Usefulness of epithelial membrane antigen (EMA) to discriminate between perineural invasion and perineural indentation in prostatic carcinoma.

AIMS: Perineural invasion (PNI) is one of the few unequivocal criteria to diagnose adenocarcinoma of the prostate. Distinguishing PNI from perineural indentation (PNIn), however, is sometimes difficult. The aim of this study was to discriminate between PNI and PNIn using EMA immunohistochemistry. METHODS AND RESULTS: We selected representative sections from 87 prostatectomies with prostatic adenocarcinoma. Normal peripheral nerves were continuously encircled with perineurium, which was immunoreactive for EMA. We identified 1319 PNI by carcinomas, 368 PNIn by carcinomas, and 303 PNIn by benign glands. We categorized the EMA immunoreactivity patterns into three classes: samples that displayed discontinuity or complete loss of the perineurium (Type A), samples where there were carcinomas or benign glands in the perineural space or peripheral nerves (Type B) and samples that showed no changes in the perineurium (Type C). For PNI we observed Type A, Type B, and Type C patterns in 55.3%, 24.8% and 19.9% of carcinomas, respectively. The incidence of each of those patterns in PNIn by carcinomas was 32.1%, 14.9% and 53.0%, respectively. Cases of PNIn by benign glands showed Type A or Type C patterns. They did not, however, exhibit Type B patterns. CONCLUSION: EMA immunostaining will aid the diagnosis of prostatic adenocarcinoma.

Alpha-synuclein-positive structures in association with diffuse neurofibrillary tangles with calcification.

alpha-Synuclein is known to be a major constituent of the Lewy bodies (LBs) in Parkinson's disease (PD) and the neuronal and glial cytoplasmic inclusions (NCIs, GCIs) in multiple system atrophy. alpha-Synuclein-positive inclusions such as LBs, NCIs and GCIs sometimes show colocalization with tau-positive neurofilaments. Studies using alpha-synuclein immunohistochemistry have often found LBs in the amygdala of patients with familial or sporadic Alzheimer's disease (AD), as well as in patients with Down's syndrome and AD. However, no studies have reported alpha-synuclein-positive structures in cases of diffuse neurofibrillary tangles with calcification (DNTC), which is characterized by numerous neurofibrillary tangles (NFTs) throughout the cerebral cortex but few, if any, senile plaques. We investigated the distribution of alpha-synuclein-positive structures in two cases of DNTC: a 65-year-old woman (brain weight, 850 g) and a 75-year-old woman (brain weight, 800 g). In both cases, severe cerebral atrophy predominant in the temporal lobe was noted. Microscopically, alpha-synuclein-positive intracytoplasmic inclusions and neurites were found in the superior temporal lobe (within the temporal pole), amygdala, parahippocampus, entorhinal cortex and insula, the regions most affected by the NFTs. alpha-Synuclein-positive intracytoplasmic inclusions were rare or absent in other regions of the cerebral cortex and brainstem. This distribution pattern differs from that of PD or dementia with LBs. Our findings suggest that the accumulation pattern of alpha-synuclein is a pathological feature of DNTC, and that DNTC is associated with accumulation of both tau and alpha-synuclein.

[An autopsied case of atypical presenile dementia which shows lobar atrophy, severe neurofibrillary tangles and calcification].

We report an autopsy case of atypical presenile dementia. Shibayama, Kosaka and others had reported similar autopsy cases. These cases had the following common pathologic characteristics: circumscribed cerebral atrophy, diffuse neurofibrillary tangles (NFTs) noted in the cerebral cortex with few senile plaques (SPs), and pathological calcification. We propose the term "dementia with cerebral calcification and tangles" (DCCT) for this atypical presenile dementia. Our patient, who was female and died at the age of 65 years, also exhibited these characteristics. Her clinical diagnosis was Alzheimer's disease. She had developed apparent dementia at the age of 55. Psychological and neurological symptoms such as memory impairment, speech disturbance and abnormal behavior slowly progressed. Gradually, she had become bedridden in her own home. When she was 65 years old, she was admitted because of pneumonia, and died soon after. In the pathologic examination of our patient, the brain weight was 850 g, and severe cerebral atrophy predominant in the temporal lobe was noted. Microscopically, diffuse and numerous NFTs were also found in the cerebral cortex and brain stem. Some NFTs were observed in the dentate nucleus of the cerebellum. However, SPs were seldom noted. Calcifications were also found in the putamen, globus pallidus and cerebellar cortex. NFTs in our case had developed without the formation of SPs. The degree of the NFT formation was correlated to the extent of cerebral cortical atrophy and neuron loss. Therefore, we suspect that NFTs with neuron loss strongly contribute to clinical symptoms such as dementia. The distribution of NFTs resembles that in patients with Alzheimer's disease, they are more prominent in the temporal lobe in our case. Although there has not been any discussion about the findings of glial cells and neuropils in DCCT, our detailed examination showed argyrophilic structures in glial cells and in neuropils. Most of the glial cells appeared to be oligodendrocytes. Calcification is also a prominent characteristic of DCCT. Using analytical electron microscopy, we examined the area of calcification in the globus pallidus and cerebellum, and found an accumulation of both Fe and Ca. The role of calcification in the pathogenesis, however, remains unclear. It is very important to examine cases of atypical presenile dementia clinicopathologically, in order to study the correlation between NFTs and SPs in neurological disease, and to understand their pathogenetic significance.

Relationship between brainstem MRI and pathological findings in progressive supranuclear palsy--study in autopsy cases.

The relationship between the features of MRI in brainstem and pathological findings was investigated in eight autopsy cases with progressive supranuclear palsy (PSP). Features of T1-weighted images at midbrain level were atrophy of tegmentum and tectum, and dilatation of aqueduct. Histologically, these findings were consistent with atrophy of periaqueductal gray matter, quadrigeminal plate, and tegmentum. In these lesions, we detected neuronal loss, decrease in density of myelinated fibers, gliosis, rarefaction of tissues, and tau-positive structures such as neurofibrillary tangles (NFTs), glial fibrillary tangles (GFTs) and neuropil threads. At pons level, atrophy of tegmentum, atrophy of pontine base, and dilatation of prepontine cistern were found. Tau-positive structures were observed not only in tegmentum but also in pontine base. The density of the tau-positive structure was closely related to the severity of atrophy. Features of T2-weighted images were high intensity in the periaqueductal lesion and tegmentum in pons. In these lesions, severe histological findings were detected. The MRI features in brainstem were closely related to the histological findings as PSP.

A clinico-neuropathological study on brain death.

A clinico-neuropathological study was conducted on 60 cases of brain death, 36 males and 24 females, ranging in age from 11 to 81 years, the average being 49.4 years. Of these, 29 patients died of cerebrovascular disease. The average duration of brain death was 99 hours. The mean weight of the brain was 1466 g. Neuropathological findings were brain edema, congestion, herniation and various subarachnoid hemorrhages. Histologically, the cytoplasm of neurons was pale and ghost-like. In the white matter, myelin staining was pale, and nuclei of the glial cells were shrunken and piknotic. Autolysis of the cerebellar granular layer and the pituitary gland was evident in all cases. No reactive astrocytosis or infiltration of the cells in or around necrotic tissue could be seen. In eight cases, there was laminar infiltration of neutrophils in the superficial area of the cerebrum and brain stem, possibly due to temporary or partial recirculation. Correlation between the degree of autolysis and duration of brain death was observed, but no relationship between the degree of autolysis and the difference of underlying disease could be found. Autolysis in the cerebral cortex, thalamus, tegmentum of the brain stem, cerebellar granular layer and pituitary gland was most prominent. However, neuropathological diagnosis of underlying diseases could be made even in brain death. Histologically, the cases of brain death differed from those of cardiac arrest-induced encephalopathy and from those of long postmortem autopsy.

[A neuropathological study on respirator brain].

A neuropathological study was conducted on 101 respirator brains. The patients comprised 62 men and 39 women, ranging in age from 11 to 84 years, the average being 49.4 years. Of these, 51 cases died of cerebrovascular disease, including 26 cases of subarachnoid hemorrhage. The average duration of mechanical supportive care was 99 hours. The mean weight of the brain at autopsy was 1,460 g. Characteristic pathological findings were brain edema, congestion, herniation and various subarachnoid hemorrhages. Brain consistency was soft despite adequate fixation. Histologically, the cytoplasm of neurons in the cerebral cortex, basal ganglia, cerebellum and brain stem was pale and ghost like. In the white matter, myelin staining was quite pale and nuclei of the glial cells were shrunken and piknotic. Autolysis of the granular layer of the cerebellar cortex and necrosis of anterior parts of the pituitary gland were evident in all of the brains examined. There were no reactive astrocytosis and no infiltration neutrophils in the superficial areas of the cerebrum and brain stem, possibly due to temporary or partial circulation. There exists some correlation between the degree of autolysis and the duration of artificial aeration. But no relationship between the former and the basic disease was found. In the respirator brains, autolysis was most prominent in the cerebral cortex, thalamus, tegmentum of the brain stem, granular layer of the cerebellar cortex and the pituitary gland. It was possible to establish the diagnoses of underlying diseases such as cerebrovascular disease, meningoencephalitis, tumor and degenerative disease in the majority of cases through neuropathological analysis on the respiratory brains.(ABSTRACT TRUNCATED AT 250 WORDS)

[An autopsied case of type II citrullinemia--transient effectiveness with either citrate or benzoate to the consciousness disturbance].

A 44-year-old man suffered from repeated impairment of consciousness associated with flapping tremor, myoclonus and generalized convulsions, and died in coma 6 months after admission. He had had a psychosomatically underdeveloped childhood, with a propensity for legumes without a family history of the same or a record of consanguinity. On admission, he had disturbed consciousness and emaciation without other physical abnormalities. The EEG revealed diffuse slow waves with occasional appearance of triphasic waves. A high level of serum citrulline (534.7 nmol/ml) was recognized and the assay of urea cycle enzymes in the liver demonstrated decreased argininosuccinate synthetase (ASS) activity (0.062 U/g liver, 7.4% of that in normal liver), although no kinetic abnormality was found. Accordingly he was diagnosed as having type II citrullinemia. In addition, this case could be classified as cluster type of localization of the ASS in the liver by immunohistochemical study. There were characteristic findings concerning his clinical picture and laboratory data, such as a significant correlation between the grade of disturbed consciousness and arterial blood gas pH (r = 0.61, p less than 0.01). However, the blood ammonia level did not always correlate with the severity of disturbed consciousness. Oral treatment with sodium citrate and sodium benzoate was very effective, though transiently, for disturbed consciousness in this case. Pathological findings of the autopsied liver were fatty change and fibrosis. Neuropathologically, characteristic findings were brain edema with cerebellar tonsilar herniation, laminar necrosis with spongy formation in cerebral cortex, and Alzheimer type II glia. The relationship between citrullinemia and other hepatic encephalopathy was also discussed.