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Show The Modern Pathologist: Lab Data Deliverer, Interpreter, and Diagnostician Daniel J. Brat, MD, PhD Awell known jab directed at the pathologist's role in patient management goes something like this: "the pathologist knows all of the answers regarding a patient's disease with absolute certitude.it's just a day too late!" Although this always gets a chuckle from clinicians, it has always seemed a bit dated and is also focused on only a small sliver of the pathologist's place in today's health care environment. Certainly, the pathologist remains responsible for hospital-based and forensic autopsies, which still have critical functions in hospital quality practice, education, and the medico-legal arena. The larger role of the modern pathologist, however, is within the laboratory setting, providing expertise and testing of patient biospecimens, either by establishing a pathological diagnosis directly or by providing laboratory data and consultation that assists in patient management. Most clinicians would agree that a definitive and accurate diagnosis is critical to proper patient care, as it represents a decision node and inflection point between patient presentation and the treatment plan. For this purpose, clinicians will frequently rely heavily on results from anatomic and clinical laboratory-based tests, performed under the watchful eye of pathologists. Just as the bank robber Willie Sutton quipped that he robbed banks because that is where the money was, most pathologist were attracted to their diagnostic discipline because that is where the data are. It has been estimated that laboratory results account for 70%-90% of data within a patient's electronic medical record. It has also been suggested that nearly 70% of all medical decisions depend on results from laboratory tests. The current issue of the Journal of Neuro-Ophthalmology includes a number of articles that highlight the importance of the pathologist in clinical practice, demonstrating their role in establishing a tissue-based diagnosis, providing laboratory test results that aid in patient management, and establishing an infra-structure for clinically relevant research that advances our understanding and treatment of disease. The report by Traynis et al (1) shows the importance of a surgical neuropathologist in establishing the diagnosis of a cerebral hemispheric lesion that extended to involve the optic chiasm and nerve of an 18-year-old man. Magnetic resonance imaging (MRI) showed widespread bilateral bright lesions on T2 images that did not enhance, consistent with an infiltrative disease process. Definitive therapy required a tissue-based diagnosis because treatment of those lesions within the differential diagnosis varies considerably. The biopsy revealed the features of an anaplastic astrocytoma, WHO grade III, with a pattern of brain involvement on MRI consistent with gliomatosis cerebri. The histological section displayed neoplastic cells with astrocytic differentiation invading individually through the brain neuro-pil. The presence of mitoses and the lack of features associated with a higher grade (necrosis or vascular hyperplasia) led to the diagnosis rendered. Further laboratory testing for purposes of patient prognosis include assessment of isocitrate dehydrogenase 1 (IDH1) mutational status and a MIB-1 proliferation index. With the diagnosis established, the multidisciplinary team had a solid framework from which to initiate the next stage of patient care, which included neurosurgical resection, radiation therapy, and chemotherapy. This case points out a source of quiet pride among anatomic pathologists: most clini-cians believe themselves to be credible, or even expert radiologists in their area of expertise, capable of interpreting MRIs and other imaging studies. However, most clinicians do not have similar confidence or skills in the more esoteric realm of pathological diagnosis and rely on their pathology colleagues to interpret histological findings within biopsied material. The series of 3 patients reported by Parker et al (2) demonstrates how the pathologist assists with the diagnosis of a rapidly developing neurodegenerative disease involving the visual cortex. All 3 patients Department of Pathology and Laboratory Medicine, Emory University Hospital, Emory University School of Medicine, Atlanta, Georgia. Address correspondence to Daniel J. Brat, MD, PhD, Department of Pathology and Laboratory Medicine, Emory University Hospital, G-167, 1364 Clifton Road, NE, Atlanta, Georgia, GA 30322; E-mail: dbrat@emory.edu Brat: J Neuro-Ophthalmol 2014; 34: 1-2 1 Editorial Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. had initial symptoms ranging from a visual field defect to cortical blindness, in combination with significant cognitive decline and psychiatric symptoms. The unifying hallmark of the diseases was the rapid pace of clinical deterioration. To establish a presumptive diagnosis of Heidenhain variant of Creutzfeldt-Jakob disease (HvCJD), the authors used the best available diagnostic tools: the clinical exam, diffusion-weighted imaging, electroencephalography, and testing of cerebrospinal fluid (CSF) for the proteins 14-3-3 and neuron specific enolase (NSE). Although none of these tests is capa-ble of establishing a definitive diagnosis by itself, the cumu-lative results provided sufficient evidence to make medical decisions based on the expected rapid clinical course of HvCJD. Definitive tissue-based diagnosis during life would require a brain biopsy, a practice that has lost favor for rapidly progressing dementias because of concerns that prions may contaminate surgical instruments. Laboratory results that were helpful included elevated CSF levels of 14-3-3 and NSE, which are shed into the CSF in destructive neurode-generative diseases and support the diagnosis of HvCJD. Patients with HvCJD unfortunately die within a very short time frame, as there is no effective treatment. Postmortem examination of tissue sections demonstrated the characteristic severe spongiform encephalopathy extensively involving the brain, whereas Western blotting and immunohistochemistry for the causative prion protein PrPsc confirmed the diagnosis of HvCJD. Postmortem laboratory testing of the PRNP gene may be warranted to determine the presence of a genotype predisposing to disease and also associated with disease pro-gression (homozygosity for the 129M allele). In the United States, most molecular testing, disease tracking, research, and education on prion diseases is being performed by a team of investigators led by neuropathologists at the National Prion Research Center at Case Western Reserve University, a center that has been central to advancing the understanding of the disease, and its variants, genetics, transmission, detection, and clinical course. Thus, these 3 cases of a rare, yet devastating, neurodegenerative disease demonstrate the full range of the pathologist in the clinical labs, in establishing a diagnosis post-mortem using ancillary testing, and in research and education. Tsang et al (3) report a highly unusual case proved to be a diagnostic and patient management challenge. Despite extensive clinical and laboratory work-up, the ultimate underlying pathological insult was not uncovered until post-mortem exam, emphasizing the important educational role of the pathologist, not only for the clinicians directly involved with patient management but also for the larger medical community through investigation and publication. The patient was a 29-year-old man who presented with flu-like symptoms, headaches, and retinopathy and was diagnosed with acute multifocal placoid pigment epitheliopathy based on fundoscopy and fluorescein angiography. Disease progres-sion was unusually rapid, leading to new onset seizures and multiple cerebral infarcts within 2 weeks. Because this syndrome can be associated with multiple infectious and autoimmune etiologies including adenovirus, measles, myco-bacteria, arthritis, and vasculitis, the clinical labs were exten-sively used to rule in or rule out specific diseases. Laboratory results were either negative or nonspecific for all infectious agents tested (human immunodeficiency virus, syphilis, toxo-plasma, Borrelia, tuberculosis, Cryptococcus, bacteria, and neurotropic viruses) and autoimmune markers (ANCA, rheu-matoid factor, angiotensin-converting enzyme, complement, and oligoclonal bands). The patient's clinical course deterio-rated rapidly with multiple cerebral infarcts and brain swell-ing leading to death within 2 weeks. A postmortem examination of the brain confirmed the neuroimaging find-ings of multiple cerebral infarctions of variable ages, consis-tent with a progressively evolving disease process. Sections of leptomeningeal vessels showed a striking giant cell arteritis involving large caliber vessels, establishing the cause of the underlying vasculopathy involving the brain that led to the fatal ischemic events. The precise relation of the vasculitis presented in this case to classic CNS angiitis is not entirely clear because the latter typically shows more transmural inflammation that is destructive of vascular walls. Nonethe-less, publication of such reports is critical to the medical community because they inform clinicians of potential path-ophysiologic mechanisms underlying specific clinical syn-dromes, which may influence future patient management. Granted, the reviews provided here are from the perspective of a pathologist, which almost certainly focus more on laboratory testing, interpretation, and diagnosis. These 3 articles demonstrate the role of the pathologist in patient management, education and research. Establishing accurate tissue-based diagnosis remains the central mission of anatomic pathology, whereas the clinical labs generate important results that guide clinical decisions. Laboratory-based testing will only increase and become more complex with new genomic and proteomic platforms quickly emerging, making the role of pathologists in data delivery and interpretation even more critical. REFERENCES 1. Traynis I, Singer S, Winterkorn J, Dinkin M. Unique case of infiltration of the optic chiasm, nerve, and disc by gliomatosis cerebri. J Neuroophthalmol. 2014;xx:xx-xx. 2. Parker SE, Gujrati M, Pula JH, Zallek SN, Kattah J. The Heidenhain variant of Creutzfeld-Jacob disease: a case series. J Neuroophthalmol. 2014;xx:xx-xx. 3. Tsang BK-T, Chauhan DS, Haward R, Whiteman I, Frayne J, McLean C. Histopathological findings in a case of fatal ischaemic stroke complicating acute multifocal placoid pigment epitheliopathy. J Neuroophthalmol. 2014;xx:xx-xx. 2 Brat: J Neuro-Ophthalmol 2014; 34: 1-2 Editorial Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
