Prognostic value of histopathological DCIS features in a large-scale international interrater reliability study.

PURPOSE: For optimal management of ductal carcinoma in situ (DCIS), reproducible histopathological assessment is essential to distinguish low-risk from high-risk DCIS. Therefore, we analyzed interrater reliability of histopathological DCIS features and assessed their associations with subsequent ipsilateral invasive breast cancer (iIBC) risk. METHODS: Using a case-cohort design, reliability was assessed in a population-based, nationwide cohort of 2767 women with screen-detected DCIS diagnosed between 1993 and 2004, treated by breast-conserving surgery with/without radiotherapy (BCS ± RT) using Krippendorff's alpha (KA) and Gwet's AC2 (GAC2). Thirty-eight raters scored histopathological DCIS features including grade (2-tiered and 3-tiered), growth pattern, mitotic activity, periductal fibrosis, and lymphocytic infiltrate in 342 women. Using majority opinion-based scores for each feature, their association with subsequent iIBC risk was assessed using Cox regression. RESULTS: Interrater reliability of grade using various classifications was fair to moderate, and only substantial for grade 1 versus 2 + 3 when using GAC2 (0.78). Reliability for growth pattern (KA 0.44, GAC2 0.78), calcifications (KA 0.49, GAC2 0.70) and necrosis (KA 0.47, GAC2 0.70) was moderate using KA and substantial using GAC2; for (type of) periductal fibrosis and lymphocytic infiltrate fair to moderate estimates were found and for mitotic activity reliability was substantial using GAC2 (0.70). Only in patients treated with BCS-RT, high mitotic activity was associated with a higher iIBC risk in univariable analysis (Hazard Ratio (HR) 2.53, 95% Confidence Interval (95% CI) 1.05-6.11); grade 3 versus 1 + 2 (HR 2.64, 95% CI 1.35-5.14) and a cribriform/solid versus flat epithelial atypia/clinging/(micro)papillary growth pattern (HR 3.70, 95% CI 1.34-10.23) were independently associated with a higher iIBC risk. CONCLUSIONS: Using majority opinion-based scores, DCIS grade, growth pattern, and mitotic activity are associated with iIBC risk in patients treated with BCS-RT, but interrater variability is substantial. Semi-quantitative grading, incorporating and separately evaluating nuclear pleomorphism, growth pattern, and mitotic activity, may improve the reliability and prognostic value of these features.

Pancreatic non-functioning neuroendocrine tumor: a new entity genetically related to Lynch syndrome.

Some pancreatic neuroendocrine tumors (P-NETs) are associated with hereditary syndromes. An association between Lynch syndrome (LS) and P-NETs has been suggested, however it has not been confirmed to date. We describe the first case associating LS and P-NETs. Here we report a 65-year-old woman who in the past 20 years presented two colorectal carcinomas (CRC) endometrial carcinoma (EC), infiltrating ductal breast carcinoma, small intestine adenocarcinoma, two non-functioning P-NETs and sebomatricoma. With the exception of one P-NET, all these conditions were associated with LS, as confirmed by immunohistochemistry (IHC) and polymerase chain reaction (PCR). LS is caused by a mutation of a mismatch repair (MMR) gene which leads to a loss of expression of its protein. CRC is the most common tumor, followed by EC. Pancreatic tumors have also been associated with LS. Diagnosis of LS is based on clinical criteria (Amsterdam II and Bethesda) and genetic study (MMR gene mutation). The association between LS and our patient's tumors was confirmed by IHC (loss of expression of proteins MLH1 and its dimer PMS2) and the detection of microsatellite instability (MSI) using PCR.

Tratamiento definitivo de las lesiones premalignas de la mama sin cirugía: la escisión percutánea Intact R-BLES / Definitive treatment of premalignant breast lesions without surgery: the Intact R-Breast Lesion Excision System (BLES)

Objetivo. El hallazgo en una biopsia de mama de lesiones proliferativas atípicas, implica la necesidad de cirugía y extirpación de dicha lesión. El objetivo del estudio fue determinar la tasa de escisiones completas mediante el uso del dispositivo IntactR-BLES de lesiones categorizadas B3 en biopsia asistida por vacío (BAV). Pacientes y métodos. Realizamos un estudio descriptivo observacional de la utilidad de este sistema que consigue, con anestesia local y ambulatoriamente, la obtención percutánea de una muestra de tejido de 20 × 20 mm, permitiendo la valoración de los márgenes de resección, llevado a cabo entre febrero de 2012 y septiembre de 2014. Resultados. Se analizaron 25 procedimientos. La biopsia inicial demostraba principalmente la presencia de atipia epitelial plana (56%) e hiperplasia ductal atípica (32%). El tamaño medio de la pieza extirpada fue de 20 × 10 × 8 mm, en un espécimen único, permitiendo la valoración de márgenes en todas ellas (100%). En el estudio anatomopatológico definitivo no se encontró lesión residual en el 68% de los casos, así como 2 casos (8%) de carcinoma intraductal (CDIS), infradiagnosticados con la biopsia inicial. El estudio de márgenes demostró estar libres en el 85% de los casos. No ha habido ningún efecto adverso importante, solo un caso de hematoma y un caso de dolor superior al normal. Conclusiones. El sistema de escisión percutánea (Intact®-BLES) permite mediante un procedimiento con anestesia local, de forma ambulatoria y sin complicaciones importantes evitar la cirugía en un 88% de los casos de lesiones premalignas en la biopsia inicial. Así mismo, permite demostrar la presencia de CDIS en un 8% de los casos (infradiagnosticados) (AU)

Objective. The finding of an atypical proliferative lesion in a breast biopsy implies the need for surgical removal of the lesion. The aim of this study was to determine the complete excision rate with the IntactR-BLES device of B3 lesions diagnosed in vacuum-assisted biopsy. Patients and methods. A descriptive study was carried out to appraise the usefulness of this system, which obtains a percutaneous 20×20 mm tissue sample under local anaesthesia and on an outpatient basis, allowing assessment of the resection margins performed between February 2012 and September 2014. Results. We analysed 25 procedures. The initial biopsy showed mostly the presence of flat epithelial atypia (56%) and atypical ductal hyperplasia (32%). The mean size of the resected specimen was 20×10×8 mm, in a single specimen, allowing assessment of margins in all of them (100%). The definitive pathological analysis reported no residual lesion in 68% of the patients and intraductal carcinoma in situ (DCIS) in 2 patients (8%), which had been underdiagnosed with the initial biopsy. Study of margins also demonstrated free margins in 85% of the patients. There were no major adverse effects, and only 1 case of haematoma and 1 case of higher-than-normal pain. Conclusions. The percutaneous excision system (Intact®-BLES) can be performed under local anaesthesia on an outpatient basis without major complications, thus avoiding surgery in 88% of cases of premalignant lesions in the initial biopsy. In addition, this procedure revealed the presence of DCIS in 8% of the patients (underdiagnosed) (AU)

Liposarcoma mixoide de mama. A propósito de un caso y revisión de la literatura / Myxoid liposarcoma of the breast. A case report and review of the literature

Presentamos el caso de una mujer de 40 años, sin antecedentes de interés, que consulta por palpación de nódulo mamario. La mamografía muestra una lesión nodular, bien delimitada, heterogénea, de 34mm, en el cuadrante superoexterno/prolongación axilar derecha. Se estudia mediante biopsia guiada por ecografía, con resultado de tumor mesenquimal con estroma mixoide, patrón vascular plexiforme y ocasionales células compatibles con lipoblastos. Con este diagnóstico se procede a la exéresis total de la lesión, que a la sección macroscópica muestra nódulo de bordes expansivos, de aspecto gelatinoso y características microscópicas de liposarcoma mixoide. Se presenta el caso y se revisa la literatura médica(AU)

A 40 year old woman presented with a palpable swelling in her right breast. She had no relevant past medical history. Mammography revealed a 34mm, well-defined heterogeneous nodular mass in the axillary tail of the upper external quadrant of the right breast. An ultrasound guided biopsy was performed, in which a mesenchymal tumour was found, with myxoid stroma, a plexiform capillary pattern and scattered cells that resembled lipoblasts. Subsequently, the tumour was excised. Macroscopy showed regular margins on the cut surface and a myxoid lesion. Microscopically the lesion was diagnosed as myxoid liposarcoma. The clinico-pathological features of the case are described and the pertinent literature discussed(AU)