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Background: Low reproducibility of histologic grading of breast carcinoma due to its subjectivity has traditionally diminished the prognostic value of histologic breast cancer grading. The objective of this study is to assess the effectiveness and reproducibility of grading breast carcinomas with automated computer-based image processing that utilizes stochastic geometry shape analysis. Methods: We used histology images stained with Hematoxylin & Eosin (H&E) from invasive mammary carcinoma, no special type cases as a source domain and study environment. We developed a customized hybrid semi-automated segmentation algorithm to cluster the raw image data and reduce the image domain complexity to a binary representation with the foreground representing regions of high density of malignant cells. A second algorithm was developed to apply stochastic geometry and texture analysis measurements to the segmented images and to produce shape distributions, transforming the original color images into a histogram representation that captures their distinguishing properties between various histological grades. Results: Computational results were compared against known histological grades assigned by the pathologist. The Earth Mover's Distance (EMD) similarity metric and the K-Nearest Neighbors (KNN) classification algorithm provided correlations between the high-dimensional set of shape distributions and a priori known histological grades. Conclusion: Computational pattern analysis of histology shows promise as an effective software tool in breast cancer histological grading.

Breast tumors are typically heterogeneous and contain diverse subpopulations of tumor cells with differing phenotypic properties. Planar cultures of cancer cell lines are not viable models of investigation of cell-cell and cell-matrix interactions during tumor development. This article presents an in vitro coculture-based 3-dimensional heterogeneous breast tumor model that can be used in drug resistance and drug delivery investigations. Breast cancer cell lines of different phenotypes (MDAMB231, MCF7, and ZR751) were cocultured in a rotating wall vessel bioreactor to form a large number of heterogeneous tumoroids in a single cell culture experiment. Cells in the rotating vessels were labeled with CellTracker fluorescent probes to allow for time course fluorescence microscopy to monitor cell aggregation. Histological sections of tumoroids were stained with hematoxylin and eosin, progesterone receptor, E-cadherin (E-cad), and proliferation marker ki67. In vitro tumoroids developed in this study recapture important features of the temporal-spatial organization of solid tumors, including the presence of necrotic areas at the center and higher levels of cell division at the tumor periphery. E-cad-positive MCF7 cells form larger tumoroids than E-cad-negative MDAMB231 cells. In heterogeneous tumors, the irregular surface roughness was mainly due to the presence of MDAMB231 cells, whereas MCF7 cells formed smooth surfaces. Moreover, when heterogeneous tumoroids were placed onto collagen gels, highly invasive MDAMB231 cell-rich surface regions produced extensions into the matrix, whereas poorly invasive MCF7 cells did not. The fact that one can form a large number of 1-mm tumoroids in 1 coculture attests to the potential use of this system at high-throughput investigations of cancer drug development and drug delivery into the tumor.

Pathologists exhibit very poor agreement in adjudicating the cause of cytologic-histologic correlation discrepancies, which contributes to problems in designing interventions to reduce discrepancy frequency. In this observational study, we developed a visual method of adjudicating discrepancy cause, termed the No-Blame Box method, which consisted of initially assessing specimen interpretability by separately evaluating specimen quality and the presence of tumor. Five pathologists blindly adjudicated the cause of discrepancy in pulmonary specimens from 40 patients. The kappa statistic of all pathologist pairs in adjudicating discrepancy cause using the No-Blame Box method ranged from 0.400 to 0.796, indicating acceptable to excellent agreement. Pathologists ranged in their assessment of specimen interpretability from 13% to 20%, and in no case did all 5 pathologists concur that a specimen was interpretable. Most discrepancies resulted from pathologists diagnosing noninterpretable samples. Pathologists who used the No-Blame Box showed significant agreement in the adjudication of discrepancy cause.

Neurofibromatosis type-1 (NF-1), also known as von Recklinghausen disease, is a common autosomal dominant condition occurring in approximately 1/3000 births. NF-1 is known to be associated with gastrointestinal neoplasms in 2–25 per cent of patients. We report the first case of gastric outlet obstruction with perforation caused by neurofibroma in a patient with NF-1. The literature is reviewed, examining 61 previously reported cases of noncarcinoid gastrointestinal (GI) neoplasms in patients with NF-1 for symptoms, location, and types of neoplasms. Neoplasms were located most often in the small intestine (72%). Neurofibromas, found in 52 per cent of patients, were the most frequently diagnosed benign neoplasms followed by leiomyomas (13%), ganglioneurofibromas (9.8%), and gastrointestinal stomal tumor (GIST) (6.5%). Adenocarcinoma was present in 23 per cent of patients. Patients with NF-1 and GI symptoms are at risk for gastrointestinal neoplasms from which symptomatic patients are likely to experience significant morbidity.

Hemangiopericytomas are rare vasoformative tumors representing varied clinical courses and histology. Sinonasal hemangiopericytomas (SNHP) are thought to be low grade malignancies with possible late local recurrences and rare metastases even after therapy. We present four cases of SNHP and evaluate the pathological features of diagnostic and prognostic significance. Our cases are compared with all previously reported SNHP series. Cases were retrieved from medical records from our teaching institutions for the last 20 years. Clinical presentation, course, and pathology were reviewed in all cases. DNA content by image analysis, proliferation antigen (MIB-1), estrogen and progesterone receptor status, and other immunohistochemical markers were performed. All patients were females with mean age at presentation of 48.5 (18–77) years. Initial therapy was surgery alone or in combination with radiation therapy. Three patients had local recurrences at 5, 9, and 10 years, one of whom died of metastatic disease 11 years after diagnosis. DNA analysis revealed that three patients had diploid tumors. The patient who died of metastatic disease had a large aneuploid population. The proliferative fraction of the tumors studied with MIB-1 was less than 5% in all tumors. Estrogen receptors were negative in all tumors, and two tumors showed 10% positivity for progesterone receptors. All tumors stained positively with antibodies to vimentin and variably positive with smooth muscle actin. SNHP patients require life-long follow-up because of possible late recurrences and the potential for metastasis. DNA content may be useful for identifying malignant potential.

Bartonella bacilliformis, a gram-negative, flagellated, motile bacterium, is the etiologic agent of verruca peruana. It isfound within the verruca, where it can form large cytoplasmic (RochaLima) inclusions in endothelial cells. Previously, an activity has been described in homogenates of B. bacilliformis that in vitro increases the proliferation of endothelial cells and their production oftissue-type plasminogen activator (t-PA) and in vivo is angiogenic. The aim ofthe present study was to determine if live B. bacilliformis similarly stimulated endothelial cells and produced the Rocha-Lima inclusion. By measuring proliferation of cells and the production of t-PA in vitro, it was found that the live bacteria increased both parameters in a fashion similar to the homogenates of B. bacilliformis. Interaction between the bacteria and endothelial cells appeared to be necessary for proliferation. On electron microscopy, bacteria penetrated the endothelial cell within I h, forming a small membrane-bound inclusion. By 12 h, a large membrane-bound inclusion, similar to the Rocha-Lima inclusion, containing numerous bacteria was present. These data provide further evidence that B. bacilliformis has an angiogenic activity and that the bacteria are at least in part responsible for the vascular proliferation of the verruca.