Showing papers in "Archives of Pathology & Laboratory Medicine in 1997"

Practice guideline for examination of the placenta: developed by the Placental Pathology Practice Guideline Development Task Force of the College of American Pathologists

Abstract: The Placental Pathology Practice Guideline Development Task Force, a multidisciplinary group, has prepared this guideline to assist those involved with placental examination. It provides recommendations related to indications and methods for placental examination as well as sample worksheets. An algorithm for the handling of placentas summarizes the recommendations of the guideline. A summary of specific findings of placental examination together with their pathogenesis and clinical associations is also provided. Recommendations related to reporting with sample reporting formats are included. The guideline is intended as an educational tool, and its use should be guided by the individual circumstances and care setting of specific cases.

Immunohistochemical and in situ localization of Crimean-Congo hemorrhagic fever (CCHF) virus in human tissues and implications for CCHF pathogenesis.

Abstract: Background Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease that occurs in parts of Africa, Asia, and eastern Europe, and that is caused by a recently emerged bunyavirus. Rapid laboratory diagnosis of CCHF infection is essential and is currently performed by virus isolation and serology. Histopathologic studies have been limited to a small number of cases, and little is known about the cellular tropism of CCHF virus and the pathogenesis of this disease. Design We conducted a retrospective case analysis of 12 patients with a diagnosis of CCHF infection, confirmed by virus isolation, who were evaluated at the Special Pathogens Unit, National Institute for Virology, South Africa. The clinicopathologic features of CCHF and the diagnostic role of virus isolation as compared with serology, immunohistochemistry, and in situ hybridization were evaluated. Additionally, the distribution of CCHF virus in human tissues was examined. Results The clinical and histopathologic features of CCHF resemble those of other viral hemorrhagic fevers. Of the 12 patients with virus isolation-confirmed CCHF infection, 5 were positive by serology, 10 by immunohistochemistry, and 5 by in situ hybridization. Immunohistochemistry and in situ hybridization analyses showed that the mononuclear phagocytes, endothelial cells, and hepatocytes are main targets of infection. Association of parenchymal necrosis in liver with viral infection suggests that cell damage may be mediated by a direct viral cytopathic effect. Conclusions The diagnosis of CCHF, suspected by history and clinical features, can be supported histopathologically. However, since the pathologic features resemble those of other viral hemorrhagic fevers, an unequivocal diagnosis can be made only by laboratory tests. The utility of immunohistochemistry as a sensitive and rapid diagnostic modality was established by the high degree of concordance with virus isolation. Infection of mononuclear phagocytes, endothelial cells, and hepatocytes may play a critical role in the pathogenesis of CCHF.

Interinstitutional comparison of frozen section turnaround time. A College of American Pathologists Q-Probes study of 32868 frozen sections in 700 hospitals

Abstract: Objectives To study the intraoperative turnaround time for performing a frozen section (FS) and to examine pathology practice variables that influence it. Design Over a 4-month period in 1995, participants in the College of American Pathologists Q-Probes laboratory quality improvement program prospectively collected data on up to 30 FS procedures performed on elective inpatient surgical cases and completed questionnaires profiling their FS practice characteristics. Setting Surgical pathology laboratories serving private and public hospitals. Participants Seven hundred institutions located in North America (667), Australia (12), New Zealand (1), the United Kingdom (3), Hong Kong (1), Mexico (1), and Norway (1). Main outcome measures The 90% FS block completion time defined as the time interval, in minutes, within which the fastest 90% of all FS blocks were completed, measured from the time pathologists received FS specimens to the time they communicated FS results to the surgeon. Results Participants submitted data on 32868 FS blocks. Ninety percent of FS procedures were completed within 20 minutes. Frozen section turnaround times exceeding 20 minutes, termed outlier turnaround times, were more likely to occur when more than one pathologist participated in the FS diagnosis, pathology residents and medical students participated in the FS procedure, the pathologist had to retrieve and review previous case material during the FS procedure, the pathologist simultaneously received additional specimens from other FS cases, the pathologist was unable to reach a final FS diagnosis, and when technical problems occurred during the FS procedure. Seventy percent of all participating hospitals completed 90% of their frozen sections within 20 minutes. The institutional 90% completion times were shorter for hospitals containing 300 or fewer occupied beds than for those containing more than 300 occupied beds. Conclusions The data suggest that 90% of FS block turnaround times can be performed within 20 minutes, measured from the time that pathologists receive FS specimens to the time that pathologists return FS diagnoses to surgeons.

Renal chromophobe cell carcinoma and oncocytoma. A comparative morphologic, histochemical, and immunohistochemical study of 124 cases.

Abstract: BACKGROUND: Renal oncocytoma has several features that overlap with other renal neoplasms, including the eosinophilic subtype of chromophobe cell carcinoma. In fact, strict criteria for renal oncocytoma have not been well defined and remain a matter of controversy. Ultrastructural studies or sophisticated methods such as flow cytometry and cytogenetic techniques can be of great use in distinguishing the two tumors, but are difficult to propose as routine methods because of their limited availability. OBJECTIVE: To further characterize the histologic criteria of these tumors, we undertook a retrospective study to define the utility of routinely available histochemical and immunohistochemical techniques. DESIGN AND SETTING: Twenty-one cases of chromophobe cell carcinoma, eosinophilic subtype, and 103 cases of oncocytoma were tested with histochemical (Perls, periodic acid-Schiff, and Hale's colloidal iron) and immunohistochemical (peanut agglutinin antigen and UEA-1 for lectins; cytokeratin KL1, epithelial membrane antigen, vimentin, S100 protein, and lysozyme) staining. RESULTS: The antibodies tested and the histochemical staining using Hale's colloidal iron allowed eosinophilic chromophobe cell carcinoma to be distinguished by its characteristic reaction pattern. Seventy-six percent of the chromophobe cell carcinomas showed a microvacuolated pattern, and 89% of the renal oncocytomas showed an apical positivity with Hale's colloidal iron staining (P < .01). Peripheral cell accentuation reactivity for cytokeratin KL1 was observed in 66% of the chromophobe cell carcinoma cases, and apical cytoplasmic positivity was observed in 37% of the renal oncocytoma cases (P = .01). Significant patterns were observed with anti-epithelial membrane antigen and anti-peanut agglutinin antigen antibodies (P = .05 and P = .01, respectively). Positive reactions for vimentin, S100 protein, lysozyme, and UEA-1 were not significant characteristics. CONCLUSION: Our study demonstrated that a precise morphologic description associated with simple histochemical and immunohistochemical techniques provides sufficient criteria for a high level of discrimination between the eosinophilic subtype of chromophobe cell carcinoma and renal oncocytoma.

Human monocytic and granulocytic ehrlichioses. Discovery and diagnosis of emerging tick-borne infections and the critical role of the pathologist

Abstract: Human monocytic ehrlichiosis and human granulocytic ehrlichiosis are emerging tick-borne infections in the United States. The clinical presentations of these two distinct, potentially life-threatening infections are fever, headache, myalgia, and other diagnostically nonspecific symptoms. Physician awareness is lacking and appropriate diagnostic tests are still not widely available. Because few documented cases have been autopsied, the pathology of human monocytic ehrlichiosis and human granulocytic ehrlichiosis is incompletely described. In human monocytic ehrlichiosis, bone marrow and hepatic granulomas and multiorgan perivascular lymphohistiocytic infiltrates have been observed. In human granulocytic ehrlichiosis, opportunistic fungal and viral infections have been important findings. To expedite an analysis of the pathology and pathogenesis of the human ehrlichioses, it is proposed that a Registry of Pathology of Human Ehrlichioses be established.

Pathology of experimental Ebola virus infection in African green monkeys. Involvement of fibroblastic reticular cells.

Abstract: Background Ebola virus has been responsible for explosive lethal outbreaks of hemorrhagic fever in both humans and nonhuman primates. Previous studies showed a predilection of Ebola virus for cells of the mononuclear phagocyte system and endothelial cells. Objective To examine the distribution of lesions and Ebola virus antigen in the tissues of six adult male African green monkeys (Cercopithecus aethiops) that died 6 to 7 days after intraperitoneal inoculation of Ebola-Zaire (Mayinga) virus. Methods Tissues were examined histologically, immunohistochemically, and ultrastructurally. Results A major novel finding of this study was that fibroblastic reticular cells were immunohistochemically and ultrastructurally identified as targets of Ebola virus infection. Conclusions The role of Ebola virus-infected fibroblastic reticular cells in the pathogenesis of Ebola hemorrhagic fever warrants further investigation. This is especially important because of recent observations indicating that fibroblastic reticular cells, along with the reticular fibers they produce, maximize the efficiency of the immune response.

Laboratory diagnosis of Cyclospora infections.

Abstract: The laboratory diagnosis of newly recognized infectious agents, such as Cyclospora cayetanensis, is frequently problematic because appropriate diagnostic techniques and algorithms are not available. The methods currently available for diagnosis of Cyclospora are described and compared, including concentration procedures, examination of wet preparations, various staining techniques, and the use of molecular-based assays. Because of the autofluorescent properties of the oocysts, particular attention is drawn to the role of fluorescent microscopy in providing a rapid, inexpensive, and sensitive technique for diagnosis of Cyclospora infections in stool samples. In addition to text descriptions, photomicrographs are provided to illustrate Cyclospora oocysts in wet and stained preparations and compare them with Cryptosporidium and Isospora oocysts, the other two most common coccidian infections in man.

Chemistry specimen acceptability: a College of American Pathologists Q-Probes study of 453 laboratories.

Abstract: Objective To determine the frequency and reasons for rejection of chemistry specimens. Design and setting College of American Pathologists Q-Probes laboratory quality improvement study prospectively recording rejected chemistry specimens in 453 laboratories. Main outcome measure Percentage of submitted specimens rejected for testing. Results Of 10,709,701 chemistry specimens submitted to the participating laboratories during the data collection period, 37,208 (0.35%) were rejected prior to testing. The institutional 10th, 50th (median), and 90th percentiles were 1.35%, 0.31%, and 0.06%, respectively. The most frequent reason for rejection was hemolysis, which occurred five times more frequently than the second most cited reason, insufficient specimen quantity to perform the test. When examined with their respective frequency of use, a higher percentage of rejected specimens were collected in microcollection tubes than in other containers. When compared with the respective frequency with which they collect specimens, laboratory personnel submitted significantly fewer rejected specimens than other in-hospital personnel groups and slightly more than out-of-hospital nonlaboratory personnel. The poorest performance was demonstrated by other in-hospital nonlaboratory personnel. Serum and plasma oxalate/fluoride specimens exhibited significantly lower rejection rates when compared with the other specimen types. Relative rejection rates were higher for nongel tubes and lower for syringes when compared with gel tubes. Conclusion Specimen rejection should be monitored on a regular basis. Institution-specific factors that are associated with rejection should be identified and targeted for improvement efforts. Action thresholds should be set sufficiently low to assure that continuous improvement is effected.

Osteopontin and p53 expression are associated with tumor progression in a case of synchronous, bilateral, invasive mammary carcinomas.

Abstract: Objective To examine the association between expression of osteopontin (OPN), p53, other molecular markers (Ki-67, c-erb B2, and estrogen receptor protein) and tumor progression in a case of synchronous, bilateral, invasive mammary carcinomas of the same histology. Design Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections. Plasma OPN level was determined by a quantitative antigen capture assay. Setting The patient was seen, treated, and followed up for a period of 5 years at the London Regional Cancer Centre, Ontario, Canada. Patient A 60-year-old woman presented with bilateral infiltrating mammary carcinomas of the same histologic type and grade. Bilateral mastectomy and axillary node dissection showed involvement of 3 of 12 right axillary and 0 of 11 left axillary lymph nodes. She later developed a right chest wall recurrence, followed by widespread metastatic disease to the skull, liver, and left femur. Results The primary tumor of the right breast was OPN- and p53-positive, whereas the tumor of the left breast was negative for both markers. The development of right axillary lymph node metastases, chest wall recurrence, and distant metastases was associated in all instances with an immunohistochemical profile of high level expression of OPN and p53. Plasma assay for OPN at the time of last admission showed a markedly elevated OPN level. Conclusions Increased p53 expression was found to be associated with increased tumor aggressiveness. The association of increased OPN expression with increased malignancy in breast cancer is a novel finding and raises the possibility of a role for OPN in tumor progression, as well as the potential for this marker in predicting clinical aggressiveness.

Frozen section evaluation of stereotactic brain biopsies: diagnostic yield at the stereotactic target position in 188 cases.

Abstract: . Objective.-Use of the image-guided stereotactic brain biopsy has facilitated the diagnosis of previously inaccessible lesions with both safety and reliability. However, few studies have assessed the diagnostic yield of frozen section evaluation of the initial stereotactic target (FS-0). We describe our experience with 188 stereotactic brain biopsies in order to evaluate the diagnostic yield of FS-0. Design.-Retrospective study of 188 stereotactic brain biopsies from 185 patients. Setting.-Tertiary referral center with a high volume of neurosurgical cases including image-guided stereotactic brain biopsies. Patients.-One hundred eighty-five patients who underwent imaged-guided stereotactic brain biopsy over a 58-month period. Results.-The patients studied included 107 males and 78 females (mean age 48 years). Eleven (6%) biopsies were nondiagnostic. Diagnoses from FS-0 included a neoplastic condition in 96 (73%) of 131 cases and a nonneoplastic condition in 23 (50%) of 46 cases. In 119 (67%) of 177 cases, a diagnosis was reached at FS-0. A correct diagnosis was made on subsequent frozen section in 28 (16%) of cases, including 21 (16%) of 131 neoplasms and 7 (15%) of nonneoplastic conditions. In 15 (54%) of 28 cases, the correct diagnosis was made on the second frozen section; in 25 (89%) of 28, the correct diagnosis was made by the fourth frozen section. In 14 (11%) of 131 neoplastic cases, a sampling error relative to the lesion resulted in an inaccurate diagnosis at FS-0. A significant error in diagnosis occurred in three cases (1.7%). Conclusions.-We conclude that (1) because 58 (33%) of 177 diagnosed cases in our series would have been potentially misdiagnosed if only one biopsy had been taken at the stereotactic target, frozen section evaluation or cytologic examination of material at the time of surgery should be performed routinely to ensure that adequate tissue has been obtained for purposes of diagnosis; (2) taking up to four biopsies increases the diagnostic yield (from 67% to 89% in this series); and (3) neoplastic lesions are more likely to be definitively diagnosed at FS-0 than nonneoplastic lesions.

Common problems in Papanicolaou smear interpretation.

Abstract: No test ever invented has been as successful as the Papanicolaou smear in preventing cancer. Despite its remarkable success in cervical cancer prevention, however, the Papanicolaou smear is not a perfect test. Sampling errors account for a significant number of false-negative cases. Diagnostic errors occur in even the finest cytology laboratories. Yet, for women who develop cervical cancer, these errors pale in comparison with failure to screen patients adequately in the first place. This paper examines some of the problems that result in failure of the Papanicolaou smear to prevent cervical cancer, with an emphasis on common problems in Papanicolaou smear interpretation.

Latent Epstein-Barr virus infection demonstrated in low-grade leiomyosarcomas of adults with acquired immunodeficiency syndrome, but not in adjacent Kaposi's lesion or smooth muscle tumors in immunocompetent patients.

Abstract: BACKGROUND Incidence of smooth muscle tumors is increased in patients with human immunodeficiency virus infection and organ transplant recipients Smooth muscle tumors in immunocompromised patients often occur in unusual locations and exhibit evidence of latent infection by clonal, presumably tumorigenic, Epstein-Barr virus (EBV) OBJECTIVE To investigate the presence of EBV latent infection in smooth muscle tumors in patients with acquired immunodeficiency syndrome and in immunocompetent patients DESIGN Twenty-two extrauterine, extraintestinal smooth muscle and myofibroblastic tumors were reviewed pathologically, and clinical charts were screened Tumors were malignant (15 patients), benign (6 patients), and borderline (1 patient) Tissue specimens were investigated for latent EBV infection by latent membrane protein immunocytochemistry and EBV-encoded RNA in situ hybridization SETTING University Hospital of the University of Nancy, France PATIENTS Patients were 18 adults and four children Two adults had acquired immunodeficiency syndrome Both had low-grade leiomyosarcomas located in adrenal gland Moreover, in patient 1, leiomyosarcoma was multifocal in pericardium and lymph node; in lymph node, muscle tumor was adjacent to nodal and skin Kaposi's lesions RESULTS In both patients with acquired immunodeficiency syndrome and leiomyosarcoma, latent infection by EBV could be demonstrated in tumor cells, contrasting with absence of detectable EBV infection in adjacent non-neoplastic tissues and nearby Kaposi's lesions Latent infection by EBV could not be demonstrated in smooth muscle and myofibroblastic tumors in immunocompetent patients CONCLUSIONS Latent EBV infection is associated with smooth muscle cell tumors in immunocompromised patients, but not in immunocompetent patients

Pathology of Penicillium marneffei. An emerging acquired immunodeficiency syndrome-related pathogen.

Abstract: Objective To summarize current knowledge regarding the opportunistic dimorphic fungal pathogen Penicillium marneffei Clinical presentation, differential diagnosis, mycology, histopathology, diagnostic serology, in vitro antifungal agent susceptibility testing, and therapy are discussed for human immunodeficiency virus-infected individuals primarily living in Southeast Asia Data sources Critical evaluation of peer-reviewed publications located through an electronic literature database search, supplemented by unpublished observations, were used to prepare this report Study selection Studies were selected based on either the fungal name Penicillium marneffei, penicilliosis, penicilliosis marneffei, or a combination of these Data extraction Articles were reviewed with appropriate data being abstracted and then synthesized into the review Data synthesis Differential diagnostic criteria for tissue diagnosis and laboratory identification of the fungus are detailed The usefulness of mycoserology and antifungal therapy are evaluated Conclusions Penicillium marneffei is an emerging pathogen, primarily among patients with acquired immunodeficiency syndrome residing in Southeast Asia Although infection caused by P marneffei is endemic to this portion of the world, cases are being diagnosed and treated involving individuals who have traveled to this region Penicilliosis marneffei can clinically resemble tuberculosis, molluscum contagiosum, cryptococcosis, and histoplasmosis The successful treatment of P marneffei infection is dependent on its rapid and accurate diagnosis

Granulomatous prostatitis on needle biopsy.

Abstract: Objective To assess pathologic findings of granulomatous prostatitis (GP) on needle biopsy. Design Ninety-four cases of granulomatous prostatitis were culled from 25,852 (incidence 0.36%) consecutive men who underwent needle biopsy; clinical correlations were obtained for 75. Cases were categorized as nonspecific (NSGP, 77.7%), infectious (IGP, 18.1%), or indeterminate (4.3%) granulomatous prostatitis based on histologic and clinical criteria. Setting Consecutive cases from a large commercial laboratory and consultation cases. Results All cases of IGP had a history of prior bacillus Calmette-Guerin therapy for transitional cell carcinoma. Histologically, 57% of NSGP cases mimicked infection and 4% mimicked cancer. Caseating necrosis was identified in 76% of cases of IGP. Significant numbers of eosinophils were found in 68% of NSGP cases, but in only 12% of IGP cases. In no case was eosinophilia documented in peripheral blood. Multinucleated giant cells were absent or rare in 69% of NSGP cases. Significant numbers of neutrophils were found in 53% of NSGP cases, but in only 29% of IGP cases. At the time of biopsy, cancer was clinically suspected in 55% of cases categorized as NSGP and 73% categorized as IGP. Serum prostate-specific antigen ranged from less than 0.5 ng/mL to 114 ng/mL (mean 12.7 ng/mL) in NSGP and from 0.9 ng/mL to 9.7 ng/mL (mean 4.2 ng/mL) in IGP. Digital rectal exam was abnormal in 69% and 91% of NSGP and IGP cases, respectively. Transrectal ultrasound was abnormal in 77% and 100% of NSGP and IGP cases, respectively. There was no correlation between the extent of core involvement with either clinical impression, prostate-specific antigen levels, transrectal ultrasound, or digital rectal exam. Thirty additional granulomatous prostatitis cases on needle biopsy were obtained from the consultation files of one of the authors. The major difference in this group was a higher percentage of cases histologically mimicking cancer (20%); two cases were misdiagnosed by the referring pathologist as high-grade cancer. Conclusions While NSGP is the most common granulomatous prostatitis seen on needle biopsy, bacillus Calmette-Guerin granulomas are not seen infrequently. Lesser known histologic features of NSGP were the frequent finding of neutrophils and eosinophils and infrequent multinucleated giant cells. Granulomatous prostatitis may be clinically indistinguishable from cancer, and NSGP may also histologically mimic carcinoma.

Eosinophilia Detected by Automated Blood Cell Counting in Ambulatory North American Outpatients Incidence and Clinical Significance

Abstract: • Objectives.-To audit a cohort of ambulatory outpa­ tients with eosinophilia detected on automated blood cell counting. Specific objectives included the determination of whether the eosinophilia had been anticipated, the etiol­ ogy of the eosinophilia, the clinical follow-up and investi­ gations performed on patients with eosinophilia, and the effect of the detection of eosinophilia on patient manage­ ment and ultimate clinical outcome. Design.-A year-long retrospective review of all patients with an absolute eosinophil count of greater than 0.7 x 1 0 9 / L. Setting.-A large outpatient laboratory system. The pa­ tient population was managed by family physicians and specialists. lntervention.-Data collection included the results of the hematology profile, the absolute eosinophil count, the clinical situation responsible for the hematologic profile determination, and the probable cause of eosinophilia. In­ dividual physicians were surveyed to determine if discovery of the eosinophilia had changed patient management plan or clinical outcome. Principal Results.-Out of 195 300 patients who had a he­ matology profile performed, 225 were found to have an ab

A new and improved "quick-hot Gram-chromotrope" technique that differentially stains microsporidian spores in clinical samples, including paraffin-embedded tissue sections.

Abstract: Objective This report describes a new and improved "quick-hot Gram-chromotrope" staining technique that detects microsporidian spores in clinical specimens, such as stool, urine, saliva, nasopharyngeal fluid, and bronchoalveolar lavage samples, as well as in formalin-fixed and paraffin-embedded tissue sections. Design In this procedure, the samples are stained in heated (50 degrees C to 55 degrees C) solutions of crystal violet and iodine used in Gram's stain, followed by a modified chromotrope solution (heated to 50 degrees C to 55 degrees C). The modified stain is composed of chromotrope 2R (1%), fast green (0.15%), and phosphotungstic acid (0.25%). Results With this stain and the new protocol, microsporidian spores are stained dark violet against a pale green background, and the total staining time is shortened to 5 minutes. Conclusions This new technique is fast, reliable, and simple. It can be easily adapted for use in clinical laboratories.

Maternal melanoma metastatic to the placenta: a case report and review of the literature.

Abstract: Metastases of maternal cancer to the placenta and fetus are rare in cases of maternal primary malignancy. This report describes a case of malignant melanoma metastatic to the placenta, reviews the literature, and discusses the clinical significance. A 33-year-old woman presented at 30 weeks' gestation with multiple metastases from a malignant melanoma diagnosed 4 years previously. Rapid maternal deterioration necessitated premature cesarean delivery, and maternal death occurred 7 days later. The placenta showed multiple metastases of malignant melanoma. The infant, however, is alive and well at 7 months of age. Melanoma in pregnancy rarely results in metastasis to the conceptus, but when it does occur there may be fatal consequences to the fetus. Therefore, the placenta should be thoroughly examined for metastasis, which, if present, should alert the clinician to monitor the infant for development of malignant disease.

Practice guidelines for autopsy pathology: the perinatal and pediatric autopsy. Autopsy Committee of the College of American Pathologists.

Abstract: The Autopsy Committee of the College of American Pathologists has prepared this guideline in conjunction with representatives of other organizations to assist pathologists in the reporting of perinatal and pediatric autopsies. The guideline is to be regarded as being primarily an educational tool. Application of these recommendations on autopsy reporting is to be made on the basis of the judgment of the pathologist engaged in a specific case.

Risk of malignancy and death in neurofibromatosis

Abstract: Objective and methods Neurofibromatoses are cancer-prone hamartomatoses that involve a variety of tissue and cell types. As part of a population-based clinical and genetic study of neurofibromatosis in northern Finland, all surgical and autopsy specimens of neurofibromatosis patients were retrieved and histologic slides were reviewed. Results Specimens were available for 69 of the 197 neurofibromatosis type 1 patients identified. Six malignant peripheral nerve sheath tumors and nine other malignant tumors were detected. In this study, the risk for neurofibromatosis-related malignancy was 8%. Nine neurofibromatosis type 1 patients died, at a mean age of 37 years. The cause of death was related to neurofibromatosis in eight. Conclusions The risk of developing malignant tumors and early death is increased in patients with neurofibromatosis, the most common malignancy being malignant peripheral nerve sheath tumors. These risks need to be recognized, and the families should be advised to seek genetic counseling and proper follow-up.

Rapid brain autopsy. The Joseph and Kathleen Bryan Alzheimer's Disease Research Center experience.

Abstract: . Objective.-To develop a system for retrieving brain tissue within 1 hour after death in an effective and useful manner. Design.-Nurse clinicians were employed as study coordinators and were available to families 24 hours each day. Setting.-Autopsies were performed at Duke University Medical Center, Durham, NC, from 1985 through 1995. Participants.-Neuropathology faculty, fellows, and residents ; autopsy technicians; and brain bank staff. Results.-Fifty-one rapid autopsies with a postmortem interval of less than 1 hour have been performed. Four of these were normal controls, three were disease controls, and 44 represented Alzheimer's disease patients. Tissue retrieved at rapid autopsy has been distributed to 93 research teams, 30 of these located at Duke University Medical Center. Many researchers have received multiple shipments of tissue. Conclusions.-The Bryan Alzheimer's Disease Research Center Rapid Autopsy Program at Duke University Medical Center has been successful in retrieving tissue from individuals with dementia and also from controls within 1 hour of death. The critical features of the success of this program have been the use of nurse clinicians who work closely with patients and their families to ensure a successful autopsy at the time of death and the maintenance of a 24-hour call schedule for nurses and neuropathology staff. Similar programs can be implemented for experimental work into the pathogenesis of a wide variety of human diseases in which the examination of human tissue is required.

Pulmonary alveolar microlithiasis: A clinicopathologic and chemical analysis of seven cases

Abstract: . Objectives.-To determine the clinical features and outcome of patients with pulmonary alveolar microlithiasis and to determine the chemical composition of the microliths. Case Material-We studied seven cases of pulmonary alveolar microlithiasis. The patients were six women and one man, aged 19 to 70 years (mean age 44.5 years). Clinically, five patients were known to have suffered from this condition for 5 to 41 years. One patient presented with shortness of breath, and another had a gradual decrease in exercise tolerance. None of the patients had a previous history of disturbances in metabolism or any other relevant medical condition. Reports on radiographic studies were available in six cases, and chest radiographs were available for review in the seventh case. They all showed diffuse bilateral pulmonary infiltrates. Open lung biopsies were performed in two patients, and autopsy lung material was reviewed in five patients. Results.-Histologically, the lung showed the typical features of pulmonary alveolar microlithiasis, that is, presence of numerous microliths filling the alveolar spaces with either a normal or thickened fibrotic interstitium. Chemical analysis performed on the lung tissue of six of these patients revealed that the microliths consisted principally of calcium and phosphorus salts. Five of these patients died of respiratory failure; however, their deaths occurred from 5 to 41 years following the initial diagnosis. No follow-up information was obtained in two patients. Conclusions.-The findings of this study confirm that pulmonary alveolar microlithiasis can be seen in any age group and that the microliths are composed principally of salts of calcium and phosphorus. Additionally, these cases confirm that the disease typically follows a protracted course.

Routine rapid Mycobacterium species assignment based on species-specific allelic variation in the 65-kilodalton heat shock protein gene (hsp65)

Abstract: OBJECTIVE To assess the utility of automated DNA sequencing strategies for Mycobacterium species assignment and surrogate rifampin susceptibility testing of Mycobacterium tuberculosis complex isolates in a hospital-based clinical microbiology laboratory. DESIGN Consecutive patient specimens (n = 161) cultured in BACTEC 12B medium (growth index of 50 or greater) or on solid media (Lowenstein-Jensen) were analyzed. A 360-bp segment of a gene (hsp65) encoding a 65-kd heat shock protein was sequenced to identify species-specific allelic polymorphism. Identification of sequence variation in the rpoB gene encoding the beta subunit of RNA polymerase was used as a surrogate method to assess rifampin susceptibility in M tuberculosis complex isolates. RESULTS The automated DNA sequencing strategies rapidly identified virtually all mycobacteria (158 [98%] of 161) to the species level and unambiguously characterized the region of rpoB that contains mutations responsible for rifampin resistance in M tuberculosis strains. With few exceptions, DNA sequence-based species assignment data agreed with diagnostic information obtained by conventional methods. All discrepancies were due to ambiguous biochemical test data or interpretation. The rifampin susceptibility phenotype was correctly predicted for all strains by rpoB sequencing. CONCLUSIONS Rapid mycobacterial species assignment based on hsp65 sequencing can be routinely performed in a hospital diagnostic microbiology laboratory setting. The method is especially useful for identification of fastidious organisms, such as Mycobacterium genavense. Sequencing of the rifampin-resistance-determining region of rpoB provides a convenient surrogate strategy for predicting rifampin susceptibility in M tuberculosis complex isolates.

Disseminated toxoplasmosis: Unusual presentations in the immunocompromised host

Abstract: Objective Owing to the increasing number of patients with acquired immunodeficiency syndrome and immunosuppressed transplant patients, disseminated Toxoplasma gondii has emerged as a potentially fatal pathogen. Common presentations include encephalitis, pneumonia, and myocarditis. The objective of this report is to describe the clinical course, histologic features, and outcome in two immunocompromised patients with disseminated toxoplasmosis presenting with parasitemia and panniculitis. Materials and methods Two cases of disseminated toxoplasmosis presenting with parasitemia (patient 1) and panniculitis (patient 2) were retrieved from the clinical, surgical, and autopsy pathology archives of Vanderbilt University Medical Center, Nashville, Tenn. The histology and diagnostic approaches used are reported. Charts were reviewed for primary diagnosis, therapy protocols, clinical presentation of infection, and outcome. Results Patient 1 developed a clinically unexplained sepsis syndrome shortly after heart transplantation; T gondii parasitemia was diagnosed by examination of peripheral blood smears. The diagnosis was confirmed at autopsy. Patient 2 was a child undergoing induction chemotherapy for lymphoma who developed rapidly progressive neurologic deterioration accompanied by a maculopapular skin rash; T gondii panniculitis was diagnosed retrospectively when histologic examination was combined with immunohistochemistry. Autopsies performed in both cases confirmed widely disseminated infection. Conclusions Disseminated toxoplasmosis should be considered in the differential diagnosis of immunocompromised patients with culture-negative sepsis syndrome, particularly if combined with neurologic, respiratory, or unexplained skin lesions. Examination of Wright's-stained peripheral blood smears or antitoxoplasma immunoperoxidase studies of skin biopsies may be diagnostic and allow rapid initiation of antibiotic therapy. Autopsy findings contributed to both of our cases by documenting the wide-spread heavy parasite burden and demonstrating numerous diagnostic T gondii cyst forms.

p53 gene mutations and p53 protein expression in human soft tissue sarcomas.

Abstract: Objective To determine the frequency of mutation and overexpression of the p53 tumor suppressor gene in human soft tissue sarcomas. Design A total of 31 soft tissue sarcomas were analyzed by immunohistochemistry for the expression of p53 protein and were subsequently investigated by the polymerase chain reaction technique and direct sequence analysis of exons 5 through 8 in the p53 gene. Setting The specimens were collected over a 3-year period in the laboratories at our large teaching hospital in Seoul, Republic of Korea. Patients Thirty-one patients with soft tissue tumor were surgically treated and diagnosed as having either malignant fibrous histiocytoma, rhabdomyosarcoma, or leiomyosarcoma. Results Overexpression of p53 was seen in 17 (55%) of 31 sarcomas, including 9 (64%) of 14 malignant fibrous histiocytomas, 4 (44%) of 9 rhabdomyosarcomas, and 4 (50%) of 8 leiomyosarcomas. Seven cases (23%) demonstrated mutations in the p53 gene. Six had a single mutation, whereas one showed triple mutations. There were seven mutations in exon 5, one in exon 6, and one in exon 7. All of the mutations were missense mutations, resulting in changes in the predicted amino acid sequence. Among the nine mutations, seven (78%) were transversions and two (22%) were transitions. Conclusions Mutation of the p53 tumor suppressor gene, with resultant overexpression of p53 protein, frequently occurs in human soft tissue sarcomas, supporting the role of p53 mutations in the pathogenesis of soft tissue sarcoma and the possible usefulness of p53 immunolocalization as a screening method for p53 mutations.

Clinically relevant breast cancer reporting: using process measures to improve anatomic pathology reporting.

Abstract: Objective Breast cancer reports form an important part of the basis of clinical decision making for patients. Our objectives were to improve breast cancer reporting in the Urban Central Region in Utah of Intermountain Health Care in a clinically relevant manner and to show that the method chosen actually improved information transfer among physicians of breast cancer patients and led to durable changes in pathologist behavior. METHODS/INTERVENTION: Pathologists designed a synoptic report based on interviews with oncologists about what data were meaningful. The report format was piloted with one hospital pathology group, modified, and implemented in three hospitals. A report evaluation of missing information was done before, immediately after, and 2 years after the intervention. Oncologists were surveyed after 2 years to evaluate satisfaction with report format. Results Changing breast cancer reporting to a synoptic format significantly decreased information missing from pathology reports. Prior to implementation, 32 of 365 reports lacked some item(s) of pathology information desirable to clinicians; after the intervention, 8 of 250 reports contained missing information. After 2 years, 1 in 190 reports contained missing data elements. Synoptic breast cancer reports continued to be used by pathologists throughout the reporting period. Oncologists responding to a survey reported uniform satisfaction with the new reporting format. Summary Pathologists are important members of the clinical oncology team. They provide patient-specific information crucial to patient care. Activities designed to improve the quality of reporting processes should use clinically relevant indicators of process improvement, such as measurement of missing information and satisfaction of clinical colleagues with format/quality of information.

Changes in emergency department turnaround time performance from 1990 to 1993. A comparison of two College of American Pathologists Q-probes studies

Abstract: Objective To compare the results of a 1990 College of American Pathologists Q-Probes Emergency Department (ED) turnaround time (TAT) study with a similar study done in 1993 and to identify factors associated with TAT improvement. Design Participants gathered data over a 4-week period on the various times of day associated with the ordering, specimen-collection, laboratory-receipt, and result-reporting stages of stat tests for potassium and hemoglobin levels, using a mail-in questionnaire that also included practice parameter questions. Participants Laboratories enrolled in the 1990 College of American Pathologists Q-Probes study on ED TAT and laboratories enrolled in the 1993 program ED TAT study. Main outcome measures Components associated with shorter ED TAT and, for those participating in both the 1990 and 1993 studies, comparison with previous results. Results Six hundred fifteen hospital laboratories returned data on up to 43,521 hemoglobin and 41,989 potassium specimens. Half of these laboratories collected and reported 90% of their ED potassium results in 53 minutes or less, compared to 61 minutes or less in 1990, and reduced the corresponding median collection-to-reporting TAT for 90% of hemoglobin results from 46 minutes or less to 39 minutes or less. The fastest 10% of laboratories showed interlaboratory median order-to-report TATs of 36 and 50 minutes for potassium and hemoglobin tests, respectively. Comparisons of TATs from 277 laboratories with 1990 and 1993 data were possible. Components found to contribute statistically to improvement of ED TAT between 1990 and 1993 were laboratory control of specimen handling, rapid transport time, and monitoring. Active monitoring was particularly important when the laboratory did not control the specimen-handling process. Conclusions Laboratories improved their control of ED TAT from 1990 to 1993 and reduced the number of TAT events exceeding 70 minutes. Internally set TAT goals, however, were not met most of the time.

Sensitivity and specificity of triphenyl tetrazolium chloride in the gross diagnosis of acute myocardial infarcts.

Abstract: Objective Myocardial infarction is the most common cause of sudden death in the United States However, the identification of early myocardial infarcts at necropsy is frequently difficult, since unequivocal gross changes of infarcts do not become apparent for 24 to 48 hours following myocardial ischemic injury The use of dyes, such as nitro-blue tetrazolium and 2,3,5 triphenyl tetrazolium chloride (TTC), that identify the dehydrogenase-deficient infarcted myocardium has been shown, largely by animal studies, to be very helpful in the macroscopic diagnosis of such cases Such animal studies could not be directly extrapolated to human autopsy studies, however, because of the assumption that autolysis may invalidate the histochemical assessment of myocardial enzymatic changes after death This study was carried out to evaluate the sensitivity and specificity of TTC in the gross diagnosis of acute myocardial infarction in the human population Design The TTC stain reactions were correlated with histologic findings in the hearts of 638 consecutive adult autopsies Results Of the 638 hearts examined by TTC, 174 hearts stained positive for acute infarction; histology confirmed myocardial infarction in 140 hearts Histologic examination revealed acute infarcts in 41 of the remaining 464 cases that had stained negatively with TTC The use of TTC in the macroscopic diagnosis of acute myocardial infarcts in the human population was found to have a diagnostic sensitivity of 774% and a specificity of 926% The predictive value of a positive test was 805%, and that of a negative test was 912% Conclusions The overall diagnostic efficiency of the TTC test (ie, number of patients correctly identified) was 88% These results show that the TTC test is a reliable, sensitive, and specific adjunct in the examination of the human heart at necropsy