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Diagnostic Cytopathology 08/2001; 25(1):78-9. · 1.16 Impact Factor
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Retina 02/2001; 21(3):281-4. · 2.81 Impact Factor
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ABSTRACT: Evaluation for circulating tumor cells and bone marrow micrometastases has generated considerable interest due to a potential association with disease recurrence and poor prognosis. In this study, we examined bone marrow and apheresis samples from Stage II, III, and IV patients (n 120) enrolled in various clinical breast cancer trials at the National Institutes of Health/National Cancer Institute. For each patient sample, two Diff-Quik-stained cytospins were reviewed for morphology, and approximately 1 x 10(6) cells were analyzed for the expression of cytokeratins using an avidin-biotin immunoperoxidase method. Keratin-positive malignant cells appearing as single cells or in small clusters were detected in bone marrow samples from Stage IV patients only (9/68, 13%) and detected in apheresis samples from both Stage III and IV patients (13/245, 5%). These findings indicate that the combination of cytomorphology with immunocytochemistry can be utilized for the investigation of circulating tumor cells and bone marrow micrometastases, and that positive results appear to correlate with high tumor stage/burden.
Diagnostic Cytopathology 06/2000; 22(5):323-8. · 1.16 Impact Factor
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ABSTRACT: We report on the flow cytometric identification of concomitant acute myeloid leukemia and chronic lymphocytic leukemia in cytology specimens submitted with minimal clinical information. A 64-year-old man presented with fever and progressive dyspnea on exertion. Chest X-ray and computed tomography scan showed a left upper lobe pulmonary mass. Pulmonary capillary pullback specimens were collected to determine infectious verses neoplastic etiology. The pulmonary capillary pullback specimens showed atypical mononuclear cells with enlarged, slightly irregular nuclei; visible nucleoli; and basophilic cytoplasm. Flow cytometric analysis of the specimen for lymphoma was requested. Flow cytometric immunophenotypic studies showed that 78% of the cells were CD34 positive, CD45 dim positive and CD11c positive, consistent with acute myeloid leukemia. About 0. 75% of the cells expressed CD5 as well as dim CD20 and were monoclonal for kappa light chains: consistent with chronic lymphocytic leukemia/small lymphocytic lymphoma. At this time the clinician communicated a history of myelodysplastic syndrome of refractory anemia subtype. Peripheral blood was obtained for further immunophenotyping and the patient was immediately treated for his acute myeloid leukemia. This case demonstrates that a diagnostic antibody panel should allow evaluation of all cell types as per the U.S./Canadian consensus recommendations on the immunophenotypic analysis of hematologic neoplasia by flow cytometry (Stewart et al.: Cytometry 30:231-235, 1997). Published 2000 Wiley-Liss, Inc.
Cytometry 05/2000; 42(2):114-7.
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ABSTRACT: The standard of practice in cytopathology does not include an individual specimen triage (IST) for sample optimization, but rather prescribes a uniform procedure, e.g., for smears, cell blocks, and cytospins. IST requires additional resources. We sought to evaluate whether IST would result in enhanced diagnostic accuracy and specimen turnaround time in effusions. In order to evaluate the efficacy of IST, 50 effusion samples (31 pleural, 16 peritoneal, and 3 pericardial), each with a minimum volume of 50 ml, were utilized. Each sample was prepared via IST to include at least two initial prepared Diff-Quik-stained cytospins on which the IST was based, as well as a standard cytopreparation protocol for nontriaged samples (NTS) which was limited to 3 smears (2 Papanicolaou-stained, and 1 Diff-Quik-stained) and a hematoxylin-eosin (H&E)-stained cell block section. All triaged and NTS were reviewed retrospectively to determine if IST offered any advantages over the standard cytopreparation protocol for effusion samples. Each was evaluated for diagnostic concordance, turnaround time for final diagnosis, and optimal preparation. In 46 cases, diagnoses in IST and NTS were 100% concordant. Four cases showed minor discrepancies between the original and the NTS diagnoses. In general, the discordant cases were due to sparse cellularity in a specimen composed largely of blood. There was no difference in turnaround time for final diagnosis. Based on a review of all samples, the combination of cell block preparation and cytospins (stained with Diff-Quik and Papanicolaou stains) were considered optimal for microscopic evaluation. IST offers no practical advantage over the NTS standard specimen preparation in relation to the accuracy of final diagnosis or turnaround time. The lysing of grossly bloody fluids with subsequent preparation of cytospins yielded superior preparations for microscopic evaluation over NTS. The standard preparation of effusion samples should include the preparation of a cell block, and cytospins stained with Diff-Quik and Papanicolaou stains, for optimal microscopic evaluation.
Diagnostic Cytopathology 01/2000; 22(1):7-10. · 1.16 Impact Factor
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ABSTRACT: The Tall cell variant of papillary carcinoma of the thyroid (TCV) is characterized by the proliferation of oxyphilic, tall, columnar cells with a height-to-width ratio of at least 2:1. TCV exhibits more aggressive clinical behavior than conventional thyroid papillary carcinoma (CPC). Cytologic features suggestive of TCV have been described in fine-needle aspiration material from primary tumors. Similarly, loss of heterozygosity (LOH) for chromosome 1 (D1S243) and the p53 gene (TP53) have been reported in TCV but not in CPC, thus making exploitation of this genetic feature a potential tool for molecular discrimination between these two neoplasms.
Cytology samples of metastatic and/or recurrent neoplasms (M/R) (12 cases) and 7 cases of primary TCV obtained from 12 patients were evaluated. The cytologic findings of these cases were compared with previously published findings. Microdissection and polymerase chain reaction for LOH for chromosome 1 and p53 (D1S243 and TP53 markers) were performed on cytologic smears from 6 cases of M/R tumors and 3 cases of primary tumors.
More then 50% of M/R showed atypical follicular cells with enlarged nuclei, granular chromatin, nuclear grooves, pseudoinclusions, and abundant finely granular cytoplasm. Cells were disposed in monolayers (58%) and papillary clusters (50%). Similar findings were present in cases of primary TCV. LOH studies showed that 4 of 6 M/R were noninformative and 2 of 3 cases of primary TCV were informative for the D1S243 marker; however, in contrast with previously published reports, no LOH was detected for the markers evaluated.
M/R and primary TCV have similar cytologic features. Additional studies of larger series of M/R and primary TCV should be performed to delineate further any potential application of LOH for chromosome 1 and the p53 gene as a tool for diagnosing TCV with cytologic preparations. Cancer (Cancer Cytopathol)
Cancer 09/1999; 87(4):238-42. · 4.77 Impact Factor
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ABSTRACT: We have previously shown that fibroblast growth factor (FGF)-1-, FGF-4-, or vascular endothelial growth factor (VEGF/VPF)-transfected MCF-7 breast carcinoma cells growing as tumors in nude mice are tamoxifen resistant and/or estrogen independent. These transfectants provide opportunity for study of in situ tumor-induced angiogenesis promoted by the individual angiogenic factors under growth-promoting versus growth-inhibiting hormonal conditions. In the present study, vessels in tumors harvested at varying times after tumor cell injection were immunohistochemically highlighted and vessel morphology and topography were scored on a scale of 0 to 4 by blinded observers. In tumors produced by all cell lines under all growth-promoting hormonal conditions, there was significantly increased abundance (P < 0.05) of edge-associated and intratumor microvessels, but not of stromally located microvessels, when compared with tumor nodules harvested under growth-inhibiting conditions, regardless of the identity of the angiogenic factor or the hormonal treatment. Image analysis of bromodeoxyuridine (BrdU)-labeled nuclei of tumors produced by all cell lines under all hormonal conditions harvested at early time points showed that mean labeling indices were highest for hormonal conditions that produced the most robust growth in that particular cell line, implying that a high BrdU labeling index is a predictor of future tumor growth in individual tumors. These results confirm previous studies that established the importance of neovascularization for tumor growth and provide validation for use of these cell lines to study the process of angiogenesis in vivo. Study of gene expression in endothelial cells in edge-associated or intratumor vessels using this model might reveal mechanisms important in tumor-induced angiogenesis in human breast cancer.
American Journal Of Pathology 01/1999; 153(6):1993-2006. · 4.89 Impact Factor
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ABSTRACT: Malignant melanoma (MM) can mimic soft tissue (ST) and epithelial neoplasms. An immunoperoxidase (IP) panel and a morphologic comparison of the primary are used in diagnosis, which can be difficult when the morphologic and IP profiles of a metastatic lesion simulate those of an ST neoplasm. Through the comparison of known genetic abnormalities in primary and metastatic neoplasms, a definitive diagnosis can be suggested on the basis of the finding of identical allelic losses through the use of microdissection (MD) and the polymerase chain reaction (PCR). Genetic alterations involving the p16 gene on chromosome 9p21 have been observed in MM. We present the case of a 56-year-old man with known MM in whom multiple metastatic lesions to the skin and an adrenal gland developed during a 5-year period. A fine-needle aspiration (FNA) of a new ST buttock lesion was performed; the specimen had cytologic features different from those of the primary neoplasm and simulated a possible primary ST neoplasm. We attempted to make a definitive diagnosis of MM in the FNA of the ST buttock lesion through a genetic comparison with the primary neoplasm as well as with the other metastatic sites. Direct-visualization MD was performed on histologic glass slides of the primary and adjacent tissue (normal control), and the metastatic lesions, along with malignant cell clusters from the buttock lesion FNA. DNA was extracted and PCR amplified with primers D9S171 and IFNA for the p16 locus at the 9p21-22 region. Loss of heterozygosity for the D9S171 marker at the p16 gene locus was identified in all of the neoplastic tissue tested. Normal skin elements did not show deletion. The combination of MD and PCR are powerful tools that can be used for the comparison of genetic abnormalities in primary and metastatic neoplasms with unusual morphologic features to help support a diagnosis with a noncontributory IP.
Modern Pathology 11/1998; 11(10):1010-5. · 4.79 Impact Factor
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Diagnostic Cytopathology 07/1998; 18(6):473-4. · 1.16 Impact Factor
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ABSTRACT: Some benign tumors categorized as "granular cell tumors" (GCTs) may have heterogenous origins despite their uniform morphologic appearance. Adult GCTs (the usual type), presumed to be of Schwannian origin, are reported to be positive for S100 protein (S100) and neuron-specific enolase (NSE). Congenital GCTs are S100- and NSE-negative and of unknown but probable non-Schwannian origin. To elucidate the histogenesis of adult and congenital GCT, we undertook a comparative immunohistochemical study using paraffin-embedded tissue from 10 cases of GCTs, of which 3 were the congenital type, 6 were the adult type, and 1 was an unusual multiple GCT involving the colonic mucosa. All of the GCTs were negative for keratin, smooth muscle actin, muscle-specific actin, desmin, CD57, CD15, and MAC387. All of the adult and multifocal GCTs involving the colonic mucosa were positive for S100, NSE, alpha-1-antitrypsin (A1AT), CD68, and vimentin. Congenital GCTs, on the other hand, were negative for S100 and NSE but positive for A1AT, CD68, and vimentin. Our study suggests that these two types of GCT have different histogeneses because S100 and NSE are positive in the adult type but negative in the congenital type. They share, however, a common immunophenotype of positive A1AT, CD68, and vimentin. Although this may seem to indicate a common histiocytic origin for adult and congenital GCT, another macrophage marker, MAC387, is negative. Furthermore, CD68 is closely related to the glycoprotein of the lysosomal membrane and is not completely specific for histiocytic cells; for example, it is positive in reactive and neoplastic Schwann cells. Thus, we conclude that positive immunoreactivity for A1AT and CD68 in GCT may be a reflection of the intracytoplasmic accumulation of phagolysosomes and that it does not imply a histiocytic origin for this tumors. We confirm that adult GCT is of Schwannian origin and that congenital GCT is of uncommitted mesenchymal cell origin.
Modern Pathology 10/1996; 9(9):888-92. · 4.79 Impact Factor