Cases reported "Carcinoma, Medullary"

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1/34. somatostatin receptor scintigraphy for early detection of regional and distant metastases of medullary carcinoma of the thyroid.

    Three patients are described who had regional and distant metastases of medullary thyroid cancer detected by somatostatin receptor scintigraphy but not by CT; two had minimal disease that was amenable to surgery. The first patient had been followed for 2 years before having a repeated scan and positive CT, with subsequent surgical removal of metastatic paratracheal nodes. The plasma calcitonin level, however, did not approach normal values after surgery, and a third scan showed persistence of focal uptake in the left paratracheal area of the lower neck, whereas CT was negative. At repeated exploration, a tumor mass of medullary carcinoma, embedded in lymphatic tissue, was removed. Nine months after the last surgical procedure, calcitonin and carcinoembryonic antigen levels were normal. The second patient underwent microdissection of the mediastinum and removal of two metastatic nodes that were demonstrable only by the scintigraphic technique. The plasma calcitonin level subsequently became normal. The third patient, with multiple endocrine neoplasia IIB and associated pheochromocytoma, had bony metastatic involvement of the left shoulder, demonstrable initially on somatostatin receptor scintigraphy and subsequently with radioiodinated metaiodobenzylguanidine but not on CT.
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2/34. Dedifferentiation of neoplastic cells in medullary thyroid carcinoma: report of a case.

    We report herein the unusual case of a man who was diagnosed as having sporadic medullary thyroid carcinoma (MTC) at the age of 29 years, and subsequently followed up for a period of 18 years. A total thyroidectomy with radical neck dissection was initially performed, followed by a stable interval of 16 years with regional metastases. He then developed widely disseminated metastases resulting in death within 2 years at the age of 47 years. While the neoplastic tissue from localized metastases in the soft tissue of the neck expressed strong immunohistochemical positivity to calcitonin (CT), calcitonin gene-related peptide, carcinoembryonic antigen, neuron-specific enolase, and chromogranin a during the stable interval, extremely weakened immunoreactivity to those markers was observed in samples from the disseminated metastases in the subcutaneous tissue after his clinical deterioration. Furthermore, only a few neoplastic cells in specimens obtained at postmortem sampling exhibited a weak response to CT. Ultrastructurally, the characteristic secretory granules in the neoplastic cells decreased remarkably in number, consistent with the immunohistochemical findings. These granules also diminished in diameter and intracytoplasmic small lumina and intercellular clefts with microvilli, interpreted as an attribute of anaplastic thyroid carcinomas, were frequently observed in tissues obtained after his clinical deterioration or at postmortem sampling. These cytological changes might represent dedifferentiation of the neoplastic cells or the anaplastic transformation of MTC.
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3/34. Mixed follicular and parafollicular thyroid carcinoma.

    A rare case of mixed follicular-parafollicular thyroid carcinoma which occurred in a 50-year-old man, is reported. The ultrastructural aspects of the tumor showed: a biphasic growth pattern with microfolliculi and solid areas; the coexpression of thyroglobulin and calcitonin antigens in the same follicle-like structures; the presence of neuroendocrine granules, microvilli and intracytoplasmic canaliculi bordered by microvilli. These characteristics lead us to a diagnosis of mixed follicular-parafollicular thyroid carcinoma.
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4/34. Normal preoperative calcitonin levels do not always exclude medullary thyroid carcinoma in patients with large palpable thyroid masses.

    Medullary thyroid carcinoma (MCT) is a sporadic or familial tumor of the parafollicular or C-cells that secretes calcitonin. The sporadic form usually presents with a palpable thyroid nodule or cervical adenopathy, by which time basal calcitonin levels are almost always elevated. Without special stains, fine-needle biopsy may fail to detect MCT. Recently, several investigators have recommended routine measurement of serum calcitonin in patients with nodular thyroid diseases for the preoperative diagnosis of MCT. A 31-year-old woman had a large palpable MCT with normal calcitonin and carcinoembryonic antigen levels before surgery. Fine-needle aspiration (FNA) demonstrated atypical cells but was not diagnostic of MCT. pathology revealed a 3 x 4.5 x 2.3 cm MCT. Immunochemical stains showed immunoreactivity for calcitonin and synaptophysin, but no immunoreactivity to thyroglobulin. Postoperative basal and pentagastrin-stimulated calcitonin levels have remained undetectable without evidence of recurrent cancer. We have evaluated six other patients with MCT that were palpable. They had preoperative calcitonin levels ranging from 322-50,032 pmol/L. This unique case of a woman with a 4.5-cm MCT and normal preoperative calcitonin levels, emphasizes the need for careful clinical evaluation and FNA biopsy in managing patients with nodular thyroid disease.
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5/34. Cytological aspects of melanotic variant of medullary thyroid carcinoma.

    We had the opportunity to examine a case of fine-needle aspiration (FNA) of a melanotic variant of medullary thyroid carcinoma (MTC) in a 20-yr-old man. The patient presented a single node, hardened and mobile upon deglutition, in the right lobe of the thyroid, for 9 mo, without symptoms of glandular dysfunction. Calcitonin (138 pg/ml), urinary calcium (177 mg/dl), and the carcinoembryonic antigen (341 ng/ml) were increased. The nodular aspirate, drawn by FNA, was represented by pleomorphic cells, with frequent intranuclear cytoplasmic inclusions, sometimes bi- or multinucleated, with abundant, finely granular cytoplasm, sometimes containing a brown pigment resembling melanin. An immunohistochemical study using monoclonal antibodies (Dako Corp., Carpinteria, CA) showed that the neoplastic cells were intensely and diffusely positive for calcitonin and chromogranin, and focally positive for HMB45. In view of these findings, the case was characterized as a melanotic variant of medullary carcinoma, a rare type of neoplasia, but having a prognosis similar to the classical variant of MTC.
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6/34. Mixed medullary-papillary carcinoma of the thyroid with lymph node metastases: report of a case.

    We report herein the case of a 77-year-old woman found to have mixed medullary-papillary carcinoma in the right thyroid with lymph node metastases 30 years after a left thyroidectomy. The preoperative values of serum calcitonin and carcinoembryonic antigen (CEA) were high, and fine-needle aspiration biopsy revealed class V, which led us to suspect papillary carcinoma. A right thyroidectomy with dissection of the right neck lymph nodes was performed. Histopathological examination of the tumor specimens revealed gradual borders between medullary carcinoma and papillary carcinoma with positive immunohistochemical staining to calcitonin, chromogranin a, CEA, and thyroglobulin. The serum levels of calcitonin and CEA decreased to normal after the operation. The point mutation of the RET proto-oncogene was found to be negative by a dna analysis of the peripheral leukocytes. This cancer seemed not to be associated with multiple endocrine neoplasia type 2 syndrome. The presence of both medullary and papillary components in the thyroid with lymph node metastases is rare and may suggest that the tumor had arisen from a common stem cell.
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7/34. Elevation of serum pro-gastrin-releasing peptide in patients with medullary thyroid carcinoma and small cell lung carcinoma.

    Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells of the thyroid gland and produces a variety of peptides such as calcitonin (CT) and gastrin-releasing peptide (GRP). Here we measured serum levels of pro-gastrin-releasing peptide (Pro-GRP), a more stable precursor of GRP, in 15 patients with MTC (4 males, 11 females) who did not show any clinical or radiologic signs of small cell lung cancer. serum Pro-GRP levels were elevated in 80% (12/15) patients. Significant correlation was observed between serum Pro-GRP and CT (r = 0.52) and carcinoembryonic antigen (CEA) (r = 0.56). serum Pro-GRP levels also correlated with tumor size (r = 0.70). serum Pro-GRP levels also decreased below the cut-off range in one patient after surgical resection. Our data suggest that Pro-GRP, which is considered to be a specific marker for small cell lung carcinoma, seems to be also helpful and additional marker for the diagnosis and monitoring the response to therapy in patients with MTC in addition to calcitonin as the main tumor marker.
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8/34. Medullary thyroid cancer, papillary thyroid microcarcinoma and Graves' disease: an unusual clinical coexistence.

    We describe the unusual case of a Caucasian woman who had a diagnosis of medullary thyroid cancer and papillary microcarcinoma 5 years after a diagnosis of Graves' disease. The patient came to our observation for recurrence of hyperthyroidism. An ultrasound scan revealed diffuse thyroid enlargement with a nodule, recently increased in size. The serum CT and carcinoembrional antigen were elevated, and the fine-needle aspiration cytology with immunocytochemical analysis for CT was suggestive for medullary thyroid carcinoma. The nodular lesion showed intense 111In-pentetreotide uptake, whereas total body scintigraphy with the same tracer and with thallium-201, 99mTc (V) dimercaptosuccinic acid was negative for lymph node and distant metastasis. The histological examination of thyroidectomy specimens confirmed the diagnosis of medullary thyroid cancer, showing a lymphocytic intratumoral infiltration. The histological analysis of the controlateral lobe showed an occult papillary microcarcinoma. Medullary thyroid carcinoma and papillary microcarcinoma showed intense staining with policlonal anti-RET antibodies, although genetic analysis was negative for RET mutations most frequently involved in familial and sporadic medullary thyroid carcinomas. Possible implications about the coexistence of the 3 thyroid diseases are discussed.
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9/34. Encapsulated cystic papillary variant of medullary carcinoma of thyroid gland.

    Papillary variant of medullary carcinoma of the thyroid (MCT) is an unusual histologic pattern with some diagnostic difficulties. A case of encapsulated papillary variant of MCT with extensive cystic appearance is reported. A euthyroid, 43-yr-old woman with bone pain was incidentally found to have a 4.0-cm solitary, cold nodule on her left thyroid lobe. Histopathologic examination revealed an encapsulated tumor composed of a large cystic cavity with small papillary projections. The papillae were lined by multiple layers of neoplastic cells with small and regular nuclei containing condensed chromatin and lacking the characteristic "ground glass" appearance of the papillary carcinoma of the thyroid gland. Immunohistochemical studies revealed specific cytoplasmic staining of the tumor cells for calcitonin, chromogranin a, neuron-specific enolase, carcinoembryogenic antigen, and cytokeratin. Specific staining for thyroglobulin was not observed in any neoplastic cell. Staining with congo red disclosed amyloid deposits within the stroma. The case was diagnosed as papillary variant of MCT. Medullary thyroid carcinomas may show a papillary pattern with a totally cystic gross appearance. Thyroid carcinomas should be classified according to their major immunoreactivity pattern rather than their morphologic pattern. Immunohistochemical and/or histochemical studies should be performed in all thyroid tumors that show unusual histologic features.
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10/34. Pediatric medullary carcinoma of the thyroid with point mutation of RET proto-oncogene associated with multiple endocrine neoplasia and initially diagnosed by fine-needle aspiration biopsy.

    A 7-year-old girl presented with a thyroid mass, elevated serum levels of calcitonin and carcinoembryonic antigen, as well as multiple mucosal nodules in the upper lip and tongue. Cytologic material obtained by fine-needle aspiration biopsy from the thyroid mass was diagnosed as medullary carcinoma and confirmed by immunohistochemical studies in the cell-block sections. Subsequent histopathologic examination showed involvement of both thyroid lobes by medullary carcinoma, and electron microscopic studies further confirmed the diagnosis. Molecular studies showed a point mutation in amino acid 918 in exon 16 of the RET proto-oncogene. Biopsies from the upper lip and tongue showed mucosal neuromas. Fine-needle aspiration biopsy is frequently used in the initial evaluation of thyroid nodules. This case illustrates the value of fine-needle aspiration biopsy as a safe and accurate diagnostic modality in the workup of pediatric thyroid nodules. Fine-needle aspiration biopsy should always be considered for the investigation of thyroid nodules in pediatric patients.
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