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D A Arber

Publications and source records attributed to D A Arber.

At least 37 records · Page 2Linked to original sources
PubMed2000

Keratin immunohistochemistry detects clinically significant metastases in bone marrow biopsy specimens in women with lobular breast carcinoma.

Some patients with breast cancer currently undergo bone marrow biopsy to make clinical decisions regarding therapy; however, lobular carcinoma can be difficult to detect in routine histologic sections. The authors reviewed retrospectively all available bone marrow biopsies from patients with lobular carcinoma diagnosed between January, 1, 1989, and September, 25, 1997, at the City of Hope National Medical Center to identify useful morphologic features and to determine the utility of pan-keratin immunohistochemical (IHC) staining. A total of 65 biopsies from 54 patients were reviewed. Thirteen of the 65 biopsies were classified initially as containing metastatic tumor based on histologic features alone. With the addition of keratin IHC, seven additional cases of metastatic disease were detected. Forty of the 54 patients received stem cell replacement or autologous bone marrow transplantation. Disease-free survival after high-dose chemotherapy with stem cell replacement or autologous bone marrow transplantation was stratified into three groups based on hematoxylin and eosin (H&E) staining and IHC results. Two-year disease-free survival was 33% for the H&E-/IHC+ group versus 90% for the H&E-/IHC- group (p = 0.005) among patients clinically free of disease at the time of stem cell replacement or autologous bone marrow transplantation. Two-year disease-free survival was 0% in the H&E+/IHC+ group (p = 0.04, compared with the H&E-/ IHC+ group). The authors conclude that routine morphologic examination without the aid of keratin IHC is unreliable in detecting clinically relevant metastatic lobular carcinoma in bone marrow biopsies. These findings suggest that pan-keratin immunostaining may be indicated on bone marrow biopsy specimens from lobular carcinoma patients if the biopsy appears histologically negative for metastatic tumor on H&E sections.

Adult↗
PubMed2000

Paraffin-section detection of CD10 in 505 nonhematopoietic neoplasms. Frequent expression in renal cell carcinoma and endometrial stromal sarcoma.

We tested 505 cases of nonhematopoietic neoplasms by immunohistochemistry using a newly characterized monoclonal antibody (clone 56C6) against the CD10 antigen. CD10 was expressed widely in neoplasms of the genitourinary tract, including 41 (89%) of 46 cases of renal cell carcinoma, 13 (54%) of 24 cases of transitional cell carcinoma, and 11 (61%) of 18 cases of prostatic adenocarcinoma. In addition, 5 (100%) of 5 endometrial stromal sarcomas, 3 (60%) of 5 rhabdomyosarcomas, 7 (50%) of 14 pancreatic adenocarcinomas, 5 (45%) of 11 cases of schwannoma, and 12 (40%) of 30 cases of malignant melanoma also were positive for CD10. Similar to normal tissue, CD10 positivity was restricted to the apical surface of malignant glandular cells of well-differentiated colonic, pancreatic, and prostatic adenocarcinoma, whereas in poorly differentiated adenocarcinoma and other tumors, such as melanoma, transitional cell carcinoma, renal cell carcinoma, and endometrial stromal sarcoma, the CD10 positivity showed diffuse cytoplasmic or membranous/Golgi patterns. The monoclonal antibody clone 56C6 is a reliable marker for CD10 in paraffin immunohistochemistry after heat-induced epitope retrieval. CD10 expression in renal cell carcinoma and endometrial stromal sarcoma may be a useful marker in the differential diagnoses of these tumors because both tumors otherwise lack specific markers.

Antigens, Neoplasm↗
PubMed2000

The use of archival bone marrow specimens in detecting B-cell non-Hodgkin's lymphomas using polymerase chain reaction methods.

The detection of B-cell non-Hodgkin's lymphoma (B-NHL) involving the bone marrow (BM) can be enhanced by assessing immunoglobulin heavy chain (IgH/JH) gene rearrangement using PCR. While the fresh BM aspirate has been the most commonly used specimen, the utility of archival BM tissues has not been extensively evaluated. We studied the BM from 13 patients with nodal B-NHL (7 low-grade and 6 intermediate grade), which were categorized into three groups based on the histologic finding of lymphoma (H) and the presence of a monoclonal IgH/JH band by PCR using fresh BM aspirates (M): (1) H(+)/M(+), 4 cases; (2) H(+)/M(-), 4 cases; and (3) H(equivocal)/M(-), 5 cases. Archival tissues available for study included paraffin-embedded trephine biopsy (TB)/aspirate clots (AC) and air-dried aspirate smears (AS). All TB (13/13) and a subset of AC (5/13) were B5-fixed, and all these tissues failed to yield analyzable DNA. In contrast, sufficient DNA was consistently obtained in AC that were formalin-fixed (8/13). Of these 8 cases, 2/3 of group 1, 3/3 of group 2, and 0/2 of group 3 had a monoclonal IgH band. Using DNA extracted from microdissected lymphoid aggregates morphologically evident in the AC sections, additional positive cases were identified: 1/3 of group 1 and 2/2 of group 3. In those 5 cases that did not have formalin-fixed TB/AC, sufficient DNA was extracted from AS in all cases; one additional positive case was identified in group 1. Overall, 4/4 (100%) of group 1, 3/4 (75%) of group 2, and 2/5 (40%) of group 3 showed molecular evidence of lymphoma. To conclude, archival BM specimens are a useful source of DNA for molecular detection of B-NHL involvement, and formalin appears to be a better fixative than B5. The use of these samples may improve the overall detection sensitivity.

Adult↗
PubMed2000

Coexisting thymic and gastric lymphomas of mucosa-associated lymphoid tissues in a patient with Sjögren syndrome.

Lymphomas of mucosa-associated lymphoid tissues (MALTomas) arising from the thymus are extremely rare. In this case report, we describe a 36-year-old woman with an 11-year history of Sjögren syndrome who was found to have a thymic MALToma coexisting with a gastric MALToma. Both tumors shared similar histologic features, showing clusters of centrocytic-like B cells, lymphoepithelial lesions, and prominent plasmacytic differentiation. They also showed the following identical immunohistochemical features: CD20(+), IgA/lambda(+), CD5(-), and CD43(-). Molecular studies using polymerase chain reaction methods revealed monoclonal gene rearrangement of the immunoglobulin heavy chain in the gastric MALToma, but not in the thymic MALToma. The possible pathogenesis of this unusual case is discussed.

Adult↗
PubMed2000

Immunophenotyping of hematopoietic neoplasms.

Advances in the staging and treatment of hematopoietic neoplasms have necessitated a high degree of accuracy in the diagnosis and classification of these tumors. A greater degree of diagnostic precision has resulted from recent advances in immunophenotyping and genotyping of hematopoietic neoplasms. This review discusses several new immunohistochemical reagents, many of which are derived from results of molecular studies.

Antibodies↗
PubMed2000

Immunohistochemical detection of CD10 in paraffin sections of hematopoietic neoplasms: a comparison with flow cytometry detection in 56 cases.

Paraffin-section immunohistochemistry with heat-induced epitope retrieval using a newly characterized monoclonal antibody (clone 56C6) against the CD10 antigen was performed on 56 hematopoietic tumors previously studied for CD10 expression by flow cytometry. The cases included 33 precursor B-lymphoblastic leukemias, 10 acute myeloid leukemias, five precursor T-lymphoblastic leukemias, five follicular lymphomas, and three Burkitt cell leukemias. Forty of the 56 cases were CD10 positive by flow cytometry studies, including all five follicular lymphomas (100%); 30 of 33 (91%) cases of precursor B-lymphoblastic leukemias, two of three (66%) cases of Burkitt cell leukemias, two of five (40%) cases of precursor T-lymphoblastic leukemias, and none of the 10 cases of acute myeloid leukemia. Thirty-nine of the 40 (97%) flow cytometric CD10-positive cases also expressed CD10 by immunohistochemistry in formalin- or B5-fixed, paraffin-embedded tissue, with only one case of precursor B-lymphoblastic leukemia being positive by flow cytometry and negative by immunohistochemistry. The 16 CD10-negative flow cytometry specimens were all also negative by immunohistochemistry. Thirty-seven CD10 immunohistochemistry positive cases showed a diffuse membranous staining pattern and two cases demonstrated a Golgi staining pattern. The fixation methods (10% neutral buffered formalin versus B5) and decalcification did not affect the CD10 immunostaining results. This study demonstrates that the new CD10 monoclonal antibody clone 56C6 is a reliable marker for detection of CD10 antigen expression in formalin-and B5-fixed paraffin-embedded tissue after heat-induced epitope retrieval when compared with flow cytometry detection of fresh tissue samples.

Antibodies, Monoclonal↗
PubMed1999

Adult precursor-B acute lymphoblastic leukemia with translocations involving chromosome band 19p13 is associated with poor prognosis.

Cytogenetic translocations involving chromosome band 19p13, the site of the E2A gene, have previously been reported in pediatric acute lymphoblastic leukemias (ALL) in association with a precursor-B cell immunophenotype and poor prognosis. We studied the frequency, pathologic findings, and clinical course of adults with leukemia with 19p13 translocations. Six patients with t(1;19) (q23;p13) and one patient with t(17;19)(q21;p13), all with ALL, were identified over an 8-year period from among 183 adult ALL patients (2.7%); t(1;19) was observed in 2.2% and t(17;19) in 0.5% of these patients. The seven patients (four females and three males) ranged from 18 to 59 years of age (median 33). All cases had a precursor-B cell immunophenotype, and a distinctive expression of surface markers (CD10, CD19, TdT, and HLA-Dr positive, usually negative for CD20, CD34, and negative for myeloid-associated antigens CD13, CD14, and CD33). The blast cells in one case expressed CD15. All patients were treated with combination chemotherapy and three patients received allogeneic bone marrow transplantation. All patients had early (range 6-20 months) relapses, and died due to progressive disease 7-29 months after diagnosis. Similar to pediatric patients, adults with 19p13 leukemias usually do not respond to intensive therapy and have short survival. The poor prognosis of this group of adult ALL patients highlights the importance of detecting 19p13 translocations by cytogenetic analysis or molecular studies.

Adolescent↗
PubMed1999

Remission of refractory Sezary syndrome after bone marrow transplantation from a matched unrelated donor.

Sezary syndrome is a leukemic variant of mycosis fungoides (MF)/cutaneous T-cell lymphoma (CTCL). Bone marrow transplantation (BMT) from a matched unrelated donor was performed in a 22-year-old woman with a 10-year history of Sezary syndrome who had failed treatment with corticosteroids, methotrexate, photochemotherapy, photopheresis, hydroxyurea, interferon-alpha, and cladarabine. At the time of BMT, she had persistent erythrodermic skin disease, adenopathy, circulating Sezary cells and bone marrow (BM) involvement. The patient underwent BMT from a 6/6 HLA-matched unrelated male donor in August 1996. A BM biopsy obtained on day 30 after BMT showed no evidence of lymphoma and complete male donor engraftment. Her skin lesions resolved within 100 days after transplant. Complete staging studies, including T-cell receptor gene rearrangement studies performed at 36 months post-BMT, showed no evidence of recurrent Sezary syndrome. This represents her first durable remission since the initial diagnosis more than 12 years ago. To our knowledge, this is the first patient with refractory Sezary syndrome who has been successfully treated with allogeneic unrelated donor BMT. Our results indicate that this modality may be effective in inducing remission in refractory MF/CTCL, including Sezary syndrome.

Adult↗
PubMed1999

Practical applications of immunohistochemistry in hematolymphoid neoplasms.

Immunohistochemistry plays a key role in the diagnosis and classification of hematolymphoid neoplasms. New cell and lineage markers are constantly being discovered and added to the existing long list of antibodies. In this review article we provide general information and new applications of the commonly used hematolymphoid markers. We also discuss the features and applications of some newly discovered markers, such as ALK, fascin, granzyme/perforin, and tryptase. There is no universal "panel" for the diagnosis of hematolymphoid neoplasms. However, in this review article, we provide suggested panels for a given hematolymphoid neoplasm that is based on our experience and that reported in the literature.

Antigens, CD↗
PubMed1999

Untreated chronic lymphocytic leukemia concurrent with or followed by acute myelogenous leukemia or myelodysplastic syndrome. A report of five cases and review of the literature.

Although it has been known that patients with chronic lymphocytic leukemia (CLL) have a higher frequency of second malignant neoplasms, the development of acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) in these patients is extremely rare. Most reported cases have been therapy-related. In this article, we report the clinical and immunophenotypic features of 5 cases of untreated CLL concurrent with or followed by the development of AML or MDS. All 5 patients were men, with ages ranging from 57 to 87 years (mean, 73.8 years). Four patients had AML and 1 patient had refractory anemia with ringed sideroblasts. In the 4 cases of AML and CLL, 2 distinct cell populations (i.e., myeloblasts and lymphocytes) were identified morphologically and/or immunophenotypically. Our findings support that this rare concurrence of AML or MDS and untreated CLL may represent 2 separate disease processes.

Aged↗
PubMed1999

Acute lymphoblastic leukemia. Survey of immunophenotype, French-American-British classification, frequency of myeloid antigen expression, and karyotypic abnormalities in 210 pediatric and adult cases.

Immunophenotypic studies are essential to distinguish acute lymphoblastic leukemia (ALL) from minimally differentiated acute myeloid leukemia (AMLM0) and to classify ALL into immunologic subtypes. Frequently, immunophenotyping identifies myeloid antigen expression in ALL, causing a potential diagnostic problem. To evaluate the immunophenotype of ALL, we studied 210 cases of pediatric and adult ALL by flow cytometry and compared the results with the French-American-British (FAB) Cooperative Group classification and the karyotypic findings. Myeloid-associated antigens were expressed in 78 (45.6%) of precursor B-cell ALL cases. Pediatric precursor B ALLs had a higher frequency of myeloid antigen expression than did adult cases. All mature B-cell ALL cases were negative for TdT and myeloid antigens. Myeloid antigen expression was less frequent in T-cell ALL cases compared with precursor B-cell ALL cases. Of the 192 cases submitted for cytogenetic analysis, 147 were abnormal. The most common chromosomal translocation was the Philadelphia chromosome, which was more likely to have L2 blast morphology and a precursor B immunophenotype. Myeloid antigen expression was present in 70.8% of Ph-positive cases (P = .008). Chromosome rearrangements involving 11q23 also showed an increased frequency of myeloid antigen expression. Chromosome translocations involving regions of T-cell receptor genes were present in 24% of T-cell ALL cases. A high percentage of ALL cases, however, had various other cytogenetic abnormalities, many of which involved less well-studied chromosomal regions.

Adolescent↗
PubMed1999

Frequency of CD43 expression in non-Hodgkin lymphoma. A survey of 742 cases and further characterization of rare CD43+ follicular lymphomas.

CD43 expression on B cells is an immunophenotypic feature suggestive of malignancy. In the light of its diagnostic importance, we performed a comprehensive survey of CD43 expression in various types of non-Hodgkin lymphoma (NHL) and determined the frequency of its expression in routinely fixed paraffin-embedded tissues. Tissue sections in 742 cases of NHL, pretreated by the heat-induced epitope retrieval technique, were immunostained using an anti-CD43 antibody. Three categories of CD43 positivity were found: (1) more than 90% of T-cell lymphoma, mantle cell lymphoma, B-cell small lymphocytic lymphoma, and Burkitt lymphoma cases were positive; (2) 20% to 40% of nodal and extranodal marginal zone lymphoma (MZL), diffuse large B-cell lymphoma, Burkitt-like B-cell lymphoma, and lymphoplasmacytoid lymphoma cases were positive; and (3) 0% to 6% of primary splenic MZL and various types of follicular lymphoma cases were positive. Most CD43+ follicular lymphomas were predominantly large cell type with focally diffuse areas; their follicular center cell origin in 4 of 8 cases was supported by the presence of CD10 immunoreactivity and/or t(14;18) fusion gene product. CD43 is frequently detectable in a subset of B-NHL, and, thus, it seems to be a highly sensitive marker for these tumors. CD43 also may be a useful marker for classifying B-cell NHLs by virtue of its differential expression in these tumors.

Adult↗
PubMed1999

Soft tissue masses of the chest wall and axilla: has metastatic melanoma been considered?

Isolated axillary and chest wall soft tissue masses are an uncommon presentation of metastatic cancer. The authors present three patients in whom malignant melanomas metastatic to these sites had been misdiagnosed, leading to inappropriate oncologic treatment planning in all three cases. The presumed diagnoses, even after fine-needle aspiration or trucut biopsies, were soft-tissue sarcoma (n = 2) and undifferentiated breast cancer (n = 1). The combination of taking a thorough history and performing proper immunohistochemical analysis of the biopsy material would have suggested the presence of malignant melanoma in all cases. As the disease appeared locoregionally limited in all patients, radical surgical resection with extended lymphadenectomy was performed without significant dysfunction of the upper extremity. One patient agreed to postoperative immunotherapy with interferon-alpha. Two patients are currently alive 17 and 14 months after operation. One patient was found to have systemic recurrence at 5 months, one experienced two isolated local recurrences in a prior operative site that were amenable to reresection and presently has no evidence of disease 12 months after resection, and one patient remains free of disease at 14 months. Clinical presentation, suggested diagnostic workup, and therapeutic implications are discussed to avoid misdiagnoses in this setting of possible clinical presentations of metastatic melanoma.

Adult↗
PubMed1999

Peripheral T-cell lymphoma with Toutonlike tumor giant cells associated with HIV infection: report of two cases.

T-cell lymphoma in patients infected with HIV is much less common than B-cell lymphoma. We describe two cases of HIV-associated extranodal lymphoma that showed Toutonlike tumor giant cells and mononuclear large lymphoma cells. Both cell types expressed T-cell-associated antigens, including CD3, CD5, CD43, and CD45RO, and were CD4- and CD30-positive and negative for all B-lineage-associated antigens. Both cases showed T-cell receptor gamma chain gene rearrangements using the polymerase chain reaction and were negative for the Epstein-Barr virus by in situ hybridization. Despite the expression of CD30 by the multinucleated cells, both cases were negative for ALK1 by immunohistochemistry and failed to show evidence of the nucleophosmin-anaplastic lymphoma kinase fusion product characteristic of t(2;5) using the reverse-transcriptase polymerase chain reaction. Although rare, CD4-positive, T-cell lymphoma with Toutonlike giant cells may be a distinct type of HIV-associated malignant lymphoma.

Adult↗
PubMed1999

Indolent T-lymphoblastic proliferation: report of a case with a 16-year course without cytotoxic therapy.

T-lymphoblastic lymphoma is a high-grade malignant lymphoma. Clinically indolent T-lymphoblastic proliferations have not been described. We present a case report of an indolent T-cell lymphoblastic proliferation studied by histopathology, immunohistochemistry, flow cytometry, antigen receptor gene rearrangement studies, and cytogenetics. The patient had recurrent masses in the upper aerodigestive tract over a 16-year period, was treated by multiple surgical excisions, and never received either chemotherapy or radiotherapy. A proliferation of lymphoblasts was present histologically. The cells were positive for terminal deoxynucleotidyl transferase, CD1, and CD3, and coexpressed CD4 and CD8. No clonal rearrangements of the T-cell receptor beta or gamma chain genes were identified. Cytogenetic studies revealed a questionable inversion of the short arm of chromosome 9, affecting the 9p21-22 region. Although ectopic thymic tissue was considered, the case was considered to be an indolent lymphoblastic proliferation. It should be recognized that rare lymphoblastic proliferations may not behave in a high grade fashion as typically seen in T-lymphoblastic lymphoma.

Adult↗
PubMed1999

Detection of t(2;5) in anaplastic large cell lymphoma: comparison of immunohistochemical studies, FISH, and RT-PCR in paraffin-embedded tissue.

Anaplastic large cell lymphoma (ALCL) is associated with the t(2;5)(p23;q35) translocation involving the anaplastic lymphoma kinase gene (ALK) and the nucleophosmin gene (NPM), which result in expression of a novel fusion protein, NPM-ALK (p80). Clinicopathologic studies have shown that ALK expression in ALCL is associated with improved 5-year survival rates when compared with ALCL lacking ALK expression. This study used paraffin-embedded tissue to compare interphase fluorescence in situ hybridization (FISH) and reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of t(2;5) with immunohistochemical analysis for the detection of ALK protein expression in 27 patients with CD30-positive ALCLs. ALK protein expression was detected with ALK1 antibody in 14 of the 27 patients. The neoplastic cells in 13 of these 14 lymphomas reacted with the p80NPM/ALK antibody. FISH, using a two-color ALK DNA probe, correlated 100% with the immunohistochemical results: a translocation involving the ALK gene was detected in all 14 lymphomas that reacted with anti-ALK1. RT-PCR, performed on 21 lymphomas, detected NPM-ALK mRNA in five of the lymphomas, all of which reacted with anti-ALK1 and showed ALK gene rearrangement by FISH. Lymphomas showing ALK1 reactivity occurred in a younger patient population (median age, 19.5 years) and were associated with improved 5-year survival rates (84%), as compared with lymphomas lacking ALK1 reactivity (median age, 68.0 years; 5-year survival rate, 35%; p = 0.008). We conclude that immunohistochemical studies, using antibody ALK1. and FISH for ALK gene rearrangement are equally effective for identifying patients with ALCL who have a favorable clinical outcome.

Adolescent↗
PubMed1998

Paraffin section detection of the c-kit gene product (CD117) in human tissues: value in the diagnosis of mast cell disorders.

The c-kit gene product (CD117) is known to be expressed by a variety of normal human tissue cell types, including breast epithelium, germ cells, melanocytes, immature myeloid cells, and mast cells. To further characterize the expression of this antigen, 117 normal human tissues and 576 human tumors were studied by paraffin section immunohistochemistry. Varying degrees of CD117 expression were identified in various normal cells and in 53% of all tumors studied. In most cases (42% of total), CD117 expression was weak. Expression was most common in mast cell disease (100%), testicular germ cell tumors (100%), endometrial carcinomas (100%), papillary and follicular thyroid carcinomas (100%), small cell carcinomas (91%), malignant melanomas (90%), and ovarian epithelial carcinomas (87%). Strong immunoreactivity was only identified in cases of mast cell disease (11 of 11 cases), serous ovarian carcinoma (3 of 16), malignant melanoma (2 of 40), small cell lung carcinoma (one of seven), and adenoid cystic carcinoma (one of one). Although the pattern of reactivity was primarily cytoplasmic, a membrane staining pattern was seen in a subset of cases, and strong membrane staining was identified in normal mast cells and all cases of mast cell disease. The lack of tumor specificity of weak expression of this antigen limits its diagnostic utility in most cases. However, the strong membrane reactivity for CD117 identified in mast cells may be useful in the diagnosis of mast cell disorders.

Antibody Specificity↗