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Biomedical subjects

J J Butler

Publications and source records attributed to J J Butler.

At least 37 records · Page 2Linked to original sources

Refractoriness to chemotherapy and poor survival related to abnormalities of chromosomes 17 and 7 in lymphoma.

PURPOSE: Lymphoma cells usually show cytogenetic abnormalities, but their relationship to prognosis has not been as extensively studied as in leukemia. A group of previously untreated cases of lymphoma with evaluable metaphases was examined for the association between cytogenetic abnormalities and clinical outcome. PATIENTS AND METHODS: The study consisted of 104 patients, from whom fresh tumor samples were obtained for cytogenetic tests. Because of the complexity of lymphoma karyotypes, the cases were divided into four patterns according to the type of abnormality of chromosome 17 or 7 present. Treatment of patients was given based on histologic grade and stage of disease. Response to treatment was evaluated according to previously described methods. RESULTS: Patients with true abnormalities of chromosome 17 or 7 (defined as those with either structural abnormalities of the short arm of these chromosomes or monosomy of these chromosomes with no associated unidentified markers) were observed to have an adverse prognosis. The overall response rate and tumor-related mortality were less favorable for patients with these cytogenetic abnormalities. By applying multivariate analysis, we found that this observation was independent of the effect of serum lactic dehydrogenase level, histologic grade, or tumor burden. CONCLUSION: True abnormalities of chromosome 17 or 7 in patients with lymphoma are associated with a poor response to chemotherapy, short time to treatment failure, and high tumor-related mortality rate. These findings raise the question of the potential involvement of some gene or oncogene, perhaps the p53 oncogene, which might impart a survival advantage to the malignant cells.

Adult↗

Fine-needle aspiration cytology of peripheral T-cell lymphoma. A cytologic, immunologic, and cytometric study.

The diagnosis of peripheral T-cell lymphoma (PTCL) is difficult. This entity can be misdiagnosed as Hodgkin's disease or a reactive process such as nonnecrotizing granulomatous lymphadenitis or it can present a problem in lymphoma classification. Fine-needle aspirates from 13 patients with histologically proven PTCL were evaluated by cytology, immunochemistry, and flow cytometry. Of the 13 patients with PTCL, initial cytologic diagnoses were atypical lymphocytic infiltrate (2), mixed-cell lymphoma (6), mixed-cell lymphoma with associated histiocytes (2), large cell lymphoma (2), and small cell lymphoma (1). Surface marker studies were performed on cytospin preparations. Antibodies against cytotoxic-suppressor (Leu-2a) and helper-inducer (Leu-3a,b) antigens were used in 11 cases. Ten lymphomas demonstrated helper phenotype and one showed phenotypic heterogeneity in two different sites. The most prominent cytologic features of PTCL were a variable combination of small, intermediate, and large lymphoid cells with irregular nuclei, presence of epithelioid histiocytes, and atypical mononuclear cells. Flow cytometry studies showed a diploid stem line with intermediate proliferative activity (mean S-phase of 6.7%) in most cases, despite the clinical aggressiveness of this neoplasm.

Adult↗

Hypocellular paratrabecular foci of treated small cleaved cell lymphoma in bone marrow biopsies.

Because of the new drug combinations being used to treat follicular lymphomas, the small cleaved cell lymphomatous foci in bone marrow biopsies appear to be altered. They become progressively hypocellular and contain a few and sometimes no small cleaved cells within oligocellular paratrabecular fibrous foci. These hypocellular paratrabecular foci (HPF) (a) are a clue that deeper sectioning is necessary to determine whether there are diagnostic foci of residual involvement by small cleaved cell lymphoma, (b) may indicate that other portions of the patient's bone marrow still contain viable foci of small cleaved cell lymphoma, and further, (c) should alert the clinician to the possibility of recurrence of small cleaved cell lymphoma in subsequent bone marrow biopsies. A comparison of patients who developed HPF in one or more of their bone marrow biopsy specimens with those who did not indicates that the changes are related to combinations of chemotherapy other than CHOP-Bleo (cyclophosphamide, adriamycin, vincristine, prednisone, bleomycin). Eighty-one percent of patients who developed HPF had received additional chemotherapeutic regimens, whereas 75% of patients whose bone marrows did not contain HPF had received only CHOP-B. The older age of the HPF-negative patients (median age 64 versus median age 43 for HPF-positive cases) may reflect more aggressive chemotherapy in the younger age group. While HPF appear to reflect some increased chemotherapeutic cytotoxicity affecting the lymphomatous foci in bone marrow, they do not appear to predict for a longer survival or cure.

Bone Marrow↗

Nucleic acid flow cytometry in large cell lymphoma.

Between 1978 and 1985, 140 patients with large cell lymphoma (27 follicular, 92 diffuse, 5 immunoblastic, and 16 transformed) had DNA-RNA cytometry performed on involved tissue. DNA-RNA features were correlated with treatment outcome and compared to other established prognostic factors in 63 newly diagnosed patients who received uniformly intensive therapy. Significantly better outcome was noted for previously untreated patients with intermediate RNA content (RNA index, 1.0-1.8), diploid DNA content, and (during the initial 12-month follow-up) low proliferative activity. Of patients followed beyond 12-24 months, those with high proliferative activity appeared to have the most durable remissions, although this was not statistically significant. These findings suggested a preferential impact of intensive chemotherapy on patients with intermediate RNA content and possibly those with high proliferative activity, since previous studies and our own experience with relapsing patients have indicated a progressively worse outlook with higher proliferative activity and RNA index values. In newly diagnosed patients, multivariate analysis identified RNA content as the most important prognostic factor, followed by proliferative activity and serum lactate dehydrogenase. Thus, for patients with large cell lymphoma, DNA-RNA cytometry appears to be a valuable prognostic parameter for identifying a subset of patients who have a high likelihood of cure with intensive chemotherapy.

Analysis of Variance↗

Lymph node enlargement in patients with unsuspected human immunodeficiency virus infections.

The histologic findings in lymph nodes were used to identify eight patients, who are not in a high-risk group, with human immunodeficiency virus (HIV) infection. In order to determine the specificity of these findings, the histologic and clinical findings in these patients were compared with the histologic and clinical findings in 40 patients whose lymph nodes exhibited reactive follicular hyperplasia and who received biopsies before 1981. While a definitive diagnosis of HIV infection cannot be made from the histologic changes in lymph nodes because the organisms cannot be identified, our findings indicate that HIV infection can be suggested, and appropriate testing warranted, when marked reactive follicular hyperplasia with mononuclear cells (and a small number of neutrophils) in parafollicular sinuses is found in a patient with unexplained lymph node enlargement at two or more noncontiguous, noninguinal sites for several months, with or without systemic symptoms.

Adolescent↗

Pancreatic acinar ectasia and intraoperative needle biopsy.

Intraoperative needle biopsy of the pancreas showing pancreatic acinar ectasia can present a problem in differential diagnosis from pancreatic carcinoma. Although this event has previously been described as an incidental postmortem finding, with the increasing use of intraoperative pancreatic biopsy, it is probable that it will be encountered more frequently. The surgical pathologist must be able to distinguish this entity from well-differentiated primary pancreatic adenocarcinoma on frozen section.

Biopsy, Needle↗

Paraimmunoblastic variant of small lymphocytic lymphoma/leukemia.

We report 16 cases of a distinctive, biologically aggressive variant of small lymphocytic lymphoma/leukemia (SLL/L) that is characterized by the diffuse proliferation of cells normally comprising the pseudoproliferation centers (so-called paraimmunoblasts). Demographically, the patients differed in no significant regard from patients with SLL/L of usual type. Rapidly progressive, generalized lymphadenopathy was the dominant clinical finding in 15 of the 16 patients; one patient presented with symptoms related to lymphomatous involvement of the stomach and regional lymph nodes. Splenomegaly was observed in five patients. Seven patients, two of whom had a history of indolent-phase chronic lymphocytic leukemia, had an absolute lymphocytosis at diagnosis. In most patients, bone marrow involvement was noted at diagnosis. It consisted predominantly of small lymphocytic infiltrates indistinguishable from those observed in SLL/L of usual type; significant paraimmunoblastic infiltration was infrequent and generally occurred late in the disease course. Immunohistochemical and cytogenetic study further substantiated the hypothesized relationship of these cases to SLL/L. Findings included (a) coexpression of sIg and Leu-1 antigen in the majority of cases and (b) the presence of a t(11;14) (q13;q32) chromosome translocation in two of three cases with analyzable metaphases. Although treatment protocols were not uniform, follow-up data indicated an accelerated clinical course. Eleven patients have died of their disease between 3 and 39 months after diagnosis; the median survival was 28 months.

Adult↗

Non-Hodgkin's lymphoma in bone. Pathologic and radiologic features with clinical correlates.

Thirty-seven lymphomas of bone were studied, including 33 diffuse large cell lymphomas, three undifferentiated (small noncleaved cell) lymphomas, and one well-differentiated (small) lymphocytic lymphoma. The large cell lymphomas were subclassified as large cleaved, large noncleaved, multilobated cell, and immunoblastic sarcoma (large cell lymphoma, immunoblastic type). Eleven of 26 large cell lymphoma patients with adequate follow-up were long-term survivors (free of disease for more than 5 years). Nineteen of the 33 large cell lymphomas were localized to one bone. The stage and histologic pattern significantly correlated with long-term survival among large cell lymphomas. Seventy-three percent of patients with localized lymphoma were long-term survivors, in contrast to 9% of those with disseminated disease. Sixty-seven percent of patients with large cleaved and multilobated cell lymphoma were long-term survivors, but only 21% of those with large noncleaved cell and immunoblastic sarcoma were. The tumors had a blastic, lytic, or mixed radiographic appearance and had either sclerotic, lytic, or permeative borders; none of the radiologic findings were diagnostically useful.

Adolescent↗

Residual fibrous masses in treated Hodgkin's disease.

Of nine patients with residual masses following therapy for Hodgkin's disease (HD), eight had nodular sclerosing HD, and one had mixed cellularity HD. One patient had Stage II disease, seven had Stage III, and one had Stage IV. Seven patients presented with bulky mediastinal disease. Regardless of the initial therapy used residual masses in the mediastinum and/or peripheral locations stabilized in 1 to 8 months. Between 5 and 10 months after initiation of therapy, five patients underwent resection of mediastinal or paratracheal masses; three patients had resection of peripheral masses, and one patient underwent laparatomy. Microscopically, the resected masses were hyalinized tissue showing a characteristic nodular configuration without evidence of active HD. Stable residual mass lesions occurring after therapy for HD should not be assumed to represent recalcitrant malignancy, as they may show only fibrosis.

Adolescent↗

Solitary plasmacytomas of bone and extramedullary plasmacytomas. A clinicopathologic and immunohistochemical study.

Twenty-two patients with solitary plasmacytoma of bone (SPB) and 13 with extramedullary plasmacytomas (EMP) were studied. The average follow-up period for SPB was 90 months and 86 months for EMP. Thirty-six percent of patients with SPB developed multiple myeloma (MM) in an average of 39 months, and 23% of patients with EMP developed MM in an average of 23 months. No significant differences in survival, incidence of MM, or interval to the development of MM were found between the two groups. The 11 cases of EMP with evaluable tissue for immunohistochemical study were either monotypic kappa or lambda, as were 9 of 10 SPB. Presence of monoclonality did not predict the development of MM. The histologic parameters of nuclear immaturity and presence of prominent nucleoli seem to be the best indicators of which patients will develop MM. Solitary plasmacytoma of bone and EMP appear to be more closely related than has been previously recognized.

Adult↗

Incidence of lymphoma in the US classified by the working formulation.

The incidence of lymphoma in the US and Puerto Rico among 13,600 patients is reported by histologic subtypes according to the Working Formulation. The most frequent histologic types were intermediate grades (five per 100,000 among whites, three per 100,000 among blacks, and two per 100,000 among Puerto Rican Hispanics). Low-grade types were next in frequency (2.7 per 100,000 in whites, 1.5 per 100,000 in blacks, and one per 100,000 in Puerto Rican Hispanics). More than 95% of patients had low-or intermediate-grade lymphomas, and of these, intermediate-grade lymphomas occurred in 65% of patients. High-grade types were infrequent in all ethnic groups. The incidence among men was significantly greater than among women in all ethnic groups. There was a distinct peak for small noncleaved cell type among white boys but not girls. For all other histologic types, there was a conspicuous absence of a young adult component, with incidence increasing steadily with age. No evidence for seasonal fluctuation in month of diagnosis was found. This delineation of incidence by histologic groupings, sex, and ethnic group will facilitate future studies using the Working Formulation.

Adolescent↗

Monosomy 21, partial duplication of chromosome 11, and structural abnormality of chromosome 1q21 in a case of lymphoma developing in a transplant recipient: characteristic abnormalities of secondary lymphoma?

Cytogenetic analysis by QFQ-banding of direct preparation of a testicular mass from a patient with secondary lymphoma revealed a modal chromosome number of 45,XY, including structural and numerical anomalies. The most consistent anomalies were the monosomy 21, duplication of the long arm of #11, and structural anomaly associated with chromosome #1 in band q21.

Adult↗

Idiopathic retroperitoneal fibrosis (sclerosing retroperitonitis).

Three cases of idiopathic retroperitoneal fibrosis, one of which was localized to the perirenal area, are presented. The predominance of plasma cells, which may be difficult to recognize because of distortion unless methyl green-pyronine staining is done, and the character of the fibrous tissue indicated the non-neoplastic nature of the processes. This diagnosis was confirmed by immunoperoxidase studies that demonstrated polyclonality of the lymphoplasmacytic component. Immunologic studies, which may be performed on paraffin-embedded tissue, are helpful in differentiating this lesion from the sclerosing lymphomas that also occur in the retroperitoneal area.

Adult↗

Ultrastructural observations in cat scratch disease.

Because the causative bacterium of cat scratch disease has not been definitively cultured or fully characterized, the authors have studied its ultrastructure in lymph node biopsies from two patients using glutaraldehyde-fixed tissue. In both specimens, the organisms were invariably extracellular, forming small groups within bundles of collagen fibrils. Their appearance was similar in necrotic and viable regions of the nodes, although in the latter sites they could not be identified by light microscopic examination with the Warthin-Starry stain. The bacteria were pleomorphic rods, and, despite faint gram-negative staining, their walls were consistently thick and homogeneous.

Adolescent↗

Follicular lymphoma mimicking progressive transformation of germinal centers.

Three cases of a morphologically distinctive "floral" variant of follicular large cell lymphoma are presented. In each instance, the diagnosis of theoretically "florid" progressive transformation of germinal centers (PTGC) was made or considered. The features that separate this pattern of lymphoma from reactive follicular hyperplasia with PTGC include involvement of all nodules without the presence of any reactive germinal centers, a homogeneous proliferation of large transformed lymphocytes with a markedly decreased or absent population of phagocytic histiocytes, and extension by abnormal cells into the perinodal adipose tissue. If the desirability of frozen section tissue immunophenotyping is anticipated, these lymphomas would be distinguished from PTGC by monotypic staining for light chains.

Adult↗

Malignant lymphoma presenting as a renal mass: four cases.

Primary lymphoma of the kidney is extremely rare; most lymphomatous renal masses represent extension from adjacent sites of disease or involvement by generalized disease (4,9,12). Three men and one woman, 45 to 71 years of age, presented with solitary renal masses clinically thought to be renal cell carcinoma. Each experienced abdominal pain, one with hematuria and one with "B" symptoms. Physical examination revealed no peripheral lymphadenopathy or hepatosplenomegaly. Lactic dehydrogenase (LDH) was elevated in three cases, and blood urea nitrogen (BUN) and creatinine were slightly increased in two. Two cases were diagnosed correctly from needle biopsy, with ultrastructural confirmation in one case and marker studies, DNA flow cytometry, and cytogenetics in the other. Because of a presumptive diagnosis of renal cell carcinoma, two patients underwent nephrectomy. Three cases were large-cell lymphoma, and one, small noncleaved cell lymphoma.

Aged↗

Stage III follicular lymphoma: durable remissions with a combined chemotherapy-radiotherapy regimen.

From 1975 to 1982, 74 patients with stage III follicular lymphoma were treated with a combined modality protocol which included chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo), and radiotherapy to involved regions. This program resulted in a complete remission (CR) rate of 81%, a 5-year survival of 75%, and 5-year relapse-free survival (RFS) of 52% for all patients. Analysis of potential factors affecting treatment outcome revealed a significantly better CR rate for patients with small cleaved cell type (97%) than for patients with mixed (73%) or large-cell (57%) histologies. The 5-year survival was significantly better for patients with small cleaved (91%) and mixed (84%) cell types than for large cell (40%). In addition, bulky abdominal disease and elevated serum lactate dehydrogenase (LDH) were significant adverse prognostic factors for CR and for survival. Toxicity was moderate. No secondary leukemias have occurred. This combined modality regimen resulted in prolonged remission and potential cure for over half of patients who achieved CR, and is particularly encouraging for those with follicular small cleaved and mixed histologies.

Adult↗

The gene located at chromosome 18 band q21 is rearranged in uncultured diffuse lymphomas as well as follicular lymphomas.

The karyotypic abnormality t(14;18)(q32;q21) is reported to occur in 75% of follicular lymphomas. This translocation results in the rearrangement of a putative oncogene bcl-2, which resides at chromosome 18 band q21 (the 18q21 gene). Using two human genomic DNA fragments cloned from the chromosome 18 band q21 as probes, we analyzed 65 uncultured human lymphoma samples by the Southern blot technique. The 18q21 gene was rearranged in 18 of 26 (69%) follicular lymphomas, 3 of 5 (60%) follicular lymphomas transformed to large cell lymphomas, 8 of 20 (40%) diffuse large cell lymphomas (DLCLs), and 2 of 7 (29%) small noncleaved cell lymphomas (SNCs). Our analysis detected rearrangement of the 18q21 gene in 10 of 13 (77%) cases in which the t(14;18)(q32;q21) translocation was found by cytogenetic techniques. Our analysis also proved helpful in difficult karyotyping situations: (a) identifying the donor chromosome fragment as chromosome 18 band q21 in 4 of 9 (44%) cases that cytogenetically displayed a 14q+ chromosome of unknown origin, and (b) identifying a rearrangement of chromosome 18 band q21 in 12 of 18 (67%) cases that cytogenetically yielded no cells in metaphase. We also demonstrated three cases of submicroscopic rearrangement of the 18q21 gene. In our studies, patients with DLCLs and rearrangement of the 18q21 gene had a significantly higher incidence of extranodal involvement when compared with patients with DLCLs and no 18q21 gene rearrangement (P = 0.03).

Bone Marrow Cells↗