Biomedical subjects

C A Sander

Publications and source records attributed to C A Sander.

63 records · Page 4Linked to original sources

PubMed1994

CD30+ anaplastic large cell lymphomas.

Within the spectrum of CD30+ lymphoproliferative diseases of the skin primary cutaneous CD30+ large cell lymphomas are now recognized as a distinct clinicopathologic entity. Once terminologic confusions are clarified the pertinent clinical, histomorphological, and immunophenotypical features essential for the diagnosis can be delineated. Clinical studies indicate a better prognosis of primary cutaneous CD30+ large cell lymphomas as compared with their nodal counterparts and with other cutaneous large cell lymphomas. Therapeutic strategies should be planned accordingly.

Adolescent↗

PubMed1993

p53 mutation is associated with progression in follicular lymphomas.

The majority of low-grade follicular lymphomas will eventually transform to an aggressive intermediate, or high-grade lymphoma. The molecular mechanisms responsible for this transformation have not been determined. We studied serial biopsies from 34 patients with follicular lymphomas that underwent histologic transformation, for abnormalities of the p53 tumor suppressor gene by a combination of immunohistochemistry, single strand conformation polymorphism analysis (SSCP), and sequencing. We found overexpression of p53 in 10 of the 34 transformed aggressive lymphomas, 9 of which contained mutations identified by SSCP analysis and subsequent sequencing. Matched pretransformation low-grade follicular lymphoma biopsies were available for 7 of the 10 cases. None of six studied by immunohistochemistry showed overexpression of p53 and only 1 of 4 studied by SSCP/sequencing showed the presence of mutation in the pretransformation biopsy. Interestingly, an eighth p53 positive transformed lymphoma recurred with a clonally related, p53 negative low-grade lymphoma 5 years after the patient had achieved a complete remission. Immunohistochemistry also showed that several pretransformation biopsies from p53 positive transformed cases showed rare p53 positive cells and in one case we could document an increase in their number over time. Twenty-five additional low-grade follicular lymphoma biopsies were also examined. Three patients had lymphomas positive for p53 mutation. One of the three subsequently transformed within a year of the biopsy studied; the second patient had an earlier (unavailable) biopsy at a different site that showed transformed histology. The third patient was treated with ProMACE-MOPP combination chemotherapy and attained a complete remission. We conclude that (1) mutations of p53 are associated with histologic transformation in approximately 25% to 30% of follicular lymphomas and (2) p53 positive cells can be detected before histologic transformation, but do not comprise a significant percentage of the neoplastic cell population (identifiable by SSCP) until late in the disease, just before or after histologic progression. Finally, the data also suggest that p53 positive low-grade lymphomas are at risk for progression and that in this subset, aggressive therapy may be warranted.

Base Sequence↗

PubMed1993

Molecular analysis of the BCL-3 locus at chromosome 17q22 in B-cell neoplasms.

To better understand the role of the BCL-3 locus at chromosome 17q22 in the pathogenesis and progression of leukemias and lymphomas, we examined its genomic configuration in 264 B-cell malignancies and its expression in a smaller subset. Cases studied included 39 chronic lymphocytic leukemias, 58 low-grade follicular lymphomas, 20 mantle cell lymphomas, 30 small noncleaved cell lymphomas, 25 acute lymphoblastic leukemias, 10 acquired immunodeficiency syndrome--related non-Hodgkin's lymphomas, and 44 diffuse mixed- or diffuse large-cell lymphomas. In addition, 38 aggressive lymphomas (transformed follicular lymphomas) derived from previously indolent follicular lymphomas were examined. Southern blot analysis showed BCL-3 locus rearrangement in 4 cases (1.5%), ie, in 3 transformed follicular lymphomas and in 1 indolent follicular lymphoma. All 4 also had BCL-2 rearrangements consistent with their follicular center cell origin. None of the BCL-3 rearranged cases showed MYC gene rearrangement, as reported for the original leukemia that led to the discovery of BCL-3. Pretransformation specimens of all three transformed follicular lymphomas showed the presence of the BCL-3 alteration before histologic progression. In 1 case, serial pretransformation biopsies showed that the BCL-3 rearrangement was acquired during the indolent follicular phase of the patient's disease. Thirty lymphomas, including 2 of the 4 with BCL-3 rearrangement, were also examined for BCL-3 message. All 30, including the 2 with BCL-3 rearrangements, expressed the normal 1.7-kb BCL-3 transcript, at approximately equivalent levels. The data indicate that, although BCL-3 locus alterations are found in only a small fraction of B-cell lymphoid malignancies, they occur primarily in a subset of follicular center cell lymphomas. Interestingly, these alterations appear to be acquired during the indolent (follicular) phase of the disease and they are maintained when histologic transformation takes place. The data also suggest that BCL-3 locus alterations do not result in gross changes of BCL-3 gene expression and do not necessarily involve the MYC gene. Although the preferential involvement of BCL-3 alterations in a small subset of follicular lymphomas that transform suggests a possible link between these abnormalities and progression, further studies are needed to ensure that these alterations are biologically relevant and not simply a manifestation of genomic instability.

B-Cell Lymphoma 3 Protein↗

PubMed1993

B-cell lymphoma after angioimmunoblastic lymphadenopathy: a case with oligoclonal gene rearrangements associated with Epstein-Barr virus.

We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), who subsequently developed large-cell immunoblastic lymphoma of B-cell immunophenotype. At the time of the initial diagnosis, histologic examination of an inguinal lymph node showed typical features of AILD, and there was no evidence of a monoclonal B-cell population by immunohistochemical analysis. In situ hybridization and Southern blot analysis for Epstein-Barr virus (EBV) were negative. At autopsy 2 years later, the patient had widespread lymph node and organ involvement by large-cell immunoblastic lymphoma of B-cell immunophenotype. Southern blot analysis performed on DNA extracted from lymph nodes, liver, and spleen showed two patterns of Ig heavy chain and kappa light chain gene rearrangements. The T-cell receptor beta chain gene was in the germline configuration. Analysis with an EBV terminal repeat region probe showed two clonal populations that paralleled the Ig gene rearrangement studies. Double-labeling immunohistochemistry and in situ hybridization confirmed the presence of EBV within the neoplastic B cells. The data support the hypothesis that EBV was not etiologically related to AILD in this case, and that EBV proliferation may occur after the onset of the disease. Further, the data suggest that some B-cell lymphomas that arise in the setting of AILD resemble EBV-associated B-cell lymphomas that arise in other immunodeficiency states.

Blotting, Southern↗

PubMed1993

Clustered mutations in the second exon of the MYC gene in sporadic Burkitt's lymphoma.

The primary tumors from 15 untreated patients with Burkitt's lymphoma were analysed for abnormalities in the coding region of the MYC gene by single stranded conformational polymorphism (SSCP) analysis followed by DNA sequencing. Fourteen of the 15 tumors had one or more clonal mutations. Forty one mutations were found in the second exon; only one occurred in the third exon. Seven tumors had mutations that clustered in a region spanning amino acids 38-63. Four of these possessed mutations that altered prolines at positions 57 (3), 60 (1), and 63 (1). Seven tumors were mutated in the central portions of the second exon. These occurred at position 95 (2), position 115 (2), position 137 (1), and position 138 (3). Analysis of the published sequences from five lymphoma cell lines and one primary tumor showed a similar clustering of mutations, with all six having mutations in codons between positions 38-63. The regions where mutations occurred have been associated with a variety of properties, including transcriptional activation and cellular transformation. The number and location of mutations showed no correlation with either chromosome 8 or chromosome 14 breakpoints or with the Epstein-Barr virus positivity of the tumors. This unexpected, frequent occurrence of clustered mutations in the second exon of the MYC gene suggests a role for the mutated MYC proteins in the pathogenesis of Burkitt's lymphoma, possibly through altered interactions of this domain with other cellular factors.

Amino Acid Sequence↗

PubMed1992

Mediastinal lymphoblastic lymphoma with an immature B-cell immunophenotype.

A 19-year-old woman presented with a large mediastinal mass, histologically shown to be malignant lymphoma of lymphoblastic type (LBL). Immunophenotypic and gene rearrangement analysis unequivocally demonstrated that the neoplasm was of B-cell lineage. The neoplastic cells expressed terminal deoxynucleotidyl transferase, the pan-B cell antigens CD19, CD20, and CD22, and were negative for immunoglobulins and numerous T-cell antigens tested. Southern blot analysis showed rearrangement of one allele of the immunoglobulin heavy chain gene while the immunoglobulin kappa and T-cell receptor beta chain genes were in the germline configuration. Thus, the immunophenotypic and molecular findings in this case correspond to an early stage of B-cell differentiation, the pre-pre B-cell stage as has been named by others. In contrast with LBL of immature T-cell lineage, precursor B-cell LBLs involving the mediastinum are truly rare. Occasional cases have been reported that have arisen elsewhere and subsequently involved the mediastinum at time of relapse or tumor progression. Well-documented examples of immature B-cell LBL arising in the mediastinum are virtually unreported. The site and cell population giving rise to this neoplasm is unknown. However, origin from precursors of normal thymic medullary B cells is proposed as one possibility.

Adult↗

PubMed1992

Lymphoproliferative lesions in patients with common variable immunodeficiency syndrome.

We reviewed our experience with 30 nodal and extranodal lymphoid lesions from 17 patients with common variable immunodeficiency (CVID). Immunohistochemical studies were performed on biopsies from 15 patients, in situ hybridization for Epstein-Barr virus in nine cases, and gene rearrangement analysis on seven lesions. The biopsies were classified into four groups: malignant lymphoma (two cases); atypical lymphoid hyperplasia (eight cases); reactive lymphoid hyperplasia (14 cases); and chronic granulomatous inflammation (six cases). The two malignant lymphomas were diagnosed using histologic criteria; tissue was not available for the assessment of clonality. In one neoplasm, Epstein-Barr virus was identified in the tumor cells by in situ hybridization. The cases of reactive lymphoid hyperplasia and chronic granulomatous inflammation had no atypical architectural, cytologic, or immunohistochemical features. The cases of atypical lymphoid hyperplasia were of particular interest, as these patients had either widespread involvement or massive disease. The diagnosis of lymphoma was considered likely by the clinicians and, in three cases, the histologic slides were originally interpreted as malignant lymphoma by the referring pathologists. Although the architecture of these lesions appeared to be effaced on hematoxylin and eosin-stained sections, immunohistochemical analysis demonstrated preserved architecture with florid expansion of B-cell and T-cell compartments. In addition, clinical follow-up of these patients was benign, and gene rearrangement analysis in three lesions revealed no evidence of clonality. We conclude that the majority of lymphoid lesions in patients with CVID are benign. Immunohistochemical and gene rearrangement studies are particularly helpful in the assessment of cases of atypical lymphoid hyperplasia.

Adolescent↗

PubMed1992

Mantle cell lymphoma: an update.

Mantle cell lymphoma is a distinctive pathologic entity that incorporates the previous histopathologic categories of centrocytic lymphoma and lymphocytic lymphoma of intermediate differentiation. These lymphomas are characterized by common histologic and immunologic characteristics that suggest derivation from the follicular mantle zone. Mantle cell lymphomas are characterized by the t(11;14) (q13;q32) translocation and its molecular counterpart bcl-1 rearrangement. This translocation activates a gene called BCL-1/PRAD-1. The identification of the BCL-1 gene product as a cyclin has added a new dimension to our understanding of the variety of mechanisms involved in lymphomagenesis.

Antigens, CD↗

PubMed1991

Lymphoblastic lymphoma presenting in cutaneous sites. A clinicopathologic analysis of six cases.

Six patients with malignant lymphoma of lymphoblastic type involving cutaneous sites at time of diagnosis are presented. Skin sites of the head and neck were involved in all patients and included the scalp (three patients), forehead (two patients), and malar region of the face (one patient). Two patients also had additional sites of skin disease (neck, breast, and anterior trunk). In two patients the skin was the predominant site of disease, whereas in the remaining patients staging workup revealed generalized lymphoma. The histologic findings in each patient were typical of lymphoblastic lymphoma; the neoplastic cells were small with blastic nuclear chromatin. In three patients the neoplastic cells were convoluted, and in three they were nonconvoluted. Immunophenotypically, four lymphomas were of pre-B cell type, and two lymphomas were of T cell type. There was no correlation between histologic features and the immunophenotype. Since the majority of lymphoblastic lymphomas are of T cell type, the predominance of pre-B cell tumors involving the skin may suggest that pre-B cell neoplasms have a predilection for cutaneous involvement. In further support of this hypothesis, both lymphomas that appear to have arisen in the skin had a pre-B cell immunophenotype.

Adult↗