316L Stainless Steel Powders for Additive Manufacturing: Relationships of Powder Rheology, Size, Size Distribution to Part Properties.

Laser-Powder Bed Fusion (L-PBF) of metallic parts is a highly multivariate process. An understanding of powder feedstock properties is critical to ensure part quality. In this paper, a detailed examination of two commercial stainless steel 316L powders produced using the gas atomization process is presented. In particular, the effects of the powder properties (particle size and shape) on the powder rheology were examined. The results presented suggest that the powder properties strongly influence the powder rheology and are important factors in the selection of suitable powder for use in an additive manufacturing (AM) process. Both of the powders exhibited a strong correlation between the particle size and shape parameters and the powder rheology. Optical microscope images of melt pools of parts printed using the powders in an L-PBF machine are presented, which demonstrated further the significance of the powder morphology parameters on resulting part microstructures.

Columnar cell lesions of the breast: the missing link in breast cancer progression? A morphological and molecular analysis.

Columnar cell lesions (CCLs) of the breast are a spectrum of lesions that have posed difficulties to pathologists for many years, prompting discussion concerning their biologic and clinical significance. We present a study of CCL in context with hyperplasia of usual type (HUT) and the more advanced lesions ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. A total of 81 lesions from 18 patients were subjected to a comprehensive morphologic review based upon a modified version of Schnitt's classification system for CCL, immunophenotypic analysis (estrogen receptor [ER], progesterone receptor [PgR], Her2/neu, cytokeratin 5/6 [CK5/6], cytokeratin 14 [CK14], E-cadherin, p53) and for the first time, a whole genome molecular analysis by comparative genomic hybridization. Multiple CCLs from 3 patients were studied in particular detail, with topographic information and/or showing a morphologic spectrum of CCL within individual terminal duct lobular units. CCLs were ER and PgR positive, CK5/6 and CK14 negative, exhibit low numbers of genetic alterations and recurrent 16q loss, features that are similar to those of low grade in situ and invasive carcinoma. The molecular genetic profiles closely reflect the degree of proliferation and atypia in CCL, indicating some of these lesions represent both a morphologic and molecular continuum. In addition, overlapping chromosomal alterations between CCL and more advanced lesions within individual terminal duct lobular units suggest a commonality in molecular evolution. These data further support the hypothesis that CCLs are a nonobligate, intermediary step in the development of some forms of low grade in situ and invasive carcinoma.

Angiogenesis in pre-invasive cancers.

BACKGROUND: To date, research in the role of angiogenesis in cancer has focused mainly on invasive diseases. Measurement of the intra-tumoural microvessel density (MVD) has also been found to be an independent prognostic marker. More recently, natural angiogenic inhibitors and pharmacological drugs capable of suppressing specific stages of neovascularisation have been reported. METHODS: This review article concentrates on those angiogenesis-related findings in pre-invasive disease. RESULTS AND CONCLUSION: The study of angiogenesis in early and preneoplastic lesions is still at a preliminary stage. Current work provides indirect evidence, either from clinical or experimental studies only, most of which have used animal models. The use of the MVD as a marker of potential tumour invasion in pre-neoplastic disease is an attractive proposition. However, its prognostic values remain to be evaluated. Measurement of angiogenic factors, or their expression in certain pre-malignant conditions, may provide further information as to which disease may become invasive, and could possibly be used as a follow-up tool. The current treatment of pre-malignant conditions is usually surgical, although the early results of anti-angiogenesis therapy in animal models show encouraging results. Prevention is always better than cure, and the identification of pre-malignant lesions with intervention to prevent malignant transformation may soon become a realistic goal.

Implications of pathologist concordance for breast cancer assessments in mammography screening from age 40 years.

Three pathologists reviewed slides and reports of cancers arising in both the study and control populations of the U.K. trial of annual mammography screening from age 40 years. A total of 875 cases were scored independently as noninvasive, microinvasive, or invasive cancer, with the last also evaluated for histology grade, type, and lymphatic vascular invasion. Of these, 870 (99.2%) were confirmed malignant, 1 case had cytology only, and 5 were judged by all reviewers as benign. Reviewer complete concordance for the three classes of malignancy was achieved in 826 (95%) and majority agreement in 31 (3.6%) of 870 with complete data. All three readers recorded grade in 736 cancers, giving a kappa statistic of 0.69, 0.52, and 0.66 for grades I, II, and III, respectively, and 0.61 overall. Agreement that the cancer was special type or not was obtained in 671 (89.0%) with complete concordance in the nature of the type in 504 and majority view in 167; another 58 (7.7%) were characterised as "part special" pattern, with type disagreement in 23 (3%). The kappa statistic for single type subcategories in those cancers was substantial, at 0.68 overall. This improved to 0.76 for the last 230 invasive cancers after the pathologists agreed more explicit criteria for type discrimination. There was almost perfect agreement between original and review diagnosis of breast malignancy for both noninvasive/microinvasive and invasive cancer (kappa 0.84 and 0.91, respectively), justifying confidence in the diagnosis of breast cancer by U.K. pathologists. The specialists agreed substantially on qualitative histology features of type and grade of cancers, and improved further for typing by defining criteria. These consensus data, along with invasive size and node status, are reliable for use as surrogate measures of outcome, and to enhance interpretation of effect, when the trial case population sources are disclosed.

Breast cancer risk in usual ductal hyperplasia is defined by estrogen receptor-alpha and Ki-67 expression.

The hypothetical multistep model for breast carcinogenesis indicates that invasive carcinoma arises via a series of intermediate hyperplastic lesions through various grades of atypia to in situ and invasive carcinoma. Non-atypical hyperplasia [hyperplasia of usual type (HUT)] is a nonobligate precursor of breast cancer. Although its further morphological subclassification is unlikely, refining is more likely to depend on defining biological markers of risk. Having assembled a cohort of benign proliferative breast lesions of known outcome, we studied the expression of estrogen receptor-alpha (ER-alpha) and Ki-67 using morphometric image analysis as well as dual-labeled immunofluorescence in HUT foci and in surrounding normal lobules of 25 patients that progressed to breast cancer and 19 controls. Those patients that progressed to breast cancer (cases) showed significantly higher ER-alpha [median, 57.00% of cells within individual HUT foci; interquartile range (IQ), 33.48 to 67.78] and Ki-67 (median, 3.82%; IQ, 0.85 to 11.28) expression in their HUT foci compared with controls (ER-alpha median, 30.27%; IQ, 19.75 to 52.50 and Ki-67 median, 0.77%; IQ, 0.0458 to 1.72, P = 0.008 and <0.001). No significant difference in expression of dual-stained cells was found between cases and controls. Although normal lobules from cases showed higher ER-alpha expression compared with controls, this was not statistically significant. Our data point to a previously undescribed hormone-dependent pathway in this particular group of breast neoplasms and suggest the possibility of selective hormonal therapy to suppress the proliferative potential of these benign but high-risk breast lesions. The findings of this study might have important implications for improving breast cancer screening and management strategies.