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Biomedical subjects

W C Pugh

Publications and source records attributed to W C Pugh.

At least 37 records · Page 2Linked to original sources
PubMed1994

Detection of subgroups of chronic B-cell leukemias by FMC7 monoclonal antibody.

Monoclonal antibody FMC7 detects subgroups of B-cell leukemias that have arisen from cells in late stages of B-cell maturation. FMC7 was studied by flow cytometry on cell samples from 192 patients with a diagnosis of chronic lymphocytic leukemia (CLL) or lymphoma. The leukemic cells from 16 patients were reactive with this antibody. These 16 cases were evaluated for other surface markers, morphology of cells, and clinical characteristics. Of the 16 patients, 14 had cells that strongly expressed surface immunoglobulin (SIg). This is atypical of CLL cells, which characteristically show weak expression of SIg. Eleven cases had kappa and five had lambda light chain. All patients' cells had consistently brighter CD20 expression than that of CD19. Fourteen patients had expression of CD5 on their leukemic cells. One patient had more than 55% prolymphocytes, meeting the criteria of prolymphocytic leukemia (PLL), two patients had CLL in prolymphocytic transformation (CLL/PL), and two other patients were classified as having a paraimmunoblastic variant of small lymphocytic lymphoma based on a high number of paraimmunoblasts and on the histologic features. Another nine patients had immature lymphoid cells distinct from prolymphocytes or paraimmunoblasts on morphologic study. The immature cells were variable in size, and the nuclear chromatin was less clumped than that of prolymphocytes. The histologic diagnoses in four of these cases were consistent with mantle cell lymphoma. Splenomegaly was observed in 11 patients (69%), and 11 patients had advanced Rai 3 or 4 disease. Among 10 patients treated with fludarabine, five responded to therapy. Monoclonal antibody FMC7 is useful for identifying a group of atypical variants of CLL, PLL, and other B-cell lymphomas in leukemic phase that can be easily confused with CLL. Careful attention to the cell morphology and histologic features is important for the differential diagnosis of FMC7-positive, B-cell lymphoproliferative diseases.

Adult↗
PubMed1994

Cell kinetic analysis of interleukin-2 receptor-tested chronic lymphocytic leukemia using the AgNOR silver stain.

B-cell chronic lymphocytic leukemia (B-CLL) is typically a low-grade neoplasm with a diploid DNA index and low proliferative activity. Interleukin-2 receptor (IL-2R/CD25) positivity often indicates increased proliferative activity and activation in both T and B lymphocytes. The argyrophilic nucleolar organizer regions (AgNORs) are loops of DNA identified by a silver staining technique and have been correlated with ploidy and proliferative activity. Two distinct AgNOR counting methods have been previously shown to correlate with DNA ploidy and proliferative activity, respectively: the mean AgNOR count (mAgNOR) correlates more with ploidy, and the percentage of nuclei with > or = 5 AgNORs/nucleus (pAgNOR) reflects proliferative activity. We studied bone marrow specimens from 32 patients with B-CLL using both anti-IL-2R on the marrow aspirates and the AgNOR silver stain on marrow biopsy specimens, applying both AgNOR counts. All tumors were CD5+, CD19+, and CD19/CD20+. Sixteen tumors were IL-2R- (< 20% IL-2+ B cells), and 16 were IL-2R+ (> or = 20% IL-2R+ B-cells). No significant difference in morphology of bone marrow involvement was noted in the two groups. A male predominance was noted in the IL-2R+ group of patients (3:1). There was also a preponderance of lambda light chain expression in the IL-2R+ tumors (11/16) compared with the IL-2R- cases (5/16). Except for two cases, all tumors had mAgNOR counts within the diploid range (< 2.4). The 16 IL-2R- tumors had pAgNOR in the range of 0% to 7% (mean, 2.31 +/- 2.18 standard deviation), whereas the IL-2R+ tumors had pAgNOR ranging from 6% to 15% (mean, 10.20 +/- 2.70 standard deviation; P < .0001). This finding suggests that IL-2R+ B-CLL might represent a subgroup of tumors with higher proliferative activity.

Adult↗
PubMed1994

Long-term prognostic importance of primary Ki-1 (CD30) antigen expression and anaplastic morphology in adult patients with diffuse large-cell lymphoma.

BACKGROUND: We retrospectively assessed the long-term prognostic importance of primary CD30 antigen expression and of anaplastic large-cell morphology (ALCL) in adult patients with previously untreated diffuse large-cell lymphoma (DLCL), including cases of immunoblastic lymphoma, and identified their clinical features. MATERIALS AND METHODS: We examined available archival paraffin-embedded or frozen pathologic material and medical records of adult patients with previously untreated DLCL seen at M.D. Anderson Cancer Center (MDACC) between January 1978 and May 1989. RESULTS: Sixty-seven cases of DLCL and seven cases of IBL (a total of seventy-four heretofore referred to as DLCL) were identified. Twenty-two of the 74 patients were positive for the CD 30 antigen. For these 22 patients the rates of complete remission, survival, and time to treatment failure (TTF) were 86%, 82%, and 77%, respectively, at 81 months. When compared with the group of 54 patients which stained negative for CD 30, the long term survival of CD 30-positive DLCL was favorable (82% vs. 49%, p = 0.08). ALCL morphology was present in two-thirds of the patients with CD 30-positive DLCL but did not affect survival and TTF rates. Among patients with CD 30-positive DLCL, 16 patients without skin involvement were younger and had a low failure rate (13%) compared with six patients with skin involvement who were older and had a high failure rate (50%); however, the latter group had a more indolent course after failure and thus both groups had similar survival rates. CONCLUSIONS: Primary CD 30 positivity is associated with a favorable long-term prognosis in adult patients with DLCL treated with doxorubicin-containing chemotherapy. ALCL morphology among these patients does not affect the outcome. Patients with CD30-positive DLCL and skin involvement have a higher failure rate than those without skin involvement, but similar overall survival.

Adolescent↗
PubMed1994

Primary mediastinal large cell lymphoma is characterized by an inverted pattern of large tumoral mass and low beta 2 microglobulin levels in serum and frequently elevated levels of serum lactate dehydrogenase.

BACKGROUND: Primary mediastinal large cell lymphoma (PMLCL) is an emerging entity. New parameters can help define it. MATERIALS AND METHODS: Retrospective analysis of medical records from 35 patients treated at The University of Texas M.D. Anderson Cancer Center from 1985 to 1990. Immunohistochemical evaluation of tissue specimens. Determination of survival (S) and time to treatment failure (TTF). RESULTS: The median age was 34 years and 69% were females. Eight-three percent presented with symptoms of mediastinal involvement. While 100% of the patients presented with bulky mediastinal disease and 72% had elevated pretreatment serum lactate dehydrogenase, only 6% presented with an elevated pretreatment serum beta 2 microglobulin. The lymphoma cells lacked CD21 staining. For the 18 patients treated initially at M.D. Anderson Cancer Center, S and TTF curves rates after doxorubicin-based regimens (plus radiotherapy in 14 cases) were 72% and 61%, respectively, at 5 years follow-up (median, 42 months). Four out of six patients who received autologous bone marrow transplant as salvage therapy are currently alive without disease at follow-up times of 21, 25, 32, and 54 months. CONCLUSION: Primary mediastinal large cell lymphoma has characteristic clinicopathological features to which another can be added, that of an inverted pattern of bulky disease, high LDH and low beta 2 M in serum. The response to therapy is comparable to that of intermediate-grade lymphomas, although the numbers in the study are small. Our preliminary data suggest a possible role for autologous bone marrow transplantation (ABMT) as salvage therapy.

Adult↗
PubMed1994

Mediastinal lymphoblastic lymphoma with non-lymphoblastic histologic features.

The clinical and pathologic features of an unusual case of mediastinal lymphoma in a 46-yr-old man are presented. Histology of the tumor was that of a diffuse, non-large cell lymphoma. The nuclear chromatin was coarse, suggesting a relatively mature stage of lymphocyte maturation, and the lymphoma was provisionally classified as diffuse small-cleaved cell lymphoma. Immunohistologic study and cell surface marker analysis revealed a common thymocytic phenotype (CD3, CD1a, CD4, CD8, and TdT positive), however, and DNA flow cytometric analysis revealed a high S+G2 M fraction of 29%. With the immunostaining profile accepted as definitive for lymphoblastic lymphoma, histologic features were reassessed in retrospect. Cells having nuclear features typical of lymphoblasts were not recognized. Occasional cases of lymphoblastic lymphoma may not be recognizable when evaluated only by histology using the generally accepted criteria for diagnosis.

Cell Cycle↗
PubMed1993

T-cell-rich B-cell lymphoma.

We analyzed 23 cases of T-cell-rich B-cell lymphomas (BCL) to determine if the clinical features are characteristic of a discrete entity. Cases encoded as T-cell-rich BCL in the hematopathology archives of the University of Texas M.D. Anderson Cancer Center between 1988 and 1991 formed the basis of this study. At least 50% of the total population of cells were required to be of T-cell phenotype. Actually, all but one patient had more than 70% T cells in the total population. Sixty-five percent of all cases were referred with other diagnosis such as Hodgkin's mixed cellularity, peripheral T-cell lymphoma (PTCL), or diffuse mixed lymphoma, and had received therapy accordingly. With the exception of splenomegaly, which occurred in 35% of cases, the other clinical characteristics and the response to therapy did not indicate that this entity represents a distinct type of lymphoma. Ann Arbor stage I-II presentations were seen in 10 of 23 (43%) T-cell-rich BCLs. Serum lactate dehydrogenase (LDH) was elevated in eight of 19 patients. Age, sex, and beta 2-microglobulin were not significantly different from classical B-cell large cell lymphoma. The clinical presentation and clinical outcome of T-cell-rich BCL did not differ from that of common B-cell large cell lymphoma, except for the higher proportion of splenomegaly seen in patients with T-cell-rich BCL. The presence of the T-cell-rich infiltrate varied: it frequently was not seen at relapse or at other sites of disease at presentation. It was thus considered an unstable parameter. The major importance of identifying this entity is to distinguish it pathologically from other disorders such as Hodgkin's disease and PTCL, which would be treated in a different manner.

Adult↗
PubMed1992

Response assessment in chronic lymphocytic leukemia after fludarabine plus prednisone: clinical, pathologic, immunophenotypic, and molecular analysis.

The goals of this study were to evaluate the response to treatment in chronic lymphocytic leukemia (CLL) according to clinical, pathologic, immunophenotypic, and molecular features, as well as to address the clinical significance of each finding. One hundred fifty-nine CLL patients with either advanced Rai stage III or IV (81 patients) or progressive Rai stage 0 to II (78 patients) were treated with fludarabine (30 mg/m2/d intravenously every day for 5 days) plus prednisone (30 mg/m2/d orally daily for 5 days). Thirty-six patients were previously untreated. The response rates were 12% complete response (CR), 30% nodular complete response (nCR), and 18% partial response (PR). In all patients who achieved a complete response (both CR and nCR) less than 30% of nucleated cells were lymphocytes on marrow aspirate differential analysis; however, nCR patients had residual nodular and/or interstitial lymphocyte involvement on marrow biopsy examination. There was no evidence of leukemic infiltration on marrow biopsy examination in CR patients. With a median follow-up of 35 months, comparison of time to progression in the CR and nCR groups at 2 years showed a projected 87% versus 55% progression-free survival (P less than .03). Residual disease assessment by flow cytometry using simultaneous dual-color staining on blood and marrow lymphocytes was also performed on each patient. Residual disease was determined by the expression of CD5 on B lymphocytes and the monoclonality of surface light-chain expression. After six courses of fludarabine plus prednisone, no residual disease was detected by flow cytometry in 89% of the CRs, 51% of the nCRs, and 19% of the PRs. Clinical residual disease in PR patients with no residual disease detectable by flow cytometry was limited to lymph-adenopathy. Time to progression at 2 years was longer in CR and nCR patients having no residual disease detected by flow cytometry (84% v 39% 2-year progression-free survival, P less than .001). Posttreatment lg gene rearrangement analysis using JH, J kappa, and C lambda probes demonstrated no rearranged bands and a return to the germline configuration in five of seven CRs and two of eight nCRs studied. The molecular studies were concordant with the dual-parameter immunophenotype results and none of the patients who reverted to a germline DNA pattern after treatment have experienced relapse. The absence of detectable minimal residual disease by bone marrow biopsy, dual-color flow cytometry, and lg gene rearrangement analysis is achieveable in CLL with fludarabine and is predictive of the response duration.

Adult↗
PubMed1992

Practicality of molecular studies to evaluate small lymphocytic proliferations in endoscopic gastric biopsies.

Fifteen endoscopic gastric biopsies (GBx) from 12 patients with small lymphocytic infiltrates morphologically raising a differential of indeterminate lymphocytic infiltrate versus mucosa-associated lymphoid tissue (MALT) lymphoma were analyzed genotypically after frozen-section identification of the abnormal lymphocytic infiltrate. Frozen-section immunoperoxidase immunophenotyping was equivocal in each case. All patients had abdominal pain attributable to superficial gastric ulceration, most often antral, without peripheral lymphadenopathy or hepatosplenomegaly. Rearrangement of the immunoglobulin heavy-chain gene (JH-R, seven patients) or kappa light-chain gene (JK-R, eight patients), was found in eight GBx from eight (seven stage IAE; one stage IBE) of 12 patients, establishing, in conjunction with the histologic features, a diagnosis of low-grade B-cell lymphoma. This diagnosis had not been tenable on multiple prior GBx, ranging from one to five per patient, over intervals of 1 month to 6.5 years (median 4.5 months). The T-cell receptor beta-chain gene retained germline configuration in all cases. Insufficient DNA for molecular studies was extracted from the GBx of two patients, one with JK-R (JH-G) on subsequent GBx and one without further GBx. One patient had two GBx, each demonstrating a single additional band in HindIII digests hybridized with the JH probe. No rearrangements were detected in either the BamHI or the EcoRI digests. Uninvolved tissue from this patient was not available for the exclusion of restriction fragment length polymorphism. Three GBx (two patients) showed germline JH genes (JH-G). One had a partial gastrectomy (histology: MALT lymphoma) in 1981 followed by GBx in 1983 (histologically benign) and in 1990 (JH-G), and negative esophagogastroduodenoscopy (EGD) in 1991 without biopsy. The other patient (two GBx with JH-G) had multiple subsequent abnormal EGD, but no biopsies since December 18, 1990. Adequate DNA for gene rearrangement studies can be extracted from GBx samples weighing as little as 20 mg. The two samples with insufficient DNA weighed 1 and 16 mg, respectively. Practically speaking, the remainder of a frozen block from a single GBx is adequate, thus allowing the screening of multiple endoscopic GBx by sequential frozen sections to determine which one contains the most extensive lymphocytic infiltrate for molecular study. Consistent results are obtained on samples weighing 40 to 60 mg. This method is a suitable alternative to kappa/lambda frozen-section immunoperoxidase immunostaining, which can be uninterpretable on endoscopic biopsies or small biopsies from other sites.

Adult↗
PubMed1990

Extended en bloc resection of a primary mediastinal parathyroid carcinoma.

Parathyroid carcinoma is a rare endocrine tumor infrequently seen in the mediastinum. This report describes a patient who underwent en bloc resection of a primary mediastinal parathyroid carcinoma. The tumor originated from the thymus and extended from the aortic arch to the thyroid; local invasion suggested malignancy. En bloc resection of this carcinoma with all surrounding tissue provided local control of the tumor and relief of symptomatic hypercalcemia.

Carcinoma↗
PubMed1990

The value of immunophenotyping on paraffin sections in the identification of T-cell rich B-cell large-cell lymphomas: lineage confirmed by JH rearrangement.

Immunophenotyping of lymphomas using paraffin-embedded lymphoid tissue, not previously distorted by frozen section, is useful in identifying the large neoplastic B cells that may be in the minority in T-cell rich B-cell lymphoma (TCRBCL). Even in cases in which frozen tissue sections are available, the improved morphology in unfrozen sections allows the proper classification of these lymphomas as large cell and identifies their B-cell lineage, which is important for clinical therapeutic studies. Seven cases initially believed to be diffuse mixed cell lymphoma of possible peripheral T-cell lineage showed the large cells to be immunoreactive with L-26 (pan B-cell marker) with the majority of smaller lymphocytes immunoreactive for UCHL-1 and Leu-22 (pan T-cell markers). K/lambda immunostaining on frozen sections was equivocal. In these cases, the diagnosis of large-cell lymphoma of B-cell lineage was confirmed by detection of immunoglobulin heavy- (all seven cases) and light- (six of seven cases) chain gene rearrangements, with germ-line configuration of the T-cell receptor beta-chain gene (all cases). Some cases of TCRBCL may not show detectable rearrangement of the immunoglobulin genes because of the low concentration of neoplastic cells in the samples submitted. The presence of rearrangements in these seven cases, however, supports the diagnosis of TCRBCL based on paraffin immunophenotyping when frozen tissue is not available or when molecular studies are not feasible. Although these seven cases are classified as large-cell lymphoma, an intermediate-grade lymphoma, the influence of the reactive T-cell population on the clinical behavior will require follow-up studies.

Adult↗
PubMed1990

Developmental and differential regulation of human MPO gene in leukemic cells.

Northern blot analysis of RNA isolated from HL-60 cells before and after differentiation induction by TPA and DMSO showed that four MPO mRNA species (3.3, 3.1, 2.7, and 2.5 kb, respectively designated alpha 1, beta 1, alpha 2, and beta 2) are expressed in HL-60 cells. However, alpha 2 and beta 2 lack part of the 3' end sequence due to different polyadenylation sites. The steady state levels of alpha 2 and beta 2 MPO mRNA increase significantly after 1 hr of induction, while all four MPO mRNA species decrease dramatically after 10 hr of induction. Our results demonstrate that MPO gene expression is developmentally and differentially regulated. Northern blot analysis of RNA isolated from blast samples of acute myelogenous leukemia (M0-M5) and chronic lymphocytic leukemia (CLL) patients indicate that four MPO mRNA species are expressed in M1-M4 but are undetectable in M5 and CLL. Primer extension and S1 nuclease protection analysis of the MPO mRNA revealed a single transcription initiation site for the MPO gene.

Base Sequence↗
PubMed1988

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↗
PubMed1988

Immunoglobulin gene rearrangement and its implications for the study of B-cell neoplasia.

Molecular biologic investigation of the process of immunoglobulin gene rearrangement has elucidated the mechanism of immunologic diversification and has provided essential tools for the study of B-cell neoplasia. The use of immunoglobulin gene probes has permitted a clearer understanding of B-cell malignancies, but has also raised new questions and pointed out new directions for ultimately clarifying the mechanism of B-cell transformation. Thus, we have a difficult challenge ahead, but with our present knowledge, we are in a better position than ever to address critical issues relating to the genesis of lymphoid neoplasia.

Animals↗
PubMed1985

Philadelphia chromosome-negative chronic myelogenous leukaemia: a morphological reassessment.

Morphological re-examination of 25 cases classified as Ph1-negative chronic myelogenous leukaemia (CML), with particular attention to the recent French-American-British (FAB) group proposals for the diagnosis of the myelodysplastic syndromes, led to reclassification of all but one of these cases. Upon review of pretreatment material, seven of the 25 cases (28%) were considered to represent myeloproliferative and reactive conditions other than CML. Of the remaining 18 cases, 17 (94%) were reclassified as myelodysplastic syndromes (MDS). These included one case of refractory anaemia (RA), three of refractory anaemia with excess of blasts (RAEB), four of RAEB in transformation (RAEBT), and nine of chronic myelomonocytic leukaemia (CMMoL). Haematological findings in these 17 patients were compared to those in 50 randomly selected patients with Ph1-positive CML. Whereas an absolute basophilia in the peripheral blood was a nearly constant feature in the Ph1-positive group, it was lacking in all but one of the patients with myelodysplastic syndromes. Differences in the pattern and degree of dysplasia were also noted. Only one of the 25 cases studied was considered morphologically and clinically indistinguishable from Ph1-positive CML. It appears that Ph1-negative CML constitutes a heterogeneous group of prognostically distinct disorders and that, in most instances, careful morphologic examination will permit precise classification.

Anemia, Aplastic↗
PubMedDate not supplied

Primary mediastinal large cell lymphoma.

PURPOSE: Primary mediastinal large cell lymphoma PMLCL is a recently described entity which has provoked considerable interest lately. The unique immunophenotype of the malignant cell, as well as conflicting reports regarding its response to therapy, prompted us to review the current literature focusing on the pathological and clinical aspects of this disease. DESIGN: We reviewed the current literature that contained details on the clinical presentation, pathological profile and clinical outcome. RESULTS: Most reports agree that PMLCL typically affects a young female population and presents with symptoms related to compression of mediastinal structures. Pathologically, the malignant cells may arise from a distinctive thymic medullary B cell subpopulation which is characterized by the following phenotype: CD19+, CD21-, CD20+, CD22+. Alterations of c-myc and lack of expression of HLA class 1 antigens on the tumour cell surface have been described. Response to treatment and clinical outcome have varied from one series to another and is possibly explained by the small number of patients in most series and by the heterogeneity of therapy. In general, the outcome does not appear to be worse than that of other large cell lymphomas although, given the young age of these patients, it might be expected to be more favourable. CONCLUSIONS: Primary mediastinal large cell lymphoma is a distinct clinico-pathological entity characterized by: (1) a predominance of young adults; (2) female predominance (female/male ratio of 2:1) in contrast to the other large cell lymphomas; (3) CD19+/CD21- immunophenotype; (4) absence of HLA-class 1 antigen expression; (5) possible involvement of c-myc; (6) frequent dissemination at relapse to unusual anatomic sites in a pattern reminiscent of Burkitt's lymphoma. The role of radiotherapy and the optimal treatment for this disorder are issues that remain unresolved.

Antineoplastic Combined Chemotherapy Protocols↗