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N L Harris

Publications and source records attributed to N L Harris.

At least 91 records · Page 5Linked to original sources
PubMed1996

The morphologic spectrum of non-Hodgkin's lymphomas with BCL1/cyclin D1 gene rearrangements.

BCL1/PRAD1 gene rearrangements involving the cyclin D1 gene are a feature of about 70% of centrocytic/mantle-cell lymphomas (CC/MCL) but are identified in only a small proportion of other B-cell non-Hodgkin's lymphomas. Of 37 lymphomas found to have BCL1/cyclin D1 (PRAD1, CCND1) gene rearrangements, 30 fit the morphologic and immunophenotypic criteria for typical CC/MCL. Seven cases with morphologic features atypical for CC/MCL were identified. CD5+ monoclonal B cells were documented in all these cases. Six cases were subsequently stained for cyclin D1 protein, and all showed nuclear positivity. Five cases had variably sized foci of cells with moderately abundant pale cytoplasm resembling parafollicular/monocytoid B cells, marginal zone cells, hairy cells, or even proliferation centers. Transformed-appearing cells were also present in some lymphomas. In one case, striking follicular colonization created a markedly nodular growth pattern mimicking a follicular lymphoma. A sixth case had a marked predominance of small, round lymphocytes at some sites, mimicking a small lymphocytic lymphoma. Five of these six cases also had areas more typical of CC/MCL. The seventh case was a CD5-positive splenic marginal zone-like lymphoma (SMZL) with plasmacytic differentiation and circulating villous lymphocytes consistent with a splenic lymphoma with villous lymphocytes (SLVL). These cases illustrate the morphologic spectrum of small B-cell lymphoid neoplasms that have BCL1/cyclin D1 gene rearrangements and overexpression of cyclin D1. Despite the BCL1 translocation and cyclin D1 overexpression, the splenic lymphoma with plasmacytic differentiation was definitely not a CC/MCL and fit the clinicopathologic entity of SMZL/SLVL. The other six cases are best considered CC/MCL variants based on a combined morphologic, immunophenotypic, and genotypic evaluation. Genotypic or immunophenotypic studies to identify cyclin D1 rearrangements and overexpression, although not pathognomonic, are useful in recognizing these variant CC/MCL cases, which can mimic almost any of the other well-described but more indolent low-grade B-cell lymphomas and leukemias. Some of the variant CC/MCL cases had features in common with the CD5+ cyclin D1+ SMZL/SLVL, suggesting a possible relationship between these two otherwise distinct entities.

Adult↗
PubMed1996

Marginal zone lymphoma (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type) of skin and subcutaneous tissue: a study of 15 patients.

Extranodal low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type occurs in the gastrointestinal tract, salivary gland, thyroid, orbit, lung, and breast. We report 15 patients with MALT-type lymphomas involving skin and subcutaneous tissue. All patients had tumors with histologic features of low-grade B-cell lymphoma of MALT type, including marginal zone cells (15 of 15 cases), plasmacytic differentiation (10 of 15 cases), Dutcher bodies (three of 15 cases), and reactive germinal centers (10 of 15 cases). All expressed pan B-cell antigens and monotypic immunoglobulin. Seven patients (five women, two men) aged 29 to 86 years (median, 53 years) had primary MALT-type lymphoma of skin (6) or subcutaneous tissue (1). One patient had persistent disease, and four patients had relapses involving skin, subcutaneous tissue, breast, orbit, and lymph node. At last follow-up (11-121 months; median, 36 months), one patient was alive with disease, and six patients had no evidence of disease. Three patients (two women, one man) aged 36 to 67 years (median, 57 years) had concurrent MALT-type lymphoma involving both subcutaneous tissue and extracutaneous sites at primary diagnosis, including lung, breast, orbit, lymph node, and bone marrow. One patient responded to treatment but relapsed with lymphoma of the skin and breast. The other two patients had persistent disease despite treatment. One patient died of disease at 25 months, and, at last follow-up (7 and 46 months), two patients were alive with disease. Five patients (four women and one man) aged 29 to 72 years (median, 63 years) had secondary skin or subcutaneous involvement by MALT-type lymphoma with primary tumors of ocular adnexa (3) or parotid gland (2). All five patients had relapses, which involved skin or subcutaneous tissue, parotid gland, lacrimal gland, breast, and lymph node. At last follow-up (61-137 months), two patients were alive with disease and three were alive with no evidence of disease. Low-grade B-cell lymphomas of MALT type may arise in or secondarily involve the skin and subcutaneous tissue and have a tendency to affect middle-aged to older women. These tumors are characterized by multiple extranodal relapses and are associated with long patient survival. Patients with primary MALT-type lymphoma of skin or subcutaneous tissue without extracutaneous involvement at diagnosis were more likely to experience prolonged disease-free survival than patients with extracutaneous spread at presentation (p < 0.03).

Adult↗
PubMed1996

Expression of CD95 antigen and Bcl-2 protein in non-Hodgkin's lymphomas and Hodgkin's disease.

CD95 (APO-1/Fas) is a member of the superfamily that includes the nerve growth factor and tumor necrosis factor receptors, OX40, CD27, CD30, and CD40. Present on a minority of resting blood lymphocytes, CD95 expression is upregulated on activated T and B lymphocytes and natural killer cells, where binding of the antigen by anti-Fas and anti-APO-1 antibodies has been shown to induce apoptosis. This CD95-mediated apoptosis is at least partially inhibited by expression of the Bcl-2 protooncogene. To evaluate possible roles of CD95 and Bcl-2 in growth regulation of lymphoid neoplasms, we studied by immunohistochemistry the expression of CD95 and Bcl-2 in 67 B- and 5 T-cell lymphomas, and 10 cases of Hodgkin's disease. In all, 29 B and 2 T cell lymphomas, and 9 cases of Hodgkin's disease expressed CD95. Compared with diffuse large B-cell and Burkitt-like lymphomas, lowgrade B-cell lymphomas more frequently expressed CD95 (52% versus 26%; P < .005). None of the B-cell small lymphocytic lymphomas or mantle cell lymphomas expressed CD95, whereas the majority of follicle center lymphomas, extranodal marginal zone B-cell lymphomas, and immunocytomas were CD95+. Of the 29 CD95+ B-cell lymphomas, only 33% of the high-grade group coexpressed Bcl-2, compared with 87% of the low-grade group (P < .04). Two of three peripheral T-cell lymphomas--including one anaplastic large cell lymphoma--expressed CD95. Staining for CD95 was seen in 9 of 10 cases of Hodgkin's disease. The infrequent expression of CD95 in high-grade B-cell lymphomas suggests an association between loss of CD95 expression/function and a more aggressive tumor grade. Whereas frequent coexpression of Bcl-2 with CD95 may protect low-grade B-cell lymphomas against CD95-mediated apoptosis, in the high-grade group such coexpression is infrequent, and other regulators besides Bcl-2 may be involved in modulating the apoptosis signal delivered by CD95.

Animals↗
PubMed1996

Subspecialization of surgical pathology at the Massachusetts General Hospital.

The anatomic pathology unit of the Massachusetts General Hospital (MGH) serves both the MGH (an 862-bed general hospital generating about 39,000 surgical accessions and 33,500 gynecologic and 8,500 nongynecologic cytology accessions annually) and the Massachusetts Eye and Ear Infirmary (MEEI, a 52-bed specialty hospital generating about 6,500 surgical accessions and 1,000 nongynecologic cytology accessions annually); the unit has 25 full-time equivalent (FTE) staff pathologists and pathology fellows providing its diagnostic services. On July 1, 1995, diagnostic specimen signout in this unit was changed to a system of complete subspecialization. The historical context and rationale for this change and the process of its implementation are presented, with a preliminary evaluation of its effects, including the impact on pathology staff, fellows, and residents. In addition, a mechanism for evaluation of equity and efficiency of pathologist work is presented, together with some discussion of the limitations of its accuracy. The authors conclude that to date the change has achieved many of its expected effects and that the process has worked smoothly. Further experience will clarify the overall results of the change.

Hospitals↗
PubMed1995

Quantitative binding site model generation: compass applied to multiple chemotypes targeting the 5-HT1A receptor.

We present enhancements to the Compass algorithm that automatically deduce interchemotype relationships and generate predictive quantitative models of receptor binding based solely on structure-activity data. We applied the technique to a series of compounds assayed for 5-HT1A binding. A model was constructed from 20 compounds of two chemotypes and used to predict the affinities and bioactive conformation of 35 new compounds, most of which had new underlying scaffolds and/or functional groups. The model's mean error of prediction was 0.5 log units (essentially the assay resolution), even on quite divergent series. The predictions are supported by an interpretable hypothesis for the binding determinants of the receptor and the geometric relationships of the chemotypes.

Algorithms↗
PubMed1995

Expression of cyclin D1 protein in centrocytic/mantle cell lymphomas with and without rearrangement of the BCL1/cyclin D1 gene.

Centrocytic/mantle cell lymphoma (CC/MCL) is a morphologically defined B-cell non-Hodgkin's lymphoma characterized by a distinctive immunophenotype, BCL1/cyclin D1 (PRAD1) gene rearrangements, and, most recently, by overexpression of cyclin D1. Even using multiple breakpoint probes for BCL1 (MTC, p94PS) and cyclin D1, however, only approximately 70% of CC/MCL have a rearrangement consistent with a t(11;14) (q13;q32). To determine whether the type of molecular translocation affects the degree of cyclin D1 expression and to evaluate lymphomas diagnosed as CC/MCL but lacking molecular evidence of a BCL1 or cyclin D1 translocation, 16 CC/MCL and four cases of small lymphocytic lymphoma/B-CL1 (SLL/B-CLL) were stained using an anti-cyclin D1 antibody. All cases with a cyclin D1 translocation detected by Southern blotting techniques as well as four of the five CC/MCL without a documentable translocation showed nuclear cyclin D1 protein expression. There was no apparent correlation between staining intensity and the precise site or presence of a detectable translocation. Cases with a mantle zone growth pattern showed infiltration of the cyclin D1 positive cells into reactive follicular centers. None of the four SLL/B-CLL showed cyclin D1 expression. These findings show overexpression of the cyclin D1 protein in virtually all CC/MCL independent of the type or presence of a documentable BCL1 or cyclin D1 molecular rearrangement. The mechanism for cyclin D1 overexpression in the cases without a documentable rearrangement and the relationship of cyclin D1 overexpression to the pathogenesis of mantle cell neoplasia remain uncertain.

Cyclin D1↗
PubMed1995

Ocular adnexal lymphoma. A clinicopathologic study with identification of lymphomas of mucosa-associated lymphoid tissue type.

PURPOSE: Extranodal marginal zone B-cell lymphoma (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue [MALT] type) is a distinctive type of lymphoma that usually arises in association with mucosa or other epithelial structures and has an indolent clinical course. The frequency and clinical features of MALT lymphomas in the ocular adnexa have not been well studied. METHODS: The authors examined the clinicopathologic features of ocular adnexal lymphoma, identified a subset of cases with MALT characteristics, and determined patient outcome. RESULTS: The 42 patients, 16 men and 26 women age 35-89 years (mean, 64) were followed an average of 4.8 years. Thirty-two patients had ocular adnexal involvement at presentation (primary ocular adnexal lymphoma) and 10 had a history of lymphoma that relapsed in the orbit (secondary ocular adnexal lymphoma). In the primary group, 23 patients had lymphoma confined to the ocular adnexa, 3 had a single lesion that invaded adjacent structures, and 6 had distant spread at the time of presentation. Twenty-five patients achieved a complete remission. Nine patients, including 6 patients whose disease was localized initially, had progression or relapse of disease in distant sites. At last follow-up, 21 patients were free of disease, 9 were alive with disease and 2 had died of lymphoma. In the secondary group, at last follow-up, 1 patient had died of other causes, free of lymphoma, 3 patients were alive with disease and 5 had died of lymphoma (outcome not known in 1 case). Using the recently described revised European-American lymphoma classification, we found 16 MALT lymphomas, 8 diffuse large B cell, 12 follicular center, 3 mantle cell, 1 B-small lymphocytic lymphoma, and 2 unclassifiable low-grade lymphomas. The most common type of primary lymphoma was MALT type (15 of 30 classifiable cases), and the most common secondary lymphoma was follicular center (6 of 10). No increased frequency of conjunctival or lacrimal gland involvement by MALT lymphomas was found. All 33 lymphomas with immunophenotyping were of B lineage. CONCLUSIONS: Ocular adnexal lymphomas are B-cell tumors that develop in older adults, predominantly among women. Primary orbital lymphomas have a favorable prognosis; a high proportion of them have MALT characteristics.

Adult↗
PubMed1995

Posttransplantation lymphoproliferative disorders in solid organ recipients are predominantly aggressive tumors of host origin.

Patients immunosuppressed after organ transplantation have an increased frequency of lymphoproliferative disorders, known as posttransplantation lymphoproliferative disorders (PTLDs). In recipients of bone marrow allografts. PTLDs are often of donor origin. In only a few cases of lymphoma arising in solid-organ transplant recipients has the origin from host or donor lymphocytes been established. The authors have analyzed 11 cases of PTLD from Massachusetts General Hospital, arising in seven male and four female patients, aged 8 to 63, five with renal, four with cardiac, and two with hepatic allografts. Using the polymerase chain reaction (PCR) to investigate genetic polymorphism at the D4S174 locus on chromosome 4, the Rb1.20 locus on chromosome 13, and the D19S178 locus on chromosome 19, only one tumor (previously reported) was of donor origin, whereas 10 were of host origin. Follow-up revealed that six patients died of PTLD, one was alive with recurrent PTLD, and four were alive and well or had died of other causes, including the patient with donor-origin PTLD. Based on these cases and on a review of previously reported cases, the authors conclude that the majority of PTLDs in solid organ recipients are of host origin. There appears to be a trend toward a greater likelihood of persistent or recurrent PTLD among solid organ recipients with host-origin tumors than among those with donor-origin tumor.

Adolescent↗
PubMed1995

Cyclin D1 expression in non-Hodgkin's lymphomas. Detection by immunohistochemistry.

Cyclin D1/PRAD1 (bcl-1) is a recently discovered proto-oncogene that is overexpressed in mantle cell lymphomas and several other human tumors. In a previous study, the authors demonstrated expression of cyclin D1 in 15 of 15 cases of mantle cell lymphoma and 1 of 8 cases of B-chronic lymphocytic leukemia (B-CLL) using a polyclonal antibody and microwave enhanced immunohistochemical staining method on paraffin-embedded tissue sections. In this study, 107 additional B- and T-cell neoplasms were studied, including 47 cases of high grade lymphoma (33 diffuse large B-cell type, 9 Burkitt and Burkitt-like, 4 precursor T-lymphoblastic lymphoma, and 1 adult T-cell lymphoma/leukemia), 38 additional cases of low grade B-cell lymphoma (18 CLL, 15 hairy cell leukemia and 5 mantle cell lymphoma), and 22 plasmacytomas for expression of cyclin D1 using the same immunohistochemical staining technique. All cases of mantle cell lymphoma showed diffuse nuclear staining. No additional cases of CLL showed cyclin D1 expression. In contrast, 1 of 15 hairy cell leukemias and 1 of 22 plasmacytomas showed cyclin D1 staining. None of the high grade lymphomas demonstrated expression of cyclin D1 protein by immunostaining, including three cases of large B-cell lymphoma that coexpressed CD5. The authors conclude that cyclin D1 is expressed in all cases of mantle cell lymphoma, and only in very rare cases of B-CLL, hairy cell leukemia and plasmacytoma/myeloma. Cyclin D1 does not appear to play an important role in high grade lymphomas. In addition, most CD5 positive high grade B-cell lymphomas do not express cyclin D1, and are not likely to be derived from mantle cell lymphoma or other lymphomas with t(11;14).

Cyclin D1↗
PubMed1995

Extramedullary tumors of lymphoid or myeloid blasts. The role of immunohistology in diagnosis and classification.

The diagnosis of primitive hematologic malignancies in extramedullary sites (lymphoblastic lymphoma of T- or B-cell type and myeloid sarcoma) on paraffin-embedded tissue sections is difficult and often impossible because of the primitive morphology of the neoplastic cells. The authors studied 21 extramedullary tumors of lymphoid or myeloid blasts. They used a panel of 22 antibodies on frozen sections and 9 antibodies on paraffin sections to determine the spectrum of immunophenotypes and to develop a practical panel for diagnosis. All but two of the cases could be classified as lymphoid or myeloid using immunohistologic analysis. Thirteen cases were classified as lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL); 10 were classified as precursor T (CD7+, CD3+/-, CD45+) and 3 as precursor B-cell (CD19+/-CD10+CD45-) type. Five cases were classified as myeloid sarcoma (CD13+ myeloperoxidase+, lysozyme+). Two LBL/ALL coexpressed either CD33 (1 case) or CD15 (1 case), and one myeloid sarcoma coexpressed TdT and CD7. One case appeared to be truly mixed lineage, coexpressing CD3 with myeloperoxidase and lysozyme, and two cases expressed no lineage-specific antigens. There were clinical differences between the three major tumor types, and within the category of T-precursor LBL/ALL, classification according to stage of thymocyte differentiation was associated with distinctive clinical features. In conclusion, the spectrum of immunophenotypes detected on frozen section was similar to that reported by flow cytometry on peripheral blood and bone marrow specimens. The most useful antigens on frozen sections were CD7 and CD3 (T cell), CD10 and CD19 (B cell), and CD13 (myeloid). TdT was coexpressed by one myeloid sarcoma and was undetectable in 40% of LBL/ALL. On paraffin sections, myeloperoxidase and lysozyme were reliable markers of myeloid lineage, but none of the markers used on paraffin sections distinguished between LBL/ALL of T- and B-precursor types. Both B-LBL/ALL and myeloid sarcomas were often CD45- on paraffin sections, which may be a obstacle in determining the diagnosis. These distinctions appear to have clinical relevance.

Adolescent↗
PubMed1995

Lymphoma of the kidney. A report of 11 cases.

We describe 11 patients first seen with symptoms or signs related to lymphoma predominantly or exclusively involving one or both kidneys. The patients were seven men and four women, aged 40-77 years (median, 67). Seven of them had one or more other prior (four), subsequent (two) or both simultaneous and subsequent (one) primary malignant or premalignant lesions. The presenting symptoms of the patients with lymphoma included local pain (five cases), loss of appetite or nausea (four cases), hematuria (two cases), weight loss (two cases) or malaise (two cases). One patient had renal failure at presentation. One lymphoma was an incidental finding at the time of aneurysm resection. Nine patients had unilateral disease; two patients had bilateral disease. Six unilateral cases were initially considered on clinical (five) or clinical and pathological (one) evaluation to be primary carcinomas of the kidney. Gross examination of nephrectomy specimens revealed fleshy or firm, yellow, tan, or gray tumors from 5.7 to 22 cm (median, 7.5) in greatest dimensions that frequently invaded perinephric fat and adjacent structures. The lymphomas were subclassified as diffuse large cell (seven cases), follicular and diffuse large cell (one case), small lymphocytic plasmacytoid (two cases), and small noncleaved cell lymphoma (non-Burkitt's type) (one case). Immunophenotyping in nine cases revealed that all were B-lineage tumors. Three patients had Ann Arbor stage I disease, three had stage II, and five had stage IV. On follow-up, ranging from 1 week to 169 months (median, 15 months), 5 patients were alive and free of lymphoma. Four patients died of progressive disease 1 week to 23 months after diagnosis. One patient is alive at 4 months but has not completed chemotherapy. One asymptomatic patient has not been treated. Renal lymphomas are predominantly large-cell lymphomas of B-lineage affecting middle-aged and older adults and often can be treated successfully. Both clinically and pathologically, they can be mistaken for carcinomas of the kidney. A high proportion of patients in this series had malignant tumors of other types.

Adult↗
PubMed1995

A practical approach to the pathology of lymphoid neoplasms: a revised European-American classification from the International Lymphoma Study Group.

This formulation includes a number of disease entities which may alarm those who believe that a lymphoma classification must be simple. The fact remains that these are the tumors that pathologists are seeing and diagnosing, and oncologists must be prepared to deal with them. If several morphologically, immunologically and genetically distinct neoplasms prove to respond identically to currently available treatment, the can be "lumped" for the purposes of clinical treatment selection (see Table 11-3). However, if new forms of treatment become available, particularly if these are directed against antigenic or genetic features, it will be important to recognize and study each disease separately. This study should be regarded as a preliminary effort to develop a consensus on lymphoma categorization, and constitutes merely a framework for further study. The ILSG has not attempted to determine the reproducibility of diagnosis of the various categories, either among different pathologists or by the same pathologist over time. No prior tumor classification has been based on reproducibility and when such studies have been done with existing classifications of lymphoma, they have shown disappointing results. 1,35,119 It is likely that recognition of clearly defined entities, which have characteristic immunophenotypes and in some cases genetic features, as well a characteristics morphology, will facilitate reproducibility among pathologists.189 Formal reproducibility studies should be undertaken, and should in general be a more frequent activity in the pathologic diagnosis of tumors. The ILSG does not have the resources to make a systematic attempt to determine the utility of these histologically and immunologically defined categories in predicting clinical outcome. The task of the pathologist is to attempt to define diseases by morphologic and other criteria applied to tissue specimens, and this has been the goal of the current endeavor. The clinical information about the different entities is taken from studies already published, which clearly show that each of the entities has distinctive clinical behavior, even if distinctive treatments are not currently available. The joint task of clinical oncologist and hematopathologists now is to undertake systematic application of the criteria presented here to defined groups of patients, to determine whether the newly-recognized categories will help to further stratify treatment response and outcome in clinical trials. Several members of the ILSG have already begun to review cases in cooperative group trials, and have found the recognition of these entities within broad Working Formulation categories can have prognostic implications (Grogan, T and Banks, PM, unpublished data from the Southwest Oncology Group [SWOG]).(ABSTRACT TRUNCATED AT 400 WORDS)

Female↗
PubMed1995

Development of extrasalivary gland lymphoma in myoepithelial sialadenitis.

Myoepithelial sialadenitis of the salivary gland is associated with an increased risk of lymphoma, but criteria that predict its development have not been clearly defined. We attempted to identify morphologic and immunologic features that correlated with the presence of extrasalivary lymphoma in patients with myoepithelial sialadenitis. Twenty-five patients (20 women, 5 men; median age, 56 yr) were studied with clinical follow-up in 22 patients; 19 were followed for 3 or more yr (median, 8.0 yr overall). Immunostains were done on paraffin sections in 28 of 31 specimens (22 of 25 patients) using antibodies to immunoglobulin light chains, CD20, CD45RO, CD3, and CD43. Morphologic features studied included density of infiltrate, lymphoepithelial lesions, follicle atypia, and pattern of monocytoid B-cells. Twenty-four of 25 patients had dense lymphoid infiltrates expanding and effacing salivary gland architecture with lymphoepithelial lesions and epimyoepithelial islands; all but one of these cases showed monocytoid B-cells in and around ducts, whereas six also had interconnecting broad strands of these cells. One case showed predominantly follicular hyperplasia. Two cases contained follicles with large atypical cells. Plasma cells were monotypic in four patients (18%) and polytypic in 18 (82%); in 18 of 28 specimens (64%) from 15 of 22 patients (68%), monocytoid B-cells coexpressed CD20 and CD43. Seven patients developed extrasalivary lymphoma, one before and six after the diagnosis of myoepithelial sialadenitis (median, 30.5 mo). Monotypic immunoglobulin in plasma cells correlated with past or subsequent extrasalivary lymphoma (P < 0.005); broad strands of monocytoid B-cells correlated with both monotypic plasma cells (P < 0.005) and extrasalivary lymphoma (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Pathology with clinical correlations of primary central nervous system non-Hodgkin's lymphoma. The Massachusetts General Hospital experience 1958-1989.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Brain Neoplasms↗