The aims of this study were to investigate the role of vascular invasion (blood and lymphatic), vessel density and the presence of tumour-associated macrophages as prognostic markers in 202 cutaneous melanoma patients. Sections of primary melanoma were stained with lymphatic-specific antibody D2-40 to assess lymphatic vessel invasion and density in intratumoural and peritumoural areas; an antibody against endothelial marker CD34 was used to determine blood vessel invasion and density, and an antibody against CD68 was used to determine macrophage counts. Immunohistochemically determined vascular invasion (combined blood and lymphatic) was compared with that determined using haematoxylin and eosin (H&E) staining. The use of immunohistochemistry increased detection of vascular invasion from 8–30% of patients, and histological exam of H&E-stained tissue was associated with a false positive rate of 64%. Lymphatic vessel invasion occurred at a much higher frequency than blood vessel invasion (27 and 4% of patients, respectively). Although immunohistochemically detected vessel invasion was significantly associated with histological markers of adverse prognosis, such as increased Breslow thickness, ulceration and mitotic rate (all P<0.001), no associations with relapse-free or overall survival were observed. High macrophage counts were significantly associated with markers of aggressive disease, such as Breslow thickness, ulceration and mitotic rate (P<0.001, P<0.001, P=0.005, respectively), and lymphatic vessel invasion and high microvessel density (P=0.002 and P=0.003, respectively). These results suggest that vascular invasion is more accurately detected using immunohistochemistry and occurs predominantly via lymphatic vessels. The association of vessel characteristics with histological characteristics of the primary melanoma provides evidence for their biological importance in melanoma, but that they were not associated with clinical outcome attests to the value of existing histological prognostic biomarkers. We note that a high macrophage count may be associated with neovascularisation and primary tumour growth, and may also promote invasion through lymphatic vessels.
Diffuse large B-cell lymphoma that develops in the setting of long-standing chronic inflammation is typically associated with Epstein-Barr virus, and usually presents as tumor mass involving body cavities, as in pyothorax-associated lymphoma. It is listed as a distinct entity in the latest World Health Organization lymphoma classification. We report four cases that were incidentally discovered on histologic examination, one each in a splenic false cyst, a long-standing hydrocele, an atrial myxoma, and metallic-implant wear debris. Microscopic foci of atypical (neoplastic) large lymphoid cells were found within the contents of the cysts or curettage material, or within the stroma of the atrial myxoma. Despite the diverse clinical scenarios, all cases showed a homogeneous phenotype: positivity for B-lineage markers (CD20 þ , CD79a þ , PAX5 þ ), non-germinal center immunophenotype (CD10À, BCL6À/ þ , MUM-1 þ ), and positivity for Epstein-Barr virus with type III latency (LMP1 þ , EBNA2 þ ). The last feature supports the hypothesis that the lymphoma has arisen in a setting of 'local immunodeficiency' as a result of long-standing chronic inflammation in an enclosed space, a characteristic pathogenetic mechanism of diffuse large B-cell lymphoma associated with chronic inflammation. These cases therefore expand the spectrum of this entity to include new clinical scenarios for the development of this lymphoma type.
Medullary carcinomas have a better prognosis than other grade 3 mammary carcinomas, but they typically show basal-like biological features, which are associated with a poor prognosis. In this study we examined the associations and prognostic relevance of medullary histological features in a series of 165 invasive carcinomas with a basal-like phenotype: triple-negative (oestrogen receptor, progesterone receptor, HER2) and expressing at least one basal marker (CK5/6, CK14, CK17 or EGFR). The following histological features were associated with each other: prominent inflammation, anastomosing sheets, absence of fibrosis, absence of infiltrative margin and absence of gland formation. Prominent inflammation and anastomosing sheets in at least 30% of the tumour were associated with a better prognosis on univariate analysis. The combination of these two features (a simplified definition of medullary-like type) was present in 17% of tumours and was an independent prognostic factor on multivariate analysis. This simplified definition had good inter-observer reproducibility (j ¼ 0.61) and is worthy of more detailed assessment in an unselected group of mammary carcinomas. A fibrotic focus was present in 36% of carcinomas. Only 3% of tumours with a fibrotic focus had features of medullary-like carcinomas. Fibrotic focus of greater than 30% of the tumour was associated with a poor prognosis. This study emphasizes the heterogeneity of morphology and behaviour of triple-negative basal-like carcinomas.
Microfluidic fuel cells eliminate the membrane by utilizing parallel colaminar flow of electrolyte between the anode and cathode electrodes. When operated on vanadium redox electrolyte, these cells also eliminate the need for catalyst. Hence, microfluidic fuel cells are promising contenders in terms of achieving useful performance levels for commercial applications while being cost-effective on a commercial scale. However, due to the inherent size of these devices the power output is relatively low and scale-up is a major challenge. In the present article, two planar cell multiplexing strategies are introduced, featuring a nonsymmetric unilateral design and a symmetric bilateral device architecture, both of which employ two cells with shared fluidic inlet ports. The fuel cell design is based on flow-through porous carbon electrodes using vanadium redox electrolytes as reactants. In both array architectures, the two cells are fluidically connected in parallel and electrically in series. The main challenge of achieving uniform flow distribution is assessed using laminar flow theory and computational fluid dynamics and validated experimentally. The normalized performance obtained with the two prototype array cells is found to be equivalent to previously reported data for single cells, in this case doubling the device level voltage and power output and reaching 820 and 1200 mW/cm2 peak power density for the nonsymmetric unilateral and symmetric bilateral array designs, respectively. It is, thus, demonstrated that both unilateral and bilateral planar multiplexing strategies are feasible for microfluidic fuel cell technologies and are shown to be particularly effective when the flow sharing between different cells is equal.
In our study, 19% of patients with a benign papillary lesion diagnosed on core biopsy were found to have atypical ductal hyperplasia or malignancy following surgery. In view of this, together with the absence of reliable predictive factors for malignancy, we recommend surgical excision of all papillary lesions diagnosed on core biopsy.
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