September 2007
MORBID ANATOMY
Newly Codified Glial Neoplasms of the 2007 WHO
Classification of Tumours of the Central Nervous
System: Angiocentric Glioma,
Pilomyxoid Astrocytoma and Pituicytoma
Brat DJ, Scheithauer BW, Fuller GN et al
The 4(th) edition of the WHO Classification of Tumours of the Nervous System (WHO 2007) introduces changes that reflect both the recognition of new brain tumour types and a better understanding of neoplastic behavior. Three new tumours, angiocentric glioma (AG), pilomyxoid astrocytoma (PMA), and pituicytoma are added to the section on gliomas. AG is a slowly growing cerebral tumour that typically presents with seizures in children and young adults. It is characterized by monomorphous, bipolar tumour cells with a striking perivascular growth pattern. Although the 'cell of origin' of AG is not clear, ultrastructural evidence points to an ependymal derivation. Typically, AG can be cured by total resection, and is designated WHO grade I. PMA is a solid, circumscribed tumour occurring mainly in the hypothalamic region of young children. It is composed of a monomorphous population of bipolar tumour cells within a rich myxoid background, with a conspicuous anglocentric arrangement. While PMA is considered a more aggressive variant of pilocytic astrocytoma, this relationship awaits further clarification. The PMA has been designated WHO grade II. The pituicytoma, involves the posterior pituitary and/or its stalk and affects adults. It is solid in architecture, composed of spindle cells and presumably derived from pituicytes. Pituicytomas are indolent tumours, and are designated WHO grade I.
Brain Pathol. 2007 Jul; 17(3):319-24.
Significance of
Intraepithelial Lymphocytes in Appendix
Kemal Deniz, , Lale Karakoç Sökmensüer et al
The aim of this study was to investigate the importance of the increase in intraepithelial lymphocytes (IELs) in the mucosa of the appendix. One hundred and four retrospective appendectomy specimens were examined to evaluate the IELs. Intraepithelial lymphocytosis was identified in 11.5% (12 cases) of the specimens. Of these 12 cases, 6 cases with intraepithelial lymphocytosis were associated with parasitic infection. No increase in IELs was found in the 36 appendices that were removed in other primary operations.
A wide range of immunologic stimuli can raise IELs in the gastrointestinal system. However, in appendectomies with clinical signs of acute appendicitis, an increase in IELs is more likely to be related to parasitic infection. This increase should be considered for the diagnosis of parasitic infections.
Pathology - Research and Practice, Volume 203, Issue 10,
The Impact of Large Sections on the Study
of in situ and Invasive Duct Carcinoma of the Breast
Foschini MP, Flamminio F, Miglio R et al
Large histologic sections (LHSs) are increasingly used in the study of normal and neoplastic breast tissue. LHSs allow the direct visualization of a large part of the breast glandular tree. Accordingly, LHSs have shown that in situ and invasive lobular carcinoma is a multilobar (and hence multifocal) neoplastic lesion in more than 50% of the cases, and that poorly differentiated duct carcinoma in situ (DCIS grade 3) is frequently unifocal, whereas it is often multifocal when the in situ lesion is a well-differentiated type (DCIS grade 1). Forty-five mastectomies were studied with large sections. Mastectomies were performed when quadrantectomy did not guarantee radical excision of the tumor with adequate cosmesis because of the large size of the lesion or because the neoplastic lesion was located below the nipple. Excluded were cases of lobular neoplasia or invasive lobular carcinoma, because they were reported separately, and cases of mastectomies performed for sarcoma or recurrent phyllodes tumor. All cases had undergone a preoperative diagnostic procedure (fine needle aspiration), and the relative positive material was reviewed. All 45 cases showed in situ duct carcinoma and 37 showed evidence of invasive duct carcinoma. Forty-two cases of DCIS were multifocal, whereas only 4 invasive duct carcinoma were shown as multifocal. When DCIS lesions were subdivided into 3 grades, no statistical significance was seen among the 3 groups of DCIS in regard to multifocality. Nevertheless, DCIS grade 1 was a widespread condition involving more than one lobe and quadrant, whereas DCIS grades 2 and 3 appeared more localized. DCIS grade 1 was more similar to that previously observed in lobular in situ neoplasia/lobular in situ carcinoma. In 66.6% of the cases, DCIS foci were found within the invasive areas, indicating a more than fortuitous occurrence (2-sided P = .0357).
Hum Pathol.
2007 Aug 20; [Epub ahead of print]
Outcome Prediction for Renal Cell
Carcinoma: Evaluation of Prognostic Factors for Tumours
divided according to Histological Subtype
Brett Delahunt; Peter B. Bethwaite; John N. Nacey
A
wide variety of parameters have been investigated for their prognostic
significance in mixed series of renal cell carcinoma (RCC). The classification
of RCC into separate types with differing morphology, genotype and probable
clinical outcome has led to a re-evaluation of many prognostic parameters with
studies confined to a single RCC morphotype. Tumour stage remains the most important predictor of RCC outcome
and recent investigations have focused upon tumour
diameter and the prognostic significance of stromal,
vascular and lymphatic invasion within the renal sinus. In large tumour series, morphotype has
been correlated with patient survival, with clear cell RCC being associated
with a less favourable outcome than chromophobe RCC and to a lesser extent papillary RCC, for
organ confined tumours. The prognostic significance
of nuclear grading remains controversial. Fuhrman grading has been shown to
have prognostic utility for clear cell RCC in some series. Recent studies have
shown that for papillary RCC, grading should be based upon nucleolar
size and that Fuhrman grading is inappropriate for chromophobe
RCC. Proliferative indices based upon a variety of markers
have been correlated with outcome for clear cell RCC (Ki-67, AgNORs, p21waf1/cip1 and p27Kip1) and
papillary RCC (Ki-67, AgNORs), although in some
series prognostic significance was lost on multivariate analysis. The presence
of tumour necrosis has been shown to predict survival
for clear cell and chromophobe RCC, and in clear cell
RCC quantification of tumour vascular density has
been correlated with outcome. Several molecular markers have been investigated
for prognostic significance, mostly in clear cell RCC. Although some of these
markers have been shown to be significantly associated with survival, these
findings remain to be confirmed in large scale follow-up studies.
Pathology,
Volume 39, Issue
Variations of Mitotic Index in Normal
Oluwole Fadare; Xiaofang Yi; Sharon X Liang et al
Cervical intraepithelial neoplasia is a premalignant (dysplastic) lesion that is characterized by abnormal cellular proliferation, maturation and nuclear atypia. The intraepithelial distribution, density, and nature (typical or atypical) of mitotic figures are routinely utilized diagnostic criteria to grade dysplasia and to distinguish high-grade dysplasia from potential histologic mimics such as transitional metaplasia, atrophy or immature squamous metaplasia. In this study, we evaluated the total mitotic indices of the cervical epithelia in hysterectomy specimens from patients with and without dysplastic lesions and investigated a possible relationship between mitotic index and hormonal status, using the endometrial maturation phase as a surrogate indicator of the latter. Two hundred seventy-four cervices from hysterectomy specimens (135 cases without dysplasia, 33, 35 and 71 cases with grades 1, 2 and 3 cervical intraepithelial neoplasia, respectively) were analyzed. A cervical mitotic index (total mitotic figures/10 high-power fields in the most proliferative area) was determined for each case. The endometrium in each case was classified into atrophic, early proliferative, late proliferative and secretory. For all three dysplasia grades, cases in the proliferative endometrium group always had a higher average mitotic index than those in the secretory and atrophic endometrium groups; this observation also held true for the benign cases. Furthermore, in all three dysplasia grades, the average mitotic index was always lowest in the atrophic endometrium group. Although the mitotic index showed expected patterns of increases with increasing dysplasia grades for most of the endometrial phases, this was not a universal finding. Notably, the average mitotic index for our cervical intraepithelial neoplasia 1 cases with late proliferative endometrium was higher than our cervical intraepithelial neoplasia 2 cases with secretory and atrophic endometrium. It is concluded that hormonal status, as reflected in endometrial maturation, can significantly affect the mitotic index of dysplastic squamous epithelium of the uterine cervix. Our findings confirm that the pathologic grading of dysplasia, especially in equivocal cases such as in metaplastic squamous epithelium, should not be solely dependent on the finding mitoses in the cervical squamous epithelium. The full composite of histopathologic features should form the basis for this determination.
Introduction
The ectocervical epithelium, as does squamous epithelium at other anatomic locations, continuously undergoes an organized program of maturation and differentiation from the basal to the superficial layers, with morphologic correlates of a progressive decrease in nuclear size, nuclear/cytoplasmic ratio and a progressive increase in nuclear chromatin density, cytoplasmic size and cytoplasmic glycogen of constituent cells. Basal cells appear to act as stem or reserve cells, whereas parabasal cells comprise the actively replicating compartment. Therefore, proliferative activity, whether evaluated by mitotic figures or the variety of available proliferative markers, should be largely confined to the lower 15% of the normal ectocervical epithelium. Accordingly, the intraepithelial distribution, density, nature (typical or atypical) of mitotic figures, as well as immunohistochemically defined proliferative activity, have emerged as important pathologic criteria to distinguish low-grade cervical intraepithelial neoplasia from high-grade cervical intraepithelial neoplasia and to distinguish high-grade cervical intraepithelial neoplasia from potential histologic mimics such as transitional metaplasia, atrophy or immature squamous metaplasia.
Compared to the endometrium and vaginal epithelium, where marked variations in the estrogen receptor (ER) content occur during the menstrual cycle, much less cyclic variation of ER expression occurs in the cervical lining. Nonetheless, it has long been recognized that cervical squamous epithelial cells contain sex-steroid receptors and hence, their proliferation and differentiation are influenced, to some extent, by the menstrual cycle and/or sex-steroid hormonal levels. Most studies have localized ERs and progesterone receptors (PRs), at minimum, to the basal and parabasal cell layers of the normal ectocervix. Data on a possible correlation between the localization and the extent of ERs and the menstrual cycle phase are less homogeneous. Kanai et al and Ciocca et al both reported that the expression and localization of steroid hormone receptors did not vary significantly with the phase of the menstrual cycle. In contrast, Scharl et al found that the intraepithelial ER localization in the proliferative phase, in postmenopausal cervices and in early gestation, were in the basal, parabasal and intermediate cells, whereas in the secretory phase, ER staining was confined to the basal and parabasal cells. Cano et al reported that the cervical epithelial ER content decreases during the secretory phase, whereas Mosny et al reported the opposite: the latter authors found that in the secretory phase, ER-positive cells may be found up to the most superficial layers, in contrast to the proliferative phase, where they are variably localized to the basal and parabasal layers. The somewhat conflicting findings of the aforementioned studies notwithstanding, it can be stated that at minimum, the cervical epithelium appears to be under some degree of hormonal influence.[20-28]
In the present retrospective analysis, we sought to explore the potential inter-relationships of these two factors -- hormonal effects on the ectocervical epithelium and intraepithelial proliferative activity. Hormonal factors that significantly affect the mitotic index of normal epithelium may also theoretically influence the mitotic index of dysplastic epithelium. However, current diagnostic criteria for cervical intraepithelial neoplasia, which as previously noted are partially dependent on mitotic index, do not take into account a possible role for the phase of menstrual cycle and/or hormonal status on the mitotic activity of the cervical epithelium. Herein, we evaluate the total mitotic index of the cervical epithelium in hysterectomy specimens from patients with and without cervical intraepithelial neoplasia lesions and investigate a possible relationship to hormonal status, using the endometrial maturation phase as a surrogate indicator of the latter.
Mod
Pathol. 2007;20(9):1000-1008.
CLINICAL PATHOLOGY
Glycemic Control and Type
2 Diabetes Mellitus: The Optimal Hemoglobin A1c Targets. A Guidance
Statement from the American College
Amir
Qaseem, Sandeep Vijan, Vincenza Snow et al
This
guidance statement is derived from other organizations' guidelines
and is based on an evaluation of the strengths and weaknesses of the
available guidelines. We used the Appraisal of Guidelines, Research
and Evaluation in
Statement 1: To prevent microvascular complications of diabetes, the goal for glycemic control should be as low as is feasible without undue risk for adverse events or an unacceptable burden on patients. Treatment goals should be based on a discussion of the benefits and harms of specific levels of glycemic control with the patient. A hemoglobin A1c level less than 7% based on individualized assessment is a reasonable goal for many but not all patients.
Statement 2: The goal for hemoglobin A1c level should be based on individualized assessment of risk for complications from diabetes, comorbidity, life expectancy, and patient preferences.
Statement 3: We recommend further research to assess the optimal level of glycemic control, particularly in the presence of comorbid conditions.
Diabetes mellitus is a leading cause of morbidity and mortality in
the
The purpose of this paper is to present the available guidelines from various organizations to help internists and other primary care physicians with effective management for glycemic control in type 2 diabetes mellitus and target level for hemoglobin A1c. The target population for this guideline is all patients with type 2 diabetes. This evidence is based on the review of the guidelines presented in this paper. This guidance statement is derived from other organizations' guidelines and is based on an evaluation of strengths and weaknesses of the available guidelines.
Statement 2: The goal for hemoglobin A1c level should be based on individualized assessment of risk for complications from diabetes, comorbidity, life expectancy, and patient preferences.
With consideration of the importance of glycemic control, the goals for glycemic control should be individualized on the basis of the life expectancy of the patient, presence or absence of microvascular and macrovascular complications, risk for adverse events related to glucose control, and patient preferences. Less stringent targets may be appropriate in patients who have short life expectancy or are at higher risk for adverse complications of therapy.
Statement 3: We recommend further research to assess the optimal level of glycemic control, particularly in the presence of comorbid conditions.
Understanding the benefits and harms of various levels of glycemic control remains challenging, particularly in complex patients with other comorbid conditions. In addition to the importance of glycemic control, management of blood pressure and lipid levels is also essential to prevent complications of diabetes. Further research that elucidates optimal level of glycemic control in patients of different ages, in patients with comorbid conditions, and in patient populations representative of those seen in practice would provide important additional guidance for management of diabetes.
Annals of Internal Medicine,
Predicting Kidney Function from Renal
Biopsy- Semiquantitative versus Quantitative Approach
Okoń K, Sułowicz W, Smoleński O, Sydor A, Chruściel B, Kirker-Nowak A, Rosiek Z, Sysło K, Stachura J.
The term glomerulonephritis encompass a heterogeneous group of diseases; these are a important cause of end stage renal disease. Although several evidence exist, that the main prognostic factors are extraglomerular lesions, no quantitative assessment is usually done. In nephropathological practice a semiquantitative approach is preferred. However, most of work on extraglomerular lesions significance was done with quantitative methods. The aim of the study was to compare the effects of quantitative and semiquantitative assessment of extraglomerular lesions in glomerulonephritis. The material consisted of 120 renal biopsies. On inspection, percentage of sclerosed glomeruli, degree of interstitial fibrosis, degree of interstitial infiltration, degree of tubular atrophy were and degree of mesangial matrix expansion assessed. For quantitative measurements AnalySIS 3.0 pro image analysis system was used. Relative interstitial volume, volume of interstitial infiltrate, with their variability--ross sectional areas of proximal and distal tubules were assessed by point counting method. Relative interstitial volume was significantly correlated to percentage of sclerosed glomeruli (R = 0.33 p < 0.001), degree of tubular atrophy (gamma = 0.57 p < 0.00001), degree interstitial fibrosis (gamma = 0.31 p < 0.0002) and mesangial matrix expansion (gamma = 0.24 p < 0.001). Semiquantitative and quantitative assessment of interstitial infiltrate was significantly correlated as well (gamma = 0.81 p < 0.001). Semiquantitatively assessed degree of tubular atrophy showed significant relation to total proximal tubular area (gamma = -0.30 p = 0,004). Percentage of sclerosed glomeruli was significantly correlated to creatinine level (R = 0.24 p = 0.03), but not to urea level (R = 0.09, NS). Semiquantitatively assessed degree of interstitial fibrosis showed only marginal correlation to creatinine level (gamma = 0.18 NS), however degree of interstitial infiltration was significantly correlated to creatinine (gamma = 0.34 p = 0.002) and urea level (gamma = 0.22 p = 0.06). Degree of tubular atrophy was significantly correlated to creatinine (gamma = 0.43 p < 0.001) and urea level (gamma = 0.28 p = 0.015). Relative interstitial volume was the very most important correlate of creatinine (R = 0.47 p < 0.0001) and urea level (R = 0.30 p < 0.01). In conclusion, it was confirmed, that the strongest correlate of renal function is relative interstitial volume. Some, but not all of semiquantitative parameters are also significantly correlated to kidney function.
Pol J Pathol. 2007;58(2):65-71.
POC Lactate: A
Marker for Diagnosis, Prognosis, and Guiding Therapy in the Critically Ill
Tissue hypoxia, a major concern in critical care medicine, correlates directly with morbidity and mortality. As a biochemical marker that identifies tissue hypoxia, blood lactate is a valuable assay because of the following: (1) it can detect tissue hypoxia and developing shock early in their appearance, (2) it provides prognostic information by giving a semiquantitative estimate of oxygen deficit, (3) it helps with differential diagnosis, and (4) it helps to monitor and direct resuscitation therapy. Rapid measurements of blood lactate at the point of care may be used for admission, early treatment, and triage decisions in the emergency department (acute myocardial infarction, trauma, sepsis, and occult illness), ensuring adequate oxygen delivery to the tissues in the operating room (high-risk surgeries) and monitoring circulatory shock in the intensive care unit (postsurgery, trauma, heart failure, sepsis, transfusion adequacy, and burns). Its value is cited in numerous other clinical applications.
Inadequate oxygen leads to tissue damage by a reduction in adenosine triphosphate (ATP) production (approximately 95%) and a net breakdown of ATP which is accompanied by acidosis and the development of a free radical precursor, hypoxanthine (under Anaerobic Metabolism in This process can occur in seconds/minutes and leads to damaged tissue (infarct) volumes that grow by the minute. The speed at which tissue damage occurs puts a very demanding turnaround time (TAT) on any marker for inadequate oxygenation.
SUMMARY
Lactate elevation is generally caused by hypoxia that results in a reduction in ATP, acidosis, and a buildup of intracellular hypoxanthine, a precursor for oxygen free radicals. These 3 factors are associated with tissue damage. To interpret lactate concentrations requires the following: (1) an understanding of the clinical circumstance leading to the increase in lactate (eg, late septic shock? exercise? liver compromise?), (2) the length of time that lactate has been elevated along with the magnitude of its elevation (requiring serial lactate analyses), and (3) whether lactate concentrations are increasing or decreasing. Correct interpretation of lactate concentrations in a given clinical setting will require a well-informed clinician.
The fact that lactate can be measured rapidly in whole blood (<2 minutes) makes it a valuable component to any POC critical care testing profile. Depending on the clinical setting, recognizing an increase in lactate as soon as possible, coupled with immediate resuscitation, is generally associated with improved outcome.
Volume 6(3), September 2007, pp 192-200
Critical Values -- More Than 3 Decades of
Experience: An Expert Interview With George D. Lundberg, MD
George D. Lundberg
Editor's Note:
Medscape Pathology & Laboratory Medicine Editorial Director David Danar, MD, interviewed George D. Lundberg, MD, about the history of the concept of critical values and his perspective on the past 30-plus years of its widespread adoption, with a look to the future.
Medscape: I understand that it's been more than 30 years since the concept of critical values initially was discussed in the literature. Tell us about the origin of the concept of "critical value" and the term itself.
Dr. Lundberg: I don't really know what the
origin of the concept was; I only know when we first happened onto it. I was,
at that time, assistant director of Laboratories and Pathology at the
Upon recognition of this, this patient-focused committee determined [that we should] look at all laboratory tests that were possible and limit them to a small number that were truly critical. Then we implemented the system that took the position that once such a critical value was recognized by a laboratory technologist in the laboratory and verified as critical, it became the responsibility of the laboratory and the people in the lab -- often -- to find the doctor of record or another doctor who would take responsibility for the patient, and to directly and personally communicate that critical value, with urgency, to that particular physician or other physician. That's the concept; that's the term; that was the initial implementation.
Medscape: It sounds like a lot of the responsibility lay, and may still lie, on the shoulders of the laboratory personnel for communicating. How much of it do you think lies with the ordering physician in terms of recognizing what could be a critical value?
Dr. Lundberg: You play with the cards that you're dealt. You control what you can control. Of course, any physician who orders a laboratory test ought to have the dedication and the compulsiveness to not rest until he or she sees the result from that laboratory test. Unfortunately, that doesn't happen. That never has happened. That never will happen. So if you're the director of a laboratory, and you're charged with creating these results, it simply has to be the responsibility of the director of the laboratory, delegated to whatever level within the laboratory is the most efficient one for this responsibility to be actually acted upon. The doctors who order it are simply not going to follow up at that level, many times. Many times they will. Many times they won't. So, although your question does speak of professionalism and appropriate practice by physicians, and as a physician I like that, as a laboratorian I know it's a never-never land that won't happen. You have to deal with the deck you have.
Medscape: How do you think the concept has changed, if at all, over the past 3 decades?
Dr. Lundberg: I think the concept is identical. The first evolution that happened was that it became recognized and adopted at an amazingly rapid rate. In the adoption, a lot of medical staffs developed these particular lists and were more lenient or liberal toward what was called a critical value. So early on, the list that others came up with included more tests than we had, and less radical values. This was because every hospital had to determine for itself when it pushes the panic button or what it calls critical, and that's the way it should be. Our hospital received, at that time, some of the sickest people in the world, had a huge number of really critically ill people, and had a very weathered group of physicians and house officers who didn't panic unless there was something really important to panic about, so different hospitals had different levels of panic. I think that was the biggest change. Since then, also, of course, the whole business of how do your computers work and how can you automate a laboratory and how you can get the results to the physician in an automated fashion online -- with printouts, with red lettering, with response requirements -- that whole field was built since this time in the early 70s when almost nobody had a lab computer system going anywhere that would do this. I think those are the 2 biggest differences: what kind of tests you put on, what the values are, and then the extent to which computers have replaced the need to use other methods. And again, there are upsides and downsides to both of those as well, but the original concept is the same.
Medscape: Can you comment on what sorts of effects you might think the concept has had on the practice of medicine, and also on the patient experience, if at all?
Dr. Lundberg: I doubt that patients have the slightest idea about this kind of thing. Unless maybe in an outpatient situation when somebody calls the patient at home and says, "Hey, we've got a critical lab value and you get yourself back in here fast," then a patient would know about it. Otherwise, I think in a hospital setting, the patient wouldn't even know about it. Its effect on the practice of medicine . . . Well, for starters, it put a liability point up there that basically said, "This is what's expected, and if you don't practice with a critical value system and do it the way you're supposed to do it, if something bad happens to a patient, you're liable for a lawsuit, and you basically have no defense." That's happened many times. I think that's unfortunate. Liability's always a problem, but if that's one of the methods of making people do what they are supposed to do,. I don't have a problem with there being liability situations there in case the system isn't up and working or in case the system has fallen through and failed to meet the requirements that are needed based upon the critical value.
I believe that the concept was adopted very quickly. I believe, to some extent, that it's a matter of crying wolf if you don't set the critical values right, and that way it can become a blunted issue, but as long as the values are truly critical, I think it still survives in about the same way it did. The notion of the practice of pathology and laboratory medicine, I think, changed dramatically to put the responsibility wholly on a lab to be sure that they would do this. Of course, the College of American Pathologists adopted this system relatively soon after we had published it. The Joint Commission [on Accreditation of] Healthcare Organizations adopted it as a requirement also relatively soon. So I believe the issue itself allowed those involved in practicing medicine to focus more on preanalytic and postanalytic factors, which were always there but sometimes ignored. [It] began to help people realize that a lab test begins when the doctor conceives of the need of it, and it ends when the doctor has taken an action based on its result, and everything that happens in between there is what I call part of the lab test. I think that kind of thinking hadn't been done much until this point, and I think that's had a major long-term attitudinal impact on who's responsible for what, and that chain is only as strong as its weakest link.
Medscape: What do you think the next 30 years will bring in terms of the role of critical value? What other trends or challenges do you see coming?
Dr. Lundberg: I think the whole issue there is interpretive clinical pathology and how the people in the laboratory, especially the physician's laboratory, can do a better job of helping clinicians order the right tests -- Helping the clinician by making sure the tests are done as well as they can be, and then making sure they get back to the place where the right interpretation is placed upon them and the proper action taken. To me, I think that's a natural extension of the critical value system -- to apply to all kinds of lab tests, not just those that have critical values. Otherwise, the laboratory test that's ordered may not be acted upon in an appropriate manner. Many times the correct action may be no action at all. But unless some action is taken, the entire cycle of test ordering and performance is, at best a waste, and at worst a tragedy. A lab test should not be ordered unless the result is going to be used in some fashion. So, I think the critical value can serve as a nidus or a launching part for the whole issue of interpretive laboratory medicine, interpretive clinical pathology, because all of us in pathology know that large numbers of clinicians haven't the foggiest notion how to properly order laboratory tests or how to interpret them correctly. I've been very disappointed over the last 30 years [by] the extent to which laboratory physicians have not been more aggressive at guiding appropriate use of laboratory, and guiding appropriate, interpretation and action based upon the results in a laboratory. I would love for the next 30 years to change that in the best interest of the patient and the best interest of quality of care and efficient use of costly services.
BOTTOM LINE
istology Safety:
Now and Then
René J. Buesa
Histology safety usually focuses on general laboratory issues, but this article concentrates on the hazards affecting the individual histotech and their evolution in the last half a century. Using the information from a survey especially designed for the occasion, the hazards were divided into 4 groups, and their prevalence was expressed as percentages for national and foreign laboratories. All the laboratories received a “safety index” (SI) with an average value of 0.77 ± 0.11 for 63 national laboratories and 0.69 ± 0.13 for 22 foreign laboratories, these 2 averages being statistically different (P < .02). The historical evolution of the SI required answering the same questionnaire retrospectively, and so it was done for 17 laboratories with an SI average of 0.27 ± 0.12 for 1955/1989 and 0.77 ± 0.13, almost 3 times larger for 1990/2007, with improvement of all safety issues. The technological, organizational, and regulatory advances before 1989 showed an unremarkable effect on the SI, and the only circumstance considered as the driving force behind the almost triple increment of the SI during 1990/2007 was the awareness that the AIDS epidemic instilled in the minds and consciences of the medical laboratory personnel in general. Even after almost tripling the average SI value in 2007, national histology laboratories obtained a grade average of “C+” only, leaving room for improvement.
Keywords: Safety hazards; Safety index; AIDS epidemic
effect on safety
Table 1. Eight hours of TWA for some chemicals frequently used in the histology laboratory
|
Toxic level at |
Chemical
substance |
|
0.01 ppb |
Silver nitrate (silver metal dust/fumes) |
|
0.02 ppb |
Osmium tetroxide |
|
0.05 ppb |
Potassium dichromate; uranyl nitratea |
|
0.1 ppb |
Iodine; picric acid (explosive) |
|
0.2 ppb |
Potassium permanganate |
|
0.5 ppb |
Chromium trioxide (chromic acid) |
|
1 ppb |
Ferric chloride; oxalic, phosphotungstic, and sulfuric acids |
|
2 ppb |
Hydroquinone; paraffin wax fumes; sodium hydroxide |
|
10 ppb |
Aluminum hydroxide; glycerin mist |
|
0.1 ppm |
Potassium iodide; sodium barbital |
|
0.2 ppm |
Glutaraldehyde (mutagenic agent) |
|
0.5 ppm |
Chlorine |
|
0.75 ppm |
Formalin; paraformaldehyde (both carcinogens) |
|
1 ppm |
Hydrogen peroxide |
|
2 ppm |
Nitric acid; sodium hydroxide |
|
5 ppm |
Formic and hydrochloric acids; phenol |
|
10 ppm |
Acetic acid |
|
25 ppm |
Ammonium hydroxide |
|
100 ppm |
Xylene |
ppb = parts per billion (equivalent to mg/m3); ppm = parts per million (equivalent to g/m3, 1 ppm = 1000 ppb).
a One
hundred milliliter of 1% aqueous solution of uranyl
nitrate undergoes about 12 000 disintegrations/s (a specific activity of
123 Bq/mL) equivalent to 0.26 μg
of radium .
Table 2. Chemical hazards
|
Source of the
chemical hazarda |
% of
laboratories |
|
|
|
United States |
Foreign |
|
Special stains are performed manually |
87 |
91 |
|
Formalin as fixative |
81 |
64 |
|
Xylene as antemedium |
59 |
41 |
|
Xylene or xylene substitutes are recycled |
54 |
27 |
|
Most staining solutions are prepared in the laboratory |
41 |
82 |
|
Coverslipping is carried out manually |
38 |
45 |
|
Alcohol is recycled |
38 |
18 |
|
Not all known carcinogens have been eliminated |
34 |
64 |
|
Both alcohol and xylene or substitutes are recycled |
27 |
14 |
|
Not all mercury-containing reagents have been eliminated |
23 |
68 |
|
Routine staining (hematoxylin and eosin) is manual |
21 |
23 |
|
Manual coverslipping is not carried out in a fume hood |
18 |
18 |
|
The chemical hygiene plan is not mandatory |
16 |
73 |
|
There have been no protocol changes to safer procedures |
16 |
9 |
|
Formalin is recycled |
15 |
0 |
|
Some tissues are processed manuallyb |
10 |
10 |
|
Casseting is not carried out in a fume hood |
6 |
14 |
|
Grossing is carried out in a poorly ventilated area |
5 |
9 |
|
Formalin, alcohol, and xylene or substitutes are all recycled |
3 |
0 |
|
All tissues are processed manually |
2 |
14 |
a US average vs foreign
average: t18 = 0.43, P > .70, NS.
b Include manually processing some small/special biopsies,
transmitted electron microscopy specimens, and tissue processing with nonautomated microwave ovens.
Table 3. Personal safety standards risks
|
Not followed
safety standarda |
% of
laboratories |
|
|
|
United States |
Foreign |
|
The safety program does not include first aid instructions |
49 |
45 |
|
Prohibitions of wearing contact lenses/applying makeup are not enforced |
43 |
64 |
|
Personnel are not tested annually for effects of exposure to chemicals |
41 |
82 |
|
Working stations are not decontaminated at the end of each shift |
38 |
41 |
|
There are no lockers for employees |
31 |
32 |
|
Pregnant employees are not assigned low-risk tasks |
31 |
27 |
|
Protective attire is not mandatory |
29 |
14 |
|
There is no lounge-designated area for employees |
23 |
41 |
|
There is no monitoring program for formalin and/or xylene exposure |
15 |
55 |
|
There are no uncontaminated working areas |
15 |
9 |
|
Prohibition of eating, drinking, and smoking are not enforced |
10 |
18 |
|
There are no special regulations/precautions for autopsies |
6 |
5 |
|
Protective equipment is not requiredb |
5 |
9 |
|
There is no written chemical hygiene plan |
5 |
18 |
|
The chemical hygiene plan does not include blood-borne pathogens |
5 |
18 |
|
The standard operating procedures are not available to all employees |
3 |
23 |
|
Material Safety Data Sheets (MSDS) are not available to all employees |
0 |
9 |
a US average vs
foreign average: t15 = 2.11, P > .90, NS.
b Include masks, respirators, goggles, face shields, gowns,
fluid-resistant laboratory jackets, and gloves.
Table.4 Evolution of some safety
issues from 1955/1983 to 2007
|
Safety issue |
% of
laboratories |
|
|
|
1955-1983 |
2007 |
|
Tissue processors are used for all tissuesa |
64 |
98 |
|
Manual processing for all or some tissues |
36b |
12c |
|
Manual routine staining (hematoxylin and eosin) |
100 |
21 |
|
Manual coverslipping |
100 |
38 |
|
Most staining solutions are prepared in the laboratory |
100 |
41 |
|
Manual special staining |
100 |
87 |
|
Formalin substitutes are used |
0 |
19 |
|
Xylene substitutes are used |
0 |
41 |
|
Airflow is tested for compliance with regulations |
18 |
87 |
|
There is a chemical monitoring program for formalin and xylene |
9 |
85 |
|
Personnel annually tested for effects of chemical exposure |
9 |
59 |
|
Grossing is done in well-ventilated areas |
36 |
95 |
|
Casseting is done under a hood |
27 |
94 |
|
Steel blades are used for all or some sectioning |
100 |
6 |
|
Disposable blades are used in most sectioning |
0 |
97 |
|
There are motorized microtomes |
0 |
56 |
|
Mercury-containing thermometers are prevalent |
100 |
16 |
|
Most working stations are designed ergonomically |
9 |
49 |
|
There are antislip/fall surfaces in exposed areas |
9 |
70 |
|
Refrigerators and freezers are explosion safe |
0 |
32 |
|
Prohibition on drinking, eating, and smoking are not enforced |
45 |
10 |
|
There are safety cabinets for flammable and explosive chemicals |
36 |
95 |
|
All working stations are decontaminated at the end of the shift |
9 |
62 |
|
Waste chemicals are disposed into the public sewer system |
82 |
16 |
|
Average SI |
0.26 ± 0.13 |
0.77 ± 0.13 |
a Tissue processors before 1980 were neither self-enclosed
nor had fume control.
b Thirty-six percent process all tissues manually.
personnel safety concerns, most
histology laboratories, especially larger ones, enacted
Conclusion
The AIDS epidemic, the most destructive in recorded history, with more than 25 million deaths so far, and the fear that it generates have been the driving force behind the histology safety improvements, but we cannot become complacent because, after all, national histology laboratories got an unimpressive grade average of just C+.
Many more improvements can take place, such as the substitution of formalin and xylene as prevalent chemical hazards, eliminating all carcinogens and mercury-containing solutions, rethinking the way recycling is carried out, completely automating routine staining and coverslipping, and changing to less hazardous procedures.
The histology laboratory should become more “ergonomically friendly,” redesigning all working stations and increasing the number of motorized microtomes. Injuries in the workplace, in the form of slip and falls, or back injuries should be reduced and the improvements continued until all the safety issues are addressed.
Are HTs any safer today? The answer is a resounding “Yes,” but we can do better, much better!
Annals of
Diagnostic Pathology, Volume
11, Issue 5, October 2007, Pages 334-339