INTRODUCTION<\/strong><\/p>\n MTC is a relatively uncommon thyroid tumor which derives from the parafollicular or C cells of the gland that synthesize and secrete the calciotropic hormone calcitonin (CT). Carcinomas of this type account for 5-10% of all thyroid malignancies. MTC may occur sporadically or may be inherited. Germline mutations of the RET oncogene lead to the manifestation of either familial medullary thyroid carcinoma (FMTC) or to the multiple endocrine neoplasia syndromes types IIa and IIb.1<\/sup><\/p>\n Metastatic dissemination to both the central and lateral cervical lymph node compartments, including the mediastinum, is a common occurrence in patients with clinically apparent MTC.2,3<\/sup> The central compartment lymph nodes tend to be affected more frequently. In this report we describe a rare patient with occult MTC who presented with an asymptomatic mediastinal mass and elevation of carcinoembryonic antigen (CEA).<\/p>\n CASE PRESENTATION<\/strong><\/p>\n A 45-year-old woman from Bulgaria, living in Greece for the last 5 years, presented with an elevated CEA detected a year prior to her admission to our Department on a routine measurement done by her gynecologist. She had a history of hysterectomy due to uterine leiomyoma two years prior to admission. Further tests were carried out to ascertain the cause of the elevated CEA, including a CT of the chest. A mediastinal mass 5 cm in diameter was found, abutting the lower margin of the right thyroid lobe. She was referred to the Endocrinology Department of our hospital for further diagnostic and therapeutic management. Hematologic workup, gastrointestinal endoscopic studies and magnetic resonance imaging (MRI) imaging of the abdomen conducted elsewhere on an outpatient basis had failed to identify the cause of the mediastinal mass. The patient was completely asymptomatic. She had a medical history of renal colic for 10 years prior to admission. The family history was negative for thyroid diseases or other endocrinopathies. The physical examination was unremarkable. There was no goiter or palpable thyroid nodules and no enlargement of regional or distant lymph nodes.<\/p>\n Ultrasound examination of the neck revealed a thyroid gland of normal size with inhomogeneous echo pattern and several small nodules of 0.5-0.6 cm in diameter in both lobes. A few small jugular lymph nodes less than 1 cm were observed. MRI examination of the chest confirmed the presence of a large mediastinal mass contiguous to the lower margin of the right thyroid lobe that displaced the trachea to the left (Figure 1).<\/p>\n Figure 1.<\/strong> MRI of the thorax showing the large mediastinal mass in touch with the lower margin of the right lobe of the thyroid and displacing the trachea to the left.<\/p>\n Because of the unusual clinical presentation, rare causes of CEA elevation associated with mediastinal masses and thyroid malignancies were considered and in this context CT was measured as well as CEA as tumor markers (Table 1<\/a> ). A CT of 603 pg\/ml was found. Therefore, the combination of a markedly elevated CT well above 100 pg\/ml, an elevated CEA and a mediastinal mass pointed to the diagnosis of MTC metastatic to the mediastinum. Other causes of elevated CT were also considered (Table 1<\/a> ) but were thought less likely on the basis of previous reports.4,5<\/sup> Based on the findings of these studies, the lack of clinical symptoms and signs and the lack of imaging findings of a neuroendocrine tumor elsewhere, no stimulatory tests such as pentagastrin or calcium infusion were deemed necessary. The patient was further investigated for pheochromocytoma preoperatively in order to exclude MEN 2 syndrome. The values of urinary catecholamines, metanephrines and VMA were within normal limits. The possibility of primary hyperparathyroidism was also considered based on the patient\u2019s clinical history of renal colics. The laboratory tests showed an elevated PTH without hypercalcemia but a low-normal plasma 25-OH-D (Table 2<\/a> ). Thus, a diagnosis of secondary hyperparathyroisism was made. The PTH levels were corrected to normal with vitamin D replacement.<\/p>\n The patient underwent resection of the mediastinal mass, total thyroidectomy and dissection of the central compartment lymph nodes. Fourteen cervical lymph nodes and the mediastinal mass were examined histologically and immunohistochemically. Histopathology confirmed the preoperative diagnosis of MTC with metastases to cervical and mediastinal lymph noses. The thyroid tumor measured 0.5 cm in diameter, was located in the right thyroid lobe and consisted of a homogeneous amyloid-rich cell population. Metastases to 9 of 14 resected cervical lymph nodes and to a block of superior mediastinal lymph nodes were also found. Figure 2.<\/strong> Histological examination showing typical morphology of medullary carcinoma. Immunohistochemistry with the alkaline phosphatase method was positive for (a) calcitonin (original X 100) and (b) chromogranin (original X40). Figure 3.<\/strong> Post-operative Octreoscan, showing uptake by metastatic lymph node. Medullary thyroid carcinoma is a thyroid tumor deriving from parafollicular C cells. MTC may be sporadic or hereditary. Hereditary MTC accounts for 25% of all cases and is transmitted as an autosomal dominant trait either alone as FMTC or as part of multiple endocrine neoplasia (MEN) type 2A or 2B. The pathogenetic mechanism has been associated with germline gain-of-function mutations of the RET proto-oncogene (RET), mainly in exons 10\u201315.6<\/sup> The biological behavior of medullary thyroid carcinoma is much less favorable than other well-differentiated thyroid carcinomas. A 10-year survival of about 50% of medullary thyroid carcinoma patients is reported in several series. Early diagnosis may result in higher probability of cure and long-term survival.7,8<\/sup><\/p>\n![\"](\"\/wp-content\/uploads\/images\/dyn\/pap12-1.jpg\")
<\/p>\n
\nThe malignant cell population immunophenotype was CK7 (+), CK18 (+), CEA (+), Calcitonin (+), Chromogranin (+), TTF-1 (+), Thyroglobulin (-) and EMA (-) (Figure 2). The patient recovered uneventfully. Three months after surgery, CT and CEA were measured and a CT scan of the neck, chest and upper abdomen was performed. The CT and CEA levels were 318 pg\/ml and 24.18 ng\/ml, respectively, indicating the presence of residual disease. The CT scan of the neck, chest and upper abdomen showed a small jugular lymph node in the right posterior cervical triangle (level V), measuring 1.15 cm in diameter with characteristics suspicious for metastasis. This finding was further investigated with 111<\/sup>In DTPA octreotide scintigraphy which showed a high concentration of the radiolabeled somatostatin analogue anterolaterally, in the lower right neck, indicating the presence of residual tumor (Figure 3). A second operation with cervical lymph node dissection (levels II, III, IV and V) on the right side of the neck was performed. Fifty-one lymph nodes were removed. Histological examination revealed metastatic dissemination of MTC to 3 of 51 lymph nodes. Following reoperation, calcitonin dropped to undetectable levels to this date. Genotype screening did not reveal mutations associated with familial forms of MTC. The study of family members revealed normal calcitonin levels.<\/p>\n![\"](\"\/wp-content\/uploads\/images\/dyn\/pap12-2.jpg\")
<\/p>\n
\n
\n<\/strong>![\"](\"\/wp-content\/uploads\/images\/dyn\/pap12-3.jpg\")
<\/p>\n
\n
\nDISCUSSION<\/strong><\/p>\n