Background &Aims: In nonalcoholic fatty liver disease (NAFLD), the distinction between steatosis and steatohepatitis (NASH) and the assessment of the severity of the disease rely on liver histology alone. The aim ...Background &Aims: In nonalcoholic fatty liver disease (NAFLD), the distinction between steatosis and steatohepatitis (NASH) and the assessment of the severity of the disease rely on liver histology alone. The aim of this study was to assess the sampling error of liver biopsy and its impact on the diagnosis and staging of NASH. Methods: Fifty-one patients with NAFLD underwent percutaneous liver biopsy with 2 samples collected. The agreement between paired biopsy specimens was assessed by the percentage of discordant results and by the κreliability test. Results: No features displayed high agreement; substantial agreement was only seen for steatosis grade; moderate agreement for hepatocyte ballooning and perisinusoidal fibrosis; fair agreement for Mallory bodies; acidophilic bodies and lobular inflammation displayed only slight agreement. Overall, the discordance rate for the presence of hepatocyte ballooning was 18%, and ballooning would have been missed in 24%of patients had only 1 biopsy been performed. The negative predictive value of a single biopsy for the diagnosis of NASH was at best 0.74. Discordance of 1 stage or more was 41%. Six of 17 patients with bridging fibrosis (35%) on 1 sample had only mild or no fibrosis on the other and therefore could have been under staged with only 1 biopsy. Intraobserver variability was systematically lower than sampling variability and therefore could not account for most of the sampling error. Conclusions: Histologic lesions of NASH are unevenly distributed throughout the liver parenchyma; therefore, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies.展开更多
The histological course of nonalcoholic fatty liver disease (NAFLD) remains undescribed. Therefore, we examined the liver histology of NAFLD patients who had undergone sequential liver biopsies. Data on 103 patients w...The histological course of nonalcoholic fatty liver disease (NAFLD) remains undescribed. Therefore, we examined the liver histology of NAFLD patients who had undergone sequential liver biopsies. Data on 103 patients who underwent serial liver biopsies in the absence of effective treatment were reviewed, and biopsies scored in a blind fashion. Mean interval between biopsies was 3.2±3.0 years (range 0.7-21.3). Fibrosis stage apparently progressed in 37%, remained stable in 34%and regressed in 29%. Severity of steatosis, inflammation, hepatocyte ballooning and Mallory’s hyaline improved significantly. Aminotransferases decreased significantly between biopsies, paralleling improvement in steatosis and inflammatory features but not fibrosis stage. The rate of fibrosis change ranged from -2.05 to 1.7 stages/year. By multivariate analysis, diabetes (P=0.007) and low initial fibrosis stage (P<0.001) were associated with higher rate of fibrosis progression, as was higher body mass index (P=0.008) when cirrhotics were excluded. Fibrosis in NAFLD progresses slowly over time with considerable variability in the rate of changes among patients. Changes of aminotransferases do not parallel changes in fibrosis stage. Diabetic patients with elevated BMI and low fibrosis stage are at risk for higher rates of fibrosis progression.展开更多
Some authors have used sebaceous epithelioma as a synonym for basal cell carcinoma (BCC) with sebaceous differentiation. However, our reviewof the literature revealed that definite cases of BCC with sebaceous differen...Some authors have used sebaceous epithelioma as a synonym for basal cell carcinoma (BCC) with sebaceous differentiation. However, our reviewof the literature revealed that definite cases of BCC with sebaceous differentiation that provide adequate clinical and histopathologic information are scarce. We present the case of a 72-year-old woman with a pigmented nodular lesion on her right ala nasi region, clinically diagnosed as pigmented BCC. Histopathologically, this nodular lesion, which was completely excised, showed typical features of BCC. It was noteworthy that within one aggregation of the presented BCC, tiny and small duct-like structures lined by cornified layers with a crenulated inner surface were seen. Vacuolated cells were scattered within a few aggregations, and they had foamy, bubbly cytoplasm and starry nuclei. The vacuolated cells were immunohistochemically positive for epithelial membrane antigen (EMA). These histopathologic findings demonstrated unquestionable sebaceous differentiation in this BCC, namely BCC with sebaceous differentiation, which should be distinguishable from both sebaceoma and sebaceous carcinoma. The small duct-like structures lined by eosinophilic cuticle, indicating apocrine differentiation, were also observed in this BCC.展开更多
Dermal clear cell tumors are not common. This group of lesions is comprised primarily of clear cell adnexal lesions, balloon cell melanocytic lesions, and metastatic clear cell carcinomas. We report the clinicopatholo...Dermal clear cell tumors are not common. This group of lesions is comprised primarily of clear cell adnexal lesions, balloon cell melanocytic lesions, and metastatic clear cell carcinomas. We report the clinicopathologic features of five cases of a novel dermal clear cell neoplasm that appears mesenchymal in nature. The affected patients included 3 men and 2 women ranging in age from 38 to 70 (median, 45 years). All the lesions occurred on the lower limb. Clinically described as smooth cutaneous nodules, size ranged from 0.5 to 2.5 cm in greatest dimension and the lesions were present from weeks to 5 years prior to excision. Situated in the reticular dermis, the tumors usually extended to involve the subcutis with sparing of the papillary dermis. The tumors were composed of large optically clear cells with vesicular nuclei. The lesions entrapped adnexal structures and thin dermal collagen fibers. Mitoses were rare (less than 1 per 25 hpf). A single case showed more pleomorphic nuclei as well as quite frequent mitoses and was considered of uncertain biologic potential. Immunohistochemistry revealed reactivity only for NKI-C3 (5/5 cases), CD68 (2/5 cases), and vimentin (2/3 cases); melanocytic, epithelial, and lymphoidmarkerswere uniformly negative. All five lesions were locally excised; the more pleomorphic and mitotically active lesion was widely reexcised and given subsequent radiation therapy. In follow-up ranging from 1.5 to 11 years (median, 5.5 years), none of these lesions has recurred. These tumors appear to be mesenchymal in nature, but their precise line of differentiation is unknown. Recognition of these lesions is important to avoid confusion with better-known malignant neoplasms.展开更多
Severe lipodystrophy is characterized by diminished adipose tissue and hypolep tinemia, leading to ectopic triglyceride accumulation.In the liver, this is asso ciated with steatosis,potentially leading to nonalcoholic...Severe lipodystrophy is characterized by diminished adipose tissue and hypolep tinemia, leading to ectopic triglyceride accumulation.In the liver, this is asso ciated with steatosis,potentially leading to nonalcoholic steatohepatitis (NASH) . We investigated the prevalence of NASH and the effect of leptin replacement in these patients. Ten patients with either generalized lipody strophy (8 patients ) or Dunnigan’s partial lipody strophy(2 patients) were included in this analys is. Paired liver biopsy specimens were obtained at baseline and after treatment with recombinant methionyl human leptin (r-metHuLeptin), mean duration 6.6 mont hs. The extents of portal and parenchymal in-flammation, steatosis, ballooning, presence of Mallory bodies,and fibrosis in liver biopsy specimens were scored u sing a previously validated system developed to assess NASH activity.Histologica l disease activity was defined as the sum of ballooning, steatosis, and parenchy mal inflammation scores. We concurrently tested serum triglycerides and aminotra nsferases and estimations of liver volume and fat content by magnetic resonance imaging. Eight of 10 patients met histological criteria for NASH at baseline. Af ter treatment with r-metHuLeptin,repeat histological examinations showed signif icant improvements in steatosis (P = .006) and ballooning injury (P = .005),with a reduction of mean NASH activity by 60%(P = .002).Fibrosis was unchanged. Significant re ductions were seen in mean seru- m triglycerides (1206→226mg/dL, P = .002),glucose(220→144 mg/dL, P = .02), i nsulin (46.4→24.8 μIU/mL, P =.004), ALT (54→24U/L, P = .02), AST (47→22 U/L, P = .046),liver volume (3209→2391 cm3, P = .007), and liver fat content(31→11 %, P = .006). In conclusion, r-metHuLeptin therapy significantly reduced trigl ycerides, transaminases, hepatom- egaly,and liver fat content. These reductions were associated with significant reductions in steatosis and the hepatocellular ballooning injury seen in NASH.展开更多
文摘Background &Aims: In nonalcoholic fatty liver disease (NAFLD), the distinction between steatosis and steatohepatitis (NASH) and the assessment of the severity of the disease rely on liver histology alone. The aim of this study was to assess the sampling error of liver biopsy and its impact on the diagnosis and staging of NASH. Methods: Fifty-one patients with NAFLD underwent percutaneous liver biopsy with 2 samples collected. The agreement between paired biopsy specimens was assessed by the percentage of discordant results and by the κreliability test. Results: No features displayed high agreement; substantial agreement was only seen for steatosis grade; moderate agreement for hepatocyte ballooning and perisinusoidal fibrosis; fair agreement for Mallory bodies; acidophilic bodies and lobular inflammation displayed only slight agreement. Overall, the discordance rate for the presence of hepatocyte ballooning was 18%, and ballooning would have been missed in 24%of patients had only 1 biopsy been performed. The negative predictive value of a single biopsy for the diagnosis of NASH was at best 0.74. Discordance of 1 stage or more was 41%. Six of 17 patients with bridging fibrosis (35%) on 1 sample had only mild or no fibrosis on the other and therefore could have been under staged with only 1 biopsy. Intraobserver variability was systematically lower than sampling variability and therefore could not account for most of the sampling error. Conclusions: Histologic lesions of NASH are unevenly distributed throughout the liver parenchyma; therefore, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies.
文摘The histological course of nonalcoholic fatty liver disease (NAFLD) remains undescribed. Therefore, we examined the liver histology of NAFLD patients who had undergone sequential liver biopsies. Data on 103 patients who underwent serial liver biopsies in the absence of effective treatment were reviewed, and biopsies scored in a blind fashion. Mean interval between biopsies was 3.2±3.0 years (range 0.7-21.3). Fibrosis stage apparently progressed in 37%, remained stable in 34%and regressed in 29%. Severity of steatosis, inflammation, hepatocyte ballooning and Mallory’s hyaline improved significantly. Aminotransferases decreased significantly between biopsies, paralleling improvement in steatosis and inflammatory features but not fibrosis stage. The rate of fibrosis change ranged from -2.05 to 1.7 stages/year. By multivariate analysis, diabetes (P=0.007) and low initial fibrosis stage (P<0.001) were associated with higher rate of fibrosis progression, as was higher body mass index (P=0.008) when cirrhotics were excluded. Fibrosis in NAFLD progresses slowly over time with considerable variability in the rate of changes among patients. Changes of aminotransferases do not parallel changes in fibrosis stage. Diabetic patients with elevated BMI and low fibrosis stage are at risk for higher rates of fibrosis progression.
文摘Some authors have used sebaceous epithelioma as a synonym for basal cell carcinoma (BCC) with sebaceous differentiation. However, our reviewof the literature revealed that definite cases of BCC with sebaceous differentiation that provide adequate clinical and histopathologic information are scarce. We present the case of a 72-year-old woman with a pigmented nodular lesion on her right ala nasi region, clinically diagnosed as pigmented BCC. Histopathologically, this nodular lesion, which was completely excised, showed typical features of BCC. It was noteworthy that within one aggregation of the presented BCC, tiny and small duct-like structures lined by cornified layers with a crenulated inner surface were seen. Vacuolated cells were scattered within a few aggregations, and they had foamy, bubbly cytoplasm and starry nuclei. The vacuolated cells were immunohistochemically positive for epithelial membrane antigen (EMA). These histopathologic findings demonstrated unquestionable sebaceous differentiation in this BCC, namely BCC with sebaceous differentiation, which should be distinguishable from both sebaceoma and sebaceous carcinoma. The small duct-like structures lined by eosinophilic cuticle, indicating apocrine differentiation, were also observed in this BCC.
文摘Dermal clear cell tumors are not common. This group of lesions is comprised primarily of clear cell adnexal lesions, balloon cell melanocytic lesions, and metastatic clear cell carcinomas. We report the clinicopathologic features of five cases of a novel dermal clear cell neoplasm that appears mesenchymal in nature. The affected patients included 3 men and 2 women ranging in age from 38 to 70 (median, 45 years). All the lesions occurred on the lower limb. Clinically described as smooth cutaneous nodules, size ranged from 0.5 to 2.5 cm in greatest dimension and the lesions were present from weeks to 5 years prior to excision. Situated in the reticular dermis, the tumors usually extended to involve the subcutis with sparing of the papillary dermis. The tumors were composed of large optically clear cells with vesicular nuclei. The lesions entrapped adnexal structures and thin dermal collagen fibers. Mitoses were rare (less than 1 per 25 hpf). A single case showed more pleomorphic nuclei as well as quite frequent mitoses and was considered of uncertain biologic potential. Immunohistochemistry revealed reactivity only for NKI-C3 (5/5 cases), CD68 (2/5 cases), and vimentin (2/3 cases); melanocytic, epithelial, and lymphoidmarkerswere uniformly negative. All five lesions were locally excised; the more pleomorphic and mitotically active lesion was widely reexcised and given subsequent radiation therapy. In follow-up ranging from 1.5 to 11 years (median, 5.5 years), none of these lesions has recurred. These tumors appear to be mesenchymal in nature, but their precise line of differentiation is unknown. Recognition of these lesions is important to avoid confusion with better-known malignant neoplasms.
文摘Severe lipodystrophy is characterized by diminished adipose tissue and hypolep tinemia, leading to ectopic triglyceride accumulation.In the liver, this is asso ciated with steatosis,potentially leading to nonalcoholic steatohepatitis (NASH) . We investigated the prevalence of NASH and the effect of leptin replacement in these patients. Ten patients with either generalized lipody strophy (8 patients ) or Dunnigan’s partial lipody strophy(2 patients) were included in this analys is. Paired liver biopsy specimens were obtained at baseline and after treatment with recombinant methionyl human leptin (r-metHuLeptin), mean duration 6.6 mont hs. The extents of portal and parenchymal in-flammation, steatosis, ballooning, presence of Mallory bodies,and fibrosis in liver biopsy specimens were scored u sing a previously validated system developed to assess NASH activity.Histologica l disease activity was defined as the sum of ballooning, steatosis, and parenchy mal inflammation scores. We concurrently tested serum triglycerides and aminotra nsferases and estimations of liver volume and fat content by magnetic resonance imaging. Eight of 10 patients met histological criteria for NASH at baseline. Af ter treatment with r-metHuLeptin,repeat histological examinations showed signif icant improvements in steatosis (P = .006) and ballooning injury (P = .005),with a reduction of mean NASH activity by 60%(P = .002).Fibrosis was unchanged. Significant re ductions were seen in mean seru- m triglycerides (1206→226mg/dL, P = .002),glucose(220→144 mg/dL, P = .02), i nsulin (46.4→24.8 μIU/mL, P =.004), ALT (54→24U/L, P = .02), AST (47→22 U/L, P = .046),liver volume (3209→2391 cm3, P = .007), and liver fat content(31→11 %, P = .006). In conclusion, r-metHuLeptin therapy significantly reduced trigl ycerides, transaminases, hepatom- egaly,and liver fat content. These reductions were associated with significant reductions in steatosis and the hepatocellular ballooning injury seen in NASH.
