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C R Kjeldsberg

Publications and source records attributed to C R Kjeldsberg.

At least 19 recordsLinked to original sources
PubMed2000

Large-cell lymphoma arising in the mediastinum in children and adolescents is associated with an excellent outcome: a Children's Cancer Group report.

PURPOSE: Large-cell lymphoma (LCL) arising in the mediastinum (LCL-M) is a heterogeneous group of non-Hodgkin's lymphoma (NHL) that includes B-cell lymphomas as well as T-cell lymphomas, including anaplastic LCL. LCL-M is well recognized in young adults but is less well characterized and infrequent in children and adolescents. METHODS: A retrospective review of Children's Cancer Group therapeutic studies for nonlymphoblastic lymphomas (CCG-551, CCG-503, CCG-552, and CCG-5911) identified 20 patients with LCL-M, representing 7.2% of all LCLs classified by central pathology review. RESULTS: The patients ranged in age from 4 to 19 years (median, 12.5 years; mean, 12 years); 55% of the patients were male. Although a variety of chemotherapy regimens were used, response was excellent, with all 20 patients (100%) achieving a complete response. Four patients (20%) experienced relapse locally or in distant sites including brain and kidney. One patient died of sepsis during therapy. For the 20 patients with LCL-M, the product-limit estimated 5-year event-free survival (EFS) and 5-year overall survival (OS) rates are 75% +/- 10% and 85% +/- 8%, respectively. For disseminated LCLs (192 cases), the EFS and OS rates were 50% +/- 4% and 63% +/- 4%, respectively, which differ significantly from the those of the LCL-M cases (EFS, P =.025; OS, P =.034). The 5-year EFS and OS rates for patients with localized LCL (67 cases) were 92 +/- 3% and 97 +/- 2%, respectively. CONCLUSION: LCL-M is a heterogeneous group of NHLs that makes up approximately 7.2% of LCL in children and adolescents. Response to therapy and OS in this young age group seems excellent and superior to that of disseminated LCLs but inferior to that of other localized LCL. Future studies of LCL-M will evaluate short intense chemotherapy administered without radiation therapy.

Adolescent↗
PubMed1999

Primary anaplastic large cell lymphoma of the small intestine.

We describe the clinicopathologic, immunophenotypic, and molecular findings in 4 cases of anaplastic large cell lymphoma (ALCL) arising in the small intestine. All patients were men with acute symptoms of gastrointestinal tract obstruction. The clinical preoperative diagnosis was gastrointestinal carcinoma in 3 cases, and pancreatic carcinoma in 1 case. Histologic examination revealed cohesive aggregates of neoplastic cells, with multiple vesicular nuclei, prominent nucleoli, and abundant amphophilic cytoplasm. There was no clinical or histopathologic evidence of enteropathy. All cases were CD30+, and all showed evidence of T-cell lineage with cytotoxic potential by expression of CD3, CD43, or CD45RO; T-cell intracellular antigen-1; or perforin. One tumor showed p80 and anaplastic lymphoma kinase (ALK) overexpression corroborated by the presence of the t(2:5). One tumor expressed Epstein-Barr virus latent membrane protein. In all cases, the tumor cells were negative for CD20, CD15, CD56, and cytokeratin. Polymerase chain reaction revealed clonal rearrangements of the T-cell receptor gamma-chain gene, without evidence of immunoglobulin heavy-chain gene rearrangement. The diagnosis of primary bowel ALCL is facilitated by immunophenotypic and molecular studies. With 24 months of clinical follow-up, only the patient with the t(2:5)-positive tumor is alive and free of disease, suggesting that p80/ALK overexpression may be a good prognostic indicator.

Adult↗
PubMed1998

Relation of cigarette smoking to non-Hodgkin's lymphoma among middle-aged men.

Because of previous inconsistencies in the observed relation of cigarette smoking to non-Hodgkin's lymphoma, this association was investigated in the Selected Cancers Study, a population-based case-control study of 1,193 non-Hodgkin's lymphoma cases and 1,903 controls, conducted between 1984 and 1988. Study subjects were men, and the median age of non-Hodgkin's lymphoma cases was 50 years (range, 32-60 years). As compared with the risk among men who had never smoked cigarettes, the risk among ever smokers was not increased (odds ratio (OR) = 1.05, p approximately 0.50), but the risk was significantly elevated among men who reported smoking > or = 2 1/2 packs per day and among men who had smoked for 30-39 years (OR = 1.45 in each group, p < 0.05). The estimated odds ratio among the 350 heavy smokers (> or = 50 pack-years) was 1.41 (95% confidence interval 1.08-1.85) after controlling for educational achievement, various occupational and medical exposures, and other potential confounders. The observed associations, however, tended to vary by age, with the odds ratio among heavy smokers decreasing from 2.8 among 32- to 44-year-olds to 1.1 among men over 55 years of age. These age-related differences, which may account for some of the inconsistencies seen in previous studies of cigarette smoking and non-Hodgkin's lymphoma, should be considered in future investigations.

Adult↗
PubMed1997

Natural killer-like T-cell lymphoma in the small intestine of a child without evidence of enteropathy.

A previously healthy 6-year-old boy developed symptoms of small intestinal obstruction and was found to have a large intraabdominal mass. At laparotomy the mass involved the jejunum and adjacent mesenteric lymph nodes, requiring resection. Microscopic and immunohistochemical studies demonstrated a T-cell non-Hodgkin's lymphoma, confirmed by finding clonal T-cell receptor-beta and -gamma gene rearrangements by Southern blot analysis. The immunophenotype of this lymphoma-CD3+CD4-CD8-CD56+TIA-1+ beta F1(-)-suggests that the tumor cells are cytotoxic natural killer (NK)-like T cells, probably of CD3+CD4-CD8- intraepithelial cell origin. Examination of the adjacent and distal small intestinal mucosa failed to show any significant pathologic change. This case was unusual because intestinal lymphomas in children are usually of B-cell origin and most commonly have small noncleaved cell morphology. Childhood intestinal T-cell lymphomas have not been the focus of specific study but appear to be rare. In adults, intestinal T-cell lymphomas often arise in the background of gluten-sensitive enteropathy (celiac disease). In contrast, this child had peripheral T-cell lymphoma, with NK-like T-cell features, in the small intestine with no clinical or histologic evidence of enteropathy.

Age Factors↗
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↗