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Medullary Thyroid Carcinoma (medullary + thyroid_carcinoma)
Kinds of Medullary Thyroid Carcinoma Selected AbstractsMEDULLARY THYROID CARCINOMA: A 20-YEAR EXPERIENCE FROM A CENTRE IN SOUTH INDIAANZ JOURNAL OF SURGERY, Issue 3 2007Philip Finny Background: Management of medullary thyroid carcinoma (MTC) remains controversial despite many advances over the past five decades. We attempt to review the presentation, management and prognosis of MTC at our institution over the last two decades. Methods: We conducted a retrospective review of the records of 40 patients with MTC over a period of 20 years. Results: Ten patients had hereditary MTC and 30 had sporadic MTC. The mean age of presentation was 41 years. Sixty-five per cent of the patients had a definite thyroid swelling and 43% had lymphadenopathy at the time of presentation. Total thyroidectomy with a central neck dissection was carried out in 82.5% of patients. Adjuvant therapy was given in 75% of patients because of extensive/residual disease. Postoperative hypercalcitoninaemia was seen 73% of patients. 131I metaiodobenzylguanidine scanning was carried out in 16 patients with persistent hypercalcitoninaemia; the uptake was positive in 10 and negative in 6, indicating a positivity of 62%. Conclusion: Medullary thyroid carcinoma accounts for 2.5% of thyroid carcinomas. There is a small male preponderance. In our series 131I metaiodobenzylguanidine scan had a better positivity than what has been reported in the published work. Persistent postoperative hypercalcitoninaemia was associated with a poorer prognosis that did not reach statistical significant. [source] Large-scale Analysis of Mutations in RET Exon 16 in Sporadic Medullary Thyroid Carcinomas in JapanCANCER SCIENCE, Issue 6 2001Torn Takano Germline mutations in the RET proto-oncogene are the cause of multiple endocrine neoplasia type 2 (MEN 2A and 2B) and familial medullary thyroid carcinoma (FMTC). Some cases of sporadic medullary thyroid carcinoma (MTC) have also been reported to have mutations in the RET gene. However, two previous reports have given discrepant results on the frequency of the mutations in RET in sporadic MTCs in Japan. To clarify this problem, we analyzed mutations in RET exon 16 in 72 sporadic MTCs by means of the two methods used in the previous studies, direct sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Mutations in exon 16 were detected in only 2 of 72 cases of sporadic MTC. These results suggest that when a MTC has a mutation in RET exon 16, it is more likely to be a hereditary MTC than a sporadic one in Japan. [source] Medullary thyroid carcinoma presenting as rectangular cell type on fine-needle aspirationDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2009Andrew M. Schreiner M.D. Abstract Medullary thyroid carcinoma typically presents as dyscohesive plasmacytoid, spindled, or polygonal cells on fine-needle aspiration smears. We recently encountered a case of sporadic medullary thyroid carcinoma that presented as a hypercellular aspirate composed of cohesive aggregates of rectangle-shaped cells. The case was mistakenly reported as a hypercellular follicular neoplasm on cytology. Subsequent thyroidectomy revealed medullary carcinoma. We draw attention to this distinctive rectangular cell type as an additional morphology for medullary thyroid carcinoma. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Secretory activity in medullary thyroid carcinoma: A cytomorphological and immunocytochemical studyDIAGNOSTIC CYTOPATHOLOGY, Issue 6 2007D.Sc., Dilip K. Das M.B.B.S., F.R.C.Path., Ph.D. Abstract Medullary thyroid carcinoma (MTC) is a relatively rare thyroid malignancy of C-cell origin that secretes calcitonin. Although its varied cytomorphologic features are well described in literature, very little is mentioned about the morphologic manifestation of its secretory activity. This study, based on nine fine needle aspiration (FNA) samples from eight MTC patients, is an attempt to present the varied cytomorphologic features suggesting secretory activity in MTC as observed in Papanicolaou and MGG stained FNA smears and correlate them with the immunocytochemical (ICC) staining for calcitonin performed on FNA smears and the serum calcitonin values. The average number of cells in these nine samples was as follows: oval/triangular/plasmacytoid (56.7%), small round (23.6%), spindle-shaped (12.7%), and miscellaneous (7.1%). The cytomorphological features suggesting secretory activity, viz., fine cytoplasmic vacuoles, azurophillic granules, marginal vacuoles, and intracytoplasmic lumina (ICL) with secretions were present in eight, eight, five, and six samples, respectively. Material likely to be amyloid, based on morphological features, was present extracellularly in three samples and both intracellularly and extracellularly in six samples. Immunocytochemically, all the nine samples stained for calcitonin and all the three stained for chromogranin showed positive cytoplasmic reaction in the neoplstic cells. The background amyloid (in six samples), the coarse cytoplasmic granules (in two samples), and the contents of ICL (in one sample) were found to be positively stained for calcitonin. The intracytoplasmic secretory material appeared to be diffusing out of some cells both in the routine MGG stained smears and in the smears stained for calcitonin. Histopathology reports of seven samples in six patients confirmed the cytodiagnosis of MTC in all. Baseline serum calcitonin values in three cases and postoperative serum calcitonin levels during follow-up in three others were high. Thus, our study highlighted the morphological manifestations of secretory activity in MTC and the nature of secretory material as calcitonin, supported by immunocytochemical staining and serum calcitonin level. Diagn. Cytopathol. 2007;35:329,337. © 2007 Wiley-Liss, Inc. [source] Medullary thyroid carcinoma and biomarkers: past, present and futureJOURNAL OF INTERNAL MEDICINE, Issue 1 2009W. Van Veelen Abstract. The clinical management of patients with persistent or recurrent medullary thyroid carcinoma (MTC) is still under debate, because these patients either have a long-term survival, due to an indolent course of the disease, or develop rapidly progressing disease leading to death from distant metastases. At this moment, it cannot be predicted what will happen within most individual cases. Biomarkers, indicators which can be measured objectively, can be helpful in MTC diagnosis, molecular imaging and treatment, and/or identification of MTC progression. Several MTC biomarkers are already implemented in the daily management of MTC patients. More research is being aimed at the improvement of molecular imaging techniques and the development of molecular systemic therapies. Recent discoveries, like the prognostic value of plasma calcitonin and carcino-embryonic antigen doubling-time and the presence of somatic RET mutations in MTC tissue, may be useful tools in clinical decision making in the future. In this review, we provide an overview of different MTC biomarkers and their applications in the clinical management of MTC patients. [source] Diagnostic and surgical dilemmas in hereditary medullary thyroid carcinomaTHE LARYNGOSCOPE, Issue 7 2009Shawn M. Allen MD Abstract Medullary thyroid carcinoma (MTC) is a rare malignancy arising from the parafollicular C cells within the thyroid gland. The majority of cases are sporadic, but at least 30% are hereditary in nature. Inherited forms of MTC occur as familial MTC or as a manifestation of multiple endocrine neoplasia type 2. Early diagnosis and aggressive surgical management, including prophylactic thyroidectomy, improve the prognosis of patients with hereditary MTC. Several issues regarding the diagnosis and treatment of MTC remain controversial. Genetic penetrance and virulence are variable. We present an index case of familial MTC to illustrate common difficulties in the initial diagnosis and dilemmas in the surgical approach, followed by a review of current literature relevant to the management of hereditary MTC. Laryngoscope, 2009 [source] Medullary thyroid carcinoma as part of a multiple endocrine neoplasia type 2B syndromeCANCER, Issue 1 2002Influence of the stage on the clinical course Abstract BACKGROUND Multiple endocrine neoplasia type 2B (MEN 2B) is an exceptional syndrome, for which the optimal age of thyroidectomy is poorly established and the course of medullary thyroid carcinoma (MTC) is ill-defined. PATIENTS All the 18 patients with a MEN 2B syndrome examined at the Institut Gustave Roussy were included in a single-center retrospective study. RESULTS There were 9 men and 9 women with a mean age of 13 years (range, 2,27 years) at diagnosis. The diagnosis of MTC was based on the presence of a thyroid nodule or involved neck lymph nodes and on dysmorphic features of MEN 2B in 60% and 40% of the cases, respectively. The classic M918T mutation in exon 16 was found in the 16 patients in whom it was investigated. At diagnosis, 2 patients had Stage I MTC, 15 patients had Stage III, and 1 patient had Stage IV disease. T1 MTC was found in 4 patients aged 2.1,3.7 years. However, two of these patients already had N1 disease. One patient with Stage I MTC, aged 3.4 years and 2 patients with Stage III disease, aged 14 and 25 years, had undetectable basal calcitonin (CT) after initial surgery. During follow-up, basal CT became detectable in one of three patients. Among the 15 other patients with an elevated postoperative CT level, metastases were demonstrated in 5 patients after a mean follow-up of 2 years. Five patients died, three of MTC, one of the MEN 2B syndrome, and one of intercurrent disease. Five- and 10-year overall survival rates were 85% and 75%, respectively. CONCLUSIONS This study confirms the need for early treatment of MTC in patients with the MEN 2B syndrome, preferably within the first 6 months of life. The phenotype of MTC occurring in the MEN 2B syndrome was not more aggressive than sporadic MTC or MTC occurring in other familial syndromes. Cancer 2002;94:44,50. © 2002 American Cancer Society. [source] Predictive value of pentagastrin test for preoperative differential diagnosis between C-cell hyperplasia and medullary thyroid carcinoma in patients with moderately elevated basal calcitonin levelsCLINICAL ENDOCRINOLOGY, Issue 1 2010F. Milone Summary Background and Objectives, Medullary thyroid carcinoma (MTC) is a calcitonin (CT)-secreting neuroendocrine tumour originating from thyroid C cells. Serum CT concentrations are helpful in the early detection of MTC, while it is still unclear whether they can be used also for the differential diagnosis between MTC and C-cell hyperplasia (CCH), a precancerous condition in familial MTCs but with unclear clinical significance in sporadic MTCs. Nowadays, surgery is recommended in all patients with basal or pentagastrin (PG)-stimulated CT value of 100 pg/ml or more, without discriminating if they are affected with MTC or CCH only. The objective of this study was to investigate the utility of the PG test for CT in distinguishing CCH from MTC before surgery. Patients and Methods, Sixteen of 20 patients with thyroid nodules and basal CT levels between 15 and 100 ng/l had a positive PG test (>100 ng/l PG CT peak) and form the basis of the data analysis. A diagnosis of MTC was histologically proved on surgical samples in seven patients and of CCH in nine other patients. Four patients with neither FNAB nor PG test consistent with a diagnosis of MTC did not undergo thyroidectomy. Results, A peak of CT of 275 ng/l after PG was able to significantly distinguish patients with MTC from patients with CCH, with 100% sensitivity and 89% specificity (P = 0·002). PG-stimulated calcitonin levels >275 ng/l had a positive predictive value (PPV) value for diagnosis of MTC of 100%, and PG-stimulated calcitonin levels <275 had a PPV for the diagnosis of CCH of 89%. Conclusions, A CT cut-off after PG of 275 ng/l is suggested to be highly predictive in distinguishing CCH from MTC before surgery, and this may be helpful in selecting patients for thyroid surgery. [source] Bilateral breast lesions in a patient with medullary thyroid carcinomaCYTOPATHOLOGY, Issue 6 2009F. Andreiuolo No abstract is available for this article. [source] Medullary thyroid carcinoma presenting as rectangular cell type on fine-needle aspirationDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2009Andrew M. Schreiner M.D. Abstract Medullary thyroid carcinoma typically presents as dyscohesive plasmacytoid, spindled, or polygonal cells on fine-needle aspiration smears. We recently encountered a case of sporadic medullary thyroid carcinoma that presented as a hypercellular aspirate composed of cohesive aggregates of rectangle-shaped cells. The case was mistakenly reported as a hypercellular follicular neoplasm on cytology. Subsequent thyroidectomy revealed medullary carcinoma. We draw attention to this distinctive rectangular cell type as an additional morphology for medullary thyroid carcinoma. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Cytomorphology of anaplastic giant cell type of medullary thyroid carcinoma,A diagnostic dilemma in an elderly female: A case reportDIAGNOSTIC CYTOPATHOLOGY, Issue 2 2008Bharat Rekhi M.D., D.N.B, M.I.A.C No abstract is available for this article. [source] Secretory activity in medullary thyroid carcinoma: A cytomorphological and immunocytochemical studyDIAGNOSTIC CYTOPATHOLOGY, Issue 6 2007D.Sc., Dilip K. Das M.B.B.S., F.R.C.Path., Ph.D. Abstract Medullary thyroid carcinoma (MTC) is a relatively rare thyroid malignancy of C-cell origin that secretes calcitonin. Although its varied cytomorphologic features are well described in literature, very little is mentioned about the morphologic manifestation of its secretory activity. This study, based on nine fine needle aspiration (FNA) samples from eight MTC patients, is an attempt to present the varied cytomorphologic features suggesting secretory activity in MTC as observed in Papanicolaou and MGG stained FNA smears and correlate them with the immunocytochemical (ICC) staining for calcitonin performed on FNA smears and the serum calcitonin values. The average number of cells in these nine samples was as follows: oval/triangular/plasmacytoid (56.7%), small round (23.6%), spindle-shaped (12.7%), and miscellaneous (7.1%). The cytomorphological features suggesting secretory activity, viz., fine cytoplasmic vacuoles, azurophillic granules, marginal vacuoles, and intracytoplasmic lumina (ICL) with secretions were present in eight, eight, five, and six samples, respectively. Material likely to be amyloid, based on morphological features, was present extracellularly in three samples and both intracellularly and extracellularly in six samples. Immunocytochemically, all the nine samples stained for calcitonin and all the three stained for chromogranin showed positive cytoplasmic reaction in the neoplstic cells. The background amyloid (in six samples), the coarse cytoplasmic granules (in two samples), and the contents of ICL (in one sample) were found to be positively stained for calcitonin. The intracytoplasmic secretory material appeared to be diffusing out of some cells both in the routine MGG stained smears and in the smears stained for calcitonin. Histopathology reports of seven samples in six patients confirmed the cytodiagnosis of MTC in all. Baseline serum calcitonin values in three cases and postoperative serum calcitonin levels during follow-up in three others were high. Thus, our study highlighted the morphological manifestations of secretory activity in MTC and the nature of secretory material as calcitonin, supported by immunocytochemical staining and serum calcitonin level. Diagn. Cytopathol. 2007;35:329,337. © 2007 Wiley-Liss, Inc. [source] Intracytoplasmic lumina in metastatic medullary thyroid carcinomaDIAGNOSTIC CYTOPATHOLOGY, Issue 4 2007Guang-Qian Xiao M.D., Ph.D. No abstract is available for this article. [source] Spurious hypercalcitoninemia in patients with nodular thyroid disease induced by heterophilic antibodiesHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 1 2010Jung Min Kim MD Abstract Background Serum calcitonin is the most useful tumor marker for the diagnosis and follow-up of medullary thyroid carcinoma (MTC). Spurious hypercalcitoninemia caused by heterophilic antibody interference (HAI) is rarely found in patients without MTC. Methods We studied 2 patients with hypercalcitoninemia and thyroid nodules, but no evidence of MTC on fine-needle aspiration cytology. We performed calcium stimulation tests, measured serum calcitonin with another calcitonin kit, performed dilution tests, and remeasured serum calcitonin after applying heterophilic blocking tubes. Results In a 31-year-old woman with no response to the calcium stimulation test, serum calcitonin was <5 pg/mL using another kit. After we applied heterophilic blocking tubes, the serum calcitonin level decreased to normal range. We concluded that patient had spurious hypercalcitoninemia. In a 63-year-old woman, all tests revealed that the patient had true hypercalcitoninemia. The patient underwent total thyroidectomy that revealed MTC. Conclusions We suggest that patients suspected for spurious hypercalcitoninemia should undergo further investigation due to HAI. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [source] Multiple endocrine neoplasia type 2BINTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2001Seiji Nakata Abstract We report a case of multiple endocrine neoplasia type 2B (MEN 2B) in a 30-year-old woman. There was no family history of MEN 2B in her family. DNA testing was carried out and a point mutation was found in exon 16, codon 918 (ATG to ACG) in the RET proto-oncogene. The woman died of medullary thyroid carcinoma, 13 years after a total thyroidectomy. [source] Medullary thyroid carcinoma and biomarkers: past, present and futureJOURNAL OF INTERNAL MEDICINE, Issue 1 2009W. Van Veelen Abstract. The clinical management of patients with persistent or recurrent medullary thyroid carcinoma (MTC) is still under debate, because these patients either have a long-term survival, due to an indolent course of the disease, or develop rapidly progressing disease leading to death from distant metastases. At this moment, it cannot be predicted what will happen within most individual cases. Biomarkers, indicators which can be measured objectively, can be helpful in MTC diagnosis, molecular imaging and treatment, and/or identification of MTC progression. Several MTC biomarkers are already implemented in the daily management of MTC patients. More research is being aimed at the improvement of molecular imaging techniques and the development of molecular systemic therapies. Recent discoveries, like the prognostic value of plasma calcitonin and carcino-embryonic antigen doubling-time and the presence of somatic RET mutations in MTC tissue, may be useful tools in clinical decision making in the future. In this review, we provide an overview of different MTC biomarkers and their applications in the clinical management of MTC patients. [source] RET receptor signaling: Dysfunction in thyroid cancer and Hirschsprung's diseasePATHOLOGY INTERNATIONAL, Issue 4 2006Naoya Asai Gain-of-function mutations within the receptor tyrosine kinase gene RET cause inherited and non-inherited thyroid cancer. Somatic gene rearrangements of RET have been found in papillary thyroid carcinoma and germline point mutations in multiple endocrine neoplasia (MEN) types 2A and 2B and familial medullary thyroid carcinoma (FMTC). Conversely, loss-of-function mutations are responsible for the development of Hirschsprung's disease, a congenital malformation of the enteric nervous system. Comparison between normal RET signaling activated by the RET ligand glial cell line-derived neurotrophic factor (GDNF) and abnormal RET signaling caused by various mutations has led to a deeper understanding of disease mechanisms. The focus of the present review is on recent progress in the study of RET signaling dysfunction in human diseases. [source] Diagnostic and surgical dilemmas in hereditary medullary thyroid carcinomaTHE LARYNGOSCOPE, Issue 7 2009Shawn M. Allen MD Abstract Medullary thyroid carcinoma (MTC) is a rare malignancy arising from the parafollicular C cells within the thyroid gland. The majority of cases are sporadic, but at least 30% are hereditary in nature. Inherited forms of MTC occur as familial MTC or as a manifestation of multiple endocrine neoplasia type 2. Early diagnosis and aggressive surgical management, including prophylactic thyroidectomy, improve the prognosis of patients with hereditary MTC. Several issues regarding the diagnosis and treatment of MTC remain controversial. Genetic penetrance and virulence are variable. We present an index case of familial MTC to illustrate common difficulties in the initial diagnosis and dilemmas in the surgical approach, followed by a review of current literature relevant to the management of hereditary MTC. Laryngoscope, 2009 [source] MEDULLARY THYROID CARCINOMA: A 20-YEAR EXPERIENCE FROM A CENTRE IN SOUTH INDIAANZ JOURNAL OF SURGERY, Issue 3 2007Philip Finny Background: Management of medullary thyroid carcinoma (MTC) remains controversial despite many advances over the past five decades. We attempt to review the presentation, management and prognosis of MTC at our institution over the last two decades. Methods: We conducted a retrospective review of the records of 40 patients with MTC over a period of 20 years. Results: Ten patients had hereditary MTC and 30 had sporadic MTC. The mean age of presentation was 41 years. Sixty-five per cent of the patients had a definite thyroid swelling and 43% had lymphadenopathy at the time of presentation. Total thyroidectomy with a central neck dissection was carried out in 82.5% of patients. Adjuvant therapy was given in 75% of patients because of extensive/residual disease. Postoperative hypercalcitoninaemia was seen 73% of patients. 131I metaiodobenzylguanidine scanning was carried out in 16 patients with persistent hypercalcitoninaemia; the uptake was positive in 10 and negative in 6, indicating a positivity of 62%. Conclusion: Medullary thyroid carcinoma accounts for 2.5% of thyroid carcinomas. There is a small male preponderance. In our series 131I metaiodobenzylguanidine scan had a better positivity than what has been reported in the published work. Persistent postoperative hypercalcitoninaemia was associated with a poorer prognosis that did not reach statistical significant. [source] 111In-labelled octreotide binding by the somatostatin receptor subtype 2 in neuroendocrine tumours,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 5 2003S. H. Hashemi Background: The aim of this study was to investigate the importance of somatostatin receptor subtype 2 (SSTR2) expression for 111In-labelled diethylenetriamine-pentaacetic acid (DTPA)- D -Phe1 -octreotide binding and uptake of 111In in neuroendocrine tumours. Methods: 111In activity concentrations in surgical biopsies from neuroendocrine tumours (midgut carcinoid and medullary thyroid carcinoma), breast carcinoma and blood were determined 1,8 days after intravenous injection of 111In-labelled DTPA- D -Phe1 -octreotide (140,350 MBq). The ratio of 111In activity concentrations between tumour tissue and blood (T/B value) was calculated. The expression of SSTR2 messenger RNA (mRNA) in tumour biopsies was quantitated by ribonuclease protection assay and SSTR2 protein was localized by immunocytochemistry. Results: T/B values were highest for tumour biopsies from midgut carcinoids (mean 160 (range 4,1200); n = 65) followed by medullary thyroid carcinoma (mean 38 (range 2,350); n = 88) and breast carcinoma (mean 18 (range 4,41); n = 4). The expression of SSTR2 mRNA (relative to the NCI-H69 cell line) was highest in tumour biopsies from midgut carcinoids (mean 2·5 (range 0·83,6·0); n = 40) followed by medullary thyroid carcinoma (mean 1·3 (range 0·20,6·0); n = 7) and breast carcinoma (mean 0·66 (range 0·29,1·0); n = 9). In tumour biopsies SSTR2 protein was localized exclusively to tumour cells. Conclusion: Midgut carcinoid tumours showed a much higher level of SSTR2 expression than medullary thyroid carcinoma in accordance with superior tumour imaging by octreotide scintigraphy. The high SSTR2 mRNA values and T/B values observed in midgut carcinoid tumours were positively correlated. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Toxicity and efficacy of combined radioimmunotherapy and bevacizumab in a mouse model of medullary thyroid carcinoma,CANCER, Issue S4 2010Pierre-Yves Salaun MD Abstract BACKGROUND: Significant antitumor effects were previously observed with radioimmunotherapy (RIT) using an anti-carcinoembryonic antigen (CEA) monoclonal antibody (F6) labeled with iodine-131 in medullary thyroid cancer (MTC)-bearing nude mice. Nevertheless, no complete response was achieved. Because angiogenesis is critical for tumor growth, bevacizumab is used to treat solid tumor in clinical practice. The present pilot study evaluated toxicity and efficacy of RIT combined with bevacizumab in mice subcutaneously grafted with TT MTC cells. METHODS: Groups of 4-6 nude mice were treated with 5 ,g/g bevacizumab twice weekly during 4 weeks and/or 100 MBq of 131I-F6. For combined therapy, bevacizumab was given at Day 0 followed by 131I-F6 at Day 30. The control group received no treatment. Animal weight, hematological toxicity, tumor volume, and serum calcitonin were monitored for 2 or 4 months. RESULTS: Bevacizumab alone induced no cytopenia and no significant weight loss. A weight loss of 12 ± 1% and 15 ± 2% was observed in mice treated by RIT alone or bevacizumab + RIT, respectively. RIT alone and combined treatment induced leukopenia and anemia. RIT alone and RIT plus bevacizumab induced tumor responses with minimum relative tumor volume of 0.38 ± 0.24 and 0.15 ± 0.07%, respectively, and time to progression of 35 ± 5 and 56 ± 11 days, respectively. CONCLUSIONS: Pretreatment with bevacizumab improved RIT efficacy, with similar toxicity as compared as RIT alone. Cancer 2010;116(4 suppl):1053,8. © 2010 American Cancer Society. [source] Very early detection of RET proto-oncogene mutation is crucial for preventive thyroidectomy in multiple endocrine neoplasia type 2 childrenCANCER, Issue 2 2002Presence of C-cell malignant disease in asymptomatic carriers Abstract BACKGROUND Multiple endocrine neoplasia type 2 (MEN 2) is an inherited disease caused by germline mutations in the RET proto-oncogene, and is responsible for the development of endocrine neoplasia. Its prognosis is dependent on the appearance and spread of medullary thyroid carcinoma (MTC). Relatives at risk can be identified before clinical or biochemical signs of the disease become evident. METHODS Twenty-one families with MEN 2 (16 families with MEN 2A and 5 families with MEN 2B) were studied. Peripheral blood DNA was amplified by polymerase chain reaction. DNA sequence or restriction enzyme analysis was performed to detect mutations of RET proto-oncogene exons 10, 11, and 16. Molecular analysis was carried out in all index patients as well as in 98 relatives of MEN 2A patients (60 juveniles, ages 6 months to 21 years, and 38 adults, ages 22 to 81 years) and in 13 relatives (6 juveniles ages 10 to 21 years, and 7 adults ages 41 to 66 years) from MEN 2B families. RESULTS Molecular studies showed a mutation at codon 634, exon 11 in all MEN 2A patients. All MEN 2B patients showed an ATG to ACG (Met918Thr) mutation. In MEN 2A families, 42 out of 98 relatives were affected. Total thyroidectomy was performed in 18 juvenile carriers ages 17 months to 21 years. Histopathologic studies of the glands revealed parafollicular cell (C-cell) hyperplasia in all of these carriers, medullary thyroid carcinoma in 15 carriers, and only one carrier with lymph node metastases. CONCLUSIONS The consistent finding of C-cell disease in all the juvenile carriers who underwent preventive thyroidectomy emphasizes the relevance of early screening in children at risk of developing MTC. The presence of MTC in the specimen of prophylactic thyroidectomy from a 17 month old girl highlights the importance of thyroidectomy as soon as the molecular diagnosis is confirmed. Cancer 2002;94:323,30. © 2002 American Cancer Society. [source] Medullary thyroid carcinoma as part of a multiple endocrine neoplasia type 2B syndromeCANCER, Issue 1 2002Influence of the stage on the clinical course Abstract BACKGROUND Multiple endocrine neoplasia type 2B (MEN 2B) is an exceptional syndrome, for which the optimal age of thyroidectomy is poorly established and the course of medullary thyroid carcinoma (MTC) is ill-defined. PATIENTS All the 18 patients with a MEN 2B syndrome examined at the Institut Gustave Roussy were included in a single-center retrospective study. RESULTS There were 9 men and 9 women with a mean age of 13 years (range, 2,27 years) at diagnosis. The diagnosis of MTC was based on the presence of a thyroid nodule or involved neck lymph nodes and on dysmorphic features of MEN 2B in 60% and 40% of the cases, respectively. The classic M918T mutation in exon 16 was found in the 16 patients in whom it was investigated. At diagnosis, 2 patients had Stage I MTC, 15 patients had Stage III, and 1 patient had Stage IV disease. T1 MTC was found in 4 patients aged 2.1,3.7 years. However, two of these patients already had N1 disease. One patient with Stage I MTC, aged 3.4 years and 2 patients with Stage III disease, aged 14 and 25 years, had undetectable basal calcitonin (CT) after initial surgery. During follow-up, basal CT became detectable in one of three patients. Among the 15 other patients with an elevated postoperative CT level, metastases were demonstrated in 5 patients after a mean follow-up of 2 years. Five patients died, three of MTC, one of the MEN 2B syndrome, and one of intercurrent disease. Five- and 10-year overall survival rates were 85% and 75%, respectively. CONCLUSIONS This study confirms the need for early treatment of MTC in patients with the MEN 2B syndrome, preferably within the first 6 months of life. The phenotype of MTC occurring in the MEN 2B syndrome was not more aggressive than sporadic MTC or MTC occurring in other familial syndromes. Cancer 2002;94:44,50. © 2002 American Cancer Society. [source] Large-scale Analysis of Mutations in RET Exon 16 in Sporadic Medullary Thyroid Carcinomas in JapanCANCER SCIENCE, Issue 6 2001Torn Takano Germline mutations in the RET proto-oncogene are the cause of multiple endocrine neoplasia type 2 (MEN 2A and 2B) and familial medullary thyroid carcinoma (FMTC). Some cases of sporadic medullary thyroid carcinoma (MTC) have also been reported to have mutations in the RET gene. However, two previous reports have given discrepant results on the frequency of the mutations in RET in sporadic MTCs in Japan. To clarify this problem, we analyzed mutations in RET exon 16 in 72 sporadic MTCs by means of the two methods used in the previous studies, direct sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Mutations in exon 16 were detected in only 2 of 72 cases of sporadic MTC. These results suggest that when a MTC has a mutation in RET exon 16, it is more likely to be a hereditary MTC than a sporadic one in Japan. [source] Predictive value of pentagastrin test for preoperative differential diagnosis between C-cell hyperplasia and medullary thyroid carcinoma in patients with moderately elevated basal calcitonin levelsCLINICAL ENDOCRINOLOGY, Issue 1 2010F. Milone Summary Background and Objectives, Medullary thyroid carcinoma (MTC) is a calcitonin (CT)-secreting neuroendocrine tumour originating from thyroid C cells. Serum CT concentrations are helpful in the early detection of MTC, while it is still unclear whether they can be used also for the differential diagnosis between MTC and C-cell hyperplasia (CCH), a precancerous condition in familial MTCs but with unclear clinical significance in sporadic MTCs. Nowadays, surgery is recommended in all patients with basal or pentagastrin (PG)-stimulated CT value of 100 pg/ml or more, without discriminating if they are affected with MTC or CCH only. The objective of this study was to investigate the utility of the PG test for CT in distinguishing CCH from MTC before surgery. Patients and Methods, Sixteen of 20 patients with thyroid nodules and basal CT levels between 15 and 100 ng/l had a positive PG test (>100 ng/l PG CT peak) and form the basis of the data analysis. A diagnosis of MTC was histologically proved on surgical samples in seven patients and of CCH in nine other patients. Four patients with neither FNAB nor PG test consistent with a diagnosis of MTC did not undergo thyroidectomy. Results, A peak of CT of 275 ng/l after PG was able to significantly distinguish patients with MTC from patients with CCH, with 100% sensitivity and 89% specificity (P = 0·002). PG-stimulated calcitonin levels >275 ng/l had a positive predictive value (PPV) value for diagnosis of MTC of 100%, and PG-stimulated calcitonin levels <275 had a PPV for the diagnosis of CCH of 89%. Conclusions, A CT cut-off after PG of 275 ng/l is suggested to be highly predictive in distinguishing CCH from MTC before surgery, and this may be helpful in selecting patients for thyroid surgery. [source] Evaluation of RET polymorphisms in a six-generation family with G533C RET mutation: specific RET variants may modulate age at onset and clinical presentationCLINICAL ENDOCRINOLOGY, Issue 1 2009Rosana Tamanaha Summary Context, We previously described a six-generation family with G533C RET mutation and medullary thyroid carcinoma, in the largest family reported do date. Of particular interest, phenotype variability regarding the age of onset and clinical presentation of the disease, was observed. Objective, We evaluate whether single SNPs within RET oncogene or haplotype comprising the RET variants (defined by Haploview) could predispose to early development of MTC in this family and influence the clinical manifestation. Design, Eight SNPs were selected based on their previous association with the clinical course of hereditary or sporadic MTC, in particular promoting an early onset of disease. The variants were initially tested in 77 G533C-carriers and 100 controls using either PCR-direct sequencing or PCR,RFLP. Association between a SNP or haplotype and age at diagnosis or presence of lymph node metastasis was tested in 34 G533C-carries with MTC. Different bioinformatic tools were used to evaluate the potential effects on RNA splicing. Results, An association was found between IVS1,126G > T and age at diagnosis. The variant [IVS8 +82A > G; 85,86 insC] was associated with the presence of lymph node metastases at diagnosis. In silico analysis suggested that this variant may induce abnormal splicing. This in silico analysis predicted that the [IVS8 +82A > G; 85,86 insC] could alter the splicing by disrupting and/or creating exonic splicing enhancer motifs. Conclusions, We here identified two RET variants that were associated with phenotype variability in G533C-carriers, which highlights the fact that the modifier effect of a variant might depend on the type of mutation. [source] Long-term prognosis of medullary thyroid carcinomaCLINICAL ENDOCRINOLOGY, Issue 3 2008G. Rendl Summary Objective, The clinical course of patients with medullary thyroid carcinoma (MTC) is variable, even in the subgroup of patients after surgery with curative intent and postoperatively persistent elevated calcitonin levels. This study aimed to evaluate the long-term prognosis of survival in patients with MTC. Patients, Long-term survival was analysed in 32 patients with MTC being treated in an endocrine centre over a 40-year period. Patients were classified as having sporadic MTC, familial MTC (FMTC), multiple endocrine neoplasia (MEN) IIA or MEN IIB. Results, Seventeen patients had sporadic MTC (53·1%), eight had MEN IIA (25%) and three had MEN IIB (9·4%); the remaining four patients (12·5%) had not undergone genetic analysis until now. The overall average age at diagnosis was 42·0 years, and the median follow-up time was 9·5 years (range 0·5,39 years). Mortality due to progressive MTC was 15·6%. The 5-year survival rate was 96% (95% CI 89,100), the 10-year survival rate 91% (95% CI 79,100), and the 15-year survival rate 85% (95% CI 78,100). The estimated mean survival time after initial diagnosis was 31 years (95% CI 26·7,37·0). There is a significant difference in survival time between patients achieving complete remission compared with patients with biochemical persistent disease (P = 0·038) or metastasis (P = 0·0003). In five patients, advanced imaging with positron emission tomography/computed tomography (PET/CT) identified additional sites of tumour load. Eight more lymph node metastases were found in four patients and one local tumour recurrence in one patient by PET/CT. Conclusion, The overall prognosis of MTC is favourable, even if the rate of biochemical cure is lower in MTC than in differentiated types of thyroid cancer. This is also true for patients with biochemically persistent disease. Whether the identification of further tumour sites by advanced imaging procedures such as PET/CT translates into a better prognosis in patients with persistently elevated calcitonin levels remains to be investigated. [source] Frequent association between MEN 2A and cutaneous lichen amyloidosisCLINICAL ENDOCRINOLOGY, Issue 2 2003Uberta Verga Summary objective Multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are genetic diseases due to activating mutations of the RET proto-oncogene. Affected patients develop medullary thyroid carcinoma (100%), in an isolated form (FMTC) or in association with phaeochromocytoma (30,50%), and primary hyperparathyroidism (10,20%) (MEN 2A). The presence of cutaneous lichen amyloidosis (CLA) has been anecdotally described in few families harbouring RET proto-oncogene mutation in codon 634. The aim of the study was to evaluate the incidence of CLA in MEN 2A/FMTC families. patients and design Ten MEN 2A/FMTC families were studied and RET gene mutations identified in all. Complete dermatological assessment was carried out in each family member. Skin biopsy for histological studies was performed in patients with CLA. results Among 10 MEN 2A/FMTC families, the presence of CLA was found only in patients belonging to the three families with MEN 2A and RET mutation in codon 634. Nine of 25 patients (36%) with codon 634 mutation presented CLA, though two of them did not show CLA skin lesions but the typical neurological pruritus in the upper back. In all patients, neurological pruritus was present since infancy as a precocious marker of the disorder. The dermatological study of patients with CLA skin lesions added further evidence that pruritus has a pivotal role in the development of CLA, the amyloid deposition being the consequence of repeated scratching. Light microscopy revealed orthokeratotic hyperkeratosis, with elongation of the rete ridges, rare intramalpighian apoptic keratinocytes and deposits of amorphous material in the superficial dermis. Examination under ultraviolet light showed thioflavin T-positive staining, confirming the presence of amyloid in the papillary dermis. The use of Capsaicin at the dilution of 0·025% had a mild efficacy on the cutaneous symptoms. conclusions Among the members of the three families with MEN 2A and RET 634 mutation, the incidence of CLA was 36%, a figure similar to that reported in the literature for phaeochromocytoma (30,50%) and even higher than that for hyperparathyroidism (10,20%). The present data confirm that CLA is linked to codon 634 RET mutations and is a precocious marker of the disorder. [source] A new identified germline mutation of the RET proto-oncogene responsible for familial medullary thyroid carcinoma in co-existence with a hyperfunctioning autonomous noduleCLINICAL ENDOCRINOLOGY, Issue 6 2002W. Maschek No abstract is available for this article. [source] Pheochromocytoma in childhood: implication for further diagnostic proceduresACTA PAEDIATRICA, Issue 12 2004O Beck We report on our experience with two patients with pheochromocytoma. One patient underwent surgery of pheochromocytoma at the age of 30 y; 18 y later, medullary thyroid carcinoma (MTC) was detected in his son. Subsequently, multiple endocrine neoplasia (MEN) type 2A was diagnosed by genetic examination in both father and son. Further diagnostic procedures also revealed an MTC in the father. The other patient suffered from bifocal pheochromocytoma of the left suprarenal gland. Diagnostic work-up revealed papillary thyroid carcinoma, which was also detected in the mother 8 mo later. Whereas a point mutation in SDHB gene was found in the son, no genetic abnormality was detected in the mother. Conclusion: Every pheochromocytoma in childhood warrants further diagnostic work-up, including genetic examination. In addition, clinical data of patients suffering from pheochromocytoma and papillary thyroid carcinoma should be collected by an international registry, and a joint effort should be undertaken in order to define possible underlying mutated genes in these patients. [source] | |||||||||||||||||||||||||