Morphometric analysis of hepatocellular nodular lesions in HCV cirrhosis.

We generated a computerized morphometric model to evaluate and quantify the morphological features in large regenerative nodules (LRN), high-grade dysplastic nodules (HGDN) and hepatocellular carcinoma (HCC). Sixteen LRN, 10 HGDN and 16 HCC in HCV-cirrhotic livers were stained with H&E, smooth muscle actin, CD34, CD31 and reticulin to evaluate volume and surface fractions. On H&E stains, the most discriminatory features between LRN, HGDN and HCC were volume fraction and the number of hepatocyte nuclei in unit volume and hepatocyte nuclear/cytoplasmic ratio. On immunohistochemistry, volume fractions of capillarised sinusoids, capillary units and isolated arteries were significantly different among all groups and highest in HCC; surface fraction of reticulin was markedly decreased in HCC. Our morphometric model is an objective method for quantification of the morphological changes of the nodular lesions, and it could be applied to studies involving histological evaluation of the spectrum of nodular lesions arising in the cirrhotic liver.

Morphometric analysis of dysplastic nodules in hepatitis C virus-related liver cirrhosis: comparison with cirrhotic and large regenerative nodules.

OBJECTIVE: To apply a computerized morphometric model to evaluate and quantify the morphologic features, including hepatic progenitor cells, in large regenerative nodules (LRN) and high grade dysplastic nodules (DN) in hepatitis C virus (HCV)-related cirrhosis. STUDY DESIGN: Thirty-two cirrhotic nodules; 10 LRN; and 8 DN were identified in cirrhotic livers with HCV-related cirrhosis removed at transplantation. All specimens were stained for routine diagnosis with hematoxylin-eosin and immunohistochemically for CD31, CD34, cytokeratin 7 (CK7) and reticulin. We determined by a computerized morphometric model on hematoxylin-eosin slices the volume fractions occupied by hepatocyte nuclei and cytoplasm, sinusoids, portal triads, fibrosis and centrilobular veins. We also investigated volume fraction of hepatocytes expressing CK7, and volume fractions of capillary units and of sinusoid capillarization expressing CD31 and CD34, respectively, and surface fraction of reticulin. RESULTS: Compared to LRN, DN showed higher volume fraction of hepatocyte nuclei, higher number of hepatocytes in unit volume, higher nuclear/cytoplasmic ratio, higher volume fractions of capillarized sinusoids, capillary units and CK7 positive hepatocytes and lower mean hepatocyte volume and surface reticulin fraction. CONCLUSION: Our morphometric model is an objective method of quantification of the morphologic changes of LRN and DN, including the hepatic progenitor compartment.

Human visceral fat in different anthropometric patterns and in diabetes: a morphometric study.

OBJECTIVE: To evaluate the cellularity of the adipose tissue and the size of adipocytes in unrelated adults and investigate any correlation between morphometric and anthropometric or clinical variables. STUDY DESIGN: Surgical biopsies of visceral fat (epiploic appendixes) were obtained from the large intestines of 56 patients. A morphometric model was applied to obtain the volume fraction occupied by adipocytes and the size distribution and number in unit volume of the adipocytes. Body mass index (BMI), lifestyle factors, significant body weight variations and clinical disorders (diabetes) were evaluated. RESULTS: Volume fraction occupied by adipocytes and size distribution and number in unit volume of the adipocytes have an opposite trend in underweight, normal and overweight subjects and subjects with referred gain, normal, or loss weight. Regression analysis reveals a significant negative linear relationship between number in unit volume of the adipocytes and BMI and body weight variations. The group of normal patients is characterized by a unimodal size distribution of adipocytes when compared with the group affected by diabetes, who show a likely plurimodal pattern. CONCLUSION: Our observations seem to confirm the hypothesis that hypertrophy, rather than adipose tissue hyperplasia, plays a fundamental role when significant ponderal variations occur in adult life.

Soft tissue facial angles in individuals with ectodermal dysplasia: A three-dimensional noninvasive study.

OBJECTIVE: To supply quantitative information about the facial soft tissues of patients with hypohidrotic ectodermal dysplasia. DESIGN: Prospective assessment. SETTING: National meetings of hypohidrotic ectodermal dysplasia patients and families. PATIENTS AND MAIN OUTCOME MEASURES: Facial and mandibular corpus convexities in the horizontal plane; facial convexity in the sagittal plane; interlabial, naso-labial, nasal convexity, and left and right soft tissue gonial angles were calculated from the three-dimensional coordinates of 11 soft tissue facial landmarks obtained in 18 male and 17 female hypohidrotic ectodermal dysplasia patients aged 3 to 41 years and in 504 reference healthy individuals. In addition, z-scores were computed and the patients were grouped by cluster analysis. RESULTS: Male and female z-scores did not differ. In the pooled group, facial convexities in the horizontal and sagittal planes were significantly (Student's t, p < .01) increased (flatter) in hypohidrotic ectodermal dysplasia patients, compared with normal controls. The naso-labial angle was significantly reduced (more acute). Upper and lower facial convexity and mandibular corpus convexity in the horizontal plane deviated less from the norm with increasing age. Facial convexity in the horizontal and sagittal planes, soft tissue gonial angles, and naso-labial and interlabial angles deviated less from the norm with increasing number of teeth present in the mouth. Cluster analysis identified three homogeneous groups, all characterized by a peculiar facial phenotype. Modifications in facial convexity and gonial and interlabial angles differentiated each cluster. CONCLUSIONS: Patients with hypohidrotic ectodermal dysplasia had flatter faces in the horizontal and sagittal planes than normal controls had. Cluster analysis revealed patterned differences in facial phenotype.

Computerized morphometry of the cirrhotic liver: comparative analysis in primary biliary cirrhosis, alcoholic cirrhosis, and posthepatitic cirrhosis.

Fibrosis and nodular regeneration are the hallmarks of liver cirrhosis. To assess the degree of fibrosis and the severity of the structural changes affecting parenchymal and extraparenchymal components in liver cirrhosis, a computerized morphometric model has been applied to liver specimens from patients undergoing liver transplantation for primary biliary cirrhosis, posthepatitic and alcoholic cirrhosis. Fifty-eight hepatectomy specimens from patients undergoing liver transplantation for cirrhosis were analyzed: 17 alcoholic, 28 posthepatitic (HBV-related and HCV-related cirrhosis), and 13 primary biliary cirrhoses. Liver specimens were fixed in 10% neutral-buffered formalin and embedded in paraffin. Sections were stained with chromotrope-aniline blue method and monoclonal antibodies against cytokeratin 7 and CD31. Volume fractions of parenchymal compartment and fibrosis were stereologically determined on the specimens stained with chromotrope-aniline blue method. Volume fractions of portal bile ducts, proliferated bile ductules, and hepatocytes with biliary metaplasia were measured on cytokeratin 7 stains, while volume fractions of capillary units have been evaluated on CD31 staining. Volume fraction of fibrosis was higher in primary biliary cirrhosis than in the other disease-induced cirrhosis. The main differences were related to immunohistochemical staining. Volume fraction of hepatocytes with biliary metaplasia was higher in HCV-related cirrhosis, whereas volume fractions of biliary structures were more prominent in HBV-related cirrhosis. Primary biliary cirrhosis was characterized by a reduced number of bile ducts and by a wider expression of cytokeratin 7 into periportal hepatocytes. Capillary units were more prominent in primary biliary cirrhosis than alcoholic and posthepatitic cirrhosis. Our computerized morphometric model well describes and quantifies the morphological alterations of the liver and it could represent an adjunctive tool to evaluate the degree of dysplastic phenomena involving parenchymal and extraparenchymal compartments.