Search

Sporadic Burkitt lymphoma (sBL) can be delineated from diffuse large B-cell lymphoma (DLBCL) by a very homogeneous mRNA expression signature. However, it remained unclear whether all three BL variants-sBL, endemic BL (eBL) and human immunodeficiency virus-associated BL (HIV-BL)-represent a uniform biological entity despite their differences in geographical occurrence, association with immunodeficiency and/or incidence of Epstein-Barr virus (EBV) infection. To address this issue, we generated micro RNA (miRNA) profiles from 18 eBL, 31 sBL and 15 HIV-BL cases. In addition, we analyzed the miRNA expression of 86 DLBCL to determine whether miRNA profiles recapitulate the molecular differences between BL and DLBCL evidenced by mRNA profiling. A signature of 38 miRNAs containing MYC regulated and nuclear factor-kB pathway-associated miRNAs was obtained that differentiated BL from DLBCL. The miRNA profiles of sBL and eBL displayed only six differentially expressed miRNAs, whereas HIV and EBV infection had no impact on the miRNA profile of BL. In conclusion, miRNA profiling confirms that BL and DLBCL represent distinct lymphoma categories and demonstrates that the three BL variants are representatives of the same biological entity with only marginal miRNA expression differences between eBL and sBL. [ABSTRACT FROM AUTHOR]

It appears more and more clear that retinoblastoma (RB) family of proteins represents key molecules in tumour suppression. This family consists of pRb/p105, p107 and pRb2/p130, which participate in a gene regulatory network that governs the cellular response to antimitogenic signals, and whose deregulation constitutes one of the hallmarks of cancer. Irrespective of their structural and biochemical similarities, RB proteins carry out different functional tasks. The expression of RB gene family in the reactive lymphoid tissues again confirms the different role of each member in cell cycle control and differentiation of normal cells. These different functional properties appear to be maintained in tumours lymphoid tissues, where alterations of the RB/p105 gene appear to be relatively rare. In this review, we will summarize the current knowledge about the role of the RB proteins in reactive and neoplastic lymphoid tissue.Oncogene (2006) 25, 5309–5314. doi:10.1038/sj.onc.1209619 [ABSTRACT FROM AUTHOR]

Leoncini L, Delsol G, Gascoyne R D, Harris N L, Pileri S A, Piris M A&Stein H(2005)Histopathology46,241–255Aggressive B-cell lymphomas: a review based on the workshop of the XI Meeting of the European Association for HaematopathologyThe generic term aggressive B-cell lymphoma includes a variety of entities, each with particular diagnostic and therapeutic issues. To define these entities better and to help confront such issues, a workshop was organized by the European Association of Haematopathology (EAHP) and the Society of Haematology during the XI Meeting of the EAHP, held in Italy in May 2002. Participants were asked to submit cases under various categories and all cases submitted were examined and reviewed by the panel members. The panel's diagnoses formed the basis for discussion at the workshop and a limited number of cases were selected to be presented in more detail and discussed during the workshop. After the workshop the panel met again to discuss the outcome, summarized in this report, which describes the panel's proposals regarding diagnostic criteria, terminology, the definition of new entities and evaluation of biological differential and new prognostic parameters. [ABSTRACT FROM AUTHOR]

Background: The Epstein-Barr virus (EBV) causes various B-cell lymphomas and epithelial malignancies, including gastric cancer (GC) at frequencies ranging from 5 to 10% in adenocarcinomas (ADK) to 80% in GC with lymphoid stroma (GCLS). Using high-sensitivity methods, we recently detected EBV traces in a large cohort of EBV-negative B-cell lymphomas, suggesting a hit-and-run mechanism. Methods: Here, we used routine and higher-sensitivity methods [droplet digital PCR (ddPCR) for EBV segments on microdissected tumour cells and RNAscope for EBNA1 mRNA] to assess EBV infection in a cohort of 40 GCs (28 ADK and 12 GCLS). Results: ddPCR documented the presence of EBV nucleic acids in rare tumour cells of several cases conventionally classified as EBV-negative (ADK, 8/26; GCLS, 6/7). Similarly, RNAscope confirmed EBNA1 expression in rare tumour cells (ADK, 4/26; GCLS, 3/7). Finally, since EBV induces epigenetic changes that are heritable and retained after complete loss of the virus from the host cell, we studied the methylation pattern of EBV-specifically methylated genes (Timp2, Eya1) as a mark of previous EBV infection. Cases with EBV traces showed a considerable level of methylation in Timp2 and Eya1 genes that was similar to that observed in EBER-ISH positive cases and greater than cases not featuring any EBV traces. Conclusions: These findings suggest that: (a) EBV may contribute to gastric pathogenesis more widely than currently acknowledged and (b) indicate the methylation changes as a mechanistic framework for how EBV can act in a hit-and-run manner. Finally, we found that the viral state was of prognostic significance in univariate and multivariate analyses. [ABSTRACT FROM AUTHOR]

Background: In 2000, an Italian non-governmental organisation (NGO) began a 9-year project to establish a surgical pathology laboratory at the Bugando Medical Centre (BMC) in Mwanza, Tanzania, a country with a low Human Development Index (HDI), and as of 2009, the laboratory was operating autonomously. The present survey aims to evaluate the reproducibility of histological and cytological diagnoses assigned in the laboratory's early years of autonomous activity. We selected a random sample of 196 histological and cytological diagnoses issued in 2010-2011 at the BMC surgical pathology laboratory. The corresponding samples were sent to Italy for review by Italian senior pathologists, who were blinded to the local results. Samples were classified into four diagnostic categories: malignant, benign, inflammatory, and suspicious. The two-observer kappa-statistic for categorised (qualitative) data was then calculated to measure diagnostic concordance between the local Tanzanian pathologists and Italian senior pathologists. The k-Cohen was calculated for concordance in the overall study sample. Concordance and discordance rates were also stratified by subset: general adult, paediatric/adolescent, and lymphoproliferative histopathological diagnoses; fluid and fine needle aspiration (FNA) cytological diagnoses; and PAP tests. Discordance was also categorised by the corresponding hypothetical clinical implications: high, intermediate, and not significant. Results: Overall concordance was 85.2% (167 of 196 diagnoses), with a k-Cohen of 0.7691 (P = 0.0000). Very high concordance was observed in the subsets of adult general pathological diagnoses (90%) and paediatric/adolescent pathological diagnoses (91.18%). Concordance in the subset of PAP tests was 75%, and for fluid/FNA cytological diagnoses it was 56.52%. Concordance among 12 histological subtypes of lymphoma was 75.86%, with substantial discordance observed in the diagnosis of Burkitt lymphoma (five cases diagnosed by Italian pathologists versus 2 by local pathologists). The overall proportion of discordance with high hypothetical clinical implications was 6.1% (12 diagnoses). Conclusion: This blind review of diagnoses assigned in Tanzania, a country with low HDI, and in Italy, a country with a very high HDI, seemed to be a sensitive and effective method to identify areas of potential error and may represent a reference point for future, more detailed quality control processes or audits of surgical pathology services located in limited-resource regions. [ABSTRACT FROM AUTHOR]

Background: Sub-Sahara Africa hosts up to 71 % of all HIV infected people in the world. With this high incidence of Human immunodeficiency virus ( HIV) comes the burden of co-morbidities such as malignant and premalignant lesions. Aids defining malignancies have been listed as Kaposi's sarcoma, Non-Hodgkin's lymphoma and invasive squamous cell carcinoma of the cervix. People with HIV/AIDS(PLWAS) have a higher risk of developing these neoplasms than the rest of the population. The pathogenesis of these neoplasms in people with HIV has been linked to immune suppression, persistent antigenic stimulation and cytokine dysregulation. Current study analyzes and presents the patterns and trends in the presentation of HIV related malignancies in patients diagnosed through histopathology at Kenyatta National Hospital. Aim: To describe the patterns of AIDS- defining and non-AIDS- defining malignancies and premalignant lesions 10 years pre- and post HAART period at Kenyatta National hospital, Kenya. Methods and techniques: This was a hospital based descriptive cross sectional study. The Formalin fixed paraffin embedded (FFPE) blocks and histological reports of patients diagnosed between 2000 and 2011 were traced from archives. The patients' demographic data and clinical presentation was entered in an excel spreadsheet and the diagnosis and coding confirmed by a histopathologist. The data was then cleaned and analyzed using SSPS version 17.0 Ink. Results: A total of 173 lesions were reviewed and analyzed. Of these 118 (68 %) were from females and 55 from males (32 %). The male to female ratio was 1:2. The age range was from two to 56 years with a median of 36 years. Kaposi sarcoma is the leading AIDS defining malignancy in Kenya while invasive squamous cell carcinoma of the conjunctiva is the leading non-AIDS defining malignancy. This is closely followed by invasive squamous cell carcinoma of the cervix and NHL. Conclusion: Kaposi sarcoma is the leading AIDS associated neoplasm in Kenya. Physicians and caretakers managing and following up on HIV/AIDS patients should look out for Kaposi sarcoma as a form of IRIS following the institution of HAART in all HIV/AIDS patients. The incidence of invasive squamous cell carcinoma of the conjunctiva is increasing in PLWAS in Kenya. There is therefore a need to introduce early screening programs for squamous intraepithelial neoplasm of the conjunctiva in HIV/AIDS patients. [ABSTRACT FROM AUTHOR]

MicroRNAs are important regulators of gene expression in normal development and disease. miR-9 is overexpressed in several cancer forms, including brain tumours, hepatocellular carcinomas, breast cancer and Hodgkin lymphoma (HL). Here we demonstrated a relevance for miR-9 in HL pathogenesis and identified two new targets Dicer1 and HuR. HL is characterized by a massive infiltration of immune cells and fibroblasts in the tumour, whereas malignant cells represent only 1% of the tumour mass. These infiltrates provide important survival and growth signals to the tumour cells, and several lines of evidence indicate that they are essential for the persistence of HL. We show that inhibition of miR-9 leads to derepression of DICER and HuR, which in turn results in a decrease in cytokine production by HL cells followed by an impaired ability to attract normal inflammatory cells. Finally, inhibition of miR-9 by a systemically delivered antimiR-9 in a xenograft model of HL increases the protein levels of HuR and DICER1 and results in decreased tumour outgrowth, confirming that miR-9 actively participates in HL pathogenesis and points to miR-9 as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Daily administration of 2-chlorodeoxyadenosine (Cladribine, CDA) is a standard treatment for hairy cell leukemia, but may cause severe neutropenia and neutropenic fever. This trial compared toxicity and efficacy of weekly versus daily CDA administration. One hundred patients were randomized to receive standard (CDA 0.14 mg/kg/day day 1-5 [Arm A]) or experimental treatment (CDA 0.14 mg/kg/day once weekly for 5 weeks [Arm B]). The primary endpoint was average leukocyte count within 6 weeks from randomization. Secondary endpoints included response rates, other acute hematotoxicity, acute infection rate, hospital admission, remission duration, event-free, and overall survival. There was no significant difference in average leukocyte count. Response rate (complete + partial remission) at week 10 was 78% (95% confidence interval (CI) 64-88%) in Arm A and 68% (95% CI 54-80%) in Arm B (p = 0.13). Best response rates during follow-up were identical (86%) in both arms. No significant difference was found in the rate of grade 3+4 leukocytopenia (94%vs. 84%), grade 3+4 neutropenia (90%vs. 80%), acute infection (44%vs. 40%), hospitalization (38%vs. 34%), and erythrocyte support (22%vs. 30%) within 10 weeks. Overall, these findings indicate that there are no apparent advantages in toxicity and efficacy by giving CDA weekly rather than daily. [ABSTRACT FROM AUTHOR]

Classification and proper treatment of extranodal lymphoma is hindered by the diversity of lymphoma types and the relative rarity of many of these tumour types. In order to review controversial issues in extranodal lymphoma diagnosis, a joint Workshop of the European Haematopathology Association (EAHP) and the Society for Hematopathology (SH) was held, where 99 selected cases were reviewed and discussed. This Workshop summary is focused on the most controversial aspect of cutaneous B-cell lymphoma, other extranodal B-cell lymphomas, plasmablastic lymphoma and anaplastic large-cell lymphoma in extranodal sites, and makes practical recommendations about diagnosis and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Schuerfeld K, Lazzi S, de Santi M M, Gozzetti A, Leoncini L & Pileri S A (2003) Histopathology 43, 491–494 Cytokeratin-positive interstitial cell neoplasm: a case report and classification issues Tumours of dendritic/accessory cell origin are rare neoplasms arising in lymph nodes. Among these, tumours derived from cytokeratin-positive interstitial reticulum cells (CIRCs), a subset of fibroblastic reticulum cells, are reported even less frequently. The International Lymphoma Study Group (ILSG) has recently proposed a classification for tumours of histiocytes and accessory dendritic cells in which CIRC tumours are not included. We report a case of a CIRC tumour arising in a submandibular lymph node of a 66-year-old male. The neoplasm was composed of spindle cells with elongated or round nuclei, prominent nucleoli and abundant cytoplasm. These cells were arranged in a diffuse fascicular and vaguely whorled pattern. The tumour cells stained diffusely for S100, vimentin, desmin, lysozyme, and focally for CD68 and cytokeratins 7, 8, 18, CK-AE1 and CK-pool. Electron microscopy was performed for further evaluation on samples taken from the paraffin block; this revealed cytoplasmic projections and rudimentary cell junctions. Histopathologist should be aware of the existence of tumours deriving from CIRCs, as these cases may be misdiagnosed as metastatic carcinoma. Careful clinical and pathological evaluation is necessary to exclude this possibility. [ABSTRACT FROM AUTHOR]

Since the emergence of the HIV pandemic, a close association between HIV infection and the development of a selected group of cancers has been acknowledged. The introduction of highly active antiretroviral therapy, however, has had a dramatic impact on the incidences of several AIDS-defining malignancies. This suggests the possibility of a direct and indirect role of HIV in HIV-related tumor genesis. The aim of this paper is to review the pathology of AIDS-related malignancies, taking into account the pathogenetic mechanisms and their potential for improving the treatment of these tumors.Oncogene (2003) 22, 6639-6645. doi:10.1038/sj.onc.1206815 [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is the commonest type of lymphoid tumour world-wide. This category was included both in the REAL and WHO Classification aiming to lump together all malignant lymphomas characterized by the large size of the neoplastic cells, B-cell derivation, aggressive clinical presentation, and the need for highly effective chemotherapy regimens. These tumours are detected as primary or secondary forms both at the nodal and extranodal levels, in immunocompetent hosts as well as in patients with different types of immunosuppression. They display a significant variability in terms of cell morphology and clinical findings, which justifies the identification of variants and subtypes. Among the latter, the primary mediastinal one does actually correspond to a distinct clinicopathological entity. Immunophenotypic, tissue microarray and molecular studies underline the extreme heterogeneity of DLBCLs and suggest a subclassification of the tumour, based on the identification of different pathogenic pathways, which might have much greater relevance than pure morphology for precise prognostic previsions and adoption of ad hoc therapies. The more recent acquisitions on the pathobiology of DLBCLs are reviewed in the light of the authors' experience, aiming to contribute to the existing debate on the topic. [ABSTRACT FROM AUTHOR]

As part of an extensive multi-institutional DIANAIDS-HIV-HPV-SIL project run in Italy (coordinated by ISS), the present study compares the performance (sensitivity, specificity, agreement) of routine cervical smear cytology with that of colposcopy in the detection of histologically-confirmed CIN lesions in 37 HIV-positive and 21 HIV-negative women, belonging to the DIANAIDS cohort of 459 women. All women were subjected to a cervical smear, colposcopy and biopsy, making possible the pairwise comparison of these techniques. In the whole series of HIV-positive and HIV-negative women, cytology had a sensitivity of 86.9% and specificity of 83.3%, the sensitivity of grade 2 abnormality on colposcopy against histology being 82.6% and specificity, 33.3%. No statistically significant difference was observed in the performance of Pap smears between the HIV-positive and HIV-negative women. The sensitivity of cytology was 89.7% vs 82.4% and the specificity, 75% vs 100%. For colposcopy, the sensitivity was 79.3% vs 88.2% and the specificity, 75% vs 50%. These data suggest that cervical Pap smear cytology is a highly sensitive and specific diagnostic tool in the clinical monitoring of lower genital tract pathology in HIV-positive women. Colposcopy, on the other hand, proved to be a somewhat less accurate diagnostic tool in these women. [ABSTRACT FROM AUTHOR]