Thyroid Diseases: Tuttle RM

Sherman SI, Angelos P, Ball DW, Byrd D, Clark OH, Daniels GH, Dilawari RA, Ehya H, Farrar WB, Gagel RF, Kandeel F, Kloos RT, Kopp P, Lamonica DM, Loree TR, Lydiatt WM, McCaffrey J, Olson JA, Ridge JA, Shah JP, Sisson JC, Tuttle RM, Urist MM, Anonymous00403. · The University of Texas M.D. Anderson Cancer Center, USA. · J Natl Compr Canc Netw. · Pubmed #17623612 No free full text.

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Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT, Anonymous00181. · Division of Endocrinology, Diabetes, Metabolism, Nutrition, and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. · Endocr Pract. · Pubmed #16033723 No free full text.

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Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT, Anonymous00249, Anonymous00250, Anonymous00251. · Mayo Clinic College of Medicine, Rochester, MN 55905, USA. · Thyroid. · Pubmed #15687817 No free full text.

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Shaha AR, Tuttle RM, Shah JP. · No affiliation provided · J Surg Oncol. · Pubmed #17192917 No free full text.

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Tuttle RM. · Joan and Sanford I Weill Medical College of Cornell University and Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA. · Endocr Pract. · Pubmed #18996800 No free full text.

Abstract: OBJECTIVE: To describe a risk-adapted management paradigm for patients with differentiated thyroid cancer. METHODS: A risk-stratification approach is described that combines the standard clinical factors available during the initial evaluation with response-to-therapy variables to predict risk of death from thyroid cancer, risk of recurrence, and risk of failing initial therapy. This classic oncologic approach views risk stratification as an active, ongoing process in which risks are adjusted on the basis of accumulated clinical data, rather than considered as a static initial assessment that does not change. RESULTS: From a clinical standpoint, accurate real-time assessment of risk can be used to guide both the initial treatment recommendations (extent of thyroid surgical resection, role of radioiodine ablation, and degree of thyrotropin suppression) and the follow-up management paradigm (intensity of testing and modalities used to detect recurrent disease). CONCLUSION: By thinking like oncologists and individualizing therapy on the basis of initial and ongoing risk assessments, we can maximize the beneficial effects of aggressive therapy in patients with thyroid cancer who are likely to benefit from it, while minimizing potential complications and side effects in low-risk patients destined to have a full healthy productive life after minimal therapeutic intervention.

Tuttle RM, Leboeuf R. · Department of Medicine, Joan and Sanford I Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA. · Endocrinol Metab Clin North Am. · Pubmed #18502335 No free full text.

Abstract: The primary goal in the follow up of thyroid cancer patients is to identify and treat persistent and recurrent disease at a time that minimizes morbidity and disease specific mortality. This article presents a risk-adapted follow-up paradigm to guide both intensity and methodology of follow-up testing based on initial risk stratification, ongoing risk stratification, and secondary risk stratification that incorporates each of the well-known risk factors for recurrence and death from thyroid cancer, with a response to therapy variable as well as duration of disease-free survival. With a proper understanding of the biology of the disease and with accurate assessments of response to therapy, clinicians are better able to tailor a risk-appropriate follow-up approach to individual patients, minimizing excessive testing while still providing adequate testing to detect clinically significant disease recurrence in a timely fashion.

Tuttle RM, Leboeuf R, Shaha AR. · Joan and Sanford I. Weill Medical College of Cornell University, New York, New York 10021, USA. · J Surg Oncol. · Pubmed #18493922 No free full text.

Abstract: Risk adapted treatment recommendations are dependent on accurate predictions of the risk of recurrence, risk of death, and likely sites of recurrence. When combined with response to therapy assessments and secondary risk stratification during follow-up, this risk adapted approach will allow the clinician to tailor the aggressiveness of therapy and follow up to the risk of recurrence and death in individual patients.

Randolph GW, Thompson GB, Branovan DI, Tuttle RM. · Thyroid and Parathyroid Surgical Divisions, Massachusetts Eye and Ear Infirmary, Endocrine Surgical Service, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #17848306 No free full text.

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Vasko V, Bauer AJ, Tuttle RM, Francis GL. · Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. · Endocr Dev. · Pubmed #17684395 No free full text.

Abstract: Benign and malignant neoplasms of the thyroid are uncommon during childhood, but they create diagnostic problems for the clinician to identify malignant legions that must be removed as well as medically important lesions that require treatment. Throughout the 20th century there was a rapid increase in the incidence of thyroid neoplasms which we now know were induced by ionizing radiation acquired from radiation therapy for benign medical conditions or from environmental sources such as nuclear testing and accidents [Cancer 1961;14:734-743]. Over recent decades, there have been major advances in our understanding of the molecular biology and clinical management of thyroid neoplasms. We hope that the reader of this chapter will find this information of benefit in the clinical management of children with thyroid neoplasms and will be encouraged to study remaining controversial issues. We have divided this chapter into two major sections, the first of which pertains to thyroid nodules and the second to well-differentiated thyroid cancers including papillary, follicular and other variants.

Tuttle RM, Leboeuf R, Martorella AJ. · Joan and Sanford I. Weill Medical College of Cornell University, and Memorial Sloan Kettering Cancer Center, Zuckerman Building, Room 834, 1275 York Avenue, New York, NY 10021, USA. · Endocrinol Metab Clin North Am. · Pubmed #17673127 No free full text.

Abstract: The last 10 years have seen a major paradigm shift in the management of thyroid cancer, with greater reliance on serum thyroglobulin and neck ultrasonography, and less emphasis on routine diagnostic whole-body radioactive iodine scanning for detection of recurrent disease. As our follow-up tests become more sensitive for detection of recurrent disease, we are finding many asymptomatic patients who have low-level persistent disease many years after initial therapy that may or may not benefit from additional testing and therapy. These difficult issues have been addressed by at least five different sets of guidelines published recently by various thyroid specialty organizations around the world. In this article, the authors compare and contrast the recommendations from the various guidelines in an attempt to define areas of consensus and explore possible reasons for differing recommendations.

Tuttle RM, Leboeuf R. · Joan and Sanford I. Weill Medical College of Cornell University, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. · J Natl Compr Canc Netw. · Pubmed #17623615 No free full text.

Abstract: Although traditional chemotherapy has yielded disappointing results in the therapy of progressive metastatic thyroid cancer, the recent development of a wide range of novel therapies targeting critical steps in the pathogenesis of thyroid cancer has led to a renewed interest in thyroid cancer clinical trials. This review provides an overview of the pathogenesis of thyroid cancer with particular emphasis on specific molecular targets that can be modulated with these novel agents. The article reviews the results for the small number of thyroid cancer patients included in published therapeutic trials and critically examines patient selection criteria for inclusion in clinical trials. Given the dramatic increase in availability of thyroid cancer clinical trials, all patients with radioactive iodine-refractory, progressive metastatic thyroid cancer should be considered for inclusion in a novel therapy trial.

Eheman CR, Garbe P, Tuttle RM. · Epidemiology and Health Services Branch, Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. · Thyroid. · Pubmed #12855012 No free full text.

Abstract: Reports of increased rates of thyroid disease in populations exposed to radiation as a result of the Chernobyl accident have increased awareness and concern about the risk of autoimmune-related thyroid disease possibly associated with environmental radiation exposure. While the association between thyroidal irradiation and an increased risk of thyroid neoplasia is well established, much less attention has been devoted to the potential effects of environmental irradiation on the function of the thyroid. However, since the Chernobyl accident new studies have been published that appear to link radiation exposure to an increased risk of autoimmune thyroiditis. In order to assess the plausibility of this association, we reviewed published studies that evaluate the possible association between environmental thyroidal radiation and the presence of antithyroid antibodies as well as autoimmune thyroid disease (hypothyroidism and hyperthyroidism). These data have not been summarized elsewhere. Although some epidemiologic evidence of an association exists, long-term, well-designed studies are needed to accurately evaluate the complex association between low-dose environmental radiation exposure and clinically significant non-neoplastic thyroid disease. The results of these studies will be important in determining the appropriate clinical follow-up of persons exposed to environmental thyroidal irradiation.

Cohen EG, Tuttle RM, Kraus DH. · Head and Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. · Otolaryngol Clin North Am. · Pubmed #12803014 No free full text.

Abstract: The large numbers of studies on the postoperative management of differentiated thyroid carcinoma allows us to use adjuvant treatment and follow-up studies more selectively based on patient risk for recurrence and mortality. Recurrent differentiated thyroid carcinoma is more easily and more effectively treated with early diagnosis. With this in mind, patients who are at high risk for life-threatening recurrent disease should be treated aggressively and followed up expectantly. In these patients, adjuvant treatment with 131I ablation and thyroid hormone suppression is appropriate. External irradiation may be considered, especially for patients with postoperative residual disease. Close follow-up with stimulated thyroglobulin and 131I whole body scans should be performed to facilitate early detection of recurrent disease. Low-risk patients may be effectively treated with more conservative management. 131I ablation has not resulted in improved survival in these patients. Follow-up with serum thyroglobulin after initial negative 131I whole body scan may be appropriate in these patients. Management of patients at intermediate risk remains controversial. Recombinant human thyrotropin allows us to obtain stimulated serum thyroglobulin and promises the ability to perform 131I ablation and whole body scan without the need for thyroid hormone withdrawal. Functional radionuclide imaging, such as FDG PET, now allows us to localize recurrent disease in patients with elevated serum thyroglobulin but negative 131I scan.

Robbins R, Drucker W, Hann L, Tuttle RM. · Cornell University, New York, USA. · Adv Intern Med. · Pubmed #11147255 No free full text.

Abstract: The challenge of detecting and anatomically localizing metastatic thyroid cancer deposits has become less daunting with the recent developments in radionuclide technology. The use of serum Tg measurements and the whole body radioiodine scan remain the mainstays of the diagnostic evaluation. The advent of recombinant human TSH makes the preparation for a diagnostic scan much less burdensome and appears to have excellent sensitivity for serious metastatic lesions. The dilemma of an elevated serum Tg associated with a negative DxWBS has been ameliorated somewhat with the newly discovered ability of FDG-PET scanning to localize these less well-differentiated lesions. The real challenge lies in the development of new therapeutic agents to treat metastatic lesions that do not concentrate radioiodine.

Tuttle RM, Becker DV. · Endocrinology Service, Memorial Sloan-Kettering Cancer Center, New York Presbyterian Hospital, Weill Medical College of Cornell University, NY 10021, USA. · Semin Nucl Med. · Pubmed #10787193 No free full text.

Abstract: A marked increase in the incidence of papillary thyroid cancer in children has been documented in regions of the former Soviet Union most heavily contaminated by radioactive fallout from the Chernobyl nuclear power plant accident in April 1986. Accumulation of radioactive iodines by normal iodine trapping mechanisms resulted in significant radiation doses to the thyroid gland. Although it has long been known that thyroidal radiation resulted in nuclear and chromosomal abnormalities visible by light microscopy, modern molecular biology techniques are beginning to identify much smaller alterations in chromosomal coding sequences that are associated with malignant transformation. Although stable chromosomal abnormalities can be detected in Chernobyl-associated thyroid cancers, they are much less prevalent than in thyroid cancers developing after external beam irradiation. However, several unique chromosomal breakpoints have been described in radiation-associated thyroid cancers that are not commonly found in spontaneously occurring thyroid cancer. Furthermore, activation of specific subtypes of the ret/PTC tyrosine kinase oncogene appears to be more common in radiation-associated thyroid cancers than in spontaneous thyroid cancers. In summary, thyroid cancers developing in the aftermath of the Chernobyl accident provide a unique opportunity to search for chromosomal abnormalities that may be specific for radiation-induced thyroid cancer.

Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Sherman SI, Tuttle RM, Anonymous00638. · Sinai Hospital of Baltimore and Johns Hopkins University School of Medicine, MD, USA. · Thyroid. · Pubmed #16420177 No free full text.

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Fenton CL, Lukes Y, Nicholson D, Dinauer CA, Francis GL, Tuttle RM. · Department of Pediatrics, Walter Reed Army Medical Center, Washington, DC 20307, USA. · J Clin Endocrinol Metab. · Pubmed #10720057 links to  free full text

Abstract: The ret/PTC rearrangements (PTC-1, PTC-2, and PTC-3) are characteristic of papillary thyroid cancer (PTC). In adults, PTC-1 is common and may be associated with an aggressive clinical course. The incidence and significance of ret/PTC mutations are less well understood in children. We examined spontaneous PTC from 33 patients (23 females and 10 males) with a median age of 18 yr (range, 6-21 yr) and a median follow-up of 3.5 yr (range, 0-13.4 yr). The ret/PTC mutations were identified in 15 tumors (45%), including 8 PTC-1 (8 of 15, 53%), 2 PTC-2 (2 of 15, 13%), 2 PTC-3 (2 of 15, 13%), and 3 (3 of 15, 20%) combined PTC mutations (PTC-1 and PTC-2). This distribution is significantly different (P = 0.001, by chi2 analysis) from that reported for children with radiation-induced PTC. There was no correlation between the presence or type of ret/PTC mutation and patient age, tumor size, focality, extent of disease at diagnosis, or recurrence. We conclude that ret/PTC mutations are 1) common in sporadic childhood PTC, 2) predominantly PTC-1, 3) frequently multiple, and 4) of different distribution than that reported for children with radiation-induced PTC.

Ricarte-Filho JC, Ryder M, Chitale DA, Rivera M, Heguy A, Ladanyi M, Janakiraman M, Solit D, Knauf JA, Tuttle RM, Ghossein RA, Fagin JA. · Human Oncology and Pathogenesis Program and Departments of Medicine and Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. · Cancer Res. · Pubmed #19487299 No free full text.

Abstract: Patients with poorly differentiated thyroid cancers (PDTC), anaplastic thyroid cancers (ATC), and radioactive iodine-refractory (RAIR) differentiated thyroid cancers have a high mortality, particularly if positive on [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET). To obtain comprehensive genetic information on advanced thyroid cancers, we designed an assay panel for mass spectrometry genotyping encompassing the most significant oncogenes in this disease: 111 mutations in RET, BRAF, NRAS, HRAS, KRAS, PIK3CA, AKT1, and other related genes were surveyed in 31 cell lines, 52 primary tumors (34 PDTC and 18 ATC), and 55 RAIR, FDG-PET-positive recurrences and metastases (nodal and distant) from 42 patients. RAS mutations were more prevalent than BRAF (44 versus 12%; P = 0.002) in primary PDTC, whereas BRAF was more common than RAS (39 versus 13%; P = 0.04) in PET-positive metastatic PDTC. BRAF mutations were highly prevalent in ATC (44%) and in metastatic tumors from RAIR PTC patients (95%). Among patients with multiple metastases, 9 of 10 showed between-sample concordance for BRAF or RAS mutations. By contrast, 5 of 6 patients were discordant for mutations of PIK3CA or AKT1. AKT1_G49A was found in 9 specimens, exclusively in metastases. This is the first documentation of AKT1 mutation in thyroid cancer. Thus, RAIR, FDG-PET-positive metastases are enriched for BRAF mutations. If BRAF is mutated in the primary, it is likely that the metastases will harbor the defect. By contrast, absence of PIK3CA/AKT1 mutations in one specimen may not reflect the status at other sites because these mutations arise during progression, an important consideration for therapies directed at phosphoinositide 3-kinase effectors.

Rivera M, Tuttle RM, Patel S, Shaha A, Shah JP, Ghossein RA. · Department of Pathology, Memorial Sloan-Kettering Cancer Center , New York, New York, USA. · Thyroid. · Pubmed #19191744 No free full text.

Abstract: BACKGROUND: Encapsulated papillary thyroid carcinoma (EPTC) can have a histologic growth pattern similar to the one seen in classical papillary thyroid carcinoma (PTC) or akin to the follicular variant of PTC (FVPTC). This study aims to assess the behavior of EPTC according to its growth pattern. METHODS: All cases of thyroid carcinomas treated at our institution between 1980 and 2000 were reviewed and reclassified according to current histopathologic criteria. RESULTS: After review by two pathologists, 106 cases were included. Forty-three (41%) of the cases were identified as encapsulated classical PTC (E-CPTC) and 63 (59%) as encapsulated FVPTC (E-FVPTC). E-FVPTC had a higher rate of vascular invasion (16/63; 25%) than E-CPTC (2/43; 5%) (p = 0.007). In contrast, E-CPTC had a higher frequency of capsular invasion (28/43; 65%) than E-FVPTC (24/63, 38%) (p = 0.01). The lymph node metastatic rate was significantly higher in E-CPTC (11/43, 26%) compared to E-FVPTC (2/63, 3%) (p = 0.0014). All 34 noninvasive E-FVPTC lacked evidence of nodal metastases while 4 of 15 (27%) noninvasive E-CPTC presented with nodal disease (p = 0.006). Distant metastasis occurred only in four cases of E-FVPTC at presentation. These four FVPTC had extensive capsular and/or vascular invasion and no nodal disease. None of noninvasive EPTC recurred, including 30 patients treated by lobectomy without radioactive iodine (RAI) therapy (median follow-up: 8.9 years). CONCLUSION: E-CPTC resembles classical PTC in its propensity to metastasize to lymph nodes and its vascular/capsular invasive pattern while E-FVPTC behaves more like follicular carcinoma/adenoma group of tumors. Meticulous search for capsular and vascular invasion can reliably predict the metastatic potential of E-FVPTC but not of E-CPTC. The latter can therefore be treated like unencapsulated classical PTC. Noninvasive E-FVPTC could be managed like minimally invasive follicular carcinoma by lobectomy without RAI therapy. Invasive E-FVPTC seem quite indolent if no distant metastases are found at presentation.

Tuttle RM, Lukes Y, Onstad L, Lushnikov E, Abrosimov A, Troshin V, Tsyb A, Davis S, Kopecky KJ, Francis G. · Endocrinology Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. · Thyroid. · Pubmed #18690796 No free full text.

Abstract: BACKGROUND: Ionizing radiation is the strongest risk factor known for the development of thyroid neoplasia. While previous studies have demonstrated a high prevalence of ret/papillary thyroid cancer (PTC) activation in cohorts of patients developing thyroid nodules after childhood exposure to ionizing radiation, no study has directly compared ret/PTC activation with individual estimates of radiation dose to the thyroid. This study combines individual thyroid dosimetry data with molecular analysis of surgically removed thyroid nodules in order to determine if ret/PTC activation in thyroid nodules is associated with increasing estimated radiation dose from Chernobyl. METHODS: This pilot study included adults and children diagnosed with PTC (n = 76) and children diagnosed with follicular adenomas (n = 24) during May 1986 through December 1999, who were living in the Bryansk Oblast of the Russian Federation at the time of the Chernobyl accident, who had paraffin-embedded thyroid surgical samples available and for whom an individual dose to the thyroid could be estimated. The frequency of ret/PTC activation was determined using RT-PCR analysis. Individual radiation doses to the thyroid were estimated using a semiempirical model, and data were collected by detailed interview, primarily of the participant's mother. RESULTS: ret/PTC oncogene activation was detected in 23.8% (5/21) and 14.5% (8/55) of the childhood and adult PTC cases, respectively, and 8.3% (2/24) of the follicular adenoma cases. No statistically significant differences were noted in age at the time of exposure or diagnosis, gender, latency period, or estimated radiation dose between PTC patients with or without ret/PTC activation. Further, no significant dose-response relationship was detected among PTC patients with ret/PTC activation. CONCLUSIONS: Factors other than individual thyroid radiation doses may influence the development and subsequent detection of ret/PTC oncogene activation in radiation related PTC arising in the Bryansk Oblast of the Russian Federation in the aftermath of the Chernobyl accident.

Terezakis SA, Lee KS, Ghossein RA, Rivera M, Tuttle RM, Wolden SL, Zelefsky MJ, Wong RJ, Patel SG, Pfister DG, Shaha AR, Lee NY. · Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18676097 No free full text.

Abstract: PURPOSE: External beam radiotherapy (EBRT) plays a controversial role in the management of nonanaplastic thyroid cancer. We reviewed our institution's outcomes in patients treated with EBRT for advanced or recurrent nonanaplastic thyroid cancer. METHODS AND MATERIALS: Between April 1989 and April 2006, 76 patients with nonanaplastic thyroid cancer were treated with EBRT. The median follow-up for the surviving patients was 35.3 months (range, 4.2-178.4). The lesions were primarily advanced and included Stage T2 in 5 (7%), T3 in 5 (7%), and T4 in 64 (84%) patients. Stage N1 disease was present in 60 patients (79%). Distant metastases before EBRT were identified in 27 patients (36%). The median total EBRT dose delivered was 6,300 cGy. The histologic features examined included medullary in 12 patients (16%) and nonmedullary in 64 (84%). Of the 76 patients, 71 (93%) had undergone surgery before RT, and radioactive iodine treatment was used in 56 patients (74%). RESULTS: The 2- and 4-year overall locoregional control rate for all histologic types was 86% and 72%, respectively, and the 2- and 4-year overall survival rate for all patients was 74% and 55%, respectively. No significant differences were found in locoregional control, overall survival, or distant metastases-free survival for patients with complete resection, microscopic residual disease, or gross residual disease. Grade 3 acute mucositis and dysphagia occurred in 14 (18%) and 24 (32%) patients, respectively. Late adverse toxicity was notable for percutaneous endoscopic gastrostomy tube use in 4 patients (5%). CONCLUSION: The results of our study have shown that EBRT is effective for locoregional control of selected locally advanced or recurrent nonanaplastic thyroid malignancies, with acceptable acute toxicity.

Rivera M, Ghossein RA, Schoder H, Gomez D, Larson SM, Tuttle RM. · Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. · Cancer. · Pubmed #18484584 links to  free full text

Abstract: BACKGROUND: Radioactive iodine-refractory (RAIR) 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) positive thyroid carcinomas represent the major cause of deaths from thyroid carcinomas (TC) and are therefore the main focus of novel target therapies. However, to the authors' knowledge, the histology of FDG-PET-positive RAIR metastatic thyroid carcinoma has not been described to date. METHODS: Metastatic tissue from RAIR PET-positive patients identified between 1996 and 2003 at the study institution were selected for histologic examination. The biopsied metastatic site corresponded to a FDG-PET positive lesion sampled within 2 years (87% of which were sampled within 1 year) of the PET scan. Detailed microscopic examination was performed on the metastatic deposit and the available primary tumors. Poorly differentiated thyroid carcinomas (PDTC) were defined on the basis of high mitotic activity (> or =5 mitoses/10 high-power fields) and/or tumor necrosis. Other types of carcinomas were defined by conventional criteria. The histology of the metastases and primary were analyzed, with disease-specific survival (DSS) as the endpoint. RESULTS: A total of 70 patients satisfied the selection criteria, 43 of whom had primary tumors available for review. Histologic characterization of the metastasis/recurrence in 70 patients revealed that 47.1% (n = 33 patients) had PDTC, 20% (n = 14 patients) had the tall cell variant (TCV) of papillary thyroid carcinoma, 22.9% (n = 16 patients) had well-differentiated papillary thyroid carcinoma (WDPTC), 8.6% (n = 6 patients) had Hurthle cell carcinoma (HCC), and 1.4% (n = 1 patient) had anaplastic carcinomas. The histopathologic distribution of the tumor in the primaries was: PDTC, 51%; TCV, 19%; WDPTC, 23%; and widely invasive HCC, 7%. A differing histology between the primary tumor and metastasis was observed in 37% of cases (n = 16 patients). In the majority of instances (63%; 10 of 16 patients) this was noted as transformation to a higher grade. Of the primary tumors classified as PTC, 70% progressed to more aggressive histotypes in the metastasis. Tumor necrosis and extensive extrathyroid extension in the primary tumor were found to be independent predictors of poorer DSS in this group of patients (P = .015). Approximately 68% of the PDTC primary tumors were initially classified by the primary pathologist as better-differentiated tumors on the basis of the presence of papillary and/or follicular architecture or the presence of typical PTC nuclear features. CONCLUSIONS: Several observations can be made based on the results of the current study. The majority of metastases in patients with RAIR PET-positive metastases are of a histologically aggressive subtype. However, well-differentiated RAIR metastatic disease is observable. Poorly differentiated disease is underrecognized in many cases if defined by architectural and nuclear features alone. The presence of tumor necrosis was found to be a strong predictor of aggressive behavior, even within this group of clinically aggressive tumors. Finally, there is a significant amount of histologic plasticity between primary tumors and metastases that may reflect the genetic instability of these tumors.

Tuttle RM, Brokhin M, Omry G, Martorella AJ, Larson SM, Grewal RK, Fleisher M, Robbins RJ. · Division of Endocrinology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. · J Nucl Med. · Pubmed #18413378 links to  free full text

Abstract: Recent studies have confirmed that radioactive iodine therapy after recombinant human TSH (rhTSH) stimulation effectively ablates the normal thyroid remnant. However, no published study has determined the effectiveness of rhTSH preparations on the important endpoint of disease recurrence. METHODS: Disease recurrence was retrospectively assessed a median of 2.5 y after radioiodine remnant ablation (RRA) in 394 consecutive thyroid cancer patients (93% papillary, 71% female, 47+/-15 y old [mean +/- SD], median (131)I dose of 3,996 MBq [108 mCi]). RESULTS: Similar rates of clinically evident disease recurrence (4% rhTSH vs. 7% thyroid hormone withdrawal [THW], P=not statistically significant) and residual thyroid bed uptake without other evidence of persistent disease (4% rhTSH vs. 7% THW, P=not statistically significant) were seen in the 320 patients undergoing rhTSH-assisted RRA and the 74 patients prepared for RRA by THW. When the definition of no clinical evidence of disease included a suppressed thyroglobulin level of less than 1 ng/mL and a stimulated thyroglobulin level of less than 2 ng/mL, rhTSH-assisted RRA was associated with significantly higher rates of no clinical evidence of disease (74% rhTSH vs. 55% THW, P=0.02) and significantly lower rates of persistent disease (19% rhTSH vs. 32% THW, P=0.02) than was RRA after THW. Patients selected for rhTSH-assisted RRA were older (48+/-15 vs. 44+/-15 y, P=0.03) and received a slightly higher administered activity of (131)I (median, 4,033 MBq [109 mCi] vs. 3,811 MBq [103 mCi], P=0.01) but did not differ with respect to sex, histology, disease stage, or mean time to recurrence (19+/-9 mo for rhTSH vs. 20+/-16 mo for THW). CONCLUSION: rhTSH-assisted RRA is associated with rates of clinically evident disease recurrence and persistent uptake in the thyroid bed that are similar to those for traditional THW.

Tuttle RM, Grewal RK, Larson SM. · Department of Radiology, Memorial Hospital, Weill Medical College of Cornell University New York, NY, USA. · Nat Clin Pract Oncol. · Pubmed #17965644 No free full text.

Abstract: BACKGROUND: A 55-year-old male was diagnosed with poorly differentiated thyroid cancer after total thyroidectomy, which was performed because of progressive enlargement of a dominant thyroid nodule. He developed an early cervical recurrence that was treated with modified neck dissection. He subsequently developed biopsy-proven progressive pulmonary metastases. INVESTIGATIONS: Neck and chest CT scans, laboratory tests, CT-guided fine-needle aspiration biopsy, [18F]-2-fluoro-2-deoxy-D-glucose-PET scan, lesional dosimetry using 124I PET scan, diagnostic radioactive iodine (RAI) scanning, whole-body and blood RAI dosimetry, and single-photon-emission CT. DIAGNOSIS: Stage IV poorly differentiated thyroid cancer. MANAGEMENT: Surgical resection of cervical recurrence, RAI therapy.

Ghossein RA, Leboeuf R, Patel KN, Rivera M, Katabi N, Carlson DL, Tallini G, Shaha A, Singh B, Tuttle RM. · Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. · Thyroid. · Pubmed #17696836 No free full text.

Abstract: BACKGROUND: The tall cell variant (TCV) is a histologic subtype of papillary thyroid carcinoma (PTC) that is more aggressive than "classical" PTC. Most authors believe that TCV's worse prognosis is related to older age at presentation, larger tumor size, and high frequency of extrathyroid tumor extension (ETE). To assess the biologic and clinical behavior of TCV without ETE, we performed a detailed comparative clinicopathologic analysis of classical PTC and TCV without ETE. METHODS: TCV was defined as a PTC harboring >50% tall cells, while classical PTC was restricted to those tumors containing >1% papillae and <30% tall cells. Microscopic analysis and chart review identified 62 cases of TCV and 83 classical PTC without ETE. These patients were analyzed for various pathologic, imaging, and clinical parameters including outcome. RESULTS: There was no statistical difference between TCV and classical PTC in relation to age, gender, tumor size, risk stratification, type of therapy, and length of follow-up. TCV displayed more invasion of the tumor capsule and more often infiltrated into the thyroid capsule (p = 0.047 and 0.0004, respectively). Among patients with microscopically assessable regional lymph node (LN), 33 of 49 (67.3%) patients with TCV had LN metastasis at presentation, while only 24 of 60 (40%) classical PTC had positive nodes (p = 0.004). In multivariate analysis, histologic subtype (TCV vs. classical PTC) was the only independent factor associated with LN metastases (p = 0.007). In patients with adequate follow-up, 4 of 62 (6.5%) classical PTC and 7 of the 47 (14.9%) TCV had thyroid cancer recurrence (p = 0.202). TCV recurred at a distant site (3 of 47, 6.4%) while none of the 62 classical PTC developed distant metastases (p = 0.077). CONCLUSION: TCV without ETE is biologically a more aggressive tumor than classical PTC without ETE independent of age, gender, and tumor size.