Metastatic Medullary Carcinoma of Thyroid Presenting as a Dural-Based Mass: Case Report and Review of Literature

Dural metastasis from medullary thyroid carcinoma (MTC) is not well established in English literature. We present the case report of MTC with unusual clinical presentation as a dural-based mass in a 39-year-old male with no family history of multiple endocrine neoplasia syndrome. Magnetic resonance imaging showed an extra-axial dural-based mass in right frontal lobe with calvarium and soft tissue extension to the right superior orbit. Histopathology showed MTC with variegated morphology and various patterns. Thyroid mass and widespread metastases from medullary thyroid carcinoma were subsequently identified.     

Sporadic medullary microcarcinoma of the thyroid

Two cases of medullary microcarcinoma of the thyroid are reported. The tumours were identified incidentally in a 60- and a 66-year-old woman each with a thyroid adenoma. These tumours were 0.8 cm and 0.5 cm in size, respectively, and located in the central portion of the right lateral lobe. In neither patient was there a family history of medullary thyroid carcinoma. Although medullary microcarcinoma with associated C-cell hyperplasia in familial form has been reported, sporadic medullary microcarcinoma is rare.     

Medullary thyroid carcinoma,follicular variant

We report here a 48-yr-old woman presenting with a solitary thyroid nodule in the left lobe of the thyroid. The aspiration cytology of the nodule was reported as follicular neoplasia and she underwent surgery. Frozen section was suspicious for medullary thyroid carcinoma and a total thyroidectomy was performed. The pathology report revealed medullary thyroid carcinoma, follicular variant. Immunohistochemical analysis was negative for thyroglobulin and positive for calcitonin. A few patients with this variant have been reported in the literature, mainly diagnosed by immunohistochemical features of the tumor. In light of the limited information we have obtained from the literature, it is reasonable to emphasize that these cases should be distinguished from the mixed medullary-follicular thyroid carcinomas and medullary carcinomas with entrapped follicles. Immunohistochemical examination with calcitonin and thyroglobulin is also essential.     

Solid cell nests of the thyroid in medullary thyroid carcinoma

Solid cell nests of the thyroid gland were studied in 44 patients with medullary thyroid carcinoma. In 10 (22.7%) patients, solid cell nests were revealed in the vicinity of tumour foci (five cases) or in the contralateral thyroid lobe and isthmus (four cases); in one case the location was indeterminate. In all seven cases in which immunohistochemical studies were carried out, solid cell nests showed negative staining for thyroglobulin, calcitonin and chromogranin A, findings which were distinct from those in medullary thyroid carcinoma. It is therefore suggested that solid cell nests of the thyroid are not precursors of this tumour.     

Concurrent lymph node metastases of medullary and papillary thyroid carcinoma in a case with <Emphasis Type="Italic">RET</Emphasis> oncogene germline mutation

We report the case of a 72 yr-old woman who underwent total thyroidectomy and resection of neck lymph nodes because of a firm nodule in the right lobe, which was consistent with medullary thyroid carcinoma (MTC) on cytological examination. Histology showed multifocal bilateral MTC; a 2 mm papillary thyroid carcinoma (PTC) was also detected in the right lobe, next to a focus of MTC; five cervical lymph nodes contained MTC. In one right perithyroidal lymph node, concurrent metastases of MTC and PTC were demonstated. DNA analysis showed a point mutation in exon 14 at codon 804 of the RET proto-oncogene locus, as frequently found in cases of familial MTC (FMTC). To our knowledge, this case represents the first documented case of concurrent lymph node metastases of MTC and PTC in a patient with RET proto-oncogene germline mutation. We report this unique case, discuss related thyroid malignancies, and suggest possible underlying pathogenetic mechanisms.     

Simultaneous occurrence of medullary and follicular carcinoma in the same thyroid lobe

A rare case of the simultaneous development of medullary and follicular carcinoma of the thyroid gland in a 51-year-old Japanese woman is examined. A preoperative diagnosis was made by needle aspiration cytology. Neoplastic cells of the medullary carcinoma were positive for calcitonin and carcinoembryonic antigen, whereas the tumor cells of the follicular carcinoma were negative for these substances. This case presents evidence that, in rare cases, two malignant epithelial neoplasms of different origins can occur in the same lobe of the thyroid.     

Renal cell carcinoma metastasis in a microfollicular adenoma of the thyroid gland

A 60-year-old woman had a nephrectomy of her left kidney because of a renal cell carcinoma. She came to us for an oncologic F-18-fluordeoxyglucose-positron emission tomography (F-18-FDG-PET). In the positron emission tomography there was a pathologic fluordeoxyglucose-uptake in the left thyroid gland lobe. Thyroid investigation and Tc-99 m pertechnetate scintigraphy of the thyroid gland was done. It showed a hyperfunctioning nodule in the left thyroid gland lobe. Surgery was suggested. Histology showed a metastasis of a clear cell renal carcinoma in a microfollicular adenoma of the thyroid gland--a very rare combination.     

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.     

FAMILIAL MEDULLARY CARCINOMA OF THE THYROID THROUGH 3 GENERATIONS

A family with high genetic penetrance of medullary carcinoma of the thyroid was reported. Seven proven (6 patients and one autopsy case) and 2 probable cases of medullary carcinoma were present in 25 members through 3 generations. An endogamy had intervened in the prior generation of these cases. Preliminary results in clinicopathological examinations of 7 proven cases were as follows; clinically, all of the cases showed B type blood group. Glycosuria was found in 2 cases, and diarrhea in one case. Serum thyrocalcitonin being estimated In two cases showed high levels. The autopsy cases coexisted with medullary carcinoma of the thyroid and pheo-chromocytoma of the right adrenal. Pathologically, the majority of tumors occurred in both thyroid lobes, and were present from the middle to upper portion of the thyroid. The tumor showed a variety of histological features even in the same tumor. In the tumor cell, numerous membrane-limited granules were seen with an electron microscope. Amyloid was demonstrated only In the tumor tissue.     

C cell carcinoma of the thyroid. Follicular variant

A case of C cell carcinoma of the thyroid with an unusual follicular growth pattern of the cancerous C cells is described. The primary tumor consisted of a mixture of medullary and follicular features while the metastatic foci in the lymph nodes and liver displayed only a medullary arrangement. Histochemical study disclosed numerous argyrophilic cells in both the follicular and medullary parts. These cells were immunohistochemically positive for calcitonin, calcitonin gene-related peptide (CGRP) and other peptides as well as carcinoembryonic antigen (CEA), but negative for thyroglobulin. Radioimmunoassay done on the tissue extract revealed a high content of calcitonin. Electron microscopy showed small intracytoplasmic secretory granules and, in the follicular lining cells, formation of microvilli. A minor component consisting of glandular structures has been reported in medullary carcinoma of the thyroid, suggesting a potentiality for glandular differentiation of the C cells. In equivocal cases, immunohistochemical examination for calcitonin and thyroglobulin is essential for accurate diagnosis of thyroid carcinoma.     

Bilateral Thyroid and Ultimobranchial Medullary Carcinoma

The ultimobranchial bodies in human embryos develop from the fourth and fifth branchial pouch complexes along with thymic and parathyroid tissue. They become incorporated within the lateral thyroid lobes and are believed to be involved in the development of C-cells. We report a case of an unusual bilateral thyroid and neck prelaryngeal medullary carcinoma in a 23-year-old male patient who belongs to a multiple endocrine neoplasia type 2a (MEN type 2a) family with thyroid tumors and pheochromocytomas. The medullary carcinoma was located in an abnormal cystic structure that seems to be a remnant of the ultimobranchial body (UBB) in the neck. Within the contralateral thyroid lobe, the medullary carcinoma was associated with C-cell hyperplasia.     

Association of urothelial carcinoma of the renal pelvis with papillary and medullary thyroid carcinomas. A new sporadic neoplastic syndrome?

We describe 2 adult women (72 and 54 years), 1 with a low-grade noninvasive papillary urothelial carcinoma of the renal pelvis, who 14 years later developed a papillary carcinoma in 1 thyroid lobe and a medullary carcinoma in the contralateral lobe. Both neoplasms were similar in size and appeared symmetrical. Despite its small size, the medullary carcinoma metastasized in multiple cervical lymph nodes. The second patient had a high-grade invasive papillary urothelial carcinoma of the renal pelvis that infiltrated the renal parenchyma and metastasized in one of the lungs. Five months later, a papillary carcinoma was discovered in the thyroid gland. The 2 papillary thyroid carcinomas were of the follicular variant. Adjacent to 1 papillary carcinoma, there was a dominant nodule of a colloid and adenomatous goiter. The medullary carcinoma contained stromal amyloid and was immunoreactive for calcitonin and carcinoembryonic antigen. There was no C-cell hyperplasia (medullary carcinoma in situ). The 2 patients are alive, 1 is living with pulmonary metastasis from the high-grade urothelial carcinoma. Twelve cases of this neoplastic association were registered in the Survey, Epidemiology, and End Results Program from 1980 to 2009. We believe that the combination of these unusual neoplasms in the same patient may represent a new sporadic neoplastic syndrome.     

Parasitic nodule of the thyroid in a patient with Graves’ disease

 We report a case of a parasitic nodule of the thyroid in a patient with Graves’ disease, which mimicked a lymph node metastasis from a primary occult thyroid carcinoma. The patient was a 67-year-old Japanese woman with a past history of subtotal thyroidectomy for Graves’ disease, who was referred to our hospital because of a right cervical mass. A lymph node-like lesion measuring 1.5 cm in diameter was palpable, distinct from the remnant of the right thyroid lobe. Thyroid scintigraphy using ¹²³I-Na revealed a hot lesion at the upper lateral portion of the right thyroid lobe, and this was resected. Microscopically, the mass showed thyroid follicles with lymphocytic infiltration and lymphoid follicles. Clear ground glass nuclei, nuclear grooving and intranuclear inclusions were not observed. No morphological evidence of the lymph node was found in the mass by reticulin staining. Parasitic nodules of the thyroid in patients with Graves’ disease may mimic a metastatic carcinoma of the thyroid. Received: 21 January 1998 / Accepted: 15 April 1998     

Simultaneous occurrence of papillary carcinoma, oncocytic carcinoma and malignant lymphoma of the thyroid gland in a female patient with Hashimoto's disease

A 51-year-old woman was admitted for a painless enlargement of the thyroid lasting over 6 months. Hashimoto's thyreoiditis was diagnosed and three tumors were found: oncocytic carcinoma, malignant lymphoma and papillary carcinoma. In the right lobe, oncocytic carcinoma and high grade malignant lymphoma composed of cells with irregular, lobulated nuclei were found. The lymphoma was confined to the thyroid gland. The oncocytic carcinoma invaded the capsule and the surrounding tissues. In the left lobe, there was a papillary carcinoma.     

C Cell Carcinoma of the Thyroid Follicular variant

A case of C cell carcinoma of the thyroid with an unusual follicular growth pattern of the cancerous C cells is described. The primary tumor consisted of a mixture of medullary and follicular features while the metastatic foci in the lymph nodes and liver displayed only a medullary arrangement. Histochemical study disclosed numerous argyrophilic cells in both the follicular and medullary parts. These cells were immunohistochemically positive for calcitonin, calcitonin gene-related peptide (CGRP) and other peptides as well as carcinoembryonic antigen (CEA), but negative for thyroglobulin. Radioimmunoassay done on the tissue extract revealed a high content of calcitonin. Electron microscopy showed small intracytoplasmic secretory granules and, in the follicular lining cells, formation of microvilli. A minor component consisting of glandular structures has been reported in medullary carcinoma of the thyroid, suggesting a potentiality for glandular differentiation of the C cells. In equivocal cases, immuno-histochemical examination for calcitonin and thyroglobulin is essential for accurate diagnosis of thyroid carcinoma. Acta Pathol Jpn 39: 393-399, 1989.     

Heat shock proteins HSP90, HSP70 and GRP78 expression in medullary thyroid carcinoma

BackgroundMedullary thyroid carcinoma management consists mainly of surgical resection and is largely chemoresistant. There is ongoing effort to discover novel therapies for medullary thyroid carcinoma. Increased levels of heat shock proteins have been associated with multiple cancers and are being studied as potential therapeutic targets. The purpose of this study was to determine the expression levels of heat shock proteins 90 and 70 and of glucose related protein 78 in medullary thyroid carcinoma tissues compared with normal thyroid tissues.Methods20 tissue specimens of medullary thyroid carcinoma and 10 specimens of thyroids without malignancy were analyzed by immunohistochemistry.ResultsMedullary thyroid carcinoma specimens showed 27% higher expression level of heat shock protein 90 immunostaining, and a 43% higher expression level of heat shock protein 70 immunostaining versus normal controls. These differences, however, were not statistically significant. A significantly higher expression level was noted for glucose related protein 78 in the medullary thyroid carcinoma specimens than in the controls.ConclusionThis study indicates increased expression levels of heat shock proteins 90 and 70 and glucose related protein 78 levels in medullary thyroid carcinoma. These findings, though preliminary imply that these proteins may have a role in medullary thyroid carcinoma's tumor biology and may have and future therapeutic options. Larger cohorts are needed to corroborate these results.     

Melanotic medullary thyroid carcinoma: A case report with review of the literature

Melanotic medullary thyroid carcinoma is morphologically defined by the presence of melanin deposits in the cytoplasm of tumor cells. It is an extremely rare variant with only 15 cases described in the literature to date and only one report of diagnosis by fine needle aspiration (FNA) biopsy. A 51-year-old woman presented with neck swelling. An ultrasound examination revealed a single solid nodule in the right thyroid lobe that measured 5.4 × 4.7 × 4.3 cm. Laboratory examination revealed elevated levels of serum calcitonin (8643.0 pg/ml), carcinoembryonic antigen (CEA) (86.2 ng/ml), and chromogranin A (123.2 ng/ml). An FNA biopsy of the thyroid nodule revealed predominantly single plasmacytoid cells with round to oval eccentric nuclei and dark brown intracytoplasmic granules. Immunohistochemical studies with Melan-A performed on a cell block slide confirmed that the granules contained melanin. The tumor cells were also positive for calcitonin, CEA, synaptophysin, AE1/AE3, CAM5.2, and HMB-45(focal); the tumor cells were negative for chromogranin, thyroglobulin, PAX8 and TTF-1. The diagnosis was reported as melanotic variant of medullary thyroid carcinoma. The patient underwent a total thyroidectomy which revealed tumor cell expression of insulinoma-associated protein 1 and confirmed neuroendocrine differentiation. Shortly after she presented with tumor recurrence in the thyroidectomy bed. The tumor cells were positive for only S100, SOX10, and Melan-A. Molecular analysis with the SEMA4 Solid Tumor Panel revealed mutations in the HRAS, PIK3CA, PIK3R1, MYC, and CCND3 genes. The final diagnosis was reported as melanocytic medullary thyroid carcinoma with high grade transformation and loss of epithelial and neuroendocrine expression.     

Thymic carcinoma of the thyroid

A highly malignant case of intrathyroidal thymic carcinoma showing morphological and biochemical evidence identical wtth medlastlnal thymoma is presented. A 32-year-old female, who had previously undergone total colectomy with lleo-proctostomy due to familial adenomatous polypnosis, was operated on for a tumor (3.4 × 4.5 cm) originating from the left thyroid lobe. A minute focus (diam. 0.8 cm) of papillary adenocarcinoma also existed in the upper pole of the right lobe. The main tumor was morphologically an epithelial thymoma with scanty lymphocyte intermixing and showed medullary differentiation with apparent Hassall's corpuscles. Mitosis was frequent and numerous tumor thrombi were in the subcapsular veins. Five months after the total thyroidec-tomy and lymph node dissection, a subcutaneous recurrence of the tumour (dlam. 2.3 cm) appeared in the anterior cervical region. The cystic contents of the recurrent tumor revealed a high titer of thymosin α1. Other organs, including thymus, lungs, and adrenals, had all been free of neoplastic changes clinically and radiologically for 5 months after her first admission until the local tumor recurrence.     

Mixed mucus-secreting and oncocytic carcinoma of the thyroid: pathologic, histochemical, immunohistochemical, and ultrastructural study of a case

We report a carcinoma that is, to the best of our knowledge, the first case of a mixed mucus-secreting and oncocytic carcinoma of the thyroid. We also describe the histochemical, immunohistochemical, and ultrastructural features of this tumor. A 59-year-old man complaining of severe bone pain and weight loss underwent clinical and radiologic investigations. The studies revealed a nodule in the left thyroid lobe that was "cold" by (131)I scintiscan and multiple lytic lesions of the skeleton that showed increased uptake by (99m)Tc-Sestamibi scintiscan. Left hemithyroidectomy was performed and the surgical specimen contained a well-circumscribed nodule of 3 cm in the greatest diameter. Light microscopy showed an oncocytic carcinoma with an area of glandular and papillary proliferation of mucin-producing cells. A double histochemical approach (Alcian blue-periodic acid-Schiff and Alcian blue-high-iron diamine) combined with ultrastructural investigation confirmed the presence of true mucus, ruling out the presence of breakdown products of thyroglobulin. Ultrastructural and immunohistochemical studies, together with clinical findings, excluded a possible metastatic origin of the mucin-producing component.     

Immunohistochemical comparison of chromogranins A and B and secretogranin II with calcitonin and calcitonin gene-related peptide expression in normal, hyperplastic and neoplastic C-cells of the human thyroid

Normal and hyperplastic thyroid C-cells and 14 cases of medullary thyroid carcinoma were investigated immunohistochemically with antibodies against chromogranins A and B, secretogranin II, calcitonin and calcitonin gene-related peptide (CGRP). Normal and hyperplastic C-cells showed strong calcitonin and chromogranin A immunoreactivity whereas CGRP, chromogranin B and secretogranin II expression was less intense. Strong calcitonin and chromogranin A immunoreactivity was also found in the majority of tumour cells in medullary thyroid carcinoma. The CGRP, chromogranin B and secretogranin II staining observed was present in variable patterns. In some cases CGRP, chromogranin B and secretogranin II could only be demonstrated in isolated tumour cells with elongated processes suggestive of neuronal differentiation of these cells. The biological function(s) of the chromogranins/secretogranins remain(s) still unclear. There is evidence that these proteins are pro-peptides which give rise to functionally active compounds. Studies on normal C-cells and medullary thyroid carcinoma may elucidate the role of chromogranins/secretogranins in endocrine and neuronal cells.