International Validation of the Immunoscore Biopsy in Patients With Rectal Cancer Managed by a Watch-and-Wait Strategy.

PURPOSE: No biomarker capable of improving selection and monitoring of patients with rectal cancer managed by watch-and-wait (W&W) strategy is currently available. Prognostic performance of the Immunoscore biopsy (ISB) was recently suggested in a preliminary study. METHODS: This international validation study included 249 patients with clinical complete response (cCR) managed by W&W strategy. Intratumoral CD3+ and CD8+ T cells were quantified on pretreatment rectal biopsies by digital pathology and converted to ISB. The primary end point was time to recurrence (TTR; the time from the end of neoadjuvant treatment to the date of local regrowth or distant metastasis). Associations between ISB and outcomes were analyzed by stratified Cox regression adjusted for confounders. Immune status of tumor-draining lymph nodes (n = 161) of 17 additional patients treated by neoadjuvant chemoradiotherapy and surgery was investigated by 3'RNA-Seq and immunofluorescence. RESULTS: Recurrence-free rates at 5 years were 91.3% (82.4%-100.0%), 62.5% (53.2%-73.3%), and 53.1% (42.4%-66.5%) with ISB High, ISB Intermediate, and ISB Low, respectively (hazard ratio [HR; Low v High], 6.51; 95% CI, 1.99 to 21.28; log-rank P = .0004). ISB was also significantly associated with disease-free survival (log-rank P = .0002), and predicted both local regrowth and distant metastasis. In multivariate analysis, ISB was independent of patient age, sex, tumor location, cT stage (T, primary tumor; c, clinical), cN stage (N, regional lymph node; c, clinical), and was the strongest predictor for TTR (HR [ISB High v Low], 6.93; 95% CI, 2.08 to 23.15; P = .0017). The addition of ISB to a clinical-based model significantly improved the prediction of recurrence. Finally, B-cell proliferation and memory in draining lymph nodes was evidenced in the draining lymph nodes of patients with cCR. CONCLUSION: The ISB is validated as a biomarker to predict both local regrowth and distant metastasis, with a gradual scaling of the risk of pejorative outcome.

Evaluación de la metilación del DNA en tejidos de cáncer colorrectal fijados en formalina y embebidos en parafina (FFPE) / Evaluation of DNA methylation in formalin-fixed, paraffin embedded colorectal cancer tissues (FFPE)

Resumen Las alteraciones en la metilación de dinucleótidos CpG en regiones promotoras es uno de los mecanismos epigenéticos implicados en cáncer que tiene uso potencial como biomarcador. Su evaluación, a partir de tejidos fijados en formalina y embebidos en parafina (FFPE), representa un gran desafío dadas la degradación parcial, el entrecruzamiento y las bajas cantidades del DNA obtenido. En esta nota técnica, describimos un protocolo para el estudio del estado de metilación del promotor distal del proto-oncogén K-RAS, a partir de varias muestras obtenidas de dos tejidos FFPE de cáncer colorrectal con antigüedad de 11 años. Se empleó un protocolo de conversión con bisulfito alternativo al usual; se usó una DNA polimerasa modificada y una PCR anidada y se optimizó la secuenciación directa del DNA convertido con bisulfito. Este protocolo podría ser aplicado para determinar estados de metilación en otros genes y tipos de cáncer en tejidos FFPE.

Abstract Alterations in the methylation of CpG dinucleotides in promoter regions is one of the epigenetic mechanisms involved in cancer that has potential use as a biomarker. Its evaluation from formalin-fixed and paraffin-embedded (FFPE) tissues represents a great challenge given the partial degradation, crosslinking, and low amounts of the obtained DNA. In this technical note we describe a protocol for the study of the methylation status of the distal promoter of the K-RAS proto-oncogene from several samples obtained from two 11-years old FFPE tissues of colorectal cancer. An alternative bisulfite conversion protocol to the usual one was used; a modified DNA polymerase and a nested PCR were used and the direct sequencing of the converted DNA with bisulfite was optimized. This protocol could be applied to determine methylation states in other genes and types of cancer.

A Diagnostic Biopsy-Adapted Immunoscore Predicts Response to Neoadjuvant Treatment and Selects Patients with Rectal Cancer Eligible for a Watch-and-Wait Strategy.

PURPOSE: No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (ISB) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy ("Watch-and-Wait"). EXPERIMENTAL DESIGN: Biopsies from two independent cohorts (n 1 = 131, n 2 = 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3+ and CD8+ T cells and quantified by digital pathology to determine ISB. The expression of immune-related genes post-nT was investigated (n = 64 patients). Results were correlated with response to nT and disease-free survival (DFS). The ISB prognostic performance was further assessed in a multicentric cohort (n = 73 patients) treated by Watch-and-Wait. RESULTS: ISB positively correlated with the degree of histologic response (P < 0.001) and gene expression levels for Th1 orientation and cytotoxic immune response, post-nT (P = 0.006). ISB high identified patients at lower risk of relapse or death compared with ISB low [HR, 0.21; 95% confidence interval (CI), 0.06-0.78; P = 0.009]. Prognostic performance of ISB for DFS was confirmed in a validation cohort. ISB was an independent parameter, more informative than pre- (P < 0.001) and post-nT (P < 0.05) imaging to predict DFS. ISB combined with imaging post-nT discriminated very good responders that could benefit from organ preservation strategy. In the "Watch-and-Wait" cohort (n = 73), no relapse was observed in patients with ISB high (23.3%). CONCLUSIONS: ISB predicts response to nT and survival in patients with LARC treated by surgery. Its usefulness in the selection of patients eligible for a Watch-and-Wait strategy is strongly suggested.

Diferencias y controversias entre el reporte de patología y la interpretación clínica en patología tiroidea. II PARTE: Aspectos patológicos y métodos diagnósticos con impacto terapéutico / Thyroid diseases: Differences and controversies between the pathology report and clinical interpretation. PART II: Pathological aspects and diagnostic methods with therapeutic impact

Resumen Como revisamos en la primera parte1 hay algunos conceptos que deben ser considerados para el adecuado manejo médico por parte del equipo clínico que recibe el reporte de patología, de esta misma manera existen aspectos por parte del patólogo que este debe conocer, los cuales tienen impacto terapéutico. En esta segunda parte queremos revisar algunos conceptos que son de importancia por parte del patólogo que aplican directamente sobre la interpretación del clínico, como: procesamiento macroscópico; estudio de la citología por aspiración con aguja fina (FNA) vs. biopsia trucut, utilidad de la biopsia por congelación y de la inmunohistoquímica, así como los métodos e imágenes diagnósticas.

Abstract As was reviewed in the first part, there are some concepts that should be considered for the appropriate medical management by the medical team that receives the pathology report. Similarly, there are some aspects that the pathologist should know, such as those that can have therapeutic impact. In this second part, a short review is presented on some of the concepts that are of importance to the pathologist that apply directly to the interpretation by the clinician, such as the macroscopic processing, the cytology study of the fine-needle aspirate (FNA) vs. "tru-cut" biopsy, the usefulness of the frozen biopsy, and immunohistochemistry, as well as diagnostic methods and diagnostic images.

Circulating Cell-Free Tumor DNA Analysis of 50 Genes by Next-Generation Sequencing in the Prospective MOSCATO Trial.

PURPOSE: Liquid biopsies based on circulating cell-free DNA (cfDNA) analysis are described as surrogate samples for molecular analysis. We evaluated the concordance between tumor DNA (tDNA) and cfDNA analysis on a large cohort of patients with advanced or metastatic solid tumor, eligible for phase I trial and with good performance status, enrolled in MOSCATO 01 trial (clinical trial NCT01566019). EXPERIMENTAL DESIGN: Blood samples were collected at inclusion and cfDNA was extracted from plasma for 334 patients. Hotspot mutations were screened using next-generation sequencing for 50 cancer genes. RESULTS: Among the 283 patients with tDNA-cfDNA pairs, 121 had mutation in both, 99 in tumor only, 5 in cfDNA only, and for 58 patients no mutation was detected, leading to a 55.0% estimated sensitivity [95% confidence interval (CI), 48.4%-61.6%] at the patient level. Among the 220 patients with mutations in tDNA, the sensitivity of cfDNA analysis was significantly linked to the number of metastatic sites, albumin level, tumor type, and number of lines of treatment. A sensitivity prediction score could be derived from clinical parameters. Sensitivity is 83% in patients with a high score (≥8). In addition, we analyzed cfDNA for 51 patients without available tissue sample. Mutations were detected for 22 patients, including 19 oncogenic variants and 8 actionable mutations. CONCLUSIONS: Detection of somatic mutations in cfDNA is feasible for prescreening phase I candidates with a satisfactory specificity; overall sensitivity can be improved by a sensitivity score allowing to select patients for whom cfDNA constitutes a reliable noninvasive surrogate to screen mutations. Clin Cancer Res; 22(12); 2960-8. ©2016 AACR.

Consenso médico de biopsia por aspiración con aguja fina de tiroides. reporte de citología tiroidea basado en el sistema de bethesda / Medical consensus of fine-needle aspiration biopsy of the thyroid. bethesda system for reporting thyroid cytopathology

En este artículo se presenta un consenso médico basado en el sistema de Bethesda del Instituto Nacionalde Cáncer (Estados Unidos) para el uso de la biopsia por aspiración con aguja fina en el manejo de nódulos tiroideos, realizado en conjunto con patólogos, radiólogos, endocrinólogos y otras especialidades médicas de Colombia, España, Chile, Venezuela, Estados Unidos y Panamá. En este trabajo se describen las indicaciones de la biopsia por aspiración con aguja fina de tiroides, requisitos previos, entrenamiento, acreditación, técnicas, terminología diagnóstica, pruebas complementarias y opciones de tratamiento. El objetivo del actual artículo es presentar ante la comunidad médica la clasificación de los reportes citológicos, el reporte de ecografía que propone usar el sistema de datos y el reporte de imágenes tiroideas (TIRADS, del inglés The Thyroid Imaging Reporting and Data System), el uso de la medición de tiroglobulina en biopsia por aspiración con aguja fina y técnicas de citología líquida;...

This article presents a medical consensus based on the Bethesda system of the National Cancer Institute (USA) for the use of fine needle aspiration biopsy in the management of thyroid nodules. This consensus was performed in conjunction with pathologists, radiologists, endocrinologists, and other medical specialties of Colombia, Spain, Chile, Venezuela, United States, and Panama. In this work was described the indications for fine needle aspiration biopsy of thyroid, prerequisites, training, accreditation, techniques, diagnostic terminology, additional tests and treatment options. The aim of this article is present to the medical community the classification of cytological report, ultrasound report using the data system, and the thyroid imaging reporting and data system (TIRADS); as well as, the use of thyroglobulin measurement in fine needle aspiration biopsy, and liquid-based cytology techniques...

IGF1R gene expression as a predictive marker of response to ionizing radiation for patients with locally advanced HPV16-positive cervical cancer.

AIM: The aim of this study was to evaluate the predictive utility of Insulin-like growth factor-1 receptor (IGF1R), IGF1, IGF2, Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and of hemoglobin levels for tumor response to exclusive radiotherapy, in patients with locally advanced Human papillomavirus (HPV) 16-positive cervical cancer. PATIENTS AND METHODS: From 102 patients treated at our institutes, 38 patients with histologically-proven HPV16-positive cervical cancer were included in this prospective case-controlled study. All patients underwent exclusive radiotherapy-only. Complete response was defined as an absence of residual disease at clinical examination and radiological imaging, three months after the completion of treatment. Gene expression levels, assessed before radiotherapy, were compared between responders and non-responders. Controls consisted of normal cervical tissue samples from 30 patients with non-oncological indications. RESULTS: Twenty patients (52.6%) showed a complete response. Gene expressions of IGF1R (34%), IGF2 (24%), and GAPDH (median=3.26 versus 2.12) were increased in cancer patients, in comparison with the control group. Higher levels of expression of GAPDH were observed in patients co-expressing IGF2 and IGF1R, who had a hemoglobin level ≤ 11 g/dl (p=0.05). Clinical characteristics in the responder and in the non-responder groups were similar. In bi-variate and multi-variate analyses, IGF1R expression was the only factor predictive of response to radiotherapy (p=0.018). Accordingly, patients with IGF1R expression had a 28.6-fold greater risk of treatment failure. CONCLUSION: In our study, IGF1R was a strong predictive marker of lack of response to radiotherapy. Larger prospective trials are needed to validate IGF1R as a biomarker of radiation response for patients with HPV16-positive cervical cancer.

Paraganglioma funcional extraadrenal, una causa infrecuente de eclampsia / Functional extradrenal paraganglioma, an infrequent cause of eclampsia

Los paragangliomas funcionales son tumores raros, originados en el tejido cromafín extraadrenal productor de catecolaminas, y su presentación durante el embarazo es aún más inusual; existen pocos casos de esta condición reportados en la literatura. No obstante, la sospecha de paraganglioma debe ser tenida en cuenta como diagnóstico diferencial en pacientes con hipertensión durante el embarazo; en especial, cuando esta se presenta de manera paroxística antes de la semana 20 de gestación, asociada a fogajes faciales, sin proteinuria ni edemas. La confirmación se realiza mediante pruebas bioquímicas e imagenológicas, y el tratamiento es principalmente quirúrgico; se da especial atención al control pre, trans y postoperatorio de las cifras tensionales y del estado hemodinámico de la paciente, dada la naturaleza del tumor. Este artículo presenta el caso de una mujer adulta con diagnóstico de paraganglioma funcional retroperitoneal, cuya primera manifestación clínica fue eclampsia. Seguidamente se hace una breve revisión de la literatura relacionada.

Functional paragangliomas are rare tumors which originate in the extra-adrenal chromaffin tissue which produces catecolaminas; and, their appearance during pregnancy is even rarer; very few cases have been reported upon in the literature. Nevertheless, the suspicion of paraganglioma should be considered as a differential diagnosis in pregnant patients with hypertension, especially when occuring paroxistically before the 20th month of gestation, and when associated with facial flushing unaccompanied by proteinuria or edemas. Confirmation is made with biochemical or imaging tests, and treatment is primarily surgical. Special attention is paid to patient´s blood pressure stats and hemodynamic state at pre-, trans- and postoperative stages, due to the nature of the tumor. This article presents the case of an adult female diagnosed with functional extradrenal paraganglioma whose first clinical manifestation was eclampsia. A brief review of the related literature is also included.

Microcarcinoma papilar de tiroides (MCPT) metastásico a hueso / Metastatic Papillary phyroid microcarcinoma (PTMC) to bone

Clásicamente se han descrito los carcinomas papilares de tiroides (CPT) como tumores de comportamiento benigno; especialmente, aquellos con lesiones menores a 1 cm y cada vez mas, se encuentran pacientes con enfermedad agresiva que recaen local, regionalmente y/o a distancia. Recientemente se propuso incluir en la clasificación patológica el término microtumor papilar de tiroides (PMiT), que corresponde a una lesión menor a 1 cm, y que no tiene factores de riesgo histopatológicos, anteriormente denominado microcarcinoma papilar (MCPT). En el Instituto Nacional de Cancerología de Colombia (INC) fue atendido un paciente masculino de 49 años, quien consultó por fractura patológica del fémur izquierdo. Con biopsia del hueso se le confirmó carcinoma papilar metastásico de origen tiroideo, por lo cual se procedió a tiroidectomía total. Su diagnóstico final fue de MCPT. Por tratarse de un caso poco común, se reporta en el presente trabajo, y, a la vez, se comenta la nueva clasificación de tumores papilares de tiroides.

The classic description of papillary thyroid carcinoma (PTC) is that it is benign; particularly in lesions less than 1 cm. However, it is often observed that patients with aggressive diseases suffer from local, regional, and/or distant relapse. A recent proposal for pathology classification is the term papillary thyroid micro tumor (PMiT), which corresponds to a lesion less than 1 cm. and which does not have histopathological risk factors previously designated as papillary thyroid microcarcinoma (PTMC). A 49-year-old male patient sought treatment at the National Cancer Institute (NCI) for pathological fracture in the left femur. Bone biopsy confirmed metastatic papillary carcinoma of thyroid origin; thus leading to total thyroidectomy. His final diagnosis was PTMC. Due to the fact that this was a rare case, it is the subject of this report which also focuses on the new classification for papillary thyroid tumors.

Tumor de Sertoli variante célula grande calcificante asociado a síndrome de peutz-jeghers / Large cell calcifying sertoli cell tumor associated with peutz-jeghers syndrome

El tumor de células de Sertoli calcificante de células grandes (TCSCCG) es una neoplasia testicular muy rara, con 60 casos descritos en todo el mundo; en Latinoamérica y Colombia son escasos los casos reportados en la literatura. Esta neoplasia se origina en el estroma gonadal/cordones sexuales, y, en general, tiende a mostrar un comportamiento biológico benigno. Se piensa que estos tumores tienen características de presentación diferente, dependiendo de si se presentan en el contexto de un síndrome congénito complejo, en cuyo caso tienden a ser bilaterales y multifocales, en contraposición a los no asociados a síndromes, que tienden a ser unilaterales y focales. El estudio de inmunohistoquímica es fundamental para el diagnóstico; en especial, para diferenciar estos tumores de neoplasias germinales. Se reportan en esta investigación tres casos de esta neoplasia, uno de ellos asociado al síndrome de Peutz-Jeghers, y haciendo énfasis en los criterios histológicos para definir malignidad.

The large cell calcifying Sertoli cell tumor (LCCSCT) is a very rare testicular tumor with 60 cases reported worldwide; in Latin America and Colombia, few cases are reported in the literature. This neoplasm originates in the gonadal stromal/sex cord, and, in general, tends to display benign biological behavior. It is thought that these tumors may display differing characteristics: depending upon whether they occur in the context of a complex congenital syndrome, in which case they tend to be bilateral and multifocal; as opposed to those not associated with syndromes, which tend to be unilateral and focal. Immunohistochemical study is essential for diagnosis, in particular, to differentiate these tumors from germ cell tumors. This study reports on three cases of this tumor--one associated with Peutz-Jeghers Syndrome—and emphasis is given to histological criteria to define malignancy.

Effects of aerobic and anaerobic fluid collection on biochemical analysis of peritoneal fluid in healthy horses and horses with colic.

OBJECTIVE: To determine whether in healthy horses and those with colic, exposure of peritoneal fluid to room air affects values obtained on biochemical analysis. STUDY DESIGN: Prospective study. ANIMALS: Adult horses with a primary complaint of acute abdominal pain (n=29) and 12 healthy horses. METHODS: Peritoneal fluid was aseptically collected under aerobic and anaerobic conditions. After collection, pH, PCO(2) , PO(2) , HCO(3) (-) , Na(+) , ionized Ca(2+) , K(+) , lactate, and glucose were immediately measured using a commercial blood gas analyzer. Biochemical variables were compared between aerobically and anaerobically obtained samples using a paired t-test. RESULTS: In healthy horses, peritoneal fluid samples collected under anaerobic conditions had higher PCO(2) and ionized Ca(2+) and lower PO(2) , HCO(3) (-) , and pH compared with samples exposed to air. No differences were observed for K(+) , Na(+) , glucose, and lactate. In horses with colic, samples collected anaerobically had higher PCO(2) , ionized Ca(2+) , Na(+) , and glucose and lower PO(2) , HCO(3) (-) , and pH value compared with samples exposed to air. No differences were observed for K(+) and lactate. CONCLUSION: Exposure of peritoneal fluid to room air had a significant effect on pH, PCO(2) , PO(2) , and variables associated or dependent on changes in pH such as HCO(3) (-) and ionized Ca(2+) . Interpretation of biochemical analysis of peritoneal fluid may be influenced by sample collection method.

Carcinoma adenoescamoso primario de vesícula biliar: reporte de un nuevo caso y consideraciones sobre su etiología / Primary adenosquamous carcinoma of gallbladder: a case report and considerations on its etiology

El carcinoma adenoescamoso primario de vesícula biliar (CAEVB), es una neoplasia infrecuente cuya etiología y comportamiento biológico no están totalmente aclarados. Describimos un caso de un paciente masculino con un carcinoma adenoescamoso infiltrante primario de vesícula biliar diagnósticado en una colecistectomía por colelitiasis. Morfológicamente se encontró asociado a los elementos glandulares y escamosos malignos, la presencia de displasia de bajo y alto grado del epitelio glandular y metaplasia escamosa entre las zonas glandulares y escamocelulares, que permiten hacer el diagnostico de este tipo de carcinoma. El estudio de inmunohistoquímica mostraba marcadores tanto de diferenciación glandular como escamosa. Por tratarse de una variante infrecuente de Carcinoma de vesícula biliar reportamos este caso por las dificultades que genera su diagnóstico. Nuestras observaciones sugieren que se trata de un adenocarcinoma con áreas de metaplasia escamosa y posterior transformación maligna de los elementos escamosos.

The adeno-squamous gallbladder carcinoma is a frequent neoplasm with blurred etiology and biological course. A case report is presented from a male with an incidental finding of a gallbladder carcinoma diagnosed during a cholecystectomy. Associated to malignant glandular and squamous morphological findings, low grade dysplasia and squamous metaplasia were observed, allowing the final diagnosis. Immunohistochemistry analyses revealed both glandular and squamous differentiation biomarkers. The report of a rare gallbladder carcinoma illustrates difficulties for proper diagnosis. The analysis suggests an adenocarcinoma with squamous metaplasia areas that evolved towardsthe malignant transformation of squamous components.

Carcinoma papilar de tiroides, variante esclerosante difusa: un subtipo histológico de difícil diagnóstico / Diffuse sclerosing variant of papillary thyroid carcinoma: a histological type with difficult diagnosis

El carcinoma papilar de tiroides constituye el tumor maligno más frecuente de la glándula tiroides y en general tienden a tener un buen comportamiento biológico, sin embargo algunas variantes histológicas, como la esclerosante difusa tienden a mostrar una mayor agresividad con compromiso locorregional y metástasis a distancia. Esta variante es un reto diagnóstico para el patólogo por las especiales características arquitecturales y citológicas, ya que puede con llevar a diagnósticos incorrectos, en especial al ser confundido lesiones benignas con una tiroiditis linfocítica. Describimos un caso de un paciente atendido en Instituto Nacional de Cancerología de Colombia con carcinoma papilar de tiroides variedad esclerosante con enfermedad metastásica pulmonar. Por tratarse de una variante infrecuente de carcinoma papilar de tiroides reportamos este caso por las dificultades que genera tanto al clínico como al patólogo tanto en su detección inicial así como en su morfología, con las subsecuentes implicaciones debido a su comportamiento biológico más agresivo.

The papillary thyroid carcinoma is the most frequent thyroid neoplasm and usually it is a non aggressive tumor; nevertheless, some histological variants such as the diffuse sclerosing variant are more aggressive producing locoregional invasion and distant metastasis. This specific variant challenges the pathological diagnosis since the architectural and cytological characteristics might be confusing, particularly regarding benign lesions such as the lymphocytic thyroiditis. We present a case report of a patient at the National Cancer Institute of Colombia with a lung metastasis from a diffuse sclerosing papillary thyroid carcinoma. The difficulties for diagnosis, for both clinical and pathology experts, are illustrated as well as their relevance for determining the biological course of the disease.

Hand-assisted laparoscopic removal of a nephroblastoma in a horse.

A 3-year-old Thoroughbred was presented for evaluation of hematuria post exercise. On physical examination, an enlarged kidney was identified, as well as serum biochemical abnormalities such as an elevated creatine kinase (CK) and hypoalbuminemia. The kidney was removed laparoscopically and a nephroblastoma was identified.

Carcinoma folicular de tiroides mínimamente invasivo en edad pediátrica / Minimally invasive follicular thyroid carcinoma in pediatric age

Los carcinomas de la glándula tiroides son poco usuales en edad pediátrica, pero su presencia ha aumentado durante los últimos años; posiblemente, debido al incremento en la irradiación de la cabeza, cuello y mediastino. Entre estas neoplasias, el carcinoma papilar es el más habitual, y los carcinomas foliculares verdaderos son, por el contrario, bastante raros y se asocian al bocio endémico, a alteraciones genéticas y al incremento de los niveles de TSH. Sus características morfológicas son particulares y ayudan a su diagnóstico, el cual ha sido redefinido recientemente. Describiremos el caso de una adolescente de 13 años con carcinoma folicular de tiroides mínimamente invasivo, con nódulo tiroideo hipocaptante en el polo inferior del lóbulo izquierdo, de 6 meses de evolución. La punción aspiración con aguja fina demostró una lesión de células foliculares sospechosa de neoplasia. Se realizó lobectomía tiroidea, con reporte de carcinoma folicular mínimamente invasivo.

Thyroid carcinomas are rare during childhood and adolescence. They have increased recently probably due to a higher frequency radiation over the head, neck and mediastinum. The papillary carcinoma is the most common and true follicular carcinoma is far less common. Follicular thyroid carcinoma is associated with endemic goiter, genetic disorders, and increased TSH levels. Its morphological characteristics are peculiar and have been recently redefined, thus helping the diagnosis. A minimally invasive follicular thyroid carcinoma in 13 years old girl is described, presenting a hypocaptant thyroid nodule in the left lobe lower pole. The fine needle aspiration biopsy revealed a follicular cell lesion suspicious of malignancy. Thyroid lobectomy was performed reporting minimally invasive follicular carcinoma.

Recomendaciones para el procesamiento de especímenes en patología ósea. Experiencia del Instituto Nacional de Cancerología de Colombia / Recommendations for processing bone specimens in pathology: practice at the National Cancer Institute of Colombia

El procesamiento y estudio de la patología ósea es un reto diario para el patólogo debido a su complejidad diagnóstica. Las muestras con componente óseos requieren procedimientos como la manipulación de grandes piezas quirúrgicas y su descalcificación para obtener tejidos evaluables al microscopio. Lo anterior retarda el reporte patológico 20 a 30 días demorando el diagnóstico definitivo y el inicio de tratamiento o la evaluación de la respuesta a terapias neoadyudantes. Se desarrolló una guía de procesamiento de especímenes óseos que reduce los tiempos hasta el diagnóstico definitivo en 2 a 3 días para biopsias y en 13 a 15 días para amputaciones y resecciones en bloque. Presentamos una guía práctica, rápida y reproducible.

The processing and study of bone biopsias represent a challenge for the pathologist due to the complexity of diagnosis. Bone samples require special processing such as the manipulation and decalcification of big surgical specimens in order to obtain evaluable tissue under the microscope. Consequently, the pathology is performed in about 20-30 days delaying the final diagnosis, the beginning of treatment, or the evaluation of neoadyuvant therapy response. A practical guideline for bone specimen processing was developed reducing layout time for final diagnosis around 2-3 days for biopsies and 13-15 days for surgical specimens. A practical, nimble, and reliable guideline is presented.

Nesidioblastosis del adulto coexistente con insulinoma / Adult Nesidioblastosis Concurrent with Insulinoma

La nesidioblastosis es poco común, pero ampliamente reconocida como causa de la hipoglucemia hiperinsulinémica persistente de la infancia. En adultos, el insulinoma es la principal causa de hipoglucemia hiperinsulinémica, pero también se han identificado casos de nesidioblastosis, los cuales se denominan ‘síndrome de hipoglucemia pancreatógena no insulinoma’. Los primeros casos de nesidioblastosis del adulto que fueron descritos se asociaron con otras condiciones, como insulinoma y tumores neuroendocrinos pancreáticos y MEN-1. En este artículo se describe un caso de nesidioblastosis coexistente con insulinoma en una paciente de 20 años; se hace una revisión de la literatura; se plantea la discusión sobre su posible etiología, presentación clínica, diagnóstico, tratamiento y, finalmente, se presenta un algoritmo para su estudio.

Nesidioblastosis is infrequent; however, it is widely recognized as the cause of persistent infant hyperinsulinemic hypoglycemia. Among adults, insulinoma is the major cause of hyperinsulinemia hypoglycemia, but identification has also been made of cases of nesidioblastosis which are designated as ´non insulinoma pancreatogena hypoglycemic syndrome´. The first case descriptions of adult nesidioblastosis were associated with other conditions such as insulinoma and neuroenodocrinal pancreatic tumors, and MEN-1. This article describes a case of nesidioblastosis concurrent with insulinoma in a 20-year old patient; the literature is reviewed; discussion is provided on possible etiology, clinical manifestation, diagnosis, treatment, and a concluding algorithm.

A non-radioactive PCR-SSCP analysis allows to distinguish between HPV 16 European and Asian-American variants in squamous cell carcinomas of the uterine cervix in Colombia.

UNLABELLED: Human Papillomavirus type 16 (HPV 16) DNA is regularly found in around 50% of all cervical carcinomas. Variants of this type have been found associated with different risks for cervical cancer development. Presence of HPV 16 variants in Colombia has not been previously reported. The aims of this study were to assess the feasibility of non-radioactive PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) analysis for determination of variability of ORF of E6, variability in the enhancer sequence of the LCR, and for establishment of the distribution of HPV 16 variants in invasive squamous cell carcinoma of the uterine cervix in Colombian women. Biopsies from 59 patients at the Instituto Nacional de Cancerología (INC) in Bogotá (Colombia) were collected. HPV detection was performed using universal primers. HPV 16 variants were detected by non-radioactive single-stranded conformational polymorphism (SSCP) analysis and direct sequencing. HPV 16 was detected in 57.6% of the tumors. The European branch was identified in 88.2% of the samples with the E-G350 class being the most prevalent variant (41.1%). The Asian-American branch was identified in 8.8% of the samples. Within this group it was possible to distinguish between c and a classes. It was not possible to determine the branch in 2.9% of the cases. A nucleotide transition (G to A) at position 7521 was the most prevalent variation (80%) found in the enhancer sequence of the LCR region. CONCLUSION: A non-radioactive PCR-SSCP analysis allowed us to distinguish between European and Asian-American branches of HPV 16, and to distinguish among classes in squamous cell carcinomas of the uterine cervix in Colombia. This method is an excellent alternative that can be used as a screening tool for identification of HPV 16 variants.

Serum levels of insulin-like growth factor-I and -II and insulin-like growth factor binding protein 3 in women with squamous intraepithelial lesions and cervical cancer.

INTRODUCTION: Pap smear has limitations as a screening test for cervical cancer. A marker that allows the identification of women who are at risk of developing cervical cancer would be useful for its prevention. A growing number of studies have demonstrated an association between insulin-like growth factors (IGF) serum levels and increased risk for various cancers. Objective. To assess whether circulating IGF-I, IGF-II, or IGF binding protein 3 (IGFBP-3) were associated with cervical cancer and low-grade and high-grade squamous intraepithelial lesions (LSIL and HSIL). MATERIALS AND METHODS: Serum levels of IGF-I, IGF-II and IGFBP-3 were measured by ELISA. Three groups of cases were analyzed: LSIL (n = 37), HSIL (n = 57), and cervical cancer (n = 41). For each case, two controls, matched by age, were included. Control subjects were women with normal, HPV-DNA-negative Pap smear. RESULTS: Significantly lower values of IGF-I (83.9 ng/ml versus 126.6 ng/ml, p < 0.001) and IGF-I:IGFBP-3 molar ratio (0.094 versus 0.137, p < 0.001) were observed among cancer cases, as compared to their control group. Women in the highest quartile of IGF-I and IGF-I:IGFBP-3 molar ratio were at an 80% (OR = 0.2, 95% CI [0.06-0.61]) and a 77% (OR = 0.23, 95% CI [0.07-0.73]) lower risk of cervical cancer, respectively, compared with women in the corresponding reference category. CONCLUSIONS: These data suggest that low values of IGF-I and IGF-I:IGFBP-3 molar ratio may be associated with cervical cancer.

Extracción de ADN, ARN y proteínas de células cervicales provenientes de cepillados cervicales tomados para citología cérvico-uterina / DNA, RNA and Protein extraction from exfoliated cervical cells taken

Introducción: La citología cérvico-uterina (CCU) en el método más empleado en el tamizaje de lesiones precancerosas de cuello uterino. Sin embargo, la CCU tiene una proporción importante de falsos positivos y negativos, y sólo una minoría delesiones precancerosas identificadas desemboca en cáncer de cuello uterino.Objetivo: Analizar si de los cepillados cervicales es posible extraer ADN, ARN y proteínas útiles para estudios de marcadores de carcinogénesis cervical.Métodos: Se recolectaron 281 cepillados cervicales. ADN, ARN y proteínas de las células cervicales fueron extraídos empleando Trizol. Se realizó PCR para el gen de la beta globina, para evaluar el ADN extraído y RT-PCR de GAPDH y UBC, para evaluar el ARN extraído. Mediante PCR en tiempo real se cuantificó el número de copias de UBC. Las proteínas fueron cuantificadasempleando el método del ácido biscinconínico. Resultados: Nueve muestras fueron negativas para PCR de beta globina (3,2%). Otras nueve fueron negativas para RT-PCRde GAPDH (3,2%), pero 176 fueron negativas para RT-PCR de UBC. Las 105 muestras restantes fueron positivas para UBC empleando PCR en tiempo real. Las proteínas extraídas estuvieron en el rango de 30 a 4559 [mi]g/ml, dos de las 281 muestras fueron negativas para proteínas por el método del ácido biscinconínico. Conclusión: De los cepillados cervicales se puede extraer ADN, ARN y proteínas útiles para la búsqueda de marcadoresmoleculares en cáncer de cuello uterino; sin embargo, por el tipo de muestra analizado se recupera menos ARN. El usode RT-PCR de GAPDH para evaluar la calidad del ADN complementario sintetizado puede dar falsos positivos debido a la presencia de seudogen procesado. Se recomienda el uso de otros genes constitutivos como UBC.

Introduction: Papanicolau (Pap) test is the most employed screening test for precancerous cervical lesions. However, this test has an important proportion of false positives and false negatives, only a minority of the identified lesions will progress to cancer. Objective: To evaluate the remnant of cervical scrapes after the preparation of the slide as source of DNA, RNA and proteinsfor search of molecular markers of progression of precancerous lesions.Methods: DNA, RNA and proteins were extracted from 281 cervical scrapes using Trizol. To evaluate the quality of DNA a PCR for beta globine was used, RNA quality was tested by RT-PCR of GADPH and UBC genes. Real time PCR was used to evaluate the number of RNA copies of UBC gene. The protein level was obtained by the biscinconinic acid method. Results: Nine samples were negative for beta globin PCR (3,2%), 9 samples were negative for GAPDH RT-PCR (3,2%) and 176 samples were negative by UBC RT PCR , the remnant 105 were positive for UBC in real-time PCR. The extracted proteinswere in a rank between 30 and 4559 [mi]g/mL, two of 281 samples were negative for proteins. Conclusion: From cervical scrapes is possible to extract DNA, RNA and proteins usable in biomarkers research, however therecovery of RNA is lower, this can due to some characteristics inherent to the cervical cells. The use of GAPDH as in RT PCR to evaluate DNA quality can generate false positives due to the presence of a processed pseudogen, it is recommended the use of other constitutive gen like UBC.