Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
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Heterogeneous biological characteristics of hepatocellular carcinoma may be attributed to the cellular origin of the tumor. Patients with hepatocellular carcinoma probably derived from hepatic progenitor cells had early tumor recurrence after surgical resection or liver transplantation, suggesting that these tumors have aggressive characteristics. Ezrin, a member of the ERM (ezrin-radixin-moesin) cytoskeleton-associated protein family, is highly expressed in several types of human cancers and correlations between its immunoreactivity and patient outcome have been shown. ⋯ Multivariate analysis revealed positive ezrin expression and multiple tumors to be independently associated with early recurrence in patients with hepatocellular carcinoma after curative surgical resection. These results suggested that hepatocellular carcinoma with ezrin expression might be at least partly derived from hepatic progenitor cells. Measurement of ezrin expression might be used to identify patients with an increased risk of early recurrence.
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Idiopathic pleuroparenchymal fibroelastosis is a rare recently described entity likely to be under- and misdiagnosed, as awareness of this entity is not yet widespread. We report two cases that show the need to include this disease in the differential diagnosis of patients with predominantly pleural and subpleural fibrotic processes. The condition is a fibrotic thickening of the pleura and subpleural parenchyma due to elastic fiber proliferation predominantly in the upper lobes. ⋯ These patients may be prone to the development of secondary spontaneous pneumothoraces and persistent postoperative bronchopleural fistulae. Continued study of newly diagnosed cases may uncover shared characteristics or features helpful in generating an etiologic hypothesis. Only with better understanding of this disease can we hope in the future to be able to offer treatments other than supportive care and ultimately lung transplantation, which are the only therapeutic options available today.
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Hematopoietic cell transplantation-associated renal injury may be related to a combination of factors including chemotherapy, radiation, infection, immunosuppressive agents, ischemia, and graft-versus-host disease. Renal biopsy specimens from hematopoietic cell transplant recipients at two institutions (Stanford University Medical Center and Oregon Health & Science University) were reviewed in correlation with clinical data. Fifteen cases were identified (post hematopoietic cell transplant time 0.7-14.5 years), including six with autologous hematopoietic cell transplant. ⋯ Of 14 patients with follow-up (2-64 months, mean 19 months), 6 had chronic renal insufficiency (serum creatinine >1.5 mg/dl), 2 had end stage renal disease, and 6 had essentially normal renal function. Our retrospective study shows that renal dysfunction in hematopoietic cell transplant recipients is often multifactorial, and biopsy may reveal treatable causes. Membranous glomerulonephritis is seen in autologous and allogeneic hematopoietic cell transplant recipients, and may respond to anti-B-cell therapy, which has implications regarding pathogenesis and relationship to graft-versus-host disease.
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Werner syndrome is a premature aging syndrome characterized by early onset of cancer and abnormal cellular metabolism of glycosaminoglycan. The WRN helicase plays an important role in the maintenance of telomere function. WRN promoter methylation and gene silencing are common in colorectal cancer with the CpG island methylator phenotype (CIMP), which is associated with microsatellite instability (MSI) and mucinous tumors. ⋯ No relations of WRN methylation with other variables (age, sex, tumor location, poor differentiation, signet ring cells, lymphocytic reactions, KRAS, BRAF, p53, p21 or 18q loss of heterozygosity) persisted after tumors were stratified by CIMP status. In conclusion, WRN methylation is associated with mucinous differentiation independent of CIMP and MSI status. Our data suggest a possible role of WRN methylation in mucinous differentiation, and may provide explanation to the enigmatic association between mucin and MSI/CIMP.
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Around 25% of hereditary breast and ovarian cancer families have mutations in the BRCA1 and BRCA2 genes. The search for other genes has until now failed, probably because there is not one single BRCAX gene, but rather various genes that may each be responsible for a small number of breast cancer families and/or may interact according to a polygenic model. We have studied 50 tumors from probands belonging to non-BRCA1/2 breast cancer families (BRCAX), using 25 immunohistochemical markers. ⋯ These latter cases were all clustered in the high-grade group and the majority of them in the basal-like subgroup. Our results show that familial non-BRCA1/2 tumors are heterogeneous and suggest a polygenic model for explaining the majority of BRCAX families. In addition we have defined a subset of them that have somatic inactivation of the BRCA1 gene.