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.

Testing of mutations on thyroid nodules with indeterminate cytology: A prospective study of 112 patients in Argentina.

BACKGROUND: The study of genetic mutations in thyroid nodules makes it possible to improve the preoperative diagnosis of and reduce unnecessary surgeries on benign nodules. In this study, we analysed the impact of implementing a 7-gene mutation panel that enables mutations to be detected in BRAF and RAS (H/N/K) and the gene fusions PAX8/PPARG, RET/PTC1 and RET/PTC2, in a population in northern Argentina. METHODS: We performed a prospective analysis of 112 fine needle aspirations diagnosed as having indeterminate cytology according to the Bethesda classification system. These include the Bethesda III or atypia of unknown significance/follicular lesion of unknown significance and Bethesda IV or follicular neoplasm/suspicious for follicular neoplasm categories. The mutations of the 7-gene panel were analysed and this information was linked to the available histology and ultrasound monitoring. RESULTS: The BRAF V600E and RET/PTC1 mutations were associated with carcinoma in 100% of cases (n = 8), whereas only 37.5% (n = 3) of the nodules with RAS and 17% (n = 1) with PAX8/PPARG mutations were associated with carcinoma. From the histological diagnosis and ultrasound monitoring of patients, we can estimate that this panel has a sensitivity of 86% in detecting malignant carcinoma, a specificity of 77%, a positive predictive value (PPV) of 54% and a negative predictive value (NPV) of 94%. In this study, it was possible to reduce the number of surgeries by 48% in the patients analysed. CONCLUSION: The implementation of the mutation panel allowed the appropriate surgical strategy to be selected for each patient, the number of two-step surgeries to be reduced, and active follow-up to be established in low-risk patients.

Testing of mutations on thyroid nodules with indeterminate cytology: A prospective study of 112 patients in Argentina. / Testeo de mutaciones en nódulos tiroideos con citología indeterminada: estudio prospectivo de 112 pacientes en Argentina.

BACKGROUND: The study of genetic mutations in thyroid nodules makes it possible to improve the preoperative diagnosis of and reduce unnecessary surgeries on benign nodules. In this study, we analysed the impact of implementing a 7-gene mutation panel that enables mutations to be detected in BRAF and RAS (H/N/K) and the gene fusions PAX8/PPARG, RET/PTC1 and RET/PTC2, in a population in northern Argentina. METHOD: We performed a prospective analysis of 112 fine needle aspirations diagnosed as having indeterminate cytology according to the Bethesda classification system. These include the Bethesda III or atypia of unknown significance/follicular lesion of unknown significance and Bethesda IV or follicular neoplasm/suspicious for follicular neoplasm categories. The mutations of the 7-gene panel were analysed and this information was linked to the available histology and ultrasound monitoring. RESULTS: The BRAF V600E and RET/PTC1 mutations were associated with carcinoma in 100% of cases (n=8), whereas only 37.5% (n=3) of the nodules with RAS and 17% (n=1) with PAX8/PPARG mutations were associated with carcinoma. From the histological diagnosis and ultrasound monitoring of patients, we can estimate that this panel has a sensitivity of 86% in detecting malignant carcinoma, a specificity of 77%, a positive predictive value (PPV) of 54% and a negative predictive value (NPV) of 94%. In this study, it was possible to reduce the number of surgeries by 48% in the patients analysed. CONCLUSION: The implementation of the mutation panel allowed the appropriate surgical strategy to be selected for each patient, the number of two-step surgeries to be reduced, and active follow-up to be established in low-risk patients.

Sobreexpresión de C-MET en carcinoma de vesícula y del tracto biliar: prevalencia y correlación clínico-molecular / Overexpression of C-MET in gallbladder and biliary tract carcinoma: prevalence and clinical-molecular correlation

El objetivo fue determinar la sobreexpresión de c-MET en pacientes con cáncer biliar y analizar asociaciones con parámetros clínicos. Este es un estudio descriptivo, longitudinal, retrospectivo y prospectivo. Se determinó la sobreexpresión por inmunohistoquímica en 58 pacientes con resultados: positivo fuerte, positivo débil y negativo. Se construyeron curvas de supervivencia global con el método de KaplanMeier en todos los pacientes y en subgrupos según estadío, género, origen tumoral y grado de diferenciación histológica. La diferencia en supervivencia global entre subgrupos se analizó por el método log-rank. La asociación entre sobreexpresión y grado de diferenciación se estudió por el método chi cuadrado. Las pruebas estadísticas se realizaron a dos colas con un valor de p 0.05. Veintinueve muestras (50%) fueron negativas, 24 (41%) positivas débiles y 5 (9%) positivas fuertes. La mediana de supervivencia fue 18.2, 11.3 y 11.7 meses en pacientes con sobreexpresión negativa, positiva débil y positiva fuerte, respectivamente. Sin embargo, la diferencia en supervivencia global entre pacientes c-MET negativos y positivos (fuerte y débil) no alcanzó significancia estadística (p 0.068). En los subgrupos los resultados fueron similares. La sobreexpresión se asoció al grado de diferenciación (p 0.015), mostrando una relación inversa; y no se correlacionó con tasa de respuesta a la quimioterapia y tiempo a la progresión. La sobreexpresión de c-MET es frecuente en cáncer biliar, se asocia al grado de diferenciación tumoral y podría tener valor pronóstico. Si la vía c-MET es importante, los fármacos inhibidores tendrían impacto en la supervivencia global (AU)

The objective was to determine the overexpression of c-MET in patients with biliary cancer and to analyze associations with clinical parameters. This is a descriptive, longitudinal, retrospective and prospective study. Overexpression was obtained by immunohistochemistry in 58 patients, with the following results: strong positive, weak positive and negative. Overall survival curves were constructed using the Kaplan-Meier method in all patients and in subgroups according to stage, gender, tumor origin and grade of histological differentiation. The difference in overall survival between groups was analyzed by the log-rank test. The association between overexpression and grade of differentiation was studied using the chisquare method. Statistical tests were two-tailed with a p value 0.05. Twenty nine samples (50%) were negative, 24 (41%) weak positive and 5 (9%) strong positive. Median survival was 18.2, 11.3 and 11.7 months in patients with negative, weak positive and strong positive overexpression, respectively. However, the difference in overall survival between negative and positive (strong and weak together) c-MET patients did not reach statistical significance (p 0.068). In the subgroup analyses the results were similar. Overexpression correlated with tumor grade (p 0.015), showing an inverse association; and was not associated neither with chemotherapy response rate nor with time to progression. Overexpression of c-MET is common in biliary cancer, is associated with grade of tumor differentiation and could have prognostic value. If the c-MET pathway is important, the inhibitory drugs would have an impact on overall survival (AU)

[Risk markers of follicular neoplasms in thyroid nodules]. / Marcadores de riesgo de neoplasia folicular en nódulos tiroideos.

Thyroid nodules of follicular origin include neoplastic and non neoplastic processes. No methods of diagnosis or cytological features (obtained by fine-needle aspiration, FNA) may differentiate both types, and therefore differential diagnosis still constitutes a dilemma.We analyzed the existing association between clinical variables and methods of diagnosis in thyroid nodules of follicular type with the aim of defining risk of neoplasm. Ninety two patients with nodular goiters, of follicular origin by cytology, previously submitted to surgical treatment were analyzed. The studied variables were: sex, age, size of the nodule, ultrasound characteristics, cytological diagnosis, TSH level and results of the scintigraphy. Of 92 cases, 74 were neoplastic nodules (56 adenomas and 18 differentiated thyroid cancer) and 18 were non neoplastic nodules. Markers, that were related to high risk of follicular neoplasm corresponded to the cytological diagnosis of proliferation of high follicular degree, in iso or hypoechoic, and hypofunctioning nodules with I131. The carcinomas presented cytology of follicular proliferation of high degree, in hipoechoic nodules, of irregular edges with microcalcifications and hypofunctioning, in male patients or patients younger than 20 years. The presence of macrocalcifications and hypercaptation would be in favor of nodules of benign origin.The correlation of diagnostic methods and clinical variables in thyroid nodules of follicular type would allow us to differentiate the risk of neoplasm or carcinoma, and plan surgical selective treatments.

Marcadores de riesgo de neoplasia folicular en nódulos tiroideos / Risk markers of follicular neoplasms in thyroid nodules

Los nódulos tiroideos de origen folicular abarcan procesos no neoplásicos y neoplásicos. No existen métodos de diagnóstico ni rasgos citológicos por punción con aguja fina (PAF) que los delimiten, constituyendo un dilema su diagnóstico diferencial. Analizamos la asociación existente entre variables clínicas y métodos de diagnóstico prequirúrgicos en nódulos tiroideos de estirpe folicular, con el objetivo de definir riesgo de neoplasia.Se estudiaron 92 pacientes con bocios nodulares de estirpe folicular por citología, tratados con tiroidectomía. Las variables analizadas fueron: sexo, edad, tamaño del nódulo, características ecográficas, diagnóstico citológico, nivel de TSH y resultados del centellograma. De los 92 casos, 74 fueron neoplásicos (56 adenomas y 18 carcinomas diferenciados) y 18 nódulos no neoplásicos, hiperplásicos o adenomatosos. Los marcadores que se relacionaron con alto riesgo de neoplasia folicular correspondieron al diagnóstico citológico de proliferación folicular de alto grado, en nódulos iso o hipoecogénicos, e hipocaptantes con I131. Los carcinomas presentaron citología de proliferación folicular de alto grado en nódulos hipoecogénicos, de bordes irregulares con microcalcificaciones e hipocaptantes, en pacientes varones o menores de 20 años. La presencia de macrocalcificaciones e hipercaptación estarían a favor de nódulo de origen benigno.La correlación de los métodos de diagnóstico y variables clínicas en nódulos tiroideos de estirpe folicular nos permitirían delimitar el riesgo de neoplasia y carcinoma para planificar un tratamiento quirúrgico selectivo.

Thyroid nodules of follicular origin include neoplastic and non neoplastic processes. No methods of diagnosis or cytological features (obtained by fine-needle aspiration, FNA) may differentiate both types, and therefore differential diagnosis still constitutes a dilemma.We analyzed the existing association between clinical variables and methods of diagnosis in thyroid nodules of follicular type with the aim of defining risk of neoplasm. Ninety two patients with nodular goiters, of follicular origin by cytology, previously submitted to surgical treatment were analyzed. The studied variables were: sex, age, size of the nodule, ultrasound characteristics, cytological diagnosis, TSH level and results of the scintigraphy. Of 92 cases, 74 were neoplastic nodules (56 adenomas and 18 differentiated thyroid cancer) and 18 were non neoplastic nodules. Markers, that were related to high risk of follicular neoplasm corresponded to the cytological diagnosis of proliferation of high follicular degree, in iso or hypoechoic, and hypofunctioning nodules with I131. The carcinomas presented cytology of follicular proliferation of high degree, in hipoechoic nodules, of irregular edges with microcalcifications and hypofunctioning, in male patients or patients younger than 20 years. The presence of macrocalcifications and hypercaptation would be in favor of nodules of benign origin.The correlation of diagnostic methods and clinical variables in thyroid nodules of follicular type would allow us to differentiate the risk of neoplasm or carcinoma, and plan surgical selective treatments.

Metástasis cerebral de carcinoma papilar no clásico de tiroides / Brain metastases from non classic papillary thyroid carcinoma

Introducción: El carcinoma papilar es la neoplasiamaligna más frecuente de la glándula tiroides. La mayoríade los tumores son de bajo riesgo (89%) con un índice decurabilidad elevado y mortalidad del 1,8%. La tendencia ametastatizar a distancia es sumamente infrecuente e inusualen cerebro. Caso clínico: Paciente femenino de 52 años queconsulta por presentar cuadro de hipertensión endocraneanade corto tiempo de evolución y bocio nodular grado II-III notratado. En la resonancia magnética nuclear de cerebro seobservaron múltiples imágenes nodulares, homogéneas conhipercaptación y edema perilesional El estudio histopatológicode las lesiones nodulares en cerebro mostró la imagende un Carcinoma Papilar metastásico no clásico con célulascolumnares-altas y expresión de tiroglobulina. La pacientefallece posterior a la cirugía. Discusión: El diagnóstico inicialcomo metástasis cerebral de un carcinoma papilar deorigen tiroideo es inusual. Este tipo de evolución se observacomo en nuestro caso en pacientes de alto riesgo, mayores,con bocios de gran tamaño y variantes histológicas de Carcinomapapilar no clásicas agresivas (AU)

Introduction: Papillary thyroid carcinoma is the commonestmalignant neoplasm in the thyroid gland. The mostof the tumours are low risk (89%) with high cure rate andlow mortality (1,8%). Distant metastases are extremely rare.Brain metastases are unusual. Case report: A 52-year oldwoman presented with a short evolution history of highintracranial pressure symptoms, including vomiting, headacheand general clinical worsening. She had grade II-III goitrewithout treatment. Magnetic resonance imaging followingintravenous gadolinium contrast, demonstrated multiplehomogeneous enhancing masses and perilesionaloedema were noted. Histopathology confirmed diagnosticof non classic papillary thyroid carcinoma, tall cell andcolumnar cell variant. Twelve days after surgery, the patientdied. Discussion: Metastases of papillary thyroid carcinomagenerally occur to regional lymph nodes. Brain metastasesare described in 0.1-5% of patients. Aggressive variantof carcinoma and older patients are related to this evolution.At the moment therapeutic modalities are being discussed (AU)

[Non-incidental papillary microcarcinomas of the thyroid]. / Microcarcinomas papilares de tiroides no incidentales.

The clinical significance of papillary microcarcinoma of the thyroid gland keeps being controversial. Its high prevalence in autopsies and as incidental findings in thyroidectomy specimens for benign pathology indicate an indolent clinical behavior. Nevertheless some of the microcarcinomas develop lymph node metastasis and local recurrence. To determine the clinical and pathological characteristics of non-incidental papillary microcarcinomas of the thyroid (PTM -NI). 18 patients with diagnosis of non-incidental papillary microcarcinoma (tumor < or = 1 cm) with nodular expression in the thyroid gland or with lymph node metastasis have been studied. Initial diagnosis, prediction factors and evolution have been evaluated. Of 18 patients with PTM-NI, 12 demonstrated lymph node metastasis. 6 patients had positive fine needle aspiration (FNA) of palpable thyroid nodules. Multifocality and extraglandular extension were associated with lymph node metastasis. Seven of the nine metastatic lymph nodes diagnosed by FNA were cystic. Histologically 83.3% of the nodules in the thyroid were non-encapsulated and showed papillary growth pattern. Multifocality and extrathyroid infiltration were associated with lymph node metastasis at presentation. 46% of the patients with thyroid nodules > or = 4 mm and lymph node involvement (N1) showed recurrence/persistence. The non-incidental intrathyroideal papillary microcarcinoma without capsular involvement, extraglandular extension or lymph node metastasis (N0) did not demonstrate recurrence. These results suggest two groups of non- incidental papillary microcarcinoma of the thyroid (PMT-NI), one intraglandular without risk of evolution -N0- and other extraglandular at risk of recurrence -N1-.

Microcarcinomas papilares de tiroides no incidentales / Non-incidental papillary microcarcinomas of the thyroid

El significado clínico de los microcarcinomas papilares de tiroides sigue siendo controvertido. La alta prevalencia en autopsias e incidental en tiroidectomías por patología benigna indican un comportamiento clínico indolente. Sin embargo, algunos desarrollan metástasis ganglionares y recurrencia local. Nuestro objetivo fue determinar características clínicas y patológicas de microcarcinonas papilares de tiroides no incidentales (MPT-NI). Se analizaron 18 pacientes con diagnóstico de microcarcinomas (tumor < 1cm) MPTNI con expresión nodular o metastásica. Se evaluaron características clínicas, histopatológicas, pronósticas y evolutivas. De los 18 pacientes con MPT-NI, 12 manifestaron expresión ganglionar inicial. En los 6 restantes, los nódulos tiroideos fueron palpables con PAAF (punción aspiración con aguja fina) positiva. La multicentricidad e infiltración extratiroidea se asoció con metástasis ganglionares en todos los casos. De los 9 diagnósticos por PAAF de metástasis ganglionares, 7 fueron quísticas. En los estudios histológicos el 83.3% de los nódulos fueron no encapsulados, con patrón de papilar clásico predominante. En la evolución, la recurrencia se manifestó en el 46% de los pacientes N1 o con metástasis ganglionar inicial, en nódulos < 4 mm. La infiltración extratiroidea estuvo presente en el 66% de los casos con recurrencia. No manifestaron recurrencia los pacientes sin compromiso ganglionar (N0) o infiltrativo capsular o extratiroideo. En el seguimiento de 10 a 122 meses todos los pacientes se encuentran libres de enfermedad demostrable. Estos resultados sugieren dos grupos de microcarcinomas tiroideos no incidentales, aquellos sin riesgo de evolución intratiroideos -N0- y con riesgo de recurrencia extratiroideos -N1-.

The clinical significance of papillary microcarcinoma of the thyroid gland keeps being controversial. Its high prevalence in autopsies and as incidental findings in thyroidectomy specimens for benign pathology indicate an indolent clinical behavior. Nevertheless some of the microcarcinomas develop lymph node metastasis and local recurrence. To determine the clinical and pathological characteristics of non-incidental papillary microcarcinomas of the thyroid (PTM -NI). 18 patients with diagnosis of non-incidental papillary microcarcinoma (tumor < 1cm) with nodular expression in the thyroid gland or with lymph node metastasis have been studied. Initial diagnosis, prediction factors and evolution have been evaluated. Of 18 patients with PTM-NI, 12 demonstrated lymph node metastasis. 6 patients had positive fine needle aspiration (FNA) of palpable thyroid nodules. Multifocality and extraglandular extension were associated with lymph node metastasis. Seven of the nine metastatic lymph nodes diagnosed by FNA were cystic. Histologically 83.3% of the nodules in the thyroid were non-encapsulated and showed papillary growth pattern. Multifocality and extrathyroid infiltration were associated with lymph node metastasis at presentation. 46% of the patients with thyroid nodules < 4 mm and lymph node involvement (N1) showed recurrence/persistence. The non-incidental intrathyroideal papillary microcarcinoma without capsular involvement, extraglandular extension or lymph node metastasis (N0) did not demonstrate recurrence. These results suggest two groups of non- incidental papillary microcarcinoma of the thyroid (PMT-NI), one intraglandular without risk of evolution -N0- and other extraglandular at risk of recurrence -N1-.

Ginecomastia (Estudio retrospectivo sobre 54 casos operados) / Gynecomastia: retrospective study of 54 cases surgically treated

Se realiza un estudio retrospectivo de 54 casos operados en el Hospital de Endocrinología y Metabolismo Dr. Arturo Oñativia de Salta. Entre los años 1987 y 2001 fueron intervenidas 63 ginecomastias que representan el 5,58 por ciento de los diagnósticos anátomo-patológicos y el 7,18 por ciento de los informes benignos. Sobre 54 pacientes con historias clínicas presentes se detallan aspectos epidemiológicos, formas de presentación, estudios practicados, diagnóstico causal, características anátomo-patológicas y se intenta cursar una guía para el estudio de la ginecomastia como así también para el tratamiento médico y quirúrgico. Por último se realiza determinación de receptores hormonales por inmunomarcación en 19 casos observando pisitividad nuclear epitelial para estrógenos en el 68,42 por ciento y de progesterona en el 47,36 por ciento.(AU)

Ginecomastia (Estudio retrospectivo sobre 54 casos operados) / Gynecomastia: retrospective study of 54 cases surgically treated

Se realiza un estudio retrospectivo de 54 casos operados en el Hospital de Endocrinología y Metabolismo Dr. Arturo Oñativia de Salta. Entre los años 1987 y 2001 fueron intervenidas 63 ginecomastias que representan el 5,58 por ciento de los diagnósticos anátomo-patológicos y el 7,18 por ciento de los informes benignos. Sobre 54 pacientes con historias clínicas presentes se detallan aspectos epidemiológicos, formas de presentación, estudios practicados, diagnóstico causal, características anátomo-patológicas y se intenta cursar una guía para el estudio de la ginecomastia como así también para el tratamiento médico y quirúrgico. Por último se realiza determinación de receptores hormonales por inmunomarcación en 19 casos observando pisitividad nuclear epitelial para estrógenos en el 68,42 por ciento y de progesterona en el 47,36 por ciento.

Correlación citológica-anatomopatológica en patología mamaria / Cytologic anatomicopathologic correlation in breast pathology

Se realiza un análisis de 1885 estudios citológicos y 522 correlaciones con la anatomía patológica. Los valores de Sensibilidad, Especialidad y Exactitud Diagnóstica se corresponden con los de la bibliografía a pesar de haber incorporado los materiales insuficientes para el estudio citológico lo mismo que los informes sospechosos. Se acentúa la importancia, seguridad y su fácil realización

Correlación citológica-anatomopatológica en patología mamaria / Cytologic anatomicopathologic correlation in breast pathology

Se realiza un análisis de 1885 estudios citológicos y 522 correlaciones con la anatomía patológica. Los valores de Sensibilidad, Especialidad y Exactitud Diagnóstica se corresponden con los de la bibliografía a pesar de haber incorporado los materiales insuficientes para el estudio citológico lo mismo que los informes sospechosos. Se acentúa la importancia, seguridad y su fácil realización