Clonal and non-clonal karyotypically abnormal cells in haemophagocytic lymphohistiocytosis

We studied chromosomes in bone marrow (BM) or peripheral blood cells of nine patients with haemophagocytic lymphohistiocytosis (HLH); three of them had a family history of HLH and four others underwent concurrent Epstein-Barr virus (EBV) infection. In addition to a large population of normal mitotic cells, karyotypically abnormal clonal cells were found in two patients, abnormal clonal cells and a nonclonal (single) abnormal cell in one, and nonclonal abnormal cells in three. All the six patients with chromosome abnormalities died of progressive disease; one of them also had EBV infection and EBV-associated clonal proliferation. Two of three patients with EBV infection and only normal mitotic cells in BM completely recovered from the disease.
Although HLH did not show histological and/or haema-tological evidence of a neoplastic disease, clonal chromosome abnormalities and the fatal clinical outcome found in some of the patients suggest that the disease may be heterogenous and include malignancy. HLH patients with karyotypically abnormal clonal cells in BM should warrant more intensive chemotherapy than that presently being applied to them and should be considered as candidates for BM transplantation.     

Inconsistent association of Epstein-Barr virus with CD56 (NCAM)-positive angiocentric lymphoma occuring in sites other than the upper and lower respiratory tract

We previously described nine cases of angiocentric lymphoma of a possible natural killer (NK)-cell lineage with a surface CD3− CD56+ phenotype occurring in sites other than the upper and lower respiratory tract. This study was performed to investigate the association of Epstein-Barr virus (EBV) with these lymphomas, using the polymerase chain reaction (PCR) for the presence of EBV-DNA, in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs) and immunohistology for EBV-determined nuclear antigen-2 (EBNA-2) and latent membrane protein-1 (LMP-1) in paraffin sections. PCR and ISH produced almost identical results, and EBERs were identified in the nuclei of the lymphoma cells of three cases, two of which exhibited LMP-1 in the cytoplasm of tumour cells without EBNA-2 expression. Molecular genetic analysis revealed EBV to be incorporated into these three EBER-positive cases either clonally or biclonally. It was revealed by re-evaluation of their morphology with the established EBV status on each case that, in contrast to the rather variable and irregular cellular composition of the EBV- positive tumours, the EBV-negative tumours stood out because of their remarkably uniform 'blastoid' appearance, and could be grouped as blastic NK-cell lymphoma. The relationship of the EBV-positive cases with nasal NK-cell tumours has yet to be clarified.     

HLA Antigens and Adult T-Cell Leukemia Virus Infection: A Community-Based Study in the Goto Islands, Japan

In order to study the genetical susceptibility to infectionby adult T-cell leukemia virus (ATLV), which is considered tobe a main causative agent of adult T-cell leukemia (ATL), theHLA profile of persons with antibody against ATLV-associatedantigen (anti-ATLA) was compared with that of antibody-negativepersons in villages A and B of the Goto Islands, a typical ATLendemic area in Kyushu, Japan. The frequency (29%) of HLA-B7in persons with anti-ATLA was significantly higher than that(8%) in anti-ATLA negatives (corrected X²=7.73, p<0.01) inone village while the frequency of HLA-B7 was around 10% inboth positive and negative persons in the other village. Theseresults do not support or deny the possibility of the existenceof individuals who are genetically susceptible to ATLV infectionin ATL endemic areas of Japan.     

Biological and Clinical Implication of Neuron-Specific Enolase and Creatine Kinase BB in Small Cell Lung Cancer

The specificity of neuron-specific enolase (NSE) and creatinekinase BB (CK-BB) for small cell lung cancer (SCLC) was determinedby biological and immunohistochemical procedures in lung cancertissues and cultured cell lines. Average values of extractableNSE and CK-BB of SCLC tissues were significantly higher thanthose of non-SCLC and normal lung tissues. A large amount ofNSE and CK-BB was demonstrated in SCLC cell lines. Immunohistochemical examination showed positive staining forNSE and CK-BB in most cases of SCLC and in a few cases of non-SCLC.From these data NSE and CK-BB should be considered to be highlyspecific for SCLC. In a clinical study serum values exceeding 10 ng/ml for NSEand 1.5 ng/ml for CK-BB were set as positive for the enzymes.Positive rates in SCLC were 71.4% for NSE and 65.3% for CK-BB,which were significantly higher than those in non-SCLC. Allpositive cases were in an advanced stage. Consecutive dailyNSE determinations during induction chemotherapy showed transientelevation immediately after the initiation of drug administration(tumor lysis syndrome), followed by a decline to the normalrange in responders. This phe nomenon seems to indicate tumorsensitivity to cytotoxic drugs. NSE positive non-SCLC was assensitive to cytotoxic drugs as SCLC. These findings indicatethat lung cancer with elevated serum NSE and CK-BB levels atdiagnosis should be strongly suspected of being SCLC in theadvanced stage.     

Regression of Gastroduodenal Mucosa-Associated Lymphoid Tissue Lymphoma after Eradication of Helicobacter pylori: A Case Report

Increasing evidence suggests that eradication therapy of Helicobacter pylori (H. pylori) may be an effective treatment for gastric lymphoma of mucosa-associated lymphoid tissue (MALToma), but it remains unclear whether a similar therapeutic effect may be obtained for MALToma at other sites. We describe here a case of regression of gastroduodenal MALToma after eradication therapy for H. pylori. A 39-year-old man underwent gastroscopy at a routine check-up, which demonstrated protruding lesions like a raised erosion in the antrum and multiple whitish granular lesions in the fornix. Simultaneously, multiple coarse nodular lesions were also found in the duodenal bulb. Forceps biopsy specimens obtained from both the stomach and bulb showed infiltration of small- to medium-sized lymphocytes with cleaved nuclei, centrocyte-like cells, together with atypical large lymphoid cells into the glandular lesion, and the rearrangement of immunoglobulin was positive, thereby allowing diagnosis of low grade MALToma with large cell transformation. H. pylori was positive in the stomach, while the presence of H, pylori was not detected microscopically in the bulb, although ectopic gastric mucosa was identified in the bulb. Regression of multiple coarse or granular lesions in both the stomach and bulb were observed three months after eradication of H. pylori. Thereafter the disappearance of MALToma was verified histologically a further six months later. There was no recurrence of MALToma detected over a two-year follow-up period. These findings suggest that eradication of H. pylori could be a treatment of first choice for MALToma occurring in the gastrointestinal tract outside the stomach.