We provide an overview of the principles of blood management: the appropriate use of blood and blood components, with a goal of minimizing their use.
To review the strategies that exploit combinations of surgical and medical techniques, technologic devices, and pharmaceuticals, along with an interdisciplinary team approach that combines specialists who are expert at minimizing allogeneic blood transfusion.
A search on Medline and PubMed for the terms English and humans used in articles published within the last 20 years.
Blood management is most successful when multidisciplinary, proactive programs are in place so that these strategies can be individualized to specific patients.
Health care as an industry is going through an evolution similar to that experienced by manufacturing and other service sectors of the world economy. When competition threatens, the traditional management approach is slash-and-burn to manage costs. This approach affects people, services, and facilities. When the slash-and-burn method runs out of fuel, organizations start to merge, thinking that bigger is better. Just getting bigger only looks like change, with a new cast of fewer people and organizational structure. The root cause for existing problems has not been fixed. The only real solution, as manufacturing and services learned, is to understand and improve work processes to ensure that the right work is being done in a high-quality manner and at a competitive price. The era of quality systems is just dawning in health care. The focus must remain on quality patient outcomes at a competitive price by improving supporting systems and processes to accomplish these goals.
Although minimally invasive (microinvasive) carcinoma (< or =0.1 cm) of the breast is a well-known and well-characterized entity in excision specimens, the significance of small foci of invasion in breast core needle biopsies has not been well described.
To define the significance of minimally invasive carcinoma in breast core needle biopsies.
Review of a large series of core needle biopsies for invasive carcinomas measuring 0.1 cm or less and correlation of the results with those of subsequent excision.
Large community hospital.
From approximately 8500 biopsies, a total of 18 cases of minimally invasive carcinoma from 16 women aged 42 to 80 years were identified. All were present on only 1 of 8 slides made from the block. Overall, the incidence was approximately 0.1% of all biopsies and 1% of all invasive carcinomas. Six cases were invasive lobular carcinomas, 1 was tubulolobular carcinoma, 3 were tubular carcinomas, and the remaining 8 were ductal carcinomas. Eight cases were associated with high-grade comedo ductal carcinomas, 2 with low-grade ductal carcinoma in situ, 3 with atypical ductal hyperplasia, 3 with atypical ductal hyperplasia and lobular carcinoma in situ, and 2 with no other lesion. From a total of 8 sections done entirely through the block, the lesion was present on the first level in 4 cases and the fifth level in 5 cases. No cases were identified in the last 3 levels. Subsequent pathology was available for 16 of the 18 cases. Invasive carcinomas measuring more than 1 cm were present in 9 cases (64%; along with 2 positive lymph nodes), invasive carcinomas less than 1 cm in 2 cases (14%), ductal carcinoma alone in 4 cases (29%), and no carcinoma in 1 case (7%). No pathologic or radiologic features were associated with the finding of invasive carcinoma at excision.
Invasive carcinoma measuring 0.1 cm or less is a rare finding in breast core needle biopsies, is commonly associated with in situ carcinomas and atypical hyperplasias, and is often associated with larger invasive foci at excision. However, invasive carcinomas smaller than 0.1 cm can occur without any other significant findings and may require relatively extensive sampling to identify.
Tissue microarrays (TMAs) have emerged as a high-throughput technology for protein evaluation in large cohorts. This technique allows maximization of tissue resources by analysis of sections from 0.6-mm to 1.5-mm core "biopsies" of standard formalin-fixed, paraffin-embedded tissue blocks and by the processing of hundreds of cases arrayed on a single recipient block in an identical manner.
To assess the expression of a series of biomarkers as a function of core size. Although pathologists frequently feel better if larger core sizes are used, there is no evidence in the literature showing that large cores are better (or worse) than small cores for assessment of TMAs.
Estrogen receptor, HER2/neu, epidermal growth factor receptor, STAT3, mTOR, and phospho-p70 S6 kinase were measured by immunofluorescence with automated quantitative analysis. One random 0.6-mm field (one 0.6-mm spot) was compared to 6 to 12 fields per spot, representing 1-mm and 1.5-mm cores, for 3 different tumor types.
We show that measurement of a single random 0.6-mm spot was comparable to analysis of the whole 1-mm or 1.5-mm spot (Pearson R coefficient varying from 0.87-0.98) for all markers tested.
Since TMA technology is now being used in all phases of biomarker development, this work shows that TMAs with 0.6-mm cores are as representative as those with any common larger core size for optimization of standardized experimental conditions. Given that a greater number of 0.6-cores can be arrayed in a single master block, use of this core size allows increased throughput and decreased cost.
Tissue microarrays (TMAs) are useful in gene/protein expression profiling of large number of tumors. Several studies have validated that a 0.6-mm core of a large tumor would give results similar to results of the whole section. However, cores from colloid-filled thyroid follicles, for example in breast carcinoma, may contain fewer cells compared to solid tumors.
The aim of this study is to validate thyroid TMAs choosing 2 core diameters, 0.6 and 2 mm, and to study the effect of core size and grid density on concordance with whole sections.
0.6-mm tissue cores were arrayed on a high-density TMA (406 cores). Two low-density TMAs (35 cores each) composed of 2-mm cores were also constructed. Immunohistochemistry was performed using primary antibodies to cytokeratin 19, HBME1, and CITED1 that have been found to be useful in the diagnosis of thyroid carcinoma. The results were compared with whole sections.
The concordance between high-density TMAs and whole sections was 61 of 77 (79%) for cytokeratin 19; 76 of 80 (95%) for HBME 1; and 67 of 75 (89%) for CITED1. The concordance between the low-density TMAs and whole sections was cytokeratin 19, 41 of 51 (80%) for cytokeratin 19; HBME1, 52 of 56 (92.8%) for HBME1 and 58 of 59 (98%) for CITED1. The most frequent discordance was negative core but positive focal heterogeneous protein expression in whole sections. On whole sections, the sensitivity of tests increased but the specificity decreased compared to TMAs; however, the accuracy remained similar (77%-83%).
Focal and heterogeneous protein expression was the most frequent reason for false negative results in TMAs. Tissue microarray remains an accurate method of screening for protein expression in a large number of thyroid tissues irrespective of core diameters or grid densities.
To develop a multi-institutional reference database of autopsy practice and performance for quality improvement purposes.
In 1990, participants in the Q-Probes quality improvement program of the College of American Pathologists (CAP) each retrospectively evaluated the 25 most recently completed consecutive autopsy reports and determined the number of deaths and autopsies that occurred in their institutions during 1989.
Hospital-based autopsies excluding forensic cases and stillborn infants.
Four hundred ten institutions in the United States and eight institutions in Canada.
Completeness of face sheet information contained in final autopsy reports, turnaround time for completion of final reports, and institutional autopsy rates.
In the aggregate database of 10003 autopsies, the following six data items (from a total of 21) were present in 95% to 100% of the final autopsy reports in at least 85% of the participating institutions: institution where autopsy was performed, patient's name, patient's sex, autopsy number, autopsy date, and prosecter's name. The turnaround times for the final autopsy reports were as follows: 30 days or less in 47.6% of the cases, 31 to 60 days in 28.8%, and more than 60 days in 23.7%. A higher median percentage of autopsy final reports were completed in 30 days or less in institutions with the following characteristics: nonteaching (P < .004), no pathology residency program (P < .002), and rural location (P < .027). A lower number of autopsies performed in 1989 was associated with a higher median percentage of final reports completed in 30 days or less (P < .007). The aggregate autopsy rate for all participating institutions was 12.4%, and the median rate was 8.3%. Median autopsy rates for teaching institutions and institutions with pathology residency training programs were 15% and 19%, respectively.
This multi-institutional study identified a core group of face sheet data items that were consistently present on final autopsy reports. However, the majority of the face sheet data items examined were inconsistently recorded. Approximately 75% of final autopsy report turnaround times were within the standard established by the Joint Commission on Accreditation of Healthcare Organizations. Nearly two thirds of the institutions reported autopsy rates for 1989 of 0% to 10%.
To examine and suggest improvements for deficiencies occurring in the specimen identification and accessioning process in the surgical pathology laboratory.
Using the College of American Pathologists' and the Joint Commission for Accreditation of Healthcare Organizations' requirements as the standard, each laboratory was asked to prospectively document deficiencies in specimen identification and accessioning for 4 months, or until a maximum of 4000 cases or 400 deficiencies were accrued.
Four hundred seventeen laboratories in the College of American Pathologists' voluntary quality improvement program, Q-Probes, participated in this study.
Identification and accessioning deficiencies were found in 60 042 (6%) out of a total 1 004 115 cases accessioned (median deficiency rate of 3.4%). Errors related to specimen identification accounted for 9.6% of these deficiencies, discrepant or missing information items were present in 77%, and 3.6% involved specimen handling. The most common deficiency was "no clinical history or diagnosis present on the requisition slip," which represented 40% of all deficiencies. Deficiencies were most often detected by the person assigned to accessioning duties or by histology personnel. In 66% of cases, no action was taken to remedy the deficiency, but this varied dramatically according to the specific type of deficiency. An action was taken to remedy deficiencies in 69% of cases involving specimen identification errors, in 58% of specimen handling errors, and in 27% of cases with discrepant or missing information. Peer group stratifiers were associated with a lower deficiency rate. Laboratories with lower numbers (<15 000) of accessioned cases and laboratories with a formal written plan for the detection of errors in accessioning and specimen identification reported lower rates of deficiencies. Factors that correlated with a higher rate of deficiencies included submitting the specimen container and requisition slip in a unique secondary container (P<.005) and labeling the specimen container with only a patient's name or unique patient identification number (as opposed to both identifiers).
The majority of deficiencies occurring in surgical pathology specimen identification and accessioning are related to missing or inaccurate clinical information. Deficiencies are detected in multiple locations, including areas not typically thought of as quality check points, such as transcription. A variable amount of effort occurs to rectify deficiencies; this effort is largely dependent on the type of deficiency involved. Finally, laboratories with a formal error detection plan had fewer deficiencies.
A 28-year-old pregnant woman was brought to the hospital complaining of epigastric pain. An exploratory laparotomy revealed acute cholecystitis with cholelithiasis, and a cholecystectomy was performed. A Gran-negative rod grew from a culture of gallbladder material. The isolate exhibited biochemical reactions consistent with Vibrio cholerae, while failing to agglutinate in Vibrio 0 group 1 antisera.
A 46-year-old man presented with pain and fever and a postphlebitic ulcer on his left leg. The wound was suppurative and open at the margins, but there was little underlying fasciitis and no apparent muscle or blood vessel involvement. Three separate wound cultures were obtained at two-day intervals, and all showed only Vibrio cholerae non-01. The patient was successfully treated with cefazolin sodium. This marks the second documented case of V cholerae non-01 type alone as a causative agent of cellulitis, and the first case where no saltwater origin could be demonstrated.
CONTEXT: Controversy exists about whether thyroid fine-needle aspirates (FNAs) should be processed with conventional smears or liquid-based preparations (LBPs).
OBJECTIVE: To compare the performance of conventional smears to LBPs for thyroid FNA slides circulated in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytology.
DESIGN: Participant responses for thyroid FNA slides were compared with the reference diagnosis at the level of 3 general diagnostic categories: negative, suspicious (which included only follicular and Hurthle cell neoplasm), and malignant. For specific reference diagnoses of benign/goiter and papillary thyroid carcinoma, the participants' specific diagnoses were analyzed and poorly performing slides were rereviewed.
RESULTS: The 47, 076 thyroid FNA slide responses, between 2001 and 2009, included 44, 478 responses (94%) for conventional smears and 2598 responses (6%) for LBPs. For the general reference category negative, participant responses were discrepant in 14.9% of conventional smears compared with 5.9% for LBPs (P < .001). The specific reference diagnosis of benign/goiter was misdiagnosed as a follicular neoplasm in 7.8% of conventional smears, compared with 1.3% of LBP. For the general reference category of malignant, participant responses were discrepant in 7.3% of conventional smears compared with 14.7% of LBPs (P < .001). The specific reference diagnosis of papillary thyroid carcinoma was misdiagnosed as benign/goiter in 7.2% of LBPs, compared with 4.8% of conventional smears (p
Rats treated with 1,2-dimethylhydrazine (DMH) exhibited colonic mucosal dysplastic foci prior to the development of tumors. Ultrastructurally, these, as well as the cancers that subsequently developed, were characterized by alterations in plasma membranes and an increase in cytoplasmic ribosomal particles, principally in stem cells and their absorptive derivatives. Rare Kulchitsky cells appeared preserved, but the mucin-producing or goblet-cell elements were compressed and atrophic. In addition, nuclear aberrations were more pronounced in the cancer than in the dysplastic foci. The principal ultrastructural difference between the so-called well-differentiated and mucinous forms of DMH-induced cancers was the presence of frequent intracytoplasmic lumens in the mucinous form. Such structures represented the analogues of signet ring cells observed by light microscopy. This experimental model of human colonic cancer shows that the mucosal stem-cell and dysplastic lesions represent their cytogenetic and histogenetic progenitors.
Light and electron microscopic characteristics of renal calcification caused by high doses of calcitriol (1,25-dihydroxycholecalciferol) were examined in suckling rats. Four daily doses of calcitriol caused greater hypercalcemia and kidney calcification in 2-week-old than in 3-week-old rats. Calcium deposits, as localized with glyoxal bis(2-hydroxyanil), von Kossa's, or alizarin red S stains, were found primarily in the renal cortex. Glomeruli and tubules were calcified in younger pups, whereas only tubules were affected in older pups. Electron-dense deposits were found primarily in proximal tubules and consisted of needlelike crystals, large mitochondrial granules, and lamellar deposits along basal laminae. The location and appearance of the deposits were similar to those described in vitamin D-treated adult rats. The deposits probably resulted from the hypercalcemia and not from a direct toxic effect of calcitriol on the kidney.
Immunoassays for prothrombin fragment 1.2 (F1.2) provide a specific measure of thrombin generation and offer potential value in detecting activation of the coagulation system and monitoring anticoagulant therapy. To standardize laboratory measurements of this analyte, it is important to define factors affecting interassay variability.
To determine the potential for standardization of F1.2 measurement by examining the effects of preanalytical variables and calibrator selection on F1.2 measurement.
Using three commercially available immunoassays, interassay and intra-assay correlations for F1.2 were determined using blood samples collected into heparin, citrate, and a solution of ethylenediaminetetraacetic acid, aprotinin, and D-phenylalanyl-L-prolyl-L-arginyl chloromethyl ketone. In a cohort of patients, interassay correlations for F1.2 were determined using blood collected from an arterial catheter. Dose-response curves were generated for each manufacturer-supplied calibrator set by substitution into each of the previously untested competing immunoassays.
F1.2 immunoassays with the same recommended specimen anticoagulant displayed stronger correlation than assays requiring different anticoagulants. Furthermore, a stronger interassay correlation was elicited by samples collected through an intra-arterial catheter as opposed to venipuncture. F1.2 calibrator sets differed quantitatively, with buffer-related matrix effects contributing to interassay variability.
Analytical standardization of F1.2 immunoassays is possible when a common anticoagulant, blood collection method, and calibrator set are used.
To evaluate the performance of the new commercial Miles H.3 RTX analyzer in counting reticulocytes.
The results from the counter were compared to those obtained from microscopic methods, following the National Committee for Clinical Laboratory Standards H44-P guidelines, and to the results from the Sysmex R-1000 counter. In total, 279 samples were analyzed in duplicate with each of the three methods. One hundred thirty-three samples were from healthy subjects, while 146 were from patients with various pathologies, 10 of whom presented with posttherapeutic aplasia of the bone marrow and 9 with iron-deficiency anemia.
The reference intervals for the normal controls are different for each of the three methods (manual: 0.35-2.35%, 16 to 116 x 10(9)/L; Miles H.3: 0.65-2.30%, 35.1 to 112.0 x 10(9)/L; Sysmex R-1000: 0.6-1.85%, 28.0 to 85.0 x 10(9)/L). The overall imprecision was lower for the instruments than for the microscopic method (Miles H.3: coefficient of variation, 11.6%; R-1000: coefficient of variation, 4.2%; microscopic method: coefficient of variation, 24.2%). The Miles H.3 shows a good correlation with the other methods, yet it overestimated the low values with respect to both the microscopic method (intercept, 0.55; slope, 0.70) and the R-1000 (intercept, 0.44; slope, 0.78). This became particularly pronounced in patients with marrow aplasia.
Miles H.3 can produce results with an acceptable degree of accuracy. The agreement with the dedicated fluorescence-based flow cytometer R-1000 at normal and high concentrations is also good. The possibility of providing reticulocyte indices as well as erythrocyte indices (mean volume, mean hemoglobin content, mean hemoglobin concentration) and the relative dispersion indices could be useful in understanding red cell pathophysiology in normal and iron deficient patients.
A clinical and pathologic analysis was made of 101 patients with surgically treated metastatic brain tumors. The most common primary site was the lung (58.4%), followed by th breast (11.9%), gastrointestinal tract (6.9%), and uterus (5.)%). In 14 patients, the disease began with cerebral symptoms. The overall average survival after craniotomy was 8.0 months, the longest survival being 8l/2 years; patients with one-year survivals composed 18.8% of the cases. The histologic features were almost the same in primary and metastatic tumors. The undifferentiated tumor metastasized most frequently to the brain, and adenocarcinoma of the papillary type also seemed to find the brain fertile ground for metastatic growth.
Lymphomas have traditionally been diagnosed on excisional biopsies of lymph nodes in order to evaluate tissue architecture and cytomorphology. Recent lymphoma classification schemes emphasize immunophenotypic, genetic, and molecular aspects in addition to morphology as diagnostic features. Core needle biopsies are increasingly being used to obtain tissue for diagnosis in patients with lymphadenopathy and a clinical suspicion of lymphoma. These procedures are rapid, minimally invasive, well tolerated, and may provide some architectural framework (unlike fine-needle aspirations), as well as material for ancillary studies.
To explore the accuracy, utility, and cost-effectiveness of this technique.
Core needle biopsies of 101 consecutive patients from 2 large community hospitals who were suspected of having primary or recurrent lymphomas were retrospectively reviewed. All patients had hematoxylin-eosin-stained sections of needle cores. Specimens morphologically suspicious for lymphoma were subjected to ancillary studies, including immunohistochemistry, flow cytometry, and/or molecular studies. Core needle biopsy diagnoses were correlated with subsequent excisional biopsies, if performed.
Core needle biopsies established a definitive pathologic diagnosis for the vast majority of cases. A diagnosis was considered sufficient to begin treatment for primary and recurrent lymphomas in most cases. Compared with an open biopsy, there is a cost savings of greater than 75%.
The accuracy of this technique, along with the cost savings and decreased morbidity, suggest that this method may be used safely and reliably as a first-line diagnostic technique.
Adjacent frozen sections of 102 consecutive female breast carcinomas were examined for the expression of the Ki-67 antibody-reactive proliferation-associated nuclear antigen and of estrogen and progesterone receptors with the use of monoclonal antibodies and peroxidase histochemistry. The results of steroid receptor stainings were semiquantitatively assessed (histoscore) on the basis of nuclear staining intensity and the percentage of positively stained carcinoma cell nuclei. Carcinomas negative for either receptor had significantly higher percentages of Ki-67-positive cells. The highest percentages of Ki-67-positive cells were observed in carcinomas negative for both estrogen and progesterone receptors. There was a highly significant decrease in receptor histoscores with increasing proliferative cell fractions as determined by Ki-67 positivity. No significant (progesterone receptor) or poor negative correlation (estrogen receptor) was observed when proliferative cell fractions were related to receptor concentrations from conventional steroid-binding assays. Immunoperoxidase staining for the Ki-67 antibody-defined proliferation antigen and steroid receptors in tissue sections provides a simple means to gain information of therapeutic and prognostic importance.
Several recent studies have detected human chorionic gonadotropin (hCG) expression in colorectal adenocarcinomas and have concluded that its expression is an adverse prognostic indicator. The patient population and length of follow-up has varied. Therefore, we reviewed a defined group of cases with long-term (> 5 years) follow-up. We studied 102 stage B2 and C2 nonmucinous adenocarcinomas immunohistochemically for the production of hCG. Expression of hCG was detected in paraffin sections, including tumor and adjacent mucosa, using immunolabeling with a polyclonal rabbit antibody and the avidin-biotin-peroxidase complex technique. Cytoplasmic positive staining was evaluated semiquantitatively in every low-power microscopic field containing tumor. Expression of hCG was noted in at least one field in 42% (43/102) of the carcinomas. There was no expression in adjacent mucosa. Although the staining was usually focal (< 5% of tumor cells), some cases did stain diffusely. There was no significant correlation of hCG expression with survival, stage, differentiation, age, race, sex, or site of tumor. We therefore conclude that hCG expression is not a significant prognostic indicator in stage B2 and C2 colorectal carcinomas.
To compare the primary diagnoses assigned by general surgical pathologists on a series of 103 consecutive colon biopsies from individuals infected with human immunodeficiency virus (HIV) with diagnoses rendered by a pathologist with extensive experience in gastrointestinal pathology in HIV/acquired immunodeficiency syndrome.
New sections were cut from paraffin blocks of 103 consecutive colon biopsies taken during colonoscopies of 82 different HIV-infected patients; all new sections were stained with hematoxylin-eosin. These individuals either had negative stool studies or had failed to respond to therapy and had chronic large bowel symptoms, such as frequent small volume-type diarrhea, tenesmus, and/or bright red blood per rectum. Immunohistochemistry for cytomegalovirus (CMV) was performed on 18 of 22 specimens originally diagnosed with CMV colitis.
The initial study yielded 70 (68%) negative or nonspecific diagnoses, 22 (21%) cases of CMV colitis, 5 (5%) Cryptosporidium diagnoses, 2 cases each of adenomatous polyps and Kaposi sarcoma, and 1 case each of spirochetosis and squamous cell carcinoma of the anorectum. Review of the recuts yielded 64 (62%) negative or nonspecific diagnoses, 12 (12%) new adenovirus infections (3 combined with CMV), and 11 (11%) lone CMV infections. Three attaching and effacing bacterial infections were diagnosed, 1 with adenovirus coinfection. A total of 4 spirochetosis cases were found on review. Seven (7%) of the biopsies showed at least 1 coinfection. Nine biopsies had features suggestive of inflammatory bowel disease.
Colonoscopy with biopsy after negative stool studies or failure to respond to therapy yielded a high proportion of negative or nonspecific diagnoses. Adenovirus and enteropathogenic bacterial infections had been totally overlooked on initial examination. It takes particular experience to evaluate gastrointestinal biopsies from HIV-infected patients.
The weights of fresh brains obtained at consecutive autopsies over a period of five years were reviewed. Brains with lesions, such as large tumor, hemorrhage, infarct, or edema, were excluded. Analysis of the brain weight of 1,261 subjects, aged 25 to 80 years, show that the mean brain weight decreases in order from white men to black men to white women to black women. These differences are statistically significant and become apparent at age 6 years. The rate of decrease for the brain weight after age 25 years is highest for white men, followed by black women, white women, and black men, and, except that between white men and white women, the differences are statistically insignificant. Contrary to earlier reports, the mass decreases rapidly after age 80 years. In evaluating an individual brain weight, it is important to compare it with the norm for each subgroup of a given age.
Operator training, quality control, and proper follow-up for out-of-range quality control (QC) events are crucial steps that must be adequately performed and documented to ensure excellent patient care and regulatory compliance.
To examine point-of-care testing (POCT) personnel training and QC documentation/compliance.
Participants in a POCT documentation study of the College of American Pathologists Q-Probes program collected data retrospectively for glucose and urine dipstick testing regarding test operators, operator competency assessment, and QC documentation. Documentation was assessed for participant adherence to 4 quality indicators: (1) whether test operator training was up to date, (2) whether the test operator names were noted in the test records, (3) whether QC was performed, and (4) whether out-of-range QC events were followed up. Data were analyzed for associations with institutional demographic and practice variables.
The institutional median number of POCT personnel was 648 for blood glucose and 76 for urine dipstick testing, with a median number of 105 948 glucose tests and 9113 urine tests performed. Ninety-four percent (3830 of 4074) of the test operators completed training or competency assessment within the prior 12 months, 96.8% (21 603 of 22 317) of the test records documented the operator, and 95.7% (19 632 of 20 514) of the expected QC events (per institutional regulations) were documented. Approximately 3% (659 of 20 514) of the QC events were outside the designated range (an average of 6 out-of-range QC events were identified per institution [n = 106]). Of the out-of-range QC events, 92.6% (610 of 659) had documentation of appropriate follow-up. Most laboratories (176 of 179; 98.3%) violated specimen requirements by storing POCT urine specimens for less than 24 hours.
There was greater than 90% compliance for POCT documentation and nearly 96% of expected QC events were properly documented.
To evaluate the ability of serum levels of 90K, previously reported as a progression marker of human immunodeficiency virus infection, to predict the future rate of CD4 lymphocyte decline.
Retrospective analysis of data from outpatients enrolled in a multi-institutional study.
One hundred five human immunodeficiency virus-positive intravenous drug users who had at least six serial CD4 lymphocyte measurements and starting CD4 levels of 200 x 10(6) cells/L or higher.
Rate of CD4 lymphocyte decline.
During a median follow-up of 28 months (range, 20-36 months), the estimated loss of CD4 cells in the whole patient population was 3.4 x 106 cells/L per month (P = .0045). Subjects who were on zidovudine treatment at study entry showed an average loss of 3.8 x 10(6) cells/L per month, significantly higher than in untreated subjects (P = .02), but similar to the loss observed for those requiring initiation of treatment during the course of the study. At baseline, 56 subjects had 90K levels of 10 microg/mL or less, and 49 had more than 10 microg/mL. The rate of CD4 decline in the high-90K group was approximately 5 x 10(6) cells/L per month (P < .0015), whereas in the low-90K group it was not different from zero (P = ns). No difference emerged in the rate of CD4 decline when subjects were stratified according to baseline 90K levels and zidovudine treatment, beta2-microglobulin, or neopterin serum levels.
90K serum levels are predictive of CD4 decline.
A variety of ischemic mechanisms, including those secondary to an arterial occlusion and those of transient cardiac arrest, injured the brain in a diverse but predictable manner. Analyses of the topographic distribution of the lesions and evaluation of the cellular responses allowed prediction of the approximate age and most likely cause of the ischemic injury. Infarcts, caused by arterial occlusions, involved the corresponding arterial territory and were either pale or hemorrhagic, depending on whether the ischemic territory was reperfused. The hemorrhage of venous infarcts was more extensive than that of arterial infarcts. An extreme instance of nonocclusive global brain ischemia resulted from massive increases in intracranial pressure, as may happen after closed head injuries, with or without intracranial bleeding. Transient global ischemia caused by a cardiac arrest, for example, resulted in multifocal lesions that involved all brain components.
Market-driven changes in the timing of elective surgeries and admissions have introduced barriers to completing pretransfusion testing in a timely manner. Consequently, blood bank personnel may not have adequate time to identify appropriate blood products for scheduled surgeries. Incomplete pretransfusion testing can delay surgery and significantly compromise patient safety.
To identify the incidence of avoidable problems associated with obtaining timely samples for adequate pretransfusion type and screen (T&S) testing, to identify the practices and characteristics associated with improved rates of pretransfusion testing completed prior to surgery, and to determine the likelihood of antibody identification problems that affect the availability of blood.
Participants in the College of American Pathologists (CAP) Q-Probes laboratory quality improvement program were asked to collect data on when a T&S was collected in anticipation of elective scheduled surgery, when the T&S was completed, when the surgery started, and the results of those T&S tests. Participants also completed questionnaires describing their facilities, procedures, and practices.
One hundred eight public and private institutions participated in this Q-Probes Study, 97% of which were located in the United States.
Type and screen collection and completion relative to the start of surgery, and the results of those tests.
Of the 8941 T&Ss, 64.6% were collected prior to the day of surgery. The median laboratory completed approximately 69% of their T&S testing for scheduled surgeries at least 1 day prior to the surgery. Of those T&S tests that were collected on the day of surgery, the median laboratory completed almost 23% after the start of surgery. For 10% of participants, more than 75% of all T&Ss collected on the same day as surgery were not complete until after the start of surgery. When red blood cell-directed antibodies were identified, 78.7% were considered clinically significant, and 95.2% were alloantibodies. Positive antibody screens were significantly associated with delayed surgery and special efforts needed to obtain blood. Of those institutions with a specific protocol in place to collect T&S samples prior to hospital admission, the median laboratory completed the T&S at least 1 day prior to surgery 74% of the time. When the institution coupled the T&S collection protocol with T&S collection earlier than 3 days prior to surgery, the median laboratory completed the T&S at least 1 day prior to surgery almost 87% of the time. Type and screen collection less than 3 days prior to surgery resulted in special efforts needed to obtain blood more than 1% of the time. Type and screen collected on the same day as surgery directly resulted in a surgery delay 0.8% of the time.
Patients are unnecessarily being placed at risk by inadequate mechanisms to ensure available blood for surgery. All T&Ss were collected for scheduled surgeries with adequate opportunity for a T&S to be completed in advance of the surgery. Specific protocols helped improve the performance in terms of completing the T&S prior to surgery, as did mechanisms that permitted T&S collections in advance of the admission. Type and screen collection time relative to surgery was significantly associated with the incidence of surgery delay due to unavailable blood; the less time between collection and surgery, the less likely blood was available.
Attempts at histochemical localization of estrogen receptor with anti-steroid antibody or some fluoresceinated estrogens have given unacceptable sensitivities and specificities when compared with biochemical methods or clinical response. In the present study a monoclonal antibody against estrogen receptor (H222 Sp gamma) was used on cryostat sections of freshly frozen breast tumors with a peroxidase-antiperoxidase immunoperoxidase technique. Biochemical receptor analyses were by dextran-coated charcoal analyses. Tumors from three separate cohorts of patients were studied as follows: population A, 62 primary breast cancers from 1983; population B, 72 primary lesions stored from 1976 to 1983; and population C, 23 patients with metastases, treated with hormonal therapy. Distinct staining was seen in the cell nucleus. A semiquantitative relationship was seen between histochemical score assessment of staining and biochemical assay in each cohort. The sensitivity and specificity using a threshold of 75 for the histochemical score and more than 20 femtomoles/mg of protein for dextran-coated charcoal analyses were as follows: population A, specificity, 89%, and sensitivity, 95%; population B, specificity, 94%, and sensitivity 88%; and for population C, the comparison was with objective clinical response yielding specificity, 89%, and sensitivity, 93%.
Clear cell sarcoma of the kidney (CCSK) is a prognostically unfavorable renal neoplasm of childhood. Previous cytogenetic studies of CCSK have reported balanced translocations t(10;17)(q22;p13) and t(10;17)(q11;p12). Although the tumor suppressor gene p53 is located at the chromosome 17p13 breakpoint, p53 abnormalities are rarely present in these tumors.
To identify cytogenetic abnormalities in CCSK and correlate these findings with other clinicopathologic parameters.
A retrospective review of CCSK patients from 1990 to 2005 was conducted at our medical center. We performed clinical and histologic review, p53 immunohistochemical and classic cytogenetics (or ploidy analysis), and p53 fluorescence in situ hybridization analyses.
Five male patients (age range, 6 months to 4 years) were identified with cytogenetic abnormalities. Of 3 cytogenetically informative cases, one revealed a clonal balanced translocation t(10;17)(q22;p13) and an interstitial deletion of chromosome 14, del(14)(q24.1q31.1), and the other 2 patients had normal karyotypes. Fluorescence in situ hybridization for p53 in the t(10;17) case revealed no deletion. Immunohistochemical evaluation of p53 demonstrated lack of nuclear protein accumulation in all cases.
Together with the published literature, our results indicate that translocation (10;17) and interstitial deletions of chromosome 14q are recurring cytogenetic lesions in CCSK. To date, 3 cases of CCSK or "sarcomatoid Wilms tumors" have been reported to exhibit t(10;17). One previously reported case of CCSK contained deletion 14q. Results of p53 immunohistochemistry and/or p53 fluorescence in situ hybridization in this report suggest lack of mutations or deletions of this tumor suppressor in these CCSK cases. The t(10;17) breakpoint and deletion of chromosome 14q24 suggest that other genes are involved in tumor pathogenesis.
Skull base chordomas are rare, locally aggressive, notochord-derived neoplasms for which prognostically relevant biomarkers are not well established.
To evaluate whether newly discovered molecular alterations in chordomas have prognostic significance similar to what has been described regarding Ki-67 proliferation index.
We conducted a retrospective study of 28 cases of primary clival chordomas.
Ki-67 proliferation index 5% or more, p53 accumulation, and epidermal growth factor receptor expression were seen in 32%, 44%, and 8% of chordomas, respectively. 1p loss of heterozygosity (LOH) and/or 1p36 hemizygous deletion was seen in 30% of tumors, while 9p LOH and/or 9p21 homozygous deletion was seen in 21% of cases. Loss of heterozygosity at 10q23 and 17p13 were identified in 57% and 52% of cases, respectively. Ki-67 proliferation index 5% or more and 9p LOH were significantly associated with a shorter overall survival, while homozygous deletion at 9p21 via fluorescence in situ hybridization approached significance. No correlation with survival was found for p53 or epidermal growth factor receptor expression, 1p36 hemizygous deletion, or LOH at 1p, 10q23, or 17p13.
Chordomas with elevated Ki-67 proliferation index or deletion at 9p21 may be at risk for a more aggressive clinical course and shorter survival. These biomarkers may thus be used to improve therapeutic stratification.
The Boehringer-Mannheim Chemstrip-9 and Ames Multistix-10SG urine dipstick assays for the detection of proteinuria were evaluated. Chemstrip-9 was more precise than Multistix-10SG (13 inconsistencies vs 32 among duplicate pairs). Precision was poorest with the group of inexperienced technologists using Multistix-10SG (Chemstrip-9 yielded two inconsistencies vs 15 for Multistix-10SG) with the use of urine supplemented with protein standard. In the evaluation of both protein-supplemented and consecutively acquired patient specimens, Multistix-10SG and Chemstrip-9 performed in a statistically similar fashion regarding sensitivity and predictive value of a negative test result: supplemented sample sensitivity, patient sample sensitivity, and a predictive value of a negative test result of 90.3%, 46.8%, and 68.6%, respectively, for Multistix-10SG compared with 80.6%, 31.5%, and 63.5%, respectively, for Chemstrip-9. We conclude that neither test is sufficiently sensitive for the detection of low levels of proteinuria (1+ range) to function as a screening test for renal disease.
Light and electron microscopy of 11 giant cell tumors of tendon sheath revealed a pleomorphic cell population in which the giant cells had similarities to osteoclasts, and the stromal cells had similarities to primitive mesenchymal cells, osteoblasts, fibroblasts, and histiocytes. I suggest that giant cell tumors of tendon sheath are derived from mesenchymal cells with partial osseous differentiation.
Pathologic study of a rare 11-deoxycorticosterone-producing adrenocortical tumor causing primary aldosteronismlike signs and symptoms, revealed several characteristic features as follows: (1) fairly large size with histologic features corresponding to those of benign zone glomerulosa-type aldosteronoma, (2) lack of spironolactone (S) bodies despite S administration, and (3) heavy mast cell infiltration. In order to explain this rare histology, the localization of mast cells in the adrenal glands and functioning adrenocortical tumors of 67 surgical specimens were investigated. The results of the study supported the view that detection of mast cells helps in the differentiation of mineralocorticoid-producing tumors from cortisol-producing ones, and that the observed mast cell infiltration was due, in part, to its production of 11-deoxycorticosterone.
To assess the expression of potential osteoclastogenic and osteolytic factors in osteolytic lesions from patients with Langerhans cell histiocytosis.
Paraffin-embedded biopsy sections from 5 such archival cases underwent immunohistochemical procedures with antibodies to detect the following antigens: CD(1a), S100 protein, interleukin 11, the latency-associated peptide of transforming growth factor beta(1), and angiotensin-converting enzyme.
Commonalities noted include (1) the presence of multinucleated osteoclast-like giant cells, (2) the expression of interleukin 11 and latency-associated peptide antigens in lesional Langerhans cells, and (3) plasmalemmal immunoreactivity for angiotensin-converting enzyme antigen on non-Langerhans cell histiocytes and, on occasion, osteoclast-like giant cells and endothelial cells.
These observations suggest a possible pathogenetic sequence for osteolysis in Langerhans cell histiocytosis that involves angiotensin II formation, leading to the activation of latent transforming growth factor beta(1) and, in turn, to the enhanced production of interleukin 11, resulting in both osteoclastogenesis and impaired remodeling of bone.
Echoviruses cause neonatal disease following intrauterine and intrapartum acquisition of the organism or by nosocomial infection. Dizygous twins apparently became infected following transplacental transmission of echovirus 11. At 5 days of age, both twins experienced poor feeding, lethargy and hypothermia, and evidence of coagulopathy and hepatitis. During the sixth week of illness, the convalescence of twin A was complicated by peritonitis and sepsis, and the infant died. Pathologic findings included scattered foci of dystrophic myocardial calcification, distortion of hepatic architecture with fibrous connective tissue surrounding regenerative nodules and large foci of dystrophic calcification, and adrenal hemorrhagic necrosis and calcification. Twin B recovered without sequelae. The disease in twin A was unusual because of the extensive myocardial involvement. Also of interest was the variability of disease in twins who presumably had received a similar inoculum of organism by the same route.
The ultrastructural characteristics of a benign adrenal adenoma that produces deoxycorticosterone and 11-deoxycortisol were examined by transmission electron microscopy. Both large, round mitochondria with a few cristae in the peripheral portion and spherical or oval mitochondria with sacrotubular cristae were observed in adenoma cells. The development of agranular or granular endoplasmic reticulum varied from cell to cell. In some cells, many vacuoles and collagenous fibers were also seen. Thus, the adrenal tumor we examined was composed of the cells derived from the fascicular zone, which are associated with Cushing's syndrome, and the cells of the glomerular zone observed in association with primary aldosteronism.
Verruca vulgaris of the larynx (VVL) is a distinctly uncommon lesion related to the human papillomavirus (HPV). The clinical and pathologic features of a case involving the true vocal cords of a 37-year-old woman are presented and compared with the seven cases previously reported in the English language literature. Papillomavirus capsid antigen was detected in the excised tissue on immunostaining, and viral particles were seen by electron microscopy. In situ hybridization with biotinylated DNA probes clearly demonstrated HPV types 6/11. To our knowledge, this is the first case of VVL in which the virus associated with VVL has been genotyped. The results were unexpected because verruca vulgaris of the skin, lips, and oral cavity is associated with HPV types 2 and 4. This implies that verruca vulgaris can be caused by HPV types other than 2 and 4. In addition, since HPV types 6 and 11 are also the same genotypes associated with multiple papillomatosis of the larynx, it further indicates that VVL is virologically more related to multiple papillomatosis of the larynx than to its counterpart on the skin, lips, and oral cavity. The clinical and pathologic features that distinguish VVL from other similar lesions of the larynx are also discussed.
In signet-ring cell carcinoma of the breast, which was recognized in 1976 as a distinct clinicopathologic variant of lobular carcinoma, more than 20% of the malignant cells appear as signet rings formed by mucin-positive intracytoplasmic vacuoles. Several recent studies have demonstrated that the neoplasm behaves aggressively and is associated with a poor prognosis. However, the literature lacks information concerning steroid hormone receptor assays and DNA ploidy profiles, especially regarding how these tests affect a patient's prognosis. During a 5-year period (1985 to 1990), 11 (8.7%) of 126 cases of invasive lobular carcinoma met the criteria for signet-ring cell carcinoma. Ten of 11 cases were positive for estrogen and progesterone receptors; six cases showed type I and five showed type III DNA histograms. The high incidence of positive hormone receptors is significant: patients with receptor positive tumors, even those with type III DNA histograms, who were treated with tamoxifen citrate therapy after surgery had a significant increase in disease-free survival (30 months). Both the pathologist and the clinician should be aware of the prognostic influence of hormone receptor studies in the management of signet-ring cell carcinoma of the breast.
Micropapillary urothelial carcinoma (MPUC) is a rare variant of urothelial carcinoma. Most studies of MPUC have focused on the urinary bladder, but MPUC of the upper urinary tract remains to be investigated.
To investigate the pathologic features and clinical significance of MPUC in the upper urinary tract.
We searched the pathology files at our institution and identified 11 cases of MPUC of the upper urinary tract. The histology slides were reviewed, and the clinical information was obtained by review of medical charts.
The average age of the patients was 64.2 years (range, 22-76 years). The tumors were located in the renal pelvis (n = 5), ureter (n = 4), and ureteropelvic junction (n = 2). In all cases, MPUC accounted for an average of 45% (range, 10%-80%) of the tumor and was associated with conventional urothelial carcinoma. Lymphovascular invasion was present in all cases, and metastasis to lymph node was present in 4 of 5 patients whose lymph nodes were dissected. Two patients presented with pT2 disease, and both were alive without evidence of disease at 85 and 119 months after surgery. The other 9 patients presented with pT3 or pT4 disease: 4 of them died of disease at an average of 18 months; 4 surviving patients developed distant metastases; and 1 surviving patient with limited follow-up (6 months) showed no evidence of disease.
Micropapillary urothelial carcinoma of the upper urinary tract often presents at an advanced stage with lymphovascular invasion and distant metastasis. The presence of MPUC, even focal, indicates a poor clinical course.
Cerebrospinal fluid (CSF) diagnoses encompass a wide spectrum of conditions. The authors review one institution's CSF cytology results over an 11-year period.
A retrospective study of 5951 CSF specimens generated between 1985 and 1995. Specimens from pediatric patients (<19 years of age) from the same time period were separately identified.
A total of 5561 adult and 390 pediatric CSF specimens were interpreted. A diagnosis of "negative for malignant cells" was assigned in 5171 (93%) of the adult cases and in 351 (90%) of the pediatric cases. Specific infectious organisms were identified in 26 adult specimens and one pediatric specimen. Cryptococcus was the most common infectious agent observed (n = 23 adults), and Toxoplasma was the sole pediatric infectious agent. Two hundred seventy-six (5%) adult cases and 31 (8%) pediatric cases were positive for malignant cells. Diagnoses included metastatic tumors (adult, 140 [51%]; pediatric, 0); lymphoma/leukemia (adult, 112 [41%]; pediatric, 4 [13%]); malignant unclassified neoplasms (adult, 9 [3%]; pediatric, 0); and primary central nervous system neoplasms (adult, 12 [4%]; pediatric, 27 [87%]). Medulloblastoma was the most common pediatric neoplasm (n = 21). There were 105 (2%) adult cases and 8 (2%) pediatric cases with atypical cells present. Atypical lymphoid cells were the most common type in adult cases (53%).
In our experience, infectious agents were rarely identified in pediatric CSF specimens. In adult specimens, the most commonly identified organisms was Cryptococcus. Primary central nervous system neoplasms accounted for a higher percentage of CSF specimens in the pediatric population than in the adult population. The most commonly identified malignancy in adults was metastatic neoplasms, and in children, medulloblastoma.
The manual microscopic examination (MME) of the urine sediment is an imprecise and labor-intensive procedure. Many laboratories have developed rules from clinical parameters or urinalysis results to limit the number of these examinations.
To determine the rate of urinalysis specimens on which an MME of the urine sediment was performed, document how various rules influence this rate, and determine whether any new information was learned from the MME.
Participants selected 10 random urinalysis tests received during each traditional shift and determined if an MME was performed until a total of 50 urinalysis tests with an MME were reviewed. Participants recorded the rules that elicited an MME and any new information learned from such an examination.
The MME rate for the median institution was 62.5%. An MME of urine was most frequently done for an abnormal urinalysis result and often resulted in new information being learned, irrespective of the rule that elicited the MME. The median institution learned new information as a result of the manual examination 66% of the time. The use of an automated microscopic analyzer was associated with fewer manual examinations (P = .005), whereas the ability of a clinician to order a manual examination was associated with more manual examinations (P = .004).
The use of an automated microscopic analyzer may decrease the number of MMEs. An MME when triggered by an abnormal macroscopic appearance of urine, a physician request, or virtually any positive urinalysis result often resulted in new information.
Angiosarcoma, one of the least common sarcomas, has become increasingly important because of its association with radiation therapy, especially for breast cancer. Most are sporadic, presenting as cutaneous tumors in the scalp/face of elderly patients. However, angiosarcoma has a wide anatomic distribution including soft tissue, visceral organ, and osseous locations. Predisposing conditions include environmental exposures to chemical or radioactive sources. Radiation-associated angiosarcoma typically presents as a cutaneous tumor several years posttherapy. The latency for radiation-associated mammary angiosarcoma is relatively short, sometimes less than 3 years. Atypical vascular lesion refers to a small, usually lymphatic-type vascular proliferation in radiated skin. Although most atypical vascular lesions pursue a benign course, they recur and very rarely progress to angiosarcoma. Distinguishing this lesion from well-differentiated angiosarcoma in a biopsy can be challenging, especially because areas indistinguishable from atypical vascular lesion are found adjacent to angiosarcoma. Recently, vascular-type atypical vascular lesion, which resembles hemangioma, has been described, thus expanding the definition of this entity.
The etiology of lymph node infarction may be difficult or impossible to determine by histologic examination. Lymph node infarction is followed by malignant lymphoma in some but not all patients. The role of immunohistochemistry in the evaluation of lymph node infarction is not well defined. Although it is widely believed that necrotic tissue is not suitable for immunohistochemical study, this view may be inaccurate.
To determine whether lymphoid antigens are preserved in infarcted lymph nodes and to determine the utility of immunohistochemical staining in the evaluation of lymph node infarction.
Retrospective immunohistochemical study of infarcted lymph nodes using archival formalin-fixed, paraffin-embedded tissue.
Academic medical center.
Eleven adult patients with lymph node infarction retrieved from pathology files.
Results of immunohistochemistry, diagnosis of lymphoma.
Preservation of lymphoid antigens was observed in 4 of 6 cases of lymph node infarction associated with malignant lymphoma, including 3 of 5 cases of diffuse large B-cell lymphoma and 1 case of peripheral T-cell lymphoma. Nonspecific staining was not encountered. In 1 case, in which an infarcted lymph node showed a benign pattern of lymphoid antigen expression, lymphoma has not developed after 5 years.
Lymphoid antigens are frequently preserved in cases of lymph node infarction, and immunohistochemical study of infarcted lymph nodes may provide clinically useful information.
Ashwagandha, a popular Ayurvedic medicine, is now available in the United States. Alkaloids found in this herb have structural similarity with digoxin.
To study potential interference of Ashwagandha with serum digoxin measurement by immunoassays. Potential interference was also investigated with immunoassays for 11 other commonly monitored drugs. In addition, interaction of components of Ashwagandha with the Fab fragment of antidigoxin antibody (Digibind) was investigated.
Two different brands of liquid extract and 1 dry powdered form of Ashwagandha were used for this investigation. Aliquots of drug-free serum were supplemented with various concentrations of Ashwagandha and apparent digoxin concentrations were measured by 3 digoxin immunoassays. Mice were fed with Ashwagandha and apparent digoxin concentrations were measured 1 and 3 hours after feeding. Potential interference of Ashwagandha with immunoassays of 11 other drugs was also investigated. Interaction of components of Ashwagandha with Digibind was studied in vitro.
Significant apparent digoxin concentrations were observed both in vitro and in vivo using the fluorescence polarization immunoassay of digoxin, whereas the Beckman and the microparticle enzyme immunoassay digoxin assay demonstrated minimal interference. Immunoassays of 11 other drugs tested were unaffected. When Ashwagandha extract was added to a serum pool containing digoxin, falsely elevated digoxin value was observed with fluorescence polarization immunoassay, but values were falsely lowered when measured by the microparticle enzyme immunoassay. Digibind neutralized digoxin-like immunoreactive components of Ashwagandha in vitro.
Components of Ashwagandha interfered with serum digoxin measurements using immunoassays. Digibind neutralized free digoxin-like immunoreactive components of Ashwagandha.
The vanishing or regressed testis is an entity well known to urologists and pediatric surgeons, affecting approximately 5% of patients with cryptorchidism. However, there is little review and discussion of this entity among pathologists with only 2 of 40 published reviews of testicular regression syndrome (TRS) found in the pathologic literature.
To assess recognition of TRS among a subset of pathologists and to determine the applicability of histologic criteria for TRS as published.
An 8-year retrospective review of cases submitted as atrophic or regressed testis was performed. Original diagnosis and diagnosis after review were compared to assess pathologic recognition of TRS. Pathologic assessment included identification of vas deferens, epididymis, dystrophic calcification, hemosiderin, dominant vein, pampiniform plexus-like vessels, and vascularized fibrous nodule formation. At minimum, the presence of a vascularized fibrous nodule (VFN) with calcification or hemosiderin or VFN with cord element(s) was required for diagnosis.
Medical records and pathologic specimens of patients undergoing surgery for cryptorchidism or with specimens reviewed at a medium-sized university hospital were analyzed.
The original diagnosis in 3 (23%) of 13 cases was that of TRS. On secondary review, 11 (85%) of 13 cases showed features consistent with TRS. The diagnoses both before and after review showed a concurrence of 23% (3/13 cases). Two (15%) of 13 cases were correctly recognized and diagnosed as TRS at primary review; 1 case originally thought to represent TRS was not confirmed. Pathologic features correlated well with those reported in the literature. Among all 13 cases, the 11 confirmed TRS cases showed VFN in 11 (85%), intranodular calcification in 8 (62%), intranodular hemosiderin in 9 (69%), vas deferens in 9 (69%), epididymal structures in 5 (38%), and a dominant venous structure in 11 (85%). The average size of the VFN was 1.1 cm.
A urologic and pediatric surgical problem, TRS may be unrecognized by many practicing pathologists. In the typical situation in which a blind ending spermatic cord is submitted for tissue analysis, characterization of such cases as consistent with regressed testis is desirable and achievable in a high percentage of cases. Pathologists may play a pivotal role in management of these patients since histologic confirmation of the testis as regressed reassures the surgeon and the family of the correctness of diagnosis and can eliminate the necessity for further intervention.
Better procedures are needed whereby national proficiency testing survey providers can assess and improve the accuracy of laboratory measurements in clinical chemistry.
The 1994 College of American Pathologists Comprehensive Chemistry Survey.
This study of matrix effects and the accuracy of laboratory measurements for 11 analytes linked the logistics of the Survey to definitive methods at the National Institutes of Standards and Technology, reference methods at the Centers for Disease Control and Prevention, proficiency testing materials, and a fresh frozen serum sample. The data were analyzed with a statistical model of laboratory measurements.
(1) Matrix biases affected the results reported from 69% of the 644 peer group/survey specimen pairs evaluated. (2) Because of matrix biases, the reference value was the correct target value only 32% of the time; thus, the traceability established by definitive method and reference method value assignments on Chemistry Survey specimens did not assure accuracy on patient samples. (3) In contrast to matrix biases, the error caused by random matrix effects with proficiency testing samples was about the same as that caused by random specimen effects with fresh frozen serum, and both were less than within-run random analytic error. (4) Calibration biases occurred in 73% of the 180 peer groups evaluated, and, after matrix biases were removed, the total variance of interlaboratory measurements was due to peer group calibration bias (48%), within-peer-group random calibration error (31 %), within-run random error (14%), and random specimen effects (7%).
An opportunity exists to improve method calibration accuracy in clinical chemistry. With improved design, national proficiency testing surveys can monitor and help reduce method calibration error by converting reported survey results to a true accuracy base that predicts accuracy on patient samples. For medical purposes, the correct target values on artificial (matrix-modified) chemistry materials are reference values adjusted for the matrix bias of each peer group. Matrix biases estimated by the use of fresh frozen serum can be used as factors to transfer the accuracy of definitive methods from artificial reference materials to patient samples.