Biomedical subjects

R K Brynes

Publications and source records attributed to R K Brynes.

At least 19 recordsLinked to original sources

PubMed1999

Using fluorescence-based human androgen receptor gene assay to analyze the clonality of microdissected dendritic cell tumors.

The clonality of dendritic cell proliferations arising in patients with previously diagnosed B-cell non-Hodgkin lymphoma has not been determined. The highly polymorphic human androgen receptor gene (HUMARA) can be used to assess the pattern of X-chromosome inactivation and, hence, the clonality of tumors in female patients. In this study, specimens from 2 female patients with dendritic cell tumor following low-grade B-cell non-Hodgkin lymphoma were analyzed. Microdissection was performed on tissue sections to obtain representative tissues for analysis. The HUMARA polymerase chain reaction was modified to include a fluorochrome (6-carboxyfluorescein)-labeled primer so the product could be assessed with the ABI Genescan Analysis program for the Macintosh (Applied Biosystems, Foster City, Calif). Our results indicate that dendritic cell proliferations associated with low-grade B-cell non-Hodgkin lymphoma are clonal lesions. Previous microdissection is very helpful in obtaining the desired cell populations for study. The use of a fluorescent primer coupled with the Genescan System is a novel, highly sensitive, quantitative system that avoids the use of radioactive materials.

Cell Division↗

PubMed1999

Untreated chronic lymphocytic leukemia concurrent with or followed by acute myelogenous leukemia or myelodysplastic syndrome. A report of five cases and review of the literature.

Although it has been known that patients with chronic lymphocytic leukemia (CLL) have a higher frequency of second malignant neoplasms, the development of acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) in these patients is extremely rare. Most reported cases have been therapy-related. In this article, we report the clinical and immunophenotypic features of 5 cases of untreated CLL concurrent with or followed by the development of AML or MDS. All 5 patients were men, with ages ranging from 57 to 87 years (mean, 73.8 years). Four patients had AML and 1 patient had refractory anemia with ringed sideroblasts. In the 4 cases of AML and CLL, 2 distinct cell populations (i.e., myeloblasts and lymphocytes) were identified morphologically and/or immunophenotypically. Our findings support that this rare concurrence of AML or MDS and untreated CLL may represent 2 separate disease processes.

Aged↗

PubMed1999

Acute lymphoblastic leukemia. Survey of immunophenotype, French-American-British classification, frequency of myeloid antigen expression, and karyotypic abnormalities in 210 pediatric and adult cases.

Immunophenotypic studies are essential to distinguish acute lymphoblastic leukemia (ALL) from minimally differentiated acute myeloid leukemia (AMLM0) and to classify ALL into immunologic subtypes. Frequently, immunophenotyping identifies myeloid antigen expression in ALL, causing a potential diagnostic problem. To evaluate the immunophenotype of ALL, we studied 210 cases of pediatric and adult ALL by flow cytometry and compared the results with the French-American-British (FAB) Cooperative Group classification and the karyotypic findings. Myeloid-associated antigens were expressed in 78 (45.6%) of precursor B-cell ALL cases. Pediatric precursor B ALLs had a higher frequency of myeloid antigen expression than did adult cases. All mature B-cell ALL cases were negative for TdT and myeloid antigens. Myeloid antigen expression was less frequent in T-cell ALL cases compared with precursor B-cell ALL cases. Of the 192 cases submitted for cytogenetic analysis, 147 were abnormal. The most common chromosomal translocation was the Philadelphia chromosome, which was more likely to have L2 blast morphology and a precursor B immunophenotype. Myeloid antigen expression was present in 70.8% of Ph-positive cases (P = .008). Chromosome rearrangements involving 11q23 also showed an increased frequency of myeloid antigen expression. Chromosome translocations involving regions of T-cell receptor genes were present in 24% of T-cell ALL cases. A high percentage of ALL cases, however, had various other cytogenetic abnormalities, many of which involved less well-studied chromosomal regions.

Adolescent↗

PubMed1999

Intravascular large B-cell lymphoma. A report of five cases initially diagnosed by bone marrow biopsy.

We report 5 cases of intravascular lymphoma (IVL) initially diagnosed by bone marrow aspiration and biopsy. Each patient had generalized symptoms; 1 also had neurologic deficits. CBC counts revealed anemia (4 patients), thrombocytopenia (4 patients), or mild leukopenia (1 patient). The bone marrow biopsy specimen was diagnostic in each case. Lymphoma cells were present in small groups or single file in sinusoids (in 1 patient, sinusoids were distended markedly by IVL) and were detected in bone marrow aspirate smears (4 patients) and peripheral blood smears (all patients). Immunohistochemical studies demonstrated that every neoplasm was of B-cell lineage, CD20+, positive for other B-cell antigens, and CD3- or CD43-. Immunophenotypic studies revealed at least 2, and possibly 3, distinct immunophenotypic groups of B-cell IVL: CD20+ CD5+ (3 neoplasms), CD20+ CD5- CD10+ (1 neoplasm), and CD20+ CD5- CD10 unknown (1 neoplasm). B-cell IVL may be detected by morphologic examination of peripheral blood and bone marrow, and involvement of these sites may be more common than is reported in the literature. Immunophenotypic studies are helpful in establishing the diagnosis and suggest that B-cell IVL is a heterogeneous group of neoplasms that may arise from more than 1 normal B-cell precursor.

Aged↗

PubMed1999

Cyclin D1 overexpression in Spitz nevi: an immunohistochemical study.

The morphologic distinction between Spitz nevus and malignant melanoma can be difficult. Because cyclin D1 has been reported to be overexpressed in malignant melanomas, but not in common acquired nevi, we hypothesized that cyclin D1 might be a useful marker to distinguish Spitz nevi from malignant melanoma. Thus, we assessed for cyclin D1 expression in 11 Spitz nevi (10 compound and 1 intradermal) and 9 malignant melanomas (4 Clark stages I-III and 5 Clark stages IV-V) using an immunohistochemical method and routinely fixed and processed tissues. The cyclin D1 results were arbitrarily divided into three groups: 0% to 10%, >10% to 25%, and >25%. We confirmed the observations reported previously by others that cyclin D1 is expressed in malignant melanomas but not in common acquired nevi. Unexpectedly, a relatively high number of cyclin D1-positive cells (i.e., >10%) was also found in all cases of Spitz nevus. However, unlike malignant melanoma, the cyclin D1 positivity in Spitz nevi was present in a zonal pattern. In other words, the number of cyclin D1-positive cells decreased as the lesion extended more deeply, with the number of positive cells in the reticular dermis being less than that in the papillary dermis. Fluorescence in situ hybridization methods were used to assess amplification of 11q13, the locus harboring the cyclin D1 gene, in four cases of Spitz nevus; all were disomic. Using the antibody MIB-1, we compared cyclin D1 expression to the proliferation rate in Spitz nevi. Despite the high cyclin D1 positivity, all Spitz nevi had a relatively low number of MIB-1-positive cells (mean=3.2%), which was significantly lower than that of malignant melanomas (mean=15.3%) (p < 0.001). Thus, unlike malignant melanoma, there appears to be a dissociation between cyclin D1 overexpression and cell proliferation in Spitz nevi.

Carrier Proteins↗

PubMed1999

Differential expression of cyclin D1 in breast papillary carcinomas and benign papillomas: an immunohistochemical study.

OBJECTIVES: Distinguishing intraductal papilloma from papillary carcinoma of the breast can be difficult using histologic criteria. Since cyclin D1, a G1 cell-cycle regulatory protein, is detectable immunohistochemically in a subset of breast carcinomas but not in benign breast tissues, we hypothesized that cyclin D1 immunoreactivity may be a marker for identifying papillary carcinoma. METHODS: Using an immunohistochemical method, we assessed for cyclin D1 expression in 8 breast papillomas and 6 papillary carcinomas, all of which were formalin fixed, routinely processed, and paraffin embedded. Cyclin D1 positivity also was compared with the overall proliferation rate, which was assessed by using the proliferation marker Ki-67. In each case, a 200-cell count was performed to obtain the percentage of cells positive for these 2 markers. RESULTS: The percentage of cyclin D1-positive cells was significantly higher in papillary carcinomas (89%+/-18%; range, 53%-98%) than in papillomas (8%+/-7%; range, 0%-19%). This difference was highly statistically significant (P < .0001). Although the difference in Ki-67 positivity between these 2 groups was also statistically significant (P = .01), separation of papillary carcinomas and papillomas by Ki-67 immunoreactivity was less clear because of overlapping values between groups: 13% +/-6%; range, 9% to 23% for papillary carcinomas versus 8%+/-2%; range, 6% to 12% for papillomas. CONCLUSIONS: These results support the notion that cyclin D1 is a useful marker for distinguishing breast papillomas from papillary carcinomas. The marker Ki-67 is also helpful, but is less useful than cyclin D1, owing to the overlap in Ki-67 results in papillomas and papillary carcinomas.

Adult↗

PubMed1999

Expression of cyclin D1 in parathyroid carcinomas, adenomas, and hyperplasias: a paraffin immunohistochemical study.

In this study, we assessed the frequency of cyclin D1 protein expression in normal and neoplastic parathyroid tissue (10 parathyroid carcinomas, 28 adenomas, 18 hyperplasias, and 32 normal parathyroid glands) with use of a monoclonal anticyclin D1 antibody and a heat-induced epitope retrieval method. Overexpression of cyclin D1 was identified in 10 (91%) of 11 biopsy specimens from 10 patients with parathyroid carcinomas and in 11 (39%) of 28 parathyroid adenomas. In addition, 11 (61%) of 18 cases of parathyroid hyperplasia also expressed cyclin D1 protein, an observation not reported previously. These results confirm the high frequency of cyclin D1 expression in parathyroid carcinomas and adenomas. In addition, the results of this study indicate that overexpression of cyclin D1 protein is not limited to neoplastic proliferations of parathyroid tissue but is also seen in non-neoplastic proliferations of parathyroid gland. Cyclin D1 protein expression was rarely (<6%) present in normal parathyroid tissue.

Adenoma↗

PubMed1998

The immunophenotype of adult acute myeloid leukemia: high frequency of lymphoid antigen expression and comparison of immunophenotype, French-American-British classification, and karyotypic abnormalities.

Immunophenotyping has become common in the diagnosis and classification of acute leukemias and is particularly important in the proper identification of cases of minimally differentiated acute myeloid leukemia (AML-M0). To evaluate the immunophenotype of adult AML, 106 cases were studied by cytochemical analysis and by flow cytometry with a panel of 22 antibodies. The results were compared with the French-American-British (FAB) Cooperative Group classification, as well as with available cytogenetic data on each case. CD45, CD33, and CD13 were the most commonly expressed antigens (97.2%, 95.3%, and 94.3%, respectively). Lymphoid-associated antigens were expressed in 48.1% of cases. CD20 was the most commonly expressed lymphoid antigen (17%), although often expressed in only a subpopulation of leukemic cells, followed by CD7 (16%), CD19 (9.8%), CD2 (7.5%), CD3 (6.7%), CD5 (4.8%), and CD10 (2.9%). Some immunophenotypes correlated with FAB type, including increased frequency of CD2 expression in AML-M3; lack of CD4, CD11c, CD36, CD117, and HLA-DR expression in AML-M3; increased frequency of CD20 and CD36 expression and lack of CD34 expression in AML-M5; increased frequency of CD5 expression in AML-M5a; and increased frequency of CD14 expression in AML-M5b, when compared with all other AMLs (P < .05). When compared with AML-M5b, AML-M5a demonstrated a lack of CD4 expression and a high frequency of CD117 expression. Complete morphologic and cytogenetic agreement between AML-M3 and t(15;17) was present, and four of five cases of AML-M4Eo demonstrated inv(16). The remaining case of M4Eo was characterized by a 6;9 translocation, and two other inv(16) cases were not classified as M4Eo. Expression of CD2 was present in two t(15;17) cases and in one inv(16) case, but expression of this antigen was not restricted to AML cases with these karyotypic abnormalities. Similarly, expression of CD19 was not specific for t(8;21) AML. All t(8;21) leukemias demonstrated M2 morphology. With the exception of M3, M4Eo, and a subgroup of M2 leukemias, the FAB classification does not appear to define cytogenetically distinct disease groups in adult AML. Immunophenotypically distinct profiles were identified in the M3 and M5 morphologic groups of the FAB classification. Immunophenotyping studies are helpful in the determination of myeloid lineage. In general, however, they are not sufficiently specific alone to be useful in precisely identifying either FAB or cytogenetically defined disease subtypes.

Acute Disease↗

PubMed1998

Surface immunoglobulin light chain-positive acute lymphoblastic leukemia of FAB L1 or L2 type: a report of 6 cases in adults.

Acute lymphoblastic leukemia (ALL) of B-cell lineage may be classified using the French-American-British (FAB) classification as L1, L2, or L3 type. L1 and L2 ALLs characteristically express terminal deoxynucleotidyl transferase (TdT) and are surface immunoglobulin (sIg)-negative. In contrast, L3 ALL is typically TdT-negative and sIg-positive. However, in a few large studies of children with ALL, sIg expression has been reported in less than 2% of L1 and L2 neoplasms. In these sIg-positive cases, IgM usually has been detected, with Ig light chain in a subset of tumors. Surface Ig expression in L1 or L2 ALL in adults is extremely rare; we found only 1 case report in the English literature. We report 6 cases of L1 or L2 ALL with an unusual immunophenotype arising in adults. In each tumor, the neoplastic cells expressed monotypic sIg light chain (4 lambda, 2 kappa) and TdT. Three tumors expressed CD34. Cytogenetic studies in 4 cases at diagnosis or relapse revealed no evidence of chromosomal translocations involving the c-myc locus, such as the t(8;14), t(2;8), or t(8;22). Three patients responded completely to chemotherapy and are alive; follow-up ranges from 18 to 57 months. Three patients died at 3, 13, and 14 months after diagnosis.

Adolescent↗

PubMed1998

Immunohistochemical detection of E2F-1 in non-Hodgkin's lymphomas: a survey of 124 cases.

E2F-1 is a transcription factor that mediates cell cycle progression from the G1 to S phase and is normally regulated by a group of proteins, including cyclin D1. Although deregulation of E2F-1 is implicated in neoplastic transformation, in situ examination of this protein has not been performed to date. Using an immunohistochemical technique applied to routinely fixed, paraffin-embedded tissue sections, we evaluated E2F-1 expression in reactive lymphoid tissues and in 124 cases of non-Hodgkin's lymphoma (NHL) of various types. In reactive lymphoid tissues, E2F-1 was expressed predominantly by large noncleaved cells in germinal centers and by a small subset of cortical thymocytes. Mantle zones and splenic marginal zones were negative. Among the NHLs, four types had a relatively high percentage (> 20%) of E2F-1-positive cells: mantle cell lymphoma (19 of 19), lymphoblastic lymphoma (5 of 5), small noncleaved cell lymphoma (4 of 6), and hepatosplenic gammadelta T-cell lymphoma (3 of 3). The consistent detection of many E2F-1-positive cells in mantle cell lymphoma is in contrast to other small B-cell NHLs (n = 29), which had relatively few (< 10%) E2F-1-positive cells. This finding suggests that immunohistochemical staining for E2F-1 as a supplement to the existing markers, such as cyclin D1, might be useful in the differential diagnosis of NHLs composed of small B cells.

Carrier Proteins↗

PubMed1998

Expression of the cell-cycle-related proteins E2F-1, p53, mdm-2, p21waf-1, and Ki-67 in multiple myeloma: correlation with cyclin-D1 immunoreactivity.

Approximately 30% of multiple myelomas (MMs) express cyclin D1 when assessed using immunohistochemical techniques. Cyclin D1 expression correlates with greater tumor burden in MM, because cyclin D1-positive cases are more frequently associated with extensive bone marrow involvement, i.e., high pathologic stage, than are cyclin D1-negative cases. The mechanisms that explain this association are unknown. To explore other differences between cyclin D1-positive and cyclin D1-negative MMs, we assessed 59 MMs immunohistochemically for several G1 cell-cycle regulatory proteins, including cyclin D1, E2F-1, p53, mdm-2, and p21waf-1, using routinely fixed and processed, paraffin-embedded bone marrow specimens. Twenty MMs (34%) were cyclin D1 positive, and 39 (66%) were cyclin D1 negative. Eighteen (90%) of 20 cyclin D1-positive MMs were Stage III, in contrast to 19 (49%) of 39 cyclin D1-negative MMs (P = .003). Cyclin D1-positive MMs were more likely to express E2F-1 (16/20 vs. 4/39, P < .001), p53 (11/20 vs. 10/39, P = .041), and p21waf-1 (12/20 vs. 7/39, P = .003). There was no significant difference in mdm-2 expression between these groups. We also assessed proliferation rate using an antibody specific for the Ki-67 antigen. A relatively high percentage (> 20%) of Ki-67-positive cells was found in cyclin D1-positive MMs compared with cyclin D1-negative MMs (13/20 vs. 3/39, P < 0.001). These results suggest that cyclin D1-positive MMs are more likely to possess additional derangements involving other G1 cell-cycle regulatory proteins. We speculate that these abnormalities might result in increased proliferation, thereby explaining the correlation between cyclin D1 expression and greater tumor burden.

Bone Marrow Cells↗

PubMed1998

Intravascular large B-cell lymphoma: the CD5 antigen is expressed by a subset of cases.

The CD5 antigen is a T-cell associated marker that is also usually expressed by two B-cell neoplasms, chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma. We observed CD5 antigen expression in a subset of cases of intravascular large B-cell lymphoma (IVLBL), and we report here five cases. The patients, two men and three women, ranged in age from 59 to 81 years. Biopsy specimens were obtained from kidney, lung, bone marrow, abdominal wall, and neck, the latter involving a lymphangioma. All of the cases had histologic features typical of IVLBL, with large and atypical lymphoid cells located predominantly within blood vessels. Immunohistochemical studies performed using routinely fixed, paraffin-embedded tissue sections showed that the neoplastic cells were B cells, positive for the CD20 antigen and negative for the CD3 or CD43 antigens. All cases were also positive for the CD5 antigen. One case had an immunoglobulin heavy chain gene rearrangement shown by using a polymerase chain reaction method. The finding of CD5 antigen expression in a subset of IVLBL cases adds to other evidence in the literature suggesting that IVLBL is a heterogeneous entity. We considered the possibility that these cases were related to or represented unusual histologic forms of transformation from either chronic lymphocytic leukemia/small lymphocytic lymphoma or mantle cell lymphoma. All of the cases, however, were negative for the CD23 antigen and cyclin D1 (bcl-1) protein, which is evidence against this interpretation. The biologic significance of CD5 antigen expression in cases of IVLBL is uncertain. These neoplasms might arise from a separate lineage of CD5-positive B cells or from a specific, early stage of B-cell differentiation. Alternatively, some investigators have suggested that CD5 antigen expression by B cells is a marker of activation.

Aged↗

PubMed1998

Cyclin D1 expression in renal carcinomas and oncocytomas: an immunohistochemical study.

Cyclin D1 plays an important role in cell cycle progression from G1 to S phase. Cyclin D1 overexpression has been identified in many human neoplasms, including a variety of carcinomas. A systematic study of cyclin D1 expression in renal carcinomas and oncocytomas has not been reported. Ninety-six renal epithelial neoplasms, 78 renal carcinomas (45 clear-cell, 18 papillary, and 15 chromophobe), and 18 oncocytomas were analyzed immunohistochemically using routinely fixed tissue sections and a cocktail of two monoclonal anti-cyclin D1 antibodies. One thousand cells were manually counted, and the percentage of cyclin D1 positive cells was calculated. Fluorescence in situ hybridization studies using chromosome 11 centromeric and 11q13 specific probes were performed on a subset of clear-cell carcinomas and oncocytomas. Cyclin D1 immunoreactivity was observed in 23 (51%) of 45 clear-cell, 5 (28%) of 18 papillary, and 2 (13%) of 15 chromophobe carcinomas. Nine (50%) of 18 oncocytomas were positive for cyclin D1. Cyclin D1 expression in clear-cell carcinomas did not correlate with survival. Fluorescence in situ hybridization studies on eight clear-cell carcinomas and seven oncocytomas revealed normal chromosome 11 number and no evidence of amplification of the 11q13 locus. Thus, cyclin D1 can be immunohistochemically demonstrated in approximately one-half of renal oncocytomas and clear-cell carcinomas and is less frequent in papillary and chromophobe carcinomas. The mechanism of cyclin D1 expression is unknown, but it does not seem to be related to extra copies of chromosome 11 or to gene amplification.

Adenocarcinoma↗

PubMed1998

The immunophenotype of blast transformation of chronic myelogenous leukemia: a high frequency of mixed lineage phenotype in "lymphoid" blasts and A comparison of morphologic, immunophenotypic, and molecular findings.

Immunophenotypic studies have a limited role in the diagnosis of chronic myelogenous leukemia (CML) but are increasingly being used in CML blast transformation (BT). Determination of the cell lineage of CML blasts is clinically important because patients with lymphoid blast transformation have a better response to chemotherapy and longer survival than those with other lineages. We studied the morphologic, cytochemical, immunophenotypic, cytogenetic, and molecular features of 20 patients with Philadelphia chromosome-positive CML and more than 10% blast cells in peripheral blood or bone marrow. The blasts were morphologically heterogeneous. CD33 was expressed in 19 cases (95%), followed by CD13 (85%), CD11c (80%), CD36 (60%), CD117 (40%), and CD15 (30%). Seven cases (35%) had a precursor-B lymphoid immunophenotype, and 13 (65%) had a predominantly myeloid immunophenotype. Of the former group, of which only one had a pure lymphoid phenotype, terminal deoxynucleotidyl transferase (TdT) and CD19 were expressed in 100%, CD10 in 85.7%, and CD20 in 14.3%. Of the latter group, all 13 expressed from 3 to 6 myeloid antigens, with 46.2% myeloperoxidase positive and 69.2% CD61 positive. No cases were interpreted as T lineage, but the T-cell antigens CD3, CD4, CD5, and CD7 were expressed in 5.0, 40.0, 5.3. and 30.0% of all cases, respectively. In most cases, the immunophenotype of the CML blasts could not be predicted from their morphologic features. Polymerase chain reaction showed that 80.0% of the lymphoid group and 37.5% of the myeloid group had immunoglobulin heavy-chain gene rearrangements. The frequent lineage infidelity of the blast cells in CML BT seems to be related to the stem cell origin of this disorder. Such lineage infidelity, however, makes classification of many cases difficult and the significance of and criteria for biphenotypic blast crisis of CML is yet to be determined.

Adult↗

PubMed1997

Acute myeloid leukemia with t(6;9) (p23;q34): association with myelodysplasia, basophilia, and initial CD34 negative immunophenotype.

The translocation (6;9)(p23;q34) is a rare cytogenetic aberration found in patients with acute myeloid leukemia (AML). The clinical, morphologic, and immunophenotypic findings of eight t(6;9) acute leukemias are described. The patients included six men and two women with a mean age of 38.5 years. The leukemias were classified in the French-American-British (FAB) system as AML FAB M2 in four cases and as FAB M4 in four cases. Underlying myelodysplasia was evident in six cases. Bone marrow basophilia was found at presentation in six of the seven cases studied. In two cases with basophilia, darkly stained granules were also present in many eosinophils. In one case, initial basophilia was absent, but was present at relapse, as were eosinophils containing darkly stained granules. Iron stains were available in five cases; four showed increased incorporation and three had ringed sideroblasts. All cases studied by flow cytometry (six at presentation and three at relapse) expressed CD13, CD33, and human leukocyte antigen-DR. At presentation, five cases were CD34 negative. In one case at presentation, a subset of blasts (18%) weakly expressed CD34. Three cases studied at relapse were positive for CD34. Two of seven cases studied were terminal deoxynucleotidyl transferase positive. The t(6;9)(p23;q34) was the only cytogenetic abnormality in five cases. Trisomy 8 was found in two cases, and ring 12 was present in one case. Three patients are living with refractory leukemia 6 weeks to 6 months after initial diagnosis, and three patients died of complications of allogeneic bone marrow transplantation. Only one patient is alive without evidence of disease 3 years after bone marrow transplantation. t(6;9) leukemia is an unusual type of AML that is associated with poor prognosis, early age of onset, basophilia, myelodysplasia with frequent ringed sideroblasts, and a CD34-negative initial phenotype.

Acute Disease↗

PubMed1997

Cyclin D1 immunohistochemical staining is useful in distinguishing mantle cell lymphoma from other low-grade B-cell neoplasms in bone marrow.

The distinction between mantle cell lymphoma (MCL) and other low-grade B-cell neoplasms is important because MCL has a more aggressive clinical course. In bone marrow biopsy specimens, this distinction can be especially difficult. We examined 70 bone marrow biopsy specimens involved by various B-cell lymphoid neoplasms to assess the utility of cyclin D1 immunostaining in distinguishing MCL from other B-cell lymphoproliferative disorders. We used a cocktail of two monoclonal anti-cyclin D1 antibodies and a heat- and sonication-induced epitope retrieval procedure. The neoplasms assessed included MCL (32 cases), small lymphocytic lymphoma/chronic lymphocytic leukemia (18 cases), follicular lymphoma (11 cases), hairy cell leukemia (5 cases), splenic marginal zone lymphoma (2 cases), and small lymphocytic lymphoma with plasmacytoid differentiation (2 cases). The diagnosis of MCL in bone marrow was confirmed by review of the original diagnostic biopsy specimens along with additional data, such as immunophenotypic or molecular studies. Most MCL (23/32; 72%) cases expressed cyclin D1 protein. In contrast, one case of small lymphocytic lymphoma/chronic lymphocytic leukemia (1/18; 6%) and one case of hairy cell leukemia (1/5; 20%) expressed cyclin D1 protein. These findings demonstrate that immunostaining for cyclin D1 protein expression is useful in distinguishing MCL from other B-cell lymphoid neoplasms in the bone marrow.

Antibodies, Monoclonal↗

PubMed1997

Myelodysplastic syndrome occurring after autologous bone marrow transplantation for lymphoma. Morphologic features.

Clonal karyotypic abnormalities characteristic of myelodysplastic syndrome (MDS) occur in up to 18% of patients who undergo autologous bone marrow transplantation (auto-BMT) for the treatment of lymphoma. Morphologic changes are often subtle and may not meet the French-American-British Cooperative Group criteria for MDS. We retrospectively assessed dysplastic changes in peripheral blood and bone marrow specimens obtained before and after transplantation from nine patients and correlated them with karyotype and survival. All patients had normal cytogenetic study results before transplantation and had clonal karyotypic abnormalities develop after auto-BMT. Four patients (with aggressive MDS) survived a short time and died of acute myelogenous leukemia or MDS-related complications, four (with indolent MDS) had a prolonged survival period, and one patient died of recurrent lymphoma. The group with aggressive MDS had significantly more bone marrow trilineage dysplasia before auto-BMT than did the group with indolent MDS or cytogenetically normal auto-BMT controls, suggesting that stem cell damage occurred before transplantation and was not detected by pretransplantation cytogenetic analysis. Comparatively greater dyserythropoiesis and dysmegakaryopoiesis were present after transplantation; these changes were similar to those seen in de novo MDS. Posttransplantation dysplasia in the group with indolent MDS was analogous to the atypia related to the transplantation process.

Adult↗

PubMed1997

Cyclin D1 protein in multiple myeloma and plasmacytoma: an immunohistochemical study using fixed, paraffin-embedded tissue sections.

In this study, we analyzed 69 plasma cell neoplasms, including 54 multiple myelomas (MMs), 3 cases of plasma cell leukemia, and 12 plasmacytomas, for expression of cyclin D1 protein using an immuno-histochemical method applied to routinely fixed, paraffin-embedded tissue sections. Cyclin D1 was expressed in 18 (26%) of 69 plasma cell neoplasms, including 16 (30%) of 54 MMs and 2 (17%) of 12 plasmacytomas. Three cases of plasma cell leukemia were negative. Cyclin D1 expression correlated with the cytologic differentiation and histologic stage of MM. Twelve (75%) of 16 MMs had intermediate or immature cytologic features and were histologic Stage III. With use of a polymerase chain reaction assay, we also analyzed six cases (three cyclin D1 positive, three cyclin D1 negative) for the t(11;14); one MM carried the t(11;14) and expressed cyclin D1 protein. We conclude that cyclin D1 expression occurs in approximately one-quarter of plasma cell neoplasms and correlates with the degree of cytologic differentiation and histologic stage. The relatively high frequency of cyclin D1 expression, compared with the less than 5% incidence of the t(11;14) detected by conventional cytogenetics reported in the literature, suggests that upregulation of cyclin D1 protein might be the result of mechanisms other than the t(11;14).

Adult↗