Classification of follicular-patterned thyroid lesions using a minimal set of epigenetic biomarkers.

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.

[Reversible retrobulbar optic neuritis due to sphenoidal sinus disorders: two case studies]. / Neuritis óptica retrobulbar reversible por sinupatía esfenoidal: dos casos clínicos.

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.

[Annexin A2 expression in head and neck squamous cell carcinoma]. / Expresión de la anexina A2 en los carcinomas epidermoides de cabeza y cuello.

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.

[Head and neck paragangliomas: revision of 89 cases in 73 patients]. / Paragangliomas de cabeza y cuello: revisión de 89 casos en 73 pacientes.

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.