An autopsy case of Balamuthia mandrillaris amoebic encephalitis, a rare emerging infectious disease, with a brief review of the cases reported in Japan.

Balamuthia mandrillaris is an amoeba found in fresh water and soil that causes granulomatous amoebic encephalitis. We report herein an autopsy case of B. mandrillaris amoebic encephalitis, which was definitely diagnosed by PCR. An 81-year-old man, who had Sjögren's syndrome, manifested drowsiness 2 months before his death with progressive deterioration. Neuroimaging demonstrated foci of T2- and fluid-attenuated inversion recovery high and T1 low-intensity with irregular post-contrast ring enhancement in the cerebral hemisphere, thalamus and midbrain. Pathologically, multiple hemorrhagic and necrotic lesions were found in the cerebrum, thalamus, midbrain, pons, medulla and cerebellum, which were characterized by liquefactive necrosis, marked edema, hemorrhage and necrotizing vasculitis associated with the perivascular accumulation of amoebic trophozoites, a few cysts, and the infiltration of numerous neutrophils and microglia/macrophages. The trophozoites were ovoid or round, 10-60 µm in diameter, and they showed foamy cytoplasm and a round nucleus with small karyosome in the center. The PCR and immunohistochemistry from paraffin-embedded brain specimens revealed angioinvasive encephalitis due to B. mandrillaris. Human cases of B. mandrillaris brain infection are rare in Japan, with only a few brief reports in the literature.

Concomitant alpha-synuclein pathology in an autopsy case of amyotrophic lateral sclerosis presenting with orthostatic hypotension and cardiac arrests.

A 74-year-old man gradually developed muscular weakness in the upper extremities, followed by dyspnea and dysarthria over a 6-month period. He was admitted to our facility and diagnosed as having amyotrophic lateral sclerosis (ALS) based on clinical and neurophysiological findings. Two months later, transtracheal positive pressure ventilation (TPPV) was started. During his clinical course, orthostatic hypotension occurred a few times. He also had two episodes of transient cardiac arrest, and he died 15 months after disease onset. At autopsy, the brain, weighing 850 g, showed diffuse cortical atrophy, preferentially involving the frontal lobes. Microscopic findings included severe loss of neurons in the motor cortex, the motor nuclei of the brainstem and the anterior horns of the spinal cord, and mild loss of axons and myelin in the corticospinal tract. Trans-activation response DNA protein 43 (TDP-43) immunoreactive cytoplasmic inclusions, the pathognomonic findings for ALS, were noted in the nucleus facialis, nucleus ambiguus, and in the anterior horn of the spinal cord. In addition, Lewy bodies and Lewy neurites were found in the brainstem and in the nucleus intermediolateralis of the thoracic cord. The concomitant alpha-synuclein pathology may have been partly related to possible autonomic dysfunction underlying the two episodes of cardiac arrest.

[Case of peritubular capillary dominant intravascular large B-cell lymphoma (PTC dominant IVLBCL) successfully treated with chemotherapy].

A 72-year-old woman developed common cold-like symptoms, diarrhea, a staggering gait, and persistent anorexia from the beginning of May 2009. In the middle of May, her general fatigue worsened, and she was transported to our hospital by ambulance. Abdominal CT showed bilateral renal enlargement, and her general condition and renal function rapidly deteriorated. The soluble interleukin-2 receptor (sIL-2R) level was elevated to 5,928 U/mL, and gallium scintigraphy showed a weak uptake in both kidneys. We considered the possibility of malignant lymphoma, and performed a renal biopsy, which showed no glomerular abnormalities, but disclosed the accumulation of large, atypical lymphoid cells with a high N/C ratio and dark chromatin in peritubular capillaries (PTC). On immunohistochemical staining, these atypical cells were found to be CD5(+), CD20 (+/-), CD10(-), CD3(-), and CD7(-), leading to a diagnosis of intravascular large B-cell lymphoma (IVLBCL). Since gallium scintigraphy showed no uptake in other organs, and examination of the cerebrospinal fluid and bone marrow revealed no tumor cells, the patient was considered to have kidney-limited IVLBCL. Chemotherapy was started immediately, which resulted in an improved general condition. Although her renal function deteriorated sufficiently to require dialysis, she was weaned from dialysis. After treatment with chemotherapy, the enlarged kidneys returned to the normal size. Subsequently, she has been receiving chemotherapy intermittently, and has remained free of recurrence. In general, IVLBCL mainly involving the kidney is difficult to diagnose antemortem, and is sometimes found at autopsy. We suggest that bilateral renal enlargement with renal failure of unknown origin should raise the suspicion of malignant lymphoma requiring a prompt renal biopsy. Cases of LBCL in which lymphoma cells fill PTC, as in this patient, have rarely been reported. We believe that this case is extremely valuable in understanding the pathogenesis of intravascular lymphoma invading the kidney; therefore, we report it with a review of the literature.

Subdural extension of recurrent olfactory neuroblastoma. Case report.

A 37-year-old man presented with olfactory neuroblastoma, which apparently recurred as diffuse extension in the subdural space of the cranial vault and spinal column 3 years after initial resection. Head and spinal magnetic resonance imaging with gadolinium demonstrated a subdural lesion. Cytological examination of the cerebrospinal fluid was negative. Histological examination of a biopsy specimen suggested recurrence of the olfactory neuroblastoma. This type of recurrence is very unusual.

A consistent region of deletion on 1p36 in meningiomas: identification and relation to malignant progression.

We analyzed the genetic aberrations on chromosome arms 1p, 10q, and 14q, which are thought to be loci that include putative tumor suppressor genes in meningiomas. We initially conducted molecular genetic testing on a total of 72 tumors including 15 atypical and 8 anaplastic meningiomas using double-target fluorescence in situ hybridization. An incidence of deletion of 1p was observed in 16.3% of histologically benign, 86.7% of atypical, and 87.5% of anaplastic meningiomas. Microsatellite analysis for loss of heterozygosity on 1p, 10q, and 14q was performed in 15 tumors (6 benign, 6 atypical, and 3 anaplastic meningiomas). We detected alimited deleted region on 1p36 in two tumors and suggest a new consistent region of deletion at 1p36.21 approximately p23 distal to D1S507 and proximal to D1S214, which spans 8.21 megabases. In addition, loss of 10q was detected in two of three secondary atypical meningiomas, and loss of 14q in two of three primary anaplastic meningiomas. We suggest that one of the putative suppressor genes is located at 1p36.21 approximately p23, and that 10q loss may contribute to the malignant progression from benign to atypical meningiomas.

Ruptured traumatic aneurysm after trivial injury mimicking acute spontaneous subdural hematoma--case report-.

A 75-year-old man suffered acute subdural hematoma shortly after trivial head trauma. Thirteen hours after a trivial brow to the occipital region, caused by contact with a mat, he suddenly deteriorated to the level of a Glasgow Coma Scale score of 6. Computed tomography demonstrated an acute subdural hematoma on the left and angiography revealed an aneurysm of the distal middle cerebral artery. An emergent craniotomy disclosed no skull fracture and exposed a thick subdural hematoma with no brain contusions. After evacuation of the hematoma, an aneurysm was found on the distal portion of posterior temporal artery, which was compatible with the angiographical findings. The neck of aneurysm was so fragile that neck clipping could not be successfully performed. Therefore, the aneurysm was extirpated, and the bleeding site coagulated with oxidized cellulose reinforcement. Histological examination of the aneurysm indicated a pseudoaneurysm during the early phase of clot formation. The acute subdural hematoma resulted from rupture of this pseudoaneurysm which was formed shortly after the minor head trauma. Rupture of a pseudoaneurysm caused by trivial trauma might be one of the origins for so-called acute "spontaneous" subdural hematoma.

Sjögren syndrome presenting with encephalopathy mimicking Creutzfeldt-Jakob disease.

A 61-year-old man developed subacute progressive dementia, general fatigue, a tonic-clonic seizure, and a decreased level of consciousness. He had a past history of chronic hepatitis type C and was diagnosed as having hepatic encephalopathy due to hyperammonemia. His level of consciousness did not improve even though the serum ammonia level improved. In addition, he had repeated general myoclonic seizures. Head MRI (diffusion-weighted imaging) showed high signal intensities in the right thalamus and the cerebral cortices in the frontal, temporal and parietal lobes (predominantly on the right side). An electroencephalogram (EEG) showed periodic lateralized epileptic discharges (PLEDs). Cerebrospinal fluid analysis revealed high total tau protein and 14-3-3 protein levels. This case was diagnosed as Creutzfeldt-Jakob disease (CJD) based on these clinical data. However, the patient gradually improved without specific treatment. The differential diagnosis was reconsidered, and an increased erythrocyte sedimentation rate and positive serum anti-SS-A and anti-SS-B antibodies were noted. A diagnosis of Sjögren syndrome (SjS) was finally made based on a biopsy of a minor salivary gland showing infiltration of lymphocytes around the gland ducts. Steroid therapy (prednisolone 40mg/day orally) was given, and his clinical condition improved. The lesions on the head MRI decreased, and the EEG findings normalized. This case suggests that SjS has a wide spectrum, including neurological disorders, and that SjS should be considered in the differential diagnosis of CJD.

Elevated expression levels of NCOA3, TOP1, and TFAP2C in breast tumors as predictors of poor prognosis.

BACKGROUND: Amplification of DNA in certain chromosomal regions plays a crucial role in the development and progression of human malignancies, specifically when protooncogenic target genes within those amplicons are overexpressed. Comparative genomic hybridization studies have revealed frequent amplification at 20q in primary breast tumors. The aim of the current study was to identify specific genes in the 20q amplicon that were likely to have clinical significance. METHODS: The authors examined 38 primary breast tumors by using a quantitative real-time reverse transcription-polymerase chain reaction assay to determine expression levels of 18 potential targets for amplification events involving 20q. Potential correlations between elevated expression of the genes in question and clinicopathologic parameters or clinical outcomes were analyzed. RESULTS: Elevated expression of NABC1 was significantly associated with positive estrogen (P < 0.001) and progesterone (P = 0.027) receptors in breast tumors, and high expression of PTK6 was significantly correlated with positive estrogen receptor status (P = 0.022) and postmenopausal status (P = 0.008). Patients whose tumors showed elevated expression of NCOA3 (AIB1) had significantly shorter disease-free (P = 0.017) and overall (P = 0.0021) survival times after surgery than did other patients with breast tumors. Reduced disease-free survival, but not reduced overall survival, was associated with high expression of TOP1 (P = 0.035) and TFAP2C (P = 0.035). CONCLUSIONS: TOP1, TFAP2C, and (particularly) NCOA3 may be prognostic indicators for patients with breast tumors.