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C R Kjeldsberg

Publications and source records attributed to C R Kjeldsberg.

At least 19 recordsLinked to original sources
PubMed1995

Immunohistochemical staining for DNA topoisomerase II in non-Hodgkin's lymphomas.

DNA topoisomerase II (topo II) is the target of several clinically useful anticancer drugs. Several of these agents, such as doxorubicin and etoposide (VP-16), are used to treat non-Hodgkin's lymphomas (NHL). To understand the therapeutic selectivity of these drugs, a series of 33 cases of NHL for topo II were analyzed using an immunohistochemical technique that detects the enzyme in formalin-fixed, paraffin-embedded tissue. The average topo II index of high grade (Working Formulation) NHL was 48.6 with a range from 24.4 to 79.7. The average topo II index of low grade (Working Formulation) NHL was 4.4 with a range from 0.9 to 11.2. These two values are statistically different (P < .01). The intermediate grade (Working Formulation) NHL are a heterogeneous group based on topo II staining. The average topo II index value for the intermediate grade neoplasms was 26.7 with a range from 1.4 to 54.9. Because the proliferation marker Ki-67 has been shown to be of prognostic importance when used in the analysis of NHL, 27 cases for also were analyzed for MIB1 (Ki-67). The average MIB1 index of the high grade NHL was 59.8 with a range from 40.7 to 80.3. This average is statistically different (P < .01) than the average MIB1 index of 11.2 (range 1.7-28.3) found in the low grade NHL. Similar to results with topo II, the intermediate grade NHL was a heterogeneous group of tumors with respect to MIBI staining and had an average MIB1 index of 49.1 with a range from 8.9 to 86.7. These results show that high grade NHL have topo II and MIB1 indices that are significantly higher than low grade NHL. Intermediate NHL are more heterogeneous and have topo II and MIB1 indices that range from low to high.

Antibodies, Monoclonal↗
PubMed1995

Immunohistochemical reference ranges for B lymphocytes in bone marrow biopsy paraffin sections.

The quantitation of B lymphocytes in paraffin-decalcified bone marrow sections is often used as supportive evidence of primary or residual B-cell lymphoproliferative disorders; however, well-defined normal ranges for B lymphocytes are not available. Thirty-four B5-fixed decalcified bone marrow sections were analyzed from a group of patients having an essentially normal bone marrow morphologic examination and lacking any evidence immunologic or hematopoietic disease. All samples were stained with CD20, CD45RA (4KB5), and DBA.44 for B cells, and CD45RO (UCHL-1) for T cells. Image analysis was performed on all cases. CD20-positive cells ranged from 0% to 5.97%. CD45RA positivity ranged from 0% to 5.48%. DBA.44 was positive in 0% to 2.07% of the cells. CD45RO positivity varied from 0% to 6.7%. These results provide useful immunohistochemical B-lymphocyte reference ranges in B5-fixed paraffin bone marrow sections.

Adult↗
PubMed1995

Work-up of lymphadenopathy in children.

Lymphadenopathy occurs frequently in childhood caused by both reactive and neoplastic origins. Correlation of clinical findings, historical information, and patient symptoms may provide important insights into the cause of lymphadenopathy. When malignancy is suspected or if a child does not respond to antibiotic therapy, nodal biopsy or cytological examination may be undertaken to establish a diagnosis. Proper handling of pathologic materials will enhance the pathologist's ability to make an accurate diagnosis and may allow for important ancillary testing to be performed.

Biopsy, Needle↗
PubMed1995

Benign lymphadenopathies in children and adolescents.

This article provides and overview of the benign causes of lymphadenopathy (LA) in the pediatric population. Because of the topics' broad nature, this review is a selective one and primarily focuses on benign conditions of lymph nodes that may be confused with malignant disorders or have been described or better defined in recent years. Specifically, these will include infectious LA caused by Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), and cat scratch disease (CSD), LA associated with vaccination, drug-associated LA, progressive transformation of germinal centers (PTGC), LA associated with autoimmune disorders, histiocytic proliferations involving lymph nodes, and Kawasaki disease.

Adolescent↗
PubMed1995

Classification of non-Hodgkin's lymphomas in children.

Pediatric non-Hodgkin's lymphomas (NHLs) comprise an important subset of childhood malignancies with characteristic clinical, histologic, cytogenetic, and immunologic findings. Lymphoblastic lymphoma, small noncleaved cell lymphoma, and large cell lymphomas comprise the vast majority of childhood NHLs. Proper distinction of these subsets of NHL has important therapeutic and prognostic implications for the patient.

Burkitt Lymphoma↗
PubMed1994

Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: a prospective Southwest Oncology Group trial.

The growth fraction of tumors from patients with non-Hodgkin's lymphomas (NHL) has been shown to correlate with survival in retrospective studies. The growth fraction can be evaluated using immunohistochemical techniques employing the Ki-67 monoclonal antibody (MoAb) that marks a nuclear protein present in cycling cells. The purpose of this study was to evaluate the clinical utility of the Ki-67 MoAb for predicting survival. Using a prospective trial design in a multi-institutional cooperative trials group, the proliferative index, clinical outcome, and statistical correlations were independently assessed for previously untreated patients with advanced stages of intermediate- and high-grade histologies of NHL treated on Southwest Oncology Group study (SWOG 8516, Intergroup 0067). The proportion of Ki-67-positive cells was determined on snap-frozen thin tissue sections. A proliferative index of 80% or greater, as determined from prior retrospective studies, identified a group of patients (18%) who had a poor outcome. Overall survival was significantly reduced in these patients with a high Ki-67-associated proliferative index compared with those with a low proliferative index (P = .001). One-year survival estimates were 82% (low proliferative index) versus 18% (high proliferative index). A multivariate regression analysis incorporating commonly used clinical prognostic features confirmed the independent effect of proliferation on survival (relative risk estimate 5.9; 95% confidence interval, 2.2, 16.1). The Ki-67 MoAb identifies a group of patients with rapidly fatal NHL for whom currently available chemotherapy is inadequate.

Adult↗
PubMed1994

Antigen expression and polymerase chain reaction amplification of mantle cell lymphomas.

Flow immunophenotyping, DNA content analysis, and polymerase chain reaction (PCR) amplification for t(11;14) and t(14;18) were performed on 11 cases of typical mantle cell lymphoma (MCL), 5 cases of apparent MCL with proliferation centers (MCL-PC), and 5 cases of small lymphocytic lymphoma (SLL). Immunophenotyping showed IgM (P < .001), Ig light (P < .001), and CD20 (P < .001) expression to be more intense in MCL than in SLL. In MCL-PC, the mean intensity of IgM, Ig light chain, and CD20 expression was intermediate to the intensities observed in MCL and SLL. Furthermore, in contrast to SLL, all MCL and 4 of 5 MCL-PC cases exhibited stronger CD20 than CD19 expression. CD10 expression was not observed in any case and CD5 expression was present in all SLL and MCL-PC cases and in 9 of 11 MCL cases. DNA content analysis showed an S-phase fraction of less than 3% in all cases studied and, except for 1 MCL case, all lymphomas were DNA diploid. The t(11;14) breakpoint junctions involving the bcl-1 major translocation cluster were amplified by PCR in 4 of 11 (36%) MCL cases and in none of the MCL-PC or SLL cases. The t(14;18) involving the bcl-2 major breakpoint region was not identified by PCR in any case. We conclude that the level of expression of surface antigens and the rapid detection of t(11;14) by PCR are potentially useful for distinguishing MCL and SLL in the clinical setting. Further investigations as to the biologic relationship between MCL, MCL-PC, and SLL, and the utility of t(11;14) PCR in these lymphomas are warranted.

Aged↗
PubMed1994

Disseminated nonlymphoblastic lymphoma of childhood: a Childrens Cancer Group study, CCG-552.

PURPOSE: To assess the efficacy of a chemotherapy-only regimen in pediatric patients with disseminated non-lymphoblastic lymphoma and acute B-cell leukemia (B-ALL). PATIENTS AND METHODS: Sixty-eight eligible patients with previously untreated disseminated non-lymphoblastic lymphoma were enrolled on a Childrens Cancer Group study. Therapy included cycles of chemotherapy, systemic and intrathecal (IT), ever 3 weeks for a total maximal duration of 57 weeks. Fifty-five patients had small non-cleaved cell lymphoma (SNCCL) and 13 had diffuse large cell lymphoma (DLCL). Forty-seven were stage III, six were stage IV, and 15 had B-ALL; 13 had central nervous system (CNS) involvement. RESULTS: Four year event-free survival (EFS) was 53% (SE +/- 12%). Stage III SNCCL patients with LDH < 500 IU/L achieved an improved EFS compared to other SNCCL patients (86% vs. 42% 4 year EFS, P = .072). The primary site of failure for advanced stage SNCCL patients was the CNS. All Ki-1-positive DLCL patients relapsed. Patterns of failure, time to relapse, and outcome following relapse differed between SNCCL and DLCL patients. CONCLUSIONS: Advanced stage SNCCL requires better CNS-directed chemotherapy to reduce the CNS failure rate; however, the achievement of durable disease-free survival in four of 11 patients with CNS disease without use of cranial irradiation suggests merit for further evaluation of chemotherapy-only strategies. DLCL patients do not need intensive CNS-directed chemotherapy.

Adolescent↗
PubMed1994

CD30 antigen expression in florid immunoblastic proliferations. A clinicopathologic study of 14 cases.

Reactive immunoblastic proliferations may be confused with certain types of non-Hodgkin's lymphoma and Hodgkin's disease on morphologic grounds. In addition, a characteristic antigen, CD30 (Ki-1; BerH2) on these neoplastic entities may be observed in morphologically atypical yet reactive florid immunoblastic proliferations such as those associated with acute infectious mononucleosis. Although it has been documented, a large series determining the frequency and extent of CD30 antigen expression on a variety of nonneoplastic immunoblastic proliferations is lacking. The authors studied 14 florid immunoblastic proliferations (9 in lymph nodes and 5 in tonsils) for CD30 antigen expression and for B- and T-cell paraffin markers. In situ hybridization to determine the presence of Epstein-Barr virus (EBV) genomes also was performed. Cases were classified into monospot-positive acute infectious mononucleosis (4 cases), EBV-related lymphoproliferative disorder suggestive of acute infectious mononucleosis (5 cases), and other etiologies (5 cases). CD30 Antigen expression was found on the immunoblasts in cases from all three categories and overall in 9 (64%) of 14 specimens. CD30 reactivity in the positive cases varied from occasional to numerous positive cells; 4 samples (3 EBV-related lymphoid proliferations and 1 vaccine-related lymphadenopathy) had numerous CD30-reactive immunoblasts. Expression of CD30 antigen on B or T cells and prominence of B or T cells within a proliferation were variable. Significant "atypia" of immunoblasts was found only in EBV-related disorders and correlated with B-cell prominence of the infiltrate. Appropriate clinical correlation and ancillary laboratory data are necessary to assist in differentiating these CD30(+)-reactive disorders from similar-appearing malignant lymphomas. Most important, a fresh tissue sample should be procured and adequately processed to allow for comprehensive determination of clonality and cellular lineage.

Adolescent↗
PubMed1994

T-cell lymphocytosis associated with invasive thymomas.

Peripheral T-cell lymphocytosis and bone marrow infiltration is a rarely associated feature of invasive thymomas. Hypotheses for the origin of the circulating lymphocytes include a spillover of tumor lymphocytes into the circulation, a neoplastic lymphoid proliferation, and a reactive proliferation of peripheral lymphocytes resulting from a thymoma-induced immunoregulatory disorder. The authors describe two cases of peripheral T-cell lymphocytosis associated with invasive thymomas with a predominantly lymphocyte-rich, cortical type histologic appearance. In both cases T cells constituted as much as 99% of the circulating lymphoid cell population, according to flow-cytometric analysis before and after treatment, and expressed a mature phenotype consistent with medullary thymic or peripheral T cells (CD2+, CD3+, CD4+ or CD8+, CD5+, CD7+) with predominant expression of the alpha/beta T-cell receptor heterodimer. Bone marrow biopsy specimens showed nodular and interstitial infiltrates of small T cells. No monoclonal rearrangement of the T-cell receptor beta gene was observed. Both cases had a normal female karyotype. Our findings confirm those of previous studies supporting a reactive origin for the peripheral lymphocytosis. Although an immunoregulatory disorder is probably involved in lymphocyte proliferation in situ, we postulate that peripheral lymphocytosis results from augmented release of the more mature thymoma-associated lymphocytes into the circulation through tumor invasiveness. A thymic origin is supported by the presence of a subset of peripheral T cells with low-intensity CD5 expression.

Aged↗
PubMed1994

Lymphoproliferative disorders of the lung: histopathology, clinical manifestations, and imaging features.

The lymphoproliferative disorders represent a spectrum of lymphoid abnormalities that can involve the chest. Plasma cell granuloma, pseudolymphoma, posttransplantation lymphoproliferative disorders, lymphoid interstitial pneumonia, and lymphomatoid granulomatosis involve the pulmonary parenchyma, whereas Castleman's disease, infectious mononucleosis, and angioimmunoblastic lymphadenopathy with dysproteinemia involve intrathoracic lymph nodes. Recent immunohistochemical techniques give us a better understanding of the lymphoproliferative disorders. Clinical and radiologic features often allow differentiation of the lymphoproliferative disorders from the more common aggressive lymphomas.

Female↗
PubMed1994

Immunohistochemical staining for DNA topoisomerase II in frozen and formalin-fixed paraffin-embedded human tissues.

DNA topoisomerase II is the molecular target of several clinically useful chemotherapeutic drugs. The sensitivity of cells to drugs that target topoisomerase II is dependent on the cellular content of this enzyme. Drug-sensitive cells have elevated amounts of type II topoisomerase. To determine relative amounts of enzyme in malignant neoplasms, we developed an in situ immunohistochemical stain for topoisomerase II. The stain uses either polyclonal or monoclonal antibodies produced against the alpha isoform of the enzyme. Staining can be done on both frozen and formalin-fixed, paraffin-embedded tissues. By using this immunostain, we found marked differences in enzyme content in several human malignancies.

Animals↗
PubMed1994

Anaplastic large-cell lymphoma presenting primarily in bone in a patient with AIDS.

Non-Hodgkin's lymphomas have been recognized as an important and frequently fatal part of the spectrum of diseases associated with HIV infection. These are most often high-grade B-cell lymphomas usually of immunoblastic and small cell non-cleaved subtypes. Sporadic reports of T-cell lymphomas associated with HIV infection are found in the literature. Two have been reported to be CD30 positive presenting with lymph node and skin involvement. We report a case of an AIDS patient with a T-cell anaplastic large-cell lymphoma that was CD30-positive and presented in bone. This is most probably a sporadic event rather than another part of the AIDS-associated spectrum of disease.

Bone Neoplasms↗
PubMed1993

Long-term follow-up of patients treated with COMP or LSA2L2 therapy for childhood non-Hodgkin's lymphoma: a report of CCG-551 from the Childrens Cancer Group.

PURPOSE: We analyzed the long-term results of a Childrens Cancer Group (CCG) randomized study comparing cyclophosphamide, vincristine, methotrexate, and prednisone (COMP) versus LSA2L2 as treatment for childhood non-Hodgkin's lymphoma. The initial results were previously reported (N Engl J Med 308:559, 1983). PATIENTS AND METHODS: A total of 429 patients are reported here, 68 with localized disease and 361 with disseminated disease. The distribution of disseminated-disease patients by histologic type was 164 lymphoblastic, 60 large-cell, and 137 undifferentiated lymphomas. Median follow-up duration of surviving patients is 8 years. RESULTS: Event-free survival (EFS) of patients with localized disease was 84% at 5 years. No differences were seen between the two treatment regimens. Results for patients with disseminated disease was dependent on histologic subtype: patients with lymphoblastic lymphoma did better when treated with LSA2L2 (5-year EFS of 64% v 35% for COMP); COMP produced better results for patients with undifferentiated lymphoma (5-year EFS of 50% v 29% for LSA2L2). Results for large-cell lymphoma patients were similar (5-year EFS of 52% for COMP v 43% for LSA2L2). Five percent of patients died of treatment-related complications while on therapy (primarily infections). Only four deaths without progression have been observed off-therapy (two from restrictive lung disease, one from an acute asthma attack, one from colon cancer). Patient survival rates after recurrence were poor. CONCLUSION: Treatment success can be expected in 84% of pediatric patients with localized non-Hodgkin's lymphoma. For patients with disseminated disease, treatment success can be expected in 64% of those with lymphoblastic and 50% of those with undifferentiated or large-cell disease. To date, late adverse events are rare.

Adolescent↗
PubMed1992

Digoxigenin-labeled probes amplified from genomic DNA detect T-cell gene rearrangements.

The detection of clonal rearrangements of the human T-cell receptor by Southern hybridization is a useful tool to diagnose morphologically difficult lymphoid proliferations. Widespread application of this method has been facilitated by the advent of sensitive nonradiolabeled probes. Although a limited number of nonradiolabeled DNA probes are commercially available, other probes must be obtained through a time-consuming and technically difficult procedure of amplification, isolation, and labeling of plasmid-cloned DNA sequences. A simple and time-saving procedure to simultaneously amplify and nonradioactively label DNA probes for use in gene rearrangement studies is described. Specifically, a method using the polymerase chain reaction to amplify and label with digoxigenin large quantities of probe to the constant region of the T-cell receptor directly from genomic DNA is described. The resultant probes are specific for the T-cell receptor-constant region, detect the appropriate germline configuration in placental DNA, and identify rearranged clonal T-cell proliferations. The polymerase chain reaction digoxigenin-labeled probes are suitable for detection by conventional colorimetric methods or by chemiluminescent detection schemes.

Amino Acid Sequence↗
PubMed1992

Identification of monoclonal B-cell populations by rapid cycle polymerase chain reaction. A practical screening method for the detection of immunoglobulin gene rearrangements.

Alternatives to Southern blot hybridization for gene rearrangement analysis are being studied because of the time, labor, cost, and radioisotopes required for this technique. We have utilized a rapid, hot air, thermocycling polymerase chain reaction (PCR) system to examine various lymphoproliferative disorders for immunoglobulin heavy chain (IgH) gene rearrangements. This unique system amplifies DNA from 10 microliters samples placed in glass capillary tubes, over a total cycle time of about 30 minutes. Amplified bands are easily visualized on ethidium bromide-stained agarose gels. Forty-one monoclonal B-cell proliferations, 27 reactive lymphoid hyperplasias, 17 T-cell lymphomas and 3 cases of Hodgkin's disease were studied. All 88 cases were fully characterized by morphologic, immunophenotypic, and genotypic (Southern blot) analyses. Each case was separately evaluated by PCR with two primer pairs: 1) IgH variable region (VH) and IgH joining region (JH) and 2) bcl-2 and JH. Thirty-four of 41 monoclonal B-cell proliferations revealed a distinct band (within an expected base pair range) with 1 or both primer combinations supporting B-cell monoclonality; the other 7 cases were considered false negatives. The 47 entities without IgH gene rearrangements detectable by Southern analysis demonstrated no amplified product or a smear of amplified DNA with no distinct band. The overall specificity of PCR was 100%, and the sensitivity was 83% when directly compared with Southern blot analysis. Although its sensitivity is currently less than optimal, PCR is a rapid and practical screening method for the detection of IgH gene rearrangements. If a positive result is obtained no further analysis is required; however, if there is a negative result, standard Southern blot analysis should be performed to definitively exclude the presence of a monoclonal B-cell population in the sample.

B-Lymphocytes↗
PubMed1990

A comparison study of two methods of peanut agglutinin staining with S100 immunostaining in 29 cases of histiocytosis X (Langerhans' cell histiocytosis)

Staining with peanut agglutinin (PNA) and with polyclonal antibody to S100 protein have both been recommended as aids in the diagnosis of histiocytosis X (Langerhans' cell histiocytosis). Although a large body of literature attests to the utility of S100 staining in this condition, the few published studies that involve PNA staining have employed varying methods of radically different results. We studied formaldehyde solution-fixed, paraffin-embedded tissue from 29 cases of histiocytosis X by using standard avidin-biotin immunostaining for S100 protein, as well as two published methods of PNA staining. All cases stained positively for S100 protein. By utilizing prior trypsinization and a three-step procedure, all cases also stained with PNA. With a two-step PNA-staining procedure, however, 9 cases failed to stain with PNA, and 3 cases showed a diffuse staining pattern that was not considered characteristic of Langerhans' and histiocytosis X cells. We concluded that both the S100 and the three-step PNA procedures are sensitive methods for the diagnosis of histiocytosis X.

Adolescent↗