Leiomiomatosis esofágica difusa gigante. Reporte de caso / Giant Diffuse Esophageal Leiomyomatosis. Case Report

Introducción: La leiomiomatosis esofágica es una neoplasia benigna con una incidencia dentro de los tumores del esófago extremadamente baja y en ocasiones difícil de categorizar como neoplasia o miopatía. Caso clínico: Se reporta el caso de una joven de 24 años que consultó por disfagia pro- gresiva de un año de evolución y antecedente de haberle descubierto una "mancha" en el pulmón diez años atrás. Las imágenes muestran masa que ocupa el tercio medio e inferior del esófago y megaesófago proximal por obstrucción a nivel de cardias. Se rea- lizó esofagectomía total, tubulización y ascenso gástrico con piloroplastía más anastomosis esófago gástrica latero lateral a nivel cervical. La patología confirmó la histología de leiomiomatosis esofágica. Conclusión: Es una patología muy rara con pocos casos reportados.

Introduction: Esophageal leiomyomatosis is a benign neoplasm with an extremely low incidence of esophageal tumors and is sometimes difficult to categorize as a neoplasm or myopathy. Clinical Case: The case of a 24-year-old girl, who consulted for progressive dysphagia of one year of evolution and a history of having discovered a "spot" on her lung ten years ago, is reported. The images show a mass that occupies the middle and lower third of the esophagus and proximal megaesophagus due to obstruction at the level of the cardia. Total esophagectomy, tubulization and gastric ascent with pyloroplasty plus lateral esophagogastric anastomosis at the cervical level were performed. The pathology confirms the histology of esophageal leiomyomatosis. Conclusion: It is a very rare pathology with few reported cases.

Síncope como presentación clínica de linfoma cardiaco: reporte de caso / Syncope as a clinical presentation of cardiac lymphoma: a case report

El linfoma cardiaco primario, un tipo extremadamente raro de linfoma no Hodgkin de células B, presenta una incidencia aproximada de 0.02-2% entre los tumores cardíacos malignos. Se asocia frecuentemente con manifestaciones como alteraciones del ritmo cardíaco, derrame pericárdico refractario y masas cardiacas. El diagnóstico definitivo se logra mediante biopsia, siendo esencial descartar diseminación hematógena con PET-CT. La literatura indica una predominancia de afectación de las cavidades derechas y una supervivencia que varía significativamente según la afectación del ventrículo izquierdo y la presencia de arritmias. Las opciones terapéuticas no están bien definidas, pero la quimioterapia como R-CHOP ha mostrado eficacia, aunque el pronóstico generalmente es pobre debido a complicaciones como progresión de la enfermedad, arritmias y sepsis. Este caso subraya la importancia de considerar el linfoma cardiaco en pacientes con síntomas cardiacos inexplicables, destacando la necesidad de un enfoque diagnóstico y terapéutico multidisciplinario y específico.

Primary cardiac lymphoma, an extremely rare type of B-cell non-Hodgkin lymphoma, has an incidence of approximately 0.02-2% among malignant cardiac tumors. It is frequently associated with manifestations such as cardiac rhythm disturbances, refractory pericardial effusion and cardiac masses. Definitive diagnosis is achieved by biopsy, being essential to rule out hematogenous dissemination with PET-CT. The literature indicates a predominance of right chamber involvement and survival that varies significantly according to left ventricular involvement and the presence of arrhythmias. Therapeutic options are not well defined, but chemotherapy such as R-CHOP has shown efficacy, although the prognosis is generally poor due to complications such as disease progression, arrhythmias and sepsis. This case underscores the importance of considering cardiac lymphoma in patients with unexplained cardiac symptoms, highlighting the need for a multidisciplinary and specific diagnostic and therapeutic approach.

Neuroprotective Potential of a Novel Soluble Guanylate Cyclase Stimulator the Riociguat Alone or in a Combination Manner with Resveratrol in Experimental Stroke Model in Rats / Potencial Neuroprotector del Novedoso Estimulador de Guanilato Ciclasa Soluble, el Riociguat solo o en Combinación con Resveratrol en un Modelo Experimental de Ataque Cerebrovascular en Ratas

SUMMARY: In this study we aimed to examine the effect of novel vasodilatory drug Riociguat co-administration along resveratrol to recover neurodegeneration in experimental stroke injury. For that purpose, thirty-five adult female rats were divided into five groups (Control, MCAO, MCAO + R, MCAO + BAY, MCAO + C) of seven animals in each. Animals in Control group did not expose to any application during the experiment and sacrificed at the end of the study. Rats in the rest groups exposed to middle cerebral artery occlusion (MCAO) induced ischemic stroke. MCAO + R group received 30 mg/kg resveratrol, and MCAO + BAY group received 10 mg/kg Riociguat. The MCAO + C group received both drugs simultaneously. The drugs were administered just before the reperfusion, and the additional doses were administered 24h, and 48h hours of reperfusion. All animals in this study were sacrificed at the 72nd hour of experiment. Total brains were received for analysis. Results of this experiment indicated that MCAO led to severe injury in cerebral structure. Bax, IL-6 and IL-1ß tissue levels were up-regulated, but anti-apoptotic Bcl-2 immunoexpression was suppressed (p<0.05). In resveratrol and Riociguat treated animals, the neurodegenerations and apoptosis and inflammation associated protein expressions were improved compared to MCAO group, but the most success was obtained in combined treatment exposed animals in MCAO + C group. This study indicated that the novel soluble guanylate stimulator Riociguat is not only a potent neuroprotective drug in MCAO induced stroke, but also synergistic administration of Riociguat along with resveratrol have potential to increase the neuroprotective effect of resveratrol in experimental cerebral stroke exposed rats.

En este estudio, nuestro objetivo fue examinar el efecto de la coadministración del nuevo fármaco vasodilatador Riociguat junto con resveratrol para recuperar la neurodegeneración en lesiones por ataques cerebrovasculares experimentales. Para ello, se dividieron 35 ratas hembras adultas en cinco grupos (Control, MCAO, MCAO + R, MCAO + BAY, MCAO + C) de siete animales en cada uno. Los animales del grupo control no fueron sometidos a ninguna aplicación durante el experimento y se sacrificaron al final del estudio. Las ratas de los grupos expuestas a la oclusión de la arteria cerebral media (MCAO) indujeron un ataque cerebrovascular isquémico. El grupo MCAO + R recibió 30 mg/kg de resveratrol y el grupo MCAO + BAY recibió 10 mg/kg de Riociguat. El grupo MCAO + C recibió ambos fármacos simultáneamente. Los fármacos se administraron antes de la reperfusión y las dosis adicionales se administraron a las 24 y 48 horas de la reperfusión. Todos los animales en este estudio fueron sacrificados a las 72 horas del experimento. Se recibieron cerebros totales para su análisis. Los resultados indicaron que la MCAO provocaba lesiones graves en la estructura cerebral. Los niveles tisulares de Bax, IL-6 e IL- 1ß estaban regulados positivamente, pero se suprimió la inmunoexpresión antiapoptótica de Bcl-2 (p <0,05). En los animales tratados con resveratrol y Riociguat, las neurodegeneraciones y las expresiones de proteínas asociadas a la apoptosis y la inflamación mejoraron en comparación con el grupo MCAO, sin embargo el mayor éxito se obtuvo en el tratamiento combinado de animales expuestos en el grupo MCAO + C. Este estudio indicó que el nuevo estimulador de guanilato ciclasa soluble Riociguat no solo es un fármaco neuroprotector potente en el ataque cerebrovascular inducido por MCAO, sino que también la administración sinérgica de Riociguat junto con resveratrol tiene el potencial para aumentar el efecto neuroprotector del resveratrol en ratas experimentales expuestas a un ataque cerebrovascular.

Immunohistochemical expression of p53, ki-67, tenascin, and fibronectin in giant cell fibroma and traumatic fibroma of the oral mucosa

Objective: This study aimed to compare the immunoexpression of p53, ki-67, tenascin, and fibronectin between giant cell fibroma (GCF) and traumatic fibroma (TF), in order to explore a benign neoplastic or a reactive nature of GCF. Methods: A cross-sectional study was conducted. Samples of GCF and TF were retrieved from the files of Oral Pathology Service, matched by site and size. Immunohistochemistry for p53, ki-67, tenascin, and fibronectin was evaluated in the superficial and deep regions of the lesions using the Image J Software. The number of positive cells was determined for p53 and ki-67, and the positive area was established for tenascin and fibronectin. Statistical analysis was performed with Mann-Whitney and independent t-tests (p≤0.05).Results: Comparing to TF, GCF showed higher expression of p53 protein in superficial (p=0.009) and deep regions (p=0.027), as well as higher tenascin expression in deep regions (p=0.000). Ki-67 and fibronectin immunoexpression did not differ between GCF and TF (p>0.05). Conclusion: The results of the present study seem supportive of a benign neoplastic nature of GCF, rather than a reactive one, especially considering the p53 and tenascin expression. Further studies with larger samples and broader markers should confirm this hypothesis. (AU)

Diagnosis of HPV-associated oropharyngeal squamous cell carcinoma in a middle-income country: report of two new cases

Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a distinct subset characterized by better treatment responses and higher survival rates. Clinical and morphological aspects are crucial for diagnosis. Here we report two additional cases of HPV-associated OPSCC. Case 1: A 46-year-old male smoker and alcoholic presented with a 6 cm asymptomatic destructive ulcer involving multiple areas of the oropharynx. Microscopic analysis revealed non-keratinizing squamous cell carcinoma (SCC) with strong and diffuse cytoplasmatic and nuclear positivity for p16 in the tumor cells on IHC and ISH for HPV16/18 revealed the presence of viral DNA in a dot-like pattern. Case 2: A 53-year-old male smoker and alcoholic complained of dysphagia and exhibited erythematous areas in the uvula. Microscopically, a basaloid SCC was observed. Assessment of p16 expression showed diffuse moderate nuclear and cytoplasmatic positivity and ISH for DNA HPV16/18 also demonstrated dot-like signals. The present cases highlight the clinical and microscopical aspects of HPV-associated OPSCC. Pathologists and clinicians must remain vigilant in identifying HPV-associated OPSCC, even in cases where there is a history of alcohol and tobacco consumption. Assessment of p16 immunohistochemical patterns and ISH analysis are crucial to better understand the scenario of HPV-associated OPSCC in middle-income countries. (AU)

Clinicopathological and immunohistochemical study of canalicular adenoma

Objective: To evaluate the clinicopathological and immunohistochemical features of an original series of canalicular adenoma. Methods: Cases diagnosed as canalicular adenoma from a single center were retrospectively retrieved and clinical data collected from patients' charts. The histopathological features of all cases were reviewed and a large immunohistochemical panel carried out. Results: Eleven cases were collected, and no gender predilection was seen. A painless upper lip nodule was the most frequent clinical presentation. All cases presented the single-layer epithelial arrangement of tumor cells in a loose stroma. It was found an increased expression of low-weight cytokeratins, absence of myogenic markers, variable positivity for vimentin, S100 and GFAP, cytoplasmic and membrane reactivity for ß-catenin and a strong CD34 positivity, whereas no lymphatic vessel was identified using D2-40 antibody. Conclusion: Canalicular adenoma is composed of luminal epithelium with strong expression of low-weight cytokeratins, and peripheral expression of ß-catenin may be involved in the architectural maintenance of the tumor. (AU)

Mycobacterium tuberculosis bacilli in oral biopsies containing granulomatous inflammation with caseous necrosis

Objetive: This cross-sectional and retrospective study aimed to investigate the presence of Mycobacterium tuberculosis bacillus in formalin-fixed paraffin-embedded (FFPE) oral samples that contained granulomas with caseous necrosis. Methods: FFPE biopsies that showed granulomas with caseous necrosis, suggestive of the diagnosis of tuberculosis, were selected. M. tuberculosiswas searched by Ziehl-Neelsen staining (ZN), immunohistochemistry (IHC), nested-PCR, and GeneXpert® MTB/RIF assays. Results: Nine samples showing granulomas with caseous necrosis were selected. The study showed a male predominance, with a ratio of 2.5:1, with a mean age of 50 (19-89) years, and the tongue was the most affected anatomical site (n=4). The ZN technique did not detect bacilli in any sample, and IHC staining showed a coarse granular pattern staining, suggestive of M. tuberculosis, in three of them. Nested-PCR and the GeneXpert® MTB/RIF assays were positive in two and three of the samples, respectively. Conclusion: Molecular tests and IHC may be useful auxiliary methods for suspected cases of oral tuberculosis. (AU)

Histological and Ultrastructural Changes in Lungs One Year Post Asymptomatic or Mild SARS-CoV-2 Infection: Evaluating the Potential for Active Virus Presence / Cambios Histológicos y Ultraestructurales en los Pulmones un Año Después de una Infección Asintomática o Leve por SARS-CoV-2: Evaluación del Potencial de Presencia Activa del Virus

SUMMARY: Prior research on post-COVID-19 or long COVID primarily focused on the presence of SARS-CoV-2 mostly in symptomatic patients. This study aimed to investigate the persistence of SARS-CoV-2 after 1 year of asymptomatic or mild COVID-19. SARS-CoV-2 infected and control K18-hACE2 transgenic mice (n=25) were studied. Moderate and severe symptomatic subjects were sacrificed after eight days, while mild or asymptomatic mice were kept in BSL-III for twelve months. Analyses included general condition, histochemistry, immunohistochemistry, transmission electron microscopy, and qRT-PCR. Lungs from the twelve-month group showed thickening of alveolar walls, with some lungs exhibiting the recruitment of inflammatory cells, the presence of SARS- CoV-2 mRNA, immunopositivity for the SARS-CoV-2 spike protein, and TEM showed viruses (60-125 nm) within vesicles, indicating continued replication. Certain lung samples showed persistent SARS-CoV-2 presence in Club cells, endothelial cells, and macrophages. The eight-day group exhibited viral interstitial pneumonitis, SARS-CoV-2 immunopositivity, and mRNA. The eight-day hearts displayed viral mRNA, while the twelve-month hearts tested negative. Some asymptomatic twelve-month subjects presented reduced surfactant, basal membrane thickening, fibrosis, and mild autonomic nerve degeneration. In this study conducted on mice, findings indicate the potential for chronic persistence of SARS-CoV-2 in the lungs one year post initial mild or asymptomatic infection, which could suggest the possibility of recurrent episodes in similar human conditions. The observed thickening of alveolar walls and potential fibrotic areas in these mice may imply an increased risk of post-COVID fibrosis in humans. Furthermore, the presence of SARS-CoV-2-positive inflammatory cells in some asymptomatic murine cases could herald a progression toward ongoing inflammation and chronic lung disease in humans. Therefore, the necessity for further studies in human subjects and vigilant monitoring of high-risk human populations is underscored.

Investigaciones anteriores sobre COVID-19 o COVID prolongado se centraron principalmente en la presencia de SARS-CoV-2 principalmente en pacientes sintomáticos. Este estudio tuvo como objetivo investigar la persistencia del SARS-CoV-2 después de 1 año de COVID-19 asintomático o leve. Se estudiaron ratones transgénicos K18-hACE2 infectados con SARS-CoV-2 y de control (n=25). Los animales con síntomas moderados y graves se sacrificaron después de ocho días, mientras que los ratones con síntomas leves o asintomáticos se mantuvieron en BSL-III durante doce meses. Los análisis incluyeron estado general, histoquímica, inmunohistoquímica, microscopía electrónica de transmisión y qRT- PCR. Los pulmones del grupo de doce meses mostraron engrosamiento de las paredes alveolares, y algunos pulmones exhibieron reclutamiento de células inflamatorias, presencia de ARNm del SARS-CoV-2, inmunopositividad para la proteína de la espícula del SARS-CoV-2 y TEM mostró virus (60 -125 nm) dentro de las vesículas, lo que indica una replicación continua. Ciertas muestras de pulmón mostraron una presencia persistente de SARS- CoV-2 en exocrinocitos bronquiolares, células endoteliales y macrófagos. El grupo de ocho días presentó neumonitis intersticial viral, inmunopositividad al SARS-CoV-2 y ARNm. Los corazones de ocho días mostraron ARNm viral, mientras que los corazones de doce meses dieron negativo. Algunos animales asintomáticos de doce meses presentaron disminución del surfactante, engrosamiento de la membrana basal, fibrosis y degeneración leve del nervio autónomo. En este estudio realizado en ratones, los hallazgos indican la posibilidad de persistencia crónica del SARS-CoV-2 en los pulmones un año después de la infección inicial leve o asintomática, lo que podría sugerir la posibilidad de episodios recurrentes en condiciones humanas similares. El engrosamiento observado de las paredes alveolares y las posibles áreas fibróticas en estos ratones puede implicar un mayor riesgo de fibrosis post-COVID en humanos. Además, la presencia de células inflamatorias positivas para SARS- CoV-2 en algunos casos murinos asintomáticos podría presagiar una progresión hacia una inflamación continua y una enfermedad pulmonar crónica en humanos. Por lo tanto, se subraya la necesidad de realizar más estudios en seres humanos y realizar un seguimiento atento de las poblaciones humanas de alto riesgo.

Leiomiomatosis pulmonar benigna metastatizante: una causa rara de nódulos pulmonares. Reporte de caso / Benign metastasizing benign pulmonary leiomyomatosis: a rare cause of pulmonary nodules. Case report.

La leiomiomatosis metastatizante benigna (LMB) es una condición rara. Fue descrita por primera vez por Forkel en 1910 y hasta el momento se han reportado al menos 150 casos en la literatura. Ocurre por la metástasis y proliferación de tejido muscular liso, a partir de un mioma uterino. A nivel imagenológico se manifiesta con múltiples nódulos localizados con mayor frecuencia en pulmón, ganglios linfáticos, peritoneo, hueso, corazón y piel. Los casos sintomáticos suelen ser llevados a resección quirúrgica, ooforectomía bilateral y/o inhibición hormonal. Presentamos el caso de una mujer de 51 años, quien acude a consulta por cuadro clínico de dos años de evolución caracterizada por disnea progresiva, asociada a tos seca y dolor torácico. Se documentó antecedente de histerectomía por hemorragia uterina disfuncional hace 14 años cuyo reporte de patología concluía diagnóstico de leiomiomatosis uterina. La tomografía de tórax reveló múltiples nódulos pulmonares aleatorios sólidos no calcificados. Las muestras obtenidas del parénquima pulmonar fueron por toracoscopia derecha realizándose lobectomía segmentaria lateral del lóbulo medio, con hallazgos histopatológicos de proliferación mesenquimal, epitelial y marcadores de inmunohistoquímica compatibles con leiomiomatosis metastásica.

Benign metastasizing leiomyomatosis (BML) is a rare condition, first described by Forkel in 1910, and at least 150 cases have been reported in the literature so far (1). It is caused by metastasis and proliferation of smooth muscle tissue from a uterine myoma. At the imaging level, it manifests with multiple nodules located most frequently in the lung, lymph nodes, peritoneum, bone, heart and skin. In symptomatic cases, they are usually taken to surgical resection, bilateral oophorectomy and/or hormonal inhibition, some cases being refractory. We present the case of a 51-year-old woman, who came for consultation due to a clinical picture of 2 years of evolution characterized by progressive dyspnea, associated with dry cough and chest pain. A history of hysterectomy for dysfunctional uterine bleeding 14 years ago was documented, and pathology report concluded a diagnosis of uterine leiomyomatosis. Chest CT scan revealed multiple non-calcified solid random pulmonary nodules. Samples obtained from the lung parenchyma were obtained by right thoracoscopy performing lateral segmental lobectomy of the middle lobe, with histopathological findings of mesenchymal proliferation, epithelial, and immunohistochemical markers compatible with metastatic leiomyomatosis.

Carcinoma mediastinal de célula pequeña primario / Primary Mediastinal Small Cell Carcinoma

El carcinoma neuroendocrino de célula pequeña mediastinal es una forma rara de carcinoma neuroendocrino. El diagnóstico se sospecha por imágenes y se confirma por patología y positividad de marcadores de inmunohistoquímica (IH). Estos tumores son agresivos y su recurrencia y metástasis complican su tratamiento. Se presenta un caso de mujer de 78 años con síntomas de cuatro meses de pérdida de peso de 4 kilogramos, tos y expectoración escasa. Examen físico torácico normal; historia de tabaquismo de 20 paquetes/año. Radiografía de tórax con efecto de masa en el reborde externo derecho del cardiomediastino, tomografía computada de tórax (TAC) con efecto de masa en mediastino superior y medio, diámetro de 4.9x4.7x7.4 centímetros, envuelve estructuras broncovasculares mayores. La biopsia se realizó por videotoracoscopia. Los análisis histológicos y la inmunohistoquimica con varios marcadores positivos confirmó el carcinoma neuroendocrino de célula pequeña.

A mediastinal small cell neuroendocrine carcinoma is a rare form of malignancy. Diagnosis requires imaging studies, pathological identification and immunohistochemistry markers. These tumors are aggressive and recurrence and metastases frequently complicate patient management. We present a case 78-year-old woman with complaints over 4 months of weight loss of four kilograms, cough and expectoration. Normal chest physical examination. History of smoking twenty pack-years. Chest X-ray showed a soft tissue density in the right border in region cardiomediastinun region. A computed tomography scan showed an infiltrative soft tissue in the right upper and middle mediastinum diameter of 4.9 x 4.7 x 7.4 centimeters involving major bronchovascular structures. The biopsy was performed by video thoracoscopy. Histologic analysis of the biopsies and inmunohistoquimical studies were positive for different markers and concluded small cell neuroendocrine carcinoma.

Nefropatía por IgA con microangiopatía trombótica / IgA nephropathy with thrombotic microangiopathy

INTRODUCTION: IgA nephropathy is the most common glomerulopathy in the world, it has a wide clinical expression, from asymptomatic to rapidly progressive glomerulonephritis. The definitive diagnosis is renal biopsy, within which the IgA pattern can be identified, including thrombotic microangiopathy. CLINICAL CASE: 28-year-old female patient, with a history of preeclampsia in the last pregnancy, presents high blood pressure, hematuria and proteinuria. Study begins with initially negative results. Renal biopsy confirms IgA nephropathy with thrombotic microangiopathy. DISCUSSION: Vascular damage is underestimated in IgA nephropathy. Thrombotic microangiopathy can be associated with various clinical manifestations, however when it is associated with IgA Nephropathy it is usually associated with proteinuria, arterial hypertension and elevation of creatinine. In the presence of microangiopathy, secondary causes must be ruled out. In general, there is no pathognomonic serological marker. Eventually patients could benefit from the use of eculizumab. CONCLUSION: IgA nephropathy is the most common glomerulopathy worldwide; there is a wide range of clinical presentations, among which thrombotic microangiopathy can be found. This presentation is associated with a higher risk of progression to end-stage renal disease.

INTRODUCCIÓN: La nefropatía por IgA es la glomerulopatía más frecuente en el mundo, tiene una amplia expresión clínica, desde asintomática hasta glomerulonefritis rápidamente progresivas. El diagnóstico definitivo es la biopsia renal, dentro de las cuales se puede identificar el patrón de la IgA, dentro de los cuales está la microangiopatía trombótica. CASO CLÍNICO: Paciente femenina 28 años, con antecedentes de preeclampsia en último embarazo, presenta hipertensión arterial, hematuria y proteinuria. Se inicia estudio con resultados inicialmente negativos. Biopsia renal confirma nefropatía por IgA con microangiopatía trombótica. DISCUSIÓN: En la nefropatía por IgA se subestima el daño vascular. La microangiopatía trombótica se puede asociar con varias manifestaciones clínicas, sin embargo, cuando está asociada a NIgA suele estar asociado con proteinuria, hipertensión arterial y elevación y creatinina. Ante la presencia de microangiopatía, se deben descartar causas secundarias de la misma. En general no existe un marcador serológico patognomónico. Eventualmente los pacientes se podrían beneficiar del uso de eculizumab. CONCLUSIÓN: La nefropatía por IgA es la glomerulopatía más frecuente a nivel mundial, existe una gran gama de presentaciones clínicas, dentro de las cuales se puede encontrar microangiopatía trombótica. Esta última presentación se asocia con mayor riesgo de progresión a enfermedad renal en etapa terminal.

Immunohistochemistry and next-generation sequencing for NTRK fusion detection in differentiated thyroid cancer of children, adolescents and young adults / Imunohistoquímica e sequenciamento nova geração para detecção de fusão NTRK em câncer diferenciado de tireoide em crianças, adolescentes e adultos jovens

INTRODUCTION: Pan-TRK immunohistochemistry staining can assess the protein expression from NTRK gene fusions. A little is known about its utility in differentiated thyroid cancer samples from children, adolescents, and young adults patients. Objective: Investigate pan-TRK immunohistochemistry sensitivity and specificity in differentiated thyroid cancer samples from children, adolescents, and young adults patients. METHODS: Tumor samples obtained from 79 children, adolescents, and young adults patients (age <21 years) diagnosed with differentiated thyroid cancer between January, 2010 and January, 2021 were retrospectively recruited from four health centers from state of Bahia e Paraíba, Brazil. NTRK gene fusion testing of all archival FFPE tumor samples: pan-TRK immunohistochemistry staining for TRKA, TRKB and TRKC protein expression were performed and then analyzed with RNA-based next-generation sequencing assay to confiC:\Users\yngrid.narciso\Desktop\CLIENTES\SITES\BJO\2024\5 - Maio\2024-05-02\siterm immunohistochemistry pan-TRK result and elucidate fusion partner. RESULTS: Pan-TRK immunohistochemistry: 3 of 79 cases had positive pan-TRK expression: next-generation sequencing; 4 were identified with NTRK gene fusion, pan-TRK immunohistochemistry was negative in all 4 NTRK next-generation sequencing-positive cases. 25 of 79 NTRK next-generation sequencing-negative control cases had concordant negative pan-TRK immunohistochemistry results. Therefore, our rate of false positive pan-TRK immunohistochemistry results was 3/25 (12%). The overall results for pan-TRK immunohistochemistry in our cohort of next-generation sequencing-negative cases was: (i) sensitivity (0%), (ii) specificity (96%), (iii) positive predictive value (94.7%), (iv) negative predictive value (91%). CONCLUSION: Pan-TRK immunohistochemistry was not a tissue-efficient screen for NTRK fusions in differentiated thyroid cancer from children, adolescents, and young adults patients. This is the largest cohort of from children, adolescents, and young adults differentiated thyroid cancer cases stained with pan-TRK immunohistochemistry, and it is the first to detail the sensitivity and specificity of pan-TRK immunohistochemistry regarding the data obtained by targeted RNA-based next-generation sequencing panel in differentiated thyroid cancer.

INTRODUÇÃO: A coloração imuno-histoquímica Pan-TRK pode avaliar a expressão proteica de fusões de genes NTRK. Pouco se sabe sobre sua utilidade em amostras diferenciadas de câncer de tireoide de crianças, adolescentes e adultos jovens. Objetivo: Investigar a sensibilidade e especificidade da imuno-histoquímica pan-TRK em amostras diferenciadas de câncer de tireoide de pacientes crianças, adolescentes e adultos jovens. MÉTODOS: Amostras tumorais obtidas de 79 pacientes crianças, adolescentes e adultos jovens (idade <21 anos) com diagnóstico de câncer diferenciado de tireoide entre janeiro de 2010 e janeiro de 2021 foram recrutadas, retrospectivamente, em quatro centros de saúde dos estados da Bahia e Paraíba, Brasil. Teste de fusão genética NTRK de todas as amostras de tumor FFPE arquivadas: coloração imuno-histoquímica pan-TRK para expressão da proteína TRKA, TRKB e TRKC foi realizada e depois analisada com ensaio de sequenciamento de próxima geração baseado em RNA, para confirmar o resultado imuno-histoquímico pan-TRK e elucidar o parceiro de fusão. RESULTADOS: Imunohistoquímica pan-TRK: 3 de 79 casos tiveram expressão pan-TRK positiva: sequenciamento de próxima geração; 4 foram identificados com fusão do gene NTRK, a imuno-histoquímica pan-TRK foi negativa em todos os 4 casos positivos para sequenciamento de próxima geração de NTRK. 25 dos 79 casos de controle negativo para sequenciamento de próxima geração de NTRK tiveram resultados de imuno-histoquímica pan-TRK negativos concordantes. Portanto, nossa taxa de resultados de imuno-histoquímica pan-TRK falsos positivos foi de 3/25 (12%). Os resultados gerais da imuno-histoquímica pan-TRK em nossa coorte de casos negativos para sequenciamento de próxima geração foram: (i) sensibilidade (0%), (ii) especificidade (96%), (iii) valor preditivo positivo (94,7%), (iv) valor preditivo negativo (91%). CONCLUSÃO: A imuno-histoquímica pan-TRK não foi uma triagem tecidualmente eficiente para fusões de NTRK em pacientes com câncer diferenciado de tireoide em crianças, adolescentes e adultos jovens. Esta é a maior coorte de casos de câncer diferenciado de tireoide de crianças, adolescentes e adultos jovens corados com imunohistoquímica pan-TRK, e é a primeira a detalhar a sensibilidade e especificidade da imunohistoquímica pan-TRK em relação aos dados obtidos por RNA direcionado baseado em um painel de sequenciamento de próxima geração no câncer diferenciado de tireoide.

Neural and Neural Crest-Derived Stem Cell Distribution in the Adult Human Dental Pulp / Distribución de Células Madre Neurales y Derivadas de la Cresta Neural en la Pulpa Dental Humana Adulta

SUMMARY: Despite comprehensive studies and reports about the properties of dental pulp stem cells (DPSCs) in vitro, we still need to confirm whether these in vitro characteristics coincide with the nature of DPSCs in situ. The anatomical location of DPSCs populations in the dental pulp has yet to be investigated. Moreover, the mesenchymal DPSCs have been much more studied than the neural crest-derived DPSCs. In this study, well-recognized neural/neural crest stem cell markers NCAM1, Nestin, SNAIL/SLUG, SOX9, and S100 are being investigated by immunohistochemistry to localize the precise location of these populations of DPSCs within the human adult dental pulp.All previously mentioned markers were expressed in the dental pulp, and their intensity and location of expression were reported.

A pesar de estudios e informes exhaustivos sobre las propiedades de las células madre de la pulpa dental (DPSC) in vitro, todavía necesitamos confirmar si estas características in vitro coinciden con la naturaleza de las DPSC in situ. La ubicación anatómica de las poblaciones de DPSC en la pulpa dental aún no se ha investigado. Además, las DPSC mesenquimales han sido mucho más estudiadas que las DPSC derivadas de la cresta neural. En este estudio, se están investigando mediante inmunohisto química marcadores de células madre de la cresta neural/ neural NCAM1, Nestin, SNAIL/SLUG, SOX9 y S100 para localizar la ubicación precisa de estas poblaciones de DPSC dentro de la pulpa dental humana adulta. Todos los marcadores mencionados anteriormente se expresaron en la pulpa dental y se informó su intensidad y ubicación de expresión.

Effective Inhibition of TNFalpha/mTOR Axis-Mediated Liver Inflammation and Fibrosis Induced by TAA Using a Combination of Metformin and Resveratrol in Association with the Inhibition of the Profibrotic Gene and Protein Expression / Inhibición Efectiva de la Inflamación Hepática Mediada por el Eje TNF-alfa/mTOR y la Fibrosis Inducida por TAA Utilizando una Combinación de Metformina y Resveratrol en Asociación con la Inhibición del Gen Profibrótico y la Expresión de Proteínas

SUMMARY: The response of the immune system to harmful stimuli leads to inflammation, and the adverse effects of the toxic hepatitis chemical, thioacetamide (TAA) on the human body are well documented. This article investigated the degree of protection provided by the combined pleotropic drug, metformin (Met) and the plant polyphenolic and the antiinflammatory compound, resveratrol (Res) on liver tissue exposed to TAA possibly via the inhibition of the inflammatory cytokine, tumor necrosis factor-α (TNF-α) / mammalian target of rapamycin (mTOR) axis-mediated liver fibrosis, as well as amelioration of profibrotic gene and protein expression. Rats were either given TAA (200 mg/kg via intraperitoneal injection) for 8 weeks beginning at the third week (experimental group) or received during the first two weeks of the experiment combined doses of metformin (200 mg/kg) and resveratrol (20 mg/kg) and continued receiving these agents and TAA until experiment completion at week 10 (treated group). A considerable damage to hepatic tissue in the experimental rats was observed as revealed by tissue collagen deposition in the portal area of the liver and a substantial increase (p<0.0001) in hepatic levels of the inflammatory marker, tumor necrosis factor-α (TNF-α), as well as blood levels of hepatocellular injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). TAA also augmented hepatic tissue levels of the signalling molecule that promotes liver fibrosis (mTOR), and profibrogenic markers; alpha-smooth muscle actin (α-SMA) protein, tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA, and matrix metalloproteinase-9 (MMP-9) mRNA. All these parameters were protected (p≤0.0016) by Met+Res. In addition, a significant correlation was detected between liver fibrosis score and inflammation, liver injury enzymes, mTOR, and profibrogenesis markers. Thus, these findings suggest that Met+Res effectively protect the liver against damage induced by thioacetamide in association with the downregulation of the TNF-α/mTOR/fibrosis axis.

La respuesta del sistema inmunológico a estímulos dañinos conduce a la inflamación y los efectos adversos de la tioacetamida (TAA), una sustancia química tóxica para el hígado, están bien documentadas. Este artículo investigó el grado de protección proporcionado por el fármaco pleotrópico combinado metformina (Met), el polifenólico vegetal y el compuesto antiinflamatorio resveratrol (Res) en el tejido hepático expuesto a TAA, posiblemente a través de la inhibición de la citoquina inflamatoria, factor de necrosis tumoral α (TNF-α)/objetivo de la fibrosis hepática mediada por el eje de rapamicina (mTOR), así como mejora de la expresión de genes y proteínas profibróticas. Las ratas recibieron TAA (200 mg/kg mediante inyección intraperitoneal) durante 8 semanas a partir de la tercera semana (grupo experimental) o recibieron durante las dos primeras semanas del experimento dosis combinadas de metformina (200 mg/kg) y resveratrol (20 mg/kg) y continuaron recibiendo estos agentes y TAA hasta completar el experimento en la semana 10 (grupo tratado). Se observó un daño considerable al tejido hepático en las ratas experimentales, como lo revela el depósito de colágeno tisular en el área portal del hígado y un aumento sustancial (p<0,0001) en los niveles hepáticos del marcador inflamatorio, el factor de necrosis tumoral-α (TNF- α), así como los niveles sanguíneos de biomarcadores de lesión hepatocelular, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). TAA también aumentó los niveles en el tejido hepático de la molécula de señalización que promueve la fibrosis hepática (mTOR) y marcadores profibrogénicos; proteína actina del músculo liso alfa (α- SMA), inhibidor tisular de las metaloproteinasas-1 (TIMP-1) mRNA y matriz metaloproteinasa-9 (MMP-9) mRNA. Todos estos parámetros fueron protegidos (p≤0.0016) por Met+Res. Además, se detectó una correlación significativa entre la puntuación de fibrosis hepática y la inflamación, las enzimas de lesión hepática, mTOR y los marcadores de profibrogénesis. Por lo tanto, estos hallazgos sugieren que Met+Res protege eficazmente el hígado contra el daño inducido por la tioacetamida en asociación con la regulación negativa del eje TNF-α/mTOR/fibrosis.

Alpaca (Vicugna pacos) Skin Analyzed Under Architecture and Structure / Piel de Alpaca (Vicugna pacos) Analizada Bajo Arquitectura y Estructura

SUMMARY: This study evaluated the morphology of alpacas skin. Biopsies were collected and samples were fixed in 10 % neutral buffered formalin for histological procedures. The sections were stained with hematoxylin and eosin, picrosirius red and Masson's trichrome. Types I, III and IV collagen were analyzed by immunohistochemistry. The derma presented sebaceous and sweat glands, as well as follicular groups with medullated fibers. Type I and type IV collagen were observed at epidermis and dermis as well as in glandular structures and hair follicles. The collagen III, was observed only in dermis.

Este estudio evaluó la morfología de la piel de alpacas. Se recogieron biopsias y las muestras se fijaron en formalina tamponada neutra al 10 % para procedimientos histológicos. Las secciones se tiñeron con hematoxilina y eosina, rojo picrosirius y tricrómico de Masson. El colágeno tipo I, III y IV se analizó mediante inmunohistoquímica. La dermis presentó glándulas sebáceas y sudoríparas, así como grupos foliculares con fibras medulares. Se observó colágeno tipo I y tipo IV en la epidermis y la dermis, así como en estructuras glandulares y folículos pilosos. El colágeno III, se observó únicamente en la dermis.

Perfil molecular de cáncer de endometrio en mujeres de Bogotá DC, Colombia / Molecular profile of endometrial cancer in women from Bogota DC, Colombia

Introducción: El cáncer de endometrio ocupa el sexto lugar en incidencia del cáncer en mujeres. La caracterización molecular de este cáncer permite optimizar la estratificación de riesgo para mejorar el tratamiento de las pacientes. Objetivo: Determinar el perfil molecular TCGA de pacientes con cáncer de endometrio en Bogotá, D.C., Colombia. Método: Estudio descriptivo en una cohorte de pacientes con cáncer de endometrio. Las mutaciones en los exones 9 a 14 del gen POLE fueron identificadas mediante amplificación por reacción en cadena de la polimerasa, seguida de secuenciación Sanger y análisis bioinformático. La expresión de las proteínas MMR y p53 se identificó mediante inmunohistoquímica. Resultados: Se incluyeron 40 pacientes con una mediana de edad de 66 años. El 15% presentaron mutaciones en el dominio exonucleasa de POLE. El 32% de las pacientes que no presentaron mutaciones manifestaron deficiencia en el sistema MMR. El 43,47% de las pacientes sin mutaciones en POLE ni alteración del sistema MMR presentaron alteración de la proteína p53. Conclusiones: La población de cáncer de endometrio analizada presenta un perfil molecular TCGA similar a lo reportado para otras poblaciones.

Introduction: Endometrial cancer ranks sixth in cancer incidence among women. Its molecular characterization allows for a more precise risk stratification with the aim of improving patient treatment. Objective: To determine the TCGA molecular profile of patients with endometrial cancer in Bogota, Colombia. Method: A descriptive study of a cohort of patients with endometrial cancer. The expression of MMR proteins and p53 was identified through immunohistochemistry. Mutations in exons 9 to 14 of the POLE gene were identified through polymerase chain reaction amplification, followed by Sanger sequencing and bioinformatic analysis. Results: Forty patients were included in the study, with a median age of 66 years, 15% of them exhibited mutations in the exonuclease domain of POLE, while 32% of patients without mutations showed deficiency in the MMR system. Forty three percent of patients without mutations in POLE or MMR alterations showed aberrant p53 protein expression. Conclusions: The analyzed population of endometrial cancer presents a TCGA molecular profile similar to that reported for other populations.

Meningioma intraóseo esfenoidal asociado a hiperostosis monostótica "un desafío diagnóstico": reporte de caso / Sphenoid intraosseous meningioma associated with monostotic hyperostosis "a diagnostic challenge": case report

El meningioma intraóseo esfenoidal se encuentra incluido dentro de los tumores cerebrales extradurales los cuales constituyen menos del 2% de los meningiomas en total. Se describe el caso de una paciente femenina de 39 años quien curso con síntomas propios de la localización de esta lesión, fue llevada a resección de la lesión, donde posteriormente se realizó diagnostico por biopsia e inmunohistoquímica de meningioma intraóseo esfenoidal asociado a hiperostosis monostótica, la importancia de este caso radica en un reconocimiento oportuno del meningioma intraóseo esfenoidal, como sus consideraciones epidemiológicas, clínicas, radiológicas y diferencial de otras entidades presentes en las cefaleas crónicas.

Sphenoidal intraosseous meningioma is included within the extradural brain tumors which constitute less than 2% of the total meningiomas. We describe the case of a 39-year-old female patient who presented with symptoms typical of the location of this lesion, was taken to resection of the lesion, where later was diagnosed by biopsy and immunohistochemistry of sphenoid intraosseous meningioma associated with monostotic hyperostosis, the importance of this case lies in a timely recognition of sphenoid intraosseous meningioma, as its epidemiological, clinical, radiological and differential considerations of other entities present in chronic headaches.

Sarcoma folicular de células dendríticas mediastinal: primer reporte de caso en Costa Rica / Mediastinal Follicular Dendritic Cell Sarcoma: First Case Report in Costa Rica

El sarcoma folicular de células dendríticas (SFCD) es una neoplasia maligna rara derivada de las células dendríticas foliculares. Ha sido clasificado, dadas sus características inmunohistoquímicas, como parte del grupo de los sarcomas, donde representa un porcentaje menor al 1%. Actualmente, existen menos de 1.000 reportes en la literatura a nivel mundial, lo cual plantea una dificultad no sólo diagnóstica, siendo confundido frecuentemente con neoplasias de tipo linfoide; sino también terapéutica al no existir un claro consenso sobre su manejo definitivo. Esta revisión de caso clínico describe el primer caso reportado de SFCD en Costa Rica.

Follicular dendritic cell sarcoma (SFCD) is a rare malignant neoplasm derived from follicular dendritic cells, which has been classified, given its immunohistochemical characteristics, as part of the group of sarcomas, where it represents less than 1%. Currently, there are less than 1000 reports in the literature worldwide, which generates a difficulty not only in diagnosis, being frequently confused with lymphoid type neoplasms; but also, as therapeutic as there is no clear consensus on its definitive management. This clinical case review describes the first reported case of SFCD in Costa Rica.

Tumor neuroectodérmico maligno del tracto gastrointestinal: a propósito de un caso / Malignant neuroectodermal tumor of the gastrointestinal tract: case report

El tumor neuroectodérmico maligno del tracto gastrointestinal es una neoplasia rara con pocos casos reportados en la literatura, especialmente en América Latina. Descrito por primera vez en 2003, se trata de una entidad sin tratamiento estandarizado y de pobre pronóstico. Se presenta el caso de una paciente de 22 años de edad que acude a la consulta por dolor abdominal, anemia y masa abdominal palpable. Luego de estudios pertinentes se decide la conducta resectiva y el posterior tratamiento oncológico. (AU)

Malignant gastrointestinal neuroectodermal tumor (GNET), formerly known as clear cell sarcoma of the gastrointestinal tract, is an extremely rare tumor of mesenchymal origin, which presents great microscopic and molecular similarity to clear cell sarcoma found in other parts of the body, such as tendons and aponeurosis. It is characterized by its rapid evolution, high recurrence rate and frequent diagnosis as metastatic disease.1,2 (AU)

Congruencia Diagnóstica Clínica-Histopatológica de Lesiones en Cavidad Oral, en la Faculta de Odontología, Universidad de Costa Rica, en el Período 2016-2019 / Clinical-Histopathological Diagnostic Consistency of Lesions in the Oral Cavity, at the Faculty of Dentistry, Universidad de Costa Rica, in the 2016-2019 Period

El conocimiento de la patología oral, y su correcto diagnóstico es fundamental en Odontología, puesto que un diagnóstico tardío, particularmente en casos de lesiones premalignas o malignas, pueden conducir a serias consecuencias para el paciente. El objetivo de este trabajo fue establecer la congruencia diagnóstica clínica - histopatológica de lesiones en cavidad oral en pacientes que asistieron a la Facultad de Odontología, Universidad de Costa Rica, y a quienes se les realizó biopsia de la lesión, durante el período 2016-2019. El estudio fue descriptivo y retrospectivo, basado en datos de reportes histopatológicos en la población mencionada, por presentar alguna lesión, de tejidos blandos o duros, en cavidad oral. La muestra estadística fue por conveniencia, no probabilística y no aleatoria. Las técnicas estadísticas utilizadas fueron descriptivas para el análisis de la información, el cual se basó en la distribución de frecuencias y cruce de variables. El procesamiento estadístico de los datos se diseñó en una base de datos creada en Excel. La muestra comprendió 160 reportes histopatológicos de los cuales se excluyeron 14. La edad promedio de los pacientes fue 42 años (rango 2 - 78 años). La proporción hombre: mujer correspondió 1:1.4, predominado el sexo femenino en 58,9 %. La congruencia del diagnóstico histopatológico con el diagnóstico clínico correspondió a 55,8 %. La congruencia de los diagnósticos demuestra el conocimiento del profesional en identificar la lesión clínicamente de forma correcta, lo que permite actuar en el momento preciso y confirmar la impresión clínica diagnóstica de una patología mediante el estudio histopatológico, el cual es el estándar oro. El problema radica en aquellos casos en que hay discrepancia diagnóstica, pues exige conocer los factores responsables de esta discrepancia, exige la búsqueda de soluciones y exige reforzar y redireccionar la formación académica del profesional y de los estudiantes para reconocer y describir estas lesiones.

Knowledge of oral pathology and its correct diagnosis is fundamental in Dentistry, since a late diagnosis, particularly in cases of premalignant or malignant lesions, can lead to serious consequences for the patient. The objective of this study was to establish the clinical- histopathological diagnostic consistency of lesions in the oral cavity in patients who attended the Faculty of Dentistry, Universidad de Costa Rica, and who underwent a biopsy of the lesion, during the period 2016-2019. The study was descriptive and retrospective, based on data from histopathological reports in the mentioned population, due to presenting some lesion, soft or hard tissue, in the oral cavity. The statistical sample was for convenience, non- probabilistic nor random. The statistical techniques used were descriptive for the analysis of the information, which was based on frequency distribution and crossing of variables. The statistical processing of the data was designed in a database created in Excel. The sample collects 160 histopathological reports, of which 14 were excluded. The average age of the patients was 42 years (range between 2 - 78 years old).The male:female ratio corresponded to 1:1.4, with a predominance of the female sex at 58.9 %.The congruence of the histopathological diagnosis with the clinical diagnosis corresponded to 55.8 %. Diagnostic consistency demonstrates knowledge of the professional in correctly identifying the lesion clinically, which allows acting at the precise moment and confirming the diagnostic clinical impression of the pathology via histopathological study which is the gold standard. The problem lies in those cases in which there is a diagnostic discrepancy, since it requires having knowledge of the underlying factors and therefore, requires searching for solutions, reinforcing and redirecting the academic training of professionals and students to recognize and describe these lesions.