic tumor survival in the thyroid (19). Due to the rarity and complexity of tumor metastasis, the mechanisms of metastasis to thyroid neoplasm are unclear. Some views suggested that the thyroid tumor makes an environment in which metastatic tumor cells can easily grow by altering the normal thyroid structure as stated above (20).

MTC originates from the parafollicular C cells, which produce the hormone calcitonin. MTC is a relatively rare type of primary thyroid carcinoma, accounting for only about 5% of all thyroid carcinomas. The majority of previously reported recipient primary thyroid carcinomas were PTC, including FVPTC (12 among 14 cases) (1, 2, 3, 5, 6, 7, 9, 11). The other two cases were oncocytic/hurthle cell carcinomas (4, 8). As far as we know, cases of metastatic tumor to MTC have not been reported previously.

FNAB diagnosis of both primary thyroid malignancy and non-thyroid malignancies metastasizing to the thyroid gland at the same time is difficult and often incorrect (18). In most cases, FNAB can diagnose primary thyroid carcinoma but not the metastases to the thyroid. In the present case, FNAB allowed us to diagnose MTC, but we did not find the colorectal cancer with the technique. After surgical resection of the thyroid gland and several specific stains, we were able to diagnose the tumor-to-tumor metastasis (MTC and colorectal cancer). Although tumor-to-tumor metastasis to the primary thyroid carcinoma is very rare, metastasis to the thyroid gland should be considered, when a patient with history of other malignancies presents with a new thyroid finding.

In this case, although the patient already had pulmonary metastasis of colonic adenocarcinoma, he underwent surgical treatment. The prognosis of the patient was determined by the coexisting advanced colon cancer.

In conclusion, metastasis to the primary thyroid carcinoma is extremely rare. The present patient is the first example of colonic adenocarcinoma metastasizing to medullary carcinoma of the thyroid.