Kakar, Sanjay

Hepatocellular adenomas are rare in children. A large study focused on pediatric patients has not been undertaken. A natural language search was performed at 5 institutions for hepatocellular adenomas in patients younger than 21 years old. Clinical characteristics as well as immunohistochemical staining profile was reviewed and adenomas subtyped per standard classification. Patients were divided into prepubescent and postpubescent age group. Thirty-one patients were included. Eleven (35%) were male and 10 (32%) were prepubescent. Fifteen (54%) of 28 patients with known clinical histories had adenomas associated with a syndrome. The percentage of the different adenoma subtypes was: 16% β-catenin activated, 10% combined inflammatory and β-catenin activated, 29% HFN1α-inactivated, 35% inflammatory, and 10% unclassified subtype by immunohistochemical staining. Interestingly 53% of patients with syndromes were male, while 85% of patients in the nonsyndromic group were female. The total number of β-catenin activated tumors was greater in the syndromic group (5/15, 33%) and prepubescent group (5/10, 50%) than in the nonsyndromic group (2/13, 16%) and postpubescent group (3/21, 14%), P=0.4 and 0.07, respectively. Inflammatory type adenoma was more frequent in the postpubescent (10/21, 48%) than in the prepubescent group (1/10, 10%), P=0.06, trending toward significance. Pediatric patients with hepatocellular adenomas frequently have syndromes, especially in the prepubescent group. In patients with syndromes a greater percentage of adenomas were β-catenin activated. In patients without a known syndrome the distribution of hepatocellular adenoma subtypes appears similar to adults.

Abstract Context. —Impairment of venous outflow manifests as zone 3 sinusoidal dilatation and congestion (SDC) in liver biopsy. However, the finding of SDC is not specific for venous outflow impairment. Objectives. —To determine the specificity of SDC in liver biopsies for venous outflow impairment and to seek an explanation for SDC in patients without clinical or radiologic features of venous outflow impairment. Design. —Liver biopsies from 51 patients with sinusoidal dilatation were reviewed. Biopsies from transplant recipients, patients with cirrhosis, and patients with hepatic neoplasms (primary or metastatic) were not included. Clinical records were reviewed for laboratory tests and final clinicopathologic diagnosis. Results. —Thirty-four patients (66.7%) had confirmed venous outflow impairment. Of the 17 cases (33.3%) without clinical and/or radiologic evidence of venous outflow impairment, vascular causes were present in 5 cases (9.8%; nodular regenerative hyperplasia in 2 cases and portal vein thrombosis, congenital absence of the portal vein, and sickle cell anemia in 1 case each). Systemic inflammatory disorders were identified in 6 patients (11.8%). These included 2 cases of Castleman disease and 1 each of sarcoidosis, Crohn disease, rheumatoid arthritis, and Still disease. Three patients (5.9%) had tumors without direct involvement of the liver (1 case each of Hodgkin lymphoma, renal cell carcinoma, and pancreatic serous pseudopapillary tumor). In the remaining 3 patients, SDC was identified in wedge liver biopsies performed at the time of surgery, including gastric bypass surgery, cholecystectomy, and splenectomy. No other disease association was apparent in these cases. Conclusion. —Sinusoidal dilatation and congestion in liver biopsy is associated with venous outflow impairment in two thirds of the cases. In the absence of clinical and/or radiological evidence of venous outflow, diagnostic considerations include other vascular conditions, such as portal vein insufficiency and nodular regenerative hyperplasia. Sinusoidal dilatation and congestion can also occur in the setting of systemic inflammatory diseases, granulomatous disorders, and neoplasms, as well as in wedge biopsies obtained during abdominal surgery.

Context Several immunohistochemical markers are available to establish the diagnosis of hepatocellular carcinoma. Judicious selection is essential to achieve a reliable diagnosis in limited tissue provided by liver biopsy. Objective To compare the efficacy of 5 hepatocellular markers for the diagnosis of hepatocellular carcinoma across various levels of differentiations. Design Immunohistochemistry for hepatocyte paraffin antigen 1 (Hep Par 1), polyclonal carcinoembryonic antigen (CEA), glypican-3, arginase-1, and bile salt export pump transporter was performed in 79 hepatocellular carcinomas, yielding 93 observations (13 well-differentiated [14%], 41 moderately differentiated [44%], and 39 poorly differentiated [42%] tumors). Results Arginase-1 and Hep Par 1 had the highest sensitivity for well-differentiated hepatocellular carcinoma, whereas arginase-1 and glypican-3 had the highest sensitivity for poorly differentiated hepatocellular carcinoma. When staining of more than 50% of the tumor was considered a positive result, arginase-1 remained the most sensitive marker for all differentiations, whereas sensitivity for Hep Par 1 in poorly differentiated hepatocellular carcinoma dropped to 30% and that of glypican-3 in well-differentiated hepatocellular carcinoma was 15%. The addition of Hep Par 1 and/or polyclonal CEA to arginase-1 did not lead to an increase in sensitivity for any differentiation. The combined use of arginase-1 and glypican-3 yielded 100% sensitivity for poorly differentiated hepatocellular carcinoma. Conclusion Arginase-1 was the most sensitive marker in all differentiations of hepatocellular carcinoma. Glypican-3 had high sensitivity for poorly differentiated cases and its combined use with arginase-1 enabled identification of nearly all cases of poorly differentiated hepatocellular carcinoma. Although bile salt export pump transporter has good overall sensitivity, it has a limited role in establishing hepatocellular differentiation when added to a panel of arginase-1 with either glypican-3 or Hep Par 1.

Abstract Purpose: The genomic instability in colon cancer can be divided into at least two major types, microsatellite instability (MSI) or chromosomal instability (CIN). Although initially felt to be mutually exclusive, recent evidence suggests that there may be overlap between the two. The aim of this study was to identify chromosomal alterations at high resolution in sporadic colon cancers with high-level microsatellite instability (MSI-H) and to compare them to those present in a set of matched microsatellite stable (MSS) tumors. Experimental Design: Array-based comparative genomic hybridization was used to analyze a set of 23 sporadic MSI-H and 23 MSS colon cancers matched for location, gender, stage, and age. The arrays consisted of 2,464 bacterial artificial chromosome clones. Results: MSI and MSS colon cancers differed significantly with respect to frequency and type of chromosomal alterations. The median fraction of genome altered was lower among MSI-H tumors than MSS tumors (2.8% versus 30.7%, P = 0.00006). However, the MSI-H tumors displayed a range of genomic alterations, from the absence of detectable alterations to extensive alterations. Frequent alterations in MSI-H tumors included gains of chromosomes 8, 12, and 13, and loss of 15q14. In contrast, the most frequent alterations in MSS tumors were gains of 7, 13, 8q, and 20, and losses of 8p, 17p, and 18. A small, previously uncharacterized, genomic deletion on 16p13.2, found in 35% of MSI-H and 21% of MSS tumors, was confirmed by fluorescence in situ hybridization. Conclusion: MSI and CIN are not mutually exclusive forms of genomic instability in sporadic colon cancer, with MSI tumors also showing varying degrees of CIN.