ABSTRACT
Objective: The minimally invasive fine-needle aspiration cytology (FNAC) is the current gold standard for the diagnosis of thyroid nodule malignancy. However, the correct discrimination of follicular neoplasia often requires more invasive diagnostic techniques. The lack of suitable immunohistochemical markers to distinguish between follicular thyroid carcinoma and other types of follicular-derived lesions complicates diagnosis, and despite most of these tumours being surgically resected, only a small number will test positive for malignancy. As such, the development of new orthogonal diagnostic approaches may improve the accuracy of diagnosing thyroid nodules. Design: This study includes a retrospective, multi-centre training cohort including 54 fresh-frozen follicular-patterned thyroid samples and two independent, multi-centre validation cohorts of 103 snap-frozen biopsies and 33 FNAC samples, respectively. Methods: We performed a genome-wide genetic and epigenetic profiling of 54 fresh-frozen follicular-patterned thyroid samples using exome sequencing and the Illumina Human DNA Methylation EPIC platform. An extensive validation was performed using the bisulfite pyrosequencing technique. Results: Using a random forest approach, we developed a three-CpG marker-based diagnostic model that was subsequently validated using bisulfite pyrosequencing experiments. According to the validation cohort, this cost-effective method discriminates between benign and malignant nodules with a sensitivity and specificity of 97 and 88%, respectively (positive predictive value (PPV): 0.85, negative predictive value (NPV): 0.98). Conclusions: Our classification system based on a minimal set of epigenetic biomarkers can complement the potential of the diagnostic techniques currently available and would prioritize a considerable number of surgical interventions that are often performed due to uncertain cytology. Significance statement: In recent years, there has been a significant increase in the number of people diagnosed with thyroid nodules. The current challenge is their etiological diagnosis to discount malignancy without resorting to thyroidectomy. The method proposed here, based on DNA pyrosequencing assays, has high sensitivity (0.97) and specificity (0.88) for the identification of malignant thyroid nodules. This simple and cost-effective approach can complement expert pathologist evaluation to prioritize the classification of difficult-to-diagnose follicular-patterned thyroid lesions and track tumor evolution, including real-time monitoring of treatment efficacy, thereby stimulating adherence to health promotion programs.
Subject(s)
Thyroid Neoplasms , Thyroid Nodule , Biomarkers , Epigenesis, Genetic , Humans , Retrospective Studies , Sensitivity and Specificity , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Thyroid Nodule/diagnosis , Thyroid Nodule/genetics , Thyroid Nodule/pathologyABSTRACT
El tratamiento quirúrgico del cáncer de laringe e hipofaringe localmente avanzado implica, en muchas ocasiones, la realización de una laringectomía total, procedimiento que implica una mutilación importante por la pérdida de la función vocal y la presencia de un traqueostoma permanente. Desde la publicación del estudio de la Veterans Affairs Laryngeal Cancer Study Group en 1991, que demostró la posibilidad de un tratamiento conservador con similares posibilidades de curación a la cirugía, se ha realizado un gran esfuerzo investigador para definir la opción terapéutica que obtiene las mejores tasas de preservación laríngea y la mayor supervivencia. En este artículo, se revisan los resultados de esta investigación, tanto en el aspecto oncológico como de función(AU)
Surgical treatment of locally advanced laryngeal and hypopharyngeal cancer often results in a total laryngectomy. This procedure leads to signifi cant mutilation, due to the loss of vocal function and the presence of a permanent stoma. Since the publication of the Veterans Affairs Laryngeal Cancer Study Group study in 1991, which demonstrated the feasibility of conservative treatment without compromising the chances of cure, intensive clinical research has been performed to defi ne the best therapeutic option in terms of laryngeal preservation and survival. In this article, we review the results of this clinical research, focusing both on oncological and functional results(AU)
Subject(s)
Humans , Male , Female , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/surgery , Laryngeal Neoplasms/surgery , Hypopharyngeal Neoplasms/surgery , Laryngectomy , Organ Preservation SolutionsABSTRACT
Optic neuritis are clinically demonstrated by a temporary but severe loss of vision and can be caused by a wide variety of diseases. It is unusual for sphenoidal sinusitis to co-exist with acute optic neuritis, so the simultaneous appearance of both diseases would invite aetiological suspicion. We present two cases where the first clinical manifestation of infectious sphenoidal pathology was retrobulbar optic neuritis, which reverted with treatment, medical in one case and surgical in the other, of the sinusitis.
Subject(s)
Optic Neuritis/etiology , Sphenoid Sinusitis/complications , Adult , Aged , Female , Humans , Male , Sphenoid Sinusitis/therapyABSTRACT
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Subject(s)
Humans , Male , Middle Aged , Jugular Veins/abnormalities , Carcinoma, Squamous Cell/surgeryABSTRACT
Las neuritis ópticas pueden estar producidas por una gran variedad de enfermedades y se manifiestan clínicamente como una pérdida de visión temporal pero severa. Es raro que sinusitis esfenoidales coexistan con neuritis ópticas agudas, por lo que su relación invita a la sospecha etiológica. Presentamos 2 casos en los que la primera manifestación de una afección infecciosa esfenoidal fue una neuritis óptica retrobulbar que revirtió tras el tratamiento, médico, en un caso, y quirúrgico, en el otro, de la sinusitis
Optic neuritis are clinically demonstrated by a temporary but severe loss of vision and can be caused by a wide variety of diseases. It is unusual for sphenoidal sinusitis to co-exist with acute optic neuritis, so the simultaneous appearance of both diseases would invite aetiological suspicion. We present two cases where the first clinical manifestation of infectious sphenoidal pathology was retrobulbar optic neuritis, which reverted with treatment, medical in one case and surgical in the other, of the sinusitis
Subject(s)
Humans , Female , Adult , Male , Middle Aged , Optic Neuritis/etiology , Sinusitis/complications , Sinusitis/diagnosis , Mucocele/diagnosis , Adrenal Cortex Hormones/therapeutic use , Tomography, Emission-Computed/methods , Scotoma/complications , Evoked Potentials, Auditory/physiologyABSTRACT
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Subject(s)
Humans , Editorial Policies , Ethics , Science , Publishing/ethicsABSTRACT
OBJECTIVE: Over-expression of annexin A2 (ANXA2) has been reported in various cancers. However, no data are available on the expression of this protein in head and neck squamous cell carcinomas (HNSCC). The objective of this preliminary study is to investigate the expression of ANXA2 in these carcinomas. MATERIAL AND METHOD: ANXA2 expression was analyzed by immunohistochemistry in paraffin-embedded sections from 9 patients with premalignant lesions and 21 patients with HNSCC. RESULTS: All dysplastic tissues showed significantly reduced ANXA2 expression compared to normal tissue. In contrast, ANXA2 expression was observed in all but one of the tumours studied. There was a significant correlation of lower ANXA2 expression with a poorer histological differentiation, larger tumours, and nodal metastases. CONCLUSIONS: Our data show for the first time that ANXA2 is expressed in head and neck squamous cell carcinomas and that its expression seems to be related with the degree of differentiation status of these tumours.
Subject(s)
Annexin A2/biosynthesis , Carcinoma, Squamous Cell/metabolism , Head and Neck Neoplasms/metabolism , Female , Humans , Male , Middle AgedABSTRACT
Objetivo: La expresión de la anexina A2 (ANXA2) se ha hallado elevada en varios cánceres. Sin embargo, no hay datos disponibles de la expresión de esta proteína en los carcinomas epidermoides de cabeza y cuello. El objetivo de este estudio preliminar es investigar la expresión de la ANXA2 en estos carcinomas. Material y método: Se analizó la expresión de la ANXA2 mediante inmunohistoquímica en muestras incluidas en parafina de 9 lesiones premalignas y 21 carcinomas epidermoides de cabeza y cuello. Resultados: Todas las lesiones con displasia mostraron una reducción en la expresión de la ANXA2 respecto al tejido normal. En contraste, se apreció expresión de la ANXA2 en todos menos uno de los tumores estudiados. La disminución de la expresión de la ANXA2 en los carcinomas se correlacionó de forma significativa con una peor diferenciación histológica, con tumores de mayor tamaño y con metástasis ganglionares. Conclusiones: Nuestros datos muestran por primera vez que la ANXA2 se expresa en los carcinomas epidermoides de cabeza y cuello e indican que su expresión se relaciona con el grado de diferenciación de estos tumores
Objective: Over-expression of annexin A2 (ANXA2) has been reported in various cancers. However, no data are available on the expression of this protein in head and neck squamous cell carcinomas (HNSCC). The objective of this preliminary study is to investigate the expression of ANXA2 in these carcinomas. Material and method: ANXA2 expression was analyzed by immunohistochemistry in paraffin-embedded sections from 9 patients with premalignant lesions and 21 patients with HNSCC. Results: All dysplastic tissues showed significantly reduced ANXA2 expression compared to normal tissue. In contrast, ANXA2 expression was observed in all but one of the tumours studied. There was a significant correlation of lower ANXA2 expression with a poorer histological differentiation, larger tumours, and nodal metastases. Conclusions: Our data show for the first time that ANXA2 is expressed in head and neck squamous cell carcinomas and that its expression seems to be related with the degree of differentiation status of these tumours
Subject(s)
Male , Female , Middle Aged , Humans , Carcinoma, Squamous Cell/diagnosis , Immunohistochemistry/methods , Annexin A2 , Head and Neck Neoplasms/diagnosis , Gene Expression Regulation, Neoplastic , Gene Expression Regulation/physiology , Laryngeal Neoplasms/diagnosisABSTRACT
INTRODUCTION: Paragangliomas (PGL) are uncommon neuroectodermal tumours. PGL are usually clinically benign tumours, although metastasis has been reported and invasive growth can occur in adjacent tissues (<10 %). Mutations in SDHB, SDHC, and SDHD, which encode sub-units of mitochondrial complex II (succinate dehydrogenase), play an important role in the pathogenesis of these tumours. MATERIAL AND METHOD: Retrospective review of 73 patients with 89 paragangliomas who had undergone resection of the PGL in our hospital. There were 8 patients who displayed multiple PGL. PGL were distributed as follows: 33 were jugular, 17 tympanic, 26 carotid body tumours, and 13 vagal paragangliomas. All these patients had a follow-up time of at least a year. The surgical approach was evaluated in terms of tumour origin, sequelae, and subsequent evolution, as well as the relapses and their relation with location of the primary tumour. RESULTS: The treatment was surgical, using complementary radiosurgery in just 1 patient. The type A infratemporal fossa approach was used in jugular paragangliomas, the approach was cervical in the carotid and vagal ones and, in the tympanics, a transmeatal or transmastoid approach was performed. In the 73 patients making up our study group, there were 11 recurrences which appeared in jugular paragangliomas (two of them in multiple PGL cases). The post-operative sequelae were mainly cranial nerve paralysis (VII, IX, X, XI, and XII), along with cerebrospinal fluid fistulas in 14 of the jugular PGLs. CONCLUSIONS: With this article we try to reflect our experience in the treatment of this type of tumour. Surgical treatment achieves excellent control of the disease with an acceptable morbidity in young or middle-aged patients. In order to diminish the probabilities of facial nerve paralysis in jugular PGL we must avoid the facial nerve transposition in the infratemporal approach.
Subject(s)
Head and Neck Neoplasms/pathology , Paraganglioma/pathology , Case-Control Studies , Head and Neck Neoplasms/surgery , Humans , Magnetic Resonance Imaging , Paraganglioma/surgery , Radiosurgery/methods , Retrospective StudiesABSTRACT
Introducción: Los paragangliomas son tumores poco frecuentes de origen neuroectodérmico. Se los considera tumores benignos, pero en algunas ocasiones tienen un comportamiento biológico similar a los tumores malignos (< 10 %). Las mutaciones germinales en los genes SDHB, SDHC y SDHD, que codifican las subunidades del mismo nombre en el complejo enzimático mitocondrial de la succinato deshidrogenasa, tienen un papel importante en la patogenia. Material y método: Se trata de un estudio retrospectivo en el que se revisa a 73 pacientes intervenidos en nuestro servicio con un total de 89 paragangliomas, ya que 8 pacientes presentaban paragangliomas múltiples. Los paragangliomas se distribuyeron de la siguiente forma: 33 yugulares, 17 timpánicos, 26 carotídeos y 13 vagales. Todos estos pacientes tuvieron un seguimiento mínimo de 1 año. Se evaluaron las vías de abordaje en función de la localización tumoral, las secuelas acaecidas y su ulterior evolución, así como las recurrencias y su relación con la localización del tumor primario. Resultados: El tratamiento fue quirúrgico, utilizando la radiocirugía como tratamiento complementario en un paciente. En los paragangliomas yugulares se realizó un abordaje infratemporal tipo A, en los carotídeos y vagales el abordaje fue cervical y en los timpánicos, transmeatal o transmastoideo. De los 73 pacientes con paragangliomas intervenidos que componen nuestra población en estudio, hubo 11 recurrencias, que aparecieron en los paragangliomas yugulares, que en 2 casos fueron paragangliomas múltiples. Las secuelas postoperatorias fueron sobre todo la parálisis de nervios craneales (VII, IX, X, XI y XII), junto con las fístulas de líquido cefalorraquídeo en el 14 % de los paragangliomas yugulares. Conclusiones: Con este artículo pretendemos reflejar nuestra experiencia en el tratamiento de este tipo de tumores. El tratamiento quirúrgico consigue un excelente control de la enfermedad con una morbilidad aceptable en pacientes de mediana edad o jóvenes. Para disminuir las probabilidades de parálisis facial en los paragangliomas yugulares, debe evitarse la transposición del facial en el abordaje infratemporal de la fosa yugular
Introduction: Paragangliomas (PGL) are uncommon neuroectodermal tumours. PGL are usually clinically benign tumours, although metastasis has been reported and invasive growth can occur in adjacent tissues (<10 %). Mutations in SDHB, SDHC, and SDHD, which encode sub-units of mitochondrial complex II (succinate dehydrogenase), play an important role in the pathogenesis of these tumours. Material and method: Retrospective review of 73 patients with 89 paragangliomas who had undergone resection of the PGL in our hospital. There were 8 patients who displayed multiple PGL. PGL were distributed as follows: 33 were jugular, 17 tympanic, 26 carotid body tumours, and 13 vagal paragangliomas. All these patients had a follow-up time of at least a year. The surgical approach was evaluated in terms of tumour origin, sequelae, and subsequent evolution, as well as the relapses and their relation with location of the primary tumour. Results: The treatment was surgical, using complementary radiosurgery in just 1 patient. The type A infratemporal fossa approach was used in jugular paragangliomas, the approach was cervical in the carotid and vagal ones and, in the tympanics, a transmeatal or transmastoid approach was performed. In the 73 patients making up our study group, there were 11 recurrences which appeared in jugular paragangliomas (two of them in multiple PGL cases). The post-operative sequelae were mainly cranial nerve paralysis (VII, IX, X, XI, and XII), along with cerebrospinal fluid fistulas in 14 of the jugular PGLs. Conclusions: With this article we try to reflect our experience in the treatment of this type of tumour. Surgical treatment achieves excellent control of the disease with an acceptable morbidity in young or middle-aged patients. In order to diminish the probabilities of facial nerve paralysis in jugular PGL we must avoid the facial nerve transposition in the infratemporal approach
Subject(s)
Humans , Paraganglioma/pathology , Head and Neck Neoplasms/pathology , Succinate Dehydrogenase , Retrospective Studies , Glomus Jugulare Tumor/therapy , Glomus Tympanicum Tumor/therapy , Aortic Bodies/pathology , Carotid Body/pathology , Neoplasm Recurrence, Local , Paraganglioma/surgery , Head and Neck Neoplasms/surgeryABSTRACT
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