Entrapment partly participates in the longitudinal progression of neuropathy with anti-MAG antibodies.

Neuropathy with anti-myelin-associated glycoprotein (MAG) antibodies commonly demonstrates distal-dominant prolongation of nerve conduction. However, recent electrophysiological studies have shown that distal motor demyelination is not always a distinct feature. We aimed to elucidate whether the longitudinal progression of nerve impairment occurs in a distal-dominant manner. Seven patients with neuropathy with anti-MAG antibodies were enrolled. Sequential nerve conduction studies revealed nerve conduction reduction only at the wrist segment in the median nerve of the patients, but not in the ulnar nerve. Median nerve entrapment at the wrist may play a role in longitudinal disease progression in neuropathy with anti-MAG antibodies.

Progressive supranuclear palsy often develops idiopathic normal pressure hydrocephalus-like magnetic resonance imaging features.

BACKGROUND AND PURPOSE: Idiopathic normal pressure hydrocephalus (iNPH) is a clinical entity without established pathological hallmarks. Previous autopsy studies reported that patients with an antemortem diagnosis of iNPH had a different postmortem diagnosis, commonly progressive supranuclear palsy (PSP). Disproportionately enlarged subarachnoid space hydrocephalus (DESH) has been reported as a characteristic feature of iNPH on magnetic resonance imaging (MRI). In addition, periventricular white matter hyperintensities (PVHs) are noted in most patients with iNPH; these PVHs are supposed to reflect transependymal movement of ventricular cerebrospinal fluid. It is hypothesized that PSP develops more iNPH-like MRI features than other neurodegenerative disorders. METHODS: Thirty-eight patients with a clinical diagnosis of PSP, 42 with Parkinson's disease (PD) without dementia, 30 with PD with dementia (PDD) and 29 with Alzheimer's disease (AD) were enrolled. The DESH score and PVH grade were measured using the conventional MRI sequence and were compared amongst the patient groups. RESULTS: Disproportionately enlarged subarachnoid space hydrocephalus score was significantly higher in patients with PSP than PD without dementia, and there was a trend that the DESH score was higher in patients with PSP than PDD or Alzheimer's disease. PVH grade was significantly larger in patients with PSP than PD without dementia. In the components of the DESH score, callosal angle was significantly smaller in patients with PSP than in PD without dementia or PDD. CONCLUSIONS: This study demonstrated that some PSP patients develop iNPH-like MRI features, suggesting the presence of iNPH-like features in the clinical spectrum of PSP. A clinical phenotype of PSP with hydrocephalus is proposed, which should be further investigated in future studies.

Impaired residual renal function predicts denosumab-induced serum calcium decrement as well as increment of bone mineral density in non-severe renal insufficiency.

Denosumab treatment of osteoporotic patients, except those with severe renal insufficiency, reduced cCa levels. Low baseline cCa, low estimated glomerular filtration rate, and high bone turnover increased the risk of lower cCa, while increasing bone mineral density. Pretreatment with antiresorptive agents was beneficial in reducing the risk of hypocalcemia. INTRODUCTION: Although denosumab-induced hypocalcemia has been frequently observed in patients with chronic kidney disease (CKD) stages 4-5D being treated with denosumab for osteoporosis, few studies have assessed the risk factors for serum-corrected calcium (cCa) reductions in patients with non-severe renal insufficiency. This study assessed the risk factors for reduced cCa concentration following denosumab administration and analyzed factors predictive of changes in bone mineral density (BMD). METHODS: Seventy-seven osteoporotic patients, not including those with CKD stages 4-5D, were treated with 60 mg denosumab once every 6 months. Biochemical parameters and BMD were analyzed from prior to the initial dose until 1 month after the second dose. RESULTS: Following the first administration of denosumab, cCa levels decreased, reaching a minimum on day 7. Multiple linear regression analyses showed that baseline cCa, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, tartrate-resistant acid phosphatase-5b (TRACP-5b), and bone alkaline phosphatase (BAP) or pretreatment with antiresorptive agents were significant factors independently associated with the absolute reduction in cCa from baseline to day 7 (ΔcCa0-7 days). ΔcCa0-7 days after the second dose of denosumab was significantly lower than that after the first dose. After 6 months of denosumab treatment, both LS-BMD and FN-BMD significantly increased from baseline. LS-BMD and FN-BMD correlated significantly with baseline TRACP-5b or BAP and eGFR, respectively. CONCLUSIONS: Both low eGFR and high bone turnover were independent risk factors for denosumab-induced cCa decrement, and for increases in BMD. Pretreatment with antiresorptive agents may reduce the risk of hypocalcemia.

Population differences in S-warfarin pharmacokinetics among African Americans, Asians and whites: their influence on pharmacogenetic dosing algorithms.

Using population pharmacokinetic analysis (PPK), we attempted to identify predictors of S-warfarin clearance (CL(S)) and to clarify population differences in S-warfarin pharmacokinetics among a cohort of 378 African American, Asian and white patients. Significant predictors of CL(S) included clinical (age, body weight and sex) and genotypic (CYP2C9*2,*3 and *8) factors, as well as African American ethnicity, the median CL(S) being 30% lower in the latter than in Asians and whites (170 versus 243 and 250 ml h-1, P<0.01). The plasma S-warfarin (Cp(S)) time courses following the genotype-based dosing algorithms simulated using the PPK estimates showed African Americans with CYP2C9*1/*1 and any of the VKORC1 genotypes would have an average Cp(S) at steady state 1.5-1.8 times higher than in Asians and whites. These results indicate warfarin dosing algorithms should be evaluated in each respective ethnic population. Further study of a large African American cohort will be necessary to confirm the present findings.

Comparing the risk of hepatitis B virus reactivation between direct-acting antiviral therapies and interferon-based therapies for hepatitis C.

Hepatitis B virus (HBV) reactivation has been reported during antihepatitis C treatment in patients with hepatitis C virus (HCV) and HBV co-infection. We aimed to evaluate the frequency and risk factors of HBV reactivation during anti-HCV therapy and compared those between interferon (IFN)-free direct-acting antiviral (DAA) therapies and IFN-based therapies. Three hundred and twenty-two patients with HCV infection receiving anti-HCV therapy were retrospectively screened. The baseline HBV infection statuses of all eligible patients and the HBV-DNA level of all patients with current or previous HBV infection were examined at the end of treatment. In patients with baseline anti-HBs positivity, changes in anti-HBs titre were evaluated. Of 287 patients who met the inclusion criteria, 157 had current (n=4) or previous (n=153) HBV infection; 85 were treated with IFN-free DAA therapies and 72 were treated with IFN-based therapies. Six patients experienced HBV reactivation (n=2) or HBV reappearance (n=4) after IFN-free DAA therapies, while no patient developed HBV reactivation after IFN-based therapies. The risk factors of HBV reactivation or reappearance were DAA therapies and a reduction in anti-HBs titre to <12 mIU mL-1 by the end of treatment. The decline changes of anti-HBs titre were significantly higher in patients treated with DAA therapies. Although HBV reactivation hepatitis was not observed, three of four patients with HBV reactivation or reappearance after achieving HCV eradication had viremia 8 weeks after completion of therapy. A significant proportion of patients develop HBV reactivation or reappearance without hepatitis after IFN-free DAA therapies. Low levels of anti-HBs and their decrease to <12 mIU mL-1 after treatment are significant risk factors for HBV reactivation or reappearance.

Polypharmacy of medications and fall-related fractures in older people in Japan: a comparison between driving-prohibited and driving-cautioned medications.

WHAT IS KNOWN AND OBJECTIVE: Polypharmacy is a risk factor for fall-related fractures. However, it is unclear whether polypharmacy itself is a direct risk factor. The aim of this study was to assess the association between the risk of fall-related fractures and polypharmacy of driving-prohibited and driving-cautioned medications in older outpatients. METHODS: We conducted a cross-sectional study of outpatients aged ≥65 years receiving any medication, using two sampling data sets from the October 2011 and October 2012 national insurance claims in Japan. Using logistic regression models, we analysed the association between the numbers of driving-prohibited or driving-cautioned medications administered or dispensed to patients and the occurrence of fall-related fractures. RESULTS AND DISCUSSION: In both analysis populations (n = 303 311 and n = 326 219), the adjusted odds ratio of driving-prohibited medications for the occurrence of fall-related fractures significantly increased as the number of these medications per patient increased (95% confidence interval: 0, 1-2, 3-4, 5-6, 7-8 and ≥9 medications; reference, 0·95-1·24, 1·18-1·79, 1·47-2·96, 1·26-5·21 and 1·50-15·2 in October 2011 and reference, 1·11-1·42, 1·39-2·03, 1·33-2·72, 1·53-5·49 and 1·30-13·0 in October 2012). The association was maintained even for sensitivity analyses restricted to medications administered orally or orally and by injection. However, a similar association was not observed for driving-cautioned medications. WHAT IS NEW AND CONCLUSION: Medication class is a more important risk factor for fall-related fractures rather than polypharmacy alone with no regard to medication class.

Diagnostic value of urine erythrocyte morphology in the detection of glomerular disease in SurePath™ liquid-based cytology compared with fresh urine sediment examination.

OBJECTIVE: To assess whether the morphology of urine erythrocytes can be an effective tool for distinguishing glomerular disease from lower urinary tract disease in SurePath™ liquid-based cytology (SP-LBC). METHODS: We examined four morphological parameters of erythrocytes: (1) irregular erythrocytes (of all types including fragmented forms) comprising greater than or equal to 20% of erythrocytes; (2) uniform erythrocytes (>80%); (3) doughnut or target-like shaped (D/T) erythrocytes (≥1%); and (4) acanthocytes (≥1%) in glomerular disease (n = 32) and lower urinary tract disease (n = 20) with SP-LBC slides in cases that had also been assessed by fresh urine sediment examination. RESULTS: Sensitivity of D/T erythrocytes and acanthocytes (dysmorphic erythrocytes) for glomerular disease were 100% and 87.5%, respectively, with urine sediment examination, and 81.3% and 46.9%, respectively, in SP-LBC slides. Specificity was 100% for D/T erythrocytes and acanthocytes using either procedure. While irregular erythrocytes were specific for glomerular disease using urine sediment examination, they were seen in 70% of those with lower urinary tract disease using SP-LBC slides as a result of the deformation of erythrocytes by the fixative. CONCLUSIONS: Although the sensitivity of D/T erythrocytes and acanthocytes for glomerular disease was lower in SP-LBC slides than fresh urine sediment examination, their specificity was equally high. Therefore, urine erythrocyte morphology is useful in the detection of glomerular disease with the SP-LBC slides. However, morphological features apart from D/T erythrocytes and acanthocytes are not useful in SP-LBC slides.

Sporadic isolations of a multi-drug resistant Pseudomonas aeruginosa clone during a 14-month epidemic in a general hospital in Hiroshima.

BACKGROUND: During 2005-2007, we experienced sporadic isolations of multidrug-resistant (MDRP) Pseudomonas aeruginosa from wards in a general hospital in Hiroshima. The objective of this study was to analyze epidemiology relationships and the mode of spread of the strains. METHODS: Clonality was assessed using pulsed-field gel electrophoresis (PFGE) and serotyping. MICs were determined using the microdilution broth method. Investigations of the affected patients' movements and environmental sampling from the affected wards were conducted. RESULTS: An abrupt increase in MDRP isolations began at the end of 2005 and ended in February 2007. A total of 25 MDRP strains were sporadically isolated from nine wards. Fourteen strains were genotypically and serologically identical. Analysis of the patients' movements identified that six of the 14 MDRP-positive patients became positive for MDRP when they were in the intensive care unit (ICU), and two became positive after the patients moved from the ICU to another nursing unit. Four MDRP strains were isolated from patients who did not stay in the ICU and were in ward E6, which had the second highest number of isolations. In July 2006, environmental sampling of the hospital identified a toilet brush in ward E6 that was contaminated with MDRP that was genotypically and serologically identical to the clinical isolates. CONCLUSIONS: Our study suggests that the sporadic increase in MDRP isolates during 2005-2007 in the general hospital in Hiroshima was due to an epidemic of an MDRP clone. Continuity and spread of infection was probably due to cross infection and contamination in the hospital with the MDRP strain.

Topical application of Aggregatibacter actinomycetemcomitans cytolethal distending toxin induces cell cycle arrest in the rat gingival epithelium in vivo.

BACKGROUND: Aggregatibacter actinomycetemcomitans is one of the etiological pathogens implicated in the onset of periodontal disease. This pathogen produces cytolethal distending toxin (CDT) that acts as a genotoxin to induce cell cycle arrest and cellular distension in cultured cell lines. Therefore, CDT is a possible virulence factor; however, the in vivo activity of CDT on periodontal tissue has not been explored. Here, CDT was topically applied into the rat molar gingival sulcus; and the periodontal tissue was histologically and immunohistochemically examined. MATERIALS AND METHODS: Recombinant purified A. actinomycetemcomitans CDT was applied to gingival sulcus of male Wistar rats and tissue samples were immunohistochemmically examined. RESULTS: One day after application, infiltration of neutrophils and dilation of blood vessels in the gingival connective tissue were found. At day three, desquamation and detachment of cells in the junctional epithelium was observed. This abrasion of junctional epithelium was not observed in rats treated with mutated CDT, in which a His274Ala mutation is present in the CdtB subunit. This indicates the tissue abrasion may be caused by the genotoxicity of CdtB. Expression of the proliferating cell nuclear antigen (PCNA), a marker for proliferating cells, was significantly suppressed using CDT treatment in the junctional epithelium and gingival epithelium. CONCLUSION: Using the rat model, these data suggest CDT intoxication induces cell cycle arrest and damage in periodontal epithelial cells in vivo.

Active and passive immunization with the Pseudomonas V antigen protects against type III intoxication and lung injury.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that can cause fatal acute lung infections in critically ill individuals. Damage to the lung epithelium is associated with the expression of toxins that are directly injected into eukaryotic cells through a type Ill-mediated secretion and translocation mechanism. Here we show that the P. aeruginosa homolog of the Yersinia V antigen, PcrV, is involved in the translocation of type III toxins. Vaccination against PcrV ensured the survival of challenged mice and decreased lung inflammation and injury. Antibodies to PcrV inhibited the translocation of type III toxins.

[Thymoma with long-term survival treated by polysurgery; report of a case].

A 50-year-old man was found to have a chest abnormal shadow during a check-up and visited our hospital in 1991. Tumor shadow was observed in the anterior mediastinum. Resection of the tumor was performed by partial thymectomy. The pathological diagnosis was a thymoma type B1 and stage I based on Masaoka' s classification. In 2004, he underwent radical thymectomy and partial resection of the lung to remove the local recurrent tumor followed by postoperative radiation therapy. In 2006, 3rd operation was performed and the tumor in the superior mediastinum was resected. Since then, the patient is well without signs of recurrence. We experienced a case of thymoma with long-term survival treated by polysurgery.

Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites.

Normalization of the increased vascular nitric oxide (NO) generation with low doses of NG-nitro-L-arginine methyl ester (L-NAME) corrects the hemodynamic abnormalities of cirrhotic rats with ascites. We have undertaken this study to investigate the effect of the normalization of vascular NO production, as estimated by aortic cyclic guanosine monophosphate (cGMP) concentration and endothelial nitric oxide synthase (eNOS) protein expression in the aorta and mesenteric artery, on sodium and water excretion. Rats with carbon tetrachloride-induced cirrhosis and ascites were investigated using balance studies. The cirrhotic rats were separated into two groups, one receiving 0.5 mg/kg per day of L-NAME (CIR-NAME) during 7 d, whereas the other group (CIR) was administrated the same volume of vehicle. Two other groups of rats were used as controls, one group treated with L-NAME and another group receiving the same volume of vehicle. Sodium and water excretion was measured on days 0 and 7. On day 8, blood samples were collected for electrolyte and hormone measurements, and aorta and mesenteric arteries were harvested for cGMP determination and nitric oxide synthase (NOS) immunoblotting. Aortic cGMP and eNOS protein expression in the aorta and mesenteric artery were increased in CIR as compared with CIR-NAME. Both cirrhotic groups had a similar decrease in sodium excretion on day 0 (0.7 versus 0.6 mmol per day, NS) and a positive sodium balance (+0.9 versus +1.2 mmol per day, NS). On day 7, CIR-NAME rats had an increase in sodium excretion as compared with the CIR rats (sodium excretion: 2.4 versus 0.7 mmol per day, P < 0.001) and a negative sodium balance (-0.5 versus +0.8 mmol per day, P < 0.001). The excretion of a water load was also increased after L-NAME administration (from 28+/-5% to 65+/-7, P < 0.05). Plasma renin activity, aldosterone and arginine vasopressin were also significantly decreased in the CIR-NAME, as compared with the CIR rats. The results thus indicate that normalization of aortic cGMP and eNOS protein expression in vascular tissue is associated with increased sodium and water excretion in cirrhotic rats with ascites.

Upregulation of aquaporin-2 water channel expression in chronic heart failure rat.

Aquaporin-2 (AQP2) mediates vasopressin-regulated collecting duct water permeability. Chronic heart failure (CHF) is characterized by abnormal renal water retention. We hypothetized that upregulation of aquaporin-2 water channel could account for the water retention in CHF. Male rats underwent either a left coronary artery ligation, a model of CHF, or were sham operated. 31-33 d after surgery, mean arterial pressure (MAP) and cardiac output were measured in conscious animals, and the animals were killed 24 h later. Cardiac output (CO) and plasma osmolality were significantly decreased and plasma vasopressin increased in the CHF as compared to the sham-operated rats. Both mRNA and protein AQP2 were significantly increased in the kidneys of the CHF rats. The effect of oral administration of a nonpeptide V2 vasopressin receptor antagonist, OPC 31260, was therefore investigated. OPC 31260 induced a significant increase in diuresis, decrease in urinary osmolality, and rise in plasma osmolality in the OPC 31260-treated CHF rats as compared to untreated CHF rats. The mRNA and protein AQP2 were significantly diminished in both cortex and inner medulla of the treated CHF rats. In conclusion, an early upregulation of AQP2 is present in CHF rats and this upregulation is inhibited by the administration of a V2 receptor antagonist. The results indicate a major role for vasopressin in the upregulation of AQP2 water channels and water retention in experimental CHF in the rat.

Upregulation of aquaporin 2 water channel expression in pregnant rats.

Water retention is characteristic of pregnancy but the mechanism(s) of the altered water metabolism has yet to be elucidated. The collecting duct water channel, aquaporin 2 (AQP2), plays a pivotal role in the renal water regulation, and we hypothesized that AQP2 expression could be modified during pregnancy. Sprague-Dawley female rats were studied on days 7 (P7), 14 (P14), and 20 (P20) of pregnancy, and expression of AQP2 in papillae was examined. Nonpregnant (NP) littermates were used as controls. Plasma osmolalities were significantly lower in pregnant rats by day 7 of gestation (P7 283.8+/-1.82, P14 284.3+/-1.64, P < 0.001, P20 282. 4+/-1.32, P < 0.0001, vs. NP 291.8+/-1.06 mosmol/kgH2O). However, plasma vasopressin concentrations in pregnant rats were not significantly different than in nonpregnant rats (NP 1.03+/-0.14, P7 1.11+/-0.21, P14 1.15+/-0.21, P20 1.36+/-0.24 pg/ml, NS). The mRNA of AQP2 was increased early during pregnancy: AQP2/beta actin: P7 196+/-17.9, P14 200+/-6.8, and P20 208+/-15.5%, P < 0.005 vs. NP (100+/-11.1%). AQP2 protein was also increased during pregnancy: AQP2 protein: P7 269+/-10.0, P14 251+/-12.0, P < 0.0001, and P20 250+/-13.6%, P < 0.001 vs. NP (100+/-12.5%). The effect of V2 vasopressin receptor antagonist, OPC-31260, was then investigated. AQP2 mRNA was suppressed significantly by OPC-31260 administration to P14 rats (AQP2/beta actin: P14 with OPC-31260 39.6+/-1.7%, P < 0.001 vs. P14 with vehicle) and was decreased to the same level of expression as NP rats receiving OPC-31260. Similar findings were found with the analysis of AQP2 protein. The decreased plasma osmolality of P14 rats was not modified by OPC-31260. The results of the study indicate that upregulation of AQP2 contributes to the water retention in pregnancy through a V2 receptor-mediated effect. In addition to vasopressin, other factors may be involved in this upregulation.

Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia.

The pathogenesis of septic shock occurring after Pseudomonas aeruginosa pneumonia was studied in a rabbit model. The airspace instillation of the cytotoxic P. aeruginosa strain PA103 into the rabbit caused a consistent alveolar epithelial injury, progressive bacteremia, and septic shock. The lung instillation of a noncytotoxic, isogenic mutant strain (PA103DeltaUT), which is defective for production of type III secreted toxins, did not cause either systemic inflammatory response or septic shock, despite a potent inflammatory response in the lung. The intravenous injection of PA103 did not cause shock or an increase in TNF-alpha, despite the fact that the animals were bacteremic. The systemic administration of either anti-TNF-alpha serum or recombinant human IL-10 improved both septic shock and bacteremia in the animals that were instilled with PA103. Radiolabeled TNF-alpha instilled in the lung significantly leaked into the circulation only in the presence of alveolar epithelial injury. We conclude that injury to the alveolar epithelium allows the release of proinflammatory mediators into the circulation that are primarily responsible for septic shock. Our results demonstrate the importance of compartmentalization of inflammatory mediators in the lung, and the crucial role of bacterial cytotoxins in causing alveolar epithelial damage in the pathogenesis of acute septic shock in P. aeruginosa pneumonia.

An Asian variant of intravascular lymphoma: unique clinical and pathological manifestation in the gallbladder.

We here present a rare case of intravascular lymphoma (IVL) in a Japanese man. 4 months after cholecystectomy due to cholecystitis, a diagnosis of intravascular lymphoma (IVL) was strongly suspected. Lymphoma cells were diffusely observed in the bone marrow parenchyma, but were absent in the vascular spaces. The patient died of respiratory failure and at autopsy a small number of lymphoma cells in the extravascular parenchyma of the adrenal gland and bone marrow were seen. Serial sections of the surgically resected gallbladder retrospectively confirmed the diagnosis of IVL. In addition, congestion and edema were observed in the connective tissue layer. It is possible that edema or ischemia in the gallbladder wall or at other anatomic sites due to the circulation disturbance induced by the intravascular obstruction of lymphoma cells may have caused the initial symptoms. In conclusion, clinicians and pathologists should keep in mind that the gallbladder may be initially involved in IVL.

Bilateral hamartoma arising in axillary accessory mammary glands. Case report.

A 57-year-old Japanese woman presented with a lump, originally noticed 10 years previously, in both axillary regions. Histologically, the axillary tumors consisted of a random admixture of ducts, lobules and fibrous stroma with predominant adipose tissue. This is the first case of bilateral ectopic hamartoma arising in the axillary regions. Surgeons and pathologists should be aware that ectopic breast hamartoma can occur in both axillary regions.

Female urethral adenocarcinoma with a heterogeneous phenotype.

We here report a very rare case of female urethral adenocarcinoma. A 77-year-old woman presented with urinary retention. Cystoscopy showed a urethral tumor and the biopsy material showed adenocarcinoma. Macroscopically, the tumor measuring 3.0 x 3.0 x 2.4 cm was predominantly observed around the periurethral area on the proximal side. Histologically, patterns of columnar/mucinous adenocarcinoma, clear cell adenocarcinoma and papillary/micropapillary carcinoma were observed, but there was no evidence of a cribriform pattern. Immunohistochemically, neoplastic cells of at least one of three components were positive for CK7 and CK20 or CA125. We suggest that female urethral adenocarcinoma with a histologically and immunohistochemically heterogeneous phenotype may originate from cells within urethral or paraurethral tissue, such as urethritis glandularis or intestinal metaplastic epithelium and Mullerian tissue.

Lung adenocarcinoma with a micropapillary pattern: a clinicopathological study of 25 cases.

Lung adenocarcinoma with a micropapillary pattern has recently been described, but its biological behavior is as yet uncertain. In this article we present a clinicopathological study of lung adenocarcinoma with micropapillary morphology. We selected 25 patients with lung adenocarcinoma with micropapillary morphology from the 2001-2004 pathology files (age range 54 to 81 years; mean 64.5 years). Micropapillary carcinoma is predominantly located at the periphery of the tumor nodule or mass and occurs irrespective of the subtype of the adenocarcinoma. A micropapillary component was seen against a mucinous background in three cases and microcalcifications resembling psammoma bodies were seen in one case. Four cases showed intensive invasive growth such as micropapillary adenocarcinoma of the breast and 21 showed alveolar type morphology with piling-up of the neoplastic cells with or without stromal invasion. Seven of twenty-three (30.4%) showed lymph node metastases at time of operation. Twelve of twenty-five (48%) showed pleural invasion. Regarding clinical outcome, 14 patients were alive without disease, 5 were alive with disease, and 5 died of the lung adenocarcinoma. No significant relationship was found between the extent of the micropapillary component and prognosis. However, the carcinoma seen in the five patients who died showed breast type histology with intensive invasive growth in three cases and alveolar type histology with intensive stromal invasion in two. Lung micropapillary carcinoma of breast type may behave more aggressively than the alveolar type.

Gastric carcinosarcoma with neuroendocrine differentiation as the carcinoma component and leiomyosarcomatous and myofibroblastic differentiation as the sarcomatous component.

Gastric carcinosarcoma with neuroendocrine differentiation is a very rare neoplasm. In this article we present such a case. The gastroendoscopic examination of a 59-year-old Japanese man disclosed gastric cancer during follow-up after operation for rectal cancer. Subsequently, total gastrectomy was carried out because of gastric cancer. A large tumor measuring 9.2 x 8.4 cm was observed in the posterior wall of the upper portion of the stomach. The tumor was composed of carcinoma and sarcomatous cells, and the histological transition of both components was observed. Immunohistochemically, carcinoma and sarcomatous cells were positive for cytokeratin CAM5.2. The carcinoma contained adenocarcinoma and malignant cells with neuroendocrine differentiation. The sarcomatous component showed leiomyosarcomatous and myofibroblastic differentiation. The present tumor is the fifth case of gastric carcinosarcoma with neuroendocrine differentiation and the first case of gastric carcinosarcoma with myofibroblastic differentiation. Pathologists should bear in mind that gastric carcinosarcoma may show various types of differentiation.