Giant cell glioblastoma with lipogenic differentiation in a patient with neurofibromatosis type 1: A case report.

A 45-year-old woman with neurofibromatosis type 1 (NF1) developed a tumor in the left frontal lobe that showed features of giant cell glioblastoma (GC-GB). In addition to the typical GC-GB features, the tumor showed lipogenic differentiation, with many atypical lipoblasts and mature adipocytes. Tumor cells, including the lipogenic cells, were immunoreactive for GFAP, S-100 protein, ATRX, and p53. They were negative for IDH1-R132H, BRAF V600E, synaptophysin, NeuN, p16, mismatch repair proteins, and CD34. The patient is free from recurrence at approximately two years postoperatively. This is the fifth reported case of NF1-associated GC-GB (the second adult case). NF1 gene mutation might have played a role in the pathogenesis of lipogenic differentiation of GC-GB. The differential diagnosis of lipidized GC-GB from gliosarcoma or anaplastic pleomorphic xanthoastrocytoma is briefly discussed.

Olfactory neuroblastoma associated with extensive "in situ" lesion and aberrant glandular and rhabdomyosarcomatous differentiation.

A case of olfactory neuroblastoma (ONB) associated with extensive intraepithelial neoplastic proliferation, evidenced by an "in situ" lesion, in the overlying olfactory epithelium and aberrant glandular and rhabdomyosarcomatous differentiation is reported. The tumor was a polypoid lesion that involved the upper nasal cavity and ethmoid sinus of a 63-year-old woman and consisted of an ONB surrounded by and mixed with a proliferative lesion of rhabdomyoblastic cells, consistent with an embryonal rhabdomyosarcoma. A few small foci of tubular glands with mucus-producing cells were also observed. In the olfactory epithelium covering the polypoid lesion, a nested or band-like arrangement of primitive-appearing small cells was found, and the tumor cells were immunoreactive for epithelial cell adhesion molecule (detected with Ber-EP4) and low-molecular weight cytokeratin (detected with CAM5.2) but not for synaptophysin or calretinin. The intraepithelial lesion was contiguous with the subepithelial cell nests of ONB and appeared to invade the subjacent stroma and show transition to ONB, and some tumor cell nests of ONB also contained small aggregates of similar primitive-appearing cells. The intraepithelial growth was considered to represent a preinvasive precursor lesion of ONB. Previous descriptions of an "in situ" lesion in ONB are limited. The aberrant glandular and rhabdomyosarcomatous differentiation noted in this case is also an exceptionally rare phenomenon of ONB.

Neuropathology of the spinal nerve roots, spinal cord, and brain in the first autopsied case of Charcot-Marie-Tooth disease 4F with a D651N mutation in the periaxin gene.

Charcot-Marie-Tooth disease (CMT) 4F is an autosomal recessive, hereditary peripheral neuropathy, mostly caused by mutations in the periaxin gene (PRX). This article reports neuropathological findings of the spinal nerve roots, spinal cord, and brain of a patient with CMT4F and a D651N missense mutation in PRX. The patient was a 74-year-old woman who had a history of peripheral neuropathy with onset at the age of 30 years. She also had a history of infantile paralysis at the age of 18 months. The most pronounced autopsy finding was diffuse enlargement of anterior and posterior nerve roots, accentuated at the lumbo-sacral levels. On microscopy, the swollen nerve roots showed a loss of large-diameter myelinated fibers and formation of numerous onion bulbs. Most of the onion bulbs lacked the central, regenerating thin myelin sheaths, and in large-diameter nerve fibers whose axons had been lost, collagen fibers occupied the center of the onion bulbs. Some nerve roots formed glial bundles at the proximal end. The spinal cord showed degeneration of the gracile fascicles, and the lumbar segment anterior horn showed an asymmetric neuronal loss with rarefaction of the neuropil. The brain did not show any notable changes except for multiple foci of a radial microcolumnar arrangement of neurons in the cerebral cortex. Degeneration of the lumbar segment anterior horn is most likely secondary to the anterior radiculopathy, but a localized circulatory disturbance is another possibility.

Genetic Creutzfeldt-Jakob disease-M232R with the cooccurrence of multiple prion strains, M1 + M2C + M2T: Report of an autopsy case.

Genetic Creutzfeldt-Jakob disease (gCJD) with a methionine to arginine substitution at codon 232 of the prion protein gene (gCJD-M232R) is rare and has only been reported in Japan. We report an autopsy case of gCJD-M232R showing alleles of codon 129 that were homozygous for methionine and the presence of multiple strains of the protease-resistant, abnormal isoform of prion protein (PrPSc ), M1 + M2C + M2T. The patient, a 54-year-old Japanese man, died after a clinical course of 21 months characterized by slowly progressive dementia and sleep disturbance. At autopsy, the neuropil of the cerebral neocortex showed a widespread and severe spongiform change. Grape-like clusters of large confluent vacuoles were admixed with fine vacuoles. Neuronal loss was moderate, but reactive astrocytosis was mild. The dorsomedial nucleus of the thalamus and the inferior olivary nucleus showed moderate and severe neuronal loss, respectively. Many amyloid plaques were present in the cerebellar molecular layer. PrPSc deposition pattern was predominantly the synaptic type in the cerebrum and corresponded to the plaques in the cerebellum. Perivacuolar deposition was also seen. Western blot analysis of PrPSc revealed the predominance of type 2. Moreover, by employing Western blot analysis in combination with the protein misfolding cyclic amplification (PMCA) method, which selectively amplifies the minor M2T prion strain, we demonstrated the presence of M2T, in addition to M1 and M2C strains, in the brain of the patient. PMCA was a powerful method for demonstrating the presence of the M2T strain, although the amount is often small and the transmission is difficult.

Benign notochordal cell tumor of the lung: Report of a case.

A surgical case of a benign notochordal cell tumor of the lung is reported. The patient was an asymptomatic 41-year-old man, who was incidentally found to have a small tumor in the subpleural region of the left lingular segment. Since wedge resection of the tumor, the patient has been free from recurrence. The tumor measured 12 mm in diameter and showed a central cystic change. It consisted of a diffuse proliferation of polygonal cells with abundant, uni- or multi-vacuolated cytoplasm and bland nuclei. The tumor did not show a lobular architecture and lacked a myxoid or fibrous connective tissue containing blood vessels. In the peripheral region of the tumor, a small number of alveolar epithelial cells were entrapped. The nuclei of tumor cells were immunoreactive for brachyury, and the cytoplasm was positive for cytokeratin and S-100 protein. The entrapment of alveolar epithelial cells suggests infiltrative growth of the tumor, and the almost complete absence of blood vessels within the tumor may have restricted tumor growth and induced a cystic change in the central region.

Chronic Chagastic cardiomyopathy associated with membranoproliferative glomerulonephritis: Report of an autopsy case.

An autopsy case of chronic Chagas disease, a debilitating disorder caused by persistent infection by protozoa, Trypanosoma cruzi (Tr. cruzi), is reported. The patient was a 73-year-old Brazilian woman of Japanese descent, who had emigrated to Japan at the age of about 40 years. She died of chronic cardiac insufficiency about 8 years after the onset of cardiac symptoms. At autopsy, the heart showed typical features of chronic Chagastic cardiomyopathy: chronic lymphocytic myocarditis with extensive fibrosis and the formation of an apical aneurysm. The pathogenic protozoa were not detected in the cardiac tissue. The kidney showed typical features of membranoproliferative glomerulonephritis (MPGN). On the basis of experimental data which suggested that chronic infection of Tr. cruzi could elicit immune complex-mediated glomerulonephritis, we considered that the chronic persistent infection by Tr. cruzi contributed to the pathogenesis of MPGN in this patient.

Acute actinomycotic brain abscess in a patient with rheumatoid arthritis.

An autopsy case of acute actinomycotic brain abscess involving a patient with rheumatoid arthritis (RA) is reported. The patient was a 72-year-old man with a seven-year history of RA and pulmonary complications, who acutely developed dysarthria and dysphagia three days before death. Autopsy revealed a fresh, non-encapsulated abscess in the "late cerebritis" stage, measuring 2 cm in diameter, in the white matter of the right parietal lobe. A small number of tiny "sulfur granules" consisting of numerous filamentous bacilli were found within the abscess. The abscess had ruptured to the lateral ventricle and elicited ventriculitis, and mild acute purulent leptomeningitis was also observed. The lung showed chronic interstitial pneumonia/pulmonary fibrosis with bronchiectasis and emphysema, and large sulfur granules were found in the lumens of a few bronchi. Less than 5% of patients with actinomycotic infection develop central nervous system lesions, and actinomycotic brain abscesses make up only 0.6% of all brain abscesses. Actinomycotic brain abscesses usually pursue a protracted clinical course, and well-formed pyogenic membranes are commonly observed. The present case is exceptional in that the very early stage of the cerebral abscess formation was pathologically captured.

Localized atrophy of the pontine base as a sequela of prolonged ischemia: Report of an autopsy case.

An 80-year-old man with a history of diabetes mellitus and hypertension died of a progressive neurological disorder characterized by truncal ataxia, extraocular movement disturbance, and muscular rigidity. Neuroradiological examination showed progressive atrophy restricted to the pontine base. Autopsy revealed localized atrophy of the pontine base, in which both neurons and nerve fibers were lost, especially in the central region. Medium-sized and small arteries in the parenchyma of the pontine base showed marked fibro-hyalinous thickening of the walls with luminal stenosis, but no distinct tissue defect as seen in lacunar infarct was observed. Perivascular lymphocytic infiltration was mostly absent, and reactive astrocytic proliferation was weak. The pontine tegmentum, midbrain, and medulla oblongata were well preserved. Localized atrophy of the pontine base is a rare pathological condition, and its pathogenesis in the present case can be best explained by a prolonged ischemic state (hypoperfusion) due to marked sclerotic changes of perforating arteries. It is unique that the lesions were restricted to the pontine base and the formation of lacunas was not observed. Localized metabolic derangement resembling that seen in central pontine myelinolysis might have also contributed to the pathogenesis of this peculiar localized atrophy.

Hormone signaling via androgen receptor affects breast cancer and prostate cancer in a male patient: A case report.

BACKGROUND: Male breast cancer (MBC) is rare, accounting for only around 1% of all breast cancers. Most MBCs are hormone-driven. Not only the estrogen receptor (ER), but also other steroid hormone receptors, including the androgen receptor (AR) and progesterone receptor (PgR) are expressed in MBC. AR activation in breast cancer cells facilitates downstream gene expression that drives tumorigenesis in a similar manner to ER. AR-mediated signalling works paradoxically in breast cancer and prostate cancer, and cancer cells expressing the AR are endocrine-sensitive. CASE PRESENTATION: We describe a case of double cancer of MBC and prostate cancer. A 69-year-old man was referred to our hospital with a lump in his left breast in the 1990s. The patient had cT3N3M0, stage IIIC breast cancer, and underwent a mastectomy and axillary lymph node dissection. Though adjuvant chemotherapy was administered, he experienced pleural metastasis 2 months after the surgery. Two years after the recurrence during endocrine therapy with oral 5-fluorouracil, he complained of frequent urination. Radiological and histological examinations revealed that the patient had cT3N0M0, stage III primary prostate cancer with a prostate-specific antigen (PSA) level of 40.5 ng/mL. Germline mutations in the BRCA1 and BRCA2 genes were not tested. He received multidisciplinary, continuous therapy for both breast and prostate cancer; however, 5 and 3 years after each diagnosis, respectively, he experienced a deep vein thrombosis in his right leg related to the endocrine therapy. Liver metastasis progressed after he stopped breast cancer therapy. However, long-term disease control had been achieved with anti-estrogen therapy for breast cancer and estrogen replacement therapy for prostate cancer. CONCLUSIONS: Several studies have shown that estrogen exposure after estrogen depletion likely causes apoptosis of ER-positive breast cancer cells. Our findings indicate that this also applies to the environment in male body. AR dominant signaling prevents breast cancer recurrence and metastasis, especially in MBC patients.

Atypical lower motor neuron disease with enlargement of Nissl substance: Report of an autopsy case.

The patient was an 81-year-old woman diagnosed with atypical motor neuron disease who died after a long clinical course (7.5 years without mechanical assistance of ventilation) characterized by lower motor neuron signs and symptoms. Upper motor neuron signs and cognitive impairment were not apparent. Autopsy demonstrated severe neuronal loss in the anterior horn of the spinal cord, and some of the remaining neurons showed enlargement of Nissl substance and apparent thickening of the nuclear envelopes. No Bunina bodies, skein-like inclusions, or structures immunoreactive for phosphorylated transactivation response DNA-binding protein 43 were found. Immunoreactivity for superoxide dismutase-1 was focally seen in the enlarged Nissl substance. Ultrastructural examination demonstrated an increase of rough-surfaced endoplasmic reticulum (rough ER) and free ribosomes, disaggregation of polyribosomes, and dispersion of free ribosomes. Cisterns of rough ER were slightly dilated, and some of them were closely attached to the nuclear envelopes. Enlargement of Nissl substance may be related to "ER stress", and the abnormal findings of rough ER and free ribosomes may represent a degenerative process. However, another possibility, that they represent a compensatory hyperplastic change, cannot be excluded. The close attachment of cisterns of rough ER to the nuclear envelopes may be a mechanism to support or compensate for the abnormally-fragile nuclear envelopes.
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Is prolongation of corrected QT interval associated with seizures induced by electroconvulsive therapy reduced by atropine sulfate?

BACKGROUND: Electrocardiogram abnormalities have been reported during electroconvulsive therapy (ECT). A corrected QT interval (QTc) prolongation indicates delayed ventricular repolarization, which can trigger ventricular arrhythmias such as torsade de pointes (TdP). We examined the QTc changes during generalized tonic-clonic seizures induced by ECT, and the effects of atropine sulfate on these QTc changes. METHODS: We analyzed heart rate, QT interval, and QTc in 32 patients with depression who underwent ECT (25 women, 67.4 ± 8.7 years of age). The QTc from -30 to 0 seconds prestimulation was used as baseline, which was compared with QTc at 20-30 seconds and 140-150 seconds poststimulus onset. RESULTS: QTc was significantly prolonged at 20-30 seconds poststimulus, then significantly decreased at 140-150 seconds poststimulus, compared with baseline. QTc prolongation induced by ECT was significantly decreased by atropine sulfate. CONCLUSIONS: These data suggest that the risk of TdP may be enhanced by ECT. Further, the risk of cardiac ventricular arrhythmias, including TdP, may be reduced by administration of atropine sulfate.

Chronic myocarditis with a long clinical course: Report of an autopsy case of probable autoimmune myocarditis.

The patient was a 54-year-old woman, who died of chronic cardiac insufficiency after a clinical course of 2 years and 4 months. She had complained of myalgia, muscle weakness, and blepharoptosis before the onset of cardiac symptoms, but there was no evidence of myasthenia gravis or collagen-vascular diseases. At autopsy, the heart (280 g) showed marked dilatation of the four chambers and thinning of the ventricular walls. Diffuse and intense lymphocytic infiltration and extensive fibrosis were noted, with the latter being accentuated in the subendocardial and subepicardial zones. Small foci of myocardial necrosis were scattered and a small number of multinucleated giant cells were found, but epithelioid cell granulomas, Aschoff's nodules, and viral inclusion bodies were not observed. Some cardiomyocytes showed the aberrant expression of the HLA-DR antigen. No viral genomes were detected in myocardial tissue using a multivirus real-time polymerase chain reaction. The protracted clinical course, presence of active inflammatory changes at autopsy, expression of the HLA-DR antigen on cardiomyocytes, and absence of viral genomes in myocardial tissue suggest that autoimmune mechanisms played an important role in the pathogenesis and persistence of myocarditis in this patient.

Novel intracytoplasmic inclusions immunoreactive for phosphorylated-TDP43 and cystatin C in anterior horn cells in a case of sporadic amyotrophic lateral sclerosis.

Novel intracytoplasmic inclusions immunoreactive for phosphorylated transactivation response DNA-binding protein 43 (p-TDP43), cystatin C, and transferrin were found in anterior horn cells in a case of sporadic amyotrophic lateral sclerosis (ALS). The patient was a 59-year-old woman, who died of ALS after a clinical course of 8 years. She had been receiving mechanical support for respiration for 6 years and in a "totally locked-in" state for 4 years prior to death. The spinal cord showed severe degeneration involving the anterior and lateral funiculi, whereas the posterior funiculus was preserved. Neurons in the anterior horn and Clarke's column were markedly lost, and many Bunina bodies and a few skein-like inclusions were found. Some remaining anterior horn cells had round and densely eosinophilic or amphophilic intracytoplasmic inclusions. They were immunoreactive for ubiquitin, p-TDP43, cystatin C and transferrin. On confocal laser microscopy, cystatin C was found to consistently surround p-TDP43 within the inclusions. The inclusions ultrastructurally consisted of granule-associated fibrils and, in the central portion, dense aggregates of fibrils were associated with masses of electron-dense, coarsely granular or amorphous material. Although their pathogenesis remains unknown, these unique inclusions may have been formed under a specific condition whereby p-TDP43 and cystatin C interacted with each other.

Well-formed cerebellum and brainstem-like structures in a mature ovarian teratoma: Neuropathological observations.

In the surgical case of a mature cystic teratoma of the ovary that arose in a 16-year-old girl, a large amount of well-differentiated and highly organized cerebellar tissue was found. Three layers of the cerebellar cortex were well formed, and synaptophysin-positive "glomeruli" were found in the granule cell layer. Some Purkinje cells exhibited focal expansion and a dysmorphic appearance of the dendrites. Adjacent to the cerebellar tissue, a large space lined by the ependymal layer and a club-shaped CNS tissue mass resembling the brainstem were found, and structures reminiscent of the midbrain tectum and pontine nuclei were distinguished within this mass. The CNS tissue was surrounded by the leptomeninges and a skull-like, bony shell. Structures consistent with the supra-tentorial CNS tissue were not found. This case represents an example of infra-tentorial CNS tissue that was well-differentiated and organized to an exceptionally high degree in an ovarian mature teratoma. Various degenerative changes have been documented in CNS tissue in ovarian teratomas, but the dendritic abnormalities of Purkinje cells seen in the present case are novel findings.

Anaplastic and meningothelial meningiomas in a single tumor: A "dedifferentiated meningioma"?

The patient was a 74-year-old man, who developed progressive cognitive impairment and gait instability. Neuroradiological examination demonstrated a large and predominantly extra-axial tumor spreading over the bilateral frontal base, indicative of olfactory groove meningioma. The greater part of the resected tumor consisted of a dense, patternless proliferation of large, round or polygonal cells, and compactly fascicular growth of spindle cells. Tumor cells showed markedly anaplastic cytological features. In small areas of the tumor, a typical meningothelial meningioma showing no cellular atypism was found. Both tumor components were closely juxtaposed and no pathological features of an intermediate grade (atypical meningioma) were noted. Shortly after the operation, the patient developed a local recurrence of the tumor and multiple metastases to the cerebrum, bone and skin. Anaplastic meningioma is a rare, highly malignant neoplasm which arises de novo or as a result of the progressive transformation of a low-grade meningioma. The coexistence of anaplastic and low-grade components in a single meningeal tumor has been rarely reported. This dimorphic appearance is reminiscent of "dedifferentiation", a phenomenon infrequently seen in various mesenchymal and salivary gland neoplasms. We think that the term "dedifferentiated meningioma" can be appropriately applied to tumors such as that reported herein.

Post-radiation fibrosarcoma of the cerebrum associated with a prominent, lace-like, perivascular, desmoplastic change.

An intra-axial tumor measuring about 4 cm was excised from the right temporal lobe of a 35-year-old woman, who had a past history of resection of craniopharyngioma and postoperative radiation 21 years earlier. The tumor involved both the cortex and white matter, but was not attached to the dura mater. It consisted of a dense, interlacing, fascicular proliferation of atypical fibroblastic cells and was associated with an extensive, lace-like, desmoplastic change mainly involving the perivascular region around the tumor and overlying the subarachnoid space. The histopathological features of the desmoplastic change resembled meningioangiomatosis, but no proliferation of meningothelial cells was noted. The patient has been free from recurrence for 12 months since the operation. The association of primary cerebral fibrosarcoma with an extensive, lace-like, perivascular, desmoplastic change has not been documented in the literature. The radiation administered 21 years previously may have played some pathogenetic role in the perivascular desmoplastic change, and a malignant transformation of fibroblasts within the perivascular collagenous tissue is considered the most likely origin of the fibrosarcoma.

Prominent apical cytoplasmic bleb formation in metanephric adenoma: report of a case.

In a case of metanephric adenoma of the kidney, many apical cytoplasmic blebs were found on the luminal surface of tumor cells. The tumor, measuring 15 mm in diameter, was found incidentally in the right kidney of a 40-year-old woman. It consisted of a dense proliferation of cuboidal cells forming small tubules of round or irregular shape. The apical portion of the cytoplasm of tumor cells exhibited club-shaped expansion or dome-like protrusion which was largely occupied by numerous free ribosomes. The neck portion of the protruded apical cytoplasm was constricted, and the apical cytoplasm appeared to have been "pinched-off" and shed into the lumen. The prominent formation of apical cytoplasmic blebs has, to our knowledge, not been documented in renal tumors except in angiomyoadenomatous tumors. Its pathological significance is unknown, but it most likely represents a response of tumor cells to some hypoxic or toxic cellular injuries.

Ductulo-insular pancreatic endocrine tumor with amyloid deposition: report of a case.

We report a case of ductulo-insular pancreatic endocrine tumor (DI-PET) in a 50-year-old woman. The patient presented with symptoms and signs of hypoglycemia, and a small tumor in the uncus of the pancreas was extirpated. The tumor predominantly consisted of a neuroendocrine tumor (NET) of grade 2, which surrounded a minor component of ductular proliferation accompanied by a desmoplastic stroma. Both components were largely juxtaposed but admixed with each other in small areas. The NET component was immunoreactive for insulin and accompanied by the marked deposition of amyloid in the stroma. The ductular component consisted of a haphazard proliferation of ductules showing mildly atypical cytological features and immunoreactivities for cytokeratins 7 and 19. DI-PET is a rare composite neoplasm that should be distinguished from mixed ductal-neuroendocrine carcinoma because of the marked differences in treatment modalities and prognoses between the tumors. DI-PET associated with stromal amyloid deposition has not been reported to date. The 'transdifferentiation' of NET cells into ductular cells is considered as the most plausible histogenetic mechanism of this tumor, although other possibilities, such as an origin from a primitive endodermal stem cell or the induction of ductular proliferation by stimulation with NET-derived humoral factors, cannot be excluded.