Closing the gap: prognostic and predictive biomarker validation for personalized care in a Latin American hormone-dependent breast cancer cohort.

BACKGROUND: Several guidelines recommend the use of different classifiers to determine the risk of recurrence (ROR) and treatment decisions in patients with HR+HER2- breast cancer. However, data are still lacking for their usefulness in Latin American (LA) patients. Our aim was to evaluate the comparative prognostic and predictive performance of different ROR classifiers in a real-world LA cohort. METHODS: The Molecular Profile of Breast Cancer Study (MPBCS) is an LA case-cohort study with 5-year follow-up. Stages I and II, clinically node-negative HR+HER2- patients (n = 340) who received adjuvant hormone therapy and/or chemotherapy, were analyzed. Time-dependent receiver-operator characteristic-area under the curve, univariate and multivariate Cox proportional hazards regression (CPHR) models were used to compare the prognostic performance of several risk biomarkers. Multivariate CPHR with interaction models tested the predictive ability of selected risk classifiers. RESULTS: Within this cohort, transcriptomic-based classifiers such as the recurrence score (RS), EndoPredict (EP risk and EPClin), and PAM50-risk of recurrence scores (ROR-S and ROR-PC) presented better prognostic performances for node-negative patients (univariate C-index 0.61-0.68, adjusted C-index 0.77-0.80, adjusted hazard ratios [HR] between high and low risk: 4.06-9.97) than the traditional classifiers Ki67 and Nottingham Prognostic Index (univariate C-index 0.53-0.59, adjusted C-index 0.72-0.75, and adjusted HR 1.85-2.54). RS (and to some extent, EndoPredict) also showed predictive capacity for chemotherapy benefit in node-negative patients (interaction P = .0200 and .0510, respectively). CONCLUSION: In summary, we could prove the clinical validity of most transcriptomic-based risk classifiers and their superiority over clinical and immunohistochemical-based methods in the heterogenous, real-world node-negative HR+HER2- MPBCS cohort.

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.

Cuando el carcinoma de tiroides no es indolente: carcinoma de alto grado derivado del epitelio folicular / When Thyroid Carcinoma is not Indolent: High-Grade Carcinoma Derived From The Follicular Epithelium

Los carcinomas de tiroides derivados de células foliculares de alto grado (HGFDTC) son tumores poco frecuentes con un pronóstico intermedio entre carcinomas tiroideos bien diferenciados y anaplásicos. La clasificación de la OMS más reciente identifica dos tipos distintos de HGFDTC: 1) carcinoma de tiroides mal diferenciado (arquitectura sólida, trabecular o insular, falta de características nucleares de núcleos nucleares papilares y contorneados, necrosis mitosis (≥3/2mm2), y 2 ) Diferenciar carcinoma de tiroides de alto grado (recuento mitótico alto (≥5/mm2) y/o necrosis). Estos tumores son frecuentemente refractarios de radioyodo, tienen una alta propensión a metástasis distantes y una mala supervivencia general a largo plazo. Desde un punto de vista molecular, HGFDTC comparten mutaciones del controlador es decir, BRAF) y, con menos frecuencia, las fusiones genéticas (es decir, NTRK, RET) con arcinomas de tiroides diferenciados. A medida que ocurre la desdiferenciación, se adquieren alteraciones secundarias (como el promotor TERT y TP53). En esta revisión, nuestro objetivo es describir las características clínicas, moleculares y patológicas de HGFDTC, así como su gestión e investigación futura

High-grade follicular cell derived thyroid carcinomas (HGFDTC) are infrequent tumors with a prognosis intermediate between well differentiated and anaplastic thyroid carcinomas. The most recent WHO classification identifies two distinct types of HGFDTC: 1) Poorly differentiated thyroid carcinoma (solid, trabecular or insular architecture, lack of nuclear features of papillary nuclear and either convoluted nuclei, necrosis or mitosis (≥3/2mm2), and 2) differentiated high-grade thyroid carcinoma (high mitotic count (≥5/mm2) and/or necrosis). These tumors are frequently radioiodine refractory, have a high propensity for distant metastases, and poor long term overall survival. From a molecular standpoint, HGFDTC share driver mutations (ie BRAF) and, less frequently, gene fusions (ie NTRK, RET) with differentiated thyroid carcinomas. As dedifferentiation occurs, secondary alterations (such as TERT promoter, and TP53) are acquired. In this review, we aim to describe the clinical, molecular and pathological characteristics of HGFDTC, as well as their management and future research

[Effectiveness of lacosamide in the treatment of refractory neuropathic pain: an open observational trial]. / Efectividad de la lacosamida en el tratamiento del dolor neuropatico refractario: estudio observacional abierto.

INTRODUCTION: Although different treatments are available for neuropathic pain, these patients are often refractory, which makes it necessary to test treatments that, as they have proven useful in other pathologies, could be effective in neuropathic pain. PATIENTS AND METHODS: The study made use of the medical records of patients who had been treated with lacosamide for neuropathic pain in different hospitals in the central area of the peninsula and who fulfilled similar characteristics in terms of refractoriness to other standard treatments, in a follow-up that lasted at least six months, or who had had to stop treatment with that drug for some reason or another. A sample of 114 patients (61 males and 53 females) with a mean age of 60.5 years was obtained from the data. RESULTS: The most common causes of neuropathic pain were: diabetic polyneuropathy (31.6%), post-herpes neuralgia (22.8%), trigeminal neuralgia (17.5%), suboccipital and lumbar-radicular neuralgia (both 12.3%). Effectiveness was good/very good in most patients, with the mean score on the visual analogue scale after six months dropping from 7.7 to 4.8. No serious side effects were reported in any of the patients, but in 12 and 10 patients no recordings were made beyond six months, due to ineffectiveness and intolerance to the treatment, respectively. CONCLUSIONS: Treatment with lacosamide in neuropathic pain due to different causes could be considered an effective and well-tolerated alternative for patients who fail to respond to standard treatments.

TITLE: Efectividad de la lacosamida en el tratamiento del dolor neuropatico refractario: estudio observacional abierto.Introduccion. Aunque se dispone de diferentes tratamientos para el dolor neuropatico, en muchas ocasiones estos pacientes son refractarios, lo que hace necesario probar tratamientos que, por su utilidad en otras patologias, podrian ser eficaces en el dolor neuropatico. Pacientes y metodos. Se recogieron las historias clinicas de pacientes que hubieran sido tratados con lacosamida para el dolor neuropatico, en diferentes hospitales de la zona centro peninsular, y que cumplieran unas caracteristicas similares en cuanto a refractariedad a otros tratamientos estandares, en un seguimiento de al menos seis meses, o que hubiesen tenido que suspender el tratamiento con dicho farmaco por cualquier motivo. Se obtuvo una muestra de 114 pacientes, 61 varones y 53 mujeres, con una edad media de 60,5 años. Resultados. Las causas de dolor neuropatico mas frecuentes fueron: polineuropatia diabetica (31,6%), neuralgia postherpetica (22,8%), neuralgia del trigemino (17,5%), neuralgia suboccipital y lumbociatalgia (un 12,3% en ambas). La eficacia fue buena/muy buena en la mayoria de los pacientes, con un descenso medio en la escala analogica visual tras seis meses de 7,7 a 4,8. No se registraron efectos secundarios graves en ningun paciente, pero en 12 y 10 pacientes no hubo registro mas alla de seis meses, por ineficacia e intolerancia al tratamiento, respectivamente. Conclusiones. El tratamiento con lacosamida en el dolor neuropatico de diferentes causas podria considerarse como una alternativa efectiva y bien tolerada para aquellos pacientes que no respondan a los tratamientos estandares.

Spindle basaloid squamous carcinoma of the upper aerodigestive tract: immunohistochemical and clinicopathological study of three cases.

We describe the clinicopathological and immunohistochemical features of three spindle (sarcomatoid) basaloid squamous carcinomas in three men aged 73, 69, and 59 years with a history of tobacco and alcohol abuse. Two tumors were located in the hypopharynx and one was located in the nasal cavity. The three tumors have a pedunculated polypoid appearance. Histologically, they were composed of conventional basaloid squamous carcinomas with extensive malignant spindle cell proliferation, comprising more than 50% of the tumor. The sarcomatoid component demonstrated immunoreactivity with one or more epithelial markers. One case in addition expressed CD99 and Bcl-2 and was originally diagnosed as monophasic synovial sarcoma; however, a subsequent biopsy disclosed basaloid squamous cell carcinoma with sarcomatoid stroma. Two patients were treated with surgery and radiation whereas one refused therapy. The patients were alive 14 (case patient 1), 10 (case patient 2), and 8 (case patient 3) months after diagnosis. In the absence of evidence from immunohistochemical or electron microscopy studies, a polypoid malignant spindle cell tumor of a mucosal surface of the upper aerodigestive tract should be considered a sarcomatoid carcinoma until proven otherwise. The type of epithelial component would determine the subtype of sarcomatoid carcinoma.

Pharyngeal teratocarcinosarcoma: review of the literature and report of two cases.

Teratocarcinosarcomas are rare malignant neoplasms histologically characterized by the presence of benign and malignant epithelial and mesenchymal elements. They are seen almost exclusively in the sinonasal tract of men. We report two cases of teratocarcinosarcomas involving the posterior pharyngeal wall in a 55-year-old male and 60-year-old men. The tumors consisted of epithelial components including squamous, neuroendocrine, and glandular structures; neuroepithelium, and mesenchymal components with prominent rhabdomyoblastic, osteoblastic and chondroid differentiation. Immunohistochemical studies demonstrated markers characteristic of each component. The tumors were resected, and the patients received postoperative radiation therapy. One patient is alive with recurrent tumor 33 months after treatment and the other died 26 months after radiation therapy with distant metastasis.

Thyroid transcription factor-1 expression in thyroid-like nasopharyngeal papillary adenocarcinoma: report of 2 cases.

We present the cases of 2 pediatric patients with low-grade nasopharyngeal papillary adenocarcinoma with features suggestive of thyroid origin. Both cases showed strong nuclear immunoreactivity for thyroid transcription factor-1 protein and positive immunostaining for cytokeratins 7 and 19. After thyroid imaging studies, local excision was performed in both patients. The patients remain free of disease 2 and 15 years after treatment, with no evidence of lesions in the thyroid or elsewhere.