Utilidad de los marcadores moleculares en el diagnóstico de nódulos tiroideos con citología indeterminada

RESUMEN Los nódulos tiroideos representan un problema clínico a nivel mundial debida a su alta prevalencia. La importancia clínica de su estudio radica en excluir malignidad, que ocurre entre el 7-15% de los mismos. El método estándar de oro para el diagnóstico de los mismos es el análisis citológico de la punción aspiración con aguja fina. Sin embargo, hasta un 30% de estos presentan citologías indeterminadas (Bethesda III o IV). Con un resultado histopatológico benigno en, aproximadamente tres de cada cuatro de estos casos, la cirugía diagnóstica (tiroidectomía parcial o lobectomía) resulta en un inconveniente ya que expone al paciente a innecesarios riesgos quirúrgicos. En el caso de lesiones malignas, una tiroidectomía en una segunda etapa es a menudo indicada, lo que se asocia con costos adicionales y mayores riesgos de complicaciones quirúrgicas. Es por esto que se requiere de una herramienta con mayor precisión para determinar la benignidad o malignidad de un nódulo tiroideo con citología indeterminada. En este contexto el análisis molecular del tejido tiroideo se convierte en un poderoso complemento para el diagnóstico preoperatorio de los nódulos tiroideos con citología indeterminada, ya que entre el 60 al 70% de los cánceres de tiroides albergan al menos una mutación genética conocida.

ABSTRACT Thyroid nodules represent a clinical problem worldwide due to its high prevalence. The clinical importance lies in excluding malignancy, which occurs between 7-15% of them. The cytological analysis is the gold standard for the diagnosis. However, up to 30% of these have indeterminate cytologies (Bethesda III or IV). In these patients, diagnostic surgeries are performed. With a benign histopathological result in approximately three out of four of these cases, surgery results in an inconvenience since it exposes the patient to unnecessary surgical risks. In the case of malignant lesions, a thyroidectomy in a second stage is often indicated, which is associated with additional costs and increased risks of surgical complications. A more precise method is needed to determine the benignity or malignancy of a thyroid nodule with indeterminate cytology. In this context, molecular analysis of thyroid tissue becomes a powerful complement for the preoperative diagnosis of thyroid nodules with indeterminate cytology, since between 60 to 70% of thyroid cancers harbor at least one known genetic mutation.

Current use of molecular profiling for indeterminate thyroid nodules. / Utilidad del estudio molecular de nódulos tiroideos con citología indeterminada.

Even though cytology remains the gold standard to assess the nature of thyroid nodules, up to 30% of the results are indeterminate (BethesdaIII and IV). In these cases, current guidelines recommend performing diagnostic surgery, which proves malignancy in only 15-30% of cases. A more precise method is needed to avoid unnecessary surgeries, surgical complications and costs in the process of diagnosing indeterminate nodules. Complementary use of molecular profiling tests seems to help in this complex scenario. We present a review of the current literature on the usefulness of molecular profiling of thyroid nodules so as to define its indications, costs and usability for clinical practice.

Contribution of scintigraphy and ultrasonography to the prediction of malignancy in thyroid nodules with indeterminate cytology / Contribuição da cintilografia e ultrassonografia para a predição de malignidade em nódulos tireoidianos com citologia indeterminada

OBJECTIVE: To evaluate the contribution of 131I scintigraphy and ultrasonography to the prediction of malignancy in thyroid nodules with indeterminate cytology in euthyroid patients. SUBJECTS AND METHODS: The sample consisted of 102 patients with thyroid nodules, submitted to FNAC and presenting an indeterminate cytological diagnosis (follicular neoplasm). RESULTS: Malignancy was observed in 19/25 (76 percent) nodules with suspicious ultrasonographic characteristics versus 5/77 (6.5 percent) without suspicious findings. When 131I scintigraphy showed a cold or hot nodule, the chance of malignancy was 38.5 percent and 2.5 percent, respectively. This exam was inconclusive in 10 percent of the patients. CONCLUSIONS: Surgery is indicated when a thyroid nodule with indeterminate cytology exhibits suspicious ultrasonographic characteristics. Otherwise, 131I scintigraphy can exclude thyroidectomy when reveals uptake in the nodule, which is observed in half the cases.

OBJETIVO: Avaliar a contribuição da cintilografia com 131I e da ultrassonografia na predição de malignidade em nódulos tireoidianos com citologia indeterminada em pacientes eutireoidianos. SUJEITOS E MÉTODOS: A amostra foi composta por 102 pacientes com nódulos tireoidianos submetidos à punção aspirativa com agulha fina (PAAF), apresentando citologia indeterminada (neoplasia folicular). RESULTADOS: Malignidade foi encontrada em 19/25 (76 por cento) nódulos suspeitos na ultrassonografia versus 5/77 (6,5 por cento) naqueles sem características suspeitas. Quando a cintilografia com 131I mostrou nódulo hipo- ou hipercaptante, a chance de malignidade foi 38,5 por cento e 2,5 por cento, respectivamente, e em 10 por cento dos pacientes esse exame foi inconclusivo. CONCLUSÕES: Cirurgia está indicada quando um nódulo tireoidiano com citologia indeterminada exibe características ultrassonográficas suspeitas. Quando não as exibe, a cintilografia com 131I pode dispensar a tireoidectomia se revelar captação correspondente ao nódulo, o que ocorre em metade dos casos.