Recommendation for standardization of haematology reporting units used in the extended blood count.

INTRODUCTION: It is desirable in the interest of patient safety that the reporting of laboratory results should be standardized where no valid reason for diversity exists. This study considers the reporting units used for the extended blood cell count and makes a new ICSH recommendation to encourage standardization worldwide. METHODS: This work is based on a literature review that included the original ICSH recommendations and on data gathered from an international survey of current practice completed by 18 countries worldwide. RESULTS: The survey results show that significant diversity in the use of reporting units for the blood count exists worldwide. The use of either non-SI or other units not recommended by the ICSH in the early 1980s has persisted despite the guidance from that time. CONCLUSION: The diversity in use of reporting units occurs in three areas: the persistence in use of non-SI units for RBC, WBC and platelet counts, the use of three different units for haemoglobin concentration and the manual reporting of WBC differential, reticulocytes and nucleated RBCs when the latter are available from automated analysis or can be expressed as absolute numbers by calculation. A new recommendation with a rationale for each parameter is made for standardization of the reporting units used for the extended blood count.

Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program Study.

Gene expression profiling (GEP) has stratified diffuse large B-cell lymphoma (DLBCL) into molecular subgroups that correspond to different stages of lymphocyte development-namely germinal center B-cell like and activated B-cell like. This classification has prognostic significance, but GEP is expensive and not readily applicable into daily practice, which has lead to immunohistochemical algorithms proposed as a surrogate for GEP analysis. We assembled tissue microarrays from 475 de novo DLBCL patients who were treated with rituximab-CHOP chemotherapy. All cases were successfully profiled by GEP on formalin-fixed, paraffin-embedded tissue samples. Sections were stained with antibodies reactive with CD10, GCET1, FOXP1, MUM1 and BCL6 and cases were classified following a rationale of sequential steps of differentiation of B cells. Cutoffs for each marker were obtained using receiver-operating characteristic curves, obviating the need for any arbitrary method. An algorithm based on the expression of CD10, FOXP1 and BCL6 was developed that had a simpler structure than other recently proposed algorithms and 92.6% concordance with GEP. In multivariate analysis, both the International Prognostic Index and our proposed algorithm were significant independent predictors of progression-free and overall survival. In conclusion, this algorithm effectively predicts prognosis of DLBCL patients matching GEP subgroups in the era of rituximab therapy.

Genomic alterations in tubular breast carcinomas.

Tubular carcinoma of the breast is a well-differentiated variant of invasive ductal carcinoma and has been shown to have an exceptionally favorable prognosis, as manifested by a low incidence of lymph node metastases and an excellent overall survival. It is unknown whether this subtype represents an early step along the continuum of development to a more aggressive, poorly differentiated ductal cancer, or whether these cancers are destined to remain well differentiated with limited metastatic potential. We undertook an analysis of 18 pure tubular carcinomas of the breast using comparative genomic hybridization to evaluate the chromosomal changes in these tumors. An average of 3.6 chromosomal alterations of the genome were identified per case. The most frequent change involved loss of 16q (in 78% of tumors) and gain of 1q (in 50% of tumors). All but one case with 1q gain also exhibited a concomitant 16q loss. Other frequent changes involved 16p gain in 7 of 18 cases (39%) and distal 8p loss in 5 of 18 cases (28%). Comparison with known genomic alterations in a mixed group of invasive cancers shows tubular cancer to have fewer overall chromosomal changes per tumor (P <.01), higher frequency of 16q loss (P <.001), and lower frequency of 17p loss (P =.007). These results strongly suggest that tubular carcinomas are a genetically distinct group of breast cancers.

Loss of chromosome 16q in lobular carcinoma in situ.

Lobular carcinoma in situ (LCIS) and infiltrating lobular carcinoma may represent different forms of the same disease based on their frequent clinical association and similar histologic features. Patients with LCIS are at increased risk of multicentric and bilateral disease. Thus, LCIS may represent both a precursor to infiltrating lobular carcinoma and a marker of risk for breast cancer. To identify genomic alterations in LCIS, comparative genomic hybridization was performed on 17 cases without concurrent invasive carcinoma. Loss involving chromosome 16q was present in 88% of cases and was the sole detected alteration in 29%. Gain involving 1q was second in frequency, occurring in 41% of tumors, and in all cases was associated with loss of 16q. Other recurrent changes were loss involving 17p (18%), 8p (12%), and 12q24 (12%). E-cadherin immunohistochemistry was performed on all LCIS cases to evaluate the correlation of loss involving 16q22, the site of the E-cadherin gene, and altered protein expression. Most cases with 16q22 loss showed altered E-cadherin expression (12 of 13). These results in LCIS are similar to changes reported in infiltrating lobular cancer, confirming a genetic relationship between them. HUM PATHOL 32:292-296.

Prognostic markers in resected stage I and II non small-cell lung cancer: an analysis of 260 patients with 5 year follow-up.

We performed a retrospective analysis of potential prognostic markers in 260 patients with surgically resected stage I and II non small-cell lung cancer (NSCLC) with a minimum 5-year follow-up. Cox proportional hazard models and Wilcoxon tests were employed to analyze the effect of patient characteristics on survival and disease-free survival (DFS). In the univariate analysis, the following were significant predictors of shorter overall survival: N-stage (N1 vs N0) (p<0.001); T-stage (T2 vs T1) (p<0.001); antigen A (loss vs presence) (p<0.01); cough (present vs absent) (p=0.01); bcl-2 expression (positive vs negative) (p=0.03); age (>63.5 vs <63.5) (p=0.03); mucin (positive vs negative) (p<0.03). The following were significant predictors of shorter DFS: N-stage (p<0.001); T-stage (p=0.001); loss of antigen A (p=0.01); mucin expression (p<0.01); cough (p=0.02); Ki-67 expression (p=0.02) and negative bcl-2 expression (p=0.03). Analysis of survival difference for histologic subtype, degree of differentiation, aneuploidy, %S-phase, codon 12 K-ras mutation, and immunohistochemistry staining for Lewisy, p53, Rb, microvessel count, HER2, E-cadherin and neuroendocrine markers did not reach statistical significance. In multivariate analysis, the following predicted for shorter overall survival: N-stage (p<0.01), antigen A (p=0.01), age (p<0.01), and bcl-2 (p=0.05); and for DFS, N-stage (p<0.01), antigen A (p<0.01), Ki-67 (p=0.03), mucin (p=0.04) and T-stage (p=0.05). Of all the clinical-pathological, proliferative, and biological markers studied, only a few carried independent prognostic significance.

Prognostic significance of Ki-67 immunostaining and symptoms in resected stage I and II non-small cell lung cancer.

The proliferative rate of a tumor has been considered predictive of its clinical course. We evaluated the expression of the proliferative marker Ki-67 and its relationship to survival, disease-free survival and other clinicopathologic variables in both stage I and stage II non-small cell lung cancer (NSCLC). A total of 260 patients with surgically resected stage I (n = 193), and II (n = 67) NSCLC with at least 5 years follow-up were identified. The median survival for patients with low expression of Ki-67 (< or = 25%) was 54 months, while for those with high expression (> 25%), it was 45 months (P = 0.1). The disease-free survival in patients with low expression of Ki-67 was 59 months while it was only 32 months for patients with high Ki-67 (P = 0.1). Out of 136 patients, 84 (62%) had both increased S-phase (> 8%) and high Ki-67 (P = 0.001). A total of 28 of 30 patients who had loss of antigen A had high expression of Ki-67 (93.3%) (P = 0.03). Ki-67 expression was also higher in squamous cell (54/63, 85.7%) compared to nonsquamous cell cancer (70/108, 64%) (P = 0.03). We also analyzed for the presence of symptoms with survival. The presence of symptoms was not found to be statistically significant, for overall survival (P = 0.33) or disease-free survival (P = 0.72). When individual symptoms were analyzed, the presence of cough was statistically significant for both overall and disease-free survival. The median survival was 39 months for patients with cough, and 57 months for patients without cough (P = 0.04). Multivariate analysis showed higher N and T stages, presence of cough and loss of antigen A, predicted for poorer overall survival. Higher N and T stages, loss of antigen A, presence of mucin and cough and increased expression of Ki-67 predicted decreased disease-free survival. Although we did not find a statistically significant difference between low and high Ki-67, there was a trend for a poorer overall and disease-free survival in patients with high Ki-67 expression. Larger studies may be needed to prove a statistically significant effect of Ki-67 on survival. Future studies should assess the potential prognostic significance of the presence of symptoms (particularly cough) in addition to clinical-pathologic variables (such as T and N stage) and biological markers in patients with early stage NSCLC.

Aberrant DNA methylation of genomic regions translocated in myeloid malignancies.

The mechanism of aberrant genetic recombinatorial events in neoplasia is vaguely understood. One hypothesis is that aberrant DNA methylation may in some way predispose genomic regions to recombination. Using the t(9;22) of chronic myeloid leukemia (CML) and the t(15;17) of acute promyelocytic leukemia (APL) as models, our laboratory and others have gathered data supporting this hypothesis. These data are reviewed.

Prolonged prothrombin time and activated partial thromboplastin time due to underfilled specimen tubes with 109 mmol/L (3.2%) citrate anticoagulant.

Underfilling of specimen tubes containing 129 mmol/L (3.8%) buffered citrate prolongs prothrombin time (PT) and activated partial thromboplastin time (APTT) values. We studied this phenomenon by using 109 mmol/L (3.2%) buffered citrate as the anticoagulant, anticipating some increase in tolerance to underfilling. Venous blood drawn from 12 healthy subjects and 30 patients receiving long-term oral warfarin therapy was mixed with 109 mmol/L buffered citrate solution in proportions equivalent to filling the collection tubes from 52% to 100% of capacity. Accurate PT values were obtained from normal specimens if the tubes were filled to 65% or more of capacity. Accurate PT results in the therapeutic range were obtained only with filling to 80% or more of capacity (using a "moderately sensitive" thromboplastin reagent, International Sensitivity Index [ISI] = 2.06) or 90% or more of capacity (using a "highly sensitive" thromboplastin reagent, ISI = 1.01). In contrast, APTT was much less tolerant to underfilling, with prolonged values observed in most specimens filled to less than 90% of capacity. No false low values were observed. Specimen tubes should be filled to at least 90% of capacity to avoid falsely elevated PT or APTT results, but values within the reference range may be acceptable even from underfilled tubes.

Normal human ejaculatory duct anatomy: a study of cadaveric and surgical specimens.

PURPOSE: W examined the anatomy of the ejaculatory ducts in normal men and correlated findings with theories of ejaculatory duct obstruction. MATERIALS AND METHODS: Gross and microscopic anatomical studies were performed on cadaveric and operative specimens derived from radical prostatectomy. RESULTS: Histologically, the ejaculatory ducts are a continuation of the seminal vesicles. However, the thick muscle wall of the seminal vesicle is not present within the ejaculatory duct. Normal ejaculatory duct luminal and wall dimensions are remarkably uniform among men. A luminal diameter of greater than 2.3 mm. defines a dilated system statistically. CONCLUSIONS: The largely collagenous ejaculatory ducts may serve as simple semen conduits instead of muscular tubes with spasmodic, sphincteric or peristaltic properties. The anatomical findings presented suggest several possible mechanisms for the prevention of urinary reflux into the ejaculatory ducts.

Diffuse leptomeningeal involvement by a ganglioglioma in a child. Case report.

Gangliogliomas are tumors composed of neuronal and glial elements that typically grow slowly by expansion only. This report describes a 20-month-old girl with a ganglioglioma that extensively involved the subarachnoid space; microscopic foci of tumor were found in the brain and spinal cord. Despite chemotherapy and radiation therapy, the child died 5 months after diagnosis. Molecular genetic analysis showed loss of chromosome 17p DNA sequences in the tumor tissue.