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Biomedical subjects

L M Weiss

Publications and source records attributed to L M Weiss.

At least 343 records · Page 19Linked to original sources

Small noncleaved cell lymphoma: an immunophenotypic study of 18 cases and comparison with large cell lymphoma.

Eighteen cases of small noncleaved cell lymphoma (SNCL) were studied with a large panel of monoclonal antibodies applied to tissue frozen sections and compared with 18 cases of immunoglobulin-expressing diffuse large cell lymphoma (DLCL). Immunoglobulin expression was seen in all cases of SNCL, with a predominance of cases showing lambda light chain restriction. Expression of mu and delta heavy chains was common, but gamma and alpha chain expression was uncommon. In the cases of SNCL T015, B1, B2, 41H, BA-1, BA-2, Ia, CALLA, and OKT10 were generally expressed, and a large percentage of cells expressed Ki-67. Only rare expression of T05, Leu-8, and Leu-9 was seen, and in no case was reactivity with anti-Tac antibodies observed. In contrast, the immunoglobulin-expressing DLCLs showed the typical predominance of cases of kappa light chain restriction, a lower proportion of cases with mu or delta expression, and a higher proportion of cases with gamma expression. A lower incidence of Leu-8, T05, and Tac expression and a higher incidence of BA-1, CALLA, Ki-67 and OKT10 were seen in the SNCLs as compared with the DLCLs. It is concluded that immunologic studies may be of considerable aid in the differential diagnosis of SNCL and DLCL.

Abdominal Neoplasms↗

Immunoglobulin gene rearrangements in Hodgkin's disease.

An initial survey of biopsy specimens from 16 cases of Hodgkin's disease revealed clonal immunoglobulin gene rearrangements in one specimen, which contained large numbers of Reed-Sternberg (R-S) cells. As a result of this finding, the configuration of immunoglobulin and T-cell receptor gene DNA was investigated in biopsy tissues from other cases that were histologically and immunophenotypically consistent with Hodgkin's disease and contained numerous R-S cells. In six of seven such specimens (all of the nodular sclerosing subtype), selected solely on the basis of high R-S cell content and sufficient frozen tissue for study, at least one immunoglobulin gene was found to be rearranged in a clonal manner. Additionally, tissue samples obtained at two different time points from the original patient who showed immunoglobulin gene rearrangements revealed identical patterns of rearrangement. In the majority of cases, only a single gene showed rearrangement, and the rearranged bands in Southern blot autoradiograms were usually considerably less intense than the germline bands. No rearrangements of T-cell receptor DNA were detected in any case with a probe for the beta T-cell receptor gene. The results suggest that clonal cell populations possessing uniform immunoglobulin gene rearrangements are present in tissue in some cases of Hodgkin's disease. It is not possible to determine which cells contain these rearranged genes, but the increased incidence of detectable rearrangements in cases with high numbers of R-S cell raises the possibility that immunoglobulin gene rearrangement occurs in these cells.

Chromosome Aberrations↗

Leu-6-expressing cells in lymph nodes: dendritic cells phenotypically similar to interdigitating cells.

Leu-6 is an antigen expressed by immature T cells, Langerhans cells, and indeterminate cells, the latter two of which are dendritic cells found predominantly within the skin. In dermatopathic lymphadenopathy, the paracortex is expanded by T cells and dendritic cells, including Langerhans cells. While the paracortex also contains Leu-6+ cells, the nature of such cells in lymph nodes has been controversial. To determine the characteristics of Leu-6+ paracortical cells, their morphologic, antigenic, and enzymatic features were studied in lymph nodes showing dermatopathic lymphadenopathy or reactive follicular hyperplasia. Immunologic studies with plastic, frozen, and paraffin sections demonstrated a dendritic cell morphology, a dendritic cell lineage phenotype (L3B12+, HLA-A,B,C+, HLA-DR+, S-100+), and the absence of T-cell lineage phenotype. These findings were corroborated by the enzymatic phenotype of these cells observed in plastic sections (membrane ATPase+, weak paranuclear acid phosphatase+, weak paranuclear alpha-napthylacetate esterase+). Although all paracortical dendritic cells were otherwise identical, only a subset of these cells were Leu-6+. The close phenotypic similarity between these Leu-6+ and Leu-6- paracortical dendritic cell subsets suggests a close ontogenetic relation. Furthermore, the greater abundance of the Leu-6+ subset in dermatopathic lymph nodes than in nodes exhibiting only reactive follicular hyperplasia, in conjunction with the presence of Leu-6+ dendritic cells within the sinuses of dermatopathic lymph nodes, suggests that at least some of the paracortical Leu-6+ cells are Leu-6+ Langerhans cells or indeterminate cells derived from the skin via the afferent lymphatics.

Antigens, Differentiation, T-Lymphocyte↗

Cutaneous follicular lymphoma.

Fifteen cases of cutaneous follicular lymphoma were evaluated clinically, histologically, and immunologically. Nine of the patients presented with skin disease alone, which showed a predilection for the scalp and forehead. The six remaining cases had either concurrent or secondary cutaneous involvement. All of the cases had a nodular configuration which was evident histologically or immunologically. In many cases, the diagnostic microscopic fields were in the deep dermis or subcutis, with nonspecific inflammation in the superficial dermis. The cases consisted of five small cleaved, seven mixed, and three large cell follicular lymphomas. A senior dermatopathologist diagnosed four of the 15 cases as benign, indicating the difficulty of diagnosis by morphology alone when the biopsy is small or the inflammatory component is prominent. This underscores the importance of large, deep biopsies for accurate histologic diagnosis. Immunological studies confirmed the B cell lineage of these lesions. An unexpectedly high proportion of immunoglobulin-negative cases (eight cases) was found, especially among the primary cutaneous follicular lymphomas (six of nine cases). Immunoglobulin-expressing cases exhibited monotypic immunoglobulin light-chain staining of tumor cells. In all cases, the dendritic reticulum cell network within lymphoma follicles lacked the polytypic immunoglobulin complexes characteristic of reactive follicles. As described previously for follicular lymphomas in lymph nodes, many cases exhibited polytypic follicular mantle zones similar to reactive follicles. The low-grade nature of these lymphomas was supported by clinical follow-up. We conclude that given adequate sampling, cutaneous follicular lymphomas can usually be diagnosed by histologic criteria similar to those used for lymph nodes; however, immunohistologic studies are an important adjunct.

Adult↗

Treatment of lymphoblastic lymphoma in adults.

Forty-four adult patients with lymphoblastic lymphoma (LBL) were treated according to one of two protocols. Both included (1) induction with cyclophosphamide, doxorubicin, vincristine, prednisone, and L-asparaginase; (2) CNS prophylaxis; and (3) maintenance therapy with methotrexate (MTX) and 6-mercaptopurine. In the second protocol, CNS prophylaxis began earlier than in the first protocol and included cranial irradiation and intrathecal (IT) MTX rather than simultaneous high-dose systemic and IT MTX. The overall response rate was 100% (95% complete). With a 26-month median follow-up, the 1-and 3-year actuarial freedom from relapse (FFR) for the composite patient group was 70% and 56%, respectively. The incidence of CNS relapse was reduced from 31% in the first protocol to 3% in the second protocol (P = .04, Gehan). Patients can be assigned retrospectively to low (n = 19) and high (n = 25) risk prognostic groups, as indicated by a multivariate analysis of pretreatment prognostic factors. High-risk is defined by Ann Arbor stage IV disease with bone marrow or CNS involvement or initial serum lactate dehydrogenase (LDH) concentration of greater than 300 IU/L (normal, less than 200). FFR of low- and high-risk groups at 5 years are 94% and 19%, respectively (P = .0006). Low-risk patients are highly curable using this approach to adult LBL. More intensive treatment for high-risk patients is warranted.

Adult↗

Clinical and phenotypic diversity of T cell lymphomas.

Forty-one cases of T cell lymphoma were identified on the basis of morphology and the expression of two or more T cell antigens with an absence of B cell markers. Mycosis fungoides and lymphoblastic lymphoma were excluded. Marked clinical, morphological, and immunologic diversity was observed. Cutaneous lymphoma was found in approximately 50% of the patient group, and 27% had a prior history of dermatologic or immunologic disease. No correlations among immunologic and morphologic phenotypes and clinical course were apparent. Survival data was comparable to that of a concurrent group of non-T cell lymphoma patients studied at this institution, suggesting that, contrary to previous reports, T cell lymphoma may not necessarily confer a more unfavorable prognosis. Prospective studies using uniform treatments are necessary to address the clinical significance of the T cell phenotype definitively, independent of established histologic and clinical features.

Adolescent↗

Lymphoblastic lymphoma: an immunophenotype study of 26 cases with comparison to T cell acute lymphoblastic leukemia.

A series of 26 lymphoblastic lymphomas (LLs) and 13 T cell acute lymphoblastic leukemias (ALLs) were investigated using a battery of monoclonal antibodies applied to tissue frozen sections. Twenty-one of the LLs were of T lineage. All but one of the T cell LLs were of immature thymic phenotype, mostly corresponding to stage II cortical thymocyte development. The T cell LLs expressed Leu-1 in 100%, Leu-4 and Leu-9 in 95%, and Leu-5 in 85% of the cases. The high percentage of Leu-4 expression in this series is probably due to detection of cytoplasmic antigen with our methods. One LL was of pre-B or B cell and two cases were of common ALL phenotype. Two cases were of undefined phenotype, expressing markers of both B and T cell differentiation. Pediatric cases showed a greater tendency toward T cell phenotype than did adult cases. The cases of T cell ALL were immunophenotypically similar to the cases of T cell LL but showed a tendency toward a more immature phenotype.

Adolescent↗

Clonal T-cell populations in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma.

Ten cases of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) and AILD-like lymphoma were studied by immunophenotypic and immunogenotypic analysis. All specimens were found to have a predominance of T cells by immunophenotypic analysis. DNA hybridization analyses showed three of five specimens of AILD and five of six specimens of AILD-like lymphoma to contain clonal rearrangements of the beta T-cell receptor gene. No rearrangements of the heavy or light chain immunoglobulin genes were seen in any case. A single case showed a progression of AILD with a germ-line pattern of beta T-cell receptor DNA to AILD-like lymphoma with detectable clonal rearrangements for beta T-cell receptor DNA. These results suggest that many, but not all, cases diagnosed histologically as AILD or AILD-like lymphoma contain a clonal proliferation of T-lymphocytes.

Aged↗

Escherichia coli sepsis from contaminated platelet transfusion.

Transfusion of pooled platelet concentrate (PC) caused a septic reaction characterized by sustained hypotension, high cardiac output, and low systemic vascular resistance. Investigation demonstrated the same strain of Escherichia coli in the patient's blood, the transfused pooled PC, and recalled packed red blood cells separated from the same unit of whole blood as one of the platelet units in the contaminated pool. Five hundred other units of PC from the same supplier were cultured prospectively, and 7% were bacterially contaminated. The level of contamination was 20 or fewer colony-forming units per milliliter in all except one unit, the only one associated with a febrile transfusion reaction. This episode illustrates the continuing importance of sepsis as a cause of platelet transfusion reactions and demonstrates the usefulness of appropriate cultures and epidemiologic information in assessing the source.

Blood Preservation↗

Follicular large cell lymphoma. An immunophenotype study.

The authors investigated 17 cases of follicular large cell lymphoma using monoclonal antibodies applied to frozen sections. The neoplastic cells in 11 cases (65%) showed evidence of immunoglobulin expression similar to the reported percentage of immunoglobulin expressing diffuse large cell lymphomas and lower than seen in low grade follicular lymphomas. All cases showed expression of the B lineage markers T015, B1, and 4G7, and HLA-DR. CALLA was present in all but 1 case, similar to that reported for follicular lymphomas, and much higher than reported for diffuse large cell lymphoma. Approximately one-half of the cases showed weak expression of Tac, 5 cases expressed B2 (C3d), and 3 cases expressed T05 (C3b). Variable expression was seen for the Ki-67 antigen. A CR4/23+, B2+, T05+ dendritic population was identified in all cases. An interfollicular host T-cell infiltrate was noted, mainly phenotypic helper cells. This study demonstrates that follicular large cell lymphoma has immunologic similarities to both diffuse large cell lymphoma and the low grade follicular lymphomas.

Cell Line↗

Clonal rearrangements of T-cell receptor genes in mycosis fungoides and dermatopathic lymphadenopathy.

Histologic diagnosis of mycosis fungoides may be difficult, especially in lymph nodes that show changes frequently associated with chronic skin disease. As an alternative approach to diagnosis, we have analyzed the configuration of DNA for the beta T-cell receptor genes in biopsy tissues from 14 patients with mycosis fungoides. Clonal rearrangements of these genes were found in each specimen tht contained histologically unambiguous mycosis fungoides. Clonal rearrangements were also found in seven of nine lymph nodes removed from patients with mycosis fungoides and considered histologically to contain only benign lymphadenopathy. Matching rearrangements of beta T-cell receptor genes were detected in benign lymph nodes and histologically involved tissues when paired specimens were available from the same cases. Our findings provide molecular evidence for the clonal T-cell origin of mycosis fungoides and indicate the high incidence of extracutaneous disease in patients with palpable lymphadenopathy. In addition, this study demonstrates that the detection of rearranged T-cell receptor genes can be a sensitive and practical method for the diagnosis and characterization of T-cell neoplasms.

Clone Cells↗

Nonimmune hydrops fetalis: a challenge in perinatal pathology.

Autopsies were performed in 40 cases of nonimmune hydrops fetalis during the period from 1975 to 1983. In 25 cases specific anatomic diagnoses, including hematologic disorders, infections, chromosomal abnormalities, congenital anomalies, and tumors, were made. In the majority the diagnosis of hydrops fetalis was made prenatally by ultrasonography. The mean gestational age at delivery was 30 weeks; 23 infants were stillborn, and 17 died during the neonatal period. Body weights were consistently increased; peripheral edema and ascites were present in all cases and pleural effusions in all but two cases. Hepatosplenomegaly, cardiomegaly, and pulmonary hypoplasia were frequent findings. The most consistent microscopic changes involved endocrine organs. Islet cell hyperplasia and Leydig cell hyperplasia were common, and thyroid hyperplasia was found occasionally. The fetal zone of the adrenal cortex was often thick and composed of swollen, vacuolated cells. Enhanced extramedullary erythropoiesis was observed in all cases. Thirty-nine placentas were examined; 34 were edematous (mean weight, 547 g), with villous edema, excess erythroblastemia and normoblastemia, and occasional intravillous hematopoiesis. Nonimmune hydrops fetalis has a range of known causes. Thorough autopsy, including placental examination, is the most useful approach for determining the etiology. In 23 cases the probable or possible cause was established in this manner. Antibody studies should also be performed in all cases to exclude an immunologic etiology. Synthesis of clinical, serologic, and pathologic data offers prospects for rational management and prediction of recurrence.

Autopsy↗

Primary mediastinal non-Hodgkin's lymphomas: a morphologic and immunologic study of 19 cases.

Nineteen, primary, non-lymphoblastic, non-Hodgkin's lymphomas were investigated by conventional morphologic studies as well as immunologic studies using the application of a battery of monoclonal antibodies to frozen tissue sections. Seventeen of the lymphomas were diffuse large cell; one was large cell immunoblastic and one was a follicular and diffuse lymphoma of intermediate differentiation. Thirty-seven percent of the lymphomas showed prominent sclerosis, sometimes associated with the superior vena cava syndrome. Six of the cases showed evidence of immunoglobulin production with light chain restriction. Twelve additional cases were shown to be of B-cell lineage by B1/T015 expression but did not show evidence of immunoglobulin production. One case was a T-cell lymphoma of helper phenotype. Ia expression was found in 14 of 18 cases studied.

Adolescent↗

Follicular lymphoma with blastic conversion: a report of two cases with confirmation by immunoperoxidase studies on bone marrow sections.

Two cases of low-grade follicular lymphoma are presented in which evolution to a blastic phase with marrow and peripheral blood involvement occurred. One case was a follicular and diffuse mixed-cell lymphoma, while the second was a follicular and diffuse small cleaved-cell lymphoma. In both cases, at two and three years after initial presentation, a clinical picture resembling acute leukemia developed, with immature blastic-appearing infiltrates in the bone marrow and circulating blastic cells. Immunoperoxidase studies on fresh frozen sections of bone marrow in both cases confirmed the B-cell nature of the infiltrates and excluded the clinical impression of acute non-lymphocytic leukemia. The differential diagnosis of hematolymphoid infiltrates in the bone marrow in patients with follicular lymphoma is discussed.

Adult↗

Heparin-induced thrombocytopenia and thrombosis: detection and specificity of a platelet-aggregating IgG.

A 46-year-old female who died as a result of thrombocytopenia associated with multiple arterial occlusions and septicemia while on heparin therapy was found to have a platelet-aggregating factor present in several plasma samples and in a sample of serum. This factor was subsequently shown to be an IgG with aggregating properties toward normal platelets that were enhanced by, but not dependent on, the presence of heparin. Further studies showed that heparin was unlikely to have acted as a hapten in initiating the IgG production but that its role was significant in aggravating the ensuing arterial thrombosis. The necessity of substitution of heparin with alternative anticoagulant/antithrombotic therapy to avoid the worst sequelae of this potentially catastrophic syndrome is discussed.

Blood Coagulation Factors↗

Canine neuroendocrine carcinoma. A tumor resembling histiocytoma.

The clinical and light- and electron microscopic features of 20 cases of canine neuroendocrine carcinoma, initially classified as atypical histiocytomas, are reported. The locally expansile well-circumscribed dermal tumor nodules were composed of solid masses of cells with high mitotic index and multinucleation, arranged in a trabecular pattern with prominent fibrovascular connective tissue stroma rich in reticulin fibers that outlined compact cell nests. Ultrastructural studies revealed evenly dispersed chromatin, focally indented nuclei and abundant cytoplasm with perinuclear filaments, membrane-bound dense core granules, and prominent interdigitating plasma membrane projections with primitive intercellular junctions. Clinical and pathological comparisons between canine neuroendocrine carcinoma, canine histiocytomas, and human Merkel cell neoplasms are discussed.

Age Factors↗

Follicular and diffuse mixed small-cleaved and large-cell lymphoma--a clinicopathologic study.

The clinical records and initial biopsy materials from 76 patients with mixed small-cleaved and large-cell lymphoma containing both a follicular and diffuse architectural pattern were reviewed. The characteristics of this group, treated at Stanford University Medical Center (SUMC) between 1963 and 1983, are described. The 5-year actuarial survival and freedom from progression are 70% and 27.5%, respectively. Classification according to the degree of follicularity indicated that patients with focally follicular areas (ie, less than 25% of the histologic section) have a significantly worse freedom from progression and overall survival at 5 years compared with those patients with a predominantly follicular architecture (ie, greater than 50% follicular areas). Based on our analysis, we feel that the degree of follicularity is an important prognostic factor and that mixed lymphoma patients with only focally follicular areas behave more like an intermediate-grade lymphoma and should be treated aggressively.

Antineoplastic Combined Chemotherapy Protocols↗