A Tetra-Panel of Serum Circulating miRNAs for the Diagnosis of the Four Most Prevalent Tumor Types.

The purpose of this study is to clinically validate a series of circulating miRNAs that distinguish between the 4 most prevalent tumor types (lung cancer (LC); breast cancer (BC); colorectal cancer (CRC); and prostate cancer (PCa)) and healthy donors (HDs). A total of 18 miRNAs and 3 housekeeping miRNA genes were evaluated by qRT-PCR on RNA extracted from serum of cancer patients, 44 LC, 45 BC, 27 CRC, and 40 PCa, and on 45 HDs. The cancer detection performance of the miRNA expression levels was evaluated by studying the area under the curve (AUC) of receiver operating characteristic (ROC) curves at univariate and multivariate levels. miR-21 was significantly overexpressed in all cancer types compared with HDs, with accuracy of 67.5% (p = 0.001) for all 4 tumor types and of 80.8% (p < 0.0001) when PCa cases were removed from the analysis. For each tumor type, a panel of miRNAs was defined that provided cancer-detection accuracies of 91%, 94%, 89%, and 77%, respectively. In conclusion, we have described a series of circulating miRNAs that define different tumor types with a very high diagnostic performance. These panels of miRNAs would constitute the basis of different approaches of cancer-detection systems for which clinical utility should be validated in prospective cohorts.

Pancreatic adenosquamous carcinoma and intraductal papillary mucinous neoplasm in a CDKN2A germline mutation carrier.

A 69-year-old woman from a kindred with familial atypical multiple mole melanoma and carrier of a germline mutation in CDKN2A, presented with abdominal pain caused by a solid-cystic pancreatic mass. The patient had an abdominal computed tomography three years before in which there was no evidence of pancreatic lesion. The endoscopic ultrasound guided fine needle aspiration showed adenocarcinoma with squamous component. After surgical resection the final diagnosis was adenosquamous pancreatic carcinoma (ASPC) arising in an intraductal papillar mucinous neoplasm (IPMN). Adenosquamous carcinomas are uncommon in the pancreas and have rarely been described in association with IPMNs. It has worse prognosis than the ordinary pancreatic ductal adenocarcinoma and some distinct features. We review the clinical, imaging, pathologic and molecular aspects of ASPC. Differential diagnosis with contamination, squamous metaplasia and pancreatic metastases from a distant squamous carcinoma is discussed. Besides, the case is an accelerated model of the adenoma (IPMN)-carcinoma sequence probably due to the CDKN2A germline mutation. Somatic CDKN2A mutations are common events in the early steps of sporadic pancreatic cancer, but germline mutation carriers have a significantly higher risk of pancreatic carcinoma.

Sprue-like enteropathy associated with olmesartan in a patient with villous atrophy, HLA-DQ2 genotype and antinuclear antibodies.

We describe a new case of enteropathy with villous atrophy in a patient suffering from arterial hypertension treated with olmesartan. The molecular and serological studies showed anti-nuclear antibodies (ANA) and haplotype HLA-DQ2 positive, as well as negative results for anti-transglutaminase, anti-endomysium and anti-enterocytes antibodies. A duodenal villous atrophy was suspected by upper gastrointestinal endoscopy, which was confirmed by histopathology. The morphological picture was suggestive of sprue-like enteropathy with severe lymphoid infiltration and predominant T lymphoid cells.

Estudio de factores histológicos predictivos de metástasis ganglionar locorregional en adenocarcinoma colorrectal mínimamente invasivo pT1 / Histological factors predicting loco-regional lymph node metastasis in early invasive colorectal adenocarcinoma pT1

INTRODUCCIÓN: El tratamiento habitual del adenocarcinoma colorrectal pT1 consiste en la resección endoscópica siempre que sea posible. Se requiere la evaluación de los ganglios linfáticos locorregionales cuando se detectan factores histológicos adversos en las polipectomías endoscópicas. MATERIALES Y MÉTODOS: Se seleccionaron 29 adenocarcinomas colorrectales pT1 incluyendo las polipectomías endoscópicas y piezas quirúrgicas correspondientes. Se evaluaron por 2 patólogos todos los parámetros histológicos asociados a N+, incluyendo: grado de diferenciación tumoral, profundidad de invasión en submucosa, invasión angiolinfática (IAL), invasión perineural, inflamación crónica, gemaciones tumorales, grupos de tumor pobremente diferenciados, adenoma preexistente, borde tumoral y margen de resección endoscópico. Se realizó un análisis de regresión logística univariante y multivariante para evaluar la capacidad individual de cada variable para predecir N+. RESULTADOS: En el análisis univariante, la localización rectal, la presencia de IAL y la presencia de grupos de tumor pobremente diferenciados se asociaron significativamente con metástasis ganglionares. De todas estas variables, la presencia de IAL presentó la mayor área bajo la curva ROC (0,875). El análisis multivariante no encontró ninguna variable independiente asociada a N+. CONCLUSIONES: La IAL y la presencia de grupos de tumor pobremente diferenciados se asocia frecuentemente con N+ en cáncer colorrectal precoz, por lo que se debe implementar rutinariamente la evaluación de estos parámetros histológicos

INTRODUCTION: Endoscopic resection is the common treatment in pT1 colorectal adenocarcinoma whenever possible. The presence of adverse histological factors requires subsequent lymph node evaluation. MATERIALS AND METHODS: We selected 29 colorectal pT1 adenocarcinoma including endoscopic polypectomies and the corresponding surgical specimens. All histologic parameters associated with N+ were evaluated by 2 pathologists, including: tumor differentiation grade, depth of invasion in the submucosa, angiolymphatic invasion (ALI), perineural invasion, chronic inflammation, tumor budding, poorly differentiated cluster, pre-existing adenoma, tumor border, and endoscopic resection margin. Univariate and multivariate logistic regression analysis were performed to assess the individual capacity of each variable to predict N+. Results In the univariate analysis, rectal tumor localization, ALI and poorly differentiated cluster was significantly associated with N+. Among the significant parameters, ALI had the highest area under the ROC curve (0.875). Multivariate analysis showed no independent variables associated with N+. CONCLUSIONS: We confirm that ALI and the presence of poorly differentiated cluster are frequently associated with N+ in early colorectal cancer. Consequently, these parameters should be routinely evaluated by pathologists

[Histological factors predicting loco-regional lymph node metastasis in early invasive colorectal adenocarcinoma pT1]. / Estudio de factores histológicos predictivos de metástasis ganglionar locorregional en adenocarcinoma colorrectal mínimamente invasivo pT1.

INTRODUCTION: Endoscopic resection is the common treatment in pT1 colorectal adenocarcinoma whenever possible. The presence of adverse histological factors requires subsequent lymph node evaluation. MATERIALS AND METHODS: We selected 29 colorectal pT1 adenocarcinoma including endoscopic polypectomies and the corresponding surgical specimens. All histologic parameters associated with N+ were evaluated by 2 pathologists, including: tumor differentiation grade, depth of invasion in the submucosa, angiolymphatic invasion (ALI), perineural invasion, chronic inflammation, tumor budding, poorly differentiated cluster, pre-existing adenoma, tumor border, and endoscopic resection margin. Univariate and multivariate logistic regression analysis were performed to assess the individual capacity of each variable to predict N+. RESULTS: In the univariate analysis, rectal tumor localization, ALI and poorly differentiated cluster was significantly associated with N+. Among the significant parameters, ALI had the highest area under the ROC curve (0.875). Multivariate analysis showed no independent variables associated with N+. CONCLUSIONS: We confirm that ALI and the presence of poorly differentiated cluster are frequently associated with N+ in early colorectal cancer. Consequently, these parameters should be routinely evaluated by pathologists.

Tumores de células granulares múltiples en el tracto gastrointestinal / Multiple granular cell tumours of the gastrointestinal tract

Los tumores de células granulares (TCG) constituyen neoplasias que inusualmente afectan al tracto gastrointestinal. En el presente estudio describimos el caso de una mujer de 55 años de edad con TCG en el colon y el esófago con antecedentes de lesiones similares en partes blandas, piel y mama. El estudio por endoscopia reveló la presencia de lesiones nodulares submucosas en el colon sigmoide, el colon ascendente, el ciego y el esófago distal. Se realizó resección endoscópica y biopsia de las lesiones, demostrándose histológicamente la presencia de nódulos con abundantes células de apariencia histiocítica con abundante citoplasma eosinofílico y granular (PAS positivo), núcleo pequeño con ausencia de nucléolos. No se observó mitosis, pleomorfismo ni necrosis. El estudio inmunohistoquímico reveló positividad intensa en las células tumorales para S100, CD56, enolasa neuronal específica, inhibina y PGP9.5, siendo negativas para actina de músculo liso y p53. El índice de proliferación celular (Ki-67) fue muy bajo, del 1%. Considerando los hallazgos anatomopatológicos e inmunohistoquímicos las lesiones fueron clasificadas como TCG benignos. En el momento actual se recomienda la resección endoscópica para el diagnóstico y tratamiento de los TCG submucosos, teniendo en cuenta que la contrapartida maligna de estos tumores es extremadamente rara en el tracto gastrointestinal (AU)

Granular cell tumours (GCTs) are rarely found in the gastrointestinal tract. We describe a case of a 55-year-old woman with GCTs in colon and oesophagus and a previous history of similar lesions in subcutaneous tissue, skin and breast. Endoscopic examination revealed submucosal tumours in the sigmoid and ascending colon, cecum and distal oesophagus. Endoscopicmucosal resection and biopsy followed by histological examination revealed the nodulesto be composed of plump histiocyte-like cells with abundant eosinophilic, granular, PAS positive cytoplasm with small nuclei lacking nucleoli. No mitosis, pleomorphism or necrosis were observed. The immunohistochemistry revealed strong positivity for S100, CD56, neuronal specific enolase, inhibin and PGP9.5 in the tumour cells, which were negative for smooth muscle actin and p53. Ki-67 showed a very low proliferation index (1%). The morphological and immunohistochemical findings led to a diagnosis of benign GCTs. At present, endoscopic mucosal resection is recommended for the diagnosis and treatment of submucosal GCTs, as their malignant counterpart is extremely rare in gastrointestinal tract (AU)

Paniculitis pancreática como forma de presentación inicial de adenocarcinoma gástrico con metástasis hepáticas / Gastric adenocarcinoma with hepatic metastases presenting as pancreatic panniculitis

El interés del caso reportado surge a raíz de la obtención de un valor de lipasa superior a 7.000 U/l en una paciente con una paniculitis en miembros inferiores de 10 meses de evolución. Se estableció el diagnóstico de paniculitis pancreática, y adenocarcinoma gástrico con metástasis hepáticas, con la peculiaridad de no encontrar afectación clínica ni radiológica del páncreas. Las paniculitis pancreáticas de origen tumoral no pancreático constituyen una rareza, y son un hecho excepcional en la literatura médica consultada. Este es el primer caso de paniculitis pancreática como signo inicial de un cáncer gástrico, con metástasis hepáticas y con mayor supervivencia reportado en la literatura, lo cual hace que su revisión clínica e histológica sea de extraordinario interés(AU)

A patient presenting with a ten month history of progressive lower limb panniculitis was found to have more than 7,000 lipase U/L. Pancreatic panniculitis and gastric adenocarcinoma with liver metastases was diagnosed, despite no clinical or radiological findings of pancreatic disease. Pancreatic panniculitis arising from a non pancreatic primary is extremely rare. To our knowledge, this is the first time pancreatic panniculitis has been reported as the presenting sign of gastric carcinoma with hepatic metastases. It is also the longest survival to be reported to date(AU)