xPath: Human-AI Diagnosis in Pathology with Multi-Criteria Analyses and Explanation by Hierarchically Traceable Evidence

Data-driven AI promises support for pathologists to discover sparse tumor patterns in high-resolution histological images. However, from a pathologist's point of view, existing AI suffers from three limitations: (i) a lack of comprehensiveness where most AI algorithms only rely on a single criterion; (ii) a lack of explainability where AI models tend to work as 'black boxes' with little transparency; and (iii) a lack of integrability where it is unclear how AI can become part of pathologists' existing workflow. Based on a formative study with pathologists, we propose two designs for a human-AI collaborative tool: (i) presenting joint analyses of multiple criteria at the top level while (ii) revealing hierarchically traceable evidence on-demand to explain each criterion. We instantiate such designs in xPath -- a brain tumor grading tool where a pathologist can follow a top-down workflow to oversee AI's findings. We conducted a technical evaluation and work sessions with twelve medical professionals in pathology across three medical centers. We report quantitative and qualitative feedback, discuss recurring themes on how our participants interacted with xPath, and provide initial insights for future physician-AI collaborative tools.Comment: 31 pages, 11 figure

A Case of Tuberculosis-related Leukocytoclastic Vasculitis Presenting With Peripheral Neuropathy.

Tuberculous granulomatous vasculitis is commonly associated with meningitis and retinitis. We describe a 39-year-old male, with a history of pulmonary tuberculosis (TB) who presented with progressive weakness, pain, tingling and numbness in the bilateral lower extremities. Significant atrophy and weakness of the lower extremities were evident along with absent reflexes. Nerve conduction studies and electromyography showed severe axonal polyneuropathy and denervation on the lower extremities. Nerve biopsy demonstrated small vessel leukocytoclastic vasculitis without any granuloma formation. Muscle biopsy was consistent with denervation and atrophy with target fiber changes. Tuberculosis-related vasculitis causing peripheral neuropathy is extremely rare and our case is unique in manifesting this presentation

Comorbidity in Dementia: Update of an Ongoing Autopsy Study

ObjectivesTo examine systemic and central nervous system (CNS) comorbidities of individuals with dementia evaluated during general autopsy.DesignRetrospective cohort study.SettingA large tertiary academic medical center in Los Angeles, California.ParticipantsIndividuals with clinically and neuropathologically diagnosed dementia who received complete autopsies (n = 86) and individuals with dementia who received partial (brain only) autopsies (n = 132).MeasurementsInformation on cause of death and systemic and CNS comorbidities was obtained from autopsy reports and clinical information as available from the medical records. Findings were tabulated with respect to type of dementia, semiquantitative assessment of the severity of cerebral amyloid angiopathy, semiquantitative assessment of the severity of cerebrovascular disease, and evidence of ischemic damage in the brain.ResultsOf 218 subjects with dementia, 175 (80.3%) had Alzheimer's disease alone or in combination with other lesions that might contribute to cognitive impairment, such as cerebrovascular disease and diffuse Lewy body disease (DLBD), 14 (6.4%) had frontotemporal dementia, and seven (3.2%) had isolated DLBD. The most common cause of death in participants with dementia was pneumonia (n = 57, 66.3%), followed by cardiovascular disease (n = 14, 16.3%). Eighteen subjects (20.9%) had lung disease, and 16 (18.6%) had evidence of an old or recent myocardial infarction. Clinically undiagnosed neoplasms included colonic adenocarcinoma, metastatic pulmonary neuroendocrine carcinoma, meningioma, and Schwannoma.ConclusionSignificant comorbidities were discovered at autopsy in individuals with dementia. Understanding the causes of death and associated comorbidities in individuals with various subtypes of dementia is important in the assessment of end-of-life care in these individuals

Brain biopsy in neurologic decline of unknown etiology.

Brain biopsies have an uncertain role in the diagnosis of patients with dementia or neurologic decline of unknown etiology. They are often performed only after an exhaustive panel of less invasive tests and procedures have failed to provide a definitive diagnosis. The objective of this study was to evaluate the sensitivity of brain biopsies in this patient group through the retrospective analysis of 53 brain biopsies performed for neurologic disease of unknown etiology at a single tertiary care institution between December 2001 and December 2011. Patients with known nonlymphomatous neoplasms thought to be associated with the neurologic symptoms or with immunodeficiency were excluded from the study. Furthermore, the clinical presentation, imaging and laboratory tests were compared between diagnostic groups to identify factors more likely to yield a diagnosis. Sixty percent of the biopsies were diagnostic (32 of 53), with the most common histologic diagnosis of central nervous system lymphoma in 14 of 53 patients (26% of total) followed by infarct in four subjects (7.5%). A few patients were found to have rare and unsuspected diseases such as lymphomatosis cerebri, neurosarcoidosis and neuroaxonal leukodystrophy. Complications from biopsy were uncommon and included hemorrhage and infection with abscess formation at the biopsy site. These results suggest that brain biopsies may be useful in difficult cases in which less invasive measures have been unable to yield a definitive diagnosis

Cerebroretinal Vasculopathies

Cerebroretinal vasculopathy (CRV) and the related diseases hereditary endotheliopathy with retinopathy, neuropathy, and stroke (HERNS), hereditary vascular retinopathy (HVR) and hereditary systemic angiopathy (HSA) [subsequently combined as retinovasculopathy and cerebral leukodystrophy (RVCL)] are devastating autosomal-dominant disorders of early to middle-age onset presenting with a core constellation of neurologic and ophthalmologic findings. This family of diseases is linked by specific mutations targeting a core region of a gene. Frameshift mutations in the carboxyl-terminus of three prime exonuclease-1 (TREX1), the major mammalian 3' to 5' DNA exonuclease on chromosome 3p21.1-p21.3, result in a systemic vasculopathy that follows an approximately 5-year course leading to death secondary to progressive neurologic decline, with sometimes a more protracted course in HERNS. Neuropathological features include a fibrinoid vascular necrosis or thickened hyalinized vessels associated with white matter ischemia, necrosis and often striking dystrophic calcifications. Ultrastructural studies of the vessel walls often demonstrate unusual multilaminated basement membranes