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N L Harris

Publications and source records attributed to N L Harris.

At least 109 records · Page 6Linked to original sources

Thymoma. Histologic subclassification is an independent prognostic factor.

BACKGROUND: Several histologic classifications of thymomas have been proposed, and attempts have been made to correlate the different histologic subtypes to clinical behavior and prognosis. Recently, Marino and Müller-Hermelink and Kirchner et al. proposed a new morphologic classification of thymomas based on the resemblance of the neoplastic cells to subtypes of the normal thymic epithelial cells. In this classification, six categories of thymic epithelial tumors are recognized. They define four categories of thymoma: medullary, mixed, organoid (predominantly cortical), and cortical, and two subgroups of thymic carcinomas: well differentiated thymic carcinoma and high grade carcinomas. METHODS: The authors studied 116 patients with thymic epithelial tumors classified according to the proposals of Marino and Müller-Hermelink and Kirchner et al. to assess the effect of histologic classification and other factors (stage, size of tumor, lymphoid hyperplasia, myasthenia gravis, age, sex, and treatment) on survival, and freedom from relapse. RESULTS: Eight cases (7%) were medullary, 32 cases (28%) mixed, 20 cases (17%) organoid (predominantly cortical), 21 cases (18%) cortical, 29 cases (25%) well differentiated carcinoma (WDTC), two cases (2%) high grade carcinoma, and four cases (3%) unclassifiable. Fifty-two patients were in stage I, 32 stage II (16 IIA, 16 IIB), 28 stage III, and four Stage IVA. Only stage (P = 0.0001; hazard ratio = 5.36) and histology (P = 0.0019; hazard ratio = 8.010) were significant in predicting recurrence. Histology was highly correlated with stage, but by multivariate analysis was an independent factor in predicting relapse (P = 0.0281; hazard ratio = 5.92). None of the medullary or mixed thymomas recurred, even though 30% were invasive. Patients with WDTC recurred more often and earlier than patients with organoid and cortical thymoma (log rank, P = 0.0001). The actuarial freedom from relapse for patients with WDTC was 58% at 5 years and 46% at 10 years compared with 100% for other subtypes. Both advanced stage (III and IV) and the WDTC histologic subtype significantly increased the risk of death from thymoma (log rank, P = 0.0001). The actuarial survival of patients with WDTC was 80% at 5 years and 54% at 10 years, whereas that of patients with the other subtypes was 100% at 5 and 10 years. Five of seven relapses and six of seven deaths from thymoma occurred in patients with WDTC. In Stage II patients, one of 16 minimally invasive (Stage IIA) tumors recurred, compared with 3 of 16 grossly invasive (Stage IIB) tumors, indicating that microscopic assessment of invasion is important in staging. CONCLUSIONS: The histologic classification of Marino and Müller-Hermelink has prognostic significance, independent of tumor stage. Medullary and mixed thymomas were benign tumors with no risk of recurrence, even when capsular invasion was present. Organoid and cortical thymoma showed intermediate invasiveness and a low, but significant, risk of late relapse, even with minimal invasion. WDTC were always invasive and had a significantly increased risk of relapse and death, even for Stage II patients. Adjuvant therapy appears unnecessary for medullary and mixed thymomas, even when invasive.

Adolescent↗

Four helix bundle diversity in globular proteins.

Four helix bundles are a common structural motif that can be observed both independently and as components of larger folding units. We examined 221 globular proteins of known structure for possible four helix bundles. Previous computational studies of four helix bundles have placed arbitrary restrictions on interhelical packing angles. In this study we develop a geometric definition of four helix bundles based in part on solvent accessibility criteria that permits the removal of constraints on interhelical packing. Based on the observed pattern of interhelical angles, a bundle taxonomy is presented. This formalism should provide a useful categorization method for future structural studies of proteins rich in alpha-helices. The helix-helix interactions within bundles were studied in detail. Central residues, contact normals, and skew angles all were observed to have non-random distributions. A simple geometric model was developed for the helix-helix interface to explain these findings. Analysis of the helix-helix interaction data collected in this work confirms the importance of including skew angles in models of helix packing, and should improve the accuracy of combinatorial strategies for the prediction of the tertiary structure of all-helical proteins. Additionally, the geometric properties observed in globular proteins provide insight into the structural organization of membrane spanning proteins.

Animals↗

Clonal analysis of posttransplant lymphoproliferative disorders, using both episomal Epstein-Barr virus and immunoglobulin genes as markers.

The authors analyzed the clonality of 15 samples of B-cell lymphoproliferations arising in eight organ allograft recipients, using immunoglobulin (Ig) gene rearrangement and the fused terminal fragment of episomal Epstein-Barr virus (EBV) DNA as independent clonal markers. The tumors arose from 1 month to 4 years following transplantation. All tumors were monomorphous, high-grade lymphomas of immunoblastic (6 cases), large-cell noncleaved (centroblastic, 1 case), or small noncleaved (1 case) type. All tumors were highly aggressive and failed to respond to decreased immunosuppression alone. Each tumor had clonal Ig gene rearrangements, including those that were negative for surface Ig. In 13 of 15 specimens (seven of the eight cases), the tumors also contained latent, circularized EBV genome. In 10 specimens from six patients, the tumors contained a single predominant form of episomal EBV DNA, indicating clonal cellular proliferation of an EBV-infected progenitor cell. Three specimens from one patient showed more than one band of episomal EBV DNA, suggesting oligoclonal expansion, despite the detection of only a single clone by Ig gene rearrangement. Linear replicating EBV DNA was not detected in any of the cases. Synchronous or metachronous specimens from multiple sites were studied in five patients, four of which were EBV-positive cases. Two patients had identical Ig gene arrangements in each specimen, indicating a single neoplastic clone at all sites; one case was EBV-negative, and the other had identical EBV episomes in each specimen. In the other three cases, apparently different Ig gene rearrangements were found at different sites. In two of these, however, the same predominant EBV episome was present at each site, indicating a common clonal origin. The third case had oligoclonal EBV bands in each specimen, with distinct patterns in at least two different sites, suggesting true multiclonality. Analysis of EBV genomes is a useful adjunct to Ig gene analysis in assessing the clonality of these lesions.

Adult↗

CD20+ T-cell lymphoma. Neoplastic transformation of a normal T-cell subset.

CD20 is a 35-kDa protein that is expressed early in B-cell ontogeny and is lost during terminal B-cell differentiation into plasma cells. It is thought to be B-cell-specific. However, the CD20 antigen, detected by the monoclonal antibody L26, has been reported in some cases of T-cell lymphoma. This report describes a case of a malignant lymphoma coexpressing T-cell-lineage antigens and CD20 and characterization of a CD20+ T-cell population in the peripheral blood of healthy donors. The tumor cells were pleomorphic medium-sized cells that expressed a range of T-cell-specific antigens, including CD2, CD3, CD4, CD5, CD6, CD7, and beta F1. In addition, the tumor cells expressed CD20 on frozen (B1) and paraffin sections (L-26). Stains for other pan-B cell antigens, including CD19 and CD22, and immunoglobulin light and heavy chains were negative. To determine whether this unusual coexpression of T-cell-lineage antigens and CD20 represented aberrant antigen expression or neoplastic transformation of an unusual normal T-cell subset, the authors examined specimens of peripheral blood lymphocytes from healthy donors for evidence of a CD20+ T-cell population by using three-color immunofluorescence analysis by flow cytometry. Two distinct populations of CD20+ cells were observed in peripheral blood. One expressed bright CD20 (6.6% to 23.7%, mean 14.47% of peripheral blood lymphocytes) and other B-cell associated antigens, whereas the other expressed dim CD20 (.94% to 11.90%, mean 3.50% of peripheral blood lymphocytes) and coexpressed CD3. Approximately two thirds (52.8% to 82.3%, mean 64.1%) of the dim CD20 cells were CD8+ and one third (19.2% to 74.1%, mean 37.5) CD4+. These cells also expressed CD5 and the alpha-beta chain of the T-cell receptor and lacked CD19 and CD22. These results indicate that CD20 is expressed on some normal peripheral blood T cells. CD20 expression by T-cell lymphomas may represent neoplastic transformation of a normal subset of CD20+ T cells rather than aberrant antigen expression by neoplastic cells. The nature of the CD20 antigen on T cells and the function of the normal population remain to be determined.

Aged↗

Malignant lymphoma of the testis, epididymis, and spermatic cord. A clinicopathologic study of 69 cases with immunophenotypic analysis.

We studied 69 cases of malignant lymphoma of the testis, epididymis, and spermatic cord, including 64 cases in which the tumor involved these sites at presentation and five cases in which lymphoma relapsed in the testis. The patients without prior lymphoma were 16 to 91 (mean, 56) years old. Fifty-two patients had diffuse large-cell lymphomas [seven large cleaved cell (two with follicular areas), 27 large noncleaved, two multilobated, six not otherwise specified (NOS), 10 immunoblastic]; six, small noncleaved cell; two, diffuse mixed small and large cell; one, diffuse small cleaved; one, follicular mixed small cleaved and large cell; and two, high grade, unclassified in the Working Formulation. Twenty-nine cases (55%) were stage I; five (9%), stage II; one (2%), stage III, and 18 (34%), stage IV. Forty patients (73%) achieved a complete remission; 23 had a relapse of tumor at 4 to 274 months (median, 13) and five were salvaged. At last follow-up, 20 (36%) patients were free of disease, six (11%) were alive with disease, and 29 (53%) had died of lymphoma. Features associated with longer disease-free actuarial survival (DFS) included stage I disease (p = 0.0001) and sclerosis (p = 0.0001). Among patients with stage I lymphoma, those with right-sided tumors (p = 0.005) or tumors with sclerosis (p = 0.0017) had longer DFS. Lymphomas with extensive sclerosis were all stage I (p = 0.0057). Four of five patients with secondary testicular lymphoma had extranodal primary sites. They ranged from 13 to 66 years (median, 35). Testicular relapses occurred 13-37 months after initial diagnosis. Three had diffuse large, noncleaved cell type; one, lymphoblastic and one, diffuse mixed small and large cell. Immunophenotyping showed B lineage in 33 cases and T lineage in one case. Most testicular lymphomas are B-lineage large-cell lymphomas, which frequently involve other extranodal sites at presentation and at relapse, and which often have an aggressive clinical course.

Adolescent↗

Nodular lymphocyte predominance Hodgkin's disease. A distinct clinicopathological entity.

This article reviews the evidence that the nodular form of lymphocyte predominance Hodgkin's disease ("nodular paragranuloma") should be recognised as a distinct clinico-pathological entity. The disease is characterised histologically by very large primary lymphoid follicles, containing polytypic small B lymphocytes and extensive meshworks of follicular dendritic cells. The "L and H" or "popcorn" cells scattered within the nodules show clear differences from classical Reed-Sternberg cells, both in their cytological appearance and in their marker profile, being frequently negative for CD15 and for the EBV genome, but often positive for B cell antigens, CD45 (leucocyte common antigen), CDw75 (LN1), epithelial membrane antigen (EMA) and J chain. These findings suggest that L and H cells may be Ig-synthesising monoclonal B cells. Nodular lymphocyte predominance Hodgkin's disease pursues a much more indolent courses that classical Hodgkin's disease, and long term survival is common. It has other distinctive clinical features, e.g. a unimodal age distribution, a predilection to involve single lymph nodes, and a very low incidence of thymic involvement. There is a tendency for diffuse large cell non-Hodgkin's lymphoma, usually of B cell type, to develop during the course of the disease. This type of Hodgkin's disease thus has many features that distinguish it from the nodular sclerosis and mixed cellularity varieties, and it is hoped that future studies will gather more information on its clinical behavior and on the nature of the putative neoplastic cells, as well as exploring different protocols for its treatment.

Hodgkin Disease↗

A proposal for classification of lymphoid neoplasms (by the International Lymphoma Study Group).

A new classification of lymphoid neoplasms, mostly based on existing terminology, is proposed by the International Lymphoma Study Group. The proposed classification was reached through a consensus of the members, despite their diverse backgrounds, and consists of a listing of currently recognized clinicopathological entities. These tumours are divided into three major categories: B-cell neoplasms, T-cell and postulated natural killer cell neoplasms, and Hodgkin's disease. The characterization of each entity is based on a synthesis of all available information. This concept departs from a purely morphological approach to lymphoma classification, which is considered to be inadequate, because many biologically distinctive lymphoma types can exhibit a broad and overlapping morphological spectrum. Some entities are provisional, pending further data to confirm that their recognition is reproducible. The salient clinicopathological features of each entity are summarized in this review.

Hodgkin Disease↗

Cyclin D1 (Bcl-1, PRAD1) protein expression in low-grade B-cell lymphomas and reactive hyperplasia.

Mantle cell (centrocytic) lymphoma (MCL) and occasional cases of B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia (B-SLL/CLL) show a characteristic translocation, t(11:14)(q13;q32) involving rearrangement of the Bcl-1 region. Recently it was shown that the key Bcl-1 region oncogene is cyclin D1/PRAD1; cyclin D1 mRNA was shown to be overexpressed in cases of MCL. We examined cyclin D1 protein expression in low-grade B-cell lymphomas and reactive lymphoid hyperplasias using polyclonal and monoclonal antibodies to cyclin D1 protein. Definite nuclear staining was seen in 15 of 15 MCLs, 1 of 7 B-SLL/CLLs, 0 of 7 reactive hyperplasias, 0 of 10 follicular lymphomas, and 0 of 4 lymphomas of mucosa-associated lymphoid tissue using immunoperoxidase stains on paraffin-embedded sections. Best results were obtained with the affinity-purified polyclonal antibody on microwave-treated, formalin-fixed, paraffin-embedded tissue. MCLs showed diffuse nuclear staining, whereas the one positive B-SLL/CLL showed dot-like or globular nuclear staining. Nuclear cyclin D1 protein can be detected in all cases of MCL and in rare cases of B-SLL/CLL using an immunohistochemical technique on formalin-fixed, paraffin-embedded tissue, and it does not appear to be detectable in reactive hyperplasias and other low-grade B-cell lymphomas. This protein may be useful in subclassification of low-grade B-cell lymphomas.

Blotting, Western↗

Richter's transformation of chronic lymphocytic leukemia with Hodgkin's-like cells is associated with Epstein-Barr virus infection.

The appearance of a high-grade lymphoma in the setting of B-cell chronic lymphocytic leukemia (CLL) is termed Richter's syndrome. Usually the high-grade component is a monomorphous, large cell lymphoma, but occasionally the high-grade component takes the form of Hodgkin's disease or a Hodgkin's-like lymphoma. Although Richter's syndrome is thought to represent clonal evolution of the underlying B-cell neoplasm in most cases, such a progression is difficult to explain when the high-grade component is Hodgkin's disease. We report two cases of Richter's syndrome in which the large cells had a morphology consistent with Reed-Sternberg cells and were found in a background of CLL. The large cells in both cases expressed the CD15 and CD30 antigens in a pattern characteristic of Reed-Sternberg cells, and the large cells in one case also expressed monotypic cytoplasmic immunoglobulin of the same type as that expressed by the underlying CLL. In both cases, Southern blot analysis of DNA from lymph nodes that contained both CLL and the Hodgkin's-like component showed single immunoglobulin gene rearrangements. Using the polymerase chain reaction, we found Epstein-Barr virus DNA in lymph nodes from both cases, and in peripheral blood lymphoid cells from one case 4 yr before the onset of Richter's syndrome. Immunoperoxidase staining showed expression of EBV latent membrane protein only in the Reed-Sternberg-like cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

bcl-2 rearrangements in de novo diffuse large cell lymphoma. Association with distinctive clinical features.

BACKGROUND: The frequency and clinical significance of bcl-2 rearrangement in de novo B-cell diffuse large cell lymphoma is largely unknown. METHODS: Using Southern blot hybridization and multiple DNA probes, the status of the protooncogene bcl-2 was investigated in frozen tissue samples from 45 carefully selected cases of de novo diffuse large cell lymphoma of B-cell origin. Results were correlated with the presenting clinical and immunophenotypic features and with the subsequent clinical course. RESULTS: Rearrangements of bcl-2 were identified in nine tumor specimens (20%). The bcl-2-positive cases more often presented as early-stage, nonmucosal associated extranodal tumors (P = 0.06) and were more often HLA-DR negative (P = 0.07). Five-year failure-free survival was poor among the bcl-2-positive cases (11% versus 48%). Overall survival was no different, however, because relapses in bcl-2-positive cases tended to be responsive to further therapy. CONCLUSIONS: Analysis of bcl-2 rearrangements in de novo diffuse large cell lymphoma may identify a subset of patients with unusual clinical features.

Adult↗

Hodgkin disease, nodular sclerosis type. Implications of histologic subclassification.

BACKGROUND: The prognostic significance of the cellular composition of the nodules of Hodgkin disease, nodular sclerosis type (HDNS), is controversial. METHODS: Tumors from 79 patients with HDNS, who had a median follow-up time of 9.3 years, were studied. RESULTS: Based on British National Lymphoma Investigation criteria, 58 cases were classified as NSI (low-grade) and 21 as NSII (high-grade). The study included 24 male and 55 female patients, aged 10-57 years (mean, 27 years), who presented with Stage I (13 patients [12A, 1B]), Stage II (45 patients [40A, 5B]), or Stage III (21 patients [16A, 5B]) disease. Fifty-three patients had no relapse, 4 died of other causes, and 49 are in complete clinical remission. Twenty-six patients had progression of disease during therapy or relapsed and 17 were successfully salvaged. Overall length of survival was significantly shorter with NSII (P = 0.0001), extensive necrosis (P = 0.0034), high stage (P = 0.0058), and B symptoms (P = 0.030). Multivariate analysis showed that grade had the strongest effect on overall survival (P = 0.0042; hazard ratio = 10.19). The 5-year survival was 100% for NSI patients and 75% for NSII patients. Only B symptoms were significantly associated with risk of relapse after initial therapy (P = 0.030). For patients who relapsed, only histologic grade predicted subsequent disease-free survival (P = 0.0023; hazard ratio = 26.5). Five-year disease-free survival after first relapse was 94% for NSI patients and 11% for NSII patients. CONCLUSIONS: Patients with NSI disease who relapse have a more successful salvage and longer period of survival than do those with NSII disease. Histologic subclassification of HDNS appears clinically relevant, and consideration of histologic subtype may be important when planning therapy.

Adolescent↗

Thymoma--morphologic subclassification correlates with invasiveness and immunohistologic features: a study of 122 cases.

We applied the classification system of Marino and Müller-Hermelink (Virchows Arch A Pathol Anat Histopathol 407:119-149, 1985) and Kirchner and Müller-Hermelink (Prog Surg Pathol 10: 167-189, 1989) to 122 thymic epithelial tumors to evaluate the utility of this classification and to determine its correlation with invasiveness, follicular lymphoid hyperplasia, myasthenia gravis, and immunophenotype. The majority of cases could be classified according to this scheme: eight cases (7%) were medullary thymoma, 34 cases (28%) were mixed thymoma, 20 cases (16%) were predominantly cortical (organoid) thymoma, 22 cases (18%) were cortical thymoma, 32 cases (26%) were well-differentiated carcinoma (WDC), two cases (2%) were high-grade carcinoma, and four cases (3%) were unclassifiable. We report a detailed histologic analysis of these subtypes, with criteria for diagnosis. We propose that the term "organoid thymoma" be replaced by "predominantly cortical thymoma." We also observed a previously unrecognized subtype of WDC with spindle-shaped epithelial cells, which must be distinguished from medullary thymoma. There was a strong correlation between histologic subtype and invasion (P < .0001). All medullary and mixed thymomas were either completely encapsulated (64%) or had only invasion through the capsule (36%). Organoid and cortical thymomas showed an intermediate degree of invasiveness, with 36% invasive into mediastinal fat and 14% into adjacent structures. All the cases of WDC were invasive either through the capsule (19%) or into adjacent structures (81%); five cases (16%) also showed distant spread in the form of pleural seeding (four cases) or lymph node metastasis (one case). Microscopic evaluation disclosed invasion in a substantial number of cases (28.5%) thought by the surgeon to be encapsulated. The presence of follicular lymphoid hyperplasia, either within the tumor, in the residual normal thymus, or in both, was a significant predictor of myasthenia gravis (P < .0015); there was an increased association of myasthenia gravis and thymomas with cortical type epithelium (organoid thymoma, cortical thymoma, and WDC). There was no correlation between epithelial cell morphology and antigen expression; however, the immunophenotype of the associated lymphocytes corresponded closely to the morphologic classification of the thymomas. The Müller-Hermelink morphologic classification can be applied to most cases of thymoma and strongly predicts invasive behavior. The correlation of lymphocyte immunophenotype with the morphologic classification of the epithelial cells suggests that it is biologically accurate.

Adolescent↗

Diffuse low-grade B-cell lymphomas. Four clinically distinct subtypes defined by a combination of morphologic and immunophenotypic features.

The authors studied 56 cases of diffuse low-grade B-cell lymphoma using frozen tissue sections and a large panel of monoclonal antibodies that distinguish subsets of normal B cells. They compared the immunophenotypes with the histologic subtypes defined by the Rappaport classification, Working Formulation, and Kiel classification to correlate antigen expression with the morphologic subtypes defined in these classification schemes and to define the contribution of immunophenotype to clinically relevant subclassification. All categories in all classifications showed some heterogeneity of antigen expression; however, antigen expression correlated better with four major subgroups defined by the Kiel classification: (1) CD5+ CD10- CD23+ CD43+: chronic lymphocytic leukemia (CLL); (2) CD5+ CD10-/+CD23- CD43+: centrocytic (mantle cell) lymphoma; (3) CD5- CD10+/- CD23-/+ CD43-: centroblastic/centrocytic (CB/CC) lymphoma; and (4) CD5- CD10- CD23-/+CD43-/+: immunocytoma, mucosa-associated lymphoid tissue (MALT)-type, and monocytoid B-cell lymphoma. These subgroups had distinctive clinical features. Patients with centrocytic lymphoma were predominantly male (5.5:1) and had a significantly worse probability of survival than those with either CLL or MALT-type lymphoma (P = 0.001). The group with CB/CC lymphoma had an equal male-female ratio and an intermediate prognosis. Most patients with MALT-type and nodal monocytoid B-cell lymphomas were female (2:1); the disease-free survival for patients with extranodal MALT-type lymphoma was significantly better than that for all patients with other lymphoma subtypes except CB/CC (P < 0.01). The group with non-MALT immunocytoma had a slight male predominance, a high frequency of monoclonal gammopathy, and an intermediate prognosis. In differential diagnosis, CD23 was useful in distinguishing B-cell CLL from centrocytic lymphoma (P < 0.0001); CD5 (P < 0.0001), CD6 (P < 0.005), and CD43 (P < 0.0001) distinguish centrocytic lymphoma from CB/CC lymphoma; and CD10 (P < 0.005), CD43 (P = 0.06), Leu-8 (P = 0.08), and Ig heavy chain (P = 0.01) may help distinguish CB/CC lymphoma from immunocytoma, monocytoid B-cell lymphoma, and MALT-type lymphoma. Differences in antigen expression and clinical features among these Kiel classification subgroups suggest that they represent distinct biologic entities. The Working Formulation categories do not delineate these diseases clearly.

Adult↗

T-cell lymphoma of the vulva in a renal allograft recipient with associated hemophagocytosis.

The risk of B-cell lymphoma is greatly increased in transplant patients, whereas T-cell lymphomas have only rarely been reported in these patients. Although T-cell lymphomas in nonimmunosuppressed patients may be associated with either human T-cell lymphotropic virus type I (HTLV-I) or Epstein-Barr virus (EBV), these viruses have not been reported in association with post-transplant T-cell lymphoma. We report a case of T-cell lymphoma of the vulva arising in a renal allograft recipient receiving azathioprine and prednisone. The unusual clinical presentation led to difficulty in diagnosis because of a resemblance to either an infectious process or squamous cell carcinoma. The large cell lymphoma involved the dermis and subcutaneous fat of the vulva and was associated with hemophagocytosis in lymph nodes and bone marrow. The tumor had a mature, aberrant T-cell immunophenotype (CD3+ CD4+ CD7+ CD2- CD5- CD30+). Rearrangement of the T-cell receptor beta and gamma chain genes was found, but there was no evidence of either EBV or HTLV-I genomes. This case adds to the clinical and morphologic spectrum of T-cell lymphomas reported in allograft recipients and suggests that known lymphotropic viruses do not commonly have a role in post-transplant T-cell lymphoma.

Antigens, CD↗

Primary T-cell lymphoma of the brainstem.

Most primary CNS lymphomas are non-Hodgkin's lymphomas of B-cell lineage. We report a case of a small lymphocytic-type T-cell lymphoma localized primarily to the brainstem and compare the characteristics of primary CNS T-cell lymphomas with those of primary CNS B-cell lymphomas.

Brain Neoplasms↗

Computationally efficient cluster representation in molecular sequence megaclassification.

Molecular sequence megaclassification is a technique for automated protein sequence analysis and annotation. Implementation of the method has been limited by the need to store and randomly access a database of all the sequence pair similarities. More than 80,000 protein sequences are now present in the public databases, and the pair similarity data table for the full protein sequence database requires over 1 gigabyte of storage. In this paper we present a computationally efficient representation of groups based on a graph theory approach where sequence clusters are described by a minimal spanning tree of highest scoring similarity pairs. This representation allows a classification of N proteins to be stored in order(N) memory. The use of this minimal spanning tree representation simplifies analysis of groups, the description of group characteristics and the manual correction of artifacts resulting from false hits. The new tree representation also introduces new possibilities for artifact generation in sequence classification. Methods for detecting and removing these artifacts are discussed.

Algorithms↗