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Biomedical subjects

D Variakojis

Publications and source records attributed to D Variakojis.

At least 37 records · Page 2Linked to original sources

DNA aneuploidy in Hodgkin's disease. A multiparameter flow-cytometric analysis with cytologic correlation.

In 15 cases of Hodgkin's disease, the authors studied the DNA content of isolated nuclei from deparaffinized tissue by using multiparameter flow cytometry. An antinucleolar antibody preparation was employed as well as a secondary antibody that had been conjugated with fluorescein isothiocyanate. By simultaneously quantitating nucleolar fluorescence and DNA content, rare but distinct aneuploid populations were detected among the nuclei with brightly stained nucleoli. DNA aneuploidy was found in each case when this multiparameter analysis was used, but was detected in only 1 case when DNA content was analyzed alone. With the multiparameter analysis, two to four aneuploid populations were found in each case. These populations exhibited incremental duplications of DNA content that suggested endopolyploidy, ie, replication of DNA without accompanying nuclear division. The aneuploid stem line was hypodiploid or hypotetraploid in 6 cases, hyperdiploid in 7 cases, and near-triploid in 2 cases. These various abnormalities in ploidy showed only some correlation with histologic subtypes. Cell sorting showed that some nuclei with more than four or nearly eight times normal DNA content resembled nuclei of typical Reed-Sternberg cells. Many nuclei with an intermediate aneuploid DNA content resembled nuclei of mononuclear Reed-Sternberg cells. The near-diploid and near-triploid nuclei corresponded to nuclei of cells which were not readily recognizable as neoplastic in histologic sections. It is concluded that multiparameter analysis of DNA content can provide further insights into the neoplastic cells in Hodgkin's disease and may offer an objective basis for studying heterogeneity in this disorder.

Aneuploidy

Histiocytosis X. Flow cytometric DNA-content and immunohistochemical and ultrastructural analysis.

A 76-year-old man developed a generalized orange-red nodular eruption associated with constitutional symptoms. A biopsy specimen of a nodule revealed an extensive infiltration of histiocytes with relatively abundant cytoplasm and folded nuclei. Electron microscopy showed Langerhans' cell granules, which confirmed the diagnosis of histiocytosis X. Results of immunohistochemical studies revealed a pattern of antigen expression usually found in histiocytosis X, including Ia, T6, and S100. Analysis of the DNA content of the cells with flow cytometry revealed an aneuploid peak. The patient responded partially to topical mechlorethamine hydrochloride therapy.

Adult

Phenotypic analysis in diffuse, large cell lymphoma. Clinical and histologic associations.

To investigate the possible relationships between immunologic phenotype, histologic subtype, and clinical features in diffuse, large cell lymphoma (DLCL), a computerized registry has been established for the prospective collection of immunologic, histologic, and clinical data. A combination of immunofluorescence and immunoperoxidase technics on single-cell suspensions, frozen tissues, and B5-fixed, paraffin-embedded specimens was used to study the first 33 biopsies. A definitive phenotype was established in all but two cases. Monoclonal antibody reagents reactive in B5-fixed, paraffin-embedded tissue sections helped assign a B-cell lineage in four cases lacking surface or cytoplasmic immunoglobulin, monoclonal light chains, and T-cell markers. There was no statistically significant association between the immunologic phenotype (whether mature B or not) and any clinical or histologic parameter, including response to therapy and survival. Bone marrow involvement was found to be associated significantly with both vague nodularity and a cleaved cell subtype. Through the use of a multifaceted approach to the immunophenotypic analysis of the DLCLs, a distinct lineage and stage of differentiation could be assigned to most biopsy specimens. That such analysis has significant clinical implications for patients with DLCL could not be demonstrated in this series.

Adult

Cat scratch disease. Identification of bacteria in seven cases of lymphadenitis.

A retrospective study of lymph node biopsy specimens from nine patients with the clinical findings and histologic features of cat scratch disease was undertaken to determine whether the recent report by Wear et al. that pleomorphic bacteria are present in the lymph nodes of cat scratch disease could be confirmed. In seven of our nine cases, pleomorphic bacteria were demonstrated with the Warthin-Starry (WS) silver stain. These were gram-negative with the Brown-Hopps tissue Gram stain and were almost at the limit of microscopic resolution. Lymph node specimens from 13 additional patients with nonspecific lymphadenitis who had neither clinical nor histologic findings of cat scratch disease were studied similarly; in none of these were bacteria demonstrated with the WS silver stain. After examining the distribution of the organisms and the related morphologic features in cat scratch disease, we conclude that demonstration of pleomorphic, gram-negative, WS-positive bacteria in the appropriate clinical and histologic setting can firmly establish the diagnosis of cat scratch disease.

Adult

Evaluation of computed tomography and radionuclide scanning in the staging of cutaneous T-cell lymphoma.

Computed tomography (CT) of the abdomen and pelvis was performed on 30 patients with cutaneous T-cell lymphoma (CTCL) as part of their pretreatment staging evaluation. Twenty-two patients also had liver-spleen radionuclide scans. Physical examination revealed limited cutaneous plaque disease in five patients, extensive plaque disease in 11 patients, cutaneous tumors in six patients, and exfoliative erythroderma in eight patients. Generalized palpable adenopathy was detected in 11 patients, localized palpable adenopathy in ten patients, and no adenopathy in nine patients. Peripheral lymph node biopsy specimens showed CTCL in seven patients and dermatopathic lymphadenitis or sinus histiocytosis in 17 patients. Two patients were at disease stage Ia, five were at stage Ib, seven were at stage IIa, two were at stage IIb, seven were at stage III, and seven were at stage IVa. The CT did not reveal intra-abdominal, retroperitoneal, or pelvic adenopathy, or hepatic or splenic abnormalities in any patient. Radionuclide scans demonstrated nonspecific abnormalities in five patients, but did not appear to reflect disease involvement. Computed tomography of the abdomen and liver-spleen radionuclide scans should not be routine staging procedures for CTCL.

Humans

Use of novel chemical supplements in the establishment of three human malignant lymphoma cell lines (NU-DHL-1, NU-DUL-1, and NU-AMB-1) with chromosome 14 translocations.

Three new cell lines have been established from patients with malignant lymphoma utilizing a human diploid feeder layer, pooled human serum, and the chemical supplements L-cysteine, iron-saturated transferrin, and bathocuproine disulfonate, a copper chelator. After a short period of growth, the 3 cell lines were successfully weaned from the feeder layers but continued to require human serum and the chemical supplements for up to 9 months of culture. The cell lines are currently grown in RPM1-1640 medium and fetal calf serum without further supplementation. The NU-DHL-1 cell line was established from the involved lymph node of a 73-year-old White male with diffuse large-cell lymphoma. The cell line expresses cytoplasmic IgM/lambda heavy and light chains, is Epstein-Barr virus (EBV)-negative, and is positive for several B-cell markers, indicating that it is derived from a mature-B-cell neoplasm. The NU-DUL-1 cell line was established from the cerebrospinal fluid of a 42-year-old White male with undifferentiated lymphoma, non-Burkitt's type, who initially presented with a mediastinal mass and had subsequent involvement of the central nervous system. The cell line is EBV-negative, but surprisingly it is positive for early B-cell markers. The NU-AmB-1 cell line was established from the abdominal mass of a 12-year-old Hispanic male with undifferentiated lymphoma, Burkitt's type. The cell line is EBV-positive and expresses early B-cell markers. All 3 cell lines are aneuploid or pseudodiploid and contain chromosome 14q+ abnormalities including a newly described complex translocation t(?;1;8;14) in the NU-AmB-1 cell line. The establishment of these cell lines was made possible by refinements in the cell culture of the human malignant lymphomas. The availability of well-characterized lymphoma cell lines with specific chromosomal translocations will aid molecular and cellular studies designed to identify the biological significance of genomic rearrangements.

Cell Line

Primary histiocytic lymphoma of the epididymis.

The first documented case of primary histiocytic lymphoma of the epididymis is presented. The tumor showed distinct nodularity, which is unusual for extranodal lymphomas, and marked sclerosis. Extensive staging work-up showed no evidence of extraepididymal spread. Unusual features included the youth of the patient at presentation and the severe diffuse atrophy of the adjacent testicular parenchyma. Following orchiectomy and radiotherapy, there has been no subsequent clinical evidence of systemic disease.

Adult

Hairy cell leukemia: an autopsy study.

Autopsy material from 5 patients with hairy cell leukemia was examined. In addition to the expected widespread involvement of the hematopoietic system and of the liver, all of the patients had various amounts of pulmonary infiltration by leukemic cells. This infiltration was so severe in one instance that the resulting pulmonary insufficiency was the cause of death. Other areas of hairy cell infiltration included the peripancreatic connective tissue in all cases, kidneys in 3 cases, pericardium in 2 cases, and skin in 1 case. Association of plasma cells with the infiltrating neoplastic cells was prominent. In one patient, foci of large, bizarre cells were found in several lymph nodes and in the pericardium. Whether these cells represent transformation of the hairy cells into a larger, less differentiated cell type, or the emergence of a second hematopoietic neoplasm, is unknown.

Adult

Pathologic stage I and II Hodgkin's disease, 1968--1975: relapse and results of retreatment.

Sixty-seven previously untreated patients with Hodgkin's disease, pathologic stages I and II, seen during a 7-year period were evaluted with respect to initial staging and treatment, as well as relapse and retreatment results. The initial treatment consisted of radiation therapy (RT) to an involved field (IF) or an extended field (EF) for patients with stages IA and IIA, or RT and, in recent cases, combination chemotherapy [cyclophosphamide, Oncovin, procarbazine, and prednisone (COPP)] for patients with stages IB and IIB. Nineteen of the 67 patients relapsed (28%), including 11 of 56 patients with stages IA and IIA (20%) and 8 of 11 patients with stages IB and IIB (73%). Seventeen of the 19 relapses occurred within 24 months after completion of the initial therapy (89%). The relapse-free survival at 5 years was 75% for the A patients and 25% for the B patients. The actuarial survival of stage IA and stage IIA patients at 5 years was 91%; there was no significant difference between patients treated initially with either IF or EF. The actuarial survival at 5 years for the patients with stages IB and IIB was 88%, as most responded to a second program of induction therapy. No correlation could be found between the pattern of relapse and the initial pathologic stage or the mode of treatment.

Adolescent

Mycosis fungoides and Hodgkin's disease occurring in the same patient: report of three cases.

The patients with the typical clinical course and pathology of Mycosis Fungoides (MF) were found also to have Hodgkin's Disease (HD), nodular sclerosing type. In two cases, HD was diagnosed 2 years after the diagnosis of MF; in the third case, both diseases were diagnosed simultaneously. Previous claims of MF transforming into second lymphomas are reviewed. The possible significance of our observed association of MF and HD is discussed.

Hodgkin Disease

Transcatheter bronchial brush and forceps biopsies. Histologic evaluation.

The histologic findings in transcatheter brush and forceps biopsies from 472 cases over a six-year period are evaluated. Diagnostic accuracy based on histologic findings was 38% and based on cytologic findings was 70%. When the two methods of examination were used, however, the overall accuracy was improved to 76%. In Hodgkin's disease and some inflammatory processes histologic examination is essential for the diagnosis. The transcatheter biopsies under fluoroscopic control are especially useful for securing tissues from the peripherally located lesions. When possible, examination of tissue obtained by transcatheter as well as forceps biopsies is encouraged.

Adenocarcinoma

Combined therapy for patients with mycosis fungoides.

In a comprehensive mycosis fungoides program, 60 patients have been seen with a pathologic diagnosis of this disease. Forty-four patients with advanced disease were referred for radiation therapy. Three treatment techniques were identified in which 14 patients were treated with localized fields using electrons or whole-body electron-beam therapy with doses of less than 3000 rads, 21 patients were treated using the Stanford technique with tissue doses of between 3000 and 4000 rads, and nine patients were treated with six cycles of mechlorethamine, vincristine, prednisone, and procarbazine or cyclophosphamide, vincristine, prednisone, and procarbazine following the electron-beam therapy. The actuarial survival rate was 45% at 1 year for the 14 patients with localized electron-beam therapy, whereas the actuarial survival rates were 83% for patients treated with whole-body electron-beam therapy and 100% for patients treated with whole-body electron-beam therapy followed by four-drug chemotherapy. The recurrence-free interval for these three groups correlates with these observations. A central nervous system recurrence has been observed in the combined-therapy group.

Adult

B cell acute lymphoblastic leukemia (ALL) with a 14q+ chromosome abnormality.

An adult patient with acute lymphoblastic leukemia associated with a 14q+ marker chromosome is presented. The abnormality resulted from a translocation of material from the long arm of chromosome 11. The leukemic cells were found to be B cells on the basis of surface immunoglobulins, lack of receptors for sheep erythrocytes, and a characteristically low level of adenosine deaminase activity. In other patients with ALL studied by us or reported by others in whom chromosome banding was done, a 14q+ chromosome was present in only one instance, also a case of B cell ALL. These two cases are the only examples of B cell ALL studied with chromosome banding reported to date. The frequent occurrence of a 14q+ chromosome in other malignant lymphoproliferative diseases of B cell origin suggests that a general association may exist between the 14q+ abnormality and B cell neoplasms. Cytogenetic analysis may therefore be useful in defining subtypes of ALL and in relating specific chromosomal abnormalities to lymphoproliferative disorders.

Adenosine Deaminase

Banding studies of chromosomal abnormalities in patients with acute lymphocytic leukemia.

Karyotypes were analyzed by routine Giemsa and quinacrine fluorescence for 16 patients with acute lymphocytic leukemia [ten adults (18 to 51 years) and six children (3 to 15 years)]. Four patients had received previous therapy, but all 16 had active disease when they were first studied. Eight patients (five untreated) had a normal karyotype initially; however, three of these developed a chromosomal abnormality during relapse. Eight patients had a chromosomal abnormality in their initial samples. Each of the 11 patients had different abnormalities. All chromosomes except Nos. 3, 5, 15, 16, and Y were involved in the various aneuploidies. One patient had a Ph1 chromosome due to a translocation with No. 21: t(21;22)(q22;q11). A patient with B-cell acute lymphocytic leukemia had a 14q+ marker in addition to other abnormalities. The median survival of patients with initially normal karyotypes may be longer than that of patients whose karyotypes are abnormal initially.

Acute Disease

Banding studies of chromosomes in a patient with mycosis fungoides.

Chromosomes from a patient with mycosis fungoides were examined in detail with banding techniques. Hyperdiploid cells from a lymph node had common anomalies of certain chromosomes which formed three similar clones. The abnormalities involved chromosomes No. 1, 2, 5, 8, 9, 10, 14, and 18, in addition to an unkwown small metacentric marker (M3). Although there were a number of mitotic cells in peripheral blood cultured both with and without PHA, none of the few cells with abnormal karyotypes was similar to the clonal cells of the lymph node. One of the abnormalities in the lymph node was a 14q rearrangement, which could be the result of a translocation of Nos. 8 and 14 involving a third chromosome, No. 2. An abnormality in the blood resulted from a translocation between the long arms of Nos. 1 and 14. These findings could be useful for studies in which mycosis fungoides is compared with the Sézary syndrome and other lymphoid malignancies.

Bone Marrow Examination