Miller D C, Hochberg F H, Harris N L, Gruber M L, Louis D N, Cohen H
Department of Pathology, Rita and Stanley Kaplan Comprehensive Cancer Center, New York University Medical Center, New York 10016.
Cancer. 1994 Aug 15;74(4):1383-97. doi: 10.1002/1097-0142(19940815)74:4<1383::aid-cncr2820740432>3.0.co;2-1.
Primary central nervous system non-Hodgkin's lymphoma (NHL-CNS) is an enigmatic disease of uncertain origin. At the Massachusetts General Hospital, 104 patients with NHL-CNS were seen from 1958 through 1989. An impression of changes in the frequency of diagnosis, character of the tumors, and therapy for this disease prompted this study of the pathologic features, clinical data, and natural history of this tumor in these 104 patients.
Histologic slides (neurosurgical specimens and autopsy tissues) were available for 99 patients. The tumors were classified by the Working Formulation classification. Immunostaining data and all clinical data were retrieved from the relevant offices and hospital charts.
Primary central nervous system non-Hodgkin's lymphoma tripled in frequency (5.66 cases per year in 1978-89 versus 1.75 cases per year in 1958-77) and now represents 6.6% of all primary brain neoplasms (versus 3.3% before 1978; chi 2 = 17.52, P < 0.01). For the 99 tumors histologically classified, 89% were high grade. Intermediate grade lymphomas, once the second most common subtype, have disappeared since 1983. All tumors had diffuse architecture; 77% (including all 11 patients with acquired immune deficiency syndrome) were large cell subtypes. Two cases were intravascular lymphoma. With one exception, all of the 41 tumors evaluated were B-cell types; 32 of 40 had monotypic surface immunoglobulin. There was 1 T-cell lymphoma. Of 64 tumor recurrences, 29 were at the initially defined site; 12 were in the leptomeninges, 29 were in other sites in the neuraxis, and 8 were in systemic sites. Systemic metastases have not occurred since 1984. Median survival for the 68 patients who survived after diagnostic surgery and for whom follow-up information could be obtained was 19 months; 9 months for those with high grade tumors and 30.5 months for those with intermediate grade tumors. This difference was not significant (P = 0.13). A separate set of seven patients had focal tumorlike lymphoid infiltrates composed of benign-appearing lymphocytes, which were associated with good long term survival. The differential histologic diagnosis of NHL-CNS was occasionally difficult, and the spectrum of this differential was broader than generally stated.
Primary central nervous system non-Hodgkin's lymphoma has increased in frequency even in nonimunocompromised patient populations. This increase has been accompanied by the disappearance of intermediate grade histologic types, suggesting a fundamental shift in the biology of the neoplasms. The introduction of chemotherapeutic regimens appears to have altered the natural history such that systemic metastases outside the central nervous system no longer occur, and there are now some long term survivors of this formerly uniformly fatal disease.
原发性中枢神经系统非霍奇金淋巴瘤（NHL-CNS）是一种起源不明的神秘疾病。1958年至1989年期间，马萨诸塞州总医院共收治了104例NHL-CNS患者。对该疾病诊断频率、肿瘤特征及治疗方法变化的印象促使对这104例患者的肿瘤病理特征、临床数据及自然病程进行研究。
99例患者有组织学切片（神经外科标本和尸检组织）。肿瘤按工作分类法进行分类。免疫染色数据和所有临床数据从相关科室和医院病历中获取。
原发性中枢神经系统非霍奇金淋巴瘤的发病率增加了两倍（1978 - 1989年每年5.66例，而1958 - 1977年每年1.75例），目前占所有原发性脑肿瘤的6.6%（1978年前为3.3%；χ² = 17.52，P < 0.01）。在99例经组织学分类的肿瘤中，89%为高级别。中级别淋巴瘤曾是第二常见的亚型，自1983年起已消失。所有肿瘤均为弥漫性结构；77%（包括所有11例获得性免疫缺陷综合征患者）为大细胞亚型。2例为血管内淋巴瘤。除1例例外，在评估的41例肿瘤中，所有均为B细胞型；40例中的32例有单型表面免疫球蛋白。有1例T细胞淋巴瘤。在64例肿瘤复发中，29例在最初确定的部位；12例在软脑膜，29例在神经轴的其他部位，8例在全身部位。自1984年以来未发生全身转移。68例诊断性手术后存活且可获得随访信息的患者的中位生存期为19个月；高级别肿瘤患者为9个月，中级别肿瘤患者为30.5个月。这种差异无统计学意义（P = 0.13）。另有一组7例患者有由外观良性的淋巴细胞组成的局灶性肿瘤样淋巴浸润，与良好的长期生存相关。NHL-CNS的组织学鉴别诊断偶尔困难，且这种鉴别的范围比一般所述更广泛。
即使在非免疫受损患者群体中，原发性中枢神经系统非霍奇金淋巴瘤的发病率也有所增加。这种增加伴随着中级别组织学类型的消失，提示肿瘤生物学发生了根本性转变。化疗方案的引入似乎改变了自然病程，使得中枢神经系统外的全身转移不再发生，现在这种以前 uniformly fatal的疾病有了一些长期存活者。
