correspondence 2625 hepatocellular carcinoma, and (in this unusual case), receipt of an "isograft" after a previous bone marrow transplantation. As our understanding of the immune response improves, the potential for developing "operational tolerance" may widen the recipient's benefits from living donor transplantation. 1. Gane EJ, Portmann BC, Naoumov NV, et al. Long-term outcome of hepatitis C infection after liver transplantation. N Engl J Med 1996;334:815-20. 2. Sanchez-Fueyo A, Restrepo JC, Quinto L, et al. Impact of the recurrence of hepatitis C virus infection after liver transplantation on the long-term viability of the graft. Transplantation 2002;73:56-63. 3. Prieto M, Berenguer M, Rayon JM, et al. High incidence of allograft cirrhosis in hepatitis C virus genotype 1b infection following transplantation: relationship with rejection episodes. Hepatology 1999;29:250-6. 4. Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR. The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology 2002;122:889-96. 5. Berenguer M. Host and donor risk factors before and after liver transplantation that impact HCV recurrence. Liver Transpl 2003;9: S44-S47.

No abstract

Adrenocortical carcinoma is a rare but highly malignant neoplasm with still limited treatment options. Epidermal growth factor receptor (EGFR) has been shown to be overexpressed in many solid tumors, but its expression in adrenocortical carcinoma has been studied only in a limited number of cases. Therefore, we analyzed the expression of EGFR in 169 adrenocortical carcinoma samples and compared it with 31 adrenocortical adenomas. Additionally, in 30 cases of adrenocortical carcinoma, exons 18-21 of the EGFR gene were cloned and sequenced. EGFR expression was found in 128 of 169 adrenocortical carcinoma samples (76%), and in 60 of these samples ( ¼ 36%) strong membrane staining was detected. However, there was no significant correlation with clinical outcome. In addition, all 30 sequenced cases revealed unmutated EGFR genes. In contrast, only 1 out of 31 adrenocortical adenomas weakly expressed the EGFR (3%). In summary, EGFR was overexpressed in more than three-quarters of adrenocortical carcinoma cases of this series. However, no mutations of the EGFR gene were found and EGFR expression was not of prognostic relevance. As EGFR is hardly expressed in adrenocortical adenomas, our results suggest that its expression in adrenocortical tumors indicates a malignant phenotype, which may be used in the differential diagnosis between adrenocortical adenomas and carcinomas.

Rare occurrence of IgVH gene translocations and restricted IgVH gene repertoire in ocular MALT-type lymphomaFISH studies on 37 ocular MALT-type lymphomas yielded chromosomal translocations affecting MALT1 and BCL10 in 1 case each, no evidence for a break in the FOXP1 locus, and trisomy 3 in 14 out of 34 cases (41%). Three out of 8 cases analyzed used the highly mutated VH3-23 gene and showed ongoing somatic hypermutations. Haematologica 2008 Feb; 93:(2) 319-320. DOI: 10.3324/haematol.11950 Extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue type (eMZBCL) arise, amongst other organs, in the ocular adnexa. Interestingly, frequency and distribution of genetic alterations, use and specifity of immunoglobulin heavy chain variable region (IgVH) genes, and the association with chronic inflammatory processes vary remarkably between affected organs and geographic regions.2 In ocular adnexal eMZBCL, some data suggest an association with chronic Chlamydia psittaci infection. 3We studied 37 biopsies of ocular adnexal eMZBCL diagnosed between 1999 and 2004 at the Reference Centre for Lymph Node Pathology in Würzburg, Germany. Cases were classified according to WHO criteria.1 For fluorescence in situ hybridization (FISH) studies, representative tissue cores from each case were assembled into a tissue microarray (TMA). FISH analyses for the detection of chromosomal breaks in BCL10 (from DakoCytomation, Germany), IgH and MALT1 loci and for trisomy 3 (all Abbott, Germany) as well as for FOXP1 4 were performed. PCR was successfully used to amplify rearranged IgVH genes in 8 cases. After subcloning, the mutational status of IgVH gene was determined using a 2% somatic mutation cut-off and compared with the corresponding germline sequences. The study was approved by the local ethics committee.Results are summarized in Table 1. FISH studies provided evidence of chromosomal breaks affecting the IGH locus in 3 cases only. In 1 case each, MALT1 and BCL10 were the putative translocation partners. In the third case, no candidate translocation partner was indicated by the FISH results. However, in this case, the BCL10 (Table 1). The VH3 family was used in 6 cases. Remarkably, VH3-23 was used in 3 cases and all of these showed evidence of intraclonal heterogeneity (ongoing mutations), whereas the remaining 5 cases carried a high load of somatic mutations without detectable intraclonal heterogeneity. Neither of the 2 cases with a detectable IgVH translocation (cases 35 and 37) showed ongoing mutations. © F e r r a t a S t o r t i F o u n d a t i o nThese results shed further light on the varying genetic and immunological features in ocular MALT-type lymphomas. In contrast to Streubel et al.2 who reported the presence of the t(14;18) involving MALT1 in 24% of ocular MALT-type lymphomas, we could only detect a single case (1 out of 34 cases, 3%) carrying this genetic alteration, whereas the frequency of trisomy 3 in our series was almost identical to the published data.2 In addition, the revelation of a prefere...

Follicular lymphoma (FL) constitutes the neoplastic equivalent of germinal center B-cells. Like its physiological counterpart, FL grows in (atypical) follicular structures, the formation of which is as yet poorly understood. Recent data indicate that in early tumour stages, neoplastic FL cells home to and colonise reactive germinal centers. Laser microdissection (LMD) and micromanipulation techniques now allow for the molecular genetic analysis of single cell mutation patterns in FL. The purpose of the present study was the analysis of the sequence and order of somatic mutations in FL, i.e. the influence of the germinal center microenvironment on the clonal evolution in different grades of FL. By generating phylogenetic trees as calculated from tumour cell sequences, the clonal evolution from a putative progenitor cell was elucidated and finally, the tumour cell migration pattern in disease progression was assessed by analyzing biopsies at different time points in relapsed tumours. Four patients suffering from FL were included in the study. A primary FL grade 1 showed clustering of genetically related subclones in distinct follicles. A moderate interfollicular exchange of tumour cells was detected. Three cases of FL grade 2 were found to show decreased subclonal clustering in follicles and an increase in the interfollicular migration. Accumulations of replacement mutations in antigen binding domains (CDR) and silent mutations in non-antigen binding domains (FR), respectively, indicating antigen influence on hypermutation were only found in the case of FL grade 1. Our conclusion is that the microenvironment in germinal centers exercises influence on clonal evolution and tumour cell distribution patterns in FL. With increasing histologic grade during disease progression, a reduced intraclonal diversity and selection of subclones also occurs outside the setting of transformation to high-grade lymphoma. Antigen-dependent hypermutations were only seen in FL grade 1, while in progressed FL, random mutation patterns and a decrease of clonal diversity were found.