Suburothelial Hematomas Masquerading as Neoplasms in a Patient with Supra-Therapeutic INR.

Suburothelial hemorrhages (Antopol-Goldman lesions) are a rare but important condition. When unsuspected in a patient with a bleeding diathesis on anticoagulation therapy, computed tomography may lead to incorrect diagnoses of renal or transitional cell carcinoma resulting in inappropriate nephrectomy. We present a patient with supratherapeutic international normalized ratio and thigh hematoma who was found to have nonenhancing solid lesions of the bilateral renal pelves consistent with suburothelial hemorrhage. The patient's INR was controlled, and he was discharged with hematology follow-up 4 weeks later.

Pathologic Evaluation and Prognostic Implications of Nodal Micrometastases in Breast Cancer.

Using modern sentinel lymph node techniques, occult nodal metastases including micrometastases or isolated tumor cells are being increasingly discovered in up to 10% of early-stage breast cancers. Furthermore, the rate of nonsentinel lymph node involvement is approximately 10%. However, the impact of these findings on disease-free survival is low, particularly with regards to axillary recurrences. Current evidence suggests small-volume lymph node involvement in breast cancer patients is only one of several factors that should guide adjuvant therapy options. In otherwise favorable patients, adjuvant radiation and systemic therapy can help mitigate the risk of recurrence when omitting axillary lymph node dissection.

Stereological study of amygdala glial populations in adolescents and adults with autism spectrum disorder.

The amygdala undergoes aberrant development in autism spectrum disorder (ASD). We previously found that there are reduced neuron numbers in the adult postmortem amygdala from individuals with ASD compared to typically developing controls. The current study is a comprehensive stereological examination of four non-neuronal cell populations: microglia, oligodendrocytes, astrocytes, and endothelial cells, in the same brains studied previously. We provide a detailed neuroanatomical protocol for defining each cell type that may be applied to other studies of the amygdala in neurodevelopmental and psychiatric disorders. We then assess whether cell numbers and average volumes differ between ASD and typically developing brains. We hypothesized that a reduction in neuron numbers in ASD might relate to altered immune function and/or aberrant microglial activation, as indicated by increased microglial number and cell body volume. Overall, average non-neuronal cell numbers and volumes did not differ between ASD and typically developing brains. However, there was evident heterogeneity within the ASD cohort. Two of the eight ASD brains displayed strong microglial activation. Contrary to our original hypothesis, there was a trend toward a positive correlation between neuronal and microglial numbers in both ASD and control cases. There were fewer oligodendrocytes in the amygdala of adult individuals with ASD ages 20 and older compared to typically developing controls. This finding may provide a possible sign of altered connectivity or impaired neuronal communication that may change across the lifespan in ASD.

Comparative analysis of the dendritic organization of principal neurons in the lateral and central nuclei of the rhesus macaque and rat amygdala.

The amygdala plays a critical role in emotional processing and has been implicated in the etiology of numerous psychiatric disorders. It is an evolutionarily ancient structure that is enlarged in primates relative to rodents. Certain amygdala nuclei, such as the lateral nucleus, show relatively greater phylogenetic expansion than other nuclei. However, it is unknown whether there is also differential alteration in neuronal features. To address this question, we examined the dendritic arbors of principal neurons, visualized by using the Golgi method, in the lateral and central nuclei of young adult rhesus macaques and rats. Total dendritic length is greater in the macaque than in the rat. Dendritic trees are increased by 250% in length in the lateral nucleus of the monkey compared with the rat (6,009 µm vs. 2,473 µm); dendritic tree length in the central nucleus is increased by 50% (1,786 µm vs. 1,232 µm). Somal volume is increased 62% between species in the lateral nucleus and 48% in the central nucleus. Spine density is lower on macaque lateral nucleus dendrites compared with rat (-22%) but equivalent in the central nucleus. Spines are equally long in the lateral nucleus of rat and macaque, but spines are longer by about 20% in the central nucleus of the macaque. The alterations in dendritic structure that we observed between the two species suggest differences in the number and spacing of inputs into these nuclei that undoubtedly influence amygdala function.

Abnormal microglial-neuronal spatial organization in the dorsolateral prefrontal cortex in autism.

Microglial activation and alterations in neuron number have been reported in autism. However, it is unknown whether microglial activation in the disorder includes a neuron-directed microglial response that might reflect neuronal dysfunction, or instead indicates a non-directed, pro-activation brain environment. To address this question, we examined microglial and neuronal organization in the dorsolateral prefrontal cortex, a region of pronounced early brain overgrowth in autism, via spatial pattern analysis of 13 male postmortem autism subjects and 9 controls. We report that microglia are more frequently present near neurons in the autism cases at a distance interval of 25 µm, as well as 75 and 100 µm. Many interactions are observed between near-distance microglia and neurons that appear to involve encirclement of the neurons by microglial processes. Analysis of a young subject subgroup preliminarily suggests that this alteration may be present from an early age in autism. We additionally observed that neuron-neuron clustering, although normal in cases with autism as a whole, increases with advancing age in autism, suggesting a gradual loss of normal neuronal organization in the disorder. Microglia-microglia organization is normal in autism at all ages, indicating that aberrantly close microglia-neuron association in the disorder is not a result of altered microglial distribution. Our findings confirm that at least some microglial activation in the dorsolateral prefrontal cortex in autism is associated with a neuron-specific reaction, and suggest that neuronal organization may degrade later in life in the disorder.

Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism.

BACKGROUND: In the neurodevelopmental disorder autism, several neuroimmune abnormalities have been reported. However, it is unknown whether microglial somal volume or density are altered in the cortex and whether any alteration is associated with age or other potential covariates. METHODS: Microglia in sections from the dorsolateral prefrontal cortex of nonmacrencephalic male cases with autism (n = 13) and control cases (n = 9) were visualized via ionized calcium binding adapter molecule 1 immunohistochemistry. In addition to a neuropathological assessment, microglial cell density was stereologically estimated via optical fractionator and average somal volume was quantified via isotropic nucleator. RESULTS: Microglia appeared markedly activated in 5 of 13 cases with autism, including 2 of 3 under age 6, and marginally activated in an additional 4 of 13 cases. Morphological alterations included somal enlargement, process retraction and thickening, and extension of filopodia from processes. Average microglial somal volume was significantly increased in white matter (p = .013), with a trend in gray matter (p = .098). Microglial cell density was increased in gray matter (p = .002). Seizure history did not influence any activation measure. CONCLUSIONS: The activation profile described represents a neuropathological alteration in a sizeable fraction of cases with autism. Given its early presence, microglial activation may play a central role in the pathogenesis of autism in a substantial proportion of patients. Alternatively, activation may represent a response of the innate neuroimmune system to synaptic, neuronal, or neuronal network disturbances, or reflect genetic and/or environmental abnormalities impacting multiple cellular populations.

Autism at the beginning: microstructural and growth abnormalities underlying the cognitive and behavioral phenotype of autism.

Autistic symptoms begin in the first years of life, and recent magnetic resonance imaging studies have discovered brain growth abnormalities that precede and overlap with the onset of these symptoms. Recent postmortem studies of the autistic brain provide evidence of cellular abnormalities and processes that may underlie the recently discovered early brain overgrowth and arrest of growth that marks the first years of life in autism. Alternative origins and time tables for these cellular defects and processes are discussed. These cellular and growth abnormalities are most pronounced in frontal, cerebellar, and temporal structures that normally mediate the development of those same higher order social, emotional, speech, language, speech, attention, and cognitive functions that characterize autism. Cellular and growth pathologies are milder and perhaps nonexistent in other structures (e.g., occipital cortex), which are known to mediate functions that are often either mildly affected or entirely unaffected in autistic patients. It is argued that in autism, higher order functions largely fail to develop normally in the first place because frontal, cerebellar, and temporal cellular and growth pathologies occur prior to and during the critical period when these higher order neural systems first begin to form their circuitry. It is hypothesized that microstructural maldevelopment results in local and short distance overconnectivity in frontal cortex that is largely ineffective and in a failure of long-distance cortical-cortical coupling, and thus a reduction in frontal-posterior reciprocal connectivity. This altered circuitry impairs the essential role of frontal cortex in integrating information from diverse functional systems (emotional, sensory, autonomic, memory, etc.) and providing context-based and goal-directed feedback to lower level systems.