Sister chromatid exchanges in leukemic patients

Sister chromatid exchange (SCE) was studied in PHA-stimulated peripheral blood lymphocytes from 36 newly diagnosed and untreated leukemic patients: 16 with acute lymphoblastic leukemia (ALL), 10 with acute nonlymphocytic leukemia (ANLL), and 10 with chronic myelocytic leukemia (CML). The metaphases analyzed show no chromosomal abnormalities. The mean SCE frequency (mean +/- SE) for each group of patients was: 6.8 +/- 0.4, 6.6 +/- 0.3, and 7.0 +/- 0.6 per mitosis, respectively, which was significantly lower than the mean SCE score for 30 controls (8.7 +/- 0.2). No differences in SCE score among ALL, ANLL, and CML and a similar SCE frequency by chromosome number and group allowed consolidation of all the cases into a single group of 36 leukemic patients (6.8 +/- 0.3). When the frequency of SCE was compared by chromosome number and group between the leukemic patients with the control group, a significant decrease in SCE frequency was observed due to a low SCE score in almost all the complements, except chromosome #1. It is suggested that the low SCE rate is related to the leukemic process itself.     

Bone marrow and peripheral blood natural killer cell activity in lymphomas. Its response to IL-2.

Natural killer (NK) cytotoxic activity was simultaneously investigated in bone marrow mononuclear cells (BMMC) and peripheral blood lymphocytes (PBL) from nine Hodgkin's disease (HD) and 15 non-Hodgkin lymphoma (NHL) untreated patients. Twenty-five PBL samples and seven bone marrow specimens from healthy individuals were also included as control group (C). NK cell activity was evaluated in basal condition and post-stimulation with human recombinant IL-2 (rIL-2). Data were expressed in K values (number of BMMC or PBL needed to lyse 50% of the target cells). In basal condition, both HD and NHL patients showed a NK cell activity comparable to the C group, both in BMMC (HD, K = 2.48 +/- 1.3; NHL, K = 3.8 +/- 2.0; C, K = 3.2 +/- 0.7) and PBL (HD, K = 2.0 +/- 1.0; NHL, K = 2.3 +/- 1.0; C, K = 2.2 +/- 0.2). Stimulation with rIL-2 induced a significant and comparable enhancement of the NK activity in PBL from HD, NHL and C while the response to rIL-2 of the BMMC in most of the HD and NHL patients was significantly greater than the C group. Responder cells were characterized by negative selection with specific MoAb plus complement as a CD3-, CD16+, CD56+ cytotoxic cell and further confirmed by flow cytometry. We postulate that IL-2 activation of bone marrow NK cell precursors, in addition to enhancing the activity of circulating NK, may be of value for the therapeutic rationale of IL-2 in patients with lymphoma.     

Sister chromatid exchange analysis in familial groups of malignant melanoma patients

Sister chromatid exchange (SCE) analysis was carried out on peripheral blood lymphocytes of 20 familial malignant melanoma (FMM) and 39 sporadic malignant melanoma (SMM) untreated patients, belonging to 10 and 39 families, respectively. The study was extended to 39 unaffected close relatives of FMM patients, to 187 unaffected close relatives of SMM patients, and to 20 unaffected unrelated individuals (control group), all examined under the same conditions. The mean SCE rates/cell were significantly higher in MM families than in the control group, and in melanoma patients than in their close relatives. The mean SCE levels of FMM and SMM patients, (8.4 +/- 0.8 and 8.0 +/- 0.3, respectively) were similar, and so were the distributions of individuals in classes of increasing SCE values (with a modal value at 7-8 SCEs/cell). The mean SCE levels of close relatives of FMM and SMM patients were also similar (5.4 +/- 0.2 and 5.4 +/- 0.1, respectively, with a modal value at 4-5 SCEs/cell), and slightly higher than in the control group (4.7 +/- 0.2 SCEs/cell). More than 7 SCEs/cell were observed in the majority (41 of 59) of FMM or SMM patients, in a smaller fraction (25 of 227) unaffected relatives, and in none of 20 unrelated unaffected individuals. These observations favor the hypothesis that higher SCE levels may be an expression of constitutional lesions predisposing to this neoplastic disease.     

Composite lymphoma. A clinicopathologic analysis of nine patients with Hodgkin's disease and B-cell non-Hodgkin's lymphoma

Nine patients had composite lymphoma in which Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) involved the same anatomic site. Two of these patients had relapses of their tumors. In one, the initial biopsy specimen contained follicular and diffuse large cell NHL with unclassifiable HD, but the relapse showed diffuse large cell NHL with nodular sclerosis HD. In the other patient, both biopsy specimens showed follicular mixed NHL; the HD component in the initial biopsy specimen was nodular sclerosis, whereas, at relapse, it had the appearance of interfollicular HD. In the remaining seven patients, the HD component was subclassified as nodular sclerosis (three specimens) or mixed cellularity (three specimens), or it was unclassifiable (one specimen). The NHL component was categorized as diffuse large cell (two specimens), diffuse large cell immunoblastic (two specimens), follicular and diffuse large cell (one specimen), diffuse mixed small and large cell (one specimen), and lymphocytic lymphoma of intermediate differentiation (modified Rappaport classification) (one specimen). Paraffin section immunoperoxidase studies were done on the NHL component in eight patients (nine specimens) and on the HD component in six patients (seven specimens). In each of these, the NHL component was leukocyte common antigen (LCA) positive and Leu-M1 negative. In addition, the neoplastic cells were L26 positive and UCHL-1 negative, indicating a B-cell phenotype. In five of seven immunophenotyped cases, Reed-Sternberg (RS) and Hodgkin's (H) cells from the HD areas were Leu-M1 positive and LCA negative, reflecting an immunophenotype that is typical of non-lymphocyte-predominant HD. In two specimens, the malignant cells were negative for Leu-M1 and LCA (with positive internal controls). Composite lymphomas composed of HD and NHL are unusual, and cases of coexistent HD of the non-lymphocyte-predominant subtype and NHL are even less common. The results of the current study and a review of the literature indicate that this phenomenon usually involves a B-cell NHL that coexists with HD, perhaps further suggesting a close relationship between the malignant cells of HD (RS and H cells) and B lymphocytes.     

Intratumoral microvascular density in malignant lymphomas of B-cell origin

Sections of surgical lymph-node biopsies of four types of malignant non-Hodgkin's lymphoma of B-cell origin (B-NHL) classified according to the R.E.A.L. terminology or lymphadenitis were immunostained in order to demonstrate endothelial CD34 (QBEnd 10) and to determine the microvascular density and vessel-size distribution using an interactive image-analysis technique. Only microvessels displaying a cross-sectional area corresponding to a diameter of between 3.2 and 34.6 microm were included. The intratumoral microvascular density (iMVD) was found to be significantly higher in chronic lymphatic leukaemia (CLL, n = 13) compared with the clinically more aggressive mantle cell lymphoma (MCL, n = 9) and diffuse large B-cell lymphoma (DLBCL, n = 14). iMVD in CLL was also higher than in the follicular neoplastic parts (FL FOLL) of follicular lymphoma (FL, n = 16). In FL FOLL the microvessel density was, moreover, significantly lower than in the surrounding non-neoplastic FL tissue. In lymphadenitis (LA, n = 10) the iMVD was higher than in DLBCL, FL FOLL and MCL. The data suggest that future studies focusing on the relationship between iMVD and the clinical outcome within each particular NHL group should be carried out in order to verify whether iMVD is a prognostic factor in NHL, as it is in carcinomas.     

Heterochromatic variants and their association with neoplasias. I. Chronic and acute leukemia

C-banding studies of the heteromorphism of chromosomes #1, #9, and #16 were performed in 120 leukemic patients: 56 with chronic myelocytic leukemia (CML), 45 with acute lymphoblastic leukemia (ALL), and 19 with acute nonlymphoblastic leukemia (ANLL). No differences were found among patients and controls with regard to sex. Our data showed a significant increase of polymorphism in chromosome #1 in the three neoplastic groups; the heterochromatic variant preferentially involved 1qh-, whereas there were no significant differences in heteromorphism in chromosomes #9 and #16.     

Radiographic staging procedures and radiotherapy of malignant lymphoma

Radiographic studies play an important role in the clinical staging of malignant lymphoma (ML). Conventional procedures are plain chest X-ray, lymphangiography, gastrointestinal series, and 67Ga scintigraphy. Gastro-intestinal series is essential in non-Hodgkin's lymphoma (NHL) of Waldeyer's ring and thyroid. 67Ga scintigraphy is a non-invasive procedure useful in the screening of ML. Recently marked improvements have been made in the diagnostic modalities. CT scan and NMR have made it very easy to diagnose ML of the central nervous system and detect the extension of tumors at all sites. In some cases with Hodgkin's disease (HD), staging laparotomy is necessary, but not in cases with NHL. If tumors are localized, subtotal or total nodal irradiation is performed for patients with HD, and generous involved field is employed for NHL with or without combined chemotherapy at our department. Good local control is obtained except for NHL of the central nervous system at a total dose of 40-50 Gy. NHL is prone to relapse outside the radiation field. Therefore we consider that combined chemotherapy is indicated for NHL such as T-cell lymphomas, those with high grade histology classified according to the Working Formulation, and with involvement of lymph nodes larger than 6 cm in diameter.     

Increased spontaneous and mitomycin C-induced sister chromatid exchanges in patients with cancer of the cervix uteri, with special reference to stage of cancer

The frequencies of spontaneous and mitomycin C (MMC)-induced sister chromatid exchange (SCE) were examined in 35 patients with cancer of the cervix uteri (stage 0, eight cases; stage I, nine cases; stage II, nine cases, and stage III, nine cases) before they had undergone cancer treatment, as well as in seven patients with uterine myoma and 18 healthy women as controls. The frequency of SCE was analyzed in reference to the stage of cancer in the cancer group and in reference to chromosome group in the cancer and normal groups. The frequencies of spontaneous and MMC-induced SCE in the cancer group were 10.0 +/- 1.8 and 20.7 +/- 2.6, respectively, and both were significantly higher than in the myoma (8.1 +/- 0.8 and 17.6 +/- 1.8) and normal (7.6 +/- 0.8 and 17.6 +/- 2.3) groups. Furthermore, the frequency of SCE in the cancer group increased with cancer stage. All chromosome groups contributed equally to the increase in SCE in the cancer group. These results indicate that an increase in the frequency of SCE in patients with cervical cancer is related to the presence of cancer, but is not related to a predisposition to cancer.     

Analysis of T-cell receptor and immunoglobulin gene rearrangements in the diagnosis of Hodgkin's and non-Hodgkin's lymphoma

The results of genotypic analysis of 29 cases of malignant lymphoma are reported and the application of this technique for differentiating between Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) is evaluated. Five cases with a differential diagnosis which included HD and NHL were analysed. These results are compared with those obtained for six B-cell NHLs, nine T-cell NHLs, and nine cases of HD. This report suggests that gene rearrangement analysis is useful in some cases in which the differential diagnoses includes HD and NHL as the absence of gene rearrangements is more consistent with a diagnosis of HD than of NHL. Two monoclonal antibodies reactive with the variable region of T-cell receptor beta-chain and molecular probes to the relevant variable region genes were used to assist in the diagnosis of T-cell lymphoma. This report confirms that genotypic analysis is useful diagnostically when the results are assessed in the context of the histopathological findings.     

Abnormalities of chromosome No. 1: Two cases with lymphocytic lymphomas

Two cases of lymphocytic lymphoma with a duplication of part of the long arm of chromosome #1, between bands 1q25 and 1q32, are presented. The coincidence between this finding with others in the literature supports the concept that this specific chromosome segment is related to the proliferative advantage of malignant cells in neoplasia.     

非霍奇金淋巴瘤患者T细胞亚群、NK细胞检测的临床意义

目的：研究非霍奇金淋巴瘤（NHL）患者外周血T淋巴细胞亚群、NK细胞检测结果的变化与该病的关系及与慢性淋巴腺炎患者细胞免疫功能的不同变化。方法：采用流式细胞仪（FCM）检测非霍奇金淋巴瘤（NHL）患者、慢性淋巴腺炎及正常人外周血T淋巴细胞亚群比例、NK细胞的变化。结果：非雹奇金淋巴瘤患者与正常人比较总的T淋巴细胞、辅助性T淋巴细胞及CD4^＋／CD8^＋比值明显下降（P〈0．05），细胞毒性T淋巴细胞明显升高（P〈0．05），NK细胞则无明显变化（P〉0．05）。非霍奇金淋巴瘤患者与慢性淋巴腺炎患者比较，细胞毒性T淋巴细胞、NK细胞明显升高（P〈0.05），而总的T淋巴细胞、辅助性T淋巴细胞无明显改变（P〉0．05），CD4^＋／CD8^＋比值略有下降但无明显统计学意义。结论：非霍奇金淋巴瘤患者细胞免疫功能明显受到抑制，T细胞亚群及NK细胞的检测对NHL的诊断、治疗、预后判断有一定的临床价值。     

Hodgkin's disease mimicking suppurative lymphadenitis: a fine-needle aspiration report of five cases.

Spontaneous, suppurative-necrotizing changes associated with Hodgkin's disease (HD) are not infrequent. They are mostly observed in the nodular sclerosis variant of HD and can cause an erroneous histologic diagnosis of suppurative lymphadenitis. Few cytologic reports describing this presentation of HD are available. We describe 5 cases of HD that showed cytologic abscess-like smears dominated by a massive neutrophilic infiltrate and necrosis. Since therapy can induce similar changes, this study did not include patients with known HD. In 2 cases erroneously diagnosed as suppurative lymphadenitis, the presence of neoplastic cells was minimal and only detected after revision. A third case was misdiagnosed as abscessified metastasic carcinoma. Two cases were correctly identified as HD, although in one, the possibility of anaplastic large-cell lymphoma could not be ruled out. In conclusion, necrosis and massive neutrophilic infiltrates can occur spontaneously and can be prominent findings in smears from patients with HD, mainly the nodular sclerosis variant. The cytopathologist should always consider this possibility in the presence of an abscessified, suppurative, lymphadenitis-like aspirate. A detailed search for the characteristic neoplastic cells of HD is mandatory in these cases.     

CD40 ligand is constitutively expressed in a subset of T cell lymphomas and on the microenvironmental reactive T cells of follicular lymphomas and Hodgkin's disease.

Although CD40 has been extensively studied in B- and T-cell non-Hodgkin's lymphomas (NHLs)/leukemias, and more recently in Hodgkin's disease (HD), little is known about the expression of its ligand (CD40L) in lymphoproliferative disorders other than T-cell NHLs/leukemias. A series of 121 lymphoma/leukemia samples, including 35 cases of HD, 34 T-cell and 39 B-cells NHLs, 2 cases of adult T-cell leukemia/lymphoma, and 11 cases of T-cell acute lymphoblastic leukemia, were evaluated for CD40L expression by immunostaining of frozen tissue sections and flow cytometry with the anti-CD40L monoclonal antibody M90. CD40L was constitutively expressed by neoplastic cells in 15 of 36 (42%) T-cell NHLs/adult T-cell leukemia/lymphomas, almost invariably those displaying the CD4+/CD8- phenotype, whereas no CD40L-expressing tumor cells could be found in B-cell NHL and HD. Among T-cell acute lymphoblastic leukemias, CD40L was detected only on 2 cases displaying a stem-cell-like phenotype. In follicular B-cell lymphomas a large number of CD40L-expressing CD3+/CD4+ T lymphocytes were found admixed with tumor cells within the neoplastic follicles and in their surrounding areas. In the nonfollicular B-cell lymphomas, CD40L-positive CD3+/CD4+ T lymphocytes were few or absent. In all HD subtypes other than the nodular lymphocytic predominance, CD40L-expressing CD3+/CD4+ T lymphocytes were numerous in the HD-involved areas and were mainly located in close proximity to the Reed-Sternberg cells. Our data indicate that in human lymphomas CD40L is preferentially expressed by a restricted subset of T-cell lymphomas, mostly with CD4 immunophenotype. Finally, we have provided morphological evidence that CD40L may play an important role in the cell contact-dependent interaction of tumor B-cells (CD40+) within the neoplastic follicles or Reed-Sternberg cells (CD40+) in HD-involved areas and the microenvironmental CD3+/CD4+/CD40L+ T lymphocytes.     

Dipeptidyl aminopeptidase-IV as a histochemical marker of differential diagnosis of large cell anaplastic CD30+-lymphoma and Hodgkin's disease

Using histochemical methods, we studied distribution of dipeptidylaminopeptidase-IV (DPP-IV) in tumor cells of 16 patients with non-Hodgkin's malignant lymphomas (NHL) including B-cell NHL (10 cases), pleomorphic T-cell lymphoma (1 case), CD30+ anaplastic large cell lymphoma (ALCL) of T-cell (1 case) and ALCL of null-cell type (4 cases) and of 13 patients with Hodgkin's disease (HD). The results indicate that tumour cells of pleomorphic T-cell NHL and ALCL of T- and null-cell type showed DPP-IV activity. In contrast, no DPP-IV activity was seen in the tumor cells of B-cell NHL (lymphocytic, centroblastic/centrocytic, centroblastic, immunoblastic), in Berezovsky-Reed-Sternberg and Hodgkin's cells of different HD variants. These results demonstrate that difference in DPP-IV activity between tumor cells of ALCL and HD may be diagnostically important for separation of ALCL from HD and moreover may be used in verification of the borderline between HD-like ALCL and ALCL-like HD. It is possible that DPP-IV activity contributes to pathogenesis of ALCL and may determine clinical behaviour of this NHL being involved in autocrine and paracrine regulation of tumor cell growth of ALCL.     

Hodgkin disease associated with T-cell non-Hodgkin lymphomas: case reports and review of the literature

Non-Hodgkin lymphoma (NHL) is more likely to develop in patients with Hodgkin disease (HD) than in the general population. Although reports of synchronous or metachronous HD and NHL are not uncommon in the literature, the biologic relationship of these 2 malignant neoplasms often is unclear. A larger-than-expected fraction of NHLs occurring in patients with HD are of the T-cell phenotype. We report 1 synchronous and 3 metachronous cases of HD and T-cell NHL. In 2 cases, the 2 tumors are unlikely to be related clonally. In the other 2 cases, however, T-cell receptor rearrangement studies demonstrated the presence of the same rearranged clone in both tumor specimens, suggesting that they share a common precursor or that one arose by transformation of the other. These observations imply that, similar to the observations in B-cell NHLs occurring with HD, a subset of synchronous and metachronous T-cell NHLs and HD may be related clonally.     

Heterochromatic variants and their association with neoplasias: V. Non-Hodgkin's lymphomas

A study of heterochromatic regions in chromosomes #1, #9, and #16 was performed on lymphocytes of peripheral blood from 55 normal individuals and 50 patients with non-Hodgkin's lymphoma (NHL). Heteromorphism was present in 90% of the NHL patients, compared with 44% in normal individuals (p less than 0.001). An increase of inv(1), 1qh-, and 9qh-variants was observed in malignant lymphoma patients with respect to controls.     

Chromosome aberrations in adult Hodgkin disease in a Danish population-based study

During a 6-year period, 31 patients with Hodgkin disease (HD) were analyzed for chromosome aberrations on lymphoid tissue. We obtained metaphases in 87% (27/31). The number of cells analyzed per case ranged from 17 to 31 (median 25), and the number of abnormal mitoses was between 1 and 17 (median 6). Chromosome aberrations were found in 59% (16/27). Numerical aberrations involved all chromosomes. The most frequently gained chromosomes were numbers 2 and 9, and the most frequently lost were numbers 10, 16, 21, 22, and X. Chromosomes most frequently involved in structural aberrations were numbers 1 and 6. The most frequent subgroups were nodular sclerosis (NS) (n = 16) and mixed cellularity (MC) (n = 10). Six NS patients and 8 patients with MC showed an abnormal clone. For the NS patients with an abnormal karyotype, 4 of 6 had a gain of chromosome 2, and all had structural aberrations of chromosome 1. Of the 6 MC patients, where a partial analysis was possible, 4 had a gain of chromosome 9, 2 had structural aberrations involving chromosome 6 and 2 of chromosome 14. In 1 case a translocation normally associated with non-Hodgkin lymphoma (NHL) was found (t[11;14]), whereas other translocations characteristic of NHL, such as t(8;14), t(14;18), and t(2;5) were not observed. A review of the literature on cytogenetic investigations in HD performed on lymphoid tissue showed that the most frequently gained or lost chromosomes were 1, 2, 5, 9, and 12 for NS and 2, 5, and 9 for MC. The most frequently affected chromosomes in structural aberrations were 1 and 6 for NS, and 1, 7, and 14 for MC. Involvement of chromosome 1, 6, and 14 in structural aberrations is characteristic of lymphoid neoplasms, as are the most frequently involved bands (1p36, 6q21–q26, 14q11, and 14q32), further supporting a B- or T-cell origin of the neoplastic cell in HD. The high hyperploidy seen in HD is not a frequent observation in NHL. Although certain chromosome aberrations seem to be characteristic of HD as opposed to NHL, specific nonrandom aberrations have yet to be identified. The rather low number of abnormal mitoses found in most HD cases underlies the importance of analyzing a large number of metaphases.     

Sister chromatid exchange analysis in the Prader-Labhart-Willi syndrome

The number of sister chromatid exchanges (SCE) and cell kinetics in lymphocytes were investigated from 16 Prader-Labhart-Willi syndrome (PLWS) patients [8 with 15q12 deletion (4 females, 4 males; mean age = 12.9y with age range of 0.3 to 24y), and 8 non-deletion (2 females, 6 males; means age = 16.8y with age range of 5 to 26y)], 18 parents of PLWS patients and age-matched control individuals. The average SCE frequency and standard deviation in PLWS patients with and without the chromosome 15 deletion was 6.6 +/- 1.3 and 6.2 +/- 0.8, respectively. Therefore no significant difference in SCE frequency or replicative index was found between the two PLWS subgroups. There was also no significant difference in SCE frequency or replicative index between the 16 PLWS patients and age-matched control subjects. The average SCE frequency and standard deviation in 8 fathers who were previously identified to have donated the chromosome 15 with the deletion in the child was 7.5 +/- 1.2, which was not significantly different from 8.5 +/- 2.0 seen in age-matched control subjects. There was also no significant difference in the SCE frequency or replicative index of 18 parents of PLWS patients with and without the chromosome 15 deletion when compared with age-matched control subjects.     

小儿胸腹部恶性淋巴瘤的CT特征

目的　探讨小儿胸腹部恶性淋巴瘤的CT表现 .方法　分析了 33例小儿胸腹部恶性淋巴瘤的CT表现 .结果　胸部 14例 ,其中非霍杰金氏淋巴瘤 (NHL) 10例 ,霍杰金氏病 (HD) 4例 .腹部 19例 ,NHL 15例 ,HD 4例 .CT表现有以下特点 :胸部恶性淋巴瘤多发生在前中纵隔 ,腹部恶性淋巴瘤多发生在腹膜后和肠系膜 ;肿瘤常融合成团 ,边缘多较清楚 ;密度多较均匀与肌肉密度相近 ;未经治疗者未见钙化 ;增强扫描大部分呈轻中度均匀强化 ,少部分不均匀强化和均匀强化并存 ;坏死囊变少见 ;强化后边缘更清楚 ,但未见包膜形成 .小儿NHL与HD有 5个不同点即发病率不同 ;发病年龄不同 ;病灶大小不同 ;发病部位不同和预后不同 .结论　小儿胸腹部恶性淋巴瘤的CT表现有一定的特点 ,CT平扫和增强检查是影像诊断的首选方法     

Assessment of erythropoietin levels and some iron indices in chronic renal failure and liver cirrhosis patients

This study was constructed to investigate the relationship between renal anaemia and erythropoietin (EPO) concentrations in chronic renal failure (CRF) patients and to evaluate the possible role of the liver. Serum EPO levels were measured in blood samples from 20 CRF patients on hemodialysis (HD), 20 liver cirrhosis (LC) patients, 20 patients having both CRF and LC and undergoing HD, and 20 normal control subjects. Blood cell counts, iron indices (iron, total iron-binding capacity (TIBC) and ferritin), renal function (blood urea nitrogen (BUN) and creatinine), hepatic function (ALT, AST, ALP and bilirubin) investigations were carried out for all the subjects enrolled in this study. CRF patients without LC had serum EPO concentration of 6.21 +/- 0.53 mU/ml (mean +/- SE), which was significantly higher than that in patients having both CRF and LC (4.32 +/- 0.52) (p < 0.01). Both groups showed significantly lower values than the controls (12.75 +/- 0.70) (p < 0.001). LC patients with intact kidneys had significantly higher EPO level (22.70 +/- 1.70) (p < 0.001). No correlation was found between EPO level and any of the hematologic or iron indices.