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T C Greiner

Publications and source records attributed to T C Greiner.

At least 37 records · Page 2Linked to original sources
PubMed1997

The detection of minimal lymphoma by molecular and combined culture-molecular methods.

Seventy-four patients from a prospective randomized trial comparing autologous bone marrow (ABM) versus blood stem cell (BSC) transplantation after high-dose chemotherapy for intermediate and high grade non-Hodgkin's lymphoma (NHL) were studied for the presence of residual lymphoma prior to transplantation. Pre-transplant bone marrow (BM), peripheral blood (PB) and the ABM or BSC harvest were studied by molecular assays immediately after collection and at weekly intervals after the initiation of in vitro cultures. B-NHLs with t(14:18) at the major breakpoint region (mbr) were monitored by detecting cells with the translocation. Other B-NHLs were monitored with tumour-specific primers and probes to the immunoglobulin heavy chain (IgH) gene complementary determining region (CDR) III. T-NHLs were similarly monitored using the T-cell receptor gamma chain gene V-J junctional region as the tumour-specific marker. Of the 74 patients, seven did not have adequate tumour biopsies for molecular characterization. Of the remaining 67 cases, 35 had identifiable markers for follow-up studies and 20/35 cases (52%) had tumour cells detected in either the pretransplant BM/PB samples or the ABM/BSC harvest. Residual tumours were detected at a high frequency in T-NHL (100%) and t(14;18)+ B-NHL (86%) but at a lower frequency in B-NHLs without t(14,18) (44%). In five cases, one or more of the samples were initially negative for residual lymphoma but became positive after a period of culture; additional studies confirmed that in vitro culture enhanced the sensitivity of tumour detection in about half of these samples. Molecular assay for minimal residual disease can be performed in the setting of multicentre prospective clinical trials. The substantial frequency of failure of obtaining tumour-specific IgH CDRIII sequences in paraffin-embedded B-NHLs argues for the storage of frozen tumour samples for possible molecular studies.

Base Sequence↗
PubMed1997

Posttransplantation lymphoproliferative disorders in bone marrow transplant recipients are aggressive diseases with a high incidence of adverse histologic and immunobiologic features.

Posttransplantation lymphoproliferative disorders (PT-LPDs) occurring in T-cell depleted (TCD) allogeneic bone marrow transplant recipients seem to be different from those that arise in solid organ recipients in their early development, the high incidence of extensive dissemination at presentation, and their aggressive course and high fatality rate. We report a series of 10 patients with PT-LPDs after TCD allogeneic bone marrow transplant. We studied the correlation between the morphology of the lesions; their clonality based on immunoglobulin (Ig) heavy chain gene rearrangement analysis and immunohistochemistry; their proliferative activity as measured by immunoperoxidase staining for the proliferating cell nuclear antigen (PCNA) and the presence of p53 gene product overexpression. Histologically, our cases corresponded to the two morphologic categories of polymorphic B-cell lymphoma (PBCL, seven cases) and malignant lymphoma immunoblastic (ML-IB, three cases). Ig light-chain staining showed monoclonality in a minority of the cases, whereas Ig gene rearrangement analysis by polymerase chain reaction revealed B-cell clonality in three of seven cases of PBCL and in all three cases of ML-IB. The Epstein-Barr virus (EBV) genome, the expression of EBV latent membrane protein or both were found in all 10 specimens. High proliferative activity (PCNA > or = 66%) was found in all cases, with a mean PCNA value of 56% in PBCL and 84% in ML-IB. Five specimens were p53+ (two of seven PBCL and three of three ML-IB). Two of four PBCL cases resolved with the administration of donor leukocytes. All of the remaining patients died of the PT-LPD within a short time from admission. Our results show that the PT-LPDs after TCD bone marrow transplantation are characterized by a high frequency of high-grade histologic subtypes, frequent monoclonality, high proliferative activity, frequent overexpression of p53 gene product, and poor prognosis. These characteristics observed in only a minority of cases of PT-LPDs occurring after solid organ transplantation may account for the less aggressive clinical behavior observed in those diseases.

Adult↗
PubMed1997

Obtaining clone-specific primer and probe for the immunoglobulin heavy-chain gene from paraffin-embedded tissue of B-cell lymphoma: technical considerations.

The complementarity determining region (CDR) III of the immunoglobulin heavy-chain (IgH) gene is a tumor-specific marker for B-cell malignancies that has been widely exploited for the monitoring of minimal residual disease in B-precursor acute lymphocytic leukemia. There are a number of technical problems in applying the same technology for B-cell non-Hodgkin's lymphoma (B-NHL). Several procedures have been useful in overcoming these unique problems encountered in obtaining the tumor-specific sequence of the IgH-CDRIII in B-NHL, including the use of denaturing gradient gel electrophoresis or micromanipulation of tissue sections in separating the tumor-specific CDRIII products from those of contaminating normal B-lymphocytes. Minor modifications of a commercial kit greatly improve the purity of the polymerase chain reaction (PCR) products for sequencing. Modifications of the 5'-ends of the VH and IH primers, coupled with the cycle sequencing technique, make it possible to obtain unambiguous sequences on direct sequencing of short PCR products. Computer informatics and programs that facilitate the design of tumor-specific primers and probes from CDRIII sequences are described.

DNA Primers↗
PubMed1996

Hepatosplenic T-cell lymphoma: a distinct clinicopathologic entity of cytotoxic gamma delta T-cell origin.

We identified eight cases of T-cell lymphoma with evidence of a gamma delta phenotype over a 13-year period. Seven of these cases conformed to a distinct clinicopathologic entity of hepatosplenic gamma delta T-cell lymphoma. Nearly all of these patients were young adult males (five of seven), with a median age at presentation of 20 years. They presented with marked hepatosplenomegaly, without lymphadenopathy or significant peripheral blood lymphocytosis. Thrombocytopenia was seen in all patients, and five of seven were mildly anemic. The clinical course was aggressive, and despite multiagent chemotherapy, the median survival duration was less than 1 year. The morphologic findings were uniform; a monomorphic population of medium-sized lymphoid cells with moderately clumped chromatin and a rim of pale cytoplasm infiltrated the sinusoids of the spleen, liver, and bone marrow. The cells had a characteristic immunophenotype: CD2+, CD3+, CD4-, CD5-, CD7+, CD16+, CD57-, CD25-, T-cell receptor (TCR)delta +, beta F1-. CD8 was positive in four of seven cases tested, and CD56 was positive in five of six. All cases expressed the cytotoxic granule-associated protein, TIA1, but perforin was detected in only one case. All cases with assessable DNA had a TCR gamma gene rearrangement, and lacked Epstein-Barr virus sequences. Isochromosome 7q was identified in two cases with cytogenetic information. The one case of cutaneous gamma delta T-cell lymphoma differed in its clinical manifestations, histologic appearance, and immunophenotype. We conclude that hepatosplenic gamma delta T-cell lymphoma is a distinct clinicopathologic entity derived from cytotoxic gamma delta T cells, and should be distinguished from other lymphomas of T-cell and natural-killer cell (NK)-like T-cell derivation.

Adolescent↗
PubMed1996

Nodular lymphocyte-predominant Hodgkin's disease associated with large-cell lymphoma: analysis of Ig gene rearrangements by V-J polymerase chain reaction.

The clonality of nodular lymphocyte-predominant Hodgkin's disease (NLPHD) and the relationship to composite or sequential large-cell lymphomas (LCLs) is poorly understood. Clonal Ig heavy-chain gene rearrangements (lgHGR) have infrequently been observed in NLPHD by Southern hybridization. The goals of this study were (1) to determine if IgHGR could be identified by polymerase chain reaction (PCR) techniques in the LCL associated with NLPHD; (2) to determine if the lgHGR identified in the LCL could also be found in the associated NLPHD; and (3) to determine if Epstein-Barr virus (EBV) played a role a role in histologic progression to LCL. Using consensus primers to conserved regions in the lgH variable (V) and joining (J) region genes, we analyzed formalin-fixed paraffin-embedded sections from the biopsies of 25 patients referred to the National Cancer Institute (NCI) registry for NLPHD and LCL using both single-step and seminested V-J PCR. The histologically aggressive component was further subclassified as frank LCL or as L&H-cell-rich, but not fulfilling criteria for LCL. Matched samples representing both NLPHD and aggressive components were available in 13 cases. In 12 cases, only one component was available (aggressive, n = 8; NLPHD, n = 4). In addition, we also amplified, with 32P labeling, 12 cases of NLPHD without associated LCL. Two clonal IgHGR were identified in 29 cases (7%) of typical NLPHD, both of which were associated with LCL containing a similar sized band by PCR. The clonal identity of the bands in the NLPHD and associated LCL was confirmed by sequencing the products in these two cases. Eight of 10 cases (80%) of LCL associated with NLPHD contained a clonal band by this technique. By contrast, none of the cases classified as L&H-cell-rich contained an IgHGR. The single-step and seminested PCR methods produced identical results. All clonal LCLs were studied for EBV sequences by in situ hybridization using the EBER1 probe, and were negative. We conclude that the LCLs associated with NLPHD are clonal B-cell malignancies. However, by these methods, the same clone can be identified in only a minority of cases of NLPHD and LCL. EBV does not appear to play a role in histologic progression. Moreover, our results suggest that many cases suspected of being LCL may actually represent NLPHD with increased numbers of L&H cells. In histologically equivocal cases, the diagnosis of LCL should be reserved for those cases in which a clonal B-cell neoplasm can be demonstrated.

Adult↗
PubMed1996

p53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis.

Mutations of the p53 tumor suppressor gene have been described in several subtypes of non-Hodgkin's lymphoma, but the incidence of p53 mutations in mantle cell lymphoma (MCL) is unknown. We hypothesized that cases of MCL with a variant or high-grade cytology would have a higher likelihood of p53 mutations than typical MCL. We were also interested in the prognostic significance of p53 mutations in MCL. Therefore, a series of 53 well-characterized cases of MCL with DNA from 62 tissue samples were analyzed by the polymerase chain reaction with denaturing gradient gel electrophoresis for exons 5-8 of p53. Immunoperoxidase studies with the antibody DO-7 to p53 protein were also performed on frozen sections. We found mutations of the p53 gene in 8 of the 53 cases (15%) of MCL. Missense mutations predominated, and 50% of the mutations occurred at known p53 hotspot codons. Of 21 cases with variant cytology (ie, anaplastic or blastic), 6 (28.6%) had p53 mutations as compared with only 2 of 32 cases (6.3%) with typical MCL cytology (P = .05), and p53 mutations preceded the development of variant cytology in 2 patients. Overexpression of p53 protein was observed in 6 of the 8 cases (75%) with p53 mutations and in none of the 45 wild-type cases. The median survival of the cases with mutant p53 was only 1.3 years (all died), whereas the median survival of cases with germline p53 was 5.1 years (P = .023). These results suggest that mutations of p53 may be one mechanism involved in the development of variant forms of MCL and indicate that p53 mutations in MCL predict a poor prognosis.

Base Sequence↗
PubMed1996

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma.

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.

Adolescent↗
PubMed1996

Clonality analysis of B-lymphoid proliferations using the polymerase chain reaction.

BACKGROUND: Polymerase chain reaction (PCR) based assays are becoming more reliable, simpler, and faster alternatives to traditional Southern blot hybridization (SBH) analysis for the detection of clonal immunoglobulin heavy chain (IgH) gene rearrangements. However, a variety of technical approaches have been reported with markedly different results. METHODS: We analyzed the frozen tissue of 147 neoplastic and hyperplastic lesions on which SBH had previously been performed. Semi-nested and single-step PCR methods were compared. Consensus primers to the joining segments and the framework region (FR) III of the variable segments of the IgH gene were used. All PCR products were analyzed by polyacrylamide gel electrophoresis (PAGE). Thirteen samples were re-analyzed using a denaturing gradient gel electrophoresis (DGGE) system. RESULTS: The overall concordance between SBH and semi-nested PCR assays was 80.2%. In the non-Hodgkin's lymphoma (NHL) group, 75% of the cases with IgH rearrangements by SBH were found to be monoclonal by PCR. Regardless of type of lesion, 71.7% of the cases with IgH rearrangements by SBH were found to be clonal by PCR. The concordance between the semi-nested and single-step procedures was 87.1%. DGGE was helpful in clarifying the results for cases in which the PAGE analysis was difficult to interpret. CONCLUSIONS: PCR analysis of IgH gene rearrangements was found to be an efficient technique for the initial determination of clonality in lymphoid proliferations. The single-step method had an advantage over the semi-nested method because of its simplicity and speed. The DGGE system was useful for the assessment of clonality in cases with equivocal results after PAGE. However, a combination of these techniques in specific cases may achieve higher specificity and sensitivity.

B-Lymphocytes↗
PubMed1996

Hodgkin's disease following solid organ transplantation.

BACKGROUND: The incidence of second malignancies is markedly increased following transplantation of solid organs. However, the development of Hodgkin's disease has been described relatively infrequently in this setting, and there is little clinical information on these patients and few details on management. PATIENTS AND METHODS: We have reviewed the pathologic specimens and clinical history of four patients who developed Hodgkin's disease following transplantation of solid organs. RESULTS: Hodgkin's disease appeared 26-68 months following transplantation of the kidney (2 cases), liver, and heart. Three cases demonstrated evidence of Epstein-Barr virus (EBV) in Reed-Sternberg cells. One case appears to have arisen after a previous EBV-driven polymorphous lymphoproliferation. Hodgkin's disease was localized in three cases and disseminated in one. All patients achieved remission with standard therapy and continue in remission between 9 and 61 months after therapy. Graft function was preserved in all patients. CONCLUSION: Hodgkin's disease occurring in the post-transplantation period should probably be treated like Hodgkin's disease in non-immunosuppressed patients. Prolonged disease-free survival is possible and function of the transplanted organ can be preserved.

Adult↗
PubMed1996

Concurrent lymphocyte predominance Hodgkin's disease and T-cell lymphoma. A report of three cases.

Lymphocyte predominance Hodgkin's disease (LPHD) is a B-cell lymphoproliferative disorder; patients with LPHD have an increased risk of developing synchronous or metachronous B-cell non-Hodgkin's lymphoma. The synchronous presence of LPHD and B-cell lymphoma in the same lymph node in some cases lends support to the argument that the B-cell lymphoma arises as a consequence of transformation or progression of LPHD. We have recently identified three cases of LPHD occurring simultaneously with T-cell lymphoma in a series of 76 cases of LPHD in the files of the Nebraska Lymphoma Study Group Registry. In large areas of the lymph nodes, atypical T cells with large, irregular, and hyperchromatic nuclei were admixed with Reed-Sternberg variants characteristic of LPHD (L&H cells). However, in all cases, areas of typical nodular LPHD without obvious T-cell lymphoma were also evident. In one case, frozen-section immunohistochemistry demonstrated the absence of expression of CD5, CD4, or CD8 by the T-cell lymphoma. The L&H cells in all cases expressed CD45 and CD20, as expected. In all three cases, clonal T-cell receptor (TCR)-gamma gene and TCR-beta gene rearrangements were documented by polymerase chain reaction analysis and Southern blotting, respectively. No clonally rearranged immunoglobulin genes were detected by either technique. To our knowledge, this represents the first report of the simultaneous occurrence of LPHD and T-cell lymphoma. Although B-cell lymphoma occurring in the setting of LPHD is a well-recognized phenomenon, previous reports of T-cell lymphoma occurring after a diagnosis of LPHD, as well as our cases with synchronous disease, suggest that the association of T-cell lymphoma and LPHD may not be uncommon as well. Furthermore, our cases indicate that T-cell lymphoma occurring in LPHD is not therapy related. However, the underlying mechanisms by which these composite lymphomas occur remain unknown.

Adult↗
PubMed1996

High-resolution analysis of immunoglobulin heavy-chain gene rearrangements using denaturing gradient gel electrophoresis.

The detection of clonality in B-cell lymphomas has been facilitated by polymerase chain reaction (PCR) analysis of the immunoglobulin heavy-chain gene (IgH) complementarity determining region 3 (CDR3) and size fractionation by polyacrylamide gel electrophoresis (PAGE). However, the detection of minor clonal populations and biallelic rearrangements and the isolation of monoclonal products from gels are sometimes problematic. This study evaluated whether denaturing gradient gel electrophoresis (DGGE), a technique that separates DNA based on nucleotide sequence rather than length, could alleviate these problems. A total of 32 selected cases was studied with a diagnosis of monoclonal (n = 10), polyclonal (n = 9), and indeterminate (n = 13) IgH gene rearrangements, which were determined by analysis of seminested IgH CDR3 PCR products in 8% PAGE. These cases were evaluated using DGGE of seminested IgH CDR3 PCR products that included a 40-bp GC clamp on the Jh primer. DGGE allowed the discrimination of monoclonal populations in 9 of 13 cases where 8% PAGE results were indeterminate. In addition, DGGE demonstrated biallelic IgH rearrangements in three cases where 8% PAGE revealed only one predominant product. DGGE facilitated the purification and isolation of clonal IgH CDR3 products for sequencing without prior cloning. As an adaptation of current IgH PCR protocols, DGGE can enhance the construction of tumor-specific CDR3 primers/probes for investigations of minimal residual disease.

Antibodies, Monoclonal↗
PubMed1996

Phase I trial of an antisense oligonucleotide OL(1)p53 in hematologic malignancies.

PURPOSE: The phosphoprotein p53 is involved in transcriptional regulation and is detected in hematologic malignancies. In vitro incubation of acute myelogenous leukemia with OL(1)p53, a 20-mer phosphorothioate oligonucleotide complementary to p53 mRNA, results in leukemic cell death. A phase I dose-escalating trial was conducted to determine the toxicity of OL(1)p53 following systemic administration to patients with hematologic malignancies. PATIENTS AND METHODS: Sixteen patients with either refractory acute myelogenous leukemia (n = 6) or advanced myelodysplastic syndrome (n = 10) participated in the trial. Patients were given OL(1)p53 at doses of 0.05 to 0.25 mg/kg/h for 10 days by continuous intravenous infusion. RESULTS: No specific toxicity was directly related to the administration of OL(1)p53. One patient developed transient nonoliguric renal failure. One patient died of anthracycline-induced cardiac failure. Approximately 36% of the administered dose of OL(1)p53 was recovered intact in the urine. Plasma concentrations and area under the plasma concentration curves were linearly correlated with dose. Leukemic cell growth in vitro was inhibited as compared with pretreatment samples. There were no clinical complete responses. CONCLUSION: A phosphorothioate oligonucleotide, OL(1)p53, can be administered systemically without complications. This type of modified oligonucleotide can be administered without complete degradation, as it was recovered from the urine intact. This oligonucleotide may be useful in combination with currently available chemotherapy agents for the treatment of malignancies.

Adult↗
PubMed1996

Molecular epidemiology of deletions and mutations of the latent membrane protein 1 oncogene of the Epstein-Barr virus in posttransplant lymphoproliferative disorders.

Latent membrane protein 1 (LMP1) is a protooncogene of the Epstein-Barr virus (EBV) that is expressed in most EBV-positive posttransplant lymphoproliferative disorders (PTLD). Small deletions in the carboxy-terminal domain of LMP1 have been recently described in Hodgkin's disease, nasopharyngeal carcinoma, and non-Hodgkin's lymphoma. We characterized the deletions and point mutations of LMP1 in 32 PTLD and 8 reactive lymphoid cases found to contain EBV by one or more methods, including LMP1 immunohistochemistry, EBV-encoded RNA in situ hybridization, LMP1 DNA amplification, or Southern blot analysis. Our goal was to study the relationship of LMP1 deletions and mutations with the PTLD morphology, clonality, EBV strain subtype, and survival of patients. We found a 30-bp deletion (Del-LMP1) in 13 of 32 (41%) PTLD cases and a similar incidence of Del-LMP1 and point mutations in 3 of 8 (38%) reactive EBV cases (rho = 0.87). The presence of the Del-LMP1 in the PTLD cases was not highly associated with a high-grade morphology or clonal immunoglobulin gene rearrangements compared with the wild-type LMP1. We found that 100% of B-strain isolates, compared with 30% of A-strain isolates, harbored the Del-LMP1. There was no significant difference in the survival of PTLD patients with or without Del-LMP1 (rho = 0.83). We conclude that the incidence of Del-LMP1 in PTLD may be reflective of the incidence of this EBV substrain in the regional population and that the Del-LMP1 sequence has no prognostic significance in PTLD.

Adolescent↗
PubMed1996

Multicentric angiofollicular lymph node hyperplasia in children: a clinicopathologic study of eight patients.

Multicentric angiofollicular lymph node hyperplasia (MAFH) is an idiopathic systemic disorder that has been reported only rarely in children. Therefore, we reviewed the clinical and pathologic features of eight patients listed in the Angiofollicular Lymph Node Hyperplasia Registry at our institution. The ages of the patients ranged from two to 17 years (median, 10 yr), and the male-to-female ratio was 1:3. The patients presented with constitutional symptoms, multifocal lymphadenopathy, hepatomegaly, and/or splenomegaly. The laboratory findings included peripheral blood cytopenias, polyclonal hypergammaglobulinemia, and renal and hepatic dysfunction. Histologically, we observed the plasma cell variant of MAFH in five patients (62.5%) and the hyaline-vascular variant in three (37.5%). Immunohistochemical stains revealed a polyclonal plasma cell population in all cases. Two of six specimens were positive for Epstein-Barr virus by RNA in situ hybridization. A clonal immunoglobulin heavy gene rearrangement was identified in one of the five specimens studied, but this had no apparent impact on the clinical course of the disease. None of the four specimens analyzed for the presence of Kaposi's sarcoma-associated herpesvirus was positive. Most patients were stable or free of disease after treatment, which included corticosteroids in six of the eight patients. We concluded that the clinical and pathologic features of MAFH in children are similar to those of adults, but MAFH seems to have a more favorable clinical course, i.e., low morbidity and mortality, in children.

Adolescent↗
PubMed1995

Clonal relationship between lymphocytic predominance Hodgkin's disease and concurrent or subsequent large-cell lymphoma of B lineage.

The occurrence of a large-cell lymphoma (LCL) concurrent with or subsequent to lymphocytic predominance Hodgkin's disease (LPHD) is well documented. Given the well-characterized B-cell nature of the Reed-Sternberg cell variants in LPHD, there may be a clonal relationship between the LPHD and the associated B-cell LCL. In this study, we adapted a highly sensitive, clonospecific assay to test whether the clone comprising the LCL exists in the corresponding LPHD tumor. Nine cases meeting the histologic criteria of nodular LPHD and B-cell LCL were identified, reviewed, and studied. Initially, clonality of both lesions was assessed using consensus primers to conserved regions in the IgH variable (frame-work III) and joining region genes in a polymerase chain reaction (PCR) assay. The PCR assay detected a clonal B-cell population in five of the LCLs, whereas analysis of eight cases of LPHD did not detect a dominant clone. Clonal products from the LCL were then sequenced, and clonospecific oligonucleotides were designed from the unique nucleotide sequence encoding the complementarity-determining region-III. These were then used as primers and/or probes in sensitive PCR-based assays on the corresponding LPHD tumors. In two cases, the clonospecific assay showed that the LPHD and LCL shared a common clone that was further confirmed by sequence analysis. This finding provides genotypic evidence that, at least in some cases, the LCL represents a clonal progression of LPHD.

Adult↗
PubMed1995

Hodgkin's disease.

BACKGROUND: Over three time periods, 1973-1977, 1978-1982, and 1983-1987, the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute collected all cases of Hodgkin's disease in designated geographic regions representative of the United States as a whole. METHODS: The authors reviewed the data pertaining to 9418 microscopically confirmed cases of Hodgkin's disease and focused on trends that emerged over the time intervals of this study. RESULTS: Hodgkin's disease had a bimodal distribution of age-specific incidence rates with two peaks in the age groups of 15-34 years and older than 55 years. Since 1973, the incidence of Hodgkin's disease in the younger age group increased progressively as a result of a marked increase in the incidence of the nodular sclerosis subtype. From the period 1973-1977 to 1983-1987, the age-adjusted incidence rate of nodular sclerosis rose from 1.1 to 1.6 per 100,000. In 1983-1987, nodular sclerosis represented 57.7% of Hodgkin's disease and occurred most often in whites, with an equal sex ratio. In females, this increase in incidence over time was most dramatic in young adult women. The overall incidence of the mixed cellularity subtype, 23.4% of Hodgkin's disease, remained stable although the age-specific incidence rate increased progressively in black males older than age 40 years. The incidence of the lymphocytic predominance subtype, 6.0% of Hodgkin's disease, remained stable over time, with a slight increase in adults older than age 50 years. The lymphocytic depletion subtype, 3.8% of Hodgkin's disease, occurred predominantly in the elderly; its incidence decreased, most likely the result of changes in diagnostic criteria, with many cases being reclassified as non-Hodgkin's lymphoma (NHL). Similarly, unclassifiable cases of Hodgkin's disease designated as miscellaneous, 9.1% of Hodgkin's disease, decreased over time, probably the result of improved classification. Nevertheless, a subset of cases of Hodgkin's disease remained difficult to subclassify. The human immunodeficiency virus (HIV) epidemic appears to be associated with an increased incidence of Hodgkin's disease in San Francisco County in adult males age 30-49 years, a population known to have a high prevalence of HIV infection. CONCLUSION: The SEER data suggest that Hodgkin's disease is a heterogeneous entity composed of at least two different diseases--nodular sclerosis and mixed cellularity. Over the time course of this study, the incidence of nodular sclerosis increased dramatically, particularly in adolescents and young adults, whereas mixed cellularity remained stable. The incidence of Hodgkin's disease in the elderly decreased, most likely the result of our improved ability to diagnose both Hodgkin's disease and NHL and the realization that many cases of NHL had been misclassified as Hodgkin's disease. This decrease in Hodgkin's disease occurred predominantly in the lymphocytic depletion and miscellaneous groups.

Adolescent↗
PubMed1995

Non-Hodgkin's lymphoma.

BACKGROUND: Significant advances in the understanding of non-Hodgkin's lymphoma (NHL) have occurred in the past two decades, resulting in changes in terminology and classification practices, which may affect the analysis of the Surveillance, Epidemiology, and End Results (SEER) data. METHODS: The incidence rates for each subgroup of NHL in the Working Formulation were reviewed from the National Cancer Institute's SEER data during three time periods: 1973-1977, 1978-1982, and 1983-1987. RESULTS: NHL has significantly increased by 50% from 1973 to 1988. The most frequently occurring NHL is diffuse large cell lymphoma, constituting nearly 30% of all lymphomas. Increased incidence rates for large cell immunoblastic and small noncleaved cell NHL observed during the 1980s are attributable largely to the acquired immunodeficiency syndrome epidemic. Exposure to environmental agents such as herbicides and hair coloring dyes have recently been identified as factors that increase the risk of NHL, but the overall contribution of these factors remains to be identified. The increase in extranodal lymphomas is in part a consequence of the application of modern immunophenotypic and genotypic methods, which lead to the reclassification of pseudolymphomas as monoclonal B-cell neoplasms. The apparent dramatic decline in the incidence of diffuse small cleaved NHL appears to be artifactual, as well, secondary to changes in classification of NHL. CONCLUSIONS: With the enhanced ability of pathologists to delineate new clinicopathologic entities by immunophenotypic and molecular biologic studies, future modifications to the collection of SEER data may be appropriate. Such an approach will address the limitations of the Working Formulation and lead to a more accurate data base for the evaluation of epidemiologic trends.

Adolescent↗