Gábor Kelényi

Follicular dendritic reticulum cell tumor mimicking inflammatory pseudotumor of the spleen.

In the course of a routine clinical check up of the 54 year old male a splenic well circumscribed tumor like mass of 12 cm in diameter was discovered. Splenectomy with removal of splenic hilar lymph nodes and liver wedge biopsy were performed. Four years later the patient is symptom free. In the removed spleen the tumor like lesion showed a pattern consistent with the diagnosis of inflammatory pseudotumor. However, besides lymphocytes, plasma cells, macrophages, eosinophils and myofibroblasts a high number of slightly polymorphic, frequently binucleated cells positive for CD 21 and CD23 were seen. These cells which were scattered or formed smaller or larger groups and fascicles were considered to represent follicular dendritic reticulum cells (FDRCs) and the lesion a FDRC tumor. Flow cytometric DNA ploidy analysis showed a hyperdiploid cell population inside the tumor like lesion. Besides FDRC tumors of high and of intermediate malignancy the present case may represent a low grade type of moderate proliferation activity. The FDRCs of the lesion and a few smaller spindle cells were EBER positive indicative of the presence of EBV. No EBER positive cells were seen in the uninvolved spleen.

Immunoglobulin VH gene mutational analysis suggests that blastic variant of mantle cell lymphoma derives from different stages of B-cell maturation

To characterise the nature of the cellular origin of the blastic variant of mantle cell lymphoma (MCL-BV), we analysed the immunoglobulin (Ig) heavy chain variable region (V(H)) genes in four cases of MCL-BV. The rearranged V(H)-D J(H) genes were PCR-amplified, cloned and sequenced. In one case, the comparison of the rearranged V(H) gene sequence to known germline V(H) gene templates showed no somatic mutations suggesting a pre-germinal centre B-cell origin for tumour cells. In the other three cases, the V(H) gene sequences showed varied number of point mutations relative to the putative germline V(H) gene sequences but the point mutations were not associated with intraclonal diversification. In one of the mutated cases, the distribution and type of the mutations indicated that tumour cells had been selected by an antigen. Since somatically mutated Ig genes are expressed by B-cells that have reached a germinal centre/post-germinal centre stage of development, these findings suggest that the MCL-BV cell of origin may also be a germinal centre or a post-germinal centre B-cell. Taken together, our findings suggest that the development of MCL-BC may not be restricted to one stage of B-cell differentiation and that they may represent transformants of B-cells at different stages of ontogeny.

Endothelial cell receptors on leukemic plasma cells

The binding of peripheral blood mononuclear cells of 7 patients with plasma cell leukemia to rat lymph node high endothelial venules has been studied in vitro. The mononuclear cells adhered selectively to the high endothelial venules. Their neoplastic origin was proved by in situ demonstration of their monoclonal cytoplasmic immunoglobulins. The in vitro binding of bone marrow mononuclear cells of 4 patients with multiple myeloma to high endothelial venules was also studied. In two patients there was no high endothelial cell binding. In the two others some adhering cells were observed. The plasmacytoid nature of these cells was, however, excluded for lack of cytoplasmic immunoglobulins. Since cells at the end stage of B-cell differentiation lose their surface receptors associated with lymphocyte recirculation, the presence of endothelium-recognizing structures on leukemic plasma cells seems to be remarkable.

EBER oligonucleotide RNA in situ hybridization in EBV associated neoplasms

In virus associated diseases identification of viruses in cells can contribute to the understanding of the pathogenesis and may also help to establish the diagnosis. In the present communication, the effects of the microwave pretreatment (MWP) and that of the proteinase-K enzymatic predigestion (PKD) on EBER RNA oligonucleotide in situ hybridization (EBER-RNA-ISH) (EBER: Epstein-Barr-Encoded-(Early)-RNA) were studied. The efficacy of two EBV detecting methods, latent membrane protein-1 (LMP-1) immunohistochemistry and EBER-RNA-ISH were also compared. Our results show that microwave pretreatment enhances the intensity of the ISH signals and preserves significantly better the structure of the tissues compared with enzymatic predigestion. EBER-RNA-ISH, mainly in the nasopharyngeal carcinoma cases, showed a more frequent positivity than the immunohistochemical reaction for LMP-1, however in case of the Warthin’s tumor only the LMP-1 protein was expressed.

Expression of an adhesion molecule and homing in B-cell chronic lymphocytic leukaemia: I. application of the HEV-binding assay to a clinical series

High endothelial venule (HEV)-binding of peripheral blood mononuclear cells (PBMCs) from 43 patients with B-cell chronic lymphocytic leukaemia (B-CLL) was investigated with a HEV-bindingin vitro assa. Immunophenotyping of HEY -adherent PBMCs proved that most of them belonged to the B-cell proliferation. B-CLL cells stringently expressed CD44 molecules (Hermes-1, -3 and H90). The patients were subgrouped according to Binet’s classification, as well as according to the organ manifestations,i.e. patients with B-cell monoclonal lymphocytosis of undetermined significance (B-MLUS) and patients with lymphocytosis (LY), lymph node enlargement (LN) and splenomegaly (SM). The HEV-binding activity of the cells wasthe highest in Binet stage A patients and in patients with B-MLUS (p<0.05 in B-MLUS versus B-CLL LY, LN, SM). Based on these findings it is suggested that B-CLL patients show not only a clinical and immunophenotypical heterogeneity, but a diverse function of adhesion molecules.

Large B-cell Lymphoma of the Leg in a Patient with Multiple Malignant Tumours

A patient who had primary gastric B-cell non-Hodgkins lymphoma, invasive ductal breast cancer and a basocellular carcinoma of the forehead in her medical history was studied. Three years after polychemotherapy and irradiation of the breast cancer, a rapidly enlarging, ulcerated violaceous tumour developed on the patients left leg. The tumour was identified by the histopathological, immunohistochemical and immunoglobulin gene rearrangement analyses as a cutaneous large B-cell lymphoma. No signs of extracutaneous involvement were detectable. Despite surgical excision, interferon-alpha2b treatment and chlorambucil + prednisone chemotherapy, a relapse occurred in the previously affected site, whereafter the patient received radiotherapy. She was lost to follow-up, and died approximately 14 months after the surgical intervention without autopsy. We discuss the clinical and histologic features and outcome of the large B-cell lymphoma of the leg, its coincidence with other diseases, and the uncommon occurrence of primary multiple malignant tumours.

Genotypic analysis in primary systemic anaplastic large cell lymphoma

This report presents an experience of polymerase chain reaction (PCR) analysis of T-cell receptor γ- and β gene (TCR γ, TCR β), and immunoglobulin heavy chain (IgH) gene rearrangements in 9 cases of primary systemic anaplastic large cell lymphoma. We showed 2 clonal IgH, 2 TCR γ 1 TCR β rearrangements. The genotype was B/T-cell in 1, T-cell in 1, B-cell in 1 and null cell-type in 6 cases. We used reverse transcriptase PCR (RT-PCR) to detect t(2;5)(p23;q35) and t(l;2)(q25;p23) translocations. T(2;5) translocation was demonstrated in 2 cases, there was no t(l;2) translocation. In most cases the molecular genetic results were found to be in agreement with immunophenotypic data.