Active surveillance is a feasible and safe strategy in selected patients with papillary thyroid cancer and suspicious cervical lymph nodes detected after thyroidectomy.

Objective: After initial treatment, up to 30% of patients with papillary thyroid cancer (PTC) have incomplete response, mainly cervical lymph node (LN) disease. Previous studies have suggested that active surveillance (AS) is a possible option for these patients. Our aim was to report the results of AS in patients with PTC and cervical LN disease. Materials and methods: In this retrospective observational study, we included adult patients treated and followed for PTC, who presented with cervical LN disease and were managed with AS. Growth was defined as an increase ≥ 3mm in either diameter. Results: We included 32 patients: 27 (84.4%) women, age of 39 ± 14 years, all initially treated with total thyroidectomy, and 22 (69%) with therapeutic neck dissection. Cervical LN disease was diagnosed 1 year (0.3-12.6) after initial management, with a diameter of 9.0 mm (6.0-19.0). After a median AS of 4.3 years (0.6-14.1), 4 (12.5%) patients had LNgrowth: 2 (50%) of whom were surgically removed, 1 (25%) was effectively treated with radiotherapy, and 1 (25%) had a scheduled surgery. Tg increase was the only predictive factor of LN growth evaluated as both the delta Tg (p < 0.0366) and percentage of Tg change (p < 0.0140). None of the included patients died, had local complications due to LN growth or salvage therapy, or developed distant metastases during follow-up. Conclusion: In selected patients with PTC and suspicious cervical LNs diagnosed after initial treatment, AS is a feasible and safe strategy as it allows effective identification and treatment of the minority of patients who progress.

ThyroidPrint®: clinical utility for indeterminate thyroid cytology.

Molecular testing contributes to improving the diagnosis of indeterminate thyroid nodules (ITNs). ThyroidPrint® is a ten-gene classifier aimed to rule out malignancy in ITN. Post-validation studies are necessary to determine the real-world clinical benefit of ThyroidPrint® in patients with ITN. A single-center, prospective, noninterventional clinical utility study was performed, analyzing the impact of ThyroidPrint® in the physicians' clinical decisions for ITN. Demographics, nodule characteristics, benign call rates (BCRs), and surgical outcomes were measured. Histopathological data were collected from surgical biopsies of resected nodules. Of 1272 fine-needle aspirations, 109 (8.6%) were Bethesda III and 135 (10.6%) were Bethesda IV. Molecular testing was performed in 155 of 244 ITN (63.5%), of which 104 were classified as benign (BCR of 67.1%). After a median follow-up of 15 months, 103 of 104 (99.0%) patients with a benign ThyroidPrint® remained under surveillance and one patient underwent surgery which was a follicular adenoma. Surgery was performed in all 51 patients with a suspicious for malignancy as per ThyroidPrint® result and in 56 patients who did not undergo testing, with a rate of malignancy of 70.6% and 32.1%, respectively. A higher BCR was observed in follicular lesion of undetermined significance (87%) compared to atypia of undetermined significance (58%) (P < 0.05). False-positive cases included four benign follicular nodules and six follicular and four oncocytic adenomas. Our results show that, physicians chose active surveillance instead of diagnostic surgery in all patients with a benign ThyroidPrint® result, reducing the need for diagnostic surgery in 67% of patients with preoperative diagnosis of ITN.

Manifestaciones periodontales de la Granulomatosis de Wegener: Reporte de un caso clínico

La granulomatosis de Wegener o granulomatosis con Poliangitis (GPA) es una enfermedad caracterizada por inflamación y necrosis de las paredes de los vasos sanguíneos. Es de etiología desconocida, baja prevalencia y alta agresividad. Esta enfermedad puede comprometer los tejidos bucales causando agrandamiento e inflamación del tejido gingival. Se reporta el caso de un paciente de género masculino que manifiesta aumento de volumen de la encía e inflamación asociado al diagnóstico de granulomatosis de Wegener. La lesión fue eliminada quirúrgicamente y el diagnóstico se logró al combinar los hallazgos serológicos del test ANCA, manifestaciones periodontales y análisis histopatológico. El paciente fue tratado con metotrexato y corticoesteroides y no presenta recidiva de la lesión luego de 2 años de control. En este artículo se analizan las manifestaciones periodontales asociadas a la GPA resaltando la importancia de un adecuado diagnóstico de lesiones periodontales caracterizadas por agradamiento gingival e inflamación.

Wegener's granulomatosis or granulomatosis with polyangiitis (GPA) is a disease characterized by inflammation and necrosis of the blood vessel walls. It is of unknown etiology, low prevalence and high degree of aggressiveness. This disease can compromise the oral tissues, causing enlargement and inflammation of the gingival tissues. The case of a male patient who presented rapidly growing gingival tissue enlargement and inflammatory characteristics associated with the diagnosis of Wegener's granulomatosis is reported. The lesion was removed surgically and the diagnosis was achieved by combining the serological findings of the ANCA test, periodontal manifestations and histopathological analysis of the lesion. The patient was treated with methotrexate and corticosteroids and the lesion did not reappear after 2 years of control. In this article, the periodontal manifestations associated with GPA are analyzed, highlighting the importance of an adequate diagnosis of periodontal lesions characterized by gingival enlargement and inflammation.

[An update on parathyroid carcinoma]. / Puesta al día: carcinoma paratiroideo.

Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic syndromes. It occurs with equal frequency in both sexes, unlike PHP caused by parathyroid adenoma that is more common in women. It should be suspected in cases of severe hypercalcemia, with high parathyroid hormone levels and a palpable cervical mass. Given the difficulty in distinguishing between parathyroid carcinoma and adenoma prior to the surgery, the diagnosis is often made after parathyroidectomy. The only curative treatment is complete surgical resection with oncologic block resection of the primary tumor to ensure free margins. Adjuvant therapies with chemotherapy or radiation therapy do not modify overall or disease-free survival. Recurrences are common and re-operation of resectable recurrent disease is recommended. The palliative treatment of symptomatic hypercalcemia is crucial in persistent or recurrent disease after surgery since morbidity and mortality are more associated with hypercalcemia than with tumor burden.

Polyostotic fibrous dysplasia (McCune-Albright) with rare multiple epiphyseal lesions in association with aneurysmal bone cyst and pathologic fracture.

Fibrous dysplasia, including McCune-Albright syndrome, is a genetic, non-inheritable benign bone disorder that may involve a single or multiple bone, typically occurring in the diaphysis or the metaphysis of long bones. In very rare instances polyostotic fibrous dysplasia present involvement of the epiphysis in long bones. Aneurysmal bone cysts are benign, expansile, lytic bone lesions formed by cystic cavities containing blood, that may occur de novo or secondary to other lesions of bone, including fibrous dysplasia. We report a case of an 18-year-old female with polyostotic fibrous dysplasia (McCune-Albright syndrome) with diaphyseal and unusual multiple foci of epiphyseal involvement of long bones as well as in the patella, and a simultaneous aneurysmal bone cyst of the left femoral neck with pathologic fracture. This is the first report of a simultaneous aneurysmal bone cyst in a patient with polyostotic fibrous dysplasia (McCune-Albright syndrome) with involvement of diaphysis and epiphysis of long bones, highlighting that fibrous dysplasia should be included in the differential diagnosis of polyostotic tumors involving the diaphysis as well as the epiphysis. In patients with polyostotic fibrous dysplasia there should be an active search for lesions in the epiphysis.

Warthin-like and classic papillary thyroid cancer have similar clinical presentation and prognosis.

OBJECTIVE: Warthin-like papillary thyroid cancer (WL-PTC) is an uncommon variant of PTC, usually associated with lymphocytic thyroiditis. Scarce evidence suggests that WL-PTC has similar clinical presentation to classic PTC (C-PTC), with no studies comparing risks of recurrence and response to treatment between both variants. Our objective was to describe the clinical presentation and prognosis of WL-PTC and compare it to C-PTC. METHODS: Retrospective analysis of a prospective cohort, including 370 (96%) patients with C-PTC and 17 (4%) with WL-PTC, consecutively treated with total thyroidectomy with or without RAI, followed for at least 6 months. We compared clinical presentation, risk of mortality and recurrence, as well as response to treatment between both variants. RESULTS: Of the total cohort: 317 (82%) female, 38 ± 13.5 years, median follow-up 4 years (0.5-28.5); most of them stage I and low/intermediate risk of recurrence. We found no differences regarding clinical-pathological data and risk of recurrence. WL-PTC was associated with a higher rate of anti-thyroglobulin antibodies (TgAb) (65% vs. 36%, p = 0.016) and lymphocytic thyroiditis (59% vs. 34%, p = 0.03). The rates of biochemical and structural incomplete responses were similar in both variants. WL-PTC had a lower rate of excellent response (23% vs. 54%, p = 0.01), which became non-significant when performing analysis by TgAb presence (50% vs. 67%, p = NS). CONCLUSION: WL-CPT and C-CPT have similar clinical presentation and rate of recurrence. The lower rate of excellent response to treatment in WL-PTC is due to a higher frequency of TgAb. WL-PCT should not be considered an aggressive variant of PTC.

Puesta al día: carcinoma paratiroideo / An update on parathyroid carcinoma

Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic syndromes. It occurs with equal frequency in both sexes, unlike PHP caused by parathyroid adenoma that is more common in women. It should be suspected in cases of severe hypercalcemia, with high parathyroid hormone levels and a palpable cervical mass. Given the difficulty in distinguishing between parathyroid carcinoma and adenoma prior to the surgery, the diagnosis is often made after parathyroidectomy. The only curative treatment is complete surgical resection with oncologic block resection of the primary tumor to ensure free margins. Adjuvant therapies with chemotherapy or radiation therapy do not modify overall or disease-free survival. Recurrences are common and re-operation of resectable recurrent disease is recommended. The palliative treatment of symptomatic hypercalcemia is crucial in persistent or recurrent disease after surgery since morbidity and mortality are more associated with hypercalcemia than with tumor burden.

Warthin-like and classic papillary thyroid cancer have similar clinical presentation and prognosis

ABSTRACT Objective Warthin-like papillary thyroid cancer (WL-PTC) is an uncommon variant of PTC, usually associated with lymphocytic thyroiditis. Scarce evidence suggests that WL-PTC has similar clinical presentation to classic PTC (C-PTC), with no studies comparing risks of recurrence and response to treatment between both variants. Our objective was to describe the clinical presentation and prognosis of WL-PTC and compare it to C-PTC. Subjects and methods Retrospective analysis of a prospective cohort, including 370 (96%) patients with C-PTC and 17 (4%) with WL-PTC, consecutively treated with total thyroidectomy with or without RAI, followed for at least 6 months. We compared clinical presentation, risk of mortality and recurrence, as well as response to treatment between both variants. Results Of the total cohort: 317 (82%) female, 38 ± 13.5 years, median follow-up 4 years (0.5-28.5); most of them stage I and low/intermediate risk of recurrence. We found no differences regarding clinical-pathological data and risk of recurrence. WL-PTC was associated with a higher rate of anti-thyroglobulin antibodies (TgAb) (65% vs. 36%, p = 0.016) and lymphocytic thyroiditis (59% vs. 34%, p = 0.03). The rates of biochemical and structural incomplete responses were similar in both variants. WL-PTC had a lower rate of excellent response (23% vs. 54%, p = 0.01), which became non-significant when performing analysis by TgAb presence (50% vs. 67%, p = NS). Conclusions WL-CPT and C-CPT have similar clinical presentation and rate of recurrence. The lower rate of excellent response to treatment in WL-PTC is due to a higher frequency of TgAb. WL-PCT should not be considered an aggressive variant of PTC.

Metástasis pancreática como debut de carcinoma papilar de tiroides: caso clínico y revisión del perfil clínico patológico y molecular / Papillary thyroid carcinoma presenting with pancreatic metastases: report of one case

Pancreatic metastases of papillary thyroid carcinoma (PTC) are exceptional. We report a 80-year-old man consulting for obstructive jaundice and dysphonia. Abdominal ultrasonography showed biliary dilation and abdominal magnetic resonance imaging (MRI) showed a pancreatic head mass of 36 mm. A left vocal cord paralysis was confirmed and cervical computed tomography (CT) showed multiple thyroid nodules of up to 35 mm associated with bilateral cervical lymph nodes (LN). Positron emission tomography ( 18 F-FDG PET/CT) evidenced hyper-metabolic activity in bilateral cervical LN, lungs, pancreas and left intercostal soft tissue, as well as left gluteus. Thyroid biopsy reported a tall-cell variant of PTC, and endoscopic ultrasound guided fine needle aspiration (EUS-FNA) of pancreatic mass confirmed PTC metastasis. The molecular study was positive for BRAFV600E. Pancreatic metastasis from PTC can be accurately diagnosed with 18 F-FDG PET/CT and EUS-FNA, which is consistent with a predominant expression of BRAFV600E mutation and, thus, an aggressive presentation with poor short-term survival.

A Thyroid Genetic Classifier Correctly Predicts Benign Nodules with Indeterminate Cytology: Two Independent, Multicenter, Prospective Validation Trials.

Background: Although most thyroid nodules with indeterminate cytology are benign, in most of the world, surgery remains as the most frequent diagnostic approach. We have previously reported a 10-gene thyroid genetic classifier, which accurately predicts benign thyroid nodules. The assay is a prototype diagnostic kit suitable for reference laboratory testing and could potentially avoid unnecessary diagnostic surgery in patients with indeterminate thyroid cytology. Methods: Classifier performance was tested in two independent, ethnically diverse, prospective multicenter trials (TGCT-1/Chile and TGCT-2/USA). A total of 4061 fine-needle aspirations were collected from 15 institutions, of which 897 (22%) were called indeterminate. The clinical site was blind to the classifier score and the clinical laboratory blind to the pathology report. A matched surgical pathology and valid classifier score was available for 270 samples. Results: Cohorts showed significant differences, including (i) clinical site patient source (academic, 43% and 97% for TGCT-1 and -2, respectively); (ii) ethnic diversity, with a greater proportion of the Hispanic population (40% vs. 3%) for TGCT-1 and a greater proportion of African American (11% vs. 0%) and Asian (10% vs. 1%) populations for TGCT-2; and (iii) tumor size (mean of 1.7 and 2.5 cm for TGCT-1 and -2, respectively). Overall, there were no differences in the histopathological profile between cohorts. Forty-one of 155 and 45 of 115 nodules were malignant (cancer prevalence of 26% and 39% for TGCT-1 and -2, respectively). The classifier predicted 37 of 41 and 41 of 45 malignant nodules, yielding a sensitivity of 90% [95% confidence interval; CI 77-97] and 91% [95% CI 79-98] for TGCT-1 and -2, respectively. One hundred one of 114 and 61 of 70 nodules were correctly predicted as benign, yielding a specificity of 89% [95% CI 82-94] and 87% [95% CI 77-94], respectively. The negative predictive values for TGCT-1 and TGCT-2 were 96% and 94%, respectively, whereas the positive predictive values were 74% and 82%, respectively. The overall accuracy for both cohorts was 89%. Conclusions: Clinical validation of the classifier demonstrates equivalent performance in two independent and ethnically diverse cohorts, accurately predicting benign thyroid nodules that can undergo surveillance as an alternative to diagnostic surgery.

Neoplasia folicular tiroidea no invasiva con características nucleares de tipo papilar (Noninvasive follicular thyroid neoplasm with papillary-like nuclear features o NIFTP): en qué estamos hoy, a propósito de un caso / Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): we are we today, about a case

Es bien conocido que ha existido en las últimas décadas un incremento en los casos de cáncer diferenciado de tiroides, especialmente los microcarcinomas. Diversos factores han contribuido a pesquisar pequeños cánceres como el aumento de la disponibilidad de exámenes imagenológicos. Estos pequeños cánceres tiroideos pueden tener un comportamiento no agresivo y no producir letalidad; esto es lo que se conoce como sobrediagnóstico. Esto último tiene implicancias tanto médicas como económicas por terapias agresivas. Así, desde el año 2015, un grupo de expertos cambia la nomenclatura en anatomía patológica del carcinoma papilar tiroideo variante folicular encapsulado (NIEFVPTC de sus siglas en inglés) por Neoplasia folicular tiroidea no invasiva con características nucleares de tipo papilar (NIFTP de sus siglas en inglés). Este cambio se basó en un estudio de Nikiforov donde los NIEFVPTC no tenían efectos adversos ni mortalidad en su seguimiento. Así, la intención inicial del cambio de nomenclatura es eliminar la palabra cáncer y evitar los sobretratamientos innecesarios. Presentamos un caso clínico de una paciente que se sometió a cirugía por un nódulo tiroideo clasificado Bethesda III donde la biopsia definitiva posterior a cirugía evidenció que se trataba de un NIFTP. A raíz de este caso analizamos la literatura hasta la fecha de esta nueva entidad y hacemos un repaso histórico de los carcinomas papilares tiroideos variante folicular. Además, desarrollamos nuevas interrogantes que se plantean desde este nuevo diagnóstico anatomopatológico, de cómo sospecharlo previo a una cirugía, cuál es la cirugía de elección, y cómo debiera ser el seguimiento una vez diagnosticado.

It is well known that there has been an increase in cases of differentiated thyroid cancer in recent decades, especially microcarcinomas. Several factors have contributed to diagnose small cancers such as the increased availability of imaging tests. These small thyroid cancers can have a non-aggressive behavior and not cause lethality, this is what is known as overdiagnosis. The latter has medical as well as economic implications for aggressive therapies. Thus, since 2015, a group of experts has changed the nomenclature in pathological anatomy of encapsulated variant papillary thyroid carcinoma (NIEFVPTC) for non-invasive thyroid follicular neoplasia with papillary nuclear characteristics (NIFTP). This change was based on a Nikiforov study where the NIEFVPTC had no adverse effects or mortality in their follow-up; thus, the initial intention of the nomenclature change is to eliminate the word cancer and avoid unnecessary over-treatments. We present a clinical case of a patient who underwent surgery for a thyroid nodule classified Bethesda III where the definitive biopsy after surgery showed that it was a NIFTP. Following this case, we analyze the literature to date of this new entity and make a historical review of the follicular variant papillary thyroid carcinomas. In addition, we develop new questions that arise from this new pathological diagnosis, how to suspect it prior to surgery, what is the surgery of choice, and what should the follow-up once diagnosed.

Manejo de nódulos tiroideos y cáncer de tiroides con lobectomía: experiencia de un equipo multidisciplinario / Management of thyroid nodules and thyroid cancer with lobectomy: experience of a multidisciplinary team

INTRODUCCIÓN: La extensión de la cirugía es motivo de controversia en el manejo de nódulos y cáncer diferenciado de tiroides (CDT). En nódulos benignos e indeterminados que requieran cirugía, la lobectomía es de elección, mientras que en CDT debe considerarse en tumores intratiroideos ≤ 4 cm. NUESTRO OBJETIVO objetivo fue reportar la primera cohorte chilena de nódulos tiroideos y CDT tratados con lobectomía por un equipo multidisciplinario. SUJETOS Y MÉTODOS: Se incluyeron pacientes sometidos a lobectomía por nódulos tiroideos y CDT que cumplieran: 1) tumor intratiroideo ≤4cm si punción aspirativa (PAF) Bethesda I, III, IV, V o VI; sin límite de tamaño si PAF Bethesda II, y 2) sin hallazgos sospechosos en la ecografía preoperatoria. En pacientes con CDT se describió presentación clínica, complicaciones y tipo de respuesta a tratamiento según ATA 2015 y MINSAL 2020. RESULTADOS: Se incluyeron 105 pacientes, edad 38±11 años, 84 (80%) mujeres, diámetro 2,2±1,5cm: 41 (39%) benignos y 64 (61%) CDT. De los CDT, 44 (69%) tenían cáncer papilar, 7 (11%) cáncer folicular y 13 (20%) NIFTP. Todos eran etapa I. Según MINSAL, 55 (85,9%) de riesgo muy bajo/bajo y 9 (14,1%) intermedio. Según ATA, 51 (80%) y 13 (20%) de riesgo bajo e intermedio, respectivamente. Se indicó totalización precoz y ablación con radioyodo en 6 (9,4%) pacientes: 4 por invasión venosa y 2 por CPT variedad sólida. De los 39 no totalizados seguidos ≥6 meses, no hubo casos de respuesta incompleta. Respecto a las complicaciones, ningún paciente tuvo hipocalcemia y 10 (9,5%) tuvieron disfonía transitoria. CONCLUSIONES: En pacientes con nódulos tiroideos o CDT seleccionados, la lobectomía es una alternativa adecuada. En CDT logra buen control de enfermedad sin necesidad de tratamiento adicional en cerca de 90% de los pacientes, con muy baja morbilidad asociada.

INTRODUCTION: The extension of surgery is a matter of debate in the management of thyroid nodules and differentiated thyroid cancer (DTC). While lobectomy is the procedure of choice in benign and indeterminate nodules that require surgery, it is an option in intrathyroidal DTC up to 4 cm. OUR OBJECTIVE was to report the first Chilean cohort of patients with thyroid nodules and DTC treated with lobectomy by a multidisciplinary team. SUBJECTS AND METHODS: We included patients with thyroid nodules treated with lobectomy, who met the following inclusion criteria: 1) intrathyroidal tumor ≤ 4cm if fine-needle aspiration biopsy (FNA) was Bethesda I, III, IV, V o VI; without size limit if FNA was Bethesda II, and 2) non-suspicious findings in preoperative ultrasound. In patients with DTC we described clinical presentation, complications and response to treatment according to ATA 2015 and MINSAL 2020. RESULTS: We included 105 patients, 38±11 years old, 84 (80%) female, diameter 2.2±1.5cm: 41 (39%) benign and 64 (61%) DTC. Among DTC, 44 (69%) had papillary thyroid cancer, 7 (11%) follicular thyroid cancer and 13 (20%) NIFTP. All had stage I DTC. According to MINSAL, 55 (85.9%) were very low/low, and 9 (14.1%) intermediate risk. According to ATA, 51 (80%) and 13 (20%) were low and intermediate risk, respectively. Six (9.4%) patients required early completion thyroidectomy and radioiodine ablation: 4 due to angioinvasion and 2 due to solid variant PTC. None of the 39 non-completed patients followed for at least 6 months had incomplete response. Regarding complications, there were no cases of hypocalcemia and 10 (9.5%) patients had transient dysphonia. CONCLUSIONS: In properly selected patients with thyroid nodules or DTC, lobectomy is an appropriate treatment option. In DTC, lobectomy accomplishes adequate disease control without need of further treatment in nearly 90% of patients, with very low associated morbidity.

The Combination of RET, BRAF and Demographic Data Identifies Subsets of Patients with Aggressive Papillary Thyroid Cancer.

The use of BRAFV600E and RET/PTC1 as biomarkers to guide the extent of surgery in patients with papillary thyroid cancer (PTC) remains controversial. We assessed the combined use of demographic data (sex and age) with mRNA expression levels and/or mutational status (BRAFV600E and RET/PTC1) to identify potential subsets of patients with aggressive histopathological features (lymph node metastases and extrathyroidal extension). In a cohort of 126 consecutive patients, BRAFV600E and RET/PTC1 mutations were found in 52 and 18%, respectively. By conditional bivariate analysis (CBVA), a 'high activity' profile of BRAF (BRAFV600E positive or high expression) and 'low activity' profile of RET (RET/PTC1 negative or low expression) was associated with extrathyroidal extension (ETE) (OR 4.48). Alternatively, a 'high activity' profile of RET (RET/PTC1 positive or high expression) and 'low activity' profile of BRAF (BRAFV600E negative or low expression) were associated with lymph node metastasis (LNM) (OR 12.80). Furthermore, in patients younger than 55 years, a low expression of BRAF was associated with LNM (OR 17.65) and the presence of BRAFV600E mutation was associated with ETE (OR 2.76). Our results suggest that the analysis of demographic and molecular variables by CBVA could contribute to identify subsets of patients with aggressive histopathologic features, providing a potential guide to personalised surgical management of PTC.

Differential expression profile of CXCR3 splicing variants is associated with thyroid neoplasia. Potential role in papillary thyroid carcinoma oncogenesis?

Papillary thyroid cancer (PTC) is the most prevalent endocrine neoplasia. The increased incidence of PTC in patients with thyroiditis and the frequent immune infiltrate found in PTC suggest that inflammation might be a risk factor for PTC development. The CXCR3-ligand system is involved in thyroid inflammation and CXCR3 has been found upregulated in many tumors, suggesting its pro-tumorigenic role under the inflammatory microenvironment. CXCR3 ligands (CXCL4, CXCL9, CXCL10 and CXCL11) trigger antagonistic responses partly due to the presence of two splice variants, CXCR3A and CXCR3B. Whereas CXCR3A promotes cell proliferation, CXCR3B induces apoptosis. However, the relation between CXCR3 variant expression with chronic inflammation and PTC development remains unknown. Here, we characterized the expression pattern of CXCR3 variants and their ligands in benign tumors and PTC. We found that CXCR3A and CXCL10 mRNA levels were increased in non-metastatic PTC when compared to non-neoplastic tissue. This increment was also observed in a PTC epithelial cell line (TPC-1). Although elevated protein levels of both isoforms were detected in benign and malignant tumors, the CXCR3A expression remained greater than CXCR3B and promoted proliferation in Nthy-ori-3-1 cells. In non-metastatic PTC, inflammation was conditioning for the CXCR3 ligands increased availability. Consistently, CXCL10 was strongly induced by interferon gamma in normal and tumor thyrocytes. Our results suggest that persistent inflammation upregulates CXCL10 expression favoring tumor development via enhanced CXCR3A-CXCL10 signaling. These findings may help to further understand the contribution of inflammation as a risk factor in PTC development and set the basis for potential therapeutic studies.

Estudio y manejo de nódulos tiroideos por médicos no especialistas. Consenso SOCHED / Study and management of thyroid nodes by non specialist physicians: SOCHED consensus

The thyroid nodule is a frequent cause of primary care consultation. The prevalence of a palpable thyroid nodule is approximately 4-7%, increasing up to 67% by the incidental detection of nodules on ultrasound. The vast majority are benign and asymptomatic, staying stable over time. The clinical importance of studying a thyroid nodule is to exclude thyroid cancer, which occurs in 5 to 10% of the nodules. The Board of SOCHED (Chilean Society of Endocrinology and Diabetes) asked the Thyroid Study Group to develop a consensus regarding the diagnostic management of the thyroid nodule in Chile, aimed at non-specialist physicians and adapted to the national reality. To this end, a multidisciplinary group of 31 experts was established among university academics, active researchers with publications on the subject and prominent members of scientific societies of endocrinology, head and neck surgery, pathology and radiology. A total of 14 questions were developed with key aspects for the diagnosis and subsequent referral of patients with thyroid nodules, which were addressed by the participants. In those areas where the evidence was insufficient or the national reality had to be considered, the consensus opinion of the experts was used through the Delphi methodology. The consensus was approved by the SOCHED board for publication.

A 10-Gene Classifier for Indeterminate Thyroid Nodules: Development and Multicenter Accuracy Study.

BACKGROUND: In most of the world, diagnostic surgery remains the most frequent approach for indeterminate thyroid cytology. Although several molecular tests are available for testing in centralized commercial laboratories in the United States, there are no available kits for local laboratory testing. The aim of this study was to develop a prototype in vitro diagnostic (IVD) gene classifier for the further characterization of nodules with an indeterminate thyroid cytology. METHODS: In a first stage, the expression of 18 genes was determined by quantitative polymerase chain reaction (qPCR) in a broad histopathological spectrum of 114 fresh-tissue biopsies. Expression data were used to train several classifiers by supervised machine learning approaches. Classifiers were tested in an independent set of 139 samples. In a second stage, the best classifier was chosen as a model to develop a multiplexed-qPCR IVD prototype assay, which was tested in a prospective multicenter cohort of fine-needle aspiration biopsies. RESULTS: In tissue biopsies, the best classifier, using only 10 genes, reached an optimal and consistent performance in the ninefold cross-validated testing set (sensitivity 93% and specificity 81%). In the multicenter cohort of fine-needle aspiration biopsy samples, the 10-gene signature, built into a multiplexed-qPCR IVD prototype, showed an area under the curve of 0.97, a positive predictive value of 78%, and a negative predictive value of 98%. By Bayes' theorem, the IVD prototype is expected to achieve a positive predictive value of 64-82% and a negative predictive value of 97-99% in patients with a cancer prevalence range of 20-40%. CONCLUSIONS: A new multiplexed-qPCR IVD prototype is reported that accurately classifies thyroid nodules and may provide a future solution suitable for local reference laboratory testing.

Desmoplastic Fibroma of the Mandible in a Pediatric Patient: A Case Report of Resection and Reconstruction With A Six-Year Follow-Up.

Desmoplastic fibroma (DF) of bone is considered a benign but locally aggressive tumor of fibroblastic origin. DF is rare, representing less than 1% of all bone tumors. Approximately 84% of patients are younger than 30 years. DF has a slow but aggressive growth potential and can recur locally when it has not been completely excised. Complete resection is the treatment of choice to decrease recurrence and morbidity. Mandibular reconstruction is mandatory in pediatric patients to ensure correct craniofacial development. The present report describes the case of a pediatric patient with mandibular DF in whom complete resection and immediate reconstruction with a fibula flap proved a satisfactory treatment option, with low morbidity and excellent esthetic and functional results at 6-year follow-up.

[Diagnostic yield of fine-needle aspiration cytology for the detection of thyroid cancer in pediatric patients]. / Concordancia de la citología por punción con aguja fina para la detección de cáncer de tiroides en pediatría.

BACKGROUND: Despite the low frequency of thyroid nodules (TN) in children, one of every four is malignant. Fine-needle aspiration cytology (FNAC) has a high accuracy detecting thyroid cancer. AIM: To evaluate the performance of FNAC in TN in Chilean children to detect thyroid cancer. PATIENTS AND METHODS: The pathological reports of 77 thyroidectomies and 103 FNAC carried out in patients aged less than 18 years, between 2002 and 2013 were reviewed. In 36 patients aged 15 ± 2 years (77% women), both the reports of the thyroidectomy and FNAC were available. The cytological specimens were reclassified based on Bethesda 2010. The histology was classified as benign (nodular hyperplasia and follicular adenoma, n = 18), or malignant (papillary, follicular and medullar carcinoma, n = 18). The concordance of the cytology with the final biopsy report was calculated. RESULTS: FNAC classified 13 specimens as definitively benign and 13 as definitively malignant. Among these, these concordances with the pathological study of the biopsy was 100%. Of six cytology tests considered "suspicious for follicular neoplasm" by FNAC, four were benign (67%), and two malignant (33%). Of four cytology tests considered "suggestive of carcinoma" by FNAC, one was benign (25%), and three malignant (75%). CONCLUSIONS: Among the studied children, there was a good concordance between FNAC and surgical biopsies. Therefore a FNAC should be carried out when malignancy is suspected in pediatric patients with a TN.

[Skin necrosis: report of eleven cases]. / Necrosis cutánea: un desafío para el médico.

Skin necrosis must be considered as a syndrome, because it is a clinical manifestation of different diseases. An early diagnosis is very important to choose the appropriate treatment. Therefore, its causes should be suspected and confirmed quickly. We report eleven patients with skin necrosis seen at our Department, caused by different etiologies: Warfarin-induced skin necrosis, loxoscelism, diabetic microangiopathy, ecthyma gangrenosum, disseminated intravascular coagulation, necrotizing vasculitis, paraneoplastic extensive necrotizing vasculitis, livedoid vasculopathy, necrotizing fasciitis, necrosis secondary to the use of vasoactive drugs and necrosis secondary to the use of cocaine. We also report the results of our literature review on the subject.