Xanthogranuloma in the External Auditory Canal in Childhood, an Unexpected Lesion.

Pedunculated lesions in the external auditory canal present a broad differential diagnosis. It is crucial to rule out malignant neoplasms and consider the possibility of xanthogranulomas, which are very rare in this location. Management is determined by associated complications, and otolaryngologists must consider this for appropriate treatment.

Next-generation sequencing of uveal melanoma with clinical and histological correlations: Prognostic value of new mutations in the PI3K/AKT/mTOR pathway.

BACKGROUND: Uveal melanoma (UM) is the eye's most common primary malignancy and there are no effective therapies for disseminated disease. It is important to try to know the patient's prognosis. The aim of this study was to reflect genetic variants, studied using NGS, of a series of 69 cases of UM and its correlation with histopathology and clinical progression. METHODS: We performed targeted NGS using a 519-gene panel. RESULTS: There were selected 28 different mutated genes, showing a total of 231 genetic variants that affected the function of the protein. The most common secondary mutations occurred in SF3B1 (in 26%), followed by BAP1 (in 23%), LRP1B (22%) and FGFR4 (20%). BAP1 mutation was associated with a greater likelihood of metastases and with greater presence of epithelioid cells. LRP1B was also associated with presence of epithelioid cells SF3B1 mutation was significantly associated with a spindle morphology. We found variants in the RAD51B, TOP2A, PTPRD, TSC2, DHX9, PDK1 and MTOR that have not been previously reported in consulted databases. The presence of a mutation in: CHEK2, DHX9 and PDK1 was associated with metastases. CONCLUSIONS: BAP1 is the most solid biomarker of a poor prognosis in UM and mutations can be detected using NGS. SF3B1 is associated with the spindle cell subtype of UM, which gives it probably a favourable prognostic value. Our study suggests that mutations in DHX9 and PDK1 can have prognostic value. These potential biomarkers are related to the PI3K/AKT/mTOR pathway and makes them candidates for developing new directed therapies.

Mitotic count: A need for standardization / Recuento mitótico: una necesidad de estandarización

PURPOSE: The mitotic count (MC), number of mitosis per unit area, is a very important parameter frequently used for classification and grading of some tumors. Traditionally, the MC has been expressed in terms of number of mitoses per high power field. The size of the field of view can vary greatly among different microscopes. In order to avoid under or overestimation of mitotic count, a conversion needs to be made. METHODS: A simple formula based on a simple rule of three has been devised to standardize the mitotic count to the reference area by multiplying the number of mitotic figures by a correction factor which has been calculated for the most frequently used microscopes and various common tumors. RESULTS AND CONCLUSIONS: We propose this simple method, which involves only a single multiplication, to standardize the mitotic count to the reference area

OBJETIVO: El recuento mitótico o número de mitosis por unidad de área, es un parámetro muy importante utilizado frecuentemente para clasificar y estadificar ciertos tumores. Tradicionalmente se ha expresado el recuento mitótico en términos de número de mitosis por campos de alta frecuencia. El tamaño del campo de visión puede variar ampliamente entre los diferentes microscopios. A fin de evitar la infraestimación o sobreestimación del recuento mitótico, debe realizarse una conversión. MÉTODOS: Por medio de una simple regla de tres, se ha obtenido una fórmula simple para estandarizar el recuento mitótico. Multiplicando el número de mitosis por un factor de corrección, se obtiene el recuento mitótico estandarizado al área de referencia. Se han calculado los factores de corrección para los microscopios más habituales y para los diferentes tumores comunes. RESULTADOS Y CONCLUSIONES: Proponemos este método simple (únicamente uno por multiplicación) para estandarizar el recuento mitótico con respecto al área de referencia

Mitotic count: A need for standardization.

PURPOSE: The mitotic count (MC), number of mitosis per unit area, is a very important parameter frequently used for classification and grading of some tumors. Traditionally, the MC has been expressed in terms of number of mitoses per high power field. The size of the field of view can vary greatly among different microscopes. In order to avoid under or overestimation of mitotic count, a conversion needs to be made. METHODS: A simple formula based on a simple rule of three has been devised to standardize the mitotic count to the reference area by multiplying the number of mitotic figures by a correction factor which has been calculated for the most frequently used microscopes and various common tumors. RESULTS AND CONCLUSIONS: We propose this simple method, which involves only a single multiplication, to standardize the mitotic count to the reference area.

Expression of dog1 in low-grade fibromyxoid sarcoma: A study of 19 cases and review of the literature.

DOG1 is a highly-sensitive marker often included in the immunohistochemical panel for the diagnosis of gastrointestinal stromal tumors (GISTs). Recent research has shown that DOG1 may also be expressed by low-grade fibromyxoid sarcomas (LGFMSs); this may give rise to diagnostic error when the sarcoma is located in the abdominal cavity. This paper reports on immnohistochemical expression of DOG1 in 19 LGFMSs using two different monoclonal antibodies: K9 (Leica, Novocastra Laboratories, Newcastle upon Tyne, UK) and SP31 (Thermo Scientific, Freemont, USA). All LGFMSs displayed the standard histological pattern of alternating myxoid and fibrous areas, low cellularity and bland spindle-cell morphology. Positive staining for MUC4 was observed in 18/19 cases (94.7%), while there was rearrangement of the FUS gene in 14/19 (73.7%) cases and of the EWR1 gene in 2/19 (10.5%). The sarcoma staining negative for MUC4 displayed FUS gene rearrangement. Whole-section immunohistochemistry revealed positive staining for DOG1 in 8/19 cases (42.1%), though only with clone K9. Cytoplasmic as well as membrane staining was observed in all cases; staining was focal (10-30%) and of varying intensity (1+ to 2+). In conclusion, DOG1 clone K9 exhibited low sensitivity (42.1%) for the diagnosis of LGFMS, although higher than clone SP31. Since the two clones display similar sensitivity and specificity for GIST diagnosis, SP31 would appear to be more specific for this purpose, since no reaction was observed here with LGFMS, a GIST-mimicking lesion.

Planos conjugados y sistema de iluminación de Köhler en microscopía óptica / Conjugate planes and Köhler illumination in optical microscopy

Un adecuado conocimiento y comprensión del concepto de planos conjugados es de capital importancia en la utilización del microscopio por cuanto que desde hace ya bastante tiempo el diseño de los microscopios se basa en la correcta situación de sus dos conjuntos de planos conjugados. En 1893 August Köhler publicó el trabajo «Un nuevo sistema de iluminación en microfotografía» donde dio a conocer los fundamentos básicos de una técnica de iluminación que actualmente lleva su nombre. El conocimiento y aplicación de los principios del sistema de iluminación de Köhler constituye el elemento de mayor importancia en el correcto manejo de un microscopio. Dichos principios no siempre son bien conocidos y comprendidos por los usuarios del microscopio constituyendo una fuente frecuente de errores en microscopía, particularmente en microfotografía. En este artículo revisamos los principios básicos del concepto de planos conjugados y del sistema de iluminación de Köhler (AU)

Adequate knowledge and understanding of the concept of conjugate planes is of paramount importance in the use of the microscope and for a long time microscope design was based on the correct location of the two sets of conjugate planes. In 1893 August Köhler published the article «A new illumination system in microphotography» in which he introduced the basics of an illumination technique that now bears his name. The knowledge and application of the principles of the Köhler illumination system is the most important element in the proper handling of a microscope. These principles are not always well known or understood by the users of microscopes, frequently leading to errors in microscopy, particularly in photomicrography. This article reviews the basic principles of the concept of conjugate planes and Köhler illumination system (AU)

Hiperplasia difusa idiopática de células neuroendocrinas de pulmón (DIPNECH): una entidad preneoplásica, infradiagnosticada y poco conocida / Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH): a little-known, underdiagnosed preneoplastic lesion

La hiperplasia difusa idiopática de células neuroendocrinas de pulmón aparece recogida en la clasificación de la OMS de tumores torácicos desde el año 1999 como una lesión epitelial preinvasiva caracterizada por una proliferación generalizada de células dispersas y aisladas, nódulos pequeños (cuerpos neuroendocrinos) o proliferaciones lineales de células neuroendocrinas pulmonares, confinadas al epitelio bronquial o bronquiolar, e incluye proliferaciones locales extraluminales (tumorlets o carcinoides). En la presente revisión se actualizan los criterios morfológicos cuantitativos establecidos recientemente y se consideran nuevos aspectos cualitativos que pueden contribuir a una mejor caracterización de la entidad (AU)

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia appears in the WHO classification of thoracic tumours since 1999 as a preinvasive epithelial lesion characterized by a proliferation of scattered and isolated cells, small nodules (neuroendocrine bodies) or linear pulmonary neuroendocrine cell proliferations, confined to the bronchial or bronchiolar epithelium, including extraluminal local proliferations (tumorlets or carcinoids). In this review we update the recently established quantitative morphological criteria and new qualitative aspects are considered to contribute to a better characterization of the entity (AU)

Epidemiología del esófago de Barrett y adenocarcinoma esofágico en España. Estudio unicéntrico / Epidemiology of Barrett's esophagus and esophageal adenocarcinoma in Spain. A unicentric study

Introducción: el esófago de Barrett (EB) es una enfermedad adquirida definida por la presencia de metaplasia intestinal en el esófago distal. Su prevalencia se ha incrementado de forma alarmante en los últimos años. Objetivos: los objetivos primarios del presente trabajo fueron analizar el comportamiento del EB y del adenocarcinoma esofágico (ACE) en un área sanitaria española durante el seguimiento del periodo del estudio. Métodos: se analizaron características sociodemográficas y el consumo de alcohol y tabaco. También se valoró el comportamiento histológico así como las causas de defunción en cada uno de los grupos. Resultados: se incluyeron 430 pacientes, 338 con EB y 92 con ACE. La tasa de incidencia pasó de 2,25 y 1,25 por 100.000 habitantes en 1996 a 6,5 y 4,75 en 2011, en EB y ACE, respectivamente. Hubo más varones, mayor edad e ingesta etílica en el grupo adenocarcinoma respecto al grupo de Barrett. La supervivencia del ACE fue de 23 meses. Las principales causas de muerte en los pacientes con Barrett fueron el cáncer no esofágico y la enfermedad cardiovascular. Conclusiones: existe una mayor incidencia y prevalencia tanto del EB como del ACE en los últimos años. Como factores de riesgo encontramos el sexo masculino, mayor edad y consumo de alcohol. El EB largo (> 3 cm) está implicado en la progresión de la displasia. El diagnóstico de ACE se hace, la mayor parte de las veces, con el debut de la enfermedad neoplásica y, en el menor de los casos, sobre un EB previo. La enfermedad cardiovascular y neoplásica no esofágica han sido las principales causas de mortalidad en los pacientes con EB (AU)

Introduction: Barrett’s esophagus (BE) is an acquired disease defined by the presence of intestinal metaplasia with goblet cells in the distal esophagus. The prevalence of BE has increased dramatically over the last years. Aims: The primary aims of the study were to analyze the characteristics of BE and esophageal adenocarcinoma (EAC) in a Spanish health district during a follow-up period. Methodology: Sociodemographic factors, alcohol consumption and cigarette smoking were analyzed. We also studied the histological behavior and cause of death in each group. Results: In the present study 430 patients were included, 338 with BE and 92 with EAC. Incidence rates have risen from 2.25 and 1.25 per 100,000 inhabitants in 1996 to 6.5 and 4.75 per 100,000 in 2011, respectively. In the EAC group, male gender, age and alcohol consumption were higher in comparison to the BE group, and the overall survival was 23 months. In the BE group, the main causes of death were non-esophageal cancer and cardiovascular disease. Conclusions: The incidence and prevalence rates of AEC and BE have risen over the past years. Risk factors for these conditions were male gender, age and alcohol consumption. Long BE (> 3 cm) is involved in dysplasia progression. AEC diagnosis mainly occurs after neoplasia is detected and, in a few cases, due to a previous BE. Cardiovascular diseases and non-esophageal cancers have been found to be the main cause of death in BE patients (AU)

Epidemiology of Barrett's esophagus and esophageal adenocarcinoma in Spain. A unicentric study.

INTRODUCTION: Barrett's esophagus (BE) is an acquired disease defined by the presence of intestinal metaplasia with goblet cells in the distal esophagus. The prevalence of BE has increased dramatically over the last years. AIMS: The primary aims of the study were to analyze the characteristics of BE and esophageal adenocarcinoma (EAC) in a Spanish health district during a follow-up period. METHODOLOGY: Sociodemographic factors, alcohol consumption and cigarette smoking were analyzed. We also studied the histological behavior and cause of death in each group. RESULTS: In the present study 430 patients were included, 338 with BE and 92 with EAC. Incidence rates have risen from 2.25 and 1.25 per 100,000 inhabitants in 1996 to 6.5 and 4.75 per 100,000 in 2011, respectively. In the EAC group, male gender, age and alcohol consumption were higher in comparison to the BE group, and the overall survival was 23 months. In the BE group, the main causes of death were non-esophageal cancer and cardiovascular disease. CONCLUSIONS: The incidence and prevalence rates of AEC and BE have risen over the past years. Risk factors for these conditions were male gender, age and alcohol consumption. Long BE (> 3 cm) is involved in dysplasia progression. AEC diagnosis mainly occurs after neoplasia is detected and, in a few cases, due to a previous BE. Cardiovascular diseases and non-esophageal cancers have been found to be the main cause of death in BE patients.

Lipoma endobronquial: una causa poco frecuente de obstrucción bronquial / Endobronchial Lipoma: A Rare Cause of Bronchial Occlusion

El lipoma endobronquial es una neoplasia benigna del árbol traqueobronquial poco frecuente. A pesar de su naturaleza benigna, puede producir la oclusión bronquial, debido a su crecimiento polipoide endoluminal. En este artículo se presentan las consecuencias de un diagnóstico tardío en este tipo de lesiones (AU)

Endobronchial lipoma is a rare benign neoplasm of the tracheobronchial tree. Despite its benign nature, associated endoluminal polypoid growth can cause bronchial occlusion. In this paper, we present the consequences of a late diagnosis of this condition (AU)

Endobronchial lipoma: a rare cause of bronchial occlusion.

Endobronchial lipoma is a rare benign neoplasm of the tracheobronchial tree. Despite its benign nature, associated endoluminal polypoid growth can cause bronchial occlusion. In this paper, we present the consequences of a late diagnosis of this condition.

Interferon-induced cutaneous sarcoidosis in melanoma.

Interferon-induced cutaneous sarcoidosis in the adjuvant treatment of melanoma is a rare side effect. We present the case of a patient who developed two histologically confirmed subcutaneous sarcoid nodules 15 months after starting adjuvant therapy with interferon for lymph node metastatic melanoma in which the primary tumor was not known. The extension study, coinciding with occurrence of the nodules, showed no systemic sarcoidosis. This therefore represents the second reported case of interferon-induced cutaneous sarcoidosis in melanoma therapy. As computed axial tomography-PET or other imaging techniques are unable to differentiate between the radiological signs of melanoma metastasis and sarcoidosis, histological evaluation of the granulomatous lesions is essential with a view to avoiding unnecessary treatments.

W43X SDHD mutation in sporadic head and neck paraganglioma.

OBJECTIVE: To analyze the presence of SDHD gene mutations in patients with sporadic head and neck paraganglioma. STUDY DESIGN: The presence of somatic and germline SDHD mutations was investigated in 10 patients by polymerase chain reaction and direct sequencing. RESULTS: Two patients displayed mutations: 259C>T (P87S) in 1 case and 129G>A (W43X) in the other. The first was considered a neutral polymorphism. The second was present in the germline of 1 of her sons, who had an apparently unrelated testicular seminoma and loss of heterozygosity (LOH) in the tumor cells. CONCLUSION: This is the first reported case of an SDHD mutation carrier showing LOH in a testicular seminoma.

Granular cell atypical fibroxanthoma: report of two cases.

Two cases of an uncommon histopathological variant of atypical fibroxanthoma (AFX) are described. Even though both lesions presented as clinically conventional atypical fibroxanthoma, histopathology disclosed a neoplasm composed of cells with granular change that was negative for S100 staining, and showed prominent pleomorphism, severe nuclear atypia, and a high mitotic index. Degenerative change may explain the granular phenotype in these two cases of AFX. The differential diagnosis with primitive nonneural granular cell tumor is discussed.

BCL-2, TP53 and BAX protein expression in superficial urothelial bladder carcinoma.

Whether TP53, BCL-2 and BAX expressions add independent prognostic information in patients with Ta/T1 bladder urothelial carcinoma remains unclear. TP53 overexpression correlated with high tumor grade (p=0.004), WHO grading categories (0.045), BAX expression (p=0.043) and pathologic stage (p=0.05). BCL-2 immunostaining was inverse associated with tumor grade (p=0.008). Lack of BAX expression was related to reduced patient's survival (p=0.028). Mortality was higher in patients with BCL-2+/TP53+ (p=0.023) or TP53+/BAX- (p=0.027) phenotype. BAX and pathologic stage were independent predictors of progression-free and overall survival, respectively. Therefore, BAX expression might be relevant in patient's prognosis.

Liposarcomas. Aspectos clínico-patológicos y moleculares / Liposarcomas. Clinicopathological and molecular aspects

Los liposarcomas constituyen el grupo más numeroso de sarcomas del adulto. Su interés actual radica fundamentalmente en los cambios conceptuales y clasificatorios que han acontecido en los últimos años merced a la aplicación de las técnicas de citogenética y de biología molecular. En la presente revisión se lleva a cabo una correlación clínico patológica de los cinco tipos básicos de liposarcomas y se comentan los aspectos citogenéticos y de biología molecular que han permitido la elaboración de la nueva clasificación de la OMS

Liposarcomas are the most common sarcoma of the adult life. Their current interest is based on the recent molecular and cytogenetic changes that have allowed the new WHO classification. In the present report we carried out a clinicopathological correlation in the five distinctive groups of the current classification and described the most relevant cytogenetics and molecular findings in each group

[Parathyroid carcinoma arising on transplanted parathyroid tissue after total parathyroidectomy for renal hyperparathyroidism]. / Carcinoma paratiroideo sobre trasplante autólogo tras paratiroidectomía total en el hiperparatiroidismo renal.

Parathyroid carcinoma usually develops in association with primary hyperparathyroidism. Only 18 cases have been reported in patients with secondary or tertiary renal hyperparathyroidism. We present a case of parathyroid carcinoma arising on transplanted parathyroid tissue after total parathyroidectomy for renal hyperparathyroidism.