L.jeffrey Medeiros - Academia.edu (original) (raw)
Papers by L.jeffrey Medeiros
American Journal of Clinical Pathology, 2009
We report 2 cases of splenic postchemotherapy histiocyte-rich pseudotumor. Each patient had a his... more We report 2 cases of splenic postchemotherapy histiocyte-rich pseudotumor. Each patient had a history of diffuse large B-cell lymphoma, treated with multiagent chemotherapy. Computed tomography scans performed on both patients showed splenic masses. A positron emission tomography scan performed on 1 patient showed increased metabolic activity. The preoperative diagnosis in both patients was recurrent lymphoma, prompting splenectomy. The splenectomy specimens showed multiple, tan-white, firm nodules, up to 3.5 cm in diameter, that were histologically composed of central necrotic B cells (CD20+/CD3−), consistent with necrotic lymphoma, surrounded by numerous lipid-laden (xanthomatous) histiocytes. Clinical staging studies at the time of splenectomy showed no other sites of disease. We conclude that these histologic and immunophenotypic findings represent chemotherapy-induced tumor necrosis with a florid histiocytic reaction mimicking residual viable lymphoma. Others have used descript...
PubMed, Sep 1, 1997
In this study, we analyzed 69 plasma cell neoplasms, including 54 multiple myelomas (MMs), 3 case... more 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).
Archives of Pathology & Laboratory Medicine, 2014
The following changes have been made to this article since it was posted as an Early Online Relea... more The following changes have been made to this article since it was posted as an Early Online Release: 1. In the Results, ALK Rearrangement, Polysomy section: The following note that appeared under ''Absent'' was deleted: ***The FISH results are normal. This finding indicates that the tumor is unlikely to respond to therapy with crizotinib. This finding may also be due to the absence of tumor cells in the tested specimen. Clinicopathologic correlation is advised. 2. In the Methods, EGFR Mutational Analysis Testing Method section: In the note, ''codons'' was changed to ''exons.'' 3. In the Methods, KRAS Codons Assessed section: option ''146'' was deleted.
American Journal of Dermatopathology, Apr 1, 1999
The morphologic distinction between Spitz nevus and malignant melanoma can be difficult. Because ... more 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.
Archives of Pathology & Laboratory Medicine, Feb 1, 1999
Distinguishing intraductal papilloma from papillary carcinoma of the breast can be difficult usin... more 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. 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. 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. 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.
Archives of Pathology & Laboratory Medicine, Feb 1, 1999
Objectives.-Distinguishing intraductal papilloma from papillary carcinoma of the breast can be di... more Objectives.-Distinguishing intraductal papilloma from papillary carcinoma of the breast can be difficult using histologic criteria. Since cyclin D1, a G 1 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 Ͻ .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.
Blood, Nov 16, 2012
Abstract 1682 Background With the success of targeted oral tyrosine kinase inhibitor (TKI) therap... more Abstract 1682 Background With the success of targeted oral tyrosine kinase inhibitor (TKI) therapy, long-term/life-long therapy for patients with chronic myelogenous leukemia (CML) can now be envisaged. Dasatinib is a second generation TKI, which in a phase I clinical trial was found to be 100–300 times more potent at inhibiting tyrosine kinases than imatinib. In vitro data suggest that dasatinib therapy also may have a direct effect on bone metabolism by interfering with c-FMS, c-SRC and the PDGF-R pathways (Boufker et al, BMC Cancer 2010, 10:298). In this study, we evaluated the effects of dasatinib monotherapy on bone homeostasis of CML patients treated at our center between 2006 and 2011. The levels of traditional biomarkers of bone health, namely serum bone specific alkaline phosphatase isoenzyme (BAP) and osteoprotegerin (OPG) were measured and were correlated with morphometric assessment of bone marrow biopsy specimens (BM Bx). We also assessed for any correlations between bone homeostasis and the results of conventional cytogenetics and molecular analysis with respect to treatment response. Methods The study group included 23 patients with chronic phase CML without evidence of clonal evolution who were treated with dasatinib. The median age was 51 years (range, 25–63) with a male to female ratio of 1.5: 1. Four different treatment groups were assessed (20mg/day, 40 mg/day, 80 mg/day and 100 mg/day). We compared paired BM specimens, obtained at initial diagnosis and 12–51 months (mos) after commencing dasatinib therapy. We performed whole slide imaging (Philips) on routinely stained BM Bx and specimen compartments were quantified using an area pixel count algorithm (Image Pro Plus system Version 6.3, MediaCybernetics, Bethesda, MD, USA) to calculate trabecular bone volume as a percentage area. The morphometric results were correlated with the results of conventional cytogenetics and molecular analysis obtained every 3 mos after enrollment. We also performed competitive inhibition ELISA assays to measure serum levels of OPG (baseline and after 12/18 mos) and BAP (every 4 mos), respectively. Results With a median follow up of 24 mos (range 12–51mo), a significant increase in trabecular bone volume (TBV) was noted (p=0.022, Figure 1); 74% (17 pts) showed an increase in TBV on therapy, with an absolute increase of 5.2% (mean). Twelve of 16 pts (75%) evaluated had a decrease in OPG after 18 mos, which correlated in 90% of pts with an increase in TBV using a linear regression model (p= 0.0017, Figure 2). No significant difference was detected in TBV changes among the four dose groups. There was no significant trend in serum BAP levels, thus no statistical correlation was performed at this time point. All patients treated with dasatinib showed cytogenetic and molecular BCR-ABL1 response. There was no correlation between the degree of TBV change and either cytogenetic or molecular response (Figure 3) Conclusions: Our results indicate that within the therapeutic range for CML patients, dasatinib therapy promotes bone formation. However, there was no correlation between the dose levels studied and degree of bone formation and no correlation between TBV change and either cytogenetic or molecular response. The combination of digital image analysis and bone biomarkers enhances our understanding of bone homeostasis in patients on dasatinib. Further studies in a larger cohort of patients will be helpful to further validate our results. Figure 1 : mean and standard deviation of TBV for each visit. Figure 2 : correlation between “percent change TBV between visit 1 and visit 2” and 18 months OPG levels (linear regression model R2 =0.292, p= 0.0017) Figure 3 : association between “percent change in TBV between visit 1 and visit 2” and “Rate of PCR response change between 3 and 12 months” (Spearman correlation coefficient = −0.05; p =0.81) Disclosures: Cortes: Ariad: research support and consulting, research support and consulting Other; Pfizer: research support and consulting, research support and consulting Other; Novartis: research support and consulting, research support and consulting Other; BMS: research support and consulting Other.
PubMed, Nov 1, 1998
Cyclin D1 plays an important role in cell cycle progression from G1 to S phase. Cyclin D1 overexp... more 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.
PubMed, Oct 1, 1998
The CD5 antigen is a T-cell associated marker that is also usually expressed by two B-cell neopla... more 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.
Cancer, Oct 28, 2011
BACKGROUND: Isolated isochromosome (17q) is a rare cytogenetic abnormality in Philadelphia chromo... more BACKGROUND: Isolated isochromosome (17q) is a rare cytogenetic abnormality in Philadelphia chromosome-negative myeloid neoplasms, usually myelodysplastic and/or myeloproliferative neoplasms (MDS/MPN). De novo acute myeloid leukemia (AML) with isochromosome 17q has rarely been reported. The frequency of genetic mutations is unknown. METHODS: The authors assessed clinicopathologic, immunophenotypic, and molecular genetic features of 22 myeloid neoplasms with isolated isochromosome 17q. RESULTS: Fourteen patients presented as MDS/MPN; 8 as de novo AML. Most presented with leukocytosis, anemia, thrombocytopenia, and splenomegaly. Morphologically, all showed myelodysplastic and myeloproliferative features, including pseudo-Pelger-Huet-like neutrophils, micromegakaryocytic hyperplasia, hypercellularity, fibrosis, and osteosclerosis. Blasts were increased (median, 40% in de novo AML; 9% in MDS/MPN). Immunohistochemical assessment of proliferation and apoptosis rates in AML were similar to a matched group without isochromosome 17q. In most patients, isochromosome 17q occurred at time of blast transformation or disease progression. DNA sequencing revealed no mutation in the uninvolved TP53 allele. Mutational analyses showed rare mutations in NRAS (3 of 10), FLT3 (2 of 16), and JAK2 (1 of 18), and no mutations in NPM1 (0 of 15), KIT (0 of 4), and CEBPA (0 of 4). The median overall survival was 14.5 months for de novo AML, and 11.0 months for MDS/MPN. With a median follow-up of 8.5 months (range, 1.5-107 months), 15 died of disease, 6 had persistent disease, and 1 was in remission after bone marrow transplantation. CONCLUSIONS: The authors conclude that myeloid neoplasms with isolated isochromosome 17q represent a distinct clinicopathologic entity with myelodysplastic and myeloproliferative features, high risk of leukemic transformation, and wild-type TP53.
Clinical Lymphoma, Myeloma & Leukemia, Aug 1, 2016
We assessed patients with chronic myelogenous leukemia for serum Ca, PO4, bone alkaline phosphata... more We assessed patients with chronic myelogenous leukemia for serum Ca, PO4, bone alkaline phosphatase, N-telopeptide, osteoprotegerin levels and trabecular bone (TBA) in bone marrow (BM) specimens before and after treatment with dasatinib. We identified a significant increase in TBA % in post-dasatinib BM (p=0.022). This suggests that dasatinib therapy can increase TBA, without significant changes in bone and mineral metabolism. Introduction-Interferences with bone homeostasis and mineral metabolism have been described in patients taking imatinib for chronic myelogenous leukemia (CML) or gastrointestinal stromal tumors. Dasatinib is a potent second generation tyrosine kinase inhibitor (TKI), designed to inhibit ABL and SRC kinases while also interfering with the c-KIT, PDGF-R and STAT5 pathways. Patients and Methods-In this study, we use a multiparameter approach to examine the "off target effects" of dasatinib in 30 patients with CML treated between 2009 and 2012. We recorded serum calcium (Ca) and phosphate (PO4) levels, analyzed markers of bone formation (bone alkaline phosphatase/ BAP) and bone resorption (N-telopeptide/NTX), measured osteoprotegerin (OPG) levels and digitally analyzed changes in trabecular bone area (TBA) in paired bone marrow biopsy specimens (BM) before and after treatment. We correlated all findings with each other and with results of conventional cytogenetic and molecular analysis.
American Journal of Clinical Pathology, Aug 1, 1998
American Journal of Clinical Pathology, Apr 1, 1999
Immunophenotypic studies are essential to distinguish acute lymphoblastic leukemia (ALL) from min... more Immunophenotypic studies are essential to distinguish acute lymphoblastic leukemia (ALL) from minimally differentiated acute myeloid leukemia (AML-M0) 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. Myeloidassociated 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
Diagnostic Pathology: Molecular Oncology, 2016
Archives of Pathology & Laboratory Medicine, 2001
Objective.—We previously surveyed cyclin D1 expression in common acquired nevi, Spitz nevi, and m... more Objective.—We previously surveyed cyclin D1 expression in common acquired nevi, Spitz nevi, and malignant melanomas and reported that benign nevi maintain a zonal pattern of cyclin D1 expression, in contrast with malignant melanomas. Our aim was to extend those observations by examining cyclin D1 expression in dysplastic nevi. Methods.—Cyclin D1 overexpression in 23 dysplastic nevi was detected by an immunohistochemical technique. The extent of atypia of the nevi was graded as mild, moderate, or severe, using previously established criteria. Results.—Cyclin D1 overexpression in dysplastic nevi maintained a zonal pattern, similar to Spitz nevi. Cyclin D1 overexpression was greatest in the region of the epidermal-dermal junction and was significantly less prominent in the papillary and reticular dermis, suggesting that cyclin D1 expression is under cell control and correlates with maturation of nevus cells. Cyclin D1 overexpression also correlated with cytologic atypia, as dysplastic ...
American Journal of Clinical Pathology, 1998
Immunophenotyping has become common in the diagnosis and classification of acute leukemias and is... more 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-MO). 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, CDllc, 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-Acute leukemias are traditionally classified by a combination of morphologic and cytochemical features on the basis of criteria of the French-American-British (FAB) C o o p e r a t i v e G r o u p. 1 ' 2 The a d d i t i o n of immunophenotypic studies is valuable in both the confirmation and precise lineage classification of acute lymphoblastic leukemia, as well as in the detection of minimally differentiated acute myeloid
American Journal of Clinical Pathology, 1999
American Journal of Clinical Pathology, 1997
The distinction between mantle cell lymphoma (MCL) and other low-grade B-cell neoplasms is import... more 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 Dl immunostaining in distinguishing MCL from other B-cell lymphoproliferative disorders. We used a cocktail of two monoclonal anti-cyclin Dl 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
The American journal of surgical pathology, Jan 11, 2016
Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of lymphoma. Patients have a poor prognosis,... more Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of lymphoma. Patients have a poor prognosis, and there is no standard of care. We evaluated 28 HSTCL patients to determine factors that may be associated with outcome. There were 19 men and 9 women with a median age of 32.5 years. Most patients had massive splenomegaly, and bone marrow showed sinusoidal involvement by lymphoma. The HSTCL cells expressed γδ T-cell receptor (TCR) in 20 (74%), αβ TCR in 5 (19%), and neither in 2 (7%) patients (1 case not assessed). Conventional cytogenetics and/or fluorescence in situ hybridization analysis in 24 patients at diagnosis showed isochromosome 7q (i7q) in 10 (42%) and trisomy 8 in 8 (33%) patients. Median overall survival (OS) and event-free survival (EFS) were each 28.3 months. Serum bilirubin level ≥1.5 mg/dL, αβ TCR expression, and trisomy 8 each correlated significantly with shorter OS and EFS. Patients with HSTCL received a variety of chemotherapy regimens with no regimen better than...
Annals of Diagnostic Pathology, 2016
Patients with chronic myelogenous leukemia (CML) present typically with an elevated white blood c... more Patients with chronic myelogenous leukemia (CML) present typically with an elevated white blood cell count (WBC) and cytogenetic or molecular genetic evidence of t(9;22)/BCR-ABL1 fusion gene. Rarely, CML patients may present with a normal or mildly elevated WBC and are asymptomatic, and we describe 7 patients in this study. The WBC in these patients ranged from 3.6 to 14.3 K/mm(3) with 50% to 73% granulocytes and 0% blasts. In all patients, t(9;22)(q34;q11.2) was detected by conventional cytogenetics, and BCR-ABL1 fusion was shown, supporting the diagnosis of preleukemic CML (pre-CML). We compared these patients with a group of 5 cases of CML in chronic phase (CML-CP) and 5 bone marrow specimens with a leukemoid reaction (n=5). Reticulin, CD34, and CD61 immunostains were performed on all bone marrow biopsy specimens. Peripheral blood absolute basophilia (≥200/mm(3)) was noted in only 4 of 7 pre-CML cases, whereas it was present in all CML-CP cases and absent in leukemoid reaction cases. The mean ±SD of microvascular density of pre-CML cases (10.0±4.3 vessels/200× field) was twice that of leukemoid reaction cases (5.0±1.0) (P=.02; Student t test) but similar to that of CML-CP cases (12.5±3.6). Microvessels in pre-CML, highlighted by CD34, were tortuous with abnormal branching, although to a lesser extent than those found in CML-CP. Microvessels in leukemoid reaction were generally straight. The percentage of small, hypolobated megakaryocytes, highlighted by CD61 in pre-CML, was 40%, 3 times that found in leukemoid reaction cases (13%) but less than that of CML-CP cases (86%). We conclude that pre-CML should be suspected in patients with a normal to mildly elevated WBC and absolute basophilia. Bone marrow examination can usually distinguish pre-CML from a leukemoid reaction based on the percentage of small, hypolobated megakaryocytes; microvascular density; and morphologic features.
American Journal of Clinical Pathology, 2009
We report 2 cases of splenic postchemotherapy histiocyte-rich pseudotumor. Each patient had a his... more We report 2 cases of splenic postchemotherapy histiocyte-rich pseudotumor. Each patient had a history of diffuse large B-cell lymphoma, treated with multiagent chemotherapy. Computed tomography scans performed on both patients showed splenic masses. A positron emission tomography scan performed on 1 patient showed increased metabolic activity. The preoperative diagnosis in both patients was recurrent lymphoma, prompting splenectomy. The splenectomy specimens showed multiple, tan-white, firm nodules, up to 3.5 cm in diameter, that were histologically composed of central necrotic B cells (CD20+/CD3−), consistent with necrotic lymphoma, surrounded by numerous lipid-laden (xanthomatous) histiocytes. Clinical staging studies at the time of splenectomy showed no other sites of disease. We conclude that these histologic and immunophenotypic findings represent chemotherapy-induced tumor necrosis with a florid histiocytic reaction mimicking residual viable lymphoma. Others have used descript...
PubMed, Sep 1, 1997
In this study, we analyzed 69 plasma cell neoplasms, including 54 multiple myelomas (MMs), 3 case... more 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).
Archives of Pathology & Laboratory Medicine, 2014
The following changes have been made to this article since it was posted as an Early Online Relea... more The following changes have been made to this article since it was posted as an Early Online Release: 1. In the Results, ALK Rearrangement, Polysomy section: The following note that appeared under ''Absent'' was deleted: ***The FISH results are normal. This finding indicates that the tumor is unlikely to respond to therapy with crizotinib. This finding may also be due to the absence of tumor cells in the tested specimen. Clinicopathologic correlation is advised. 2. In the Methods, EGFR Mutational Analysis Testing Method section: In the note, ''codons'' was changed to ''exons.'' 3. In the Methods, KRAS Codons Assessed section: option ''146'' was deleted.
American Journal of Dermatopathology, Apr 1, 1999
The morphologic distinction between Spitz nevus and malignant melanoma can be difficult. Because ... more 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.
Archives of Pathology & Laboratory Medicine, Feb 1, 1999
Distinguishing intraductal papilloma from papillary carcinoma of the breast can be difficult usin... more 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. 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. 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. 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.
Archives of Pathology & Laboratory Medicine, Feb 1, 1999
Objectives.-Distinguishing intraductal papilloma from papillary carcinoma of the breast can be di... more Objectives.-Distinguishing intraductal papilloma from papillary carcinoma of the breast can be difficult using histologic criteria. Since cyclin D1, a G 1 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 Ͻ .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.
Blood, Nov 16, 2012
Abstract 1682 Background With the success of targeted oral tyrosine kinase inhibitor (TKI) therap... more Abstract 1682 Background With the success of targeted oral tyrosine kinase inhibitor (TKI) therapy, long-term/life-long therapy for patients with chronic myelogenous leukemia (CML) can now be envisaged. Dasatinib is a second generation TKI, which in a phase I clinical trial was found to be 100–300 times more potent at inhibiting tyrosine kinases than imatinib. In vitro data suggest that dasatinib therapy also may have a direct effect on bone metabolism by interfering with c-FMS, c-SRC and the PDGF-R pathways (Boufker et al, BMC Cancer 2010, 10:298). In this study, we evaluated the effects of dasatinib monotherapy on bone homeostasis of CML patients treated at our center between 2006 and 2011. The levels of traditional biomarkers of bone health, namely serum bone specific alkaline phosphatase isoenzyme (BAP) and osteoprotegerin (OPG) were measured and were correlated with morphometric assessment of bone marrow biopsy specimens (BM Bx). We also assessed for any correlations between bone homeostasis and the results of conventional cytogenetics and molecular analysis with respect to treatment response. Methods The study group included 23 patients with chronic phase CML without evidence of clonal evolution who were treated with dasatinib. The median age was 51 years (range, 25–63) with a male to female ratio of 1.5: 1. Four different treatment groups were assessed (20mg/day, 40 mg/day, 80 mg/day and 100 mg/day). We compared paired BM specimens, obtained at initial diagnosis and 12–51 months (mos) after commencing dasatinib therapy. We performed whole slide imaging (Philips) on routinely stained BM Bx and specimen compartments were quantified using an area pixel count algorithm (Image Pro Plus system Version 6.3, MediaCybernetics, Bethesda, MD, USA) to calculate trabecular bone volume as a percentage area. The morphometric results were correlated with the results of conventional cytogenetics and molecular analysis obtained every 3 mos after enrollment. We also performed competitive inhibition ELISA assays to measure serum levels of OPG (baseline and after 12/18 mos) and BAP (every 4 mos), respectively. Results With a median follow up of 24 mos (range 12–51mo), a significant increase in trabecular bone volume (TBV) was noted (p=0.022, Figure 1); 74% (17 pts) showed an increase in TBV on therapy, with an absolute increase of 5.2% (mean). Twelve of 16 pts (75%) evaluated had a decrease in OPG after 18 mos, which correlated in 90% of pts with an increase in TBV using a linear regression model (p= 0.0017, Figure 2). No significant difference was detected in TBV changes among the four dose groups. There was no significant trend in serum BAP levels, thus no statistical correlation was performed at this time point. All patients treated with dasatinib showed cytogenetic and molecular BCR-ABL1 response. There was no correlation between the degree of TBV change and either cytogenetic or molecular response (Figure 3) Conclusions: Our results indicate that within the therapeutic range for CML patients, dasatinib therapy promotes bone formation. However, there was no correlation between the dose levels studied and degree of bone formation and no correlation between TBV change and either cytogenetic or molecular response. The combination of digital image analysis and bone biomarkers enhances our understanding of bone homeostasis in patients on dasatinib. Further studies in a larger cohort of patients will be helpful to further validate our results. Figure 1 : mean and standard deviation of TBV for each visit. Figure 2 : correlation between “percent change TBV between visit 1 and visit 2” and 18 months OPG levels (linear regression model R2 =0.292, p= 0.0017) Figure 3 : association between “percent change in TBV between visit 1 and visit 2” and “Rate of PCR response change between 3 and 12 months” (Spearman correlation coefficient = −0.05; p =0.81) Disclosures: Cortes: Ariad: research support and consulting, research support and consulting Other; Pfizer: research support and consulting, research support and consulting Other; Novartis: research support and consulting, research support and consulting Other; BMS: research support and consulting Other.
PubMed, Nov 1, 1998
Cyclin D1 plays an important role in cell cycle progression from G1 to S phase. Cyclin D1 overexp... more 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.
PubMed, Oct 1, 1998
The CD5 antigen is a T-cell associated marker that is also usually expressed by two B-cell neopla... more 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.
Cancer, Oct 28, 2011
BACKGROUND: Isolated isochromosome (17q) is a rare cytogenetic abnormality in Philadelphia chromo... more BACKGROUND: Isolated isochromosome (17q) is a rare cytogenetic abnormality in Philadelphia chromosome-negative myeloid neoplasms, usually myelodysplastic and/or myeloproliferative neoplasms (MDS/MPN). De novo acute myeloid leukemia (AML) with isochromosome 17q has rarely been reported. The frequency of genetic mutations is unknown. METHODS: The authors assessed clinicopathologic, immunophenotypic, and molecular genetic features of 22 myeloid neoplasms with isolated isochromosome 17q. RESULTS: Fourteen patients presented as MDS/MPN; 8 as de novo AML. Most presented with leukocytosis, anemia, thrombocytopenia, and splenomegaly. Morphologically, all showed myelodysplastic and myeloproliferative features, including pseudo-Pelger-Huet-like neutrophils, micromegakaryocytic hyperplasia, hypercellularity, fibrosis, and osteosclerosis. Blasts were increased (median, 40% in de novo AML; 9% in MDS/MPN). Immunohistochemical assessment of proliferation and apoptosis rates in AML were similar to a matched group without isochromosome 17q. In most patients, isochromosome 17q occurred at time of blast transformation or disease progression. DNA sequencing revealed no mutation in the uninvolved TP53 allele. Mutational analyses showed rare mutations in NRAS (3 of 10), FLT3 (2 of 16), and JAK2 (1 of 18), and no mutations in NPM1 (0 of 15), KIT (0 of 4), and CEBPA (0 of 4). The median overall survival was 14.5 months for de novo AML, and 11.0 months for MDS/MPN. With a median follow-up of 8.5 months (range, 1.5-107 months), 15 died of disease, 6 had persistent disease, and 1 was in remission after bone marrow transplantation. CONCLUSIONS: The authors conclude that myeloid neoplasms with isolated isochromosome 17q represent a distinct clinicopathologic entity with myelodysplastic and myeloproliferative features, high risk of leukemic transformation, and wild-type TP53.
Clinical Lymphoma, Myeloma & Leukemia, Aug 1, 2016
We assessed patients with chronic myelogenous leukemia for serum Ca, PO4, bone alkaline phosphata... more We assessed patients with chronic myelogenous leukemia for serum Ca, PO4, bone alkaline phosphatase, N-telopeptide, osteoprotegerin levels and trabecular bone (TBA) in bone marrow (BM) specimens before and after treatment with dasatinib. We identified a significant increase in TBA % in post-dasatinib BM (p=0.022). This suggests that dasatinib therapy can increase TBA, without significant changes in bone and mineral metabolism. Introduction-Interferences with bone homeostasis and mineral metabolism have been described in patients taking imatinib for chronic myelogenous leukemia (CML) or gastrointestinal stromal tumors. Dasatinib is a potent second generation tyrosine kinase inhibitor (TKI), designed to inhibit ABL and SRC kinases while also interfering with the c-KIT, PDGF-R and STAT5 pathways. Patients and Methods-In this study, we use a multiparameter approach to examine the "off target effects" of dasatinib in 30 patients with CML treated between 2009 and 2012. We recorded serum calcium (Ca) and phosphate (PO4) levels, analyzed markers of bone formation (bone alkaline phosphatase/ BAP) and bone resorption (N-telopeptide/NTX), measured osteoprotegerin (OPG) levels and digitally analyzed changes in trabecular bone area (TBA) in paired bone marrow biopsy specimens (BM) before and after treatment. We correlated all findings with each other and with results of conventional cytogenetic and molecular analysis.
American Journal of Clinical Pathology, Aug 1, 1998
American Journal of Clinical Pathology, Apr 1, 1999
Immunophenotypic studies are essential to distinguish acute lymphoblastic leukemia (ALL) from min... more Immunophenotypic studies are essential to distinguish acute lymphoblastic leukemia (ALL) from minimally differentiated acute myeloid leukemia (AML-M0) 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. Myeloidassociated 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
Diagnostic Pathology: Molecular Oncology, 2016
Archives of Pathology & Laboratory Medicine, 2001
Objective.—We previously surveyed cyclin D1 expression in common acquired nevi, Spitz nevi, and m... more Objective.—We previously surveyed cyclin D1 expression in common acquired nevi, Spitz nevi, and malignant melanomas and reported that benign nevi maintain a zonal pattern of cyclin D1 expression, in contrast with malignant melanomas. Our aim was to extend those observations by examining cyclin D1 expression in dysplastic nevi. Methods.—Cyclin D1 overexpression in 23 dysplastic nevi was detected by an immunohistochemical technique. The extent of atypia of the nevi was graded as mild, moderate, or severe, using previously established criteria. Results.—Cyclin D1 overexpression in dysplastic nevi maintained a zonal pattern, similar to Spitz nevi. Cyclin D1 overexpression was greatest in the region of the epidermal-dermal junction and was significantly less prominent in the papillary and reticular dermis, suggesting that cyclin D1 expression is under cell control and correlates with maturation of nevus cells. Cyclin D1 overexpression also correlated with cytologic atypia, as dysplastic ...
American Journal of Clinical Pathology, 1998
Immunophenotyping has become common in the diagnosis and classification of acute leukemias and is... more 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-MO). 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, CDllc, 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-Acute leukemias are traditionally classified by a combination of morphologic and cytochemical features on the basis of criteria of the French-American-British (FAB) C o o p e r a t i v e G r o u p. 1 ' 2 The a d d i t i o n of immunophenotypic studies is valuable in both the confirmation and precise lineage classification of acute lymphoblastic leukemia, as well as in the detection of minimally differentiated acute myeloid
American Journal of Clinical Pathology, 1999
American Journal of Clinical Pathology, 1997
The distinction between mantle cell lymphoma (MCL) and other low-grade B-cell neoplasms is import... more 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 Dl immunostaining in distinguishing MCL from other B-cell lymphoproliferative disorders. We used a cocktail of two monoclonal anti-cyclin Dl 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
The American journal of surgical pathology, Jan 11, 2016
Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of lymphoma. Patients have a poor prognosis,... more Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of lymphoma. Patients have a poor prognosis, and there is no standard of care. We evaluated 28 HSTCL patients to determine factors that may be associated with outcome. There were 19 men and 9 women with a median age of 32.5 years. Most patients had massive splenomegaly, and bone marrow showed sinusoidal involvement by lymphoma. The HSTCL cells expressed γδ T-cell receptor (TCR) in 20 (74%), αβ TCR in 5 (19%), and neither in 2 (7%) patients (1 case not assessed). Conventional cytogenetics and/or fluorescence in situ hybridization analysis in 24 patients at diagnosis showed isochromosome 7q (i7q) in 10 (42%) and trisomy 8 in 8 (33%) patients. Median overall survival (OS) and event-free survival (EFS) were each 28.3 months. Serum bilirubin level ≥1.5 mg/dL, αβ TCR expression, and trisomy 8 each correlated significantly with shorter OS and EFS. Patients with HSTCL received a variety of chemotherapy regimens with no regimen better than...
Annals of Diagnostic Pathology, 2016
Patients with chronic myelogenous leukemia (CML) present typically with an elevated white blood c... more Patients with chronic myelogenous leukemia (CML) present typically with an elevated white blood cell count (WBC) and cytogenetic or molecular genetic evidence of t(9;22)/BCR-ABL1 fusion gene. Rarely, CML patients may present with a normal or mildly elevated WBC and are asymptomatic, and we describe 7 patients in this study. The WBC in these patients ranged from 3.6 to 14.3 K/mm(3) with 50% to 73% granulocytes and 0% blasts. In all patients, t(9;22)(q34;q11.2) was detected by conventional cytogenetics, and BCR-ABL1 fusion was shown, supporting the diagnosis of preleukemic CML (pre-CML). We compared these patients with a group of 5 cases of CML in chronic phase (CML-CP) and 5 bone marrow specimens with a leukemoid reaction (n=5). Reticulin, CD34, and CD61 immunostains were performed on all bone marrow biopsy specimens. Peripheral blood absolute basophilia (≥200/mm(3)) was noted in only 4 of 7 pre-CML cases, whereas it was present in all CML-CP cases and absent in leukemoid reaction cases. The mean ±SD of microvascular density of pre-CML cases (10.0±4.3 vessels/200× field) was twice that of leukemoid reaction cases (5.0±1.0) (P=.02; Student t test) but similar to that of CML-CP cases (12.5±3.6). Microvessels in pre-CML, highlighted by CD34, were tortuous with abnormal branching, although to a lesser extent than those found in CML-CP. Microvessels in leukemoid reaction were generally straight. The percentage of small, hypolobated megakaryocytes, highlighted by CD61 in pre-CML, was 40%, 3 times that found in leukemoid reaction cases (13%) but less than that of CML-CP cases (86%). We conclude that pre-CML should be suspected in patients with a normal to mildly elevated WBC and absolute basophilia. Bone marrow examination can usually distinguish pre-CML from a leukemoid reaction based on the percentage of small, hypolobated megakaryocytes; microvascular density; and morphologic features.