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.

Adult cerebral high-grade glioneuronal tumor with perivascular or pseudopapillary growth co-existing with low-grade tumor: a case report.

An unusual, small cell-predominant, high-grade glioneuronal tumor in the occipital lobe of a 49-year-old man that co-existed with a low-grade tumor is reported. The tumor consisted of two distinct components: the major component was a dense proliferation of primitive small cells showing bidirectional neuronal and glial differentiation; and the minor component consisted of a proliferation of well-differentiated astrocytes intermingled with mature neuronal cells. In the former component, perivascular pseudorosette-like or pseudopapillary growth reminiscent of ependymoma or papillary glioneuronal tumor (PGNT), respectively, was prominent, and hypertrophic astrocytic cells were located just outside the central blood vessels. Small cells were immunoreactive for Olig2, synaptophysin, and, less frequently, for glial fibrillary acidic protein. The low-grade component included Rosenthal fibers, hemosiderin deposition, and perivascular lymphocytic infiltration, thus closely resembling ganglioglioma. Cytogenetic studies did not demonstrate any mutations or rearrangements of the genes IDH1, IDH2, H3F3A, BRAF, FGFR1, or TERT promoter. The tumor recurred and spread along the ventricular surface three years after total removal. The small cell-predominant, high-grade component was considered to have evolved from the ganglioglioma-like, low-grade component. The histopathologic resemblance of the high-grade component to PGNT was a special feature.

Reactive hyperplasia of vascular pericytes in meningioma: immunohistochemical and ultrastructural studies of two cases.

An isolated proliferation of pericytes is a unique vascular reaction seen almost exclusively in the stroma of secretory meningioma. We report the results of immunohistochemical and ultrastructural studies of a pericytic proliferation that was found in two cases of meningioma (a secretory meningioma of the sphenoid ridge and a parasagittal atypical meningioma showing predominantly fibroblastic features). Pericytes had hyperchromatic nuclei and scant cytoplasm, and showed stratification or formed small clusters within the walls of small blood vessels. They occasionally showed close contact with pseudopsammoma bodies in secretory meningioma. Pericytes showed immunoreactivity for α-smooth muscle actin but were not immunoreactive for desmin. They also exhibited characteristic ultrastructural features of pericytes, including the presence of microfilaments and abundant pinocytotic vesicles, and investment by the basal lamina. This isolated pericytic proliferation is likely a peculiar response of the vascular wall, probably induced by some cytokines secreted from neoplastic meningothelial cells. The close contact of proliferating pericytes with pseudopsammoma bodies suggests a close pathogenetic association between them. The occurrence of pericytic proliferation that was found in our second case (atypical meningioma with predominantly fibroblastic features) is exceptional and has not been documented to date.

Extremely intricate labyrinthine structures: an electron microscopic observation of peculiar invaginations of the plasma membrane found in secretory meningioma.

Large, extremely intricate labyrinthine structures were observed during an electron microscopic examination of a secretory meningioma that originated in the sphenoid ridge of a 73-year-old man. In many neoplastic cells, these labyrinthine structures formed round-shaped regions within the cytoplasm, and profiles indicated their internal structure consisted of numerous thin fragments of cytoplasm and intervening flocculent material. These labyrinthine structures did not exhibit apparent topographic association with pseudopsammoma bodies, and direct communication with the extracellular space by very thin channels was rarely observed. The structures resembled the "intracytoplasmic lumina" commonly seen in epithelial neoplasms; but they did not appear to be true "intracytoplasmic" closed structures but rather deep and elaborate invaginations of the plasma membrane into the cytoplasm. These structures are distinct from pseudopsammoma bodies and might represent another expression of the epithelial properties of neoplastic cells in this subtype of meningioma. Although their pathogenesis or significance remain unknown, these structures may significantly increase the surface area of neoplastic cells and facilitate the uptake of extracellular material.

Esophageal Intramural Pseudodiverticulosis: A Histopathological and Immunohistochemical Study of 2 Cases.

Esophageal intramural pseudodiverticulosis (EIPD) is a rare disorder characterized by an abnormal, cyst-like dilatation of the excretory ducts of esophageal submucosal glands. We aimed to elucidate the histopathological features and immunohistochemical properties of the epithelial lining of the cyst-like lesions in EIPD. We performed a histopathological and immunohistochemical study of 2 cases (one autopsy and one surgical) of EIPD. The ductal walls consisted of inner ductal cells, which were cytokeratin (CK) 7-positive and CK5/6-negative, and outer basal cells, which were CK7-negative and CK5/6-positive. The ductal epithelium frequently showed squamous metaplasia and rarely simulated a false diverticulum. Immunohistochemistry for CK7 was useful for distinction between the conditions because the surface epithelium was negative for CK7. We also confirmed that myoepithelial cells in the acinar portion of submucosal glands were well-preserved in EIPD, the finding that explained the periodic opening and closing movements of orifices of cyst-like lesions in this disorder. The immunohistochemical properties of the epithelial lining of cyst-like lesions in EIPD were essentially similar to those of the normal ducts of submucosal glands.

Disseminated Cunninghamella bertholletiae mucormycosis with protracted clinical course and formation of a large intra-ventricular mural thrombus.

We report the autopsy findings of a case of disseminated mucormycosis caused by Cunninghamella bertholletiae, a rare pathogenic fungus of the family Mucoraceae. The patient was a 49-year-old woman with B-lymphoblastic leukemia with hyperdiploidy, who died of progressive heart failure 4 months after induction chemotherapy successfully brought about complete remission of the leukemia. Granulocyte colony-stimulating factor (G-CSF) had been administered along with anti-neoplastic drugs, and her blood neutrophil count was markedly elevated. Autopsy revealed disseminated mycotic thromboembolism and abscess formation in the heart, lung, liver, kidney, and spleen. The most marked feature was a large mural thrombus in the left ventricle containing numerous fungal hyphae. In the myocardium and disseminated foci in visceral organs, giant cell-rich, fibrotic reactions to the mycotic infection were observed. Both the formation of a large intra-ventricular mural thrombus and giant cell reactions are rare findings in mucormycosis. We considered that the recovery and marked increase in neutrophil count induced by chemotherapy and G-CSF administration prolonged the clinical course and pathologically elicited an atypical, giant cell reaction to the mycotic infection. The prolonged clinical course also contributed to the formation of an unusually large intra-ventricular mural thrombus.

Occurrence of a Duodenal Polypoid Lesion During Long-Term Acid Suppression Therapy and Its Regression After Drug Discontinuation.

Formation of multiple fundic gland polyps or hyperplastic polyps in the gastric mucosa is one of the well-known adverse effects of the long-term acid suppression therapy for peptic ulcer disease. However, similar phenomenon has not been reported to occur in the duodenum. We report a case of duodenal polypoid lesion that developed after the long-term use of acid suppressants and disappeared after the cessation of the treatment. The patient was a 76-year-old man with a history of heavy cigarette smoking and excessive alcohol intake who had been treated with medication of gastric acid suppressants, including proton pump inhibitors and potassium-competitive acid blockers, for refractory gastroesophageal reflux disease. After receiving the acid suppression therapy for 3 years, a polypoid lesion of 10 mm in diameter was found at the portion of the duodenal bulb. This polypoid lesion disappeared 1.5 months after the cessation of treatment. We hypothesized that changes in serum gastrin levels caused by acid suppression therapy might have been associated with the development and regression of the duodenal polypoid lesion.

Development of Epidermoid Metaplasia of the Mucosa in Association with Esophageal Intramural Pseudodiverticulosis and Candidiasis.

We report a case of epidermoid metaplasia of the esophageal mucosa that developed in a patient with a long history of esophageal intramural pseudodiverticulosis (EIPD) complicated by candidiasis. The patient, a 69-year-old man, had been treated for about 3 years for EIPD with candidiasis. After candidiasis improved, the development of epidermoid metaplasia of the esophageal mucosa was observed. It comprised longitudinally arranged, multiple, small, whitish flecks with a scaly appearance on the mucosa of the middle to lower esophagus, and pathological examination demonstrated several fine keratohyalin granules in superficial layers of the squamous epithelium. Six months later, candidiasis was almost cured, but these small flecks had slightly increased in size, and pathological examination demonstrated epidermoid metaplasia consisting of a thick, acellular keratin layer and well-developed granular layer beneath it. We considered that chronic candida esophagitis played the principal pathogenetic role in the development of epidermoid metaplasia. EIPD may have provided an environment suitable for the growth of fungi, and mucinous material contaminated by Candida and excreted from the orifices of EIPD may have irritated the mucosa and induced epidermoid metaplasia.

Multiple Gastric Carcinomas Associated with Epstein-Barr Virus and Helicobacter pylori: A Thought-Provoking Case.

BACKGROUND Epstein-Barr virus (EBV) and Helicobacter pylori (HP) infections are associated with gastric carcinoma (GC). We present a thought-provoking case of multiple GCs associated with EBV and HP infections. CASE REPORT HP infection was incidentally detected in an asymptomatic 60-year-old man. Upper endoscopy revealed gastric "kissing" ulcers. The lesions were located in the body of the stomach and measured 25 and 27 mm, respectively. They were diagnosed on pathology as moderately differentiated tubular adenocarcinoma. Imaging revealed no enlarged lymph nodes or distant metastatic lesions. Distal gastrectomy with lymphadenectomy was performed and surgical cure was obtained. The multiple GCs were categorized on pathology as infß ly0 v0 pT1b(SM)UL1N0M0H0P0CY0 pStage IA according to the Japanese classification and as T1bN0M0 Stage IA according to the tumor, node, metastasis classification. Pathological examination revealed remarkable lymphocytic infiltration into the stroma, as shown by in situ hybridization of EBV. These lymphocytic infiltrations were observed only at the sites of GC. In the immunohistochemical examination, in situ hybridization of EBV was positive for EBV-encoded small ribonucleic acid. The patient's postoperative course was uneventful. Hence, an unexpected relationship between EBV infection and multiple GCs was suggested by pathology. Quantitative determination of EBV DNA in peripheral blood was normal postoperatively. Adjuvant chemotherapy was not recommended. HP eradication therapy was successful. The patient remained asymptomatic and developed no recurrence or metastasis for 3 years after surgery. CONCLUSIONS This thought-provoking case suggests that coinfection with EBV and HP increases GC occurrence.

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.

Segmental arterial mediolysis of the middle colic artery: report of a case with special reference to lesions of small arteries and veins.

We report a case of segmental arterial mediolysis (SAM) that involved the middle colic artery, and present some pathologic alterations found in mesenteric small arteries and veins. The patient, a 52-year-old woman, underwent an emergency laparotomy for acute intra-abdominal hemorrhage, and a segment of the transverse colon with hemorrhagic mesocolon was excised. Microscopic examination demonstrated two separate lesions of SAM in the middle colic artery. The involved arterial segments showed a partial to circumferential loss of the media (mediolysis) and intima associated with the formation of a pseudoaneurysm. Smooth muscle cells adjacent to the mediolysis showed various degenerative changes. In addition, we found multiple, tiny foci of degenerative lesions affecting the outer media in the wall of small arteries. Subendothelial vacuoles and nodular intimal proliferation were also noted in small veins. Whereas SAM chiefly affects large or medium-sized arteries, small blood vessels, including veins, are also affected. The present case is unusual in that degeneration of medial smooth muscle cells was clearly observed in the arterial walls, and the small veins were affected by lesions similar to those in arteries. We suspect that a phenotypic modulation of vascular smooth muscle cells induced by some genetic vulnerability plays a role in the pathogenesis of SAM.

Solitary pancreatic metastasis of occult pulmonary small cell carcinoma diagnosed by EUS-FNA cytology: a case report.

A 74-year-old man presented with symptoms suggestive of acute pancreatitis, and a mass lesion measuring 25 mm was detected in the pancreatic head. Cytological and histopathological examinations of EUS-FNA specimens taken from the lesion demonstrated small cell (neuroendocrine) carcinoma. Tumor cells were immunoreactive for cytokeratin, synaptophysin, chromogranin A, CD56, and TTF-1, and PET-CT of the chest revealed a small tumor in the upper lobe of the left lung. Pulmonary carcinoma, particularly small cell carcinoma, infrequently presents with a solitary metastatic lesion in the pancreas as an initial manifestation and clinically simulates a primary pancreatic neoplasm. Because primary small cell carcinoma of the pancreas is very uncommon, metastasis from the lung should always be considered when evaluating pancreatic neoplasms showing a "small cell" morphology. Immunohistochemistry for TTF-1 is useful for determining the pulmonary origin of this type of neoplasm, and its application to cytology specimens is recommended.

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.

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.

Pathological evidence of demyelination in the recurrent laryngeal, phrenic, and oculomotor nerves in Charcot-Marie-Tooth disease 4F.

We present pathology of the peripheral nerves of a patient with Adult-onset Charcot-Marie-Tooth disease 4F caused by periaxin gene mutation p.D651N. The patient was a 72-year-old woman. She had hoarseness and underwent continuous positive airway pressure therapy at night due to sleep apnea. The patient died abruptly. Remarkable demyelination with tomacula formation was found in the phrenic nerve, vagal nerve, recurrent laryngeal nerve, and oculomotor nerves. The cause of death could have been insufficient reactivity to the aspiration or sudden onset of bilateral vocal cord palsy. We must pay attention to respiratory function and cranial nerve palsies in hereditary demyelinating neuropathies.

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.

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.