In-Stent Restenosis with "Inflammatory" Neointima Following Everolimus-Eluting Stent Implantation.

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.

Multiple small intestinal ulcers associated with protein-losing enteropathy secondary to cholesterol crystal embolism:a case report.

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 99mTc-HSA scintigraphy was positive, and alpha-1 antitrypsin clearance was high;therefore, the hypoalbuminemia was thought to be secondary to a protein-losing enteropathy. A small bowel series revealed multiple, ring-shaped, longitudinal ulcers in the ileum. Balloon-assisted enteroscopy from the anus showed severe stenosis with an ileal ulcer. Since we were not able to diagnose the ulcers, mesalazine and supplemental nutritional care were provided. Four years after the hypoalbuminemia had been diagnosed, the patient died because of pulmonary congestion secondary to renal failure. An autopsy revealed severe atherosclerosis in his aorta and multiple cholesterol embolisms in his small intestine, kidney, stomach, colon, liver, and spleen. The multiple ulcers in the small intestine were thought to be caused by cholesterol crystal embolism, which should be considered in the differential diagnosis of small intestinal ulcers in elderly men or patients after cardiovascular intervention.

Gangliocytic paraganglioma: a multi-institutional retrospective study in Japan.

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.

Primary central chondrosarcoma of long bone, limb girdle and trunk: Analysis of 174 cases by numerical scoring on histology.

The aims of this study were: (i) to elucidate clinicopathological characteristics of pcCHS of long bones (L), limb girdles (LG) and trunk (T) in Japan; (ii) to investigate predictive pathological findings for outcome of pcCHS of L, LG and T, objectively; and (iii) to elucidate a discrepancy of grade between biopsy and resected specimens. Clinicopathological profiles of 174 pcCHS (79 male, 95 female), of L, LG, and T were retrieved. For each case, a numerical score was given to 18 pathological findings. The average age was 50.5 years (15-80 years). Frequently involved sites were femur, humerus, pelvis and rib. The 5-year and 10-year disease-specific survival (DSS) rates [follow-up: 1-258 months (average 65.5)] were 87.0% and 80.4%, respectively. By Cox hazards analysis on pathological findings, age, sex and location, histologically higher grade and older age were unfavorable predictors, and calcification was a favorable predictor in DSS. The histological grade of resected specimen was higher than that of biopsy in 37.7% (26/69 cases). In conclusion, higher histological grade and older age were predictors for poor, but calcification was for good prognosis. Because there was a discrepancy in grade between biopsy and resected specimens, comprehensive evaluation is necessary before definitive operation for pcCHS.

Mucinous adenocarcinoma arising from supratentorial intramedullary neuroenteric cyst with broncho-pulmonary differentiation.

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.

A case of fibromuscular dysplasia related intracerebral hemorrhage without angiographically cerebral abnormal vessels.

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 case of primary mucinous carcinoma with endocrine differentiation of the skin].

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.

Bloody Bronchial Cast Formation Due to Alveolar Hemorrhage Associated with H1N1 Influenza Infection.

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.

[Multiple cerebral artery occlusion due to non-bacterial thrombotic endocarditis: an autopsy case report].

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.

Multiple rectal carcinoid tumors in monozygotic twins.

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.

Cytoplasmic non-epithelial mucin accumulation associated with CD44 in an astrocytic tumor with signet ring features.

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.

Trigonal cavernous malformation with intraventricular hemorrhage: a case report and literature review.

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.

Claudin expression profiles in Epstein-Barr virus-associated nasopharyngeal carcinoma.

Claudins are a family of proteins that are structural and functional components of tight junctions and have crucial roles in the maintenance of cellular arrangement, adhesion and paracellular transport. Recent studies have shown that changes and/or loss of claudin expression plays an important role in tumorigenesis and tumor progression, and altered expression of claudins has been reported in various human carcinomas. Non-keratinizing nasopharyngeal carcinoma (NPC) is a common Epstein-Barr virus (EBV)-associated carcinoma with characteristic clinicopathological features. The aim of this study was to investigate claudin expression profiles in EBV-associated non-keratinizing NPC. We analyzed expressions of claudin-1, -2, -3, and -4 in 18 cases of EBV-associated non-keratinizing NPC by immunohistochemical methods. Claudin-1 was expressed in all 18 cases, but claudin-2 was not expressed in any of the 18 cases. Claudin-3 expression was variable, with 8 of the 18 cases (45%) showing no immunoreactivity for claudin-3. Claudin-4 displayed positive immunoreactivity in all cases, even in claudin-3-negative cases. Claudin-3 and -4 are receptors for cytotoxic Clostridium perfringens enterotoxin (CPE) and CPE has emerged as a potential therapeutic target for malignant tumors expressing claudin-3 and/or -4, because CPE specifically and rapidly lyses cells expressing these proteins. Clinically, treatment of distant metastases is a serious problem in EBV-associated non-keratinizing NPC, because frequently there is lymph node involvement and distant metastasis before detection of the primary tumor. Therefore, CPE therapy may be a potential therapeutic target for EBV-associated non-keratinizing NPC, since our results clearly showed claudin-3 and/or -4 expression in all cases studied.

Quercetin enhances tumorigenicity induced by N-ethyl-N'-nitro-N-nitrosoguanidine in the duodenum of mice.

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<0.05) than in group A (2.32±0.31). The size of the duodenal tumors increased significantly in group B (1.79±0.09 mm, p<0.001) compared with group A (1.43±0.09 mm). In contrast, no duodenal tumor was induced in group D. The present findings suggest that excessive intake of quercetin occasionally is a risk factor for carcinogenesis of some specific organs such as the upper intestine.