[Lymphoma in patients who have undergone organ transplantation: severe and variable clinical presentation]. / Lymfoom bij patiënten na een orgaantransplantatie: ernstig en variabel ziektebeeld.

Two patients presented with post-transplant lymphoproliferative disorder (PTLD). PTLD encompasses a broad range ofoften malignant proliferations of lymphoid tissue arising in the immunocompromised host after transplantation. The first patient, a 62-year-old woman, received a bilateral lung transplant due to end-stage emphysema and was diagnosed with PTLD 27 days after transplantation. Treatment consisted of reduction in immunosuppression and administration of rituximab. The PTLD regressed. The second patient, a 57-year-old woman, presented with a massively disseminated PTLD 12 years after kidney transplantation. Immunosuppression was reduced and rituximab was administered, but no response was observed. Despite salvage chemotherapy, the patient died due to progressive disease. These two cases illustrate the heterogeneous presentation of PTLD. The condition is caused by the proliferation of B lymphocytes infected with Epstein-Barr virus (EBV) that are no longer controlled by EBV-specific cytotoxic T lymphocytes, due to the immunosuppressive medication given to prevent transplant rejection. Regression of the lymphoma may be achieved by reducing the immunosuppression or treating with rituximab, which attacks B lymphocytes.

Cortactin expression predicts poor survival in laryngeal carcinoma.

Amplification of the 11q13 region is one of the most frequent aberrations in squamous cell carcinomas of the head and neck region (HNSCC). Amplification of 11q13 has been shown to correlate with the presence of lymph node metastases and decreased survival. The 11q13.3 amplicon carries numerous genes including cyclin D1 and cortactin. Recently, we reported that FADD becomes overexpressed upon amplification and that FADD protein expression predicts for lymph node positivity and disease-specific mortality. However, the gene within the 11q13.3 amplicon responsible for this correlation is yet to be identified. In this paper, we compared, using immunohistochemical analysis for cyclin D1, FADD and cortactin in a series of 106 laryngeal carcinomas which gene correlates best with lymph node metastases and increased disease-specific mortality. Univariate Cox regression analysis revealed that high expression of cyclin D1 (P=0.016), FADD (P=0.003) and cortactin (P=0.0006) predict for increased risk to disease-specific mortality. Multivariate Cox analysis revealed that only high cortactin expression correlates with disease-specific mortality independent of cyclin D1 and/or FADD. Of genes located in the 11q13 amplicon, cortactin expression is the best predictor for shorter disease-specific survival in late stage laryngeal carcinomas.

Parotid gland biopsy compared with labial biopsy in the diagnosis of patients with primary Sjogren's syndrome.

OBJECTIVE: To assess the value of the parotid biopsy as a diagnostic tool for primary Sjögren's syndrome (pSS), and to compare the parotid biopsy and the labial biopsy with regard to diagnostic value and biopsy-related morbidity. METHODS: In 15 consecutive patients with pSS and 20 controls, the parotid biopsy was assessed as a diagnostic tool based on the presence of lymphocytic foci, benign lymphoepithelial lesions and lymphoid follicles. These new histological criteria were compared with established diagnostic criteria for the labial biopsy in 35 consecutive patients suspected for pSS who underwent simultaneous biopsies from both sites. In addition, both biopsies were compared for morbidity. RESULTS: The first analysis revealed a focus score of >or=1 or lymphocytic infiltrates (not fulfilling the criterion of a focus score of 1) combined with benign lymphoepithelial lesions as diagnostic criteria for pSS. When comparing the parotid biopsy with the labial biopsy sensitivity and specificity were comparable (sensitivity 78%, specificity 86%). Level of pain was comparable and no loss of motor function was observed. No permanent sensory loss was observed after parotid biopsy, while labial biopsy led to permanent sensory loss in 6% of the patients. Malignant lymphoma was detected in one parotid biopsy by chance, without involvement of the labial salivary gland. CONCLUSION: A parotid biopsy has a diagnostic potential comparable with that of a labial biopsy in the diagnosis of pSS, and may be associated with less morbidity.

Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936.

Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms. However, lack of standardized PCR protocols resulting in a high level of false negativity has hampered comparability of data in previous clonality studies. In order to address these problems, 22 European laboratories investigated the Ig/TCR rearrangement patterns as well as t(14;18) and t(11;14) translocations of 369 B-cell malignancies belonging to five WHO-defined entities using the standardized BIOMED-2 multiplex PCR tubes accompanied by international pathology panel review. B-cell clonality was detected by combined use of the IGH and IGK multiplex PCR assays in all 260 definitive cases of B-cell chronic lymphocytic leukemia (n=56), mantle cell lymphoma (n=54), marginal zone lymphoma (n=41) and follicular lymphoma (n=109). Two of 109 cases of diffuse large B-cell lymphoma showed no detectable clonal marker. The use of these techniques to assign cell lineage should be treated with caution as additional clonal TCR gene rearrangements were frequently detected in all disease categories. Our study indicates that the BIOMED-2 multiplex PCR assays provide a powerful strategy for clonality assessment in B-cell malignancies resulting in high Ig clonality detection rates particularly when IGH and IGK strategies are combined.

The relationship between HLA class II polymorphisms and somatic deletions in testicular B cell lymphomas of Dutch patients.

Several risk factors including immune deficiencies, infections, and autoimmune diseases have been established for non-Hodgkin's lymphoma (NHL). For diffuse large B cell lymphoma (DLBCL), the most common type of lymphoma, no risk factors have been described, which may be due to the intrinsic heterogeneity of this disorder. Previously we reported that, in contrast to nodal DLBCLs, the majority of testicular DLBCLs manifested complete loss of HLA-DR and -DQ expression associated with homozygous deletions of the corresponding genes. To determine the correlation between HLA class II polymorphisms and these lymphomas, we applied DNA typing for HLA-DRB1 and HLA-DQB1 on 50 Dutch patients with testicular and 48 with nodal DLBCL and compared the frequencies with a cohort of healthy Dutch controls. Both the patients with nodal and those with testicular DLBCL manifested significantly higher frequencies of HLA-DRB1*15 than the controls (p < 0.018, odds ratio 2.09 and p < 0.013, odds ratio 2.12, respectively). Moreover, a positive association was seen with HLA-DRB1*12 (p = 0.043, odds ratio 4.17) in the patients with testicular DLBCL, and a negative association was seen with HLA-DRB1*07 (p = 0.022, odds ratio 0.13) in the patients with nodal DLBCL. Homozygous deletions of the HLA-DR/DQ region, evaluated by interphase fluorescence in situ hybridization were seen in 20 of 48 testicular tumors. No preferential loss or retention of a particular HLA-DR or -DQ allele was seen because all alleles were at least once retained or involved in a homozygous deletion.

Chronic lymphocytic leukaemia: a review of the immuno-architecture.

Immunophenotyping of B cell chronic lymphocytic leukaemia (B-CLL) is usually performed by flow cytometry on cell suspensions obtained from peripheral blood, bone marrow or biopsied tissue. Immunohistochemical analysis on routine sections is less commonly performed; however, this approach allows the pathologist and the researcher to appreciate the immuno-architecture of the involved tissues and to gain insight into some of the events that influence the biology of the disease. In this review the authors focus on the following issues: immuno-architecture of the proliferation centres, expression of CD23, MUM1/IRF-4 and cyclin D1, tyrosine phosphorylation and detection of the ZAP-70 kinase. Whenever possible, an attempt is made to interpret the immunohistochemical findings from a functional point of view.

Gender and age-related differences in Burkitt lymphoma--epidemiological and clinical data from The Netherlands.

Although Burkitt's lymphoma (BL) is classified as one entity in the World Health Organisation (WHO) classification, we wondered whether BL should not be considered as a different disease in children compared with adults. Netherlands Cancer Registry (NCR) data were obtained from 1994 to 1998 (n=203). Detailed clinical data from two treatment protocols were compared: one for adults up to the age of 65 years (n=27) and one for children (n=80). All slides of the two clinical studies were centrally reviewed which included immunophenotyping and when necessary breakpoint analysis of MYC/8q24. Only cases with an unambiguous diagnosis of BL (classical and atypical BL) were accepted. The age distribution of BL-patients showed a bimodal distribution with a peak at the paediatric age and a steady increase after approximately 60 years of age. Most of the patients were males (89% for children and 78% for adults) and only male patients showed this bimodality. Children more often had extranodal disease (81% vs. 59%), whereas adults more often had nodal disease (89% vs. 53%). Based on epidemiology and clinical presentation, the concept that BL is one disease should be re-challenged.

Non-Hodgkin's lymphoma in the Netherlands: results from a population-based registry.

The Comprehensive Cancer Centre West (CCCW) population based non-Hodgkin's lymphoma (NHL) registry contains information on all newly diagnosed NHL patients living in the region covered by the CCCW. Patients were entered from June 1st 1981 to December 31st 1989. Follow-up is still ongoing, median follow-up is 113 months (1-191 months) for patients alive. In this study, patient and tumor characteristics, data on patterns of care, response and (relative) survival are described. As follicular lymphomas and diffuse large B-cell lymphomas are the most frequently occurring NHL subtypes in the database, a separate analysis is performed to characterize the clinical picture of these disease entities in the CCCW population. Our data illustrate that NHL patients in the general population are substantially older than patients included in trials and hospital based series. Due to older age, treatment is withheld or adapted for a substantial number of patients. The resulting survival and relative survival rates are a reflection of these choices.

Enteropathy-associated T-cell lymphoma presenting with eosinophilia.

Hypereosinophilia can be related to various diseases; when it occurs without an obvious cause it is called idiopathic hypereosinophilic syndrome (IHES). We describe a patient with increasing eosinophilia, which in spite of extensive diagnostic procedures initially remained unexplained. However, during follow-up it became apparent that this patient had a lethal enteropathy-associated T lymphoma (EATL) causing the hypereosinophilia.