Liver biopsy samples taken from the right and left hepatic lobes differed in histological grading and staging in a large proportion of chronic hepatitis C virus patients; however, differences of more than one stage or grade were uncommon. A sampling error may have led to underdiagnosis of cirrhosis in 14.5% of the patients. These differences could not be attributed to intraobserver variation, which appeared to be low.
Questions of reproducibility and efficacy of histologic malignancy grading relative to alternative proliferation index measurements for outcome prediction remain unanswered. Microsections of specimens from the Cooperative Breast Cancer Tissue Resource (CBCTR) were evaluated by seven pathologists for reproducibility of grade and classification. Nuclear figure classification was assessed using photographs. Grade was assigned by the Bloom-Richardson method, Nottingham modification. Proliferation index was evaluated prospectively by deoxyribose nucleic acid precursor uptake with thymidine (autoradiographic) or bromodeoxyuridine (immunohistochemical) labeling index using fresh tissue from 631 node-negative breast cancer patients accessioned at St Luke's Hospital. A modified Nottingham-Bloom-Richardson grade was derived from histopathologic data. Median post-treatment observation was 6.4 years. Agreement on classification of nuclear figures (N ¼ 43) was less than good by kappa statistic (j ¼ 0.38). Grade was moderately reproducible in four trials (N ¼ 10,10,19, 10) with CBCTR specimens (j ¼ 0.50-0.59). Of components of Bloom-Richardson grade, agreement was least for nuclear pleomorphism (j ¼ 0.37-0.50), best for tubularity (j ¼ 0.57-0.83), and intermediate for mitotic count (j ¼ 0.45-0.64). Bloom-Richardson grade was a univariate predictor of prognosis in node-negative St Luke's patients, and was improved when mitotic count was replaced by labeling index (low, mid, or high). When labeling index was added to a multivariate model containing tumor size and vessel invasion, grade was no longer a significant predictor of tumor-specific relapse-free or overall survival. Mitotic index predicted best when intervals were lowered to 0-2, 3-10, and 410 mitotic figures per ten 0.18 mm 2 highpower fields. We conclude that Nottingham-Bloom-Richardson grades remain only modestly reproducible. Prognostically useful components of grade are mitotic index and tubularity. The Nottingham-BloomRichardson system can be improved by lowering cutoffs for mitotic index and by counting 20-30 rather than 10 high-power fields. Measurement of proliferation index by immunohistochemically detectable markers will probably give superior prognostic results in comparison to grade.
A minimum of four specimens, preferably those that are nonfragmented and that sink, should be obtained with 14-gauge US-guided breast biopsy.
Vasculitides are currently classified according to the size of the vessels involved and characteristic clinical and histopathologic findings. Antineutrophil cytoplasmic antibodies (ANCA) and other serologic tests have been used to further characterize small vessel vasculitides. Large vessel involvement in ANCA-associated small vessel vasculitides has been overlooked in the medical literature. Here, we report a case of fatal aortitis and aortic dissection in a patient with microscopic polyangiitis and review reported cases of large vessel involvement in ANCA-associated vasculitides since 1990. We have attempted to characterize this subgroup of patients. Large vessel disease in ANCA-associated vasculitis may present as stenosing large vessel arteritis, aneurysmal disease, aortic dissection, aortic rupture, aortic regurgitation, and death. Prominent perivascular inflammation may present as mediastinal, cervical or abdominal soft tissue masses. ANCA-associated large vessel disease should be considered in the differential diagnosis of these disorders. The epidemiologic, clinical and pathologic characteristics of these patients differ from those of the well-defined large vessel vasculitides such as giant cell (temporal) arteritis or Takayasu's arteritis. We suggest that large vessel involvement is part of the spectrum of ANCA-associated vasculitis rather than an overlap with other large vessel vasculitides. It occurs in both myeloperoxidase- and proteinase 3-positive patients with either Wegener's granulomatosis or microscopic polyangiitis, but has not been reported in Churg-Strauss syndrome. Large vessel vasculitis can precede small vessel vasculitis or occur in the absence of small vessel involvement. We hope this report will contribute to the ongoing development of classification systems for the vasculitic syndromes.
BackgroundEarly detection of melanoma is of great importance to reduce mortality. Discovering new melanoma biomarkers would improve early detection and diagnosis. Here, we present a novel approach to detect volatile compounds from skin.Methods and FindingsWe used Head Space Solid Phase Micro-Extraction (HS-SPME) and gas chromatography/mass spectrometry (GC/MS) to identify volatile signatures from melanoma, naevi and skin samples. We hypothesized that the metabolic state of tissue alters the profile of volatile compounds. Volatiles released from fresh biopsy tissue of melanoma and benign naevus were compared based on their difference in frequency distribution and their expression level. We also analyzed volatile profiles from frozen tissue, including skin and melanoma.ConclusionsThree volatiles, 4-methyl decane, dodecane and undecane were preferentially expressed in both fresh and frozen melanoma, indicating that they are candidate biomarkers. Twelve candidate biomarkers evaluated by fuzzy logic analysis of frozen samples distinguished melanoma from skin with 89% sensitivity and 90% specificity. Our results demonstrate proof-of-principle that there is differential expression of volatiles in melanoma. Our volatile metabolomic approach will lead to a better understanding of melanoma and can enable development of new diagnostic and treatment strategies based on altered metabolism.
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