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Biomedical subjects

K Sheibani

Publications and source records attributed to K Sheibani.

At least 55 records · Page 3Linked to original sources

Monocytoid B-cell lymphoma. Clinicopathologic study of 21 cases of a unique type of low-grade lymphoma.

The morphologic and immunologic features of three cases of an unusual and distinct B-cell lymphoma were recently described and termed monocytoid B-cell lymphoma (MBCL) because of the striking resemblance of the neoplastic cells to reactive monocytoid B-lymphocytes. The morphologic spectrum and the clinical behavior of MBCL were investigated in a series of 21 patients. This study indicates that patients with MBCL usually present with lymphadenopathy and Stage I or II disease. MBCL also occurs at extranodal sites including the salivary gland. Because four of the patients with MBCL had Sjögren's syndrome with characteristic laboratory profiles, these results raise the possibility that there may be a relationship between MBCL and Sjögren's syndrome. Eight patients were male and 13 female (M:F = 1:1.6), and MBCL primarily involved the elderly (median age, 66 years). The most striking clinical findings were high percentages of complete remissions and long survival times indicating that MBCL is a low-grade lymphoma. Of 21 patients investigated, 18 were in complete remission at the time of completion of this study. Two patients died with the disease and one was lost to follow-up. Patients with localized MBCL may have a better survival rate than those with generalized disease. Like other low-grade lymphomas, MBCL can progress to a higher grade lymphoma of large cell type. Unlike other low-grade lymphomas, in MBCL splenomegaly, bone marrow involvement, and leukemic conversion are uncommon.

Adult↗

T-cell-rich lymphoproliferative disorders. Morphologic and immunologic differential diagnoses.

To differentiate peripheral T-cell lymphomas (PTCL), the authors evaluated the results of T11 monoclonal antibody studies on consecutive cell suspensions prepared from 509 lymph nodes from various lymphoproliferative disorders (LPD). They used T11 (CD2) positivity to identify those LPD in which the content of T cells was high. There were 266 (52%) cell suspensions which contained more than 50% T11-positive cells. More than 75% of the following non-Hodgkin's lymphomas had over 50% T11-positive cells: diffuse mixed cell (DM), diffuse atypical poorly differentiated lymphocytic and lymphoblastic lymphomas; mycosis fungoides; and true histiocytic lymphoma. Eleven cell suspensions had more than 90% T11-positive cells; four were involved by B-cell lymphomas. The cell suspensions prepared from nine of 14 diffuse large cell lymphomas of the T-cell type had more than 50% T11-positive cells. Of these, three of five cases of the polymorphous subtype had fewer than 50% T11 cells, but six of seven lymph nodes of the clear-cell type had more than 50% T11-positive cells. Each of seven DM samples of the T-cell type contained over 50% T11 cells; none had a polymorphous appearance. In the 112 cases of reactive LPD studied, more than 75% of cases of necrotizing lymphadenitis, dermatopathic lymphadenitis, angioimmunoblastic lymphadenopathy, and those with lymph nodes with no specific reactive pattern had more than 50% T11-positive cells. The authors' findings indicate that T11 positivity is a reliable T-cell marker in reactive and neoplastic LPD except for those cases of PTCL with a polymorphous appearance; these tend to lose T11-expression. A multi-parameter diagnostic approach is required in the following LPD: (1) PTCL which are T11-negative; (2) PTCL of small lymphocytic type having an unremarkable T-cell phenotype; (3) SIg-negative B-cell lymphomas which are rich in nonneoplastic T cells; (4) non-Hodgkin's lymphomas with minimal disease which are rich in reactive T cells; and (5) polymorphous large cell proliferations.

Antigens, Differentiation, T-Lymphocyte↗

Variability in interpretation of immunohistologic findings in lymphoproliferative disorders by hematopathologists. A comprehensive statistical analysis of interobserver performance.

Eight hematopathologists independently reviewed 56 consecutive cases of benign and malignant lymphoproliferative disorders (LPD) to determine: (1) the degree of interobserver agreement on the interpretation of immunologic findings on fresh-frozen sections alone and on that of the immunologic findings in conjunction with corresponding hematoxylin and eosin (H & E)-stained histologic sections; (2) whether prior knowledge of morphologic characteristics influences the interpretation of immunohistologic sections; (3) whether immunologic phenotype could be predicted reliably based solely on study of histologic sections; and (4) the significance of immunologic data as an aid in the interpretation of histologic sections. The study was carried out in three independent review sessions consisting of (1) review of immunohistologic sections only, (2) review of the same immunohistologic sections together with histologic sections, and (3) review of the histologic sections alone. A consensus diagnosis was defined as agreement of five or more pathologists on the final diagnosis and identification of the immunophenotype. When the authors compared the total number of major disagreements in the first review session with those in the second, the accuracy of the determination of immunophenotype in the second session was clearly superior (P less than 0.05). Similarly, the total number of major disagreements in the second review session was significantly lower than that in the third review session (P less than 0.001). When histologic diagnoses in the second session were compared with those in the third session, it became apparent that the immunologic data helped the pathologist to correct major misinterpretations in 14 cases (25%). This study is the first to demonstrate quantitatively that (1) knowledge of morphologic features influences and greatly enhances the accuracy of the interpretation of immunologic findings, (2) the immunophenotype of LPD cannot be predicted based on morphologic findings alone, and (3) immunologic findings improve the accuracy of interpretation of histologic findings in situations in which a diagnosis cannot be made from morphologic features only.

Diagnosis, Differential↗

Tumor DNA content as a prognostic indicator in squamous cell carcinoma of the head and neck region.

Our purpose in this study was to determine whether tumor DNA content is a prognostic factor independent of other standard clinical and histologic parameters in squamous cell carcinoma (SCC) of the head and neck region. Tumor DNA content was determined in 76 patients with primary resectable SCC of the oral cavity, larynx, or pharynx who were treated from 1978 to 1984 at the City of Hope. In addition, we measured various clinical and pathologic parameters in all patients. In comparison to patients with diploid SCC, those with aneuploid SCC had significantly decreased relapse-free and overall survival rates (p less than 0.001 for both). A Cox regression analysis demonstrated that tumor DNA content was a prognostic factor independent of all clinicopathologic features examined. By regression analysis, it was the single most important prognostic factor in determining relapse and death from SCC (p less than 0.001 for both).

Aged↗

Antigenic phenotype of Langerhans cell histiocytosis: an immunohistochemical study demonstrating the value of LN-2, LN-3, and vimentin.

In order to determine the antigenic phenotype of the proliferating cells in Langerhans cell histiocytosis (LCH), we studied 15 such examples by using formalin- and B5-fixed, paraffin-embedded tissues. We used a panel of antibodies that are known to react with lymphocyte- and histiocyte-associated antigens. These included LN-1, LN-2, and LN-3 monoclonal antibodies (MoAbs), MoAbs to leukocyte common antigen (LCA), Leu-M1 antigen, vimentin, and epithelial membrane antigen (EMA), as well as polyclonal antibodies to lysozyme and S100 protein. The antigens encountered most frequently in LCH cells were S100 protein (93% of cases), vimentin (86%), and those detected by LN-2 (80%) and LN-3 (82%). Lysozyme was detected focally in two cases and diffusely in one case. The LCH cells were negative for LN-1, LCA, Leu-M1, and EMA. There was only one specimen in which S100 protein was not demonstrated; in this case, LN-3, vimentin, and T6 on frozen section were positive. The phenotype of LCH cells is similar to that of Langerhans' cells and interdigitating histiocytes. Our results demonstrate the value of using a panel of antibodies, including anti-vimentin MoAb, LN-2, and LN-3 for the immunophenotypic diagnosis of LCH in addition to an antibody to S100 protein.

Antibodies, Monoclonal↗

Hashimoto's thyroiditis lacks detectable clonal immunoglobulin and T cell receptor gene rearrangements.

The development of B cell lymphoma, predominantly of the large-cell type, in patients with autoimmune diseases such as Hashimoto's thyroiditis or Sjogren's syndrome is well known. In Sjogren's syndrome, it has been recently shown that the benign-appearing lymphocytic infiltrates of the lymphoepithelial lesions in the salivary glands have clonal rearrangements of immunoglobulin genes in their DNA, even in the absence of malignant lymphoma. To investigate whether a similar situation occurs in Hashimoto's thyroiditis, we studied the thyroid glands from four patients with this disease. In all four cases, there was a benign-appearing lymphocytic infiltrate in the thyroid, with eosinophilic changes in the Hurthle cells. In immunologic studies, we determined that the lymphocytes were polyclonal in each case. We extracted DNA from the frozen tissue blocks of these four patients and analyzed it by molecular hybridization for the presence of clonal immunoglobulin (IgH, kappa, and lambda) and T cell receptor beta chain gene rearrangements, and detected none in any case. Therefore, we conclude that the lymphocytes in Hashimoto's thyroiditis are immunologically and immunogenetically polyclonal proliferations of cells, and that the initial lesion of Hashimoto's thyroiditis does not contain a detectable clone of cells that may eventually develop into malignant lymphoma.

Gene Rearrangement, B-Lymphocyte↗

Immunoarchitecture of the "pseudofollicles" of well-differentiated (small) lymphocytic lymphoma: a comparison with true follicles.

Some human malignant lymphomas of the B-cell type have morphologic and immunologic similarities to follicles seen in nonneoplastic reactive lymph nodes. In contrast, a peculiar, vaguely nodular pattern of growth called "pseudonodules" or "pseudofollicular proliferation centers," which is morphologically distinguishable from "true" follicles, is seen in malignant lymphoma, well-differentiated (small) lymphocytic type (WDL). To characterize the cellular components of "pseudofollicles," we undertook a detailed, comparative immunohistologic study of the architectural relationship and distribution of T cells, B cells, and follicular dendritic reticulum cells (DRCs) in reactive follicles, neoplastic follicles, and pseudofollicles. We report several observations on the presence of DRCs and T-cell subset topography in pseudofollicles. Immunohistologic staining for the C3d complement receptor on DRCs revealed that DRC networks associated with "true" follicles were present in all cases of reactive follicular hyperplasia (RFH) and malignant lymphoma, nodular, poorly differentiated lymphocytic type (PDL) studied. Surprisingly, DRC networks were also identified in 8 of 23 cases of WDL. Although the size distribution of DRC network diameters was nearly identical in RFH and PDL, the sizes were markedly diminished in WDL. Immunohistologic staining for Leu 3+ and Leu 2+ T-cell subsets confirmed cellular arrangements in RFH and PDL reported by others. In only 2 of 23 cases of WDL could T cells localized to "pseudofollicles" in frozen tissue sections be identified in a nonrandom arrangement.

Adolescent↗

Expression of sialylated Leu-M1 antigen in histiocytosis X.

The purpose of this study is to determine the versatility of the monoclonal antibody anti-Leu-M1 in histiocytosis X diagnosis. This antibody recognizes an unsialylated lacto-N-fucopentaose III (hapen X) carbohydrate moiety that is linked to the cell membrane protein in interdigitating reticulum cells and Langerhans' cells. Previously, the authors have shown that anti-Leu-M1 can be used to stain Reed-Sternberg cells, which are likely related to interdigitating reticulum cells. In this study, the authors tested the usefulness of anti-Leu-M1 in staining formalin-fixed and paraffin-embedded tissue sections from eight patients with histiocytosis X. For staining of histiocytosis X cells, unlike Reed-Sternberg cells in Hodgkin's disease, neuraminidase treatment was required for removal of sialic acid residues from the Leu-M1 antigen. The staining characteristics of anti-Leu-M1 in histiocytosis X cells resembled those of normal Langerhans' cells and lymphocyte and histiocyte variants (L & H cells) in the lymphocyte-predominant type of Hodgkin's disease. The significance of sialylation of Leu-M1 antigen in histiocytosis X cells has yet to be determined in order to correlate the prognosis of the disease. The authors suggest that anti-Leu-M1 used together with neuraminidase treatment is a valuable tool in the diagnosis of histiocytosis X when electron microscopy or frozen sections for OKT6 immunostaining are not available.

Adult↗

Signet-ring cell melanoma. A rare morphologic variant of malignant melanoma.

We recently received in consultation a lymph node involved by metastatic malignant melanoma with unusual and previously undescribed morphologic features. The neoplastic cells had a striking signet-ring appearance, similar to the signet-ring cells normally seen in mucin-producing adenocarcinoma and signet-ring cell lymphoma. Review of our consultation files of malignant melanomas revealed an additional case in which the neoplastic cells had a signet-ring cell appearance. Electron microscopic studies revealed that formation of signet-ring cells is caused by the presence of abundant vimentin filaments in the cytoplasm of neoplastic cells. Immunologic studies using a series of monoclonal and polyclonal antibodies, including S-100 protein, HMB-45, vimentin, cytokeratin, leukocyte common antigen, and Leu-M1, on both cases clearly established the diagnosis of this morphologically unusual variant of malignant melanoma for which we propose the term "signet-ring cell melanoma."

Adult↗

Human immunodeficiency virus-associated T-cell lymphoblastic lymphoma in AIDS.

A patient with multiple infections whose serum had antibodies to a human immunodeficiency virus (HIV) developed a T-cell lymphoblastic lymphoma (T11+, Leu-1+, Leu-3a+, TdT+, B1-, common ALL-). Antibodies to human T-lymphotropic virus-I (HTLV-I) were absent. T-cell leukemia-lymphoma may be associated with HIV infection.

Acquired Immunodeficiency Syndrome↗

Antigenically defined subgroups of lymphoblastic lymphoma. Relationship to clinical presentation and biologic behavior.

A large panel of monoclonal antibodies and polyclonal antisera were used to ascertain the immunophenotypic characteristics of 36 lymphoblastic lymphomas (LBL). Results showed that this group of lymphomas have significant immunologic heterogeneity. Of the 36 cases, 33 were positive for T-cell antigens; among these, 22 cases were classified as T-cell LBL (TLBL, Group 1) based on their expression of T-cell-restricted and T-cell-associated antigens, and five expressed the common acute lymphoblastic leukemia antigen in addition to T-cell-associated antigens (Group 2). Six cases showed strong reactivity with anti-Leu-11 antibody, which defines a specific subtype of lymphocytes considered to have a natural killer (NK) function (Group 3). Two additional cases had a "pre-B" cell phenotype (Group 4), as determined by reactivity with BA-1 and BA-2 monoclonal antibodies, which react with immature and pre-B-lymphocytes. The neoplastic cells in the remaining case showed monoclonal surface membrane immunoglobulin of the IgMD heavy chain and kappa light chain type (Group 5). Despite immunophenotypic heterogeneity, the morphologic features were essentially similar in all cases. When the clinical features for each immunologic group were compared, however, two statistically significant findings resulted: (1) the frequency of mediastinal masses was highest in TLBL (Group 1, P less than 0.01), and (2) the male-female ratio was significantly lower in patients with LBL expressing NK-associated antigens (Group 3) than in the other groups of patients (P less than 0.01). Our data indicate that LBL can be divided into several immunologic subtypes; larger, prospective clinicopathologic studies are required to determine the clinical significance of the immunophenotypic classifications of LBL.

Adolescent↗

Antigenic phenotype of the lymphocytic component of medullary carcinoma of the breast.

Medullary carcinoma of the breast, which is usually associated with a dense lymphocytic infiltrate, carries a better prognosis than do most other histologic subtypes of breast carcinoma. We studied cryostat-cut fresh frozen sections from 12 patients with medullary carcinoma and, as controls, nine patients with infiltrating ductal carcinoma in order to determine and compare the antigenic phenotype of the lymphocytic components of these tumors. We used a large panel of monoclonal antibodies and polyclonal antisera for T-cells (Leu-1, Leu-2a, Leu-3a, Leu-9, T-3, T-6, T-10, T-11, and TQ-1), pre-B and B-cells (BA-1, B-1, B-2, B-4, and J5), NK cells (Leu-7 and Leu-11b), and cell activation associated antigens (T-9, HLA-Dr, and Tac). The most commonly encountered antigens on the lymphocytic components of both medullary carcinoma and infiltrating ductal carcinoma were: T-3, T-11, Leu-1, Leu-2a, Leu-3a, and Leu-9. There was little staining for NK-, pre-B-, or B-cell associated antigens in either type of carcinoma. However, the lymphocytes in the control cases tended to express HLA-Dr and T-10 more often than did the lymphocytes in the cases of medullary breast carcinoma. Our data indicate that: the antigenic phenotypes of the lymphocytic infiltrates of medullary carcinoma and those of infiltrating ductal carcinoma of the breast are essentially similar; and the lymphocytes in these carcinomas are composed predominantly of peripheral T-lymphocytes. We therefore conclude that the favorable biologic behavior of medullary carcinoma of the breast cannot readily be explained by the immunophenotype of its lymphocytic component.

Antigens, Surface↗

Imaging of colon carcinoma with 111-indium-labeled anti-CEA monoclonal antibodies (Indacea) prior to surgery.

Patients with primary and/or metastatic colorectal cancer who had been scheduled for operative intervention were injected intravenously with 200 micrograms of a high-affinity anti-carcinoembryonic antigen (CEA) monoclonal antibody labeled with 2 mCi of 111-indium (Indacea). Patients were imaged by gamma camera at 24 and 48 hours. Primary tumors were identified in 3/10 cases and were not visualized in 3/10 cases. Four scans were considered equivocal. Hepatic metastases were identified as image defects in 5/13 cases and were not visualized in 8/13 cases. All tumors contained CEA by immunoperoxidase staining. In all cases, the primary tumor uptake (5.44 +/- 1.07% ID/kg) was much higher than the uptake of the adjacent fat (0.18 +/- 0.04% ID/kg). There was a direct correlation between tumor CEA content, tumor radioactivity, and the imaging of primary tumor by Indacea. High liver uptake (30.3 +/- 3.0% ID/kg), seen when scanning all patients, was the main limitation of imaging and led to photopenic visualization of hepatic metastases. These results suggest that selection of patients with colorectal carcinoma on the basis of tumor CEA content will lead to improved rates of tumor imaging by Indacea in post-surgical scanning.

Antibodies, Monoclonal↗

Lymphoblastic lymphoma expressing natural killer cell-associated antigens: a clinicopathologic study of six cases.

We describe six patients with lymphoblastic lymphoma (LBL) whose neoplastic lymphoid cells expressed surface antigens associated with natural killer (NK) cells. The six cases were selected from a series of 38 specimens diagnosed as LBL based on morphologic criteria and further subclassified by the use of an extensive panel of monoclonal and polyclonal antibodies. Although the morphologic features in all six cases were similar to those previously reported for LBL, their expression of NK-associated antigens was unique. All cases were positive with anti-Leu 11b, an antibody which appears to define a specific subtype of lymphocytes considered to have NK function; and all cases expressed T11, a T-cell-restricted antigen. The most commonly encountered immunophenotype of our cases of LBL was: Leu 11b+, T11+, Leu7+, TdT+, Leu 3a+, Ia+, pre-B-, and B-. As compared with more classical LBL of T-cell type, LBL of NK-cell type in our series occurred primarily in females and non-whites. Whereas treatment of classical LBL by multi-agent chemotherapy may lead to long-term survival, only two of our six patients were long-term survivors. The data derived from this study raise the possibility that LBL with the antigenic phenotype of NK cells may represent a biologic subtype of LBL.

Adolescent↗

Concurrent presence of two clonal populations in small lymphocytic lymphoma of the lung.

In a patient with small lymphocytic proliferation (SLP) involving the right middle and right lower lobes of the lung, immunophenotypic studies showed that the neoplastic lymphoid cells in the right middle lobe expressed kappa light chains, whereas those in the right lower lobe expressed lambda light chains on their surface. Gene rearrangement studies with Southern-blot hybridization confirmed the disparate surface immunoglobulin expression, and showed that the SLPs in the two lobes were derived from separate clones. The findings indicate that even morphologically identical lymphomas in the same organ may be immunophenotypically and genotypically heterogeneous. Our findings demonstrate that immunologic and DNA gene rearrangement analyses may complement each other in the study of lymphomas. This case is unique in that it is the first reported case of the concurrent presence of two immunologically distinct clonal populations in an extranodal site.

B-Lymphocytes↗

A systematic approach to the immunohistologic classification of lymphoproliferative disorders.

From the study of over 3,000 immunologically well characterized cases, we have developed a systematic approach for the immunohistologic evaluation of lymphoproliferative disorders (LPD). By using a basic screening panel of antibodies on fresh-frozen sections, LPD can be reliably immunophenotyped. Fourteen patterns of immunoreactivity have been identified that can be used in differential diagnosis and the establishment of the correct diagnosis. A comprehensive table has been developed for systematically recording for each case the results of immunohistologic evaluation of fresh-frozen sections. The information recorded is easily computerized for later studies of large numbers of cases. We also propose a strategy for the further characterization of rare cases that are not easily defined with the basic screening panel of immunologic reagents. The proposed systematic approach allows the rapid recognition of the predominant immunologic pattern, the determination of the differential diagnoses, and the establishment of the correct diagnosis. In many cases, the final diagnosis can be predicted on the basis of patterns of immunoreactivity in the fresh-frozen section prior to the evaluation of the paraffin-embedded histologic material. Moreover, this systematic approach may provide an additional method to classify LPD more precisely and reproducibly.

Antigens, Differentiation, T-Lymphocyte↗

Monoclonal small (well-differentiated) lymphocytic proliferations of the gastrointestinal tract resembling lymphoid hyperplasia: a neoplasm of uncertain malignant potential.

Three histologically benign-appearing or diagnostically equivocal small lymphocytic proliferations of the gastrointestinal tract were examined by fresh-frozen section immunohistologic techniques. In one case, a dense infiltrate in the small intestine, consisting of small lymphocytes with round nuclei, was limited almost entirely to the mucosa. In another case, a localized colonic polyp was formed by mucosal and submucosal lobules of benign-appearing lymphoid aggregates with centrally located germinal centers. The third case, a penetrating gastric ulcer, was surrounded by histologically hyperplastic lymphoid tissue which included germinal centers. The small lymphocytes in all three cases were strongly positive for B-cell-associated antigens (B1, B2, BA-1), and all exhibited monoclonal light-chain restriction. Even though treatment consisted only of surgical resection of the lesions, no patient has had progressive disease during follow-up periods ranging from 24 to more than 50 months. We believe that the infiltrates in these cases are analogous to the morphologically benign monoclonal small lymphocytic proliferations common to the lung and orbit and that they have an uncertain, but probably low, malignant potential.

Adult↗