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K Foucar

Publications and source records attributed to K Foucar.

At least 19 recordsLinked to original sources

False-positive flow cytometric platelet glycoprotein IIb/IIIa expression in myeloid leukemias secondary to platelet adherence to blasts.

Because neither morphologic nor routine cytochemical features are pathognomonic, the diagnosis of acute megakaryoblastic leukemia (AML-M7) is difficult, requiring either specialized ultrastructural or immunologic techniques. Because the ultrastructural techniques are cumbersome, immunologic assays for expression of several platelet-specific antigens, such as CD41a (platelet glycoprotein IIb/IIIa), have become the primary method used to detect megakaryoblastic differentiation. In our flow cytometric analysis of the immunophenotypes of over 1,000 cases of AML from patients registered to Southwest Oncology Group (SWOG) Treatment Protocols, we found that 38% of cases demonstrated CD41a reactivity. Because this frequency of CD41a expression by flow cytometry greatly exceeded the number of morphologically defined cases of AML-M7, we postulated that the reaction may be caused by platelets adherent to leukemic blasts. To investigate this hypothesis, we performed a side-by-side comparison of flow cytometric and cytospin immunofluorescence studies on 37 cases of adult de novo AML that demonstrated a wide range of CD41a expression by flow cytometric analyses. We found that the expression of CD41a detected by flow cytometric techniques was secondary to adherent platelets or platelet fragments in 85% of cases. Many of these cases also expressed the lineage-specific carbohydrate, LNF III (CD15), which may mediate platelet adhesion to mature monocytes and neutrophils. Only 15% of the CD41a flow cytometrically positive cases demonstrated true diffuse membrane and cytoplasmic positivity on cytospin slides indicative of megakaryoblastic differentiation. Cytospin immunofluorescence for CD41a should be performed on all cases of suspected AML-M7. If only flow cytometric techniques are used, adherent platelets may result in the erroneous diagnosis of this AML subtype.

Adult

Prenatal diagnosis of transient myeloproliferative disorder via percutaneous umbilical blood sampling. Report of two cases in fetuses affected by Down's syndrome.

Since its initial description in 1982, percutaneous umbilical blood sampling has become useful in diagnosing, monitoring, and even treating a variety of fetal disorders. Recently two percutaneous umbilical blood samples were evaluated in which the white blood cell count was markedly elevated with many circulating blasts. Both samples exhibited the morphologic features of a transient myeloproliferative disorder, characteristically seen in neonates and infants with Down's syndrome. In both cases, antenatal clinical and ultrasound abnormalities also were suggestive of Down's syndrome, which was confirmed by cytogenetic studies. Although the peripheral blood abnormalities persisted at birth, both patients experienced spontaneous remission of the transient myeloproliferative disorder by 5 weeks of age. To our knowledge, these two cases of Down's syndrome represent the first reported examples of the intrauterine diagnosis of transient myeloproliferative disorders.

Adult

A comparative analysis of cytoplasmic mu (C mu) expression in acute lymphoblastic leukemia by molecular and immunologic techniques. Identification of leukemia cases expressing C mu mRNA transcripts in the absence of detectable C mu proteins.

Among acute lymphoblastic leukemias derived from the B-cell lineage, the subset of cases expressing cytoplasmic mu heavy chain proteins (C mu) in the absence of surface immunoglobulin has been designated pre-B-cell acute lymphoblastic leukemia. This group, traditionally identified using immunologic smear techniques, has been associated with a poor prognosis in some series. In a comparative study, 25 cases of B-lineage acute lymphoblastic leukemia were analyzed for C mu expression using molecular and immunologic techniques. RNA derived from cryopreserved blast cells was hybridized in both Northern and slot-blot analyses using a probe (pBZ311) containing four exons of the human immunoglobulin heavy chain mu constant region gene. Expression of C mu proteins was assessed simultaneously by slide immunofluorescence and flow cytometric techniques in all samples. These studies were correlated with immunoglobulin heavy and light chain gene rearrangements, cell-surface immunophenotype, cytogenetics, and other clinicopathologic features. C mu mRNA transcripts were detected in 14 of 25 cases, whereas C mu proteins were detected in only 9 of these cases using flow cytometric techniques. Only four of these nine cases were positive by slide immunofluorescence techniques. These studies imply that molecular and flow cytometric techniques may be a more sensitive means to assess C mu expression. The identification of five cases that expressed C mu mRNA transcripts in the absence of detectable C mu proteins also suggests that molecular techniques may be valuable in identifying a unique subgroup of pre-B-cell acute lymphoblastic leukemia cases that contain C mu mRNA transcripts, but lack C mu proteins.

Adolescent

Survival of children and adolescents with acute lymphoid leukemia. A study of American Indians and Hispanic and non-Hispanic whites treated in New Mexico (1969 to 1986).

During the period 1969 to 1986, 196 American Indian and Hispanic and non-Hispanic white children and adolescents (ages, 0 to 19 years) were treated for acute lymphoid leukemia (ALL) at the University of New Mexico affiliated institutions. There were 28 American Indians (14%), 91 Hispanic whites (46%), and 77 non-Hispanic whites (39%). Median survivals for patients undergoing antileukemic therapy ranged from 8 months for American Indian boys to 140 months for non-Hispanic white girls. American Indian boys had the highest initial median leukocyte count (WBC) at 23.8 X 10(9)/l. Compliance problems occurred most commonly among American Indian children of both genders. Other clinical and pathologic features evaluated in this study were distributed similarly among the ethnic gender groups. Multi-variate analysis revealed that independent prognostic variables for survival included initial WBC, age, and gender. Ethnicity and compliance problems were possible, but confounded, prognostic variables. To the authors' knowledge this represents the most comprehensive study to date of ALL in American Indian patients.

Adolescent

Do random (non-clonal) chromosome abnormalities in bone marrow predict a clone to come? Southwestern Oncology Group of Leukemia Cytogenetics Subcommittee.

The biologic significance of clonal karyotypic abnormalities in human neoplasms is becoming better understood, but the significance of rare chromosomal aberrations is uncertain. Useful, yet arbitrary, cytogenetic definitions of a clone have been established and cases with a frequency of chromosome aberrations less than the accepted convention are explained by random loss, karyotypic instability/evolution, or other technical artifact. Are non-clonal chromosomal abnormalities that may predict future clinically significant clones being ignored? A brief case report is presented raising two such issues in the same myelodysplastic patient. This child had monosomy 7 and, later, trisomy 8, as well as increased numerical/structural aberrations seeming to predict relapse. Preliminary data from the Southwestern Oncology group is also presented. Non-clonal data should be included, when appropriate, in the clinical report.

Adolescent

Chromosome analysis of cryopreserved cells.

We describe a technique for freezing and thawing human leukemic cells for cytogenetic studies. We studied 64 harvests on 26 cryopreserved samples from 20 individuals. Chromosome quality was best in the samples from patients with myeloid disturbances. Successful chromosome studies of approximately 50% of the samples were accomplished. Cryopreservation of leukemic cells is not a substitute for fresh material because the method produces relatively few metaphases and mediocre chromosome spreading and banding. However, when rigid and appropriate research objectives are applied, chromosome analysis of cryopreserved leukemic cells can be a viable alternative to analysis of fresh cells.

Adolescent

The mononuclear phagocyte and immunoregulatory effector (M-PIRE) system: evolving concepts.

The phagocytic activity of macrophages and related cells has been recognized for over a century. Within the last decade a variety of other functions has been attributed to these same cell types. Examples include antigen processing and antigen presentation to B and T cells, and synthesis of a large number of immunoregulatory proteins. This recent explosion of information regarding the functions and cell types of this complex cell system has had little impact on the practice of pathology in that nomenclature, concepts of disease classification, and our diagnostic approach to the majority of "histiocytic" disorders have not been revised. As the mysteries of this complex cell system are unraveled, older names, such as the mononuclear phagocyte system that focus on only one function, have become obsolete. Because recent evidence shows that this cell system also plays a pivotal and multifaceted role in immunity, the designation mononuclear phagocyte and immunoregulatory effector (M-PIRE) system is recommended. Diverse cell types, including bone marrow precursor cells, histiocytes, various dendritic cells, and Langerhans cells, comprise the M-PIRE system, and these are located in tissues throughout the body. Although mature macrophages and dendritic cells are strikingly different in morphology and function, evidence from studies of both normal cells and proliferative disorders suggests a common cell of origin. There also is provocative evidence suggesting that transitions between cell types may occur, analogous to those observed in the lymphoid cell system. In this report, a conceptual overview of the M-PIRE system including origin, normal function, proposed transitional cell forms, and disease states is presented.

Animals

High-grade non-Hodgkin lymphoma relapsing as low-grade follicular lymphoma: so-called downgraded lymphoma.

Evolution of low-grade Non-Hodgkin Lymphoma (NHL) into a more aggressive neoplasm is a common, well-documented event in NHL. The reverse process, in which a less aggressive component becomes evident during the course of treatment for a higher-grade NHL, has only recently been recognized. This lymphoma "downgrading" has been reported at the time of relapse in both radiation- and chemotherapy-treated patients who initially presented with high- or intermediate-grade lymphoma. The etiology of this unusual transformation has not yet been determined. We present the clinical, morphologic, immunologic, and flow-cytometric features of a patient with diffuse immunoblastic lymphoma who achieved a complete response to chemotherapy and then relapsed with follicular small-cleaved-cell lymphoma 3 years later. Morphologic and immunophenotypic findings suggest that both immunoblasts and small cleaved cells were present in the initial biopsy. DNA content analysis of the initial and relapse biopsies suggests that the immunoblastic component was more susceptible than the small cleaved cells to the chemotherapy that the patient received. Successful eradication of the rapidly proliferating immunoblasts with survival of less rapidly proliferating small cleaved cells may account for the unusual histologic transformation seen in this case.

Adult

Plasma cell dyscrasia: a case of POEMS syndrome with a unique dermatologic presentation.

POEMS (polyneuropathy, organomegaly [hepatosplenomegaly or lymphadenopathy], endocrinopathy, M protein, and skin changes) syndrome is an uncommon plasma cell dyscrasia with diverse manifestations, including lymphadenopathy as well as those that comprise the acronym. Dermatologic changes may include hyperpigmentation, thickened skin, hypertrichosis, and papular angiomas. These changes are believed to result from humoral products of the plasma cell clone and frequently resolve with treatment of the neoplasm. We describe a man with typical POEMS syndrome with a unique skin lesion: a large, sharply circumscribed, pigmented plaque on the anterior chest wall centered over a plasmacytoma of the sternum. Results of histologic examination showed a proliferation of capillaries of varying size, enlarged fibroblasts, and increased amounts of collagen and proteoglycan from the dermis to the periosteum. Because the outer cortex of the sternum was eroded, peptide mediators of vascular and fibroblast proliferation may have diffused directly from the plasma cell lesion into the tissues of the chest wall.

Adult

Peripheral blood morphologic changes after high-dose antineoplastic chemotherapy and recombinant human granulocyte colony-stimulating factor administration.

The peripheral blood morphologic findings in 17 patients with cancer who had received high-dose cytotoxic chemotherapy followed by recombinant human-granulocyte colony-stimulating factor (rh-GCSF) were reviewed and compared with a control group of patients who received only high-dose chemotherapy. Both groups showed dysmyelopoiesis (abnormal granulation and nuclear lobulation) in the granulocytic series during the period of bone marrow recovery that followed the cytotoxic chemotherapy. Most of these morphologic abnormalities were more prominent in the rh-GCSF-treated group. Monocytic cells in both groups showed prominent vacuolation and immature nuclei. The percentages and absolute numbers of large granular lymphocytes were increased in the rh-GCSF group compared with the control group. No quantitative or qualitative abnormalities of eosinophilic or basophilic granulocytes were detected in either group. Both groups showed nonspecific red blood cell abnormalities, and large platelets were present in half of the control group smears. This report provides the first detailed peripheral blood morphologic description in patients treated with rh-GCSF and high-dose chemotherapy.

Adult

Atypical cutaneous lymphoproliferative disorder resembling mycosis fungoides in AIDS. Report of a case with concurrent Kaposi's sarcoma.

A variety of neoplastic disorders have been described in patients with AIDS. Kaposi's sarcoma is the most common neoplasm and is recognized as one of the diagnostic criteria for AIDS. Unusual mucocutaneous carcinomas have also been reported in these patients, as have a variety of lymphoid neoplasms, including Hodgkin's and non-Hodgkin's lymphomas (NHLs). The NHLs that occur in AIDS patients are usually of B-cell or non-B, non-T-cell phenotype. In contrast, T-cell lymphomas have only rarely been reported in this patient population. We present the clinical, morphologic, and immunologic features of an atypical, cutaneous lymphoproliferative disorder resembling mycosis fungoides that developed in a 28-year-old homosexual man with AIDS and disseminated mucocutaneous Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome

Flow cytometric analysis of lymphoma and lymphoma-like disorders.

The use of flow cytometry (FC) represents the most recent advance in the phenotypic analysis of lymphocyte subsets, and has emerged as a valuable adjunct in the diagnosis of malignant non-Hodgkin's lymphoma (NHL). In a review of over 200 cases of nodal and extranodal suspected lymphomas studied in the Immunophenotyping Laboratory at the University of New Mexico, the diagnostic utility of FC was assessed. Among cases of NHL, FC was able to confirm a morphologic diagnosis of lymphoma and determine B or T cell lineage in greater than 85% of the samples submitted. Difficulty in lineage determination in the remaining cases of morphologic NHL was multifactorial. Among cases of reactive lymph nodes and Hodgkin's disease, FC showed no characteristic patterns, although several cases exhibited phenotypic profiles suggestive of B or T cell clonality. When combined with routine morphologic review and accompanied by other specialized diagnostic techniques when necessary, the use of FC represents a precise and reproducible method for rapidly and easily studying lymphoproliferative disorders in solid tissue.

Flow Cytometry

Hematogones: a multiparameter analysis of bone marrow precursor cells.

Morphologically distinct lymphoid cells with homogeneous, condensed chromatin and scant cytoplasm can be observed in large numbers in the bone marrow of children with a variety of hematologic and nonhematologic disorders. In some patients, these cells may account for greater than 50% of the bone marrow cells, creating a picture that can be confused with acute lymphoblastic leukemia (ALL) or metastatic tumor. Although originally called hematogones (HGs), a variety of other names have been proposed for these unique cells. The clinical significance of expanded HGs has not been resolved, and the biologic features of these cells are incompletely described. In this study, we correlate the clinical, morphologic, cytochemical, flow cytometric, molecular, and cytogenetic properties of bone marrow samples from 12 children with substantial numbers of HGs (range 8% to 55% of bone marrow cells). Diagnoses in these patients included anemia, four; neutropenia, one; anemia and neutropenia, one; idiopathic thrombocytopenic purpura, two; retinoblastoma, two; Ewing's sarcoma, one; and germ cell tumor, one. Flow cytometric analyses of bone marrow cells demonstrated a spectrum extending from early B-cell precursors (CD10+, CD19+, TdT+, HLA-Dr+) to mature surface immunoglobulin-bearing B cells in these patients, corroborating our morphologic impression of HGs, intermediate forms, and mature lymphocytes. DNA content was normal, and no clonal abnormality was identified by either cytogenetic or immunoglobulin and T-cell receptor (TCR) gene rearrangement studies. Follow-up ranged from 3 months to 3 years. None of the patients has developed acute leukemia or bone marrow involvement by solid tumor. The possible role of HGs in immune recovery and hematopoiesis is presented.

Biomarkers, Tumor

Organization and operation of a flow cytometric immunophenotyping laboratory.

Technical advances in the field of flow cytometry have made it feasible for many academic and private hospital laboratories to purchase relatively inexpensive "user friendly" flow cytometers that do not require dedicated flow cytometer operators, special rooms, or a significant amount of laboratory space. Because the financial and physical constraints in operating a flow cytometer have been substantially reduced, many pathologists may now be considering such a purchase. By chronicling the clinical activities of a single flow cytometric immunophenotyping laboratory, this report will answer a variety of questions that may be asked by pathologists regarding both the utility of flow cytometers in clinical diagnosis and the mechanics of operating an immunophenotyping laboratory. The types of tissues that can be evaluated by flow cytometry will be detailed, and we will summarize the number and type of flow cytometric clinical studies performed in our laboratory since its development in 1983. Practical aspects of laboratory operation including technical staff requirements, specimen handling and processing procedures, monoclonal antibody selection, and quality control procedures will be presented. In addition, a comprehensive review of flow cytometric immunophenotyping studies as applied to the diagnosis of leukemias, lymphomas, and immunodeficiency disorders will be presented along with case examples that illustrate our approach to the interpretation of immunophenotyping results.

Adult

Bone marrow examination in the diagnosis of acute and chronic leukemias.

This article presents a brief review of the morphologic and cytochemical features of acute and chronic leukemias, followed by a discussion about new techniques that can be applied to the diagnosis of leukemias. The four techniques described include immunophenotyping, DNA content and cell cycle analysis, cytogenetics, and molecular studies. The utility of these specialized techniques in establishing a diagnosis of leukemia and in predicting prognosis is presented.

Antigens, Surface

Nonleukemic granulocytic sarcoma of the heart: a report of a fatal case.

We report the clinical and pathological features of a cardiac fatality caused by granulocytic sarcoma in a young adult man with no evidence of leukemia involving bone marrow or peripheral blood. At autopsy, walls of the four cardiac chambers were massively infiltrated by tumor, resulting in a cardiac weight of almost three times normal. Routine cytochemical stains plus immunoperoxidase staining for OKM1 confirmed the diagnosis. Although subclinical cardiac infiltrates are commonly detected at autopsy in patients with acute nonlymphoblastic leukemia (ANLL), massive cardiac granulocytic sarcoma in the absence of bone marrow disease has not been previously described. Cytochemical and immunological methods of diagnosing granulocytic sarcoma in fixed tissues are reviewed.

Adult