A Tissue Microarray-based Comparative Analysis of Novel and Traditional Immunohistochemical Markers in the Distinction Between Adrenal Cortical Lesions and Pheochromocytoma
ABSTRACT We have encountered an increasing number of image-guided adrenal mass biopsies in which the differential diagnosis is adrenal cortical lesion versus pheochromocytoma. This distinction is sometimes difficult because of confounding clinical presentations, overlapping morphologies, and some degree of immunophenotypic overlap including focal staining with markers of purported lineage specificity. Interventional radiologists commonly use narrow gauge biopsy needles in this setting, which yield scant diagnostic tissue and further complicate pathologic evaluation. In this study, a detailed immunoprofile of 63 adrenal cortical lesions (3 adrenal rests, 6 adrenal cortical hyperplasias, 43 adrenal cortical adenomas, 4 adrenal cortical neoplasms of uncertain malignant potential, and 7 adrenal cortical carcinomas) was compared with 35 pheochromocytomas using traditional (calretinin, chromogranin, inhibin, melanA, and synaptophysin) and novel [steroidogenic factor-1 (SF-1), microtubule-associated protein 2, and mammalian achaete-scute homolog-1] antibodies, using tissue microarray technology to simulate small image-guided biopsies. Staining extent and intensity were each scored semiquantitatively for each antibody. A comparison of sensitivity and specificity using different intensity thresholds required for a "positive" result (> or = 1+ vs. > or = 2+) was performed. Staining results based on a > or = 1+ and (> or = 2+) intensity threshold were as follows: calretinin-95% (89%) in adrenal cortical lesions and 14% (0%) in pheochromocytomas; chromogranin-0% in adrenal cortical lesions and 100% in pheochromocytomas; inhibin-97% (86%) in adrenal cortical lesions and 6% (0%) in pheochromocytomas; microtubule-associated protein 2-29% (16%) in adrenal cortical lesions and 100% (89%) in pheochromocytomas; mammalian achaete-scute homolog-1-0% in both adrenal cortical lesions and pheochromocytomas; melanA-94% (86%) in adrenal cortical lesions and 6% (0%) in pheochromocytomas; SF-1-87% (86%) in adrenal cortical lesions and 0% in pheochromocytomas; synaptophysin-67% (59%) in adrenal cortical lesions and 100% in pheochromocytomas. Using an antibody panel consisting of chromogranin plus the nuclear antibody SF-1 and either calretinin or inhibin, while requiring a high-staining intensity threshold, helps to eliminate interpretative issues of artifactual or background reactivity, improves diagnostic sensitivity/specificity, and makes for an effective immunohistochemical approach in distinguishing adrenal cortical lesions from pheochromocytomas.
Conference Paper: Fuzzy models for producers from natural resources[Show abstract] [Hide abstract]
ABSTRACT: The electricity distribution planning problem consists of deciding which facilities (injection points and feeders) to construct to meet future injections. The uncertainty on future demands and independent producers' injections in the distribution network introduce additional difficulties to the problem. This paper presents a framework to cope with the uncertainties, resulting from natural resources producers (mini-hydro and wind generation), based on fuzzy descriptions of the dispersed generation injections, leading to detailed models to be used in planning tools. The models considered include basic uncertainty and linguistic modifiers when extra information, from experts, is available. The approach proposed is useful both for operation and planning purposesFuzzy Systems Proceedings, 1998. IEEE World Congress on Computational Intelligence., The 1998 IEEE International Conference on; 06/1998
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ABSTRACT: Hemangioblastoma is a benign tumor that can occur sporadically, or in association with von Hippel-Lindau disease in approximately one-quarter of the cases. Only exceptionally does it occur outside the central nervous system. This report describes 2 cases of sporadic renal hemangioblastoma, with 1 patient presenting with hematuria and polycythemia, and the other low back pain. Histologically, the tumors were circumscribed, and composed of sheets of large polygonal cells traversed by arborizing thin-walled blood vessels. Many of the tumor cells showed pleomorphic nuclei, but the mitotic figures were rare. The cytoplasm was eosinophilic, and occasionally finely vacuolated indicating the presence of lipid. The diagnosis of hemangioblastoma was confirmed by negative immunostaining for cytokeratin, and positive staining for α-inhibin, S100, and neuron-specific enolase. This benign neoplasm which can be mistaken for various malignancies such as renal cell carcinoma, epithelioid angiomyolipoma, adrenal cortical carcinoma, and paraganglioma, deserves wider recognition for its occurrence as a primary renal tumor.The American journal of surgical pathology 09/2010; 34(11):1695-700. DOI:10.1097/PAS.0b013e3181f2d9b8 · 4.59 Impact Factor
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ABSTRACT: The diagnosis of metastatic clear cell renal cell carcinoma may be difficult in some cases, particularly in the small image-guided biopsies that are becoming more common. As targeted therapies for renal cell carcinoma are now standard treatment, the recognition and diagnosis of renal cell carcinoma has become even more critical. Many adjunctive immunohistochemical markers of renal epithelial lineage such as CD10 and RCCma have been proposed as aids in the diagnosis of metastatic renal cell carcinoma, but low specificities often limit their utility. More recently described markers (PAX-2, PAX-8, human kidney injury molecule-1, hepatocyte nuclear factor-1-β, and carbonic anhydrase-IX) offer the potential for greater sensitivity and specificity in this diagnostic setting; however, knowledge of their expected staining in other neoplasms and tissues is critical for appropriate use. In this review, we discuss the most widely used immunohistochemical markers of renal lineage with an emphasis on their sensitivity and specificity for metastatic clear cell renal cell carcinoma. Subsequently, we present a variety of organ-specific differential diagnostic scenarios in which metastatic clear cell renal cell carcinoma might be considered and we propose immunopanels for use in each situation.Advances in anatomic pathology 11/2010; 17(6):377-93. DOI:10.1097/PAP.0b013e3181f89400 · 3.10 Impact Factor