Search PubMed⌕ Search

Biomedical subjects

E S Jaffe

Publications and source records attributed to E S Jaffe.

At least 253 records · Page 14Linked to original sources

Development of non-Hodgkin lymphoma in a cohort of patients with severe human immunodeficiency virus (HIV) infection on long-term antiretroviral therapy.

OBJECTIVE: To describe the incidence of non-Hodgkin lymphoma in a group of patients with symptomatic human immunodeficiency virus (HIV) infection receiving long-term dideoxynucleoside antiretroviral therapy. DESIGN: We examined the records of all patients with the acquired immunodeficiency syndrome (AIDS) or severe AIDS-related complex who were entered into three long-term phase I trials of zidovudine (azidothymidine, AZT) or zidovudine-containing regimens at the National Cancer Institute between 1985 and 1987. SETTING: The Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland. PARTICIPANTS: Fifty-five HIV-infected patients with AIDS or severe AIDS-related complex. MEASUREMENTS AND MAIN RESULTS: Eight of fifty-five patients (14.5%; 95% CI, 6.5% to 26.7%) developed a high-grade non-Hodgkin lymphoma of B-cell type, a median of 23.8 months (range, 13 to 35 months) after starting antiretroviral treatment. Using the method of Kaplan and Meier, the estimated probability of developing lymphoma by 30 months of therapy was 28.6% (CI, 13.7% to 50.3%) and by 36 months, 46.4% (CI, 19.6% to 75.5%). The patients who developed lymphoma had less than 100 T4 cells/mm3 for a median of 17.8 months (range, 7 to 35 months) and less than 50 T4 cells/mm3 for a median of 15.3 months (range, 5.5 to 35 months) before the diagnosis. All patients presented with non-Hodgkin lymphoma in extranodal sites, and two developed primary brain involvement in the setting of Toxoplasma infection. CONCLUSION: Patients with symptomatic HIV infection who survive for up to 3 years on antiretroviral therapy may have a relatively high probability of developing non-Hodgkin lymphoma. Prolonged survival in the setting of profound immunosuppression with substantial T4-cell depletion is probably an important factor in the development of these lymphomas. However, a direct role of therapy itself cannot be totally discounted. As improved therapies for the treatment of HIV infection and its complications result in prolonged survival, non-Hodgkin lymphoma may become an increasingly significant problem.

AIDS-Related Complex↗

Molecular genetics of gastrointestinal non-Hodgkin's lymphomas: unusual prevalence and pattern of c-myc rearrangements in aggressive lymphomas.

Thirty-two extranodal lymphomas of the gastrointestinal (GI) tract underwent molecular genetic analysis by Southern blotting using probes for the immunoglobulin genes and the bcl-1, bcl-2, and c-myc loci, commonly involved in lymphomagenesis. No bcl-1 rearrangements were found. There was only one large-cell lymphoma with a bcl-2 rearrangement. A rearrangement of the c-myc gene was found in six of eight Burkittlike lymphomas of the intestine. In five of these six cases, a chromosomal translocation t(8;14) with an unusual breakpoint was demonstrated by comigration of the rearranged c-myc and a rearranged JH sequence. This pattern of rearrangement has not been previously associated with a specific group of non-Hodgkin's lymphomas. In contrast to all six low-grade lymphomas, c-myc rearrangements were found in 6 of 12 large-cell or high-grade mucosa-associated lymphomas of the stomach. No comigration of c-myc and immunoglobulin heavy-chain gene sequences were found. We conclude that primary GI lymphomas have different molecular genetic characteristics compared with node-based follicle center-cell lymphoma and as a group are not related to these lymphomas. In addition, the prevalence and patterns of c-myc rearrangements in the gastric large-cell lymphomas and ileocecal Burkittlike lymphomas are noteworthy and suggest a different and distinct pathogenesis for these tumors.

Blotting, Southern↗

Lymphocytic lymphoma of intermediate differentiation: morphologic, immunophenotypic, and prognostic factors.

Diffuse intermediately differentiated lymphocytic lymphoma (IDL) is a rare (approximately 2.5%) histologic subtype of malignant lymphoma. We have reviewed the morphologic, immunophenotypic, and clinical features of this disease in 23 patients treated at the National Cancer Institute in the 25-year period between 1963 and 1988. These tumors are uniformly of B-cell origin, but most of them express the T-cell antigen CD5; lambda light chain was expressed nearly twice as frequently as kappa. Median age at diagnosis was 58 years; all patients presented with stage III or IV disease, and the natural history of disease in these patients was heterogeneous. Median survival of patients was more than 5 years, but those with liver involvement documented by biopsy had a significantly shorter survival. No other prognostic factor or combination of prognostic factors significantly affected survival in this small series; however, patients with high expression of the proliferation-associated nuclear antigen Ki-67, absence of cell-surface antigens CD9 and CD10, and blastic morphology appeared to have poorer survival. Treatment was heterogeneous, but patients who achieved a complete response to combination chemotherapy survived longer than patients who failed to achieve a complete response. Only two patients had complete responses lasting longer than 2 years. Unlike patients with follicular lymphoma, those with relapsed IDL did not undergo histologic progression of the disease to an aggressive lymphoma. However, as with patients with follicular lymphoma, it was possible to observe patients with IDL without therapy for periods up to 5 years. Although a significant minority of patients may have very aggressive disease, it appears that, in most patients, IDL behaves similarly to other lymphomas with indolent histology, and thus, an optimal therapeutic approach has not yet been defined.

Adult↗

Surface light chain phenotype in indolent lymphomas: lack of prognostic significance.

The indolent follicular and diffuse lymphomas are neoplasms of B-cell origin. In several other B-cell neoplastic disorders, including multiple myeloma, hairy cell leukemia, and chronic lymphocytic leukemia, the light chain isotype of the surface immunoglobulin has been reported to have prognostic significance. Patients with tumors expressing lambda light chains usually fare more poorly than those with kappa light chain-bearing tumours. We analyzed the clinical data and immunologic phenotype of 101 patients with indolent lymphoma. Eighty-nine of the 101 patients demonstrated surface immunoglobulin of only one light chain type (kappa-47, lambda-42). Patients in both groups were matched for known prognostic factors. There were no significant differences in disease-free survival or overall survival between the two groups or within histologic subtypes. These results indicate that the immunologic light chain phenotype in indolent lymphoma, unlike other B-cell neoplasms, is not a prognostic indicator of survival.

Humans↗

Synovitis in angioimmunoblastic lymphadenopathy with dysproteinemia simulating rheumatoid arthritis.

We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia who developed a symmetric, rheumatoid-like, peripheral polyarthritis. Radiographs of the involved joints revealed soft tissue swelling without erosions or cartilage loss. Rheumatoid factor and fluorescent antinuclear antibodies were negative, and C-reactive protein and erythrocyte sedimentation rate were normal. Synovial fluid analysis showed an inflammatory effusion (white blood cell count of 3,500/mm3, with 76% polymorphonuclear leukocytes). A closed synovial biopsy of the wrist revealed a mononuclear infiltrate consistent with angioimmunoblastic lymphadenopathy with dysproteinemia. Monthly parenteral chemotherapy treatment with high-dose methyl-prednisolone and cyclophosphamide resulted in remission of all manifestations of disease, including arthritis.

Arthritis, Rheumatoid↗

Malignant lymphoma involving a Warthin's tumor: a case with immunophenotypic and gene rearrangement analysis.

We describe a Warthin's tumor which was involved by malignant lymphoma. The lymphoma was classified in the Working Formulation as follicular and diffuse, mixed small cleaved and large cell type. Frozen section immunohistochemical studies revealed an abnormal immunophenotype: immunoglobulin-negative and B-lineage. Gene rearrangement analysis confirmed the diagnosis by demonstrating rearrangements of both the immunoglobulin heavy and kappa light chain genes. The bcl-2 gene was also rearranged, consistent with the presence of the t(14;18) (q32;q21) translocation which is typically seen in follicular lymphomas. The T-cell receptor beta chain gene retained the germline configuration. The results in this case highlight an advantage of molecular techniques as compared with immunophenotypic analysis: gene expression is not required to demonstrate clonality.

Adenolymphoma↗

Phenotypic analysis of T-cell acute lymphoblastic leukemia in Egypt.

Leukemic cells from 46 T ALL cases were studied with a wide panel of mAb reacting with T cells using an immunoperoxidase technique. The cases included 15 adults (16 years or over) and 31 children (less than 16 years). The mAb used in the panel were: CD1, (T6), CD2 (T11, X11, D66, clone 2), CD3 (T3/Leu4), CD4, (T4/Leu3a), CD5 (Leu1, T1, A50, I73D9), CD7 (Leu9, I21), CD8 (T8/Leu2a) and HNK1. Based on their reactivity with the mAb panel all cases were assigned to one of the intrathymic differentiation compartments. Among the adults, five cases were assigned to compartment I, six to compartment II and four to compartment III. The pediatric cases included eight in compartment I, eighteen in compartment II and five in compartment III. Fifteen L1 cases studied included four in compartment I, seven in compartment II and four in compartment III; while thirty L2 cases showed nine in compartment I, sixteen in compartment II and five cases in compartment III. The most frequently observed CD groups among T ALL cells were CD5 (100% and 88.9% in children and adults respectively), CD7 (93.1% and 84.6%) and CD2 (76.7% and 76.9%). The most frequently reactive mAb in our series was Leu1 (81.8% followed by I21 (71.1%) and Leu9 (68.9%). The most frequently reactive combination of two mAb was Leu1/I21 (100%) followed by Leu1/T11 (97.4%). Five of the 46 cases reacted with HNK1, suggesting an origin from the natural killer (NK) subset. Our results indicate that in T-cell ALL in Egypt the surface phenotype is similar to that of intermediate or late thymocytes in more than 66% of cases. CD5, CD7 and CD2 were the most frequently detected antigens. Studies of the association between T-cell phenotype and socioeconomic status are warranted.

Adolescent↗

Acute infectious mononucleosis. CD30 (Ki-1) antigen expression and histologic correlations.

Lymph nodes from patients with acute infectious mononucleosis (AIM) typically show marked paracortical expansion and a prominent immunoblastic proliferation that can occur in nodules and sheets, as well as within sinuses. The marked immunoblastic proliferation, coupled with Reed-Sternberg-like cells and a polymorphous inflammatory cell background, may simulate either non-Hodgkin's lymphoma or Hodgkin's disease. A recently described entity, Ki-1-positive lymphoma, or large cell anaplastic lymphoma, shares some clinicopathologic and phenotypic features with AIM and must be considered in the differential diagnosis. The present case describes a 20-year-old male who had signs and symptoms consistent with AIM, which he was later proven serologically to have, but whose cervical lymph node showed features suspicious for large cell anaplastic lymphoma. In addition, the Ki-1 (CD30) antigen was expressed by some of the atypical immunoblasts, further raising this possibility.

Acute Disease↗

Lymphocytic lymphoma of intermediate differentiation. Morphologic and immunophenotypic spectrum and clinical correlations.

All cases of lymphocytic lymphoma of intermediate differentiation (IDL) referred to the National Cancer Institute were reviewed in order to define the histopathologic spectrum of the disease and to investigate morphologic and immunophenotypic features with potential prognostic relevance. Thirty-three cases were classified as IDL according to histologic criteria. Immunophenotypic analysis was performed in 27 cases, and clinical records were available for 22 patients. The median age was 58 years, and the male-to-female ratio, 3.4:1. All patients presented with stage III or IV disease, and five had extranodal presentations. Median survival was 56.3 months, with only three patients having a prolonged relapse-free survival (greater than 2 years). Morphologically, 14 cases were diffuse or only vaguely nodular; 18 cases showed a mantle zone pattern with naked germinal centers. There was a trend toward prolonged median survival for patients with the mantle zone (77.4 months, p = 0.098). The neoplastic population was composed of irregular or cleaved small lymphoid cells with a mitotic rate ranging from 5 to 62 per 20 high-power fields (hpf). A histologically distinctive variant with blastic cytologic features was identified (seven cases). The blastic variant was associated with a higher mitotic index (51.3 versus 19.0) and shortened survival (24.9 months). In contrast to the histologic progression often observed in follicular lymphomas, in no case was transformation to a large-cell or small noncleaved lymphoma observed. All cases had a mature B-cell phenotype demonstrating monoclonal Ig and B-cell surface antigens. Seventy-eight percent were CD5 positive; three of six CD5-negative cases presented in mucosal-associated extranodal sites. CD10 and CD25 were expressed in 52% and 44%, respectively, but did not show clinical correlations. The proliferative rate measured by Ki-67 positivity correlated with the mitotic index, but neither of these parameters had a statistically significant influence on survival.

Abdominal Neoplasms↗

Cytomegalovirus-infected cells express Leu-M1 antigen. A potential source of diagnostic error.

The authors examined cytomegalovirus (CMV)-infected tissues and Hodgkin's Disease (HD) cases with immunohistochemical assays for Leu-M1 and CMV. The cytologic characteristics were correlated with immunostaining patterns. Cytomegalovirus-infected cells in lymph node, lung, and esophagus sections showed Cowdry type A inclusions, and many had granular cytoplasmic inclusions. All infected cells showed nuclear staining with an anti-CMV antibody. Leu-M1 reacted with CMV-infected cells in cytoplasmic areas, particularly near the nucleus simulating the characteristic staining pattern of Reed-Sternberg (R-S) cells. Cytoplasmic staining intensified as the intranuclear inclusions increased in size. Reed-Sternberg cells showed characteristic Leu-M1 positivity along the cell membrane and golgi zone. At times, Leu-M1 staining of CMV-infected cells was indistinguishable from that of R-S cells. None of the R-S cells reacted with the antibody to CMV. Recognition of the reactivity of Leu-M1 with CMV-infected cells is important in avoiding misdiagnosis of CMV lymphadenitis as HD.

Adult↗

The histiocytoses: clinical presentation and differential diagnosis.

The histiocytoses, whether reactive or neoplastic, can be related histologically and immunophenotypically to their normal counterparts within the histiocytic system. This system has two subsets: The dendritic (antigen-presenting) cells and the phagocytic histiocytic (antigen-processing) cells. Dermatopathic lymphadenitis and Langerhans cell histiocytosis (histiocytosis X) are reactive proliferative disorders of dendritic cells. Malignancies of dendritic cells exist, but they are very rare. Benign proliferations of phagocytic histiocytes include the hemophagocytic syndromes, both familial and reactive, as well as sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) and histiocytic necrotizing lymphadenitis (Kikuchi's disease). Neoplasms of phagocytic histiocytes include acute monocytic leukemia and the very rare entities, malignant histiocytosis and true histiocytic lymphoma. The latter must be distinguished from sinusoidal, large cell anaplastic lymphomas.

Diagnosis, Differential↗

Human T-cell leukemia virus-I and hematologic malignancies in Panama.

Serum samples were obtained in a 2-year period (November 1, 1984-December 31, 1986) from 136 Panamanian patients with hematologic malignancies identified by a population-based registry designed for studies investigating human T-cell lymphotropic virus (HTLV)-I. Only three patients had clinical and serologic findings of HTLV-I-associated adult T-cell leukemia/lymphoma (ATLL). The authors conclude that although classical HTLV-I-associated ATLL occurs in the Panamanian population, it is not as prevalent as in other Caribbean populations.

Aged↗

Immunological phenotypic pattern of acute lymphoblastic leukaemia in Egypt.

We have performed immunophenotyping studies on 186 untreated cases of acute lymphoblastic leukemia (ALL) in an Egyptian population, using panels of monoclonal antibodies (mAb) and an avidin-biotin-immunoperoxidase detection system. Sixty-two of these cases were tested with a panel of mAb directed against the T-cell markers CD2, CD4, CD8, B-cell markers CD20, kappa and lambda, the common ALL antigen (common ALLa) and class II HLA antigens. The remaining 124 cases were also tested with additional markers of T- and B-cell precursors, namely CD7 and CD19. The common leukocyte antigen, T200, was used to exclude nonhemopoietic neoplasms. Cases that remained unclassifiable were further tested with a wider panel of T-cell markers, including CD1, CD2, CD3 and CD5. In some cases multiple mAb directed against the same antigens were used. The relative frequencies of common ALL and B ALL were calculated from the total number of cases and were found to be 39.2% and 3.2%, respectively. The proportions of T-cell and null leukemias were calculated from the better characterized subgroup of 124 cases, and were found to be 50% and 4.8%, respectively. In our series, the age distribution of common ALL revealed a peak at 2-5 yr, but this was partially obscured in the entire series by the high proportion of T-cell cases, which had an age peak between 4 and 12 yr of age. Our results demonstrate marked differences in the phenotypic pattern of ALL in Egypt compared to Western Countries, the predominant finding being a relative excess of T-cell ALL and a paucity of common ALL cases. At present it is not clear whether this results from an increased incidence of T-cell ALL or a decreased incidence of common ALL.

Adolescent↗

Quality control in immunohistochemistry. Report of a workshop sponsored by the Biological Stain Commission.

Although immunohistochemical methods are increasingly applied in diagnostic histopathology, there has been little standardization or quality control of immunoreagents; and published reports have not standardized Material and Methods for meaningful comparisons of results among clinicians. The Biological Stain Commission-sponsored workshop was convened to address the following issues: a manufacturers' testing program for probity of commercial antibodies, development of a manual for performance criteria and quality control assurance procedures, standardization of package inserts, standardization of information provided in the Materials and Methods sections of publications, establishment of a reagent and procedure clearing house, study of the effects of different fixation regimes on tissue antigens, and investigation of the environmental conditions needed for antigen-antibody interaction. The recommendations of the ad hoc committee and their implications for the future are discussed.

Antigen-Antibody Complex↗

Leukaemic phase of mantle zone (intermediate) lymphoma: its characterisation in 11 cases.

Sixteen patients presented with B cell leukaemia (white cell count 26-269 x 10(9)/l) which could not be classified as chronic lymphocytic (CLL), prolymphocytic leukaemia, or follicular lymphoma in leukaemic phase. Eleven patients (10 men, one woman) corresponded histologically to intermediate (INT) or mantle zone lymphoma, and five, with less well defined features, were designated small lymphocytic lymphoma with cleaved cells. The blood films showed a pleomorphic picture with lymphoid cells of predominantly medium size with nuclear irregularities and clefts. The membrane phenotype of the circulating cells showed strong immunoglobulin staining and reactivity with CD5 and FMC7 in all cases tested; CD10 was positive in six out of nine cases. The membrane phenotype of two of the five cases of small lymphocytic lymphoma was close to those of B-CLL and three resembled INT lymphoma. Bone marrow trephine biopsy specimens showed a diffuse pattern of infiltration in INT lymphoma. The median survival of these patients was less than two years, suggesting that a leukaemic presentation is associated with poor prognosis. By combining data from histology, membrane markers, and peripheral blood morphology, the leukaemic phase of typical INT lymphoma can be defined in most cases.

Adult↗