Molecular characterization and survival analysis of a cohort of glioblastoma, IDH-wildtype.

Glioblastoma, IDH-wild type, the most common malignant primary central nervous system tumor, represents a formidable challenge in clinical management due to its poor prognosis and limited therapeutic responses. With an evolving understanding of its underlying biology, there is an urgent need to identify prognostic molecular groups that can be subject to targeted therapy. This study established a cohort of 124 sequential glioblastomas from a tertiary hospital and aimed to find correlations between molecular features and survival outcomes. Comprehensive molecular characterization of the cohort revealed prevalent alterations as previously described, such as TERT promoter mutations and involvement of the PI3K-Akt-mTOR, CK4/6-CDKN2A/B-RB1, and p14ARF-MDM2-MDM4-p53 pathways. MGMT promoter methylation is a significant predictor of improved overall survival, aligned with previous data. Conversely, age showed a marginal association with higher mortality. Multivariate analysis to account for the effect of MGMT promoter methylation and age showed that, in contrast to other published series, this cohort demonstrated improved survival for tumors harboring PTEN mutations, and that there was no observed difference for most other molecular alterations, including EGFR amplification, RB1 loss, or the coexistence of EGFR amplification and deletion/exon skipping (EGFRvIII). Despite limitations in sample size, this study contributes data to the molecular landscape of glioblastomas, prompting further investigations to examine these findings more closely in larger cohorts.

Molecular and clinicopathologic characteristics of CNS embryonal tumors with BRD4::LEUTX fusion.

Central nervous system (CNS) embryonal tumors are a heterogeneous group of high-grade malignancies, and the increasing clinical use of methylation profiling and next-generation sequencing has led to the identification of molecularly distinct subtypes. One proposed tumor type, CNS tumor with BRD4::LEUTX fusion, has been described. As only a few CNS tumors with BRD4::LEUTX fusions have been described, we herein characterize a cohort of 9 such cases (4 new, 5 previously published) to further describe their clinicopathologic and molecular features. We demonstrate that CNS embryonal tumor with BRD4::LEUTX fusion comprises a well-defined methylation class/cluster. We find that patients are young (4 years or younger), with large tumors at variable locations, and frequently with evidence of leptomeningeal/cerebrospinal fluid (CSF) dissemination. Histologically, tumors were highly cellular with high-grade embryonal features. Immunohistochemically, 5/5 cases showed synaptophysin and 4/5 showed OLIG2 expression, thus overlapping with CNS neuroblastoma, FOXR2-activated. DNA copy number profiles were generally flat; however, two tumors had chromosome 1q gains. No recurring genomic changes, besides the presence of the fusion, were found. The LEUTX portion of the fusion transcript was constant in all cases assessed, while the BRD4 portion varied but included a domain with proto-oncogenic activity in all cases. Two patients with clinical follow up available had tumors with excellent response to chemotherapy. Two of our patients were alive without evidence of recurrence or progression after gross total resection and chemotherapy at 16 and 33 months. One patient relapsed, and the last of our four patients died of disease one month after diagnosis. Overall, this case series provides additional evidence for this as a distinct tumor type defined by the presence of a specific fusion as well as a distinct DNA methylation signature. Studies on larger series are required to further characterize these tumors.

Molecular Analysis of Liquid Vitreous Biopsy Reveals Occult Lymphoma Following Cytology-Negative Biopsies of the Brain and Vitreous.

PURPOSE: Primary central nervous system lymphoma (PCNSL) is a rare but deadly malignancy that principally affects adults in the fifth and sixth decades of life. Despite diagnostic advances in analyses of cerebral spinal fluid and neuroimaging, definitive diagnosis of PCNSL requires primary brain tissue biopsy. While small neurosurgical biopsy volumes are pursued to minimize removal of normal brain tissue, the spatial margins to precisely biopsy pathologic tissue are narrow and can result in missed diagnoses. Furthermore, prior steroid treatment can significantly reduce tumor burden increasing the likelihood of a non-diagnostic biopsy. METHODS: A retrospective case report from a tertiary referral center using a combination of neuroradiological studies, sterotactic tissue biopsy, and molecular testing for genome mutations. RESULTS: A 72-year-old woman with strong suspicion for PCNSL clinically and radiologically, but cerebral spinal fluid and primary brain tissue biopsy were negative for tumor. However, vitreous liquid biopsy molecular testing for a MYD88 mutation as well as B-cell clonality (IGH/IGK rearrangement) were positive, indicating the presence of secondary vitreoretinal lymphoma from PCNSL. Only after autopsy of her brain was histopathological and immunohistochemical evidence of PCNSL confirmed. CONCLUSION: This case illustrates the unique contribution of liquid biopsy neuropathology-oriented molecular testing in a challenging case with high clinical suspicion of PCNSL in which gold-standard diagnostic testing failed to yield a diagnosis.

A Contemporary Approach to Intraoperative Evaluation in Neuropathology.

CONTEXT.­: Although the basic principles of intraoperative diagnosis in surgical neuropathology have not changed in the last century, the last several decades have seen dramatic changes in tumor classification, terminology, molecular classification, and modalities used for intraoperative diagnosis. As many neuropathologic intraoperative diagnoses are performed by general surgical pathologists, awareness of these recent changes is important for the most accurate intraoperative diagnosis. OBJECTIVE.­: To describe recent changes in the practice of intraoperative surgical neuropathology, with an emphasis on new entities, tumor classification, and anticipated ancillary tests, including molecular testing. DATA SOURCES.­: The sources for this review include the fifth edition of the World Health Organization Classification of Tumours of the Central Nervous System, primary literature on intraoperative diagnosis and newly described tumor entities, and the authors' clinical experience. CONCLUSIONS.­: A significant majority of neuropathologic diagnoses require ancillary testing, including molecular analysis, for appropriate classification. Therefore, the primary goal for any neurosurgical intraoperative diagnosis is the identification of diagnostic tissue and the preservation of the appropriate tissue for molecular testing. The intraoperative pathologist should seek to place a tumor in the most accurate diagnostic category possible, but specific diagnosis at the time of an intraoperative diagnosis is often not possible. Many entities have seen adjustments to grading criteria, including the incorporation of molecular features into grading. Awareness of these changes can help to avoid overgrading or undergrading at the time of intraoperative evaluation.

Neuropathologic Features in Chronic Methamphetamine Use.

ABSTRACT: Methamphetamine is a psychostimulant that exerts its euphoric and stimulant effects by increasing cytosolic monoamine concentration at the nerve terminal. In addition to its known systemic cardiovascular effects, there is compelling evidence to suggest a direct neurotoxic effect of methamphetamine; however, the existing body of literature includes very few human tissue studies. This exploratory analysis used postmortem human brain specimens to examine histologic and immunohistochemical features associated with chronic methamphetamine use. This retrospective cohort study included 60 decedents who were autopsied at the University of Iowa Hospitals and Clinics between the years 2015 and 2021. Logistic regression models demonstrated no definite pathologic changes in the hippocampi of individuals with a history of chronic methamphetamine use. Decedents with a history of methamphetamine use had a marginally increased odds of basal ganglia arteriosclerosis, which did not reach statistical significance (odds ratio, 3.33; 95% confidence interval, 0.6-19.2; P = 0.17), which may be independent of the systemic hypertensive effects of methamphetamine. Future studies that include targeted examination of brain regions of interest, such as the basal ganglia and specifically the striatum, may prove revealing.

The neuropathologic findings in a case of progressive cavitating leukoencephalopathy due to NDUFV1 pathogenic variants.

Pathogenic variants in the NDUFV1 gene, which codes for complex I of the mitochondrial respiratory chain, have been associated with a variety of clinical phenotypes, including a progressive cavitating leukoencephalopathy. The neuropathology of NDUFV1-associated leukoencephalopathy is not well-described. We present a report of a 24-year-old female with two pathogenic variants in the NDUFV1 gene, together with antemortem skeletal muscle biopsy and postmortem neuropathologic examination. Autopsy neuropathology showed a cavitating leukoencephalopathy with extensive white matter involvement, regions of active demyelination, and sparing of the subcortical U-fibers. Muscle biopsy showed subtle but distinct histologic abnormalities by light microscopy, and ultrastructural analysis demonstrated mitochondrial abnormalities including abnormal subsarcolemmal mitochondrial accumulation, electron-dense inclusions, and enlarged mitochondria with abnormal cristae. Our report is the first comprehensive description of the neuropathology in a patient with compound heterozygous variants in the NDUFV1 gene and progressive cavitating leukoencephalopathy. This case is evidence of pathogenicity of one NDUFV1 variant (c.565 T > C, p.S189P), which has not been previously described as pathogenic. These findings, in combination with the ultrastructural abnormalities in the mitochondria by electron microscopy, support the mitochondrial nature of the pathology. Together, this case highlights the link between mitochondrial abnormalities and demyelinating processes in the central nervous system (CNS).

COVID-19-associated necrotizing encephalopathy presenting without active respiratory symptoms: a case report with histopathology.

Acute necrotizing encephalopathy (ANE) is a rare complication of coronavirus disease 2019 (COVID-19) secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The condition is typically diagnosed based on characteristic neuroimaging findings in the context of active viral respiratory symptoms. We present a rare case of COVID-19-associated ANE presenting with expressive aphasia and encephalopathy in the absence of active respiratory symptoms. Initial evaluation revealed bilateral thalamic lesions and a mild neutrophilic-predominant pleocytosis on cerebrospinal fluid analysis, the latter of which has not been described in previously published cases. Presence of these atypical features prompted extensive diagnostic evaluation. Metagenomic next-generation sequencing on cerebrospinal fluid did not detect the presence of pathogenic nucleic acids. Thalamic biopsy revealed perivascular neutrophilic inflammation suggestive of small vessel vasculitis with surrounding hemorrhage and necrosis. Ultimately, the diagnosis was made following detection of SARS-CoV-2 serologies and after exclusion of alternative etiologies. The patient was successfully treated with a short course of high-dose methylprednisolone with favorable outcome.

OpenSRH: optimizing brain tumor surgery using intraoperative stimulated Raman histology.

Accurate intraoperative diagnosis is essential for providing safe and effective care during brain tumor surgery. Our standard-of-care diagnostic methods are time, resource, and labor intensive, which restricts access to optimal surgical treatments. To address these limitations, we propose an alternative workflow that combines stimulated Raman histology (SRH), a rapid optical imaging method, with deep learning-based automated interpretation of SRH images for intraoperative brain tumor diagnosis and real-time surgical decision support. Here, we present OpenSRH, the first public dataset of clinical SRH images from 300+ brain tumors patients and 1300+ unique whole slide optical images. OpenSRH contains data from the most common brain tumors diagnoses, full pathologic annotations, whole slide tumor segmentations, raw and processed optical imaging data for end-to-end model development and validation. We provide a framework for patch-based whole slide SRH classification and inference using weak (i.e. patient-level) diagnostic labels. Finally, we benchmark two computer vision tasks: multiclass histologic brain tumor classification and patch-based contrastive representation learning. We hope OpenSRH will facilitate the clinical translation of rapid optical imaging and real-time ML-based surgical decision support in order to improve the access, safety, and efficacy of cancer surgery in the era of precision medicine. Dataset access, code, and benchmarks are available at https://opensrh.mlins.org.

The Neuropathology of 1p36 Deletion Syndrome: An Autopsy Case Series.

1p36 deletion syndrome is the most common terminal deletion syndrome, manifesting clinically as abnormal facies and developmental delay with frequent cardiac, skeletal, urogenital, and renal abnormalities. Limited autopsy case reports describe the neuropathology of 1p36 deletion syndrome. The most extensive single case report described a spectrum of abnormalities, mostly related to abnormal neuronal migration. We report the largest published series of 1p36 autopsy cases, with an emphasis on neuropathologic findings. Our series consists of 3 patients: 2 infants (5-hours old and 23-days old) and 1 older child (11 years). Our patients showed abnormal cortical gyration together with a spectrum of neuronal migration abnormalities, including heterotopias and hippocampal abnormalities, as well as cerebellar hypoplasia. Our findings thus support the role of neuronal migration defects in the pathogenesis of cognitive defects in 1p36 deletion syndrome and broaden the reported neuropathologic spectrum of this common syndrome.

Brain Histopathology of Adult Decedents After Extracorporeal Membrane Oxygenation.

OBJECTIVE: To test the hypothesis that brain injury is more common and varied in patients receiving extracorporeal membrane oxygenation (ECMO) than radiographically observed, we described neuropathology findings of ECMO decedents and associated clinical factors from 3 institutions. METHODS: We conducted a retrospective multicenter observational study of brain autopsies from adult ECMO recipients. Pathology findings were examined for correlation with demographics, clinical data, ECMO characteristics, and outcomes. RESULTS: Forty-three decedents (n = 13 female, median age 47 years) received autopsies after undergoing ECMO for acute respiratory distress syndrome (n = 14), cardiogenic shock (n = 14), and cardiac arrest (n = 15). Median duration of ECMO was 140 hours, most decedents (n = 40) received anticoagulants; 60% (n = 26) underwent venoarterial ECMO, and 40% (n = 17) underwent venovenous ECMO. Neuropathology was found in 35 decedents (81%), including microhemorrhages (37%), macrohemorrhages (35%), infarctions (47%), and hypoxic-ischemic brain injury (n = 17, 40%). Most pathology occurred in frontal neocortices (n = 43 occurrences), basal ganglia (n = 33), and cerebellum (n = 26). Decedents with hemorrhage were older (median age 57 vs 38 years, p = 0.01); those with hypoxic brain injury had higher Sequential Organ Failure Assessment scores (8.0 vs 2.0, p = 0.04); and those with infarction had lower peak Paco2 (53 vs 61 mm Hg, p = 0.04). Six of 9 patients with normal neuroimaging results were found to have pathology on autopsy. The majority underwent withdrawal of life-sustaining therapy (n = 32, 74%), and 2 of 8 patients with normal brain autopsy underwent withdrawal of life-sustaining therapy for suspected neurologic injury. CONCLUSION: Neuropathological findings after ECMO are common, varied, and associated with various clinical factors. Further study on underlying mechanisms is warranted and may guide ECMO management.

Rapid, label-free detection of diffuse glioma recurrence using intraoperative stimulated Raman histology and deep neural networks.

BACKGROUND: Detection of glioma recurrence remains a challenge in modern neuro-oncology. Noninvasive radiographic imaging is unable to definitively differentiate true recurrence versus pseudoprogression. Even in biopsied tissue, it can be challenging to differentiate recurrent tumor and treatment effect. We hypothesized that intraoperative stimulated Raman histology (SRH) and deep neural networks can be used to improve the intraoperative detection of glioma recurrence. METHODS: We used fiber laser-based SRH, a label-free, nonconsumptive, high-resolution microscopy method (<60 sec per 1 × 1 mm2) to image a cohort of patients (n = 35) with suspected recurrent gliomas who underwent biopsy or resection. The SRH images were then used to train a convolutional neural network (CNN) and develop an inference algorithm to detect viable recurrent glioma. Following network training, the performance of the CNN was tested for diagnostic accuracy in a retrospective cohort (n = 48). RESULTS: Using patch-level CNN predictions, the inference algorithm returns a single Bernoulli distribution for the probability of tumor recurrence for each surgical specimen or patient. The external SRH validation dataset consisted of 48 patients (recurrent, 30; pseudoprogression, 18), and we achieved a diagnostic accuracy of 95.8%. CONCLUSION: SRH with CNN-based diagnosis can be used to improve the intraoperative detection of glioma recurrence in near-real time. Our results provide insight into how optical imaging and computer vision can be combined to augment conventional diagnostic methods and improve the quality of specimen sampling at glioma recurrence.

Medical Examiner Review of the Characteristics of Fire-Related Homicides.

While fire-related deaths are regularly encountered by medical examiners, fire-related homicides are relatively uncommon. Although some large retrospective studies of fire-related deaths have been performed, few large studies have specifically reviewed fire-related homicides. Autopsy, scene investigation, and ancillary studies were reviewed for 38 fire-related homicides evaluated at the Wayne County Medical Examiner's Office in Detroit, Michigan. The largest proportion of cases were inhalation-related deaths in dwelling fires (n = 21, 55%), followed by deaths from thermal injury after immolation (n = 8, 21%) and traumatic death with contemporaneous or subsequent immolation (n = 8, 21%). There was one case of postmortem immolation. Although carboxyhemoglobin (COHb) levels played a significant role in evaluation of these cases, no single factor was diagnostic of a particular cause or manner of death. Fire-related homicides present unique diagnostic challenges because multiple insults frequently contribute to the cause death. Death at the scene and COHb level above 10% are the most useful factors in establishing smoke and soot inhalation as the cause of death. Some autopsy findings are helpful in establishing or ruling out smoke and soot inhalation as contributing to or sole cause of death, but an evaluation of the entire circumstances and autopsy findings is necessary.

Multiple system atrophy pathology is associated with primary Sjögren's syndrome.

BACKGROUNDOur objective was to investigate whether primary Sjögren's syndrome (pSS) is associated with multiple system atrophy (MSA).METHODSWe performed a retrospective cohort study assessing (a) rates of MSA in a cohort of patients with pSS and (b) rates of pSS in a cohort of patients with MSA. These data were compared with rates in respective control groups. We additionally reviewed the neuropathologic findings in 2 patients with pSS, cerebellar degeneration, parkinsonism, and autonomic dysfunction.RESULTSOur cohort of 308 patients with pSS had a greater incidence of MSA compared with 4 large population-based studies and had a significantly higher prevalence of at least probable MSA (1% vs. 0%, P = 0.02) compared with 776 patients in a control cohort of patients with other autoimmune disorders. Our cohort of 26 autopsy-proven patients with MSA had a significantly higher prevalence of pSS compared with a cohort of 115 patients with other autopsy-proven neurodegenerative disorders (8% vs. 0%, P = 0.03). The 2 patients we described with pSS and progressive neurodegenerative disease showed classic MSA pathology at autopsy.CONCLUSIONOur findings provide evidence for an association between MSA and pSS that is specific to both pSS, among autoimmune disorders, and MSA, among neurodegenerative disorders. The 2 cases we describe of autopsy-proven MSA support that MSA pathology can explain neurologic disease in a subset of patients with pSS. These findings together support the hypothesis that systemic autoimmune disease plays a role in neurodegeneration.FUNDINGThe Michigan Brain Bank is supported in part through NIH grant P30AG053760.

Incidental Massive Hydrocephalus Associated With an Unruptured Choroid Plexus Arteriovenous Malformation and Complete Agenesis of the Corpus Callosum Found in an Adult at Autopsy.

Undiagnosed significant hydrocephalus is an uncommon finding at forensic autopsy as many cases present in life with complex neurological symptoms. We present a case of a 46-year-old man with no neurological deficits or history of head trauma that was incidentally found to have a massive hydrocephalus at autopsy. This was found to be associated with an unruptured arteriovenous malformation completely confined to the choroid plexus as well as complete agenesis of the corpus callosum. The arteriovenous malformation was found to form a calcified obstruction at the foramen of Monro analogous to a mass lesion, such as a colloid cyst of the third ventricle. The association of this malformation and agenesis of the corpus callosum has never been described. Histologic examination of the brain confirmed significant loss of white matter tracts and thinning of the cortical ribbon due to pressure atrophy of the ependymal lining without significant gliosis, cortical dysplasia, or evidence of other developmental malformations. Autopsy is a vital tool in the evaluation of such rare cases, enhances epidemiologic data, and increases the understanding of these pathophysiological associations.

Sudden Death Due to Calcifying Pseudoneoplasm of the Neuraxis: A Case Report and a Review of Sudden Death Due to Undiagnosed Central Nervous System Mass Lesions.

We present a case of a 22-year-old man who died unexpectedly after a seizure due to a previously undiagnosed calcifying pseudoneoplasm of the neuraxis (CAPNON). Calcifying pseudoneoplasm of the neuraxis is a rare entity, and this is, to our knowledge, the first described case of sudden death due to CAPNON. Sudden death due to undiagnosed central nervous system mass lesions is rare, and most cases are attributable to hemorrhage, hydrocephalus, or increased intracranial pressure due to mass effect. Seizure is a rare cause of sudden death due to central nervous system mass lesions. This case highlights that mass lesions may cause sudden death due to seizure, even without other pathologic evidence of a cause of death, such as hemorrhage or edema. Furthermore, benign, reactive, and low-grade mass lesions may cause sudden death due to seizure. Seizure should remain in the autopsy differential as a cause of death, even where there is no pathologically evident mechanism by which a mass lesion caused death.

Atherosclerotic and Hypertensive Cardiovascular Disease are Associated with Death at Sublethal Carboxyhemoglobin Levels: A Postmortem Study.

Residential fires are a significant cause for morbidity and mortality in the United States. Death is often the result of soot and smoke inhalation causing carbon monoxide (CO) toxicity. The approximate lethal level of carboxyhemoglobin (COHb) in healthy adults has been well described. However, a significant number of medical examiner cases involve infirmed decedents, often elderly, with complex cardiovascular disease burdens. It is well known that death in these cases will occur at sublethal levels of COHb; however, increased lethality has been largely documented via anecdotal experience and lacks quantification. Fifty-five cases were identified where death resulted from smoke and soot inhalation suffered in a residential fire. The control group, with no cardiovascular disease, had an age-adjusted mean COHb level of 61.6% at the time of death. Presence of hypertensive cardiovascular disease showed a 30% reduction in COHb (age-adjusted mean 43.2%), atherosclerotic disease showed a 33% reduction (age-adjusted mean 41.5%), and combined disease presentation accounted for 41% reduction (age-adjusted mean 36.3%). When controlling for age, atherosclerotic and hypertensive cardiovascular diseases were each associated with statistically significant decreases in COHb (p < 0.01). Increasing age was associated with decreased COHb levels at 2.8% per 10 years of life (p < 0.01), even when modeled with hypertensive and atherosclerotic disease. These findings carry important public health significance, as well as practical significance for the medical examiner when interpreting COHb levels in cases of suspected deaths due to smoke and soot inhalation.

Improving your spectacle patients' in-practice experience with contact lenses during frame selection.

PURPOSE: A market research survey was conducted to assess the impact of offering complimentary contact lenses (CLs) to spectacle-only wearing patients during frame selection with regards to their in-office experience, the transaction amount for their eyewear purchase and the likelihood of proceeding with a comprehensive contact lens fitting. METHODS: Five optometry offices in the US participated. An initial interviewing phase served as a control during which optometrists treated spectacle-only wearing patients in the usual manner for frame selection. After this, the offices transitioned into a test phase where patients were offered the opportunity to wear CLs while selecting new spectacle frames. Only patients 18 or older who had not expressed an interest in CLs were invited to participate. A brief survey was completed on an iPad following the visit by all patients in both control and test phases. RESULTS: 410 patients (205 test, 205 control) participated. 63% of the test group elected to wear CLs (40% spherical, 20% toric, 35% multifocal, 5% monovision). Patients wearing CLs spent more on their eyewear purchase ($708 vs $593, p = 0.04), were greater than 2.5X more likely to have received or scheduled a CL fit (p = 0.01), and were greater than 3X more likely to consider scheduling a CL fitting in the future (p = 0.0003). Additionally, 93% reported that they were highly satisfied with the experience and 86% said they would wear CLs to select frames again (86%). CONCLUSIONS: Offering CLs to spectacle-only patients positively impacts eyewear selection and purchase and can grow the overall CL business.

Cardiac Involvement in Sarcoidosis Deaths in Wayne County, Michigan: A 20-Year Retrospective Study.

BACKGROUND: Sarcoidosis is a disease of unknown etiology characterized by the formation of noncaseating, nonnecrotizing granulomas in various organ systems. METHODS: Reviews of 84 cases of natural death with sarcoidosis between the years 1996 and 2017 autopsied at Wayne County. RESULTS: The median age of decedents was 44 years (29 - 59 years of age). Blacks comprised 95% of the cohort, and 52% were female. Sarcoidosis or direct sequelae were the cause of death in 79% of cases. Twenty-nine percent of patients had a documented history of sarcoidosis and 70% of patients had evidence of systemic sarcoidosis. The most common sites of involvement were lungs or hilar lymph nodes (92%), heart (45%), liver (39%), and spleen (30%). Decedents with cardiac involvement were more likely to have no documented history of sarcoidosis (87% vs. 59%, p=0.004), more likely to have died of a sarcoidosis-related cause (97% vs. 65%, p<0.001), and died at a younger mean age (41 years vs. 46 years, p=0.001). In addition, individuals with cardiac involvement commonly had concurrent multiorgan involvement including lungs (90%), lymph nodes (38%), liver (40%), spleen (32%), and kidneys (7%). CONCLUSIONS: Cardiac sarcoidosis is a uniquely poor prognostic factor and carries an increased risk of sudden death as shown by a disproportionate representation among medical examiner cases of sarcoidosis. Our findings suggest that approximately 40% may have asymptomatic cardiac involvement. The distribution of sarcoidosis within our cohort suggests that there is potentially a large undiagnosed and/or underdiagnosed demographic within large urban centers, such as Detroit, Michigan.