Renal medullary carcinomas: Histopathologic phenotype associated with diverse genotypes
Department of Pathology, Creighton University School of Medicine, Omaha, NE 68131, USA.Human pathology (Impact Factor: 2.77). 07/2011; 42(12):1979-88. DOI: 10.1016/j.humpath.2011.02.026
Chromosomal abnormalities and gene mutations have become major determinants in the classification of kidney carcinomas. Most renal medullary carcinomas develop in patients with hereditary sickle cell disease, but sporadic cases unassociated with sickle cell disease have also been described, for which underlying genetic abnormality is unknown. We evaluated 3 patients with renal medullary carcinoma (1 patient with sickle cell disease and 2 patients without sickle cell disease) for germ line and somatic mutations in genes commonly involved in pathogenesis of renal carcinomas using denaturing high-performance liquid chromatography and direct sequencing. Chromosomal abnormalities were studied by the conventional cytogenetic and SNP arrays analysis. Expression of hypoxia-inducible factor 1α was examined using immunohistochemistry. Two new mutations in the gene for fumarate hydratase were identified in 1 case of medullary renal carcinoma without sickle cell disease: a germ line mutation in exon 6 (R233H) and an acquired (somatic) mutation in exon 8 (P374S). No fumarate hydratase mutations were identified in the other 2 patients. The second sporadic case of renal medullary carcinoma harbored double somatic mutations in von Hippel-Lindau gene, and renal medullary carcinoma in the patient with sickle cell disease showed von Hippel-Lindau gene promoter methylation (epigenetic silencing). No consistent pattern of chromosomal abnormalities was found between 2 cases tested. All 3 cases showed increased hypoxia-inducible factor 1α expression. Medullary renal carcinomas from patients with or without sickle cell disease show involvement of genes important in hypoxia-induced signaling pathways. Generalized cellular hypoxia (in sickle cell disease) or pseudohypoxia (in tumors with fumarate hydratase and von Hippel-Lindau mutations or epigenetic silencing) may act alone or in concert at the level of medullary tubular epithelium to promote development of this rare type of renal carcinoma, which could then be genetically reclassified as either fumarate hydratase-associated renal carcinomas or high-grade clear cell renal cell carcinomas.
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ABSTRACT: To compare the characteristics and predictors of cancer-specific survival (CSS) of 2 rare distal nephron tumors--medullary renal cell carcinoma (MRCC) and collecting duct carcinoma (CDC). All cases of histologically verified MRCC and CDC reported to The Surveillance, Epidemiology and End Results (SEER) database between 1995 and 2007 were considered. A number of characteristics were compared by tumor histology. Subset analyses were performed for metastatic patients and those managed surgically. CSS was analyzed using Cox proportional hazard models. Overall, 21 cases of MRCC and 227 cases of CDC met the criteria for analysis. Patients with MRCC were younger (median 24 vs 63 years, P < .001), more often black (71.4% vs 22.7%, P < .001), metastatic at presentation (71.4% vs 27.8%, P < .001), and less likely to undergo surgery (61.9% vs 85.6%, P = .015) compared with patients with CDC. Tumor size was similar between MRCC and CDC (median 6 vs 5 cm, P = .70). Median survival was 5 months for MRCC and 30 months for CDC (P < .001). In metastatic MRCC and CDC patients, surgery predicted CSS (HR 4.61 and 2.24, both P ≤.05) despite having larger primary tumors than those managed nonsurgically (median 7.5 vs 5.0 cm, P < .01). Patients with MRCC present younger, at a later stage, and are more often black than patients with CDC. The stage migration toward localized kidney cancer is not apparent for these tumors. Although both cancers have a poor prognosis, the clinical and survival characteristics are distinct. Patients selected for cytoreductive surgery have improved survival.Urology 05/2012; 80(1):140-6. DOI:10.1016/j.urology.2012.03.034 · 2.19 Impact Factor
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ABSTRACT: Characteristic skin neoplasms are associated with a large number of hereditary tumor syndromes and their knowledge and early detection may facilitate the diagnosis of the underlying malignancies. We will review the clinical and dermatopathological aspects of cutaneous and visceral lesions and the recent progresses in understanding the etiology, pathogenesis and therapies of selected tumor syndromes. The skin neoplasms we chose to consider are multiple neurofibromas in neurofibromatosis, cylindromas and trichoepitheliomas in Broke-Spiegler syndrome, sebaceous tumors and keratoacanthomas in Muir-Torre syndrome, Gardner fibromas in Gardner syndrome, multiple basal cell carcinomas in nevoid basal cell carcinoma (Gorlin) syndrome, multiple tricholemmomas in Cowden syndrome, multiple fibrofolliculomas in Birt-Hogg-Dubé syndrome and multiple leiomyomas in hereditary leiomyomatosis and renal cell cancer. Hereditary cancers have distinct biological and clinical features as compared to their sporadic counterparts; for this reason, we are now able to experiment new treatment approaches involving not only tumor detection and prevention, but also tailored therapeutic strategies focusing on the peculiar druggable molecular targets.Critical reviews in oncology/hematology 07/2012; 85(3). DOI:10.1016/j.critrevonc.2012.07.001 · 4.03 Impact Factor
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ABSTRACT: To describe the pathologic and molecular characteristics of genitourinary malignancies relevant to the implications for the practice of oncology nurses. Actual cases from the author's clinical experience, original scientific papers, review articles, and pathology books. Accurate pathologic diagnosis and identification of serum and molecular markers are critical for the accurate classification, staging, and choice of appropriate treatment for patients with genitourinary malignancies. Because decisions of treatment initiation, discontinuation, and prognosis are in large part based on pathologic diagnosis and staging, oncology nurses should be knowledgeable about the process of pathologic tissue review and understand the importance of appropriate tumor acquisition.Seminars in Oncology Nursing 08/2012; 28(3):143-53. DOI:10.1016/j.soncn.2012.05.003
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