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D A Arber

Publications and source records attributed to D A Arber.

At least 73 records · Page 4Linked to original sources

Paraffin section immunophenotyping of acute leukemias in bone marrow specimens.

The immunohistochemical evaluation of acute leukemia specimens has been limited in the past due of the inability to detect many lineage-related antigens in paraffin sections. With the improvement in immunohistochemical methods as well as the introduction of new antibodies, these limitations are now reduced. To evaluate the diagnostic utility of paraffin section immunohistochemistry in the lineage determination of acute leukemias, 77 previously immunophenotyped acute leukemias were studied with a panel of antibodies that included antibodies directed against CD3, CD20, CD34, CD43, CD68, CD79a, HLA-DR, myeloperoxidase (MPX), and terminal deoxynucleotidyl transferase (TdT). The cases included 48 acute myeloid leukemias, 18 precursor B-cell acute lymphoblastic leukemias, 6 T-cell acute lymphoblastic leukemias, and 5 mixed precursor B/myeloid leukemias. This immunohistochemical panel correctly identified the lineage of 96% of both acute myeloid leukemias and acute lymphoblastic leukemias and identified evidence of mixed lineage in 60% of mixed lineage leukemias. Antibodies directed against CD3, CD79a, MPX, and TdT were found to be the most useful, although the latter three alone were not entirely lineage specific. These findings suggest a role for paraffin section immunohistochemistry in the lineage determination of some cases of acute leukemia.

Acute Disease↗

Angiomatoid fibrous histiocytoma.

This article reports a case of angiomatoid fibrous histiocytoma (AFH), a rare fibrous tissue tumor with unique clinical characteristics. Formerly, this tumor was classified as angiomatoid malignant fibrous histiocytoma. First described in 1979, AFH was felt to be a variant of malignant fibrous histiocytoma (MFH). One dominant characteristic that differentiates this tumor from the remainder of MFH subtypes is that it most often presents in individuals younger than 20 years of age. The usual MFH occurs in the seventh decade of life. Because of its rarity, AFH has been difficult to classify and, during this current year, has been designated as a separate entity, rather than a subtype of MFH. Clinically, the tumor presents as a soft-tissue mass in the subcutis or deep dermal layers of the body, often presenting on the extremities or neck. Local recurrence has been reported, but mortality figures are very favorable and wide local removal is sufficient treatment.

Age Factors↗

Coexistence of Hodgkin's disease and giant lymph node hyperplasia of the plasma-cell type (Castleman's disease).

Coexistence of Hodgkin's disease and giant lymph node hyperplasia (Castleman's disease) is well documented in the literature. We present a unique case in which the original lymph node biopsy revealed interfollicular Hodgkin's disease (CD15+, CD30+, CD45-, Reed-Sternberg cells) with coexistent histologic features of the plasma-cell variant of Castleman's disease. The patient experienced a long-term remission following combined chemotherapy and radiation therapy. He presented at 18 years and again at 22 years later with clinical, hematologic, and histologic features of a multicentric plasma-cell variant of Castleman's disease without evidence of Hodgkin's disease. This unique case report further strengthens the association of Castleman's disease and Hodgkin's lymphoma. Two pathogenetic mechanisms for this association have been suggested: (1) secretion of interleukin-6 by Hodgkin's Reed-Sternberg cells and histiocytes, and (2) manifestation of an abnormal immune state associated with Hodgkin's disease. These two mechanisms may, indeed, be related.

Aged↗

Utility of a rapid polymerase chain reaction panel for the detection of molecular changes in B-cell lymphoma.

OBJECTIVE: To evaluate the utility of a polymerase chain reaction (PCR)-based, B-cell-related molecular panel in the diagnostic workup of hematologic specimens. DESIGN, SETTING, AND PATIENTS: A PCR panel was applied to 89 specimens from 87 patients, including 55 cases (57 specimens) of known monoclonal B-cell lymphoma, 10 cases of Hodgkin's disease, 2 cases of T-cell lymphoma, and 20 specimens of polyclonal reactive lymphoid tissues. The panel comprised a seminested PCR procedure for immunoglobulin heavy-chain (IgH) gene rearrangement and unnested PCR detection of t(14;18) and t(11;14). RESULTS: Immunoglobulin heavy-chain was detected in 63%, evidence of t(14;18) in 35%, and evidence of t(11;14) in 3.5% of all the B-cell lymphoma cases. Seventy-seven percent of all cases demonstrated IgH- and/or bcl-2-associated translocations using these primers. The IgH primers alone detected clonality in 82% (28/34) of the nonfollicular lymphomas and 35% (8/23) of the follicular lymphomas, with no false positives in the non-B-cell lymphoma specimens. The addition of two primer sets for the detection of both IgH and bcl-2/JH significantly improved the detection of molecular abnormalities in the follicular lymphoma group from 35% to 70% (16/23). However, no change was noted in the overall detection rate for the nonfollicular lymphoma group. Adding primers for bcl-1/JH did not change the overall detection rate for either group. CONCLUSIONS: Seminested PCR for IgH detected monoclonality in the majority of the nonfollicular lymphomas and is a valuable diagnostic tool in this group. The combination of different primer sets for the detection of IgH gene rearrangement and bcl-2/JH is most desirable for follicular lymphomas.

Base Sequence↗

CD79 alpha expression in acute myeloid leukemia. High frequency of expression in acute promyelocytic leukemia.

CD79 alpha is a subunit of an intracytoplasmic protein reported to be specific for B lymphocytes, including immature B lineage cells. To evaluate expression of the CD79 alpha antigen in acute myeloid leukemia (AML), we studied forty-eight cases of AML by paraffin section immunohistochemistry. The cases included four MO, nine M1, nine M2, ten M3, ten M4, and six M5 AMLs using criteria of the French-American-British cooperative group. Eleven cases demonstrated cytoplasmic staining for the CD79 alpha antigen, including one M1, nine M3, and one M5 AML. These CD79 alpha-positive cases represented 5% of all non-promyelocytic AMLs and 90% of all acute promyelocytic leukemias studied. All acute promyelocytic leukemias had the characteristic t(15;17)(q24;q21), including two cases of the microgranular variant (M3v). No other B-lineage-associated antigens were found in the CD79 alpha-positive cases, with the exception of a subpopulation of CD19-positive leukemic cells in one patient. The two non-promyelocytic leukemias that expressed CD79 alpha had no evidence of t(15;17) and did not express any additional B-lineage-associated antigens that might suggest a mixed lineage proliferation. This study demonstrates that CD79 alpha expression in acute leukemia is not restricted to B-lineage acute lymphoblastic leukemias and that CD79 alpha expression is frequently associated with t(15;17) acute myeloid leukemia.

Acute Disease↗

Numerical cytogenetic abnormalities of chromosomes 3, 7, and 12 in marginal zone B-cell lymphomas.

Monocytoid B-cell lymphoma, low-grade B-cell lymphoma of mucosa-associated lymphoid tissue, and primary splenic marginal zone cell lymphoma (SMZCL) were originally described as distinct clinicopathologic entities. On the basis of morphologic and immunologic similarities, monocytoid B-cell lymphoma and lymphoma of mucosa-associated lymphoid tissue recently have been grouped together as nodal and extranodal types of marginal zone B-cell lymphomas (MZBCLs) in the Revised European-American Classification of Lymphoid Neoplasms. Primary SMZCL, although related, is considered a separate provisional entity. Trisomies 3, 7, and 12 are common in non-Hodgkin's lymphomas. Several recent studies reported that MZBCLs arising in sites of mucosa-associated lymphoid tissue have a high frequency of trisomy 3. To assess whether similar numerical cytogenetic abnormalities are present in MZBCLs with prominent monocytoid B-cell cytologic features, we performed a retrospective study, using formalin-fixed, paraffin-embedded tissue blocks from 36 cases. By use of fluorescence in situ hybridization to detect chromosome trisomies, we identified trisomy 3 in 11 (85%) of 13 extranodal MZBCLs with monocytoid B cells (MZBCL-Es), in 6 (50%) of 12 nodal MZBCLs of monocytoid B-cell type (MZBCL-Ns), but in only 2 (18%) of 11 SMZCLs. Trisomies 7 and 12 were found at lower frequencies. These data suggest that trisomy 3 is a common numerical chromosomal abnormality of MZBCL-Es and MZBCL-Ns with monocytoid B-cell features. Despite similar morphologic and immunophenotypic characteristics, the low incidence of trisomy 3 in the SMZCL cases implies that this process may be genetically distinct.

Cell Line↗

Frequent presence of the Epstein-Barr virus in inflammatory pseudotumor.

Inflammatory pseudotumor is a presumably nonneoplastic, hematopoietic, and spindled fibrous proliferation that may occur at a variety of anatomic sites. The origin of these proliferations is generally unknown. To evaluate the role of the Epstein-Barr virus (EBV) in inflammatory pseudotumor, 18 specimens from 17 patients were studied by in situ hybridization for EBV ribonucleic acid (RNA), and the morphological and immunologic characteristics of the infected cells were evaluated. These specimens included 10 lymph nodes, six splenic masses, and two hepatic masses. Overall, EBV RNA was detected in 41.2% (seven of 18) of the cases. These included two of 10 (20%) lymph nodes, four of six (66.7%) splenic pseudotumors, and one of two (50%) hepatic lesions. The degree of EBV infection was significantly greater within the tumors in comparison with the surrounding, uninvolved tissue. Two morphologically different EBV-positive cell types, spindled and round cells, were evident, and the infected cell type differed significantly when the nodal and extranodal cases were compared. All of the positive extranodal cases shown, numerous EBV-positive spindled cells, whereas no positive spindle cells (only positive round cells, morphologically consistent with lymphocytes) were noted in the two EBV-positive lymph node pseudotumors. Double-labeling immunohistochemical and in situ hybridization studies in some cases identified rare EBV-positive B cells and rare EBV positive T cells in four and three cases, respectively. Most EBV-positive cells in all cases failed to immunoreact with any B- or T-cell markers. Three of five cases studied, however, did show a subpopulation of smooth muscle actin/EBV-positive spindled cells, five of seven cases showed vimentin/EBV-positive spindled cells, and one of four cases had EBV-positive spindled cells that immunoreacted as follicular dendritic cells. These results suggest that EBV plays a role in a significant number of cases of inflammatory pseudotumor with differences in the incidence of EBV infection and the cell type (spindled vs round cell) infected when extranodal and nodal cases are compared, suggesting a difference in pathogenesis. The cell type infected in extranodal cases seemed to be of mesenchymal origin but could not be clearly defined.

Adolescent↗

Pathologic features of nodular lymphocyte predominance Hodgkin's disease in extranodal sites.

We describe the gross and histologic features of nodular lymphocyte predominance Hodgkin's disease (NLPHD) occurring in extranodal sites. Fifty-one specimens of NLPHD from 16 patients were studied. The sites of involvement were the spleen, liver, tonsil, salivary glands, skin, colon, soft tissue, and bone marrow, and the morphologic features were similar to those described in node-based NLPHD, including characteristic lymphocytic and/or histiocytic (L&H) cells that were easily identified in a background of a nodular proliferation of small lymphocytes and histiocytes. In the spleen, the normal architecture was generally preserved, and the tumor was found predominantly in the white pulp; the red pulp was rarely involved. In the liver, the tumor involved both the portal and parenchymal areas. In the tonsil, the lympohproliferation closely resembled the typical appearance of NLPHD in a lymph node. In all specimens with materials available for immunohistochemical studies, there were demonstrable L&H cells with an immunophenotype similar to node-based NLPHD, that is, CD45-positive, CD20-positive, and CD15-negative. The unique morphologic and immunologic characteristics of NLPHD are preserved in extranodal sites and allow its distinction from classic Hodgkin's disease and other lymphoproliferative malignancies that may occur in extranodal sites.

Adolescent↗

Neuroendocrine differentiation in prostatic adenocarcinoma and its relationship to tumor progression.

BACKGROUND: Neuroendocrine differentiation has been demonstrated by immunohistochemical preparations in many cases of acinar type prostatic adenocarcinoma (CAP). Some studies have suggested that this differentiation may indicate an adverse prognosis. METHODS: Tissue samples from 38 consecutive patients with clinical Stage II (AJCC) CAP who underwent radical retropubic prostatectomy (RRP) were studied after preparations were made with antichromogranin (ChA) and neuron-specific enolase (NSE). All patients were followed for at least 4 years post-RRP or until disease progression was documented by rising serum prostate specific antigen concentration, X-ray evidence of recurrence, or a positive tissue biopsy. RESULTS: Nine of the 38 RRP specimens (24%) were positive for NSE, and 11 (29%) were positive for ChA. Neither of these neuroendocrine markers showed a significant correlation with tumor progression. Neuroendocrine differentiation in needle biopsy specimens from these same patients (when available) did not correlate with tumor progression either. Of the patients with tumor progression, 9 of 11 (82%) had pathologic Stage III disease after RRP; of those with no progression of CAP, only 7 of 27 (26%) had pathologic Stage III disease. CONCLUSIONS: Neuroendocrine differentiation, as demonstrated by NSE and ChA preparations, was not helpful in predicting tumor progression of CAP.

Biomarkers, Tumor↗

UCL3D3 and UCL4D12 reactivity in small B-cell neoplasms with special emphasis on monocytoid B-cell lymphoma.

Two recently described monoclonal antibodies, UCL3D3 and UCL4D12, have been reported to have some specificity for mantle zone B lymphocytes and marginal zone/follicular center B lymphocytes, respectively, in the spleen. Forty-nine B-cell neoplasms, including 20 cases of monocytoid B-cell lymphoma (MBCL), were studied by frozen section immunohistochemistry with these antibodies to evaluate their utility. Tonsil, lymph node, and reactive spleen also were studied with the antibodies. Although a wide overlap was observed among the different lymphomas, a majority of cases of MBCL and half of cases of hairy cell leukemia (HCL) reacted with both markers, suggesting both marginal/follicular and mantle cell antigen expression. None of four cases of mantle cell lymphoma reacted with the proposed mantle cell marker UCL3D3, whereas three of these cases immunoreacted with UCL4D12. This marker is known to react with a subpopulation of follicular center cells and possibly with marginal zone lymphocytes. A comparison of nodal and extranodal neoplasms failed to show a significant difference in the pattern of immunoreactivity with these antibodies. Tonsil and lymph node controls showed some mantle zone staining with both antibodies, and there was a slight overlap in mantle and marginal zone staining of the spleen controls. These findings suggest an immunologic similarity between some cases of HCL and MBCL. However, the findings also would suggest that these antibodies, particularly UCL4D12, have less specificity than has been previously assumed, and UCL4D12 may not have practical utility in the evaluation of low grade B-cell lymphomas.

Adolescent↗

Nasal T-cell lymphoma.

Nasal T-cell lymphomas represent a controversial subset of malignant lymphomas and include lesions previously termed midline malignant reticulosis, lymphomatoid granulomatosis, and polymorphic reticulosis. Nasal T-cell lymphomas are rare in Western populations and much more prevalent in Asian countries. Clinically, adult males are most often affected. Histologically, an angiocentric infiltrate composed of a spectrum of atypical cells is usually present. Phenotypically, the neoplastic cells lack expression of B-lineage markers, and usually express the T-lineage-associated markers CD2, CD45RO, and CD43; however, they often lack other pan-T-lineage markers. They often express the natural killer marker CD56, but usually lack the natural killer markers CD16 and CD57. Gene rearrangement studies have shown a germline configuration for the antigen receptor genes in the majority of cases. To date, evidence of Epstein-Barr virus has been consistently demonstrated, regardless of the geographic region studied. In situ hybridization studies have localized the Epstein-Barr virus to the atypical cells.

Female↗

Non-Hodgkin's lymphoma involving the breast.

Breast involvement by non-Hodgkin's lymphoma is rare. Differences between primary and secondary breast lymphoma have been reported, and a relationship between primary breast lymphoma and lymphomas of mucosa-associated lymphoid tissue has been suggested. We reviewed 61 cases of breast lymphoma (41 primary, 13 secondary, and 7 unclear) that included 28 right-sided masses at presentation, 17 left-sided, 12 bilateral, and 4 in which the side was not known. A subgroup of bilateral breast lymphomas was identified that occurred in young women, four of which were pregnant or postpartum. A high incidence of intermediate- and high-grade lymphomas were present in both cases of primary and secondary lymphomas as was a high frequency of B-cell phenotype. Additional immunohistochemical studies failed to demonstrate evidence of marginal or mantle cell differentiation in seven of eight cases studied. Lymphoepithelial lesions were identified in a majority of cases, including 67% of primary and 64% of secondary lymphomas. This study failed to demonstrate a morphologic difference between primary or secondary lymphomas of the breast and suggests that breast lymphomas differ from other extranodal lymphomas in that the latter are frequently low grade.

Adolescent↗

Follicular small lymphocytic lymphoma.

We herein provide evidence for the existence of a distinct morphologic form of small lymphocytic lymphoma (SLL) that we term follicular small lymphocytic lymphoma (FSLL). Nine specimens of FSLL from eight patients were studied. The lymphomas in this study showed a true follicular pattern that was independent of tissue planes; the cytologic composition was identical to that seen in SLL. All six of the specimens (from five patients) for which paraffin tissue was available marked as B cell phenotype and were positive for bcl-2 protein. Polymerase chain reaction studies performed on deparaffinized tissue sections showed bcl-2 major breakpoint region rearrangements in four of five cases for which study tissue was available. Clinical information was available for all eight patients. All patients presented with lymph node disease, and three patients also had extranodal involvement at the time of presentation. Three of the patients had a relapse of disease after 33-95 months, and two of these patients died soon after relapse. Another two of the eight patients never responded to chemotherapy and died of their disease after 2 and 8 months, respectively. Two patients died of causes unrelated to their lymphoma and unrelated to any lymphoma therapy. Only one patient remains disease-free, after 65 months; this patient had a relapse at 44 months. The finding of bcl-2 rearrangements suggests that the pathogenesis of FSLL is more closely related to follicular small cleaved cell lymphoma than to classic SLL.

Aged↗

Extramedullary myeloid cell tumors. An immunohistochemical and morphologic study of 28 cases.

In an attempt to correlate the morphologic and immunophenotypic findings in extramedullary myeloid cell tumors (EMT), we studied 28 cases with a large panel of antibodies using paraffin section immunohistochemistry. A previous or concurrent diagnosis of acute myelogenous leukemia or chronic myelogenous leukemia was made in 25 cases. Six EMT were morphologically classified as well differentiated (WD-EMT), 17 as poorly differentiated (PD-EMT), and five as blastic EMT. The WD-EMT were easily recognized morphologically and displayed a relatively mature myeloid phenotype, with elastase, CD15, and CD68 positivity in all cases. On the other hand, the five blastic-EMT displayed no morphologic evidence of myeloid derivation, were completely negative for CD15, and were weakly positive for elastase in only one case. The PD-EMT, with a morphologic appearance that resembles large cell non-Hodgkin's lymphoma, variably expressed CD15 and elastase. CD68 and lysozyme were present in the majority of PD-EMT, with some variability, but were negative in most blastic-EMT. CD45 (LCA) was detected in 75% of all EMT and CD34 was positive in 36%; neither antigen was significantly associated with a specific morphology. CD30 reactivity was not evident in any case, but slight positive staining was seen with CD20 (L26) in one WD-EMT. CD43 (Leu 22) was the only antibody that was positive in 100% of cases; staining was always intense and widespread. Antimyeloperoxidase (MPO) was positive in all cases but two, both with a blastic morphology. We conclude that (a) an immunohistochemical panel including CD20, CD43, CD68, and MPO can successfully identify the vast majority (96%) of EMT in paraffin sections, and (b) there is an association between morphology and phenotype in these lesions.

Antigens, Differentiation↗

Vimentin-negative epithelioid sarcoma. The value of an immunohistochemical panel that includes CD34.

Virtually all reported cases of epithelioid sarcoma have been vimentin rich, and the coexpression of vimentin and keratin is considered a characteristic immunophenotype in these tumors. We report three cases of soft tissue tumors with histologic and clinical features consistent with epithelioid sarcoma, all of which failed to immunoreact by standard immunohistochemistry for vimentin using two different monoclonal antibodies. Antigen retrieval demonstrated focal vimentin staining in one case, whereas the other two remained negative. An extensive panel of immunohistochemical stains revealed strong diffuse staining with keratin and epithelial membrane antigen in all three cases as well as patchy membrane staining with an antibody to CD34. CD34 positivity is commonly seen in epithelioid sarcoma, but it is very rarely found in carcinomas. We conclude that these cases represent a unique immunophenotypic variant of epithelioid sarcoma that can be immunohistochemically confirmed, despite the lack of identifiable vimentin, by their immunoreactivity for keratin and CD34.

Adult↗

The bone marrow agar section: a morphologic and immunohistochemical evaluation.

A technique for agar embedding of bone marrow aspirate particles is compared with the conventional aspirate smear and bone marrow biopsy by reviewing 503 consecutive bone marrow specimens. Immunohistochemical studies were performed on both agar sections and bone marrow biopsies on 43 paired specimens to compare the results between the two preparations. The results were also compared with traditional clot sections from ten control cases. Of the 382 cases with agar sections, 97.7% contained material in the agar that was diagnostic alone or supportive of the diagnosis made with the biopsy and aspirate smear. In two cases (0.4%), focal involvement by lymphoma was identified on the agar section but not in the biopsy sections or aspirate smears. The immunohistochemical studies showed superior immunoreactivity in agar sections by lymphoproliferative disorders when compared with bone marrow biopsy sections. Similar results between agar and conventional biopsy sections were found in cases of metastatic carcinoma and plasma cell dyscrasias.

Adolescent↗