原发胃非何杰金恶性淋巴瘤：附83例临床分析

报告天津肿瘤医院３６年来，外科治疗原发非何杰金恶性淋巴瘤（ＰＧＬ）８３例，术前确诊率为３７％。Ｉ期６例，Ⅱ期２７例，Ⅲ期２１例，Ⅳ期２９例。根治性切除的５年生存率９０％，高于胃癌的３３％。总的８３例３、５、１０、１５、２０年的生存率分别为４８％，３８％，２１％，１０％，８％，并重点讨论了影响预后的因素。     

Occult systemic Non-Hodgkin's Lymphoma (NHL) in patients initially diagnosed as Primary Central Nervous System Lymphoma (PCNSL): How much staging is enough?

Objective To demonstrate the extent of staging necessary to exclude occult systemic stage IV NHL before making a diagnosis of stage I AE PCNSL.Background The diagnosis of PCNSL requires the demonstration of malignant lymphocytes within the CNS (usually by biopsy) and finding no evidence of systemic NHL. Different staging approaches have been recommended, ranging from extensive systemic evaluation (including bone marrow examination) to a more focused approach (abdominal and pelvic CT) to no systemic evaluation. We have employed a staging regimen that included: ophthalmologic evaluation (including slit lamp examination); CT of chest, abdomen, and pelvis; bilateral iliac crest aspirate and biopsy; flow cytometry of circulating lymphocytes; and, in men, testicular ultrasound.Design/methods We carried out a retrospective review of 128 patients entered into the Mayo Lymphoma Project data bank (1975–1994).Results Between the years 1975 and 1994, five patients (3.9%) were identified who fulfilled criteria for the diagnosis of PCNSL (typical clinical history, pathognomonic neuro-imaging, and histologie proof of NHL in brain tissue) but who had occult systemic NHL on staging (bone marrow 1, abdominal lymph nodes 3), or at autopsy (colon 1). Case histories are presented.Conclusions Patients with apparent PCNSL may have systemic NHL. Complete staging is essential to the initial management of patients presenting as PCNSL to exclude systemic stage IV disease.Presented at the First Congress of the European Association for Neuro-Oncology October 17, Maastricht, The Netherlands     

Dissemination and tissue invasiveness in murine acute leukemia associated with acquisition of p53 mutation and loss of wild-type p53

Approximately 60% of mice treated with split-dose radiation develop leukemias that disseminate widely through the body, whereas 40% of the treated mice incur leukemias that are contained entirely within the thymus. We studied the status of p53 in non-cultured samples of thymic leukemias and in cell lines established from these leukemias. In those mice with disseminated disease, primary samples were also obtained from visceral leukemic organs, and cell lines were established from these leukemic organs for further study. Using single-strand conformation polymorphism (SSCP), nucleic acid sequencing, and immunochemical analysis, we found that mutation of both p53 alleles occurred in leukemic cell lines developed from nine of 10 disseminated leukemias; mutation of one p53 allele with the other remaining wild-type occurred in one disseminated leukemia. A p53 mutation unique for each mouse was found in all cell lines established from the different leukemic organs of each mouse. The same mutation was also found in the non-cultured leukemic tissues of each mouse, indicating that the mutations originated in vivo and were clonal. Seven of seven non-disseminating thymomas possessed wild-type p53 only. Hence, in vivo dissemination and tissue invasiveness were associated with the loss of wild-type p53 by mutation of both alleles or by mutation and loss of heterozygosity, as revealed by studies of cell lines established from them. The selective in vivo dissemination of leukemia cells possessing p53 mutations had a parallel in vitro. Leukemia cell lines from mice harboring disseminating leukemia were established more readily (success rate greater than 80%) than lines from mice harboring thymic nondisseminating leukemia (success rate less than 10%). Additionally, while mice with disseminating leukemia harbored a mixture of wild-type and mutant p53—encoding thymoma cells, only cell lines possessing mutant p53 became established in culture. Mutations found in thymoma cell lines were always detectable by SSCP and sequencing of DNA extracted from non-cultured thymoma tissue. However, in non-cultured leukemic tissue of visceral organs, the clonal p53 mutations found in cell lines established from them were often not detectable by SSCP or sequencing but were detectable by immunochemical analysis or polymerase chain reaction amplification. This indicates an unexpected degree of masking of mutant genes by wild-type genes present in the leukemic tissue. Masking was evident even in leukemic organs that were grossly larger than normal organs. Hence, routine screening of leukemic tissue by SSCP and sequencing may result in a highly significant underestimation of the incidence of p53 mutations. The widely reported discrepancies between the loss of tumor suppressor genes (e.g., p16^INK4) in human tumors compared with the incidence of loss in cell lines established from the tumors may, in part, result from similar detection difficulties. © 1995 Wiley-Liss, Inc.     

热效应在淋巴瘤诊断与研究中的应用

石蜡包埋组织免痘组化染色是淋巴瘤病理诊断与研究的重要手段之一，由于常规组织处理过程造成抗原封闭与结构改变，使一些抗体不能用于石蜡切片或厦应微弱，我们应用热介导抗原恢复效应引起蛋白结构改变原理，对组织切片在高压铸内进行热处理，使原来只用于冰冻切片的某些抗体现可用于石蜡切片，扩大了抗体的使用范围，提高了免覆组化在淋巴瘤诊断与研究中的应用价值，增强了免疫染色的敏感性，使抗体稀释度增加0～20倍．使多数淋巴瘤得到准确诊断。     

Reactivity of anti-AraC-resistant cell monoclonal antibody, YU-311, in formalin-fixed paraffin-embedded specimens of various hematopoietic disorders

YU-311 is a monoclonal antibody reacting with cytosine arabinoside (AraC)-resistant human leukemic cell line and identifies a 92 kDa membrane protein. We have examined YU-311 reactivity with various hematopoietic disorders by an immunohistochemical method and evaluated a correlation between YU-311 expression and refractoriness to chemotherapy, retrospectively. YU-311 reacted with AraC-resistant human leukemia cell lines, in which a 92 kDa membrane protein was identified by Western blotting, whereas drug-resistant cell lines to other than AraC failed to express YU-311 antigen. The frequency of YU-311 positivity was significantly increased in relapsed cases. Only five cases were positive for YU-311 at diagnosis and 24 cases at relapse. Unexpectedly, only eight cases of relapsed leukemia/lymphoma expressed YU-311 and P-glycoprotein simultaneously. Most of the YU-311-positive relapsed cases showed clinical refractoriness for chemotherapy and then failed to induct complete remission or relapsed at short periods with short disease-free duration. These findings indicate that YU-311 expression is closely associated with some aspects of drug resistance, especially with AraC resistance.     

54例原发胃非何杰金淋巴瘤预后因素分析

目的 :分析原发胃非何杰金淋巴瘤 (PG- NHL )经不同方法治疗后的结果及预后因素。材料与方法 :1984年～ 1992年共收治 5 4例 PG- NHL ( 期 19例 , 期 2 3例 , 期 6例 , 期 6例 .4 5例作胃根治术 ,7例作探查术 .术后无辅助治疗 2例 ,4 3例作放疗、化疗或放疗加化疗综合治疗。结果 : ～ 期 5年生存率分别为 94 .7%± 13.5 %、79.1%± 12 %、80 .0 %± 2 5 .3%和 16 .7%± 15 .2 % (生命表法μ检验 )。影响预后的主要因素是病理分期与术后辅助治疗的策略 ,其次是原发肿瘤的体积、单发或多发。结论 :肿瘤侵及粘膜层或浅肌层属于 期早 ,根治术后有 /无辅助治疗 ,其疗效相同。已侵及胃全层的 期晚和 期应作全腹放疗 , 期宜先放疗后化疗 , 期应先化疗后放疗的综合治疗。放疗腹部中平面剂量为 4 0～ 4 5 Gy,化疗常用阿霉素、环磷酰胺、长春新碱、平阳霉素和强的松 (CHOP- BLM)的方案 ,4～ 6周期     

850例非何杰金氏恶性淋巴瘤的分析

本文对辽宁省部分地区850例非何杰金氏恶性淋巴瘤进行了回顾性分析。结果:B细胞型淋巴瘤占全部病例的70%,其中滤泡型淋巴瘤17例,核裂、无核裂及混合细胞型淋巴瘤占79.44%,而浆细胞及免疫母细胞型较少。T细胞型淋巴瘤占总数的28%,其中透明细胞型和多形细胞型占大多数。并提出分型意见和各型的鉴别要点。     

Therapy of primary central nervous system lymphoma with pre-irradiation methotrexate, cyclophosphamide, doxorubicin, vincristine, and dexamethasone (MCHOD)

Prior studies have suggested that pre-irradiation methotrexate (MTX)-based chemotherapy improves duration of response and survival in primary central nervous system lymphoma (PCNSL). To circumvent the potential emergence of drug resistance, we combined high-dose MTX with agents highly active against systemic lymphoma. Patients received three week cycles of CHOD (cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², and vincristine 1.4 mg/m² [2 mg maximum] on day 1; dexamethasone 10 mg/m² days 1–5), and MTX (3.5 gm/m²) with leucovorin rescue on day 8 (or on recovery from the CHOD nadir). Whole brain irradiation (WBRT) was planned after at least three cycles. Eighteen patients were treated. Complete responses were seen in eleven patients, and partial responses in three. Four progressed during therapy, three succumbing to progressive disease and one subsequently responding to WBRT Response duration was 37.5 months in those responding to therapy. The time to progression for all eighteen patients was 19.5 months. Medial survival was 25.5 months. Disease-free survival was 50% at 38 months in MCHOD responders. Grade 3 or 4 myelotoxicity was seen in 19 of 50 cycles. There were three instances of neutropenic fever, three of azotemia, two of deep vein thrombosis, and one each of community-acquired pneumonia, intracranial hemorrhage, superior vena cava syndrome, and hepatotoxicity. Late radiation-related toxicities were seen in two patients. Pre-irradiation MCHOD has activity against PCNSL, but appears to be no better than MTX monotherapy and has greater toxicity.     

Primary Non-Hodgkin Malignant Lymphoma of the Male Breast

A case of primary non-Hodgkin lymphoma of the male breast isreported. The patient was a 76-year-old Japanese with a historyof bilateral gynecomastia. After the patient had received sexhormone treatment for the gynecomastia, rapid growth of a tumorin the right breast was noted, with regression of a contralateralbreast lesion. Clinically, inflammatory breast cancer was suspected,and right mastectomy with ipsilateral axillary lymph node dissectionwas performed after intraarterial infusion chemotherapy usinga cis-platinum derivative. The histology of the surgical specimenwas non-Hodgkin malignant lymphoma of the diffuse large celltype, with focal tumor necrosis. Immunohistochemically, thetumor cells showed a B-cell nature. The patient is currentlywell without disease 39 months after surgery.     

Metastatic Potential of Lymphoma/Leukemia Cell Lines in SCID Mice Is Closely Related to Expression of CD44

To investigate whether the lymphocyte homing receptors, adhesion molecules regulating normal lymphocyte traffic, influence the dissemination of lymphoma cells, 24 lymphoma/leukemia cell lines were inoculated into SCID mice subcutaneously, and the correlation between the expression of the adhesion molecules and the metastatic potential of the cell lines was examined. Among the six adhesion molecules examined (LFA-1, ICAM-1, CLA, VLA-4, L-selectin and CD44), L-selectin increased the incidence of lymph node metastasis, and CD44 expression was related to both lymph node and organ (hematogenous) metastasis. A monoclonal antibody to the standard form of CD44 (CD44s), Hermes-3, inhibited the local growth and remote metastasis of CD44⁺ cell lines. Thus, it is concluded that at least CD44s expression is important in both lymphatic and hematogenous metastasis.