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Biomedical subjects

P J Cornbleet

Publications and source records attributed to P J Cornbleet.

At least 19 recordsLinked to original sources

Natural killer cell precursor acute lymphoma/leukemia presenting in an infant.

Lymphoma/leukemia derived from immature natural killer (NK) cells occur most commonly in adults and are characterized by blastic cytologic features and an aggressive outcome. Predilection for extranodal sites and absence of the Epstein-Barr virus associated with mature NK cell malignancies further distinguish this entity. We present a NK precursor acute lymphoma presenting with multiple masses in an infant without circulating blasts or marrow replacement by disease. The diagnostic difficulty arose from several factors, including young age, presentation with multiple masses, blastic cytologic features mistaken for a small, round, blue cell tumor, and the absence of lineage-specific markers. The CD56+, CD34+, CD33+, MPO-, cytoplasmic CD3+, CD45-, CD7-, HLA-DR-, and TdT- immunophenotype of this neoplasm overlaps with previously reported cases of myeloid/NK precursor acute leukemia and blastic NK cell lymphoma/leukemia. This case emphasizes the need for a strong index of suspicion to recognize this rare entity and to distinguish it from solid tumors and other hematolymphoid neoplasms that occur in infancy.

Acute Disease↗

Blastic/blastoid transformation of follicular lymphoma: immunohistologic and molecular analyses of five cases.

Progression of follicular lymphoma to a higher-grade malignancy frequently heralds a poor prognosis. Clinical transformation is variably accompanied by a spectrum of histologic changes characterized by alteration in growth and cytology. Although several cytogenetic events and potential oncogenes have been documented in this progression, the underlying molecular mechanisms are largely unknown. We present five patients with an unusual histologic transformation of follicular lymphoma manifested by blastic/blastoid morphology. This transformation is histologically distinct from other types of transformation of follicular lymphoma. All five cases exhibited the t(14;18) translocation and expressed the BCL-2 protein. In addition, two of the five patients showed increased levels of the p53 protein within neoplastic cells implicating a possible role for this oncogene in blastic/blastoid transformation. The lack of BCL-1 and myeloid antigens by immunohistochemistry and flow cytometry studies served to distinguish blastic/blastoid transformation of follicular lymphoma from its morphologic mimics. This distinction is clinically important because lymphoblastic and myeloid leukemias require significantly different therapeutic modalities and show better prognosis. Moreover, the lack of Epstein-Barr virus-specific mRNA suggests that this virus is unlikely to participate in blastic/blastoid transformation of follicular lymphoma.

Adult↗

Aggressive natural killer-like T-cell malignancy with leukemic presentation following solid organ transplantation.

NK-like T-cell malignancies are part of a spectrum of lymphoproliferative diseases that complicate immunosuppression associated with solid organ transplantation. We describe 2 patients with long-standing immunosuppression following solid organ transplantation. Both patients had systemic symptoms that included fever, myalgia, and weight loss. Organ involvement and lymphadenopathy were not initially observed. Unique to these 2 cases are the initial leukemic symptoms, which led to further characterization and identification of NK-like T-cell malignancies. Both patients exhibited an anomalous T/NK phenotype, CD56 positivity, and atypical blastic architecture of the large granular lymphocytes. Clonal rearrangement of T-cell receptor genes was detected in both patients. In 1 patient, a cytogenetic abnormality involving 8q24 was demonstrated. The disease course in both patients was aggressive, with involvement of multiple sites and rapid demise. This study emphasizes the importance of including NK-like T-cell malignancies in the differential diagnosis of lymphoproliferative disorders associated with immunosuppression and recognizing that an aggressive clinical course may follow leukemic presentation of disease.

Adult↗

IgM myeloma: case report with immunophenotypic profile.

Immunoglobulin (Ig)M myeloma is a distinct subtype of multiple myeloma (MM) displaying clinical and pathologic features of both MM and Waldenström's macroglobulinemia (WM). Although the immunophenotypic characteristics of classic MM and WM have been reported, the surface antigen expression of IgM myeloma has not been reported. We report a case of IgM myeloma and describe its immunophenotypic profile using flow cytometry. The cells showed a hybrid MM-WM phenotype, strongly expressing CD38 but lacking CD45 and DR, typical for plasma cells; however, pan-B cell antigens CD20 and FMC7 as well as weak monoclonal surface Ig also were positive, resembling B-cell lymphoproliferative malignancies. Discordant B-cell antigen expression was present, in that pan-B antigens CD19 and CD22 were absent. In addition, B-cell activation antigen CD23, early B-precursor antigen CD10, and pan-T antigen CD5 were not expressed. Although CD20 and weak surface Ig expression have been reported in MM, FMC7 positivity has not been seen. The data therefore suggest that IgM myeloma may have a unique phenotype with characteristics of both MM and WM.

Aged↗

Treatment of cutaneous T-cell lymphoma with chimeric anti-CD4 monoclonal antibody.

Chimeric anti-CD4 monoclonal antibody was administered intravenously as a single dose to eight patients with mycosis fungoides. The dose was escalated throughout the study between patients groups, and individual patients received 50, 100, or 200 mg per dose. Seven of eight patients responded to treatment with an average freedom from progression of 25 weeks (range, 6 to 52 weeks). The treatment was well tolerated, and there was no clinical evidence of immunosuppression. Following treatment, there was significant suppression of peripheral blood CD4 counts in all patients for 1 to 22+ weeks. Only one patient made a very low titer human antichimeric antibody response. All but two patients made primary antibody and T-cell proliferative responses to a foreign antigen administered 24 hours after antibody infusion. However, there was generally marked, but temporary suppression of T-cell proliferative responses in vitro to phytohemagglutinin (PHA), tetanus toxoid, and normal donor lymphocytes. We conclude that at the dose levels studied, this antibody (1) had clinical efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4) decreased T-cell proliferative responses in vitro, and (5) did not induce tolerance to a foreign antigen.

Adult↗

Hematogones in the bone marrow of adults. Immunophenotypic features, clinical settings, and differential diagnosis.

Hematogones (HGs) comprise a B-lineage lymphoid precursor cell population in the bone marrow (BM) that may simulate acute lymphoblastic leukemia or lymphoma. Increased numbers of HGs have been noted in children, but few reports describe their occurrence in adults. We identified 13 adult patients with significant numbers of BM lymphoid cells with the morphologic and immunophenotypic features of HGs. Common features in these patients included (1) presence of small numbers of lymphoid cells in the BM aspirate with morphologic features of HGs; (2) absence of cytologic atypia or abnormal localization of lymphoid cells in the BM biopsy; (3) absence of abnormal morphology or CD10 (common acute lymphoblastic leukemia antigen) expression in circulating lymphocytes; (4) normal BM karyotype; (5) persistence of cytopenia(s) without apparent cause, often for a prolonged period of time; and (6) no evidence of neoplastic marrow involvement, confirmed by clinical follow-up. Flow cytometry demonstrated surface expression of CD10, CD19, a lower percentage of CD20, minimal expression of CD22, and limited but polyclonal immunoglobulin light chain. Nine patients had received previous immunosuppressive therapy or BM transplantation or both, seven for hematolymphoid neoplasia. However, four patients with cytopenias of unknown etiology had no antecedent history of malignancy or marrow suppressive therapy. These findings demonstrate the clinical, morphologic, and immunophenotypic features of HGs in adults, and emphasize the difficulty in distinguishing these cells from residual marrow blasts after chemotherapy.

Adult↗

CD5+ chronic B-cell leukemia with features intermediate to chronic lymphocytic leukemia and hairy cell leukemia.

Chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL) are differentiated B-cell leukemias with well-described clinical, morphologic, and immunologic characteristics. We encountered two patients with indolent chronic B-cell leukemia showing overlapping features of these malignancies. The patients had progressive splenomegaly, minimal lymphadenopathy, and abnormal lymphoid cells with abundant cytoplasm and villi, which were strongly positive for surface antigens CD22 and CD11c, features associated with HCL. However, blood counts showed lymphocytosis without neutropenia and monocytopenia, and the bone marrow biopsies demonstrated tightly aggregated nodules of lymphocytes. In addition, the lymphoid cells were dual positive for CD19 and CD5, displaying weak-to-moderately positive monoclonal surface immunoglobulin, findings strongly suggestive of CLL. One patient failed to respond to therapy with chlorambucil and prednisone. The second patient showed a partial response to treatment with 2-chlorodeoxyadenosine. We compare our patients with similar variants of differentiated B-cell leukemias reported in the literature, including disorders described as hairy cell variant (HCL-V) or splenic lymphoma with villous lymphocytes (SLVL).

Aged↗

Body fluid microscopy in US laboratories. Data from two College of American Pathologists surveys, with practice recommendations.

Questionnaires addressing laboratory practices in cerebrospinal fluid and body fluid (serous, synovial) microscopy were distributed to participants in the Clinical Microscopy Survey of the College of American Pathologists, Northfield, Ill, in 1985 and 1989. In both Surveys, cell enumeration was performed primarily by hemocytometry, while nearly all respondents used Wright-stained microscopy. There was little formal quality control to assess the accuracy of counts or differential cell count. Less than 55% of laboratories used the cytocentrifuge. About half of respondents performed a differential cell count on every sample. Slides with atypical or malignant cells were usually (> 85%) reviewed by physicians without automatic referral to the cytopathology section. Only about half of respondents examined every synovial fluid specimen with polarized microscopy for crystals. Other than a modest increase in use of the cytocentrifuge, the 1989 Survey showed little interval change in practices. In 1989, there was equal dependence on Wright's and Papanicolaou's stains for an infrequent diagnosis of malignancy. The low rate of positives may have related to the high prevalence of wedge smears, a suboptimal technique. The Hematology and Clinical Microscopy Resource Committee of the College of American Pathologists makes recommendations for optimal laboratory handling of body fluid specimens for microscopy.

Body Fluids↗

Evaluation of the Coulter STKS five-part differential.

The authors evaluated the Coulter STKS (Coulter Corp., Hialeah, FL) five-part differential in a tertiary-care hospital using samples with a broad range of distributional and morphologic abnormalities. Particular attention was given to the performance of the instrument-generated suspect flags that occur as an aid to identify samples with abnormal leukocytes. A morphologically abnormal, or positive, blood smear was defined by the presence of any blasts, malignant lymphoid cells, grossly dysplastic neutrophils, nucleated red blood cells (nRBC), platelet clumps, or reactive lymphocytes of more than 5%. The presence of any white blood cell-related suspect flag, except for Immature Granulocyte/Bands (i.e., Blasts, Variant Lymph, NRBC, Platelet Clumps, Review Slide, or WBC*R), was considered to be a positive instrument result. The STKS showed excellent quantitative results for the WBC differential compared with the manual differential when these "morphologic abnormalities" were absent in a 400-cell manual differential or low in numbers (< or = 5%). Specificity of these non-immature granulocyte/band suspect flags was good, with a false-positive rate of only 11.7%. Overall sensitivity in 113 samples with morphologic abnormalities was 67.3%. Sensitivity to detection of > or = 1% abnormal WBCs or > or = 1 nRBC/100 WBCs (a subset of 78 samples) was 80.8%. Sensitivity to detection of more than 5% abnormal WBCs or more than 5 nRBC/100 WBCs (a subset of 53 samples) was 84.9%. The primary deficiency was the inability of the STKS to flag samples with lymphoma cells, lymphoid blasts, or more than 5% reactive lymphocytes.

Blood Cells↗

Ciliated cell remnants in peritoneal dialysis fluid.

Ciliocytophthoria are anucleate remnants of ciliated epithelial cells derived from the lower respiratory tract and female reproductive tract. We report a case of ciliocytophthoria found in the effluent dialysis fluid of a young woman undergoing long-term ambulatory peritoneal dialysis. Inability to identify these "organisms" initially led to an extensive search for parasitic contamination or infection of the peritoneum. After identifying these "organisms" as ciliocytophthoria, a prospective study showed that ciliated cell remnants occur frequently in the effluent dialysate of young women, but not in older women or men. With increasing use of peritoneal dialysis, laboratory personnel can expect to see ciliocytophthoria in peritoneal dialysate effluent and should recognize them as benign, normal findings in young women.

Adult↗

Evaluation of the CELL-DYN 3000 differential.

The CELL-DYN 3000 (Unipath Corp., Mountain View, CA) differential was evaluated in a tertiary care hospital using samples with a broad range of distributional and morphologic abnormalities. Particular attention was directed to the performance of the instrument-generated suspect flags that occur as an aid to identify samples with abnormal leukocytes, as well as the estimates of abnormal cells that are made by the instrument. The CELL-DYN 3000 showed excellent quantitative results for the white blood cell differential compared with a 400-cell manual differential, in which morphologic abnormalities were absent or occurred in low numbers (< or = 5%). Specificity of the BLAST, VARIANT LYMPH, NRBC, WBC, or DIFF suspect flags (with the requirement that the blast estimate and variant lymphocyte estimate by the instrument be > or = 1%) was 82.6%. Sensitivity of these flags to detection of more than 5% "abnormal" leukocytes (blasts, malignant lymphoid cells, grossly dysplastic neutrophils, nucleated red blood cells, or reactive lymphocytes) or significant platelet clumping was 81.6%. The primary deficiency was the inability of the CELL-DYN 3000 to flag samples with small numbers (< or = 5%) of nucleated erythrocytes, lymphoid blasts, or hairy cells, or more than 5% reactive lymphocytes. Specificity of the IG flag (with immature granulocyte estimate > or = 3%) for immature granulocytes (metamyelocytes, myelocytes, or promyelocytes) was 94.9%. Sensitivity of the immature granulocyte flag varied from 41.7% for identifying IG > or = 1% to 100% for the three samples with immature granulocytes > or = 3%. Calculation of sensitivity and specificity to varying percentages of bands showed poor flagging performance, with many false-positive and false-negative results at all levels.

Blood Cells↗

Accuracy of low platelet counts on the Coulter S-Plus IV.

Recent improvements have occurred in the flagging criteria for erroneous platelet counts on Coulter S-Plus series instruments. The authors tested the accuracy of the S-Plus IV on over 400 patient samples with low platelet counts (less than 50,000/microL) as compared with phase microscopy. Only a small number of samples gave discrepant results (difference greater than 10,000/microL), and, when investigated, most often were found to be due to erratic phase microscopy results. Approximately one-third of all low platelet counts in our laboratory were flagged ("error code 10") by the instrument and required determination by phase microscopy. In addition, to prevent erroneous results due to giant platelets or microcytic red blood cells, the platelet histogram should be inspected for return to baseline at 20 cubic micrometers (fL).

Evaluation Studies as Topic↗

Red cell distribution width on the Coulter Model S-Plus.

Red cell distribution width (RDW) on the Coulter S-Plus has many limitations. Normal values (mean +/- 2 SD) were found to be sex dependent: 10.7 +/- 2.4 for males, and 9.8 +/- 1.8 for females. These ranges are broader than the normal range of 10.0 +/- 1.5 given by Coulter. When these broader ranges were applied, none of 29 patients with iron deficiency anemia showed an elevated RDW. Furthermore, a decrease in RDW with room temperature storage was observed and may contribute to erroneous results. The Coulter S-Plus RDW may not be as useful in quantitating anisocytosis as other methods of measuring the dispersion of the red cell volume histogram.

Anemia, Hypochromic↗

Incorrect least-squares regression coefficients in method-comparison analysis.

The least-squares method is frequently used to calculate the slope and intercept of the best line through a set of data points. However, least-squares regression slopes and intercepts may be incorrect if the underlying assumptions of the least-squares model are not met. Two factors in particular that may result in incorrect least-squares regression coefficients are: (a) imprecision in the measurement of the independent (x-axis) variable and (b) inclusion of outliers in the data analysis. We compared the methods of Deming, Mandel, and Bartlett in estimating the known slope of a regression line when the independent variable is measured with imprecision, and found the method of Deming to be the most useful. Significant error in the least-squares slope estimation occurs when the ratio of the standard deviation of measurement of a single x value to the standard deviation of the x-data set exceeds 0.2. Errors in the least-squares coefficients attributable to outliers can be avoided by eliminating data points whose vertical distance from the regression line exceed four times the standard error the estimate.

Blood Chemical Analysis↗