Correlation of cystoscopic impression with histologic diagnosis of biopsy specimens of the bladder.

There is a paucity of information in the contemporary literature that would permit assessment of the urologist's ability to endoscopically discriminate between benign and malignant lesions of the bladder or to predict the grade and stage of papillary neoplasms. This prospective study evaluates the correlation between cystoscopic impression of urothelial lesions and final histologic diagnoses. Sixty-four patients with 68 urothelial abnormalities requiring formal biopsy or endoscopic resection were evaluated prospectively. At the time of endoscopy, treating urologists completed questionnaires documenting the surgeon's endoscopic impression of disease type and extent and performed standard biopsy or resection of all suspicious lesions. Specimens were submitted for routine histopathologic analysis, and the results were correlated with the questionnaire data. Endoscopic evaluation correctly discriminated between dysplastic/malignant and benign/reactive lesions in this study with a sensitivity of 100%, specificity of 100%, and positive and negative predictive values of 100%. Urologists could not readily distinguish between low- and high-grade papillary urothelial lesions and were frequently unable to determine if a tumor was invasive, particularly if the degree of invasion was microscopic. Endoscopic impression at the time of bladder biopsy or resection is accurate and discriminates between the presence and absence of cancer. Endoscopic impression alone is a relatively poor staging tool with respect to extent of invasive disease and must be coupled with careful histopathologic analysis of biopsy material, bimanual examination when appropriate, and axial imaging for complete assessment of a given tumor.

A rapid postmortem cardiac troponin T assay: laboratory evidence of sudden cardiac death.

Postmortem examination may be useful in establishing the cause of sudden unexpected death. In many instances, however, limitations of staffing, budget, and time may force the pathologist to triage cases to external examination rather than autopsy. A rapid assay for cardiac troponin T (cTnT) to document suspected cardiac-related deaths may optimize the use of the time and resources of the autopsy pathologist. Peripheral blood was sampled percutaneously before each of 40 autopsies and placed in the well of the Cardiac T Rapid Assay unit in accordance with the included instructions, and the results were read after 15 minutes. The assay result, decedent age, postmortem interval, and evidence of cardiopulmonary resuscitation were tabulated and subsequently correlated with the cause of death. On final sign-out of each of the autopsies, the cause of death was determined to be cardiac-related (n = 20) versus the cause in non-cardiac control subjects (n = 20). This determination was made while the investigators were blinded to the cTnT assay result. Of the 20 cardiac deaths, 17 (85%) showed positive results for cTnT compared with 6 (30%) false-positive results among the 20 control cases; this result was statistically significant according to the chi-square test. In the over-50 age group, the sensitivity of this assay in detecting cardiac-related death was 91%, with a specificity of 86%. Perimortem cardiopulmonary resuscitation did not appear to result in false-positive results. In the appropriate setting, this rapid assay for cTnT can provide valuable data supportive of a cardiac-related death. This inexpensive test may best be used in triaging sudden deaths in persons over 50 to external examination versus complete autopsy.

Evaluation of characteristics associated with acute splenitis (septic spleen) as markers of systemic infection.

CONTEXT: Acute splenitis, also known as acute splenic tumor or septic spleen, is loosely defined as a neutrophilic infiltrate and congestion within the red pulp accompanied by splenomegaly. Standard pathology texts state that the histologic finding of acute splenitis is reflective of septic states. However, this association has seldom been tested in the medical literature. OBJECTIVE: The purpose of this study was to determine if sepsis can be predicted by the presence of quantitative characteristics used to identify acute splenitis. METHODS: The postmortem splenic tissue of 20 clinically diagnosed cases of sepsis and 20 noninfectious control cases were retrospectively examined in a blinded fashion for amount of neutrophilic infiltration, weight (obtained from autopsy report), and presence of congestion. RESULTS: No significant correlation could be found between the parameters of neutrophilic infiltrate or splenic weight and clinically diagnosed septicemia. The presence of splenic congestion was unexpectedly found to be more likely with noninfectious causes of death. CONCLUSION: Acute splenitis is presently ill defined, and no available evidence convincingly shows that its presence suggests a septic state.

Correlation of Ki-67 and p53 with the new World Health Organization/International Society of Urological Pathology Classification System for Urothelial Neoplasia.

OBJECTIVE: The present study examines p53 and Ki-67 staining patterns of the diagnostic entities included within the new World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification of urothelial neoplasms. DESIGN: We retrospectively studied 151 bladder biopsies from 81 patients with the following neoplasms: normal urothelium (n = 34 biopsies); low-grade intraurothelial neoplasia (LGIUN; n = 19); high-grade intraurothelial neoplasia (HGIUN; n = 20); papillary hyperplasia (n = 4); papilloma (n = 3); papillary neoplasm of low malignant potential (LMP; n = 12); low-grade papillary carcinoma (n = 28); and high-grade papillary carcinoma (n = 31). Sections were labeled immunohistochemically with antibodies to p53 and Ki-67 (MIB-1). Two hundred cells from each lesion were visually counted, and the percentage of positive cells was tabulated without knowledge of the WHO/ISUP diagnosis. RESULTS: In flat lesions, p53 positivity was of limited diagnostic utility; the marker was present in 6 of 34 benign biopsies, 6 of 19 LGIUNs, and 10 of 20 HGIUNs. In one case in which HGIUN was present elsewhere in the bladder, 29% of the benign urothelial cells were p53 positive. In papillary lesions, p53 positivity was not seen in 4 of 4 cases of papillary hyperplasia, 3 of 3 papillomas, and 8 of 12 LMP tumors. In contrast, p53 was detected in 18 of 28 low-grade and 26 of 31 high-grade papillary urothelial carcinomas. A p53 labeling index (LI) greater than 30% was only seen in HGIUNs and high-grade papillary carcinomas. In flat lesions, an increased Ki-67 LI separated out benign urothelium (mean LI, 0.62%) from dysplasia (mean LI, 3.3%) and HGIUN (mean LI, 11.6%). In papillary lesions, Ki-67 positivity was as follows: papillary hyperplasia (mean LI, 1.1%); papilloma (mean LI, 4.3%); LMP tumors (mean LI, 2.5%), low-grade papillary carcinoma (mean LI, 7.3%); and high-grade carcinoma (mean LI, 15.7%). A Ki-67 LI greater than 10% was seen only in low- and high-grade papillary carcinomas, HGIUN, and single cases of LGIUN and papillary neoplasm of LMP. CONCLUSIONS: An increased proliferative index as demonstrated by immunohistochemical staining for Ki-67 (MIB-1) is most often seen in papillary carcinoma and HGIUN. Marked p53 positivity is also characteristic of carcinoma but may be seen in benign-appearing urothelium, suggesting a "field effect" with occult molecular aberration.

Pathology residents' use of a Web-based tutorial to improve Gleason grading of prostate carcinoma on needle biopsies.

Little is known about pathology residents' ability to Gleason grade or their ability to learn surgical pathology using Internet-based technology. A free Web-based program (available at www.pathology. jhu.edu/prostate) was developed that consisted of 20 pretutorial images for grading, 24 tutorial images, and the same 20 posttutorial images for Gleason grading. The grading images were selected from cases that had a consensus Gleason grade from 10 uropathology experts. In 2.5 months, 255 residents visited the website, and 151 (59%) completed it. Of those who completed the website, their year in training was known in 85 (56%): 1st year, 25.8%; 2nd year, 20%; 3rd year, 22.3%; 4th year, 14.1%; 5th year, 15.3%; and 6th year, 2.4%. Eighty percent learned Gleason grading in residency versus being self-taught, and 66% were male. In a multivariate analysis, higher pretutorial scores were associated with both their year in training (P = .001) and their hospital size (P = .003). Improvements in grading posttutorial were not related to the residents' year in training. Overall, the website significantly improved grading in 11 of 20 images and had no effect in 9 of 20 images. Improvements were noted in 1 of 1 Gleason score 4; 2 of 7 Gleason score 5 to 6; 2 of 6 Gleason score 7; and 6 of 6 Gleason score above 7 tumors. In summary, a Web-based tutorial improved Gleason grading accuracy by pathology residents to an equal extent regardless of their year in training. It is more difficult to teach residents to grade Gleason scores 5 to 7 tumors, and additional training should be concentrated in this area.

Isolation and identification of female DNA on postcoital penile swabs.

After sexual assault, cells originating from the assailant may be recovered from the victim. Through polymerase chain reaction (PCR)-based technology, positive scientific identification of the assailant may be made from these cells. Described is a prospective study describing a method for positively identifying cells from a female sex partner obtained from postcoital swabs of the penis of the male sex partner. Swabs were taken from the penis of a man at 1- to 24-hour intervals after coitus. DNA was isolated from each swab through standard organic extraction methods. The presence of female DNA was detected using the gender-specific amelogenin marker. Extracted DNA was amplified for eight different genetic loci using the Promega PowerPlex kit (Promega) and Amplitaq Gold (Perkin Elmer). Amplified samples were electrophoresed on precast sequencing gels (Hitachi) and were analyzed fluorescently using Hitachi's FMBIO 2 fluorescent scanner and software. Each sample obtained from a penile swab or condom was compared to male and female buccal controls. Female DNA was isolated from all postcoital penile swabs as determined by exclusive amplification of the X-chromosome specific 212 base pair amelogenin marker. In all cases, scientific identification of the female DNA from the swabs was determined by coamplification of eight STR loci (PowerPlex) and was compared to female and male control profiles. Cells shed from a female victim during sexual intercourse can be retrieved from the penis of a male offender after sexual intercourse during a 1- to 24-hour postcoital interval. DNA can be extracted from these cells and can be used to scientifically identify the female sexual participant through PCR-based technology. It is suggested that penile swabs be taken from alleged perpetrators of sexual assaults to associate them with a female victim.

Stereolithography: a potential new tool in forensic medicine.

Stereolithography is a computer-mediated method that can be used to quickly create anatomically correct three-dimensional epoxy and acrylic resin models from various types of medical data. Multiple imaging modalities can be exploited, including computed tomography and magnetic resonance imaging. The technology was first developed and used in 1986 to overcome limitations in previous computer-aided manufacturing/milling techniques. Stereolithography is presently used to accurately reproduce both the external and internal anatomy of body structures. Current medical uses of stereolithography include preoperative planning of orthopedic and maxillofacial surgeries, the fabrication of custom prosthetic devices; and the assessment of the degree of bony and soft-tissue injury caused by trauma. We propose that there is a useful, as yet untapped, potential for this technology in forensic medicine.

Characteristics of hormone-treated prostate carcinoma: stressing the need for clinician-pathologist communication.

OBJECTIVE: Patients scheduled for prostatectomy often receive androgen deprivation therapy to make malignant tumors more amenable to resection and improve the postoperative course. These hormonal therapies may significantly alter the histomorphology of carcinoma of the prostate detected on subsequent needle biopsies. METHODS: Needle specimens were obtained from resected prostates harboring biopsy-proven carcinoma previously treated with leuprolide. The tissue was examined by light microscopy to note architectural and cytologic characteristics. RESULTS: A high proportion of treated carcinomas had an atrophic, infiltrative appearance. Nuclear and nucleolar enlargement were consistently observed. Macronucleoli, blue-tinged mucin, and intraluminal pink amorphous material was frequently identified. CONCLUSIONS: The markedly atrophic nature of the cells and glands may result in either overgrading of prostate carcinoma or failure to recognize the more subtle patterns of this malignant neoplasm. It is imperative that clinicians convey a history of hormone treatment to pathologists when core biopsies of the prostate are submitted for histologic evaluation.

The role of Clostridium septicum in paraneoplastic sepsis.

CONTEXT: Clostridium septicum infections are rare but often associated with serious if not fatal outcomes. Clostridium septicum infection does not appear to be associated with a single specific defect in cellular or humoral immunity. It has been associated with multiple medical problems, including but not limited to leukemia, malignancy of the bowel, other solid tumors, cyclic neutropenia with enterocolitis, diabetes mellitus, and severe arteriosclerosis. Most cases of C septicum are associated with malignancy, and mortality approaches 100% if care is not rendered within 12 to 24 hours. OBJECTIVES: To evaluate outcomes of patients with C septicum bacteremia, whether treated medically or surgically or both, and to note associated conditions. DESIGN: Retrospective evaluation of patients found to have C septicum bacteremia in the past 6 years. SETTING: Two teaching hospitals, Brooke Army Medical Center (250 beds) and Wilford Hall Medical Center (292 beds), were the source of our patients. PATIENTS: All patients found to have C septicum bacteremia during hospitalization or postmortem examination were included in the study. There were no exclusion criteria. MAIN OUTCOME MEASURE: Mortality associated with C septicum infection. RESULTS: In our case series, mortality was 33%, which is slightly lower than reported in prior studies (43%-70%). CONCLUSION: Presumptive identification based on Gram stain, awareness of C septicum infection as a paraneoplastic syndrome, and prompt, clear communication between laboratory personnel and clinicians are necessary for early diagnosis of C septicum infection. Early institution of antibiotic therapy improves prognosis.

A simplified method for postmortem coronary angiography using gastrograffin.

OBJECTIVE: To assess the adequacy of perfusion of the heart at autopsy with a gastrograffin and dye mixture to obtain rapid postmortem angiograms while simultaneously documenting the vascular distribution of the myocardium. BACKGROUND: Postmortem coronary angiography is occasionally used in the evaluation of suspected cardiac deaths. Angiography provides legal documentation and can serve to guide subsequent cardiac dissection. Multiple techniques have been suggested in the literature for coronary angiography using infusion of radio-opaque silicone or gelatin. These techniques are cumbersome and require equipment generally not available in autopsy suites. METHODS: Following removal of the heart, a mixture of gastrograffin and colored dyes is injected into each coronary artery via a syringe. The coronary arteries are ligated and radiographs are obtained. After fixation, the heart is dissected in the usual manner. RESULTS: Adequate postmortem coronary angiograms are routinely obtained with this method. The coronary arterial distribution within the myocardium is easily documented at both the gross and microscopic levels because of the presence of differential coloration. CONCLUSIONS: The aforementioned technique using a gastrograffin and dye mixture provides a simplified approach to postmortem angiography. The novelty of the procedure stems from the low cost, ease of implementation, dual ability to assess vascular anatomy radiologically (gastrograffin), and gross distribution and histologic findings of dependent tissue using the light microscope (colored dye). This technique is inexpensive, rapid, and easily used, making it more suitable for general hospital practice and medical examiners' offices than previously described methods.

A case of familial angiolipomatosis with Lisch nodules.

Familial angiolipomatosis is a rare syndrome that may be confused clinically with neurofibromatosis type 1. This condition is most often inherited in an autosomal recessive manner; however, several reports have been published suggesting an autosomal dominant mode of inheritance. Angiolipomatosis, although somewhat disfiguring, is a benign condition with no known association with malignant neoplasms. This is in contradistinction to neurofibromatosis, an autosomal dominant syndrome associated with a myriad of benign and malignant neoplasms. It is, therefore, important to discriminate this entity from neurofibromatosis when a patient presents with multiple subcutaneous tumors and a family history of similar lesions. Described is a case of a prison inmate with a history of seizures and "neurofibromatosis" without clinical documentation. Lisch nodules were noted on the irides. Postmortem examination showed multiple subcutaneous yellow tumors on the chest and arms. Fine-needle aspiration of 1 mass yielded adipose tissue with prominent vessels; histologic sections of another mass showed angiolipoma. The remainder of the autopsy showed significant coronary artery disease and a remote cerebral infarction of the temporal lobe but no signs of neurofibromatosis. We feel that the presence of multiple angiolipomas in combination with Lisch nodules lends credence to the proposed relationship between fatty tumors and neurofibromatosis suggested by other authors.

Collecting duct meningeal carcinomatosis.

Collecting duct carcinoma (CDC) is an aggressive primary renal neoplasm that represents a distinct subtype of renal cell carcinoma. Histochemical (eg, mucicarmine) and immunohistochemical (eg, Ulex europaeus) studies, taken in concert with the gross and histologic findings, allow differentiation of CDC from the conventional varieties of renal cell carcinoma in most cases. Collecting duct carcinoma generally pursues a more aggressive course than conventional renal cell carcinoma. Metastases to regional lymph nodes, bone, adrenal glands, lung, and skin have been reported in CDC. We describe the case of a 26-year-old man who presented with a clinical and radiologic impression of multifocal meningioma. Biopsies of the meninges and extracranial soft tissues revealed metastatic adenocarcinoma; subsequent studies suggested metastatic CDC. Ultrasound-guided biopsy was performed on a subsequently identified renal mass, which showed features consistent with CDC. To our knowledge, this is the first reported case of meningeal carcinomatosis due to CDC. The diagnostic features of this tumor are discussed.

Multifactorial analysis of firearm wounds to the head with attention to anatomic location.

Firearm wounds to the head are often fatal and are routinely encountered in the practice of forensic pathology in the United States. Often, the anatomic site of the entrance wound is used to support or refute the manner of death indicated by the scene investigation and/or circumstances of the case. The present retrospective study of 120 fatalities resulting from 140 firearm wounds to the head correlates the anatomic region of the entrance wound and range of fire with the manner of death. Other demographic data analyzed include age, race, and gender of the decedents, as well as evidence of drug and/or ethanol use. It is hoped that this study will provide concrete data to support the largely anecdotal associations between the specific site of entry of firearm injuries to the head and the manner of death.

Postmortem percutaneous core biopsy of the liver.

Unexpected deaths related to significant hepatopathology are encountered daily by forensic pathologists. After investigation, a decision will be made regarding whether or not to perform an autopsy. In considering the options available to assess the degree of hepatopathology, a study was undertaken to evaluate the potential role of percutaneous core biopsy of the liver at the time of postmortem examination. Postmortem percutaneous hepatic core biopsy was attempted at the time of external examination in 28 nonconsecutive cases examined at the Office of the Chief Medical Examiner, State of Maryland; hepatic tissue was obtained in 26 cases. In 21 of these cases, hepatic tissue was obtained during subsequent partial or complete autopsy and submitted for histologic correlation. There was complete histologic correlation of tissue obtained via percutaneous biopsy with hepatic tissue obtained by open biopsy in 18 of 20 cases (86%). Significant hepatopathology was identified by core biopsy in 5 of 9 cases (56%) with a history of ethanol abuse and in 8 of 19 cases (42%) with a negative ethanol history. The sensitivity of this technique was 82% and the specificity was 100%. This study has shown that core biopsy of the liver can provide information related to the cause of death in cases with and without a history of alcohol consumption. In cases in which a complete autopsy is deferred because of familial religious objections, infectious disease, or time/budgetary constraints, this modality can be used to obtain diagnostic tissue.

Tissue distribution of tramadol and metabolites in an overdose fatality.

Tramadol (Ultram) is a centrally acting, synthetic analgesic agent. Although it has some affinity for the opiate receptors, tramadol is believed to exert its analgesic effect by inhibiting the re-uptake of norepinephrine and serotonin. There are several published cases of tramadol's involvement in drug-related deaths and impairment. Reports of deaths involving tramadol alone with associated tissue concentrations are rare. This report documents a case in which tramadol overdose was identified as the cause of death. The following tramadol concentrations were found in various tissues: blood, 20 mg/L; urine, 110.2 mg/L; liver, 68.9 mg/kg; and kidney, 37.5 mg/kg. Tissue distributions of the two primary metabolites, N-desmethyl and O-desmethyl tramadol, are also reported. In each tissue or fluid except urine, the tramadol concentration was greater than either metabolite, consistent with other reports of drug-impaired drivers and postmortem cases. The O-desmethyl metabolite concentration was greater than the N-desmethyl metabolite concentration in all tissues; this is in contrast to other postmortem reports, in which the majority of cases report concentrations of O-desmethyl as less than those of N-desmethyl. This may be useful as an indicator of time lapse between ingestion and death.

A study of various morphologic variables and troponin I in pericardial fluid as possible discriminators of sudden cardiac death.

Pathologists frequently examine victims of sudden cardiac death. In some cases, a firm diagnosis of cardiac-related death can be made based on conclusive gross and histologic findings. In many other cases, we find evidence supportive of, but not diagnostic of, cardiac death (e.g., atherosclerotic coronary artery disease, cardiomegaly, myocardial scarring). A final cohort consists of cases of sudden death with minimal to mild cardiac disease, no other significant pathology, and negative toxicologic studies. This prospective study compared 38 cardiac-related deaths with 52 control cases with respect to concentrations of pericardial cardiac troponin I (cTnI), heart weight, evidence of old and/or recent myocardial injury, and presence of significant coronary artery disease. The influence of documented chest trauma and/or perimortem cardiopulmonary resuscitation (CPR) on levels of cTnI was also analyzed. Even though median cTnI levels were significantly higher in cardiac deaths than in controls (p = .003), cTnI was not found to be a significant predictor of cardiac deaths, as determined by discriminant analysis (p = .52). Heart weight >500 g, evidence of old and recent myocardial injury, and significant coronary artery disease were seen statistically more often in cardiac deaths than in controls (p < or = .005 in each case), and median age was significantly higher in cardiac deaths than in controls (p = .001). Based on a stepwise logistic regression model, significant coronary artery disease, old and recent myocardial injury, and heart weight >500 g were found to contribute significantly to the prediction of cardiac death. Finally, neither chest injury nor CPR significantly affected concentrations of cTnI in pericardial fluid. These data confirm that the presence of acute and remote myocardial injury, significant coronary artery disease, and cardiomegaly (heart weight >500 g) strongly supports the diagnosis of a cardiac-related death. In contrast to a recently published report, we do not find that elevated concentrations of cTnI in pericardial fluid are strong indicators of cardiac-related deaths using our methodology.

Accuracy of death certification in two tertiary care military hospitals.

To determine the number and type of errors in death certifications, death certificates and corresponding postmortem examination results for 98 patients were analyzed at two tertiary care military hospitals. Of the 98 death certificates, errors were found in 36 (37%). The most prevalent type of error was the use of a nonspecific diagnosis as the underlying cause of death (22 of 36 errors, 61%). No errors were found in the listed manner of death. Given the high prevalence of errors found in death certification, recommendations are made to ensure the proper completion of death certificates. In addition, it is suggested that for patients who are to undergo postmortem examination, the immediate, any intermediate, and the underlying cause of death may be listed as "pending" so that the clinician can use the autopsy results in the completion of the death certificate.

Holmium:YAG lithotripsy: photothermal mechanism converts uric acid calculi to cyanide.

PURPOSE: Holmium:YAG lithotripsy fragments stones through a photothermal mechanism. Uric acid when heated is known to be converted into cyanide. We test the hypothesis that holmium: YAG lithotripsy of uric acid calculi produces cyanide. MATERIALS AND METHODS: Human calculi of known uric acid composition were irradiated with holmium:YAG energy in water. Stones received a total holmium:YAG energy of 0 (control), 0.1, 0.25, 0.5, 0.75, 1.0 or 1.25 kJ. The water in which lithotripsy was performed was analyzed for cyanide concentration. A graph was constructed to relate holmium:YAG energy to cyanide production. RESULTS: Holmium:YAG lithotripsy of uric acid calculi in vitro produced cyanide consistently. Cyanide production correlated with total holmium:YAG energy (p <0.001). CONCLUSIONS: Holmium:YAG lithotripsy of uric acid calculi risks production of cyanide. This study raises significant safety issues.

Suggested guidelines for platform presentations.

A platform presentation at an academic meeting requires preparation, practice, and self-discipline. Our observations and discussions of presentations made at national meetings of forensic scientists over the past several years compelled us to review the essentials of public speaking in the academic arena. We translated this review into a compilation of recommendations for the prospective presenter. Application of these recommendations will result in more informative, efficient, and enjoyable platform presentations.