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Background: Fibromuscular dysplasia (FMD) can cause cerebral aneurysms and dissection, which can lead to stroke. Angiographic findings are important in the diagnosis. We report a case of FMD in which the cause of hemorrhage could not be determined by angiography. Case Description: A 73-year-old woman suffered from intracerebral hemorrhage (ICH) associated with FMD without abnormal angiography cerebral vessels. She presented with headache and nausea. Subsequent head-computed tomography-revealed ICH in the left frontal lobe, and contrast-enhanced magnetic resonance imaging revealed a gadolinium-enhancing lesion in the perihematoma area and in the genu of the corpus callosum. Although cerebral angiography revealed a string of beads appearance in the bilateral extracranial internal carotid arteries, no abnormality explaining the hemorrhage was identified. The hematoma was removed and the pathological diagnosis was FMD. In the pathological specimen, various patterns of vulnerable vessels, such as aneurysmal dilatation and obstruction, were observed, which could easily collapse and result in hemorrhage. In the case of ICH of unknown origin, microscopic vessel disruption due to FMD should also be considered. Conclusion: FMD can cause ICH in microscopic vascular lesions that are undetectable on angiography.

A 53-year-old male presented with acute myocardial infarction and was subsequently implanted with a 4.0 × 28 mm everolimus-eluting platinum chromium stent in his proximal left anterior descending artery. Eight months after the implantation, he developed exertional angina and underwent coronary angiography, which revealed significant in-stent restenosis (ISR). Percutaneous coronary intervention was performed 1 month later, and the pre-procedural optical coherence tomography (OCT) revealed a diffusely bordered and rapidly attenuated signal-poor region with invisible stent struts at ISR site, potentially indicating a "lipid-laden" neointima. The ISR lesion was excised using a novel directional coronary atherectomy catheter. The histological analysis of the retrieved restenotic tissues revealed substantial inflammation characterized by abundant foamy macrophages and T-cell infiltration. This "inflammatory" neointimal tissue with numerous macrophages (without a necrotic core) detected on OCT was not expected owing to the absence of a known feature of macrophages on OCT (i.e., high backscattering with remarkable attenuation). The current histological confirmation of in vivo OCT findings of restenotic neointima indicated that a "lipid-laden" neointima on OCT may not necessarily reflect necrotic core accumulation, and this could be attributed to substantial inflammation with abundant macrophages.

We report multiple rectal carcinoid tumors in monozygotic twins who, respectively, had 42 and 36 carcinoid tumors in the lower rectum. This is the first report about carcinoid tumors in monozygotic twins. Both twins developed a similar number of rectal carcinoids with a similar distribution. Investigation of their genetic background may provide information about the origin of these tumors.

A 60-year-old man was admitted to our hospital because of vertigo and repeated vomiting, which suddenly occurred 25 hours before admission. Neurologic examination revealed Wallenberg syndrome on the left side, and brain MRI showed acute infarcts in the left lateral medulla as well as in the left internal carotid artery (ICA) territory. MR angiography did not depict the left vertebral artery (VA) and the left ICA. Despite antithrombotic treatment, he developed bulbar palsy, and then, brain herniation due to infarct growth in the left middle cerebral artery territory. He died on day 9. Histopathlogical examination found verruca involving the mitral leaflet, which was consistent with non-bacterial thrombotic endocarditis (NBTE). Atherosclerosis was also found in the systemic arteries, and there was sclerotic stenosis with calcification at the portion of piercing dulla matter in the left VA and at the cavernous segment of the left ICA. Because the cerebral emboli in the narrowed lumen presented a histologic appearance similar to that of the verruca, the diagnosis of brain embolism due to NBTE was confirmed.

A 53-year-old male presented with acute myocardial infarction and was subsequently implanted with a 4.0 × 28 mm everolimus-eluting platinum chromium stent in his proximal left anterior descending artery. Eight months after the implantation, he developed exertional angina and underwent coronary angiography, which revealed significant in-stent restenosis (ISR). Percutaneous coronary intervention was performed 1 month later, and the pre-procedural optical coherence tomography (OCT) revealed a diffusely bordered and rapidly attenuated signal-poor region with invisible stent struts at ISR site, potentially indicating a "lipid-laden" neointima. The ISR lesion was excised using a novel directional coronary atherectomy catheter. The histological analysis of the retrieved restenotic tissues revealed substantial inflammation characterized by abundant foamy macrophages and T-cell infiltration. This "inflammatory" neointimal tissue with numerous macrophages (without a necrotic core) detected on OCT was not expected owing to the absence of a known feature of macrophages on OCT (i.e., high backscattering with remarkable attenuation). The current histological confirmation of in vivo OCT findings of restenotic neointima indicated that a "lipid-laden" neointima on OCT may not necessarily reflect necrotic core accumulation, and this could be attributed to substantial inflammation with abundant macrophages.

A previously healthy 55-year-old man with H1N1 influenza A presented with severe respiratory failure and cardiac arrest. Following the return of spontaneous circulation, venovenous extracorporeal membrane oxygenation was required to maintain oxygenation. On day 2, bronchoscopy revealed a bloody bronchial cast obstructing the right main bronchus. A pathological examination revealed that it was composed of intrabronchial and intra-alveolar hemorrhagic tissue. Unfortunately, the patient died due to severe brain ischemia; a subsequent autopsy revealed marked alveolar hemorrhage. It is possible that anticoagulant therapy, alveolar collapse, and neuromuscular blocking agents provoked cast development in this case.

A 78-year-old man with hypertension, nephrosclerosis, and angina pectoris visited his family doctor with a history of fatigue and leg edema. He had a history of percutaneous coronary intervention 5 years prior, and was taking low-dose aspirin. Blood tests revealed hypoalbuminemia, gastrointestinal

We reported a case of trigonal cavernous malformation (CM) with intraventricular hemorrhage. This 67-year-old woman experienced sudden onset of loss of consciousness and her Glasgow Coma Scale (GCS) was 5 points (E1V1M3) on admission. CT scan demonstrated intraventricular hemorrhage and acute hydrocephalus. Angiography did not demonstrate any vascular abnormality. Ventricular drainage was performed for acute hydrocephalus and the postoperative course was good. CT showed a hyperdense lesion in the left trigone, which was contrast-enhanced on T1-weighted MR. Removal of CM was performed via the left middle temporal sulcus. We conducted a Pub Med search for trigonal CM and found 17 cases. Herein we discuss the symptoms, CT and MR findings and treatment.

We report two cases of hematomyelia. Both patients developed rapidly progressing paralysis. Spinal MR imaging showed characteristic hematomas with massive peripheral edema. We carefully resected the hematomas in both cases. There was no evidence of angioma observed in either case. The patients showed gradual improvement of their neurological symptoms.

Background Gangliocytic paraganglioma (GP) is an extremely rare benign tumor that commonly arises from the second part of the duodenum. Since GP exhibit neither prominent mitotic activity nor Ki-67 immunoreactivity, this tumor is often misdiagnosed as neuroendocrine tumor (NET) G1 (carcinoid tumor). However, patients with GP may have a better prognosis than patients with NET G1. This fact emphasizes the importance of differentiating GP from NET G1, but few studies have reported the epidemiology and histopathology of GP because of its rarity. To differentiate GP from NET G1 with ease, we conducted a multi-institutional retrospective study analyzing the morphometric and immunohistochemical features of this tumor. Methods Since only a limited number of patients with GP could be identified in our institute, we conducted a multi-institutional retrospective study of GP in Japan, which was approved by the Ethics Committee of our medical institute. The obtained tissue sections underwent detailed morphometric and immunohistochemical analyses. Additionally, to differentiate GP from NET G1 with ease, immunohistochemical findings were compared. Results In our examination of 12 cases of duodenal GP, we found that epithelioid cells of GP exhibited positive reactivity for progesterone receptor and pancreatic polypeptide, whereas tumor cells of NET G1 were completely negative reactivity for both. Additionally, although GP is considered to be an extremely rare NET, we found that four (40.0%) of the ten patients at our institute with duodenal NET G1 actually had GP. Conclusions Although GP is regarded as a rare NET, our results suggest that it accounts for a substantial percentage of duodenal NETs. Additionally, confirmation of immunoreactivity for progesterone receptor and pancreatic polypeptide can assist in differentiating GP from NET G1.

Quercetin, a flavonoid, widely distributed in many fruits and vegetables, is well known to have an antitumor effect despite its mutagenicity. In this study, we examined the effect of dietary quercetin on duodenum-tumorigenicity of mice induced by a chemical carcinogen, N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG). Eight-week-old male C57BL/6 mice were divided into 4 groups; ENNG without quercetin (group A), ENNG with 0.2% quercetin (group B), ENNG with 2% quercetin (group C), and 2% quercetin without ENNG (group D). ENNG was given in drinking water for the first 4 weeks, and thereafter quercetin was given in a mixed diet. At week 20, the average number of duodenal tumors per mouse was significantly higher in group C (mean±SE, 7.26±1.75, p

Neuroenteric cysts are benign intradural endoderm cysts lined by gastrointestinal (GI) or tracheobronchial epithelial cells. Their malignant transformation is extremely rare and only six cases have been reported. In these cases, tissue lineage of the cystic endoderm cells giving rise to carcinoma was not clearly identified either as respiratory or as GI type. Herein, we report a case of mucinous adenocarcinoma arising from the neuroenteric cyst with broncho-pulmonary differentiation in the right cerebral hemisphere of a Japanese woman in her late 50s. The cyst wall was entirely lined by the following respiratory epithelial components: stratified bronchial ciliated columnar epithelium with basal cells positive for CK5 and p63, terminal bronchiolar Clara cells positive for thyroid transcription factor (TTF)-1, surfactant B and negative for surfactant C, type I pneumocytes positive for TTF-1, negative for surfactant B and C, and type II pneumocytes positive for TTF-1 and surfactant B and C. In addition, nests of hyperplastic single layered mucinous epithelial cells with bronchial goblet cell phenotype were also demonstrated, and histologic features were almost the same as the pulmonary type I congenital adenomatoid malformation (CCAM) with mucinous epithelial proliferation. The mucinous epithelial nests of type I CCAM are liable to develop mucinous adenocarcinoma and frequently accompany K-ras mutation and expression of p16. However, K-ras mutation and p-16 expression were not detected in this case.

Neuroblastoma demonstrates various clinical behaviors, ranging from spontaneous regression to rapid progression regardless of the therapy used. To study the possibility that progression occurs in neuroblastoma through the accumulation of genetic aberrations, we analyzed the clonal constitution of the primary tumor and metastatic tumor samples from a stage-4 patient. Using cytofluorometry and FISH analyses, intratumor clonal heterogeneity was revealed. In the initial primary tumor sample, the nuclear DNA content indicated the coexistence of diploid and aneuploid clones, and the copy number of chromosome 1 varied from two to six. The chromosome 1 aneusomy population was composed of MYCN-amplified and 1p-deleted clones, whereas, in the chromosome 1 disomy population, coexistence of MYCN-amplified and non-amplified clones as well as 1p-deleted and 1p-intact clones was revealed. In the primary tumor after chemotherapy, the DNA-diploid component had become predominant, although the coexistence of MYCN-amplified and non-amplified clones could still be demonstrated in poorly- and well-differentiated tumor regions, respectively. This contrasted with the findings in the metastatic tumors, in which either diploid or aneuploid clone with MYCN amplification and 1p deletion dominated completely in each metastatic site. The findings suggest that the aneuploid clones had evolved from a diploid clone with MYCN amplification and a 1p deletion which, in turn, may have evolved from a diploid clone with neither MYCN nor 1p abnormality. This illustrates how various stages of multiple-step tumorigenesis may provide clues to a better understanding of the clinical heterogeneity of neuroblastoma. Genes Chromosomes Cancer 22:42–49, 1998. © 1998 Wiley-Liss, Inc.

Neuroenteric cysts are benign intradural endoderm cysts lined by gastrointestinal (GI) or tracheobronchial epithelial cells. Their malignant transformation is extremely rare and only six cases have been reported. In these cases, tissue lineage of the cystic endoderm cells giving rise to carcinoma was not clearly identified either as respiratory or as GI type. Herein, we report a case of mucinous adenocarcinoma arising from the neuroenteric cyst with broncho-pulmonary differentiation in the right cerebral hemisphere of a Japanese woman in her late 50s. The cyst wall was entirely lined by the following respiratory epithelial components: stratified bronchial ciliated columnar epithelium with basal cells positive for CK5 and p63, terminal bronchiolar Clara cells positive for thyroid transcription factor (TTF)-1, surfactant B and negative for surfactant C, type I pneumocytes positive for TTF-1, negative for surfactant B and C, and type II pneumocytes positive for TTF-1 and surfactant B and C. In addition, nests of hyperplastic single layered mucinous epithelial cells with bronchial goblet cell phenotype were also demonstrated, and histologic features were almost the same as the pulmonary type I congenital adenomatoid malformation (CCAM) with mucinous epithelial proliferation. The mucinous epithelial nests of type I CCAM are liable to develop mucinous adenocarcinoma and frequently accompany K-ras mutation and expression of p16. However, K-ras mutation and p-16 expression were not detected in this case.

We report a case of an atypical astrocytic tumor rich in signet ring cells with cytoplasmic mucin and glycogen in the left lower temporal lobe of the brain found in a Japanese female tricenarian. The signet ring cell cytoplasm contained bovine testicular hyaluronidase sensitive non-epithelial mucin together with CD44 and laminin. Glycogen was also detected. After subtotal resection, the residual tumor rapidly enlarged; hence, it was finally extirpated 8 months later followed by post-surgical irradiation. The recurrent tumor did not have signet ring cells and was entirely comprised of solid nests of large pale polygonal cells filled with glycogen and hyperchromatic nuclei. Mucin was not demonstrated in their cytoplasm, but their surface was diffusely coated with non-epithelial mucin together with CD44. The results of our analysis revealed that non-epithelial mucin could accumulate in or on the surface of neoplastic astrocytes in close association with CD44, findings that give new insights into the spectrum of non-epithelial mucin metabolism in astrocytic tumors. The tumor has not recurred for more than 3 years after the irradiation therapy following the second surgery, but further clinical observation is needed to evaluate the exact clinical behavior of this unusual tumor.

Primary mucinous carcinoma of the skin (MCS) is a rare skin appendage tumor and only a few cases of MCS with endocrine differentiation have been reported. Here we report an additional case of primary pure MCS with endocrine differentiation arising in the face. Histopathologically, the tumor was located in the dermis and subcutis, and nests of slight atypical epithelial cells were floating in the mucinous pools. This tumor did not accompany carcinoma in situ or invasive non-mucinous carcinoma and was difficult to differentiate from metastatic mucinous carcinoma of the skin. There was no tumor in the other organs and synaptophysin and chromogranin A were sporadically shown immunohistochemically in the tumor cells; a diagnosis of primary pure MCS with endocrine differentiation was made. MCS resembles mammary mucinous carcinoma not only in morphological appearance but also in immunohistochemical phenotypes, such as positive immunoreactivity to gross cystic disease protein fluid-15, MUC2, MUC6, estrogen receptor and progesterone receptor. It is presumed that MCS is derived from the apocrine gland, which is closely related to the mammary gland. Although endocrine differentiation is not uncommon in pure mucinous carcinoma of the breast, there have been only a few reports published on endocrine differentiation in MCS. To clarify the difference and/or similarity between mucinous carcinoma of the breast and MCS, immunohistochemical and cytogenetic analyses of additional cases of MCS are required.

The abundant chromosome abnormalities in most carcinomas are probably a reflection of genomic instability present in the tumor, so the pattern and variability of chromosome abnormalities will reflect the mechanism of instability combined with the effects of selection. Chromosome rearrangement was investigated in 17 colorectal carcinoma-derived cell lines. Comparative genomic hybridization showed that the chromosome changes were representative of those found in primary tumors. Spectral karyotyping (SKY) showed that translocations were very varied and mostly unbalanced, with no translocation occurring in more than three lines. At least three karyotype patterns could be distinguished. Some lines had few chromosome abnormalities: they all showed microsatellite instability, the replication error (RER)+ phenotype. Most lines had many chromosome abnormalities: at least seven showed a surprisingly consistent pattern, characterized by multiple unbalanced translocations and intermetaphase variation, with chromosome numbers around triploid, 6–16 structural aberrations, and similarities in gains and losses. Almost all of these were RER−, but one, LS411, was RER+. The line HCA7 showed a novel pattern, suggesting a third kind of genomic instability: multiple reciprocal translocations, with little numerical change or variability. This line was also RER+. The coexistence in one tumor of two kinds of genomic instability is to be expected if the underlying defects are selected for in tumor evolution.

To trace the sequence of numerical chromosomal aberrations during tumor progression of colorectal tumors, we studied intratumoral heterogeneity of chromosomal copy number by a combined fluorescence in situ hybridization (FISH) and ploidy analysis. We used six formalin-fixed paraffin-embedded tumors of which the mucosal lesions were preserved. Nuclear suspensions were made from the tumor tissues that were scraped from several small regions in 100 μm thick sections. Copy number of chromosomes 1, 7, 17, and 18 were examined by FISH with centromeric repetitive probes. DNA ploidy was monitored by cytofluorometry, and was correlated to the chromosomal copy number on the smear slides of identical nuclear suspension from each tumor portion. All the tumors examined included the DNA-diploid regions in the mucosa, where cancer cells commonly showed monosomy 18 and/or trisomy 7. These chromosomal changes may be quite common early events before the occurrence of DNA-aneuploidy in the development of colorectal tumors. Three out of the 6 tumors included neartetraploid (3.6–4.1C) cells in deeper invasive regions. Chromosomal constitution of DNA-aneuploid cells was suggested to derive from that of DNA-diploid cells through ploidy duplication with or without additional loss or gain of chromosomes.

Background. Stomach cancers show various growth patterns. It remains to be clarified how this variability is related to the genetic changes that occur during tumor progression. Methods. To estimate the genetic changes from tumor ploidy, maps were made (using DNA cytofluorometry of metaphase cells in histologic sections) of 39 advanced signet ring cell carcinomas of the human stomach and correlated with tumor stage and the size of the primary mucosal lesion. Results. Aneuploid area and multipattern aneuploidy were particularly common in advanced cancers with primary mucosal lesions smaller than 2 cm in diameter, of which a large portion were predominantly aneuploid and already diffusely infiltrating. As the tumor stage advanced, the incidence of aneuploidy in the mucosal lesion increased, whereas predominantly aneuploid tumors were less common as primary mucosal lesions became larger. Purely diploid areas with an incidence of polyploidy as low as in early cancers were common in advanced cancers. In addition, there were diploid-appearing cancer cells that infiltrated diffusely and were accompanied by polyploid as often as aneuploid cells. Some of these were aneuploid at the chromosomal level. Conclusions. In signet ring cell carcinoma, aneuploid cells show higher invasive activity toward the extramucosal part and may occur incidentally in originally diploid tumors, depending on the degree of genetic instability. An analysis of polyploidy is useful for differentiating cytometrically diploid (but actually, aneuploid) cells from diploid cells with minor genetic abnormalities. Cancer 1993; 71:1938-47.

Signet-ring-cell carcinomas were induced in the stomach of 12 beagle dogs by p.o. administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), and the morphology and modes of cell proliferation in an incipient stage of cancer growth were studied with bromodeoxyuridine (BrdUrd) incorporation. From 5 to 27 months after the completion of 8 months' carcinogen treatment, minute carcinomas were found in the stomachs of 9 dogs. Before sacrifice, the dogs were given a single or repeated i.v. injections of BrdUrd for 1-3 days. Minute signet-ring-cell carcinomas were found to form a layered structure, in which the cancer cells proliferated in the lamina propria at the gland-neck level and differentiated to postmitotic signet-ring cells at the upper and lower levels of the mucosa. From repeated injections of BrdUrd, the time required for all the proliferative cells to be labelled with BrdUrd (reflecting the maximum cell-cycle time) was estimated to be 1.7 days for the normal glands, and 2.7 days for minute signet-ring-cell carcinomas. From the labelling index with BrdUrd as well as from the morphology, earliest carcinomas were identified in the single gland. There remained atrophic normal epithelium commonly in the single-gland lesions. Proliferative atypical cells appeared to be shed into the stroma passively through the atrophy and subsequent collapse of the gland rather than through active invasion. This may be a reason why cancer cells in minute signet-ring cell carcinomas preserved the normal pattern of cell renewal movement to form the layered structure.