Biomedical subjects

Sherrie L Perkins

Publications and source records attributed to Sherrie L Perkins.

At least 19 recordsLinked to original sources

PubMed2007

Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents.

The prognosis for higher risk childhood B-cell non-Hodgkin lymphoma has improved over the past 20 years but the optimal intensity of treatment has yet to be determined. Children 21 years old or younger with newly diagnosed B-cell non-Hodgkin lymphoma/B-cell acute lymphoblastic leukemia (B-NHL/B-ALL) with higher risk factors (bone marrow [BM] with or without CNS involvement) were randomized to standard intensity French-American-British/Lymphoma Malignancy B (FAB/LMB) therapy or reduced intensity (reduced cytarabine plus etoposide and deletion of 3 maintenance courses M2, M3, M4). All patients with CNS disease had additional high-dose methotrexate (8 g/m2) plus extra intrathecal therapy. Fifty-one percent had BM involvement, 20% had CNS involvement, and 29% had BM and CNS involvement. One hundred ninety patients were randomized. The probabilities of 4-year event-free survival (EFS) and survival (S) were 79% +/- 2.7% and 82% +/- 2.6%, respectively. In patients in remission after 3 cycles who were randomized to standard versus reduced-intensity therapy, the 4-year EFS after randomization was 90% +/- 3.1% versus 80% +/- 4.2% (one-sided P = .064) and S was 93% +/- 2.7% versus 83% +/- 4.0% (one-sided P = .032). Patients with either combined BM/CNS disease at diagnosis or poor response to cyclophosphamide, Oncovin [vincristine], prednisone (COP) reduction therapy had a significantly inferior EFS and S (P < .001). Standard-intensity FAB/LMB therapy is recommended for children with high-risk B-NHL (B-ALL with or without CNS involvement).

Adolescent↗

PubMed2007

Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients.

A previous study (LMB89) of the French Society of Pediatric Oncology for childhood mature B-cell lymphoma (B-NHL) demonstrated a 92% 3-year event-free survival (EFS) for intermediate-risk group B defined as "non-resected" stage II/I and CNS-negative advanced-stage IIV/IV (70% of cases). We performed the FAB/LMB96 trial to assess the possibility of reducing treatment in children/adolescents with intermediate-risk B-NHL without jeopardizing survival. "Early responding" patients (tumor response > 20% at day 7) were randomized in a factorial design between 4 arms, 2 receiving half-dose of cyclophosphamide in the second induction course with cyclophosphamide, Oncovin (vincristine), prednisone, Adriamycin (doxorubicin), methotrexate (COPADM) and 2 not receiving the maintenance course M1. A total of 657 patients were randomized (May 1996 to June 2001) and 637 were analyzed. The analysis showed no significant effect of any of the treatment reductions on EFS and survival. The 4-year EFS was 93.4% and 90.9% in the groups with full-dose and half-dose of cyclophosphamide (RR = 1.3, P = .40) and 91.9% and 92.5% in the groups with and without M1 (RR = 1.01, P = .98). There was no interaction between the 2 treatment reductions or between each treatment reduction and LDH level or histologic subtypes (Burkitt/Burkitt-like or large B-cell). Children/adolescents with intermediate-risk B-NHL who have an early response and achieve a complete remission after the first consolidation course can be cured with a 4-course treatment with a total dose of only 3.3 g/m2 cyclophosphamide and 120 mg/m2 doxorubicin.

Adolescent↗

PubMed2007

Chromosome abnormalities in advanced stage lymphoblastic lymphoma of children and adolescents: a report from CCG-E08.

Among pediatric non-Hodgkin lymphomas, one of the most frequent types is lymphoblastic lymphoma (LBL). Specific chromosome abnormalities are associated with prognosis in childhood acute lymphoblastic leukemia, but have not been evaluated for prognostic value in pediatric LBL. For the Children's Cancer Group protocol CCG-E-08 Etiologic Study of Non-Hodgkin Lymphoma in Childhood, 13 patients were enrolled with cytogenetic analysis of LBL and on treatment protocol CCG-502. Pathology material and karyotypes at initial diagnosis were given central review. The patients were aged 6-13 years (median 9 years), with a male-to-female ratio of 12:1. All patients had advanced disease. Disease relapsed in six patients (event-free survival 54% +/- 14%, median 10.8 years). Chromosome abnormalities were identified in 11 (85%), and translocations at 14q11.2 likely involving the T-cell receptor alpha/delta locus (TCR A/D) occurred in 4 (31%). For patients with relapse, four had translocations t(1;14)(p32;q11.2), t(8;14)(q24.1;q11.2), t(11;14)(p13;q11.2), or t(9;17)(q34;q23), involving breakpoints in the regions of TAL1, MYC, LMO2, and NOTCH1, respectively. Pediatric advanced LBLs have a high frequency of chromosome abnormalities; in this limited study, these often involved translocations at 14q11.2, the site of TCR A/D. Translocations possibly involving TAL1, MYC, LMO2, or NOTCH1 may have contributed to poor outcome. Further studies are warranted in larger cohorts of children and adolescents with LBL to evaluate the prognostic significance.

Adolescent↗

PubMed2007

Human herpesvirus 8 and iron staining are useful in differentiating Kaposi sarcoma from interstitial granuloma annulare.

We studied 20 granuloma annulare (GA) cases (10 interstitial and 10 palisaded) and 19 Kaposi sarcoma (KS) cases (9 "early" and 10 typical). Tissue sections were stained for iron, Hale colloidal iron, human herpesvirus 8 (HHV-8), CD31, CD34, CD68, collagen IV, factor XIIIa, and MIB-1. Iron staining of dermal tissue associated with the lesion was confirmed in all KS cases and no GA cases. Immunohistochemical stains for HHV-8 were positive in all 9 cases of early KS and most cases (9/10) of typical KS. All 20 cases of GA were HHV-8-. CD31, CD34, CD68, factor XIIIa, and MIB-1 were also stained but were difficult to interpret and did not seem specific for GA or KS. Iron staining and immunohistochemical HHV-8 staining in combination were reliable markers for KS compared with interstitial GA. MIB-1 fractions of less than 5% favored a diagnosis of GA, whereas fractions greater than 10% favored a diagnosis of KS. This study provides novel data characterizing iron staining in KS and details the use of iron staining, HHV-8, and MIB-1 to distinguish KS from GA.

Granuloma Annulare↗

PubMed2006

Gene expression profiling reveals intrinsic differences between T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL) and are often thought to represent a spectrum of a single disease. The malignant cells in T-ALL and T-LL are morphologically indistinguishable, and they share the expression of common cell surface antigens and cytogenetic characteristics. However, despite these similarities, differences in the clinical behavior of T-ALL and T-LL are observed. PROCEDURE: We analyzed the gene expression profiles of T-ALL and T-LL samples obtained from Children's Oncology Group (COG) tumor banks using DNA arrays. Immunohistochemistry was also performed to validate the expression of selected targets. RESULTS: Unsupervised hierarchical clustering of all samples showed complete segregation of T-ALL and T-LL into distinct clusters. Next, we identified the top 201 genes that best differentiated T-ALL from T-LL using significance analysis of microarrays (SAM), a supervised statistical approach. Genes representing several functional groups were differentially expressed in T-LL and T-ALL. Prediction analysis of microarrays (PAM) identified a subset of genes, which accurately classified all 19 T-ALL and T-LL samples with an overall misclassification error rate of 0. Immunohistochemical validation of protein expression of selected genes identified by microarray analysis confirmed overexpression of MLL-1 in T-LL tumor cells compared to T-ALL and CD47 in T-ALL tumors cells when compared to T-LL. CONCLUSIONS: Despite significant similarities between the malignant T-cell precursors, clear differences in the gene expression profiles were observed between T-ALL and T-LL implying underlying differences in the biology of the two entities.

Bone Marrow↗

PubMed2006

Complex secondary chromosome abnormalities in advanced stage anaplastic large cell lymphoma of children and adolescents: a report from CCG-E08.

Among pediatric non-Hodgkin lymphomas, one of the most distinctive types is anaplastic large cell lymphoma (ALCL). Specific chromosomal abnormalities are associated with prognosis in childhood acute lymphoblastic leukemia, but chromosome abnormalities have not been evaluated for prognostic value in pediatric ALCL. For Children's Cancer Group protocol CCG-E-08 Etiologic Study of Non-Hodgkin Lymphoma in Childhood, three patients were enrolled with cytogenetic analysis of ALCL and simultaneously enrolled on treatment protocol CCG-552. Pathology material and karyotypes at initial diagnosis underwent central review. Demographics included ages of 9, 12, and 14 years, and a male/female ratio of 1:2. All patients had advanced disease (stage III). Disease progressed or relapsed in two patients, and one died. Chromosomal abnormalities, including t(2;5)(p23;q35), the ALK/NPM fusion gene, and complex karyotypes with multiple additional abnormalities, were identified in all three patients. In two patients with progressive disease or relapse, additional chromosomal abnormalities at 1q21 and 10q24, possibly involving MCL1 and HOX11/TCL3, respectively, may have contributed to worse outcome. Pediatric ALCL cases frequently have complex karyotypes and usually involve ALK/NPM translocations in this limited study. Additional chromosome abnormalities may be involved in the pathogenesis of ALCL. Further studies are warranted in larger cohorts of children and adolescents with ALCL.

Adolescent↗

PubMed2006

Mature B-cell lymphoma in children and adolescents: International group pathologist consensus correlates with histology technical quality.

In pediatric mature B-cell non-Hodgkin lymphoma, international pathologist diagnostic agreement was previously evaluated using the Revised European-American Lymphoma Classification. Surgical biopsy histology technical quality (HTQ) is variable and may affect diagnostic accuracy. This study evaluated diagnostic agreement correlated with HTQ. Surgical biopsies obtained from international protocol FAB LMB96 Treatment of Mature B-Cell Lymphoma/Leukemia for Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and high-grade B-cell lymphoma Burkitt-like (BLL), were independently reviewed by hematopathologists from 3 national groups (Children's Cancer Group, Société Française d'Oncologie Pédiatrique, and United Kingdom Children's Cancer Study Group) to determine each national diagnosis and a final diagnosis. HTQ grades for microscopic tissue sections included: good; medium; low; inconclusive. Final diagnoses in 187 cases included: BL 87 (47%); BLL 20 (11%); DLBCL 64 (34%); other 16 (9%). HTQ grades included: good 10 (5%); medium 100 (54%); low 75 (40%); inconclusive 2 (1%). The rate of uniform agreement between the national diagnoses was significantly higher with good or medium HTQ (62%) than with low HTQ (33%) (P = 0.001). In conclusion, in pediatric mature B-cell non-Hodgkin lymphoma, international pathologist diagnostic agreement is significantly higher in surgical biopsies with better HTQ. Poor HTQ may adversely impact diagnostic ability and affect prognosis and therapeutic management when different treatment regimens are employed for DLBCL versus BL/BLL.

Adolescent↗

PubMed2006

Tumor cell nuclei extraction from paraffin-embedded lymphoid tissue for fluorescence in situ hybridization.

In this study the authors evaluated a technique for isolating intact tumor nuclei from paraffin-embedded lymphoma samples before performing FISH testing to detect the lymphoma-specific trans-location t(11;14) that defines mantle cell lymphoma. Well-characterized surgical pathology cases of mantle cell lymphoma were identified from pathology archives. Thin sections were cut from the paraffin-embedded tissue blocks. One section was stained using hematoxylin and eosin and an area composed exclusively of malignant cells was identified and marked on the slide. The corresponding area of the tissue block corresponding to this region underwent needle core biopsy, and the tissue was processed to isolate tumor cell nuclei and deposited onto a glass slide. The paired sample preparations underwent routine FISH testing for detection of the t(11;14)(q13;q32) chromosomal trans-location. DNA probe hybridization quality was compared between the tissue and isolated nuclei. Individual tumor cell nuclei were successfully extracted from each of the tissue blocks. The t(11;14) trans-location was detected by FISH in all of the samples diagnosed as mantle cell lymphoma. The hybridization signals found in the nuclei of extracted tumor cells were bright, planar, and easily identified. Detection of signal was superior to that on whole tissue samples, where signals often overlapped or were truncated. This technique produces intact nuclei for analysis, preserves the tissue block for additional studies, and allows sampling of a specific area of the tissue block. This approach may be particularly useful when the amount of diagnostic tissue is limited.

Cell Nucleus↗

PubMed2006

Usefulness (or lack thereof) of immunophenotyping in atypical cutaneous T-cell infiltrates.

Our purpose was to evaluate the interobserver concordance for the diagnoses of mycosis fungoides (MF), atypical dermatoses (AD), and benign dermatoses (BD) and the impact of T-cell immunophenotyping on the diagnoses MF, AD, and BD. Specimens of MF (n = 57), AD (n = 27), BD and normal skin (n = 54) were reviewed by 2 hematopathologists and 1 dermatopathologist to establish diagnostic interobserver concordance by routine morphologic examination. Immunophenotyping was performed to evaluate expression of CD2, CD3, CD4, CD5, CD7, CD8, CD20, CD30, and MIB-1. The interobserver concordance was fair to moderate compared with the original diagnosis. Partial deletion of CD2 alone was associated significantly with MF. Epidermal deletions of 2 or 3 T-cell antigens or 2 T-cell antigens not including CD7 were associated significantly with MF. An elevated CD4/CD8 ratio correlated with MF. Morphologic features were most diagnostic of MF. Immunophenotyping generally resulted in downgrading of the reaction pattern but was helpful in distinguishing MF from benign dermatoses.

Adult↗

PubMed2006

Teaching pediatric laboratory medicine to pathology residents.

CONTEXT: Laboratory data are essential to the medical care of fetuses, infants, children, and adolescents. However, the performance and interpretation of laboratory tests on specimens from these patients, which may constitute a significant component of the workload in general hospitals and integrated health care systems as well as specialized perinatal or pediatric centers, present unique challenges to the clinical pathologist and the laboratory. Therefore, pathology residents should receive training in pediatric laboratory medicine. OBJECTIVE: Children's Health Improvement through Laboratory Diagnostics, a group of pathologists and laboratory scientists with interest and expertise in pediatric laboratory medicine, convened a task force to develop a list of curriculum topics, key resources, and training experiences in pediatric laboratory medicine for trainees in anatomic and clinical pathology or straight clinical pathology residency programs and in pediatric pathology fellowship programs. DATA SOURCES: Based on the experiences of 11 training programs, we have compiled a comprehensive list of pediatric topics in the areas of clinical chemistry, endocrinology, hematology, urinalysis, coagulation medicine, transfusion medicine, immunology, microbiology and virology, biochemical genetics, cytogenetics and molecular diagnostics, point of care testing, and laboratory management. This report also includes recommendations for training experiences and a list of key texts and other resources in pediatric laboratory medicine. CONCLUSIONS: Clinical pathologists should be trained to meet the laboratory medicine needs of pediatric patients and to assist the clinicians caring for these patients with the selection and interpretation of laboratory studies. This review helps program directors tailor their curricula to more effectively provide this training.

Child↗

PubMed2005

Childhood and adolescent non-Hodgkin lymphoma: new insights in biology and critical challenges for the future.

Pediatric non-Hodgkin lymphoma (NHL) is a common and fascinating group of diseases with distinctive underlying genetic events that characterize the major histologic subtypes: diffuse large B-cell lymphoma, Burkitt lymphoma, anaplastic large cell lymphoma and lymphoblastic lymphoma. With systematic improvements in therapy over recent decades, the vast majority of children with NHL of all subtypes are now cured. The similarities and differences between adult and childhood presentations of disease, and whether or not some subtypes of NHL and leukemia are the same or different disease entities, are interesting questions that will be addressed with advances in our understanding of the molecular and genetic bases of these diseases. As is the case with other pediatric malignancies, growing emphasis is now being placed on the development of less toxic, targeted therapeutic approaches, and this review highlights some of the biological discoveries that will potentially open these avenues.

Adolescent↗

PubMed2005

Morphologic and immunohistochemical evaluation of splenic hematopoietic proliferations in neoplastic and benign disorders.

Spleen is a common site of extramedullary hematopoiesis. Extramedullary hematopoiesis seen in non-neoplastic conditions can occasionally be extensive and raise concerns for a myeloid neoplasm. We compared the morphologic and immunohistochemical features of splenic hematopoietic proliferations seen in neoplastic myeloid disorders (eg chronic myeloproliferative disorders, myelodysplastic/myeloproliferative disorders and acute myeloid leukemias) to extramedullary hematopoiesis seen in a variety of reactive conditions. In all, 80 spleen specimens were reviewed. The presence of each marrow-derived lineage, dysplasia and immunohistochemical results were evaluated (CD34, CD117, myeloperoxidase, CD68, p53, TdT, CD42b and hemoglobin). Neoplastic hematopoietic proliferations in chronic myeloproliferative disorders are characterized by trilineage hematopoiesis with significant dysplasia in all cell lineages. Acute myeloid leukemia showed an increase in immature forms, which were highlighted by immunohistochemistry. Reactive extramedullary hematopoiesis showed variability in histologic features. Post-bone marrow transplant and thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome spleens showed extramedullary hematopoiesis with some morphologic features of immaturity, which could simulate chronic myeloproliferative disorder. However, they lacked characteristic immunohistochemical features of neoplastic myeloid disorders such as positivity for CD34 or CD117.

Adolescent↗

PubMed2005

Childhood anaplastic large cell lymphoma has a high incidence of ALK gene rearrangement as determined by immunohistochemical staining and fluorescent in situ hybridisation: a genetic and pathological correlation.

Anaplastic large cell lymphoma (ALCL) comprises 10-15% of childhood non-Hodgkin lymphomas (NHL). Systemic ALCL is highly associated with anaplastic lymphoma kinase (ALK) gene translocations with over-expression of ALK protein. We studied ALK rearrangements using fluorescence in situ hybridisation (FISH) and ALK immunohistochemical staining in 43 paediatric systemic ALCLs. FISH (performed on 35 cases) identified a translocation in 29 cases (83%). Immunohistochemistry identified ALK over-expression in 42/43 cases (97%) with the single ALK-negative case demonstrating an ALK rearrangement by FISH, indicating 100% incidence of ALK translocations.

Adolescent↗

PubMed2005

TCL1 expression and Epstein-Barr virus status in pediatric Burkitt lymphoma.

Elevated T-cell leukemia-1 (TCL1) oncoprotein expression might promote human Burkitt lymphoma (BL) because increased TCL1 causes Burkitt-like lymphomas in TCL1 transgenic mice. Epstein-Barr virus (EBV) infection has been implicated as a cause of increased TCL1 expression in multiple BL cell lines, suggesting a critical connection between EBV and TCL1-induced BL. The TCL1 expression and EBV status of 14 sporadic pediatric BL cases was determined by immunohistochemical staining for TCL1 and in situ hybridization for EBV-encoded RNA (EBER). Our results showed TCL1 protein in 11 cases, predominantly in the nucleus with strong-intensity staining. EBER was positive in 4 cases, with 3 of these cases also TCL1+. In the 10 cases that were EBER-, TCL1 was strongly positive in 8. These data indicate that the TCL1 oncoprotein is expressed strongly in most pediatric BL cases. However, persistent EBV is not essential for increased TCL1 expression, although elevated TCL1 and c-MYC coexpression might cooperate in the development of most pediatric and adult BL cases.

Adolescent↗

PubMed2005

Hairy cell leukemia variant: fact or fiction.

Hairy cell leukemia variant (HCL-V) is a poorly described, rare B-cell lymphoproliferative disorder typically positive for CD103 and CD11c, while lacking CD25. Splenic marginal zone lymphomas (SMZL) also have this unusual phenotype in 15% to 25% of cases, have other overlapping clinical or morphologic features, and are more common than HCL-V. The purpose of our study was to better characterize HCL-V and determine whether most cases could be distinguished from SMZL. Cases with an HCL-V phenotype were identified from our flow cytometry service, and 10 were selected for further study based on bone marrow or splenic tissue availability. All cases had cytologic features consistent with HCL-V, and 9 of 10 patients had lymphocytosis. Bone marrow involvement was mostly interstitial and/or sinusoidal without lymphoid nodules. Coexpression of preswitched with postswitched heavy chain isotypes, an unusual feature of HCL, was seen in 2 of 4 cases. This study better defines HCL-V and establishes that most cases do not represent SMZL.

Aged↗

PubMed2005

Histogenetic phenotypes of B cells in posttransplant lymphoproliferative disorders by immunohistochemical analysis correlate with transplant type: solid organ vs hematopoietic stem cell transplantation.

We immunohistochemically defined the histogenesis of posttransplantation lymphoproliferative disorders (PTLDs; B-cell phenotype) occurring after allogeneic T cell-depleted hematopoietic stem cell transplantation (HSCT; n = 15) or solid organ transplantation (SOT; n = 11) to determine whether transplantation type or morphologic subtype of PTLD affected the histogenetic subtype. Immunohistochemical stains using histogenetic markers for germinal center (GC) B cells, late GC and post-GC B cells, and post-GC B cells were performed on paraffin-embedded samples. Morphologically, 14 cases were polymorphic; 12 were monomorphic. Histogenetic marker expression was as follows: 1 monomorphic case (4%), GC phenotype expressing bcl-6 and CD10; 17 cases (65%; polymorphic, 9; monomorphic, 8), late GC-early post-GC phenotype expressing MUM1/IRF4; 8 cases (31%; polymorphic, 5; monomorphic, 3), post-GC phenotype expressing MUM1/IRF4 and CD138 but not bcl-6. PTLD cases after HSCT more frequently were post-GC phenotype than after SOT (7/15 vs 1/11, respectively; P = .040) and were independent of morphologic subclassification. Results suggest that most PTLDs are late GC-early post-GC phenotype with a minor group of post-GC phenotype and rare cases of GC phenotype. Findings also suggest a correlation between histogenetic phenotype of B-cell PTLD and type of transplantation.

Adult↗

PubMed2005

Flow cytometric analysis of different CD14 epitopes can help identify immature monocytic populations.

Accurate diagnosis of monocytic neoplasms often is dependent on quantitating monoblasts, promonocytes, and monocytes. However, distinguishing these populations by morphologic assessment alone can be difficult and subject to significant intraobserver variability. We evaluated a 4-color flow cytometry technique using different anti-CD14 antibodies that recognize the MO2 and MY4 epitopes to identify monoblasts, promonocytes, and monocytes. Normal control specimens and 18 cases of monocytic neoplasia were evaluated and results correlated with morphologic findings. We found the MY4 epitope first appearing at the early promonocyte stage and the MO2 epitope appearing only on mature monocytes after the promonocyte stage. Expression of the MY4 and MO2 epitopes by neoplastic monocyte populations was found to usually parallel the normal monocyte differentiation patterns, although exceptions were noted. Our study suggests that 4-color flow cytometry may be an especially useful adjunct for morphologically difficult cases by providing an immunophenotypic measure of neoplastic monoblasts and promonocytes.

Epitopes↗

PubMed2005

T-cell large granular lymphocyte leukemias have multiple phenotypic abnormalities involving pan-T-cell antigens and receptors for MHC molecules.

T-cell large granular lymphocyte (T-LGL) leukemias represent monoclonal T-cell expansions that express CD16, CD56, or CD57 and cause cytopenias. The identification of T-LGL leukemias can be difficult because reactive T-LGL cells also can express CD16, CD56, and CD57, and many leukemia cases show only mild lymphocytoses. In this study, 23 T-LGL leukemia cases were analyzed by 3- and 4-color flow cytometry to identify markers that could aid in discriminating leukemic from normal T-LGL. In most cases (18/23), abnormalities (bright, dim, or negative expression) of 2 or more pan-T-cell antigens were identified, with all cases showing abnormal CD5 levels. Abnormal expression of CD94 was identified in 22 of 23 cases, and 15 of 21 cases also showed abnormal expression of class 1 MHC receptor molecules identified by antibodies against CD158a, CD158b, CD158e, CD158i, CD158k, and CD94. These studies help define abnormal phenotypic features typical of T-LGL leukemia that may have important diagnostic value.

Adult↗