Factors affecting autopsy rates, autopsy request rates, and autopsy findings at a large academic medical center.

Autopsy rates continue to decline in the United States. To assess the impact of various objective factors (time of death, day of death, age at death, patient gender, clinical service, and length of hospital stay) on the autopsy request rate, autopsy rate, successful request rate, and percentage of cases in which the autopsy examination added to or altered the clinical assessment of the patient, we prospectively studied all hospital deaths at a major academic medical center for the 3-year period from 1996 through 1998. The autopsy rate decreases significantly with patient age, both because of a decreasing request rate and because family members are less likely to grant permission. An autopsy is less likely to be requested for deaths in the emergency department or on general surgery services and most likely to be requested for fetal, medicine, cardiothoracic surgery, and pediatric deaths. Families more commonly grant permission for autopsy on fetal deaths, pediatric deaths, and emergency department deaths. Forty percent of autopsies reveal significant information about the patient's death beyond what was known premortem. This is least frequent among the fetal deaths, but relatively constant for adults of all ages. Patients who die in the emergency department are most likely to have significant unexpected findings at autopsy. Increasing the request rate for adult patients who die in the emergency department and on the medicine services will result in the greatest increase in information learned from autopsy.

Quality improvement on an academic autopsy service.

CONTEXT: Autopsy rates continue to decline in the United States. OBJECTIVE: Although many of the causes of this decline are external to pathology departments, we hypothesized that intradepartmental efforts to improve the quality of the service we provide to our clinical colleagues could increase our autopsy rate. METHOD: We developed a multifaceted quality improvement program for our autopsy service aimed at increasing the visibility of the service, improving the service's reporting, and increasing the amount and quality of data available from the service. SETTING: A large academic medical center that performs approximately 250 autopsies each year. RESULTS: After implementation of our quality improvement program, the decline in our autopsy rate has not only stopped, but rates have even begun to increase. Additionally, physician satisfaction surveys conducted before and after implementation of our quality improvement initiatives showed an across-the-board improvement in clinician perception of the service. CONCLUSION: Pathologists can and should be proactive in addressing the declining autopsy rate, rather than viewing it as someone else's problem or hoping that someone else will protect this important quality assurance tool for medical care.

Implementation of a practical digital imaging system for routine gross photography in an autopsy environment.

BACKGROUND: The autopsy environment places stringent requirements on a digital imaging system. These requirements must be addressed if the system is to be functional, easy to use, and reliable. DESIGN: After clearly defining the requirements for such a system, we implemented routine digital imaging in a busy academic autopsy suite. RESULTS: The new technology was immediately accepted by both the resident staff and the technical staff. Although a 35-mm camera was always available for traditional photography, it was rarely used. An interesting side effect of implementing digital imaging was a nearly twofold increase in the number of images taken per autopsy case. The requirements, features, and utility of a digital imaging system are discussed. CONCLUSION: Digital imaging in an autopsy environment can be both practical and cost-effective. It provides many advantages over traditional 35-mm photography and can be the first step toward numerous additional improved services.

Immunohistochemical distinction of ocular sebaceous carcinoma from basal cell and squamous cell carcinoma.

BACKGROUND: Diagnosis of sebaceous carcinoma of the periorbital region is often delayed. Clinically, this lesion can mimic several inflammatory disorders. Histopathologically, it can mimic either squamous cell or basal cell carcinoma. OBJECTIVE: To identify an immunohistochemical approach to assist in the diagnosis of periorbital sebaceous carcinoma. METHOD: The immunohistochemical profiles of several cases of periorbital sebaceous, basal cell, and squamous cell carcinoma were examined. RESULTS: Although at least focal epithelial membrane antigen (EMA) staining can effectively distinguish sebaceous carcinoma (10 of 11 were positive) from basal cell carcinoma (1 of 16 were positive), most squamous cell carcinomas examined were also focally EMA positive (11 of 14). However, Cam 5.2 reactivity was seen in most sebaceous carcinomas (8 of 11) but no squamous cell carcinomas (0 of 14). In addition, at least focal BRST-1 reactivity was also seen in most sebaceous carcinomas (7 of 11) but no basal cell carcinomas (0 of 16). CONCLUSIONS: Periorbital sebaceous, basal cell, and squamous cell carcinomas have different immunohistochemical staining profiles; a panel of commonly available antibodies, including anti-EMA, BRST-1, and Cam 5.2, may help distinguish these diseases from each other when that distinction cannot be clearly made by light microscopy alone.

Malignant transformation of an optic disk melanocytoma.

PURPOSE: To report a case of malignant transformation of an optic disk melanocytoma with a second melanocytoma in the ciliary body. METHODS: Clinical data including visual acuity, visual fields, color fundus photographs, fluorescein angiogram, and ultrasonogram and histopathologic studies of this case were reviewed. RESULTS: The right eye of a 65-year-old white woman was diagnosed with melanocytoma of the optic nerve. Four years later, the tumor became significantly larger. The best-corrected visual acuity declined from 20/40 to counting fingers and the size of the tumor increased fourfold in 2 years. The right globe was enucleated. Histopathologic studies demonstrated moderately pigmented spindle-B malignant melanoma cells adjacent to and within a population of large, polyhedral, heavily pigmented melanocytoma cells that extended to the lamina cribrosa and optic nerve. There was also a deeply pigmented melanocytoma in the ciliary body. CONCLUSION: This is a rare case of malignant melanoma transformed from an optic disk melanocytoma. Periodic follow-up of the patient with optic disk melanocytoma is necessary.

Sebaceous carcinoma presenting as a unilateral papillary conjunctivitis.

PURPOSE: To describe a previously unreported presentation of sebaceous carcinoma, an aggressive tumor that often presents insidiously with minimal symptoms and nonspecific signs. METHODS: We report a 71-year-old man who presented with unilateral ocular irritation and ipsilateral, idiopathic, papillary changes of the superior palpebral conjunctiva. The patient underwent incisional biopsy of the palpebral conjunctiva followed by full-thickness excision of the involved eyelid. RESULT: Histopathologic examination established the diagnosis of sebaceous carcinoma. CONCLUSION: Unexplained asymmetric, papillary changes of the palpebral conjunctiva should arouse suspicion of sebaceous carcinoma.

Pigmented villonodular synovitis of the temporomandibular joint: diagnostic imaging and endovascular therapeutic embolization of a rare head and neck tumor.

We report a case of pigmented villonodular synovitis involving the temporomandibular joint that presented as a rapidly growing tumor with extension through the skull base into the middle cranial fossa. The case is of interest not only because of the unusual extensive infiltration of this tumor but also because of the role modern diagnostic imaging and endovascular therapeutic techniques played in its diagnosis and management.

Exclusion of the stomatin, alpha-adducin and beta-adducin loci in a large kindred with dehydrated hereditary stomatocytosis.

Defects in stomatin, alpha-adducin, and beta-adducin have been implicated in erythrocyte disorders of cation permeability. We performed linkage analysis of the genetic loci for these proteins in a large kindred with xerocytosis (dehydrated hereditary stomatocytosis). Using polymerase chain reaction-based genotyping techniques, all three loci are excluded as disease gene candidates.

Albumin gene expression in adenocarcinomas with hepatoid differentiation.

Two cases of hepatoid adenocarcinomas were studied with an in situ hybridization technique (ISH) using a RNA probe for human albumin mRNA. In case 1 the urinary bladder of a 67-year-old woman was affected; in case 2 the tumour was located in the gastric antrum of an 80-year-old woman. In neither case had alpha fetoprotein (AFP) been determined preoperatively. Histologically these cases showed adenocarcinomatous features intermingled with hepatoid areas. These latter areas were characterized by cords of polygonal cells, each with an oval nucleus and prominent nucleoli, separated by a fine network of sinusoids. In the hepatoid areas the immunohistochemical profile was similar to that observed in hepatocellular carcinomas, in that the tumour cells were positive with AFP, alpha-1-antitrypsin (A1AAT) and albumin antisera and there was a canalicular type of reactivity with polyclonal anti-CEA (pCEA) antibody. ISH revealed albumin mRNA in virtually all hepatoid cells in case 1, and in about 50% of those in case 2. In addition, in case 2 occasional cells in the adenocarcinomatous areas showed albumin transcripts of ISH. Our findings confirm that ISH for albumin mRNA probe is a valuable method of establishing hepatocellular differentiation, and that hepatoid adenocarcinomas are tumours with true extrahepatic hepatocellular differentiation.

Orbital melanoma presenting as orbital cellulitis: a clinicopathologic report.

Most choroidal melanomas are diagnosed when the tumor is still relatively small and confined to the globe. Rarely, these tumors can escape detection and extend through the sclera. They can reach a large size and create significant orbital inflammation. The authors describe a 71-year-old man with orbital cellulitis secondary to a necrotic choroidal melanoma that invaded the orbit. This tumor had minimal intraocular involvement with a large extrascleral component. On histopathologic analysis, the lesion was best classified as a spindle B melanoma with epithelioid areas (mixed melanoma). The patient was treated with an enucleation and postoperative radiation. This report demonstrates that malignancies in the orbit can present as acute infections. Early suspicion, diagnosis, and treatment of these lesions offer the best chance for survival.

Utilization of an 86 bp exon generates a novel adducin isoform (beta 4) lacking the MARCKS homology domain.

A novel isoform of beta-adducin has been amplified and characterized from a human bone marrow cDNA library (GenBank #U43959). This isoform arises from the insertion of an 86 bp alternatively spliced and previously unrecognized exon (now termed exon 15) within codon 581 of the human red blood cell beta-adducin sequence. This results in an insertion of 28 novel amino acids. The remainder of the red cell beta-adducin mRNA is then translated in a different reading frame, adding an additional 35 novel amino acids prior to the stop codon. This new isoform, thus, replaces beta 1-adducin sequence after residue 580 with a total of 63 new amino acids. Sequences from genomic clones of the human beta-adducin gene show that this alternate exon is flanked by splice consensus sequences and is appropriately located in the genomic map between exons encoding up-stream and down-stream sequences, thus defining a new exon. The COOH-terminus of this new isoform, which we designate beta 4, lacks a 22 amino acid lysine-rich sequence common to both the human red cell alpha- and beta-adducin subunits and homologous to a highly conserved region in MARCKS, a filamentous actin-cross linking protein regulated by protein kinase C and calcium/calmodulin. beta 4-adducin preserves a previously identified calmodulin binding domain. PCR analysis indicates that this new beta-adducin isoform is expressed in fetal brain and liver, bone marrow, and NT-2 (neuroepithelial) cells, but is not detected in several other tissues. We anticipate that this new beta 4 isoform of beta-adducin will display unique and tissue-specific functional properties.

Metastatic liposarcoma to the orbit.

PURPOSE: To report a woman with blurred vision and proptosis who harbored an orbital liposarcoma that had metastasized from her abdomen. METHODS: The patient underwent an orbital biopsy, followed by postoperative intravenous corticosteroids and radiation. RESULTS: Pathology showed a dedifferentiated liposarcoma. The patient's visual acuity improved from 20/200 to 20/50 after treatment. CONCLUSIONS: Physicians should suspect the presence of this rare orbital tumor in a person with a history of liposarcoma who has proptosis. Liposarcomas usually exhibit a higher grade of malignancy with recurrence, as shown in this patient.

Neuronal loss from the subthalamic nuclei in a patient with progressive chorea.

We present a case of an 80-year-old man who developed a seizure disorder at age 66 and was treated with chronic phenytoin. In the last 3 years of his life, he developed multiple neurological deficits, including bilateral chorea, ataxic gait, sensory neuropathy, and progressive dementia. After death from pneumonia, autopsy examination of the patient's brain was most remarkable for a selective loss of neurons from both subthalamic nuclei and Purkinje cell loss in the cerebellum. This pattern of injury is consistent with a toxic process and does not fit previously characterized pathological syndromes known to be associated with movement disorders or dementia or both. Phenytoin has been shown to cause choreiform movements, peripheral neuropathy, and cognitive decline in some patients, but the pathological basis for these changes has not been elucidated. The patient's chorea was very likely the result of neuronal loss in the subthalamic nuclei, but causes for his dementia and neuropathy were not found. The pathological findings may represent either an unusual form of chronic phenytoin toxicity or a previously undescribed primary degenerative brain syndrome.

Reduced alpha-catenin and E-cadherin expression in breast cancer.

BACKGROUND: The expression of the homotypic cell adhesion protein, E-cadherin, is reduced in many types of cancer. The loss of this protein may be associated with metastasis because alteration of its function is required for invasion in vitro, and decreased expression has been associated with more aggressive tumor behavior in vivo. It is likely that the loss of downstream effector elements in the cadherin adhesion cascade may also disrupt cell-cell interactions and thereby promote invasion, but direct evidence for this has been lacking. One such effector element is alpha-catenin, a cytoplasmic protein related to vinculin that is associated in vivo with E-cadherin. EXPERIMENTAL DESIGN: In the present study, antibodies prepared to recombinant human alpha-catenin and recombinant human E-cadherin have been used to explore by immunocytochemistry the steady state levels of these proteins in a series of 26 cancers of the breast. RESULTS: The expression of alpha-catenin was reduced or lost more frequently (81% of cases) than was the expression of E-cadherin (63% of cases). Cases with absent E-cadherin expression uniformly lacked alpha-catenin. Eight of the 26 patients (31%) had known metastatic disease at the time of biopsy; yet, all patients with normal alpha-catenin staining in their tumors were free of known metastatic disease (four patients). CONCLUSIONS: Together with previous data on E-cadherin, these results suggest that reduced steady state levels of alpha-catenin may be a sensitive marker for disturbances in the adhesive function of the junctional complex and suggest that failure of at least one component of the cadherin-mediated cell-cell adhesion cascade is a common feature of breast, and presumably other, epithelial tumors.

Hepatoid adenocarcinoma in the urinary bladder. Unusual localization of a newly recognized tumor type.

A tumor mass resected from the anterior bladder wall of a 68-year-old woman displayed unusual histologic features: sheets of hepatoid cells merging focally with a secondary glandular pattern of adenocarcinoma. Intracytoplasmic hyaline globules and bile production within the solid areas supported the impression of hepatocytic differentiation. Immunoreactivity for alpha-fetoprotein (AFP) and alpha-1-antitrypsin and a striking canalicular immunostaining pattern for carcinoembryonic antigen and epithelial membrane antigen all indicate hepatocellular differentiation within this bladder tumor. This represents a case of a hepatoid adenocarcinoma located in the urinary bladder. The use of the term "hepatoid" in the literature is reviewed and the reported cases are grouped into two distinct categories of tumors: (1) germ cell tumors with focal hepatoid areas and (2) true hepatoid adenocarcinomas that meet histologic and immunohistochemical criteria for hepatocellular differentiation. AFP-producing tumors without any other feature of hepatocellular differentiation should not be considered as hepatoid tumors. This classification of hepatoid tumors is likely to be important in elucidating the histogenesis and clinicopathologic features of these unusual neoplasms.

Cardiogenic shock due to progression of cutaneous T-cell lymphoma.

We describe a patient with progressive cutaneous T-cell lymphoma (CTCL) and development of subacute cardiac failure. Symptomatic lymphomatous involvement of the heart may be more common in patients with CTCL than in other lymphomas because the former is more likely to be associated with circulating tumor cells and hematogenous spread to the myocardium. No single symptom or sign is highly predictive of cardiac involvement, but unexplained tachyarrhythmias, conduction disturbances, low voltage on ECG, and unexplained cardiac enlargement should arouse clinical suspicion. Although echocardiography may be helpful in suggesting cardiac involvement, endomyocardial biopsy should be considered in patients with a reasonable chance of responding to chemotherapy or radiation.

Effects of moderate hypothermia on O2 consumption at various O2 deliveries in a sheep model.

The effects of modest hypothermia on oxygen consumption (VO2) were studied at various levels of oxygen delivery (DO2) in six sheep. Each animal was placed on cardiopulmonary bypass by extrathoracic cannulations. DO2 was varied by changing blood flow through an extracorporeal circuit. VO2 was measured spirometrically across a membrane lung. VO2 was initially measured at various levels of DO2 at normothermic temperatures (39 degrees C). The animals were then cooled to 33 degrees C. DO2 was varied, and the corresponding VO2's were determined. The data at both temperatures demonstrated the biphasic relationship of VO2 to various levels of DO2. A critical level of DO2 (DO2 crit) was defined to reflect the transition area between the dependent and independent portions of the consumption-delivery curve. The average baseline VO2's on the delivery independent portion of the curve were calculated to be 5.33 and 3.17 ml O2.kg-1.min-1 at 39 and 33 degrees C, respectively (P less than 0.001). The corresponding DO2 crit's were 6.17 and 4.57 ml O2.kg-1.min-1 (P less than 0.05). The oxygen extraction ratios at DO2 crit for each of these temperatures did not differ significantly. We conclude that hypothermia, by lowering baseline VO2, reduces DO2 crit. Hypothermia may therefore reduce or eliminate the anaerobic metabolism and subsequent acidosis that would otherwise occur during normothermia at low levels of DO2.

Early experience with adult extracorporeal membrane oxygenation in the modern era.

In 1980 we stopped using extracorporeal membrane oxygenation for adults because only 1 of 20 patients treated between 1973 and 1979 survived. In October 1988 we returned to adult extracorporeal life support (ECLS) with a modified protocol including venovenous access when possible, large oxygenators for CO2 clearance, activated clotting time of 180 to 200 seconds, and case selection based on 90% mortality (30% transpulmonary shunt). Of 19 patients referred, 14 met criteria for ECLS. Three of these 14 patients with isolated respiratory failure died before ECLS could be started, and 1 patient refused ECLS and died. Ten were placed on ECLS for 2 to 24 days. Indications were pneumonia (3), post-cardiac operation (2), and adult respiratory distress syndrome (5). Five recovered and 5 died. The cause of early death was progressive pulmonary injury (3), hemorrhage (1), and ventricular arrhythmia (1). One late death occurred at 3 months secondary to intraabdominal complications related to liver transplantation. In conclusion, 10 adult patients with severe respiratory failure were treated with extracorporeal life support; 5 patients recovered lung function and 4 of these patients survived and were discharged to home. Surviving patients were typically younger and were placed on ECLS early in their disease process, emphasizing that early intervention is one key factor to a successful outcome.