When leucocytosis is not leukaemia.

A female aged 84 years with a history of Clostridium difficile-associated diarrhoea presented from an extended care facility with altered mental status and respiratory distress. She was haemodynamically unstable and initial laboratory results revealed hyperleucocytosis (110.3×109/L). The presence of immature myeloid precursors, thrombocytopenia and respiratory distress, raised concern for an acute leukaemic process requiring emergent leucapheresis. However, on evaluation of the peripheral smear, prominent left shift and toxic granulation were noted, along with absence of blast cells. Considering her history of C. difficile infection, a CT scan of the abdomen and pelvis was obtained, which was suggestive of toxic megacolon. She was taken to the operating room for emergent colectomy. The pathology specimen showed pseudomembrane formation consistent with fulminant C. difficile infection. She was treated with oral vancomycin and intravenous metronidazole, followed by clinical improvement and resolution of leucocytosis and thrombocytopenia.

Assessment of bone marrow plasma cell infiltrates in multiple myeloma: the added value of CD138 immunohistochemistry.

Assessment of bone marrow involvement by malignant plasma cells is an important element in the diagnosis and follow-up of patients with multiple myeloma and other plasma cell dyscrasias. Microscope-based differential counts of bone marrow aspirates are used as the primary method to evaluate bone marrow plasma cell percentages. However, multiple myeloma is often a focal process, a fact that impacts the accuracy and reliability of the results of bone marrow plasma cell percentages obtained by differential counts of bone marrow aspirate smears. Moreover, the interobserver and intraobserver reproducibility of counting bone marrow plasma cells microscopically has not been adequately tested. CD138 allows excellent assessment of plasma cell numbers and distribution in bone marrow biopsies. We compared estimates of plasma cell percentages in bone marrow aspirates and in hematoxylin-eosin- and CD138-stained bone marrow biopsy sections (CD138 sections) in 79 bone marrows from patients with multiple myeloma. There was a notable discrepancy in bone marrow plasma cell percentages using the different methods of observation. In particular, there was a relatively poor concordance of plasma cell percentage estimation between aspirate smears and CD138 sections. Estimates of plasma cell percentage using CD138 sections demonstrated the highest interobserver concordance. This observation was supported by computer-assisted image analysis. In addition, CD138 expression highlighted patterns of plasma cell infiltration indicative of neoplasia even in the absence of plasmacytosis. We conclude that examination of CD138 sections should be considered for routine use in the estimation of plasma cell load in the bone marrow.

DRAQ5-based DNA content analysis of hematolymphoid cell subpopulations discriminated by surface antigens and light scatter properties.

BACKGROUND: Analysis of cell cycle kinetics offers important information regarding the behavior of normal and neoplastic cells. Most often, cell cycle determinations by flow cytometry (FCM) have been performed using whole-sample analysis with intercalating dyes like propidium iodide (PI). The cell cycle phase assessment in individual cell subsets in heterogeneous samples is best performed using combined antigen/scatter and DNA analysis. DRAQ5, a novel DNA binding dye that excites at 488 nm and emits in the far red spectra, rapidly penetrates intact live cells while preserving their light scatter properties and expression of surface antigens. We evaluated the ability of this dye to measure cell cycle phases in a variety of clinical hematolymphoid samples. METHODS: We first compared whole sample DRAQ5 and PI cell cycle analyses in 26 clinical hematolymphoid samples. Next, we analyzed cell subpopulations in 39 samples of nonpathologic bone marrow by performing simultaneous CD45/CD34 and DRAQ5 staining. We assessed cell cycle characteristics specific to each population identified by CD45/CD34/side light scatter: lymphocytes, monocytes, immature and mature granulocytes, nucleated erythroid cells, and early precursors. RESULTS: Whole sample DNA cell cycle analyses by DRAQ5 and PI showed no significant differences in S-phase. DRAQ5, however, produced slightly larger coefficients of variation. DRAQ5-based DNA content analysis was easily performed on the distinct marrow cell subpopulations, since light scatter and antigen expression were completely preserved. Significant differences in S-phase were noted between subpopulations of cells exhibiting different degrees of maturation. CONCLUSIONS: Because of its simplicity of use, excitability with 488 nm lasers, and the ability to stain viable cells, DRAQ5 should prove most useful in the kinetic evaluation of normal and neoplastic hematolymphoid cell subsets identified by light scatter and antigenic expression.

Strategies for reducing cancer incidence and mortality in African American and Arab American and Chaldean communities in the Detroit metropolitan area.

OBJECTIVES: We studied the feasibility of implementing a community-based participatory process (CBPP) that addressed cancer education, prevention, and screening in 2 ethnic minority populations by evaluating the improvement in rates of cancer screening compared with historical benchmarks. METHODS: From 2003 to 2009, 2281 community members participated in CBPPs conducted by the Beaumont Cancer Institute in cooperation with the Arab American and Chaldean (AAC) Council, the National Cancer Institute, and the American Cancer Society. The study population consisted of 1067 individuals who completed a postcancer forum survey: 642 from the African American (AA) and 425 from the AAC forums. Data were collected on participants' screening history and participation in subsequent screening tests after the previous year's CBPP. RESULTS: Following attendance of at least one cancer forum the previous year, 329 (30.8%) of the 1067 participant respondents underwent some type of cancer screening, 32% in the AA forums and 28.9% in the AAC forums. Compared with published controls, the CBPPs led to a 38.6% increase in mammographic screening and a 28.7% increase in prostate-specific antigen screening; the AA cohort had 39.7% and 28.4% increases whereas the AAC cohort had 36.3% and 28.9% increases in mammographic and prostate-specific antigen screening, respectively. CONCLUSIONS: The results of this study suggest that implementing CBPPs are feasible in underscreened ethnic minority populations. Further studies need to be performed to determine the absolute benefit of CBPPs compared with baseline levels of screening within these ethnic minority populations.

Composite biclonal marginal zone lymphoma of lung and chronic lymphocytic leukemia: pathologic, phenotypic, cytogenetic, and molecular study.

The simultaneous diagnosis of marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare. This study reports a patient with composite synchronous biclonal occurrence of MALT lymphoma of the lung and CLL/SLL. The morphology of the lung and peripheral blood showed features of MALT lymphoma and CLL, respectively. The cytogenetic evaluation of the lung specimen revealed a t(1;14) (p22;q32), a frequent genetic abnormality in MALT lymphoma. Flow cytometry analysis of the lung tissue showed features of MALT lymphoma and CLL/SLL with different light chain restriction, whereas the blood showed phenotypic evidence of CLL/SLL. Fluorescence in situ hybridization study of the blood showed a deletion of 13q14 and 17p13. Immunoglobulin heavy chain (IgH) gene rearrangement study of the lung tissue and blood showed a monoclonal IgH gene rearrangement with distinct light chain restriction, suggesting that the immunophenotypically different cell populations originated from separate clones.

Correlating metabolic activity with cellular proliferation in follicular lymphomas.

PURPOSE: The aim of this study was to correlate metabolic behavior of follicular lymphoma with proliferative index (Ki67). MATERIALS AND METHODS: Pre-treatment 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography-computed tomography scans of 23 patients with pathologic diagnosis of follicular lymphoma were retrospectively analyzed together with Ki67. The maximal standardized uptake value (SUV) was measured and corrected to glucose level of 100 mg/dl over the biopsy region (BxSUV100) and at the highest tumor activity of the body (BmSUV100). RESULTS: BxSUV100 was significantly correlated with Ki67 (p = 0.037). There was an increasing trend of metabolic activity across the pathologic grades of follicular lymphomas. BmSUV100 and BxSUV100 were also significantly different (p < 0.0005), suggesting potential pitfalls of sampling error by histology. CONCLUSION: The increasing trend of metabolic activity across follicular lymphoma grades correlates with cellular proliferation. The metabolic information from positron emission tomography-computed tomography may offer another useful parameter in the management of follicular lymphomas.

Exceptionally low metabolic activity in aggressive peripheral T-cell lymphoma.

PURPOSE: To investigate metabolic behavior of aggressive peripheral T-cell (PTC) lymphoma compared with other aggressive T-cell (OTC) nonHodgkin's lymphomas (NHLs) and the various grades (1, 2, 3) of follicular B-cell (FC) NHL as a reference cell type for indolent to aggressive behavior. MATERIALS AND METHODS: Pretreatment 2-deoxy-2-[¹8F] fluoro-d-glucose positron emission tomography-computed tomography scans of 33 patients with pathologic diagnosis of aggressive T-cell NHL and FC (FC1 = 6, FC2 = 8, FC3 = 9, PTC = 6, OTC = 4) were analyzed. The maximal standardized uptake value (SUV) was measured over biopsy region (BxSUV) and the highest tumor activity of the body (BmSUV). RESULTS: There were significant differences in both BxSUV (P = 0.036) and BmSUV (P = 0.026) among these five groups with significantly lower metabolic activity in PTC compared with other aggressive NHL (FC3, OTC). BmSUV in PTC was significantly lower than that in OTC (8.2 ± 2.5 vs. 22.3 ± 7.0, P = 0.029) and was similar to that of FC1 (9.4 ± 1.9) and FC2 (9.7 ± 1.4) but lower than that of FC3 (14.6 ± 2.7). Similar findings were noted in BxSUV between PTC and OTC (6.7 ± 2.5 vs. 20.4 ± 7.2, P = 0.035). CONCLUSION: Although 2-deoxy-2-[¹8F]fluoro-d-glucose positron emission tomography has been found to reflect metabolic activity for the aggressiveness of B-cell NHL, PTC has an exceptionally low metabolic activity, similar to that of low-grade B-cell FC1 and FC2.

FDG positron emission tomography/computed tomography scan may identify mantle cell lymphoma patients with unusually favorable outcome.

OBJECTIVE: Patients diagnosed with mantle cell lymphoma (MCL) have generally poor prognosis, but a minority have a longer survival. There are no markers to identify this group and no generally established prognostic index for MCL. Our objective was to assess the prognostic value of the staging FDG PET/computed tomography (CT) scan. METHODS: We retrospectively analyzed initial scans performed at three institutions on biopsy-proven, cyclin D (+) MCL patients. The association of the SUVmax of the 'hottest focus' with overall survival (OS) and failure-free survival (FFS) was evaluated. Receiver operating characteristic analysis of SUVmax versus survival was used to establish a cut-off point of 4.83. In addition, PET findings were compared with contrast-enhanced CT performed within 3 weeks in patients from one institution. RESULTS: Both the OS and FFS for patients with SUVmax greater than 5 were significantly decreased (P<0.01 and <0.001, respectively) as compared with the patients with SUV < or = 5. The 5-year OS for group with SUVmax < or = 5 was 87.7% and for SUVmax greater than 5 it was 34%. For SUVmax < or = 5, the median FFS was 45.3 months as compared with 10.6 months for SUVmax greater than 5. PET changed the stage as compared with CT alone in 45% of patients. CONCLUSION: Staging FDG PET/CT is superior to CT and may be used in the future for identification of a subset of MCL patients with a better outcome than otherwise expected.

Detection of T-regulatory cells has a potential role in the diagnosis of classical Hodgkin lymphoma.

Previous studies have demonstrated an increase in T-regulatory cells in the involved lymph nodes and peripheral blood of patients with Hodgkin lymphoma. Our study examined whether the detection of T-regulatory cells by flow cytometry could distinguish classical Hodgkin lymphoma (CHL) from benign cases and B-cell non-Hodgkin lymphomas (B-NHL). We measured CD4, CD25, and CD152 in 14 CHLs, 2 nodular lymphocyte-predominant Hodgkin lymphomas, 31 B-NHLs, and 54 benign cases. All T-regulatory cell parameters, including percent lymphocytes CD4+/CD152+ and CD4+/CD25+/CD152+, and mean and median CD152 expression in CD4+/CD25+ lymphocytes, were higher in CHL than in B-NHL and benign. Mean CD152 in CD4+/CD25+ lymphocytes distinguished CHL from benign with 79% sensitivity and 100% specificity, and from B-NHL with 71% sensitivity and 90% specificity. Overall, our results show that T-regulatory cells are increased in CHL and their detection may be a useful tool in differentiating CHL from other entities.

Polycythemia vera in a child following treatment for acute lymphoblastic leukemia.

Polycythemia vera (PV), a hematologic stem cell disorder characterized by predominant erythroid proliferation, is extremely rare in childhood. Some PV patients develop acute leukemia, especially acute myelogenous leukemia, but cases of PV occurring after treatment of acute leukemia are rare. The authors describe a girl with an atrioventricular canal who was diagnosed with acute lymphoblastic leukemia (ALL) at 23 months of age, was cured with chemotherapy, and developed PV 7 years later. She went on to develop hepatic complications of PV that culminated in death from liver disease at 20 years of age, without recurrence of ALL.