Gopesh Srivastava

Expression of p53 and its relationship with human papillomavirus in penile carcinomas.

We studied p53 over-expression in a series of 42 primary penile carcinomas (seven verrucous carcinomas, 14 well-differentiated, 15 moderately-differentiated and six poorly-differentiated squamous cell carcinomas) from Chinese patients using the p53 protein specific mouse monoclonal antibody DO-7 on paraffin sections. p53 protein was detected in 40% (17 cases) of the tumours. The p53 staining was not observed in the penile warts (n = 6) and verrucous carcinomas (n = 7). Positive p53 staining was identified only in the less differentiated tumour cells in the periphery of the tumour cell nests in all the cases. The non-invasive dysplastic epithelium next to the tumours could also be positive for p53 protein (three out of 10 cases in which the dysplastic epithelium adjacent to the tumour was adequately sampled). Furthermore, 100% of the human papillomavirus (HPV)-positive cases showed positive p53 staining. It is concluded that p53 over-expression is present in penile squamous cell carcinomas and adjacent non-invasive tumour cells. An inverse correlation between HPV and p53 gene mutation is not observed in penile cancers.

Absence of Epstein-Barr virus in penile carcinoma. A study of 42 cases using in situ hybridization.

Background. The relationship between Epstein–Barr virus (EBV) and carcinomas of the lower female genital tract has been the focus of some studies in recent years. However, the association between EBV and penile carcinoma never has been investigated. The aim of this study was to identify the possible role of EBV in penile carcinoma of Chinese patients.

BCL10 somatic mutations rarely occur in gastric lymphoma:: detection of high frequency of polymorphisms in BCL10 coding region

The BCL10 gene, recently isolated due to its involvement in the t(1;14)(p22;q32) of mucosa-associated lymphoid tissue B cell non-Hodgkin lymphoma (MALToma), was shown to have frequent somatic mutations and short deletions within the coding region in MALToma and a variety of other lymphomas and solid tumors. These observations have been recently questioned. In this study, we examined BCL10 gene mutations by direct sequencing of the entire coding region of the BCL10 gene, amplified from paired normal and tumor genomic DNAs, as well as tumor cDNAs, in 23 cases of primary gastric B cell non-Hodgkin lymphomas, comprising of 6 cases of MALToma and 17 cases of diffuse large cell (DLC) lymphoma. Heterozygosity due to three types of known polymorphisms in codon 5 (17.3%), codon 8 (21.7%), and codon 213 (8.6%) were observed in both normal germline DNA and tumor DNAs and tumor cDNAs in individual cases. In one case (4.3%) G/C heterozygosity in codon 8 in normal germline DNA was reduced to homozygosity (LOH) in tumor DNA and cDNA. Mutations inactivating BCL10 gene product function were not found in any of these cases. Moreover, post-transcriptional alterations were not indicated by abnormalities in BCL10 mRNA sequence in tumor cDNAs in these gastric lymphoma cases. Our results show that somatic mutations in the BCL10 gene rarely occur in gastric lymphoma and indicate that this gene is unlikely to be of pathogenetic significance in the majority of gastric lymphomas.

A unique case of B cell lymphoma relapsing as CD4/CD56 blastic neoplasm

A patient with history of B cell lymphoma treated with rituximab-based chemotherapy relapsed with a blastic CD4+/CD56+ neoplasm that was negative for CD20, CD79a and CD3. The relapse morphology and immunophenotyping were unusual and plasmacytoid dendritic cell (PDC) tumor enters the differential diagnosis. However, expressions of Oct-2 and CD10 in the relapse tumor were both more compatible with B cell than PDC lineage. Molecular investigations showed clonal rearrangements for both immunoglobulin heavy chain (IgH) and T cell receptor (TCR) γ chain gene by polymerase chain reaction (PCR). Furthermore, a clonal relationship with the original B cell lymphoma was demonstrated for all PCR products. Our case illustrated the potential pitfalls and ambiguity of lineage classification based on morphology and immunophenotyping alone, especially for rare and poorly defined entities.

Post-rituximab Burkitt transformation of PTLD: loss of CD20 expression accompanied by a switch in light-chain expression.

Dear Editor, A 53-year-old woman, with cadaveric liver transplant for primary biliary cirrhosis 7 years ago, presented with generalized lymphadenopathy (Fig. 1a). A biopsy showed post-transplantation lymphoproliferative disease (PTLD; Fig. 1b). The lymphoma cells expressed CD20, CD79a, κ-chain, and Epstein Barr virus-encoded RNA (EBER). Her bone marrow examination was normal but a serum immunoelectrophoresis showed a monoclonal protein (IgGλ 8.2 g/l). Cyclosporin was stopped, and she was treated with R-CEOP×6 (rituximab, cyclophosphamide, epirubicin, vincristine, and prednisolone). This was followed by acute liver rejection, requiring tacrolimus, prednisolone, and mycophenolate mofetil treatment. A remission lasted for 4 years, with undetectable circulating EBV-DNA and monoclonal protein. However, she relapsed with fever, renal shutdown, and hepatosplenomegaly (Fig. 1c). A marrow aspirate showed sheets of Burkitt-like cells (Fig. 1d), expressing CD19, CD22, CD23, EBER, and λ-chain, but not CD10, CD20, CD34, and FMC-7. There was spontaneous tumor lysis (lactate dehydrogenase 4,760 IU/ml, normal 200–360; urate 1,120 mmol/l, normal 160–380), accompanied by an upsurge in circulating EBVDNA and a new monoclonal band (IgMκ 4.6 g/l). She was treated with COMP×4 (cyclophosphamide, vincristine, methotrexate, and prednisolone). Tacrolimus was continued but she died of isolated brain relapse 6 months later. The two EBV-related lesions had different morphology, immunophenotype, light-chain expression, and clinical behavior. Interestingly, in both instances, the PTLD lightchain expression was discordant with the concomitant circulating M-band, although the presence of monoclonal proteins and PTLD are known to be unrelated after most solid transplants [1]. The clinical history is best explained by continued selection among multiple subclones of abnormal EBV-driven B cells since initial presentation. Polymerase chain reaction (PCR) analysis was performed on DNA extracted from the presenting and relapsing lesions (Fig. 1e) using concensus sets of immunoglobulin heavy chain primers covering the three hypervariable complementary determining regions and three conserved framework regions [2]. The existence of different subclones was confirmed by different PCR product sizes in the two samples in two experiments. Since the VH3 PCR products showed two bands for each sample, to resolve the issue of biclonal disease versus bi-allelic arrangement, the products were cloned, sequenced, and aligned as reported (Fig. 1e and f) [3]. All four bands were clonally related (Fig. 1g, left), supporting biclonal evolution within each sample, and divergent evolution from a common occult EBV immortalized ancestral B-cell clone (Fig. 1g, right) [4]. From the clinical point of view, the initial dramatic and sustained clinical response of the disseminated PTLD Ann Hematol (2010) 89:97–99 DOI 10.1007/s00277-009-0769-8