Non-invasive follicular neoplasm with papillary-like nuclear features: a challenging and infrequent entity in Argentina.

PURPOSE: Non-invasive encapsulated follicular variant of papillary thyroid cancer was reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). These neoplasms have an extremely low malignant potential. The aim of this study was (1) to assess the prevalence of NIFTP in patients with papillary thyroid carcinoma, (2) to evaluate their outcomes, and (3) to determine their molecular profile. METHODS: Multicenter, descriptive, retrospective study. Patients with papillary thyroid cancer diagnosed from January 2006 to December 2016 from 11 referral centers were included. Diagnosis of NIFTP was based on criteria described by Nikiforov et al. in 2018. At least two pathologists agreed on the diagnosis. Two thousand six hundred and seventy-seven papillary thyroid cancer patients were included; 456 (17%) of them were follicular variant papillary thyroid cancer, and 30 (1.12%) fulfilled diagnostic criteria for NIFTP. RESULTS: Each of the 30 included patients underwent a total thyroidectomy, and 50% were treated with radioiodine (median dose 100 mCi). After a median follow-up of 37 months, 84% of patients had an excellent response, 3% had an indeterminate response and data was missing in the remaining 13%. No metastatic lymph nodes, distant metastases or recurrences were found. RAS mutations were detected in 4 patients (13%). CONCLUSION: The prevalence of NIFTP in our series is amongst the lowest reported. Excellent outcomes of patients underscore their low malignant potential. Molecular findings differ from other series, probably related to environmental or ethnic features of our population and the meticulous criteria for diagnosing NIFTP.

Acromegaly and thyroid cancer: analysis of evolution in a series of patients.

BACKGROUND: Acromegaly is associated with higher morbidity and mortality mainly due to cardiovascular disease. Data on the incidence and evolution of thyroid cancer in acromegaly are controversial. Our objective was to describe the characteristics of a group of acromegalic patients with differentiated thyroid carcinoma (DTC) and analyze their evolution. METHODS: This is a retrospective multicenter study of 24 acromegalic patients with DTC. The AJCC Staging System 8th Edition was used for TNM staging, and the initial risk of recurrence (RR), initial response and response at the end of follow-up (RFU) were defined according to the 2015 ATA Guidelines. As a control group, 92 patients with DTC without acromegaly were randomly included. Statistical analyses were done using SPSS Statistics 20.0. RESULTS: Median age of patients at diagnosis of acromegaly was 49.5 years (range 12-69). The median delay in diagnosis of acromegaly was 3 years (range 0.5-23). Mean baseline IGF-1 level was 2.9 ± 1.1 ULN. Median age at DTC diagnosis was 51.5 years (18-69). At the moment of diagnosis of DTC, 58.3% of the patients had active acromegaly. Median time from DTC diagnosis to acromegaly control was 1.25 years (0.5-7). Mean DTC tumor diameter of the biggest lesion was 14.6 ± 9.2 mm, being multifocal in 37.5%. All tumors were papillary carcinomas, two cases being of an aggressive variety. Lymph node dissection was performed in 8 out of 24 patients and 62.5% had metastases. Only one patient had distant metastases. Radioiodine ablation was given to 87.5% of patients. Nineteen patients (79%) were stage I, four (17%) stage II and one (4%) stage IVb. Initial RR was low in 87% (21/24), intermediate in 9% (2/24) and high in 4% (1/24) patient. RFU was: 83% (19/23) patients with no evidence of disease, 9% (2/23) with indeterminate response, 4% (1/23) with biochemical incomplete response and 4% (1/23) with structural incomplete response, at a median time of FU of 36.5 months. When comparing RFU between acromegalics and controls no statistically significant differences were found. CONCLUSIONS: Patients with acromegaly and DTC mostly had a low initial RR. When compared with the control group, we found that DTC patients with acromegaly did not have a worse evolution.

Differentiated thyroid carcinoma in sporadic and familial presentations of acromegaly: A case series.

BACKGROUND: In acromegaly, chronic growth hormone (GH) and insulin-like growth factor-1 (IGF-1) exacerbate comorbidities in multiple organs. Differentiated thyroid carcinoma (DTC) has been reported as being a comorbid condition in acromegaly. Acromegaly is usuallysporadic, but 5% of cases may be genetic. The most frequent inheritable form of acromegaly is related to germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Epidemiological data on the relationship between active acromegaly, its familial forms and DTC are sparse. We present the investigation of a FIPA family (familial isolated pituitary adenoma) with homogeneous acromegaly and 6 sporadic acromegaly patients with DTC. PATIENTS AND METHODS: A study of 59 acromegaly patients assessed thyroid nodules on ultrasound and fine-needle aspiration biopsy following the ATA 2015 criteria. We diagnosed 7 differentiated thyroid carcinomas. Resected thyroid carcinoma tissues were stained using an anti-AIP antibody. Analysis of germline and tumor-derived DNA for variants in the AIP and MEN1 genes were performed in the FIPA kindred. RESULTS: We describe one FIPA patient and 6 sporadic acromegaly cases with DTC. The FIPA family (AIP mutation negative) consisted of two sisters, one of whom had a DTC with intermediate risk and incomplete structural response to therapy. In our study, DTC in sporadic acromegaly had a low recurrence rate (6/6), and excellent response to therapy (6/6). Immunohistochemistry for AIP showed similar or increased staining intensity in DTC versus normal thyroid tissue. CONCLUSION: In our cohort of sporadic and familial forms of acromegaly with DTC, AIP did not appear to influence thyroid cancer progression.

Autoimmune and non-autoimmune thyroid dysfunction in HCV infected and HCV-HIV co-infected patients before and after interferon alpha therapy: A prospective study / Disfunción tiroidea autoinmune y no autoinmune en pacientes monoinfectados con VHC y coinfectados con VIH, antes y después del tratamiento con interferón alfa: un estudio prospectivo

INTRODUCTION: Autoimmune thyroid diseases are reported in no treated hepatitis C virus (HCV) infection. The standard interferon alpha (IFNΑ) treatment is associated with an increase of thyroid damage and dysfunction. The present cohort prospective study compared thyroid function and autoimmunity in HCV patients' monoinfected and coinfected HCV-HIV at baseline, during and after IFNΑ therapy. METHODS: We studied 790 HCV infected patients: G1 (monoinfected HCV: N = 580) and G2 (HCV-HIV coinfected: N = 210). They were evaluated for thyroid function and thyroid tiroperoxidase antibodies (TPOAb) at baseline and 235 patients (G1: 183; G2: 52) post IFNΑ therapy. If thyroid dysfunction (TD) was diagnosed, they were reevaluated at 12 month after discontinuation to determine whether the TD was transitory or definitive. RESULTS: No difference was found in the prevalence of TD at baseline in G1 (7.6%) and G2 (9%). However, monoinfected patients showed a higher prevalence of TPOAb positivity with a women preponderance in this group. There was no difference in TD between both groups during IFNΑ therapy (G1 23.5% vs G2 19.2%). In G1 the autoimmune TD was higher than in G2 (67.4% vs 30%, p = 0.02). Autoimmune TD during IFNΑ tended to evolve to definitive hypothyroidism and non-autoimmune TD recovered euthyroidism after IFN #913; discontinuation. The presence of positive TPOAb (RR 3.55) and female gender (RR 2.4) were associated with the development of TD with IFNΑ therapy. CONCLUSIÓN: Our hypothesis is the importance of HCV in G1 and G2, combined with IFNΑ in triggering TD and TPOAb positivity, not described in other diseases' applications

INTRODUCCIÓN: El presente estudio prospectivo de cohorte evaluó y comparó la función y la autoinmunidad tiroidea en pacientes con virus de la hepatitis C (VHC) monoinfectados y coinfectados con VHC-virus de la inmunodeficiencia humana (VIH) al inicio, durante y después de la terapia estándar con interferón alfa (IFNΑ). MÉTODOS: Se estudiaron 790 pacientes infectados por VHC: G1 (VHC monoinfectados: N = 580) y G2 (coinfección por VHC-VIH: N = 210). Se evaluó la función tiroidea y los anticuerpos anti-tiroperoxidasa (ATPO) al inicio del estudio, y a 235 pacientes tratados con IFNΑ (G1: 183; G2: 52). Si se diagnosticó disfunción tiroidea (DT), estos fueron reevaluados 12 meses posteriores al tratamiento para determinar si esta era transitoria o definitiva. RESULTADOS: No se encontraron diferencias en la prevalencia de DT en forma basal G1 (7,6%) vs. G2 (9%). Los pacientes monoinfectados mostraron una mayor prevalencia de positividad de ATPO, siendo preponderante el sexo femenino en el G1. No hubo diferencias en la DT entre ambos grupos con IFNΑ (G1 23,5 vs. G2 19,2%). En G1, la DT autoinmune fue mayor que en G2 (67,4 vs. 30%; p = 0,02). La DT autoinmune con IFNΑ tendió a evolucionar hacia un hipotiroidismo definitivo, mientras que la DT no autoinmune fue transitoria. Tuvieron mayor riesgo de DT durante el tratamiento los pacientes que presentaban ATPO positivos previos (RR: 3,55) y el sexo femenino (RR: 2,4). CONCLUSIONES: Planteamos como hipótesis la importancia del VHC en G1 y G2, combinado con IFNΑ en el desarrollo de la DT y positividad de los ATPO, no descripta en su uso en otras enfermedades

Autoimmune and non-autoimmune thyroid dysfunction in HCV infected and HCV-HIV co-infected patients before and after interferon alpha therapy: A prospective study.

INTRODUCTION: Autoimmune thyroid diseases are reported in no treated hepatitis C virus (HCV) infection. The standard interferon alpha (IFNα) treatment is associated with an increase of thyroid damage and dysfunction. The present cohort prospective study compared thyroid function and autoimmunity in HCV patients' monoinfected and coinfected HCV-HIV at baseline, during and after IFNα therapy. METHODS: We studied 790 HCV infected patients: G1 (monoinfected HCV: N=580) and G2 (HCV-HIV coinfected: N=210). They were evaluated for thyroid function and thyroid tiroperoxidase antibodies (TPOAb) at baseline and 235 patients (G1: 183; G2: 52) post IFNα therapy. If thyroid dysfunction (TD) was diagnosed, they were reevaluated at 12 month after discontinuation to determine whether the TD was transitory or definitive. RESULTS: No difference was found in the prevalence of TD at baseline in G1 (7.6%) and G2 (9%). However, monoinfected patients showed a higher prevalence of TPOAb positivity with a women preponderance in this group. There was no difference in TD between both groups during IFNα therapy (G1 23.5% vs G2 19.2%). In G1 the autoimmune TD was higher than in G2 (67.4% vs 30%, p=0.02). Autoimmune TD during IFNα tended to evolve to definitive hypothyroidism and non-autoimmune TD recovered euthyroidism after IFNα discontinuation. The presence of positive TPOAb (RR 3.55) and female gender (RR 2.4) were associated with the development of TD with IFNα therapy. CONCLUSION: Our hypothesis is the importance of HCV in G1 and G2, combined with IFNα in triggering TD and TPOAb positivity, not described in other diseases' applications.

Outcomes of patients with bone metastases from differentiated thyroid cancer.

Objective Bone metastases (BM) from differentiated thyroid cancer (DTC) are associated with poor survival rates. Due to the low frequency of this entity, we performed a multicentric retrospective study that aimed to evaluate the presentation, outcome and causes of death in this population. Subjects and methods We reviewed file records from 10 databases. BM were diagnosed by: i) biopsy and/or ii) radioiodine (RAI) bone uptake + elevated thyroglobulin (Tg) levels and/or c) bone uptake of 18-FDG in the PET-CT scan + elevated Tg levels. Results Fifty-two patients with DTC were included (44% male, mean age 54 years); 58% had papillary histology. BM were synchronous with DTC diagnosis in 46% of the participating cases. BM were symptomatic in 65% of the cases. Multiple BM were present in 65% of patients, while simultaneous metastatic disease in additional sites was found in 69%. Ninety-eight percent of patients received treatment for the BM, which included RAI therapy in 42 patients; 30 of them received cumulative RAI doses that were larger than 600 mCi 131I. The mean follow-up after a BM diagnosis was 34 months. The 2- and 5-year survival rates after diagnosis of the first BM were 64% and 38%, respectively. The status on the last evaluation was DTC-related death in 52% of the patients; 26% of them died from direct complications of BM or their treatments. Conclusion BM are usually radioiodine-refractory and are associated with a short overall survival, although most of the patients died of causes not directly related to the BM.

Outcomes of patients with bone metastases from differentiated thyroid cancer

ABSTRACT Objective Bone metastases (BM) from differentiated thyroid cancer (DTC) are associated with poor survival rates. Due to the low frequency of this entity, we performed a multicentric retrospective study that aimed to evaluate the presentation, outcome and causes of death in this population. Subjects and methods We reviewed file records from 10 databases. BM were diagnosed by: i) biopsy and/or ii) radioiodine (RAI) bone uptake + elevated thyroglobulin (Tg) levels and/or c) bone uptake of 18-FDG in the PET-CT scan + elevated Tg levels. Results Fifty-two patients with DTC were included (44% male, mean age 54 years); 58% had papillary histology. BM were synchronous with DTC diagnosis in 46% of the participating cases. BM were symptomatic in 65% of the cases. Multiple BM were present in 65% of patients, while simultaneous metastatic disease in additional sites was found in 69%. Ninety-eight percent of patients received treatment for the BM, which included RAI therapy in 42 patients; 30 of them received cumulative RAI doses that were larger than 600 mCi 131I. The mean follow-up after a BM diagnosis was 34 months. The 2- and 5-year survival rates after diagnosis of the first BM were 64% and 38%, respectively. The status on the last evaluation was DTC-related death in 52% of the patients; 26% of them died from direct complications of BM or their treatments. Conclusion BM are usually radioiodine-refractory and are associated with a short overall survival, although most of the patients died of causes not directly related to the BM.

Effects of sample storage and diluents in the reliability of thyroglobulin measurement in the washout of fine needle aspirates.

OBJECTIVE: To evaluate two variables affecting Thyroglobulin stability in the washout of fine needle aspiration biopsies of thyroid nodules and metastatic lymph nodes. MATERIALS AND METHODS: Thyroglobulin stability after storage at -20 °C up to 14 days was studied in washout performed with normal saline solution and further dilutions with normal saline solution from five metastatic thyroid nodes and six benign thyroid nodules. We also studied thyroglobulin stability in diluents compared with normal saline solution: 4% bovine serum albumin in normal saline solution and diluents free from thyroglobulin or Calcitonin or parathyroid hormone in paired and simultaneous thyroglobulin measurements of washout dilutions from 5/6 benign thyroid nodules and 2/5 metastatic lymph nodes. Thyroglobulin and Thyroglobulin antibodies were measured by a chemiluminescent assay. Positive samples with thyroglobulin antibodies in serum and/or washout were excluded. RESULTS: Thyroglobulin decreased with storage in washout or dilutions of washout performed in normal saline solution (p < 0.05). Lower thyroglobulin concentrations, close to the commonly used cut-off (1.1 ng/mL), showed the highest decrease as soon as after 1 day of storage. Diluents other than normal saline solution stabilized thyroglobulin in dilutions of all washout. CONCLUSIONS: The results suggest that the reliability of thyroglobulin measurements in washout of fine needle aspirates could be preserved by immediate measure of thyroglobulin or the use of stabilizing diluents to perform washout.

Thyroid nodules in acromegaly.

OBJECTIVE: We made a prospective study evaluating the prevalence of thyroid nodular disease in acromegalic patients. SUBJECTS AND METHODS: Thyroid ultrasound and ultrasound-guided fine needle aspiration biopsy were performed when nodules were detected. Nodules were characterized by cytology and histopathology. RESULTS: We found high prevalence of nodular thyroid disorder, 23/34 (67%) in acromegalic patients. High risk and malignant cytology were significantly higher in acromegalic patients than in our non-acromegalic population (25% vs. 9%). Differentiated thyroid carcinoma was present in 11% of the acromegalic patients. CONCLUSIONS: We strongly recommend periodic thyroid evaluation by ultrasound in patients with acromegaly. Fine needle aspiration biopsy should be performed in nodules larger than 10 mm, and in all suspicious nodules, regardless of the size.

Thyroid nodules in acromegaly / Nódulos tiroideanos na acromegalia

OBJECTIVE: We made a prospective study evaluating the prevalence of thyroid nodular disease in acromegalic patients. SUBJECTS AND METHODS: Thyroid ultrasound and ultrasound-guided fine needle aspiration biopsy were performed when nodules were detected. Nodules were characterized by cytology and histopathology. RESULTS: We found high prevalence of nodular thyroid disorder, 23/34 (67%) in acromegalic patients. High risk and malignant cytology were significantly higher in acromegalic patients than in our non-acromegalic population (25% vs. 9%). Differentiated thyroid carcinoma was present in 11% of the acromegalic patients. CONCLUSIONS: We strongly recommend periodic thyroid evaluation by ultrasound in patients with acromegaly. Fine needle aspiration biopsy should be performed in nodules larger than 10 mm, and in all suspicious nodules, regardless of the size.

OBJETIVO: Realizamos um estudo prospectivo avaliando a prevalência de patologia nodular tireói­dea em 34 pacientes acromegálicos. SUJEITOS E MÉTODOS: Avaliamos os pacientes com ecografia tireóidea e punção biópsia com agulha fina quando se detectavam nódulos. RESULTADOS: Encontramos uma alta prevalência de patologia nodular tireóidea 23/34 (67%) em acromegálicos. A citologia tireóidea de alto risco e maligna foi significativamente mais elevada em pacientes acromegálicos que em uma população não acromegálica (25% vs. 9%). O grupo acromegálico apresentou carcinoma diferenciado de tireoides em 11%. CONCLUSÕES: Recomendamos fortemente a ecografia periódica tireóidea em pacientes acromegálicos. Uma punção biópsia aspirativa com agulha fina deve ser realizada em presença de nódulos tireóideos maiores que 10 mm e daqueles com critérios ecográficos suspeitos de malignidade, independentemente do tamanho deles.

Valoración de la punción biopsia con aguja fina y de la biopsia por congelación en el diagnóstico y tratamiento del nódulo tiroideo / Determine the role of frozen section and fine needle aspiration biopsy of thyroid nodules

Antecedentes: el advenimiento de la PBA ha posibilitado una mejor selección de pacientes portadores de patología tiroidea para la cirugía. Objetivo: determinar el rol de la punción y la biopsia por congelación en el manejo quirúrgico de la patología tiroidea. Lugar de aplicación: Servicio de Cirugía General División A; Servicio de Endocrinología y Servicio de Anatomía Patológica del Hospital de Agudos J.M. Ramos Mejía. Diseño: retrospectivo consecutivo. Método: se evaluó la correlación de los hallazgos de la PBA, la congelación y el estudio histopatológico final en el diagnóstico de la patología tiroidea. Población: se analizaron 541 pacientes estudiados con PBA y congelación operados en el Hospital Ramos Mejía. Resultados: de los 541 operados se diagnosticó cáncer en 163 pacientes (30 por ciento). La PBA diagnosticó 111 que fueron confirmados por la congelación e informó 104 casos como dudosos de los cuales 31 fueron cáncer. Dentro del grupo de los "dudosos" hubo mayor prevalencia de carcinoma en los subgrupos "sospechoso de malignidad" y en las "proliferaciones foliculares de alto grado". Conclusiones: se podría prescindir de la utilización de la biopsia por congelación ante una PBA maligna. En cambio ante una benigna o dudosa consideramos completar con la congelación intraoperatoria. Debido a la diferencia de prevalencia de carcinoma en el grupo de los dudosos justificamos mantener separadas las categorías citológicas: SM (sospechoso de malignidad), PFAG (proliferación folicular de alto grado), PFBG (proliferación folicular de bajo grado), PFH (proliferación folicular de H³rthle) (AU)

Valoración de la punción biopsia con aguja fina y de la biopsia por congelación en el diagnóstico y tratamiento del nódulo tiroideo / Determine the role of frozen section and fine needle aspiration biopsy of thyroid nodules

Antecedentes: el advenimiento de la PBA ha posibilitado una mejor selección de pacientes portadores de patología tiroidea para la cirugía. Objetivo: determinar el rol de la punción y la biopsia por congelación en el manejo quirúrgico de la patología tiroidea. Lugar de aplicación: Servicio de Cirugía General División A; Servicio de Endocrinología y Servicio de Anatomía Patológica del Hospital de Agudos J.M. Ramos Mejía. Diseño: retrospectivo consecutivo. Método: se evaluó la correlación de los hallazgos de la PBA, la congelación y el estudio histopatológico final en el diagnóstico de la patología tiroidea. Población: se analizaron 541 pacientes estudiados con PBA y congelación operados en el Hospital Ramos Mejía. Resultados: de los 541 operados se diagnosticó cáncer en 163 pacientes (30 por ciento). La PBA diagnosticó 111 que fueron confirmados por la congelación e informó 104 casos como dudosos de los cuales 31 fueron cáncer. Dentro del grupo de los "dudosos" hubo mayor prevalencia de carcinoma en los subgrupos "sospechoso de malignidad" y en las "proliferaciones foliculares de alto grado". Conclusiones: se podría prescindir de la utilización de la biopsia por congelación ante una PBA maligna. En cambio ante una benigna o dudosa consideramos completar con la congelación intraoperatoria. Debido a la diferencia de prevalencia de carcinoma en el grupo de los dudosos justificamos mantener separadas las categorías citológicas: SM (sospechoso de malignidad), PFAG (proliferación folicular de alto grado), PFBG (proliferación folicular de bajo grado), PFH (proliferación folicular de Hürthle)