Tiroid Kanserleri II
Eur J Surg Oncol. 2006 Jun;32(5):577-82. Epub 2006 Apr 27.
Advanced thyroid carcinoma: an experience of 385 cases.
Freschi G, Landi L, Castagnoli A, Taddei A, Bechi P, Bucciarelli G.
Department of Surgical Pathology, University of Florence, Italy.
giancarlo.freschi@unifi.it
AIMS: To report clinical outcomes of a large series of cases with advanced thyroid cancer.
STUDY DESIGN: Three hundred and eighty-five patients at the UICC stages III and IV were selected for the study with thyroid cancer.
RESULTS: Papillary carcinoma and sclerosing carcinoma have better survival than the Hürthle cell and insular types. Lymphatic metastasis does not appear to worsen the prognosis. All the tumour forms offer the chance of long survival.
CONCLUSIONS: Surgical treatment is the primary treatment of thyroid carcinoma.
The combined treatments of surgery, metabolic beam therapy, suppressive hormone therapy, radiotherapy and chemotherapy cure a high percentage of patients with the tumour at an advanced stage.
Clin Oncol (R Coll Radiol). 2010 Aug;22(6):486-97. Epub 2010 Apr 24.
Anaplastic thyroid carcinoma: pathogenesis and emerging therapies.
Smallridge RC, Copland JA.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida 32224, USA. smallridge.robert@mayo.edu
Anaplastic thyroid carcinoma ranges from 1.3 to 9.8% of all thyroid cancers globally. Mutations, amplifications, activation of oncogenes and silencing of tumour suppressor genes contribute to its aggressive behaviour, and recent studies (e.g. microarrays, microRNAs) have provided further insights into its complex molecular dysregulation. Preclinical studies have identified numerous proteins over- or underexpressed that affect critical cellular processes, including transcription, signalling, mitosis, proliferation, cell cycle, apoptosis and adhesion, and a variety of agents that effectively inhibit these processes and tumour growth. In clinical studies of 1771 patients, 64% were women, the median survival was 5 months, and 1-year survival was 20%. The variables associated with survival in some series included age, tumour size, extent of surgery, higher dose radiotherapy, absence of distant metastases at presentation, co-existence of differentiated thyroid cancer and multimodality therapy. However, considerable bias exists in these non-randomised studies.
Although more aggressive radiotherapy has reduced locoregional recurrences, the median overall survival has not improved in over 50 years. Newer systemic therapies are being tried, and more effective combinations are needed to improve patient outcomes.
Arch Otolaryngol Head Neck Surg. 2008 May;134(5):536-8.
Consensus statement on the classification and terminology of neck dissection.
Robbins KT, Shaha AR, Medina JE, Califano JA, Wolf GT, Ferlito A, Som PM, Day TA; Committee for Neck Dissection Classification, American Head and Neck Society.
Division of Otolaryngology, Southern Illinois University School of Medicine, Springfield, IL 62794-9677, USA. trobbins@siumed.edu
OBJECTIVE: To update the guidelines for neck dissection terminology, as previously recommended by the American Head and Neck Society.
PARTICIPANTS: Committee for Neck Dissection Classification, American Head and Neck Society; representation from the Committee for Head and Neck Surgery and Oncology, American Academy of Otolaryngology-Head and Neck Surgery (T.A.D.).
EVIDENCE: Review of current literature on neck dissection classification.
CONSENSUS PROCESS: Semiannual face-to-face meetings of the Committee for Neck Dissection Terminology and e-mail correspondence.
CONCLUSIONS: Standardization of terminology for neck dissection is important for communication among clinicians and researchers. New recommendations have been made regarding the following: boundaries between levels I and II and between levels III/IV and VI; terminology of the superior mediastinal nodes; and the method of submitting surgical specimens for pathologic analysis.
Thyroid. 2009 Jun;19(6):565-612.
Medullary thyroid cancer: management guidelines of the American Thyroid
Association.
American Thyroid Association Guidelines Task Force, Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, Moley JF, Pacini F, Ringel MD, Schlumberger M, Wells SA Jr.
Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, The Arthur G. James Cancer Hospital, Columbus, Ohio 43210, USA. richard.kloos@osumc.edu
BACKGROUND: Inherited and sporadic medullary thyroid cancer (MTC) is an uncommon and challenging malignancy. The American Thyroid association (ATA) chose to create specific MTC Clinical Guidelines that would bring together and update the diverse MTC literature and combine it with evidence-based medicine and the knowledge and experience of a panel of expert clinicians.
METHODS: Relevant articles were identified using a systematic PubMed search and supplemented with additional published materials. Evidence-based recommendations were created and then categorized using criteria adapted from the United States Preventive Services Task Force, Agency for Healthcare Research and Quality.
RESULTS: Clinical topics addressed in this scholarly dialog included: initial diagnosis and therapy of preclinical disease (including RET oncogene testing and the timing of prophylactic thyroidectomy), initial diagnosis and therapy of clinically apparent disease (including preoperative testing and imaging, extent of surgery, and handling of devascularized parathyroid glands), initial evaluation and treatment of postoperative patients (including the role of completion thyroidectomy), management of persistent or recurrent MTC (including the role of tumor marker doubling times, and treatment of patients with distant metastases and hormonally active metastases), long-term follow-up and management (including the frequency of follow-up and imaging), and directions for future research.
CONCLUSIONS: One hundred twenty-two evidence-based recommendations were created to assist in the clinical care of MTC patients and to share what we believe is current, rational, and optimal medical practice.
Clinics (Sao Paulo). 2009;64(7):699-706.
Hypercalcitoninemia is not pathognomonic of medullary thyroid carcinoma.
Toledo SP, Lourenço DM Jr, Santos MA, Tavares MR, Toledo RA, Correia-Deur JE.
Unidade de Endocrinologia Genética, Laboratório de Investigação Médica (LIM-25), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo/SP, Brasil. toldo@usp.br
Hypercalcitoninemia has frequently been reported as a marker for medullary thyroid carcinoma. Currently, calcitonin measurements are mostly useful in the evaluation of tumor size and progression, and as an index of biochemical improvement of medullary thyroid carcinomas. Although measurement of calcitonin is a highly sensitive method for the detection of medullary thyroid carcinoma, it presents a low specificity for this tumor. Several physiologic and pathologic conditions other than medullary thyroid carcinoma have been associated with increased levels of calcitonin. Several cases of thyroid nodules associated with increased values of calcitonin are not medullary thyroid carcinomas, but rather
are related to other conditions, such as hypercalcemias, hypergastrinemias, neuroendocrine tumors, renal insufficiency, papillary and follicular thyroid carcinomas, and goiter. Furthermore, prolonged treatment with omeprazole (>2-4 months), beta-blockers, glucocorticoids and potential secretagogues, have been associated with hypercalcitoninemia. An association between calcitonin levels and chronic auto-immune thyroiditis remains controversial. Patients with calcitonin levels >100 pg/mL have a high risk for medullary thyroid carcinoma (approximately 90%-100%), whereas patients with values from 10 to 100 pg/mL (normal values: <8.5 pg/mL for men, <5.0 pg/mL for women; immunochemiluminometric assay) have a <25% risk for medullary thyroid carcinoma.In multiple endocrine neoplasia type 2 (MEN2), RET mutation analysis is the gold-standard for the recommendation of total preventive thyroidectomy to relatives at risk of harboring a germline RET mutation (50%). False-positive calcitonin results within MEN2 families have led to incorrect indications of preventive total thyroidectomy to RET mutation negative relatives. In this review, we focus on the differential diagnosis of hypercalcitoninemia, underlining its importance for the avoidance of misdiagnosis of medullary thyroid carcinoma and consequent incorrect recommendation for thyroid surgery.
Endocrinol Metab Clin North Am. 2008 Jun;37(2):481-96, x-xi.
Management of medullary thyroid carcinoma.
Jiménez C, Hu MI, Gagel RF.
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Unit 435, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.
Medullary thyroid carcinoma (MTC) is responsible for 13.4% of the total deaths attributable to thyroid cancer in human beings and research on MTC over the last 40 years has identified the RET proto-oncogene as a very relevant component of development of both sporadic and hereditary MTC. An activating germline RET proto-oncogene mutation responsible for a multiple endocrine neoplasia syndrome type 2 (MEN2) or a familial hereditary MTC syndrome is carried by 25% to 35% of
patients with MTC. The recognition of RET proto-oncogene mutations by genetic sequencing has allowed us to differentiate hereditary from sporadic MTC, so that it is now possible to identify and treat children at risk for this disease before development of metastasis. Thanks to this discovery, we can now establish the association of MTC with other tumors in the context of MEN2 syndrome; determine
adequate follow-up, prognosis, and treatment for patients with hereditary disease; and use this information to develop new therapies against both sporadic and hereditary MTCs.
Orphanet J Rare Dis. 2006 Nov 14;1:45.
Multiple endocrine neoplasia type 2.
Marini F, Falchetti A, Del Monte F, Carbonell Sala S, Tognarini I, Luzi E, Brandi ML.
Regional Center for Hereditary Endocrine Tumors, Department of Internal Medicine, University of Florence, Florence, Italy. f.marini@dmi.unifi.it
Multiple Endocrine Neoplasia Type 2 (MEN2) is a rare hereditary complex disorder characterized by the presence of medullary thyroid carcinoma (MTC), unilateral or bilateral pheochromocytoma (PHEO) and other hyperplasia and/or neoplasia of different endocrine tissues within a single patient. MEN2 has been reported in approximately 500 to 1000 families worldwide and the prevalence has been
estimated at approximately 1:30,000. Two different forms, sporadic and familial, have been described for MEN2. Sporadic form is represented by a case with two of the principal MEN2-related endocrine tumors. The familial form, which is more frequent and with an autosomal pattern of inheritance, consists of a MEN2 case with at least one first degree relative showing one of the characteristic
endocrine tumors. Familial medullary thyroid carcinoma (FMTC) is a subtype of MEN2 in which the affected individuals develop only medullary thyroid carcinoma, without other clinical manifestations of MEN2. Predisposition to MEN2 is caused by germline activating mutations of the c-RET proto-oncogene on chromosome 10q11.2. The RET gene encodes a single-pass transmembrane tyrosine kinase that is
the receptor for glial-derived neurotrophic growth factors. The combination of clinical and genetic investigations, together with the improved understanding of the molecular and clinical genetics of the syndrome, helps the diagnosis and treatment of patients. Currently, DNA testing makes possible the early detection of asymptomatic gene carriers, allowing to identify and treat the neoplastic
lesions at an earlier stage. In particular, the identification of a strong genotype-phenotype correlation in MEN2 syndrome may enable a more individualized treatment for the patients, improving their quality of life. At present, surgical treatment offers the only chance of cure and therefore, early clinical and
genetic detection and prophylactic surgery in subjects at risk are the main therapeutic goal.
Am J Surg Pathol. 2007 Aug;31(8):1256-64.
Poorly differentiated thyroid carcinoma: the Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach.
Volante M, Collini P, Nikiforov YE, Sakamoto A, Kakudo K, Katoh R, Lloyd RV, LiVolsi VA, Papotti M, Sobrinho-Simoes M, Bussolati G, Rosai J.
Department of Clinical and Biological Sciences at San Luigi Hospital, University of Turin, Turin, Italy. marco.volante@unito.it
Poorly differentiated (PD) thyroid carcinomas lie both morphologically and behaviorally between well-differentiated and undifferentiated (anaplastic) carcinomas. Following the original description of this entity, different diagnostic criteria have been employed, resulting in wide discrepancies and
confusion among pathologists and clinicians worldwide. To compare lesions occurring in different geographic areas and the diagnostic criteria applied in those countries, we designed a study with a panel of internationally recognized thyroid pathologists to develop consensus diagnostic criteria for PD carcinomas. Eighty-three cases were collected from Europe, Japan, and the United States, and
circulated among 12 thyroid pathologists. Diagnoses were made without any knowledge of the clinical parameters, which were subsequently used for survival analysis. A consensus meeting was then held in Turin, Italy, where an agreement was reached concerning the diagnostic criteria for PD carcinoma. These include (1) presence of a solid/trabecular/insular pattern of growth, (2) absence of the
conventional nuclear features of papillary carcinoma, and (3) presence of at least one of the following features: convoluted nuclei; mitotic activity >or=3 x 10 HPF; and tumor necrosis. An algorithmic approach was devised for practical use in the diagnosis of this tumor.
Surg Oncol Clin N Am. 2009 Jan;18(1):39-52, viii.
Thyroid cancer genetics: multiple endocrine neoplasia type 2, non-medullary familial thyroid cancer, and familial syndromes associated with thyroid cancer.
Richards ML.
Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA. richards.melanie@mayo.edu
Familial thyroid cancer accounts for 25% of medullary thyroid cancer (MTC) and 5% of non-medullary thyroid cancer. All patients who have familial MTC have one of three variants of multiple endocrine neoplasia type 2 that are defined by specific mutations in the rearranged during transfection (RET) proto-oncogene. Patients who have familial nonmedullary familial thyroid cancer most likely have
a mutation that is autosomal dominant with reduced penetrance. Thyroid cancer also is associated with a number of familial syndromes. This article focuses on the genetics and management of familial thyroid cancers and the syndromes associated with thyroid cancer.
