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.

Remodeling of the pulmonary artery induced by metastatic gastric carcinoma: a histopathological analysis of 51 autopsy cases.

BACKGROUND: Gastric carcinoma remains the second commonest cause of cancer deaths worldwide. Presence of the carcinoma cell in the pulmonary artery is serious condition that might cause remodeling of the pulmonary artery. The present study conducted detailed histopathological analyses to elucidate how gastric carcinoma cells may affect the structure and hemodynamics of pulmonary arteries. METHODS: Remodeling of the pulmonary artery was assessed based on measurements of arterial diameters and stenosis rates from the autopsies, and their correlation were also validated. We additionally calculated 95 percent confidential intervals (CIs) for the rate of stenosis in groups of pulmonary arteries of different caliber zones (under 100, 100 to 300, and over 300 micrometer). The right ventricular thickness was measured and examined whether it correlated with the rate of pulmonary arterial stenosis. RESULTS: A total of 4612 autopsy cases were recorded at our institute, among which 168 had gastric carcinoma. Finally, 51 cases of the gastric carcinoma were employed for the study which had carcinoma cells in the lumen of the pulmonary artery. The mean right ventricular wall thickness of these cases was 3.14 mm. There were significant positive associations between the rates of pulmonary arterial stenosis and right ventricular thickness from pulmonary arteries of diameter under 100, 100 to 300, and over 300 micrometer. In these zones, 31, 31, and 33 cases had rates of pulmonary arterial stenosis that were below the lower limit of the 95 percent CI values, respectively. On the other hand, among cases with significant pulmonary stenosis, 17 of 18 cases with stenosis in the over 300 micrometer zone involved pulmonary arteries of both in the under 100 and 100 to 300 micrometer zones. CONCLUSION: One-third of autopsy with advanced gastric carcinoma had carcinoma cells in lumen of pulmonary artery, but implantation and proliferation may be essential to induce intimal thickening that causes an increasing of pulmonary arterial pressure, because our study revealed a significant positive association between the rate of pulmonary arterial stenosis and right ventricular thickness. In addition, diffuse type gastric carcinoma may be apt to cause the remodeling of the pulmonary artery.

Development of a peptide nucleic acid probe to Trichosporon species and identification of trichosporonosis by use of in situ hybridization in formalin-fixed and paraffin-embedded (FFPE) sections.

In order to identify Trichosporon species in formalin-fixed and paraffin-embedded sections from which visual discrimination of non-glabrata Candida species is mostly ineffective but critical for the choice of antifungals, we tested the usefulness of a newly designed peptide nucleic acid probe (PNA) for in situ hybridization (ISH). Results confirmed the usefulness of ISH with our PNA probe in identifying Trichosporon species from Candida albicans.

Histopathological implications of Aspergillus infection in lung.

This paper opens with a discussion on the significance of invasive fungal infections in advanced contemporary medicine, with an emphasis on the intractability of disease management and the difficulties of diagnosis. This is followed by a discussion concerning classification, histopathological features, and pathophysiology. While it has been largely accepted that Aspergillus species is recognized by cellular receptors and attacked by neutrophils, the radiological and macroscopic findings linking infection with neutropenia remain unconfirmed. In an effort to gain a better understanding of the pathophysiology and pathogenesis of invasive aspergillosis, we wish to emphasize the utility of radiological and histopathological examinations since these can provide detailed information on the extremely complex interaction between the causative microbes and tissue responses. A review of noninvasive or semi-invasive aspergillosis is also provided, with particular emphasis on chronic necrotizing pulmonary aspergillosis, which is recognized as a transition form of simple pulmonary aspergilloma and invasive pulmonary aspergillosis, although few findings have been reported in this area.

How histopathology can contribute to an understanding of defense mechanisms against cryptococci.

Invasive fungal infections, particularly those considered opportunistic, have become a common and significant complication of procedures performed in advanced contemporary medicine. Among such infections, cryptococcosis, which is usually caused by infection with Cryptococcus neoformans and Cryptococcus gattii, is particularly problematic because this fungal infection occurs in immunocompromised and apparently immunocompetent individuals. It has been largely accepted that Cryptococcus species are recognized by cellular receptors and that Th1-type immune responses play an important role in defense mechanisms against the yeast. However, the interaction between the yeast and host tissue varies depending on the characteristics of the yeast and the immune status of the host. To gain a better understanding of the pathophysiology of cryptococcosis, we wish to emphasize the usefulness of histopathological examinations, because it allowed more detailed information of an extremely complex interaction between the causative yeasts and tissue response. In the present review, we describe the pathophysiology of cryptococcosis as largely revealed in our previous histopathological investigations of the experimental infection.

The biological activity of a novel pyrethroid: metofluthrin.

Metofluthrin (commercial name: SumiOne(®), Eminence(®)) is a novel pyrethroid insecticide developed by Sumitomo Chemical Co., Ltd. Metofluthrin has extremely high insecticidal activity to various pest insects, especially to mosquitoes. In addition, Metofluthrin has relatively high volatility and low mammalian toxicity. Metofluthrin is therefore suitable for use not only in conventional mosquito control formulations such as coils and liquid vaporizers, but also in a variety of novel devices that do not require heating, such as fan vaporizers and paper and resin emanators. Here we describe the insecticidal activity of Metofluthrin mainly against mosquitoes in various formulations in both laboratory and field trials.

Gene expression analysis of a murine model with pulmonary vascular remodeling compared to end-stage IPAH lungs.

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investigated factors playing an important role in IPAH by searching discrepant or controversial expression patterns between our murine model and those previously published for human IPAH. We employed the mouse model, which induced muscularization of pulmonary artery leading to hypertension by repeated intratracheal injection of Stachybotrys chartarum, a member of nonpathogenic and ubiquitous fungus in our envelopment. METHODS: Microarray assays with ontology and pathway analyses were performed with the lungs of mice. A comparison was made of the expression patterns of biological pathways between our model and those published for IPAH. RESULTS: Some pathways in our model showed the same expression patterns in IPAH, which included bone morphogenetic protein (BMP) signaling with down-regulation of BMP receptor type 2, activin-like kinase type 1, and endoglin. On the other hand, both Wnt/planar cell polarity (PCP) signaling and its downstream Rho/ROCK signaling were found alone to be activated in IPAH and not in our model. CONCLUSIONS: Activation of Wnt/PCP signaling, in upstream positions of the pathway, found alone in lungs from end stage IPAH may play essential roles in the pathogenesis of the disease.

Efficacy of pyriproxyfen-treated nets in sterilizing and shortening the longevity of Anopheles gambiae (Diptera: Culicidae).

Pyrethroid-resistant malaria vectors have become a serious threat for malaria control, and bed nets that reduce the development of resistance are urgently needed. Here, we tested the effects of bed nets treated with the insect growth regulator pyriproxyfen against adult female Anopheles gambiae Giles (Diptera: Culicidae) under laboratory conditions. Noninsecticidal nets made of 195 denier monofilament polyethylene with a mesh size of 75 holes per square inch (equivalent to the Olyset Net) were dipped in a 0.1, 0.01, or 0.001% (wt:vol) alcohol solution of pyriproxyfen and dried overnight. Adult females of an insecticide-susceptible An. gambiae strain were exposed to treated and untreated nets before and after a bloodmeal. Bioassays showed that females were completely sterilized after exposure to 0.1% (35 mg [AI]/m2) and 0.01% pyriproxyfen-treated nets both before and after a bloodmeal. In addition, adult longevity decreased after exposure to the pyriproxyfen-treated nets in a concentration-dependent manner. The sterilizing and life-shortening effects of pyriproxyfen on the vector mosquito indicate that the combined use of pyriproxyfen and pyrethroids on bed nets has the potential to provide better malaria control and prevent the further development of pyrethroid resistance in malaria vectors.

Trends in the prevalence of invasive fungal infections from an analysis of annual records of autopsy cases of Toho University.

Clinical diagnosis of invasive fungal infections (IFIs) is sometimes difficult, and obtaining an accurate assessment of trends concerning the prevalence of IFIs is a challenge. The aim of this study was to determine trends in the prevalence of IFIs from an autopsy survey. The retrospective review of autopsy records stored in Toho University was performed on all documented cases with fungal infection from 1955 to 2006. A total of 411 cases of IFIs were detected among 10 297 autopsies. The prevalence of candidiasis decreased from 3.6% (1981-93) to 2.0% (1994-2006), and that of aspergillosis increased throughout the 52-year period and reached 2.0% (1994-2006). The prevalence of IFIs in the patient group comprising haematological disorders was significantly higher (19.9%) than in other patient groups (2.9%), of which the odds ratio was 18.4 for mucormycosis and 10.0 for aspergillosis. The lung was the most common organ involved irrespective of major fungal species, and most cases with candidiasis showed multiple-organ infection. Results confirmed the increasing prevalence of aspergillosis and high risk of IFIs in the patient group with haematological disorders. IFIs were also detected in an immunocompromised state caused not only by primary disease but also by treatment with anti-tumour drugs and corticosteroids.

Literature survey on epidemiology and pathology of gangliocytic paraganglioma.

BACKGROUND: Although gangliocytic paraganglioma (GP) has generally been regarded as a neuroendocrine tumor, its origin remains unclear. We therefore aimed to investigate the details of this disease by carefully analyzing and extracting common features of the disease as presented in selected publications. METHODS: We searched for English and Japanese cases of GP using the PubMed and IgakuChuoZasshi databases on August 2010. We then extracted and sampled raw data from the selected publications and performed appropriate statistical analyses. Additionally, we evaluated the expression of hormone receptors based on our previously reported case. RESULTS: 192 patients with GP were retrieved from the databases. Patient ages ranged from 15 y to 84 y (mean: 52.3 y). The gender ratio was 114:76 (male to female, 2 not reported). Maximum diameter of the tumors ranged from 5.5 mm to 100 mm (mean: 25.0 mm). The duodenum (90.1%, 173/192) was found to be the most common site of the disease. In 173 patients with duodenal GP, gastrointestinal bleeding (45.1%, 78/173) was found to be the most common symptom of the disease, followed by abdominal pain (42.8%, 74/173), and anemia (14.5%, 25/173). Rate of lymph node metastasis was 6.9% (12/173). Our statistical analysis indicated that significant differences were found for gender between GP within the submucosal layer and exceeding the submucosal layer. Furthermore, our immunohistochemical evaluation showed that both epithelioid and pancreatic islet cells showed positive reactivity for progesterone receptors. CONCLUSIONS: Our literature survey revealed that there were many more cases of GP exceeding the submucosal layer than were expected. Meanwhile, our statistical analyses and immunohistochemical evaluation supported the following two hypotheses. First, vertical growth of GP might be affected by progesterone exposure. Second, the origin of GP might be pancreatic islet cells. However, it is strongly suspected that our data have been affected by publication bias and to confirm these hypotheses, further investigation is required.

Leiomyosarcoma with partial rhabdomyoblastic differentiation: first case report of primary cardiac origin.

BACKGROUND: Leiomyosarcoma occurring as a primary cardiac tumor has been known as an extremely rare condition. Previous studies of leiomyosarcoma with rhabdomyoblastic differentiation have conducted to those arisen from another site, and they indicated a poorer prognosis of this tumor. CASE PRESENTATION: A 69-year-old woman was referred to our hospital for an operation concerning umbilical hernia. Subsequent imaging examinations before an operation indicated the presence of primary cardiac malignant tumor due to its atypical shape. And then, it was surgically removed. Histopathologically, tumor cells consisted of two different types: spindle and polyhedral cells. Immunohistochemically, it is interesting to note that 2.1% of spindle cells and 23.1% of polyhedral cells showed positive reactivity for myogenin. Furthermore, we performed double-immunostaining for alpha-smooth muscle actin (SMA) and myogenin. The rates of alpha-SMA and myogenin double negative, alpha-SMA single positive, myogenin single positive, and alpha-SMA and myogenin double positive in spindle cells were estimated as 69.1%, 28.8%, 1.1% and 1.0%, respectively. In contrast, the rates in polyhedral cells were estimated as 76.9%, 0.0%, 23.1%, and 0.0%, respectively. CONCLUSION: Our immunohistochemical evaluation suggested that rhabdomyoblastic differentiation in leiomyosarcoma might be generated not only by de novo generation from mesenchymal cells. To the best of our knowledge, this is the first case of primary cardiac leiomyosarcoma with partial rhabdomyoblastic differentiation.

Neuroendocrine Differentiation in Breast Cancer: Clinicopathological Significance of Bcl-2 Positive Solid Papillary Carcinoma.

Solid papillary carcinoma (SPC) is considered a rare malignant breast tumor. Maluf and Koerner first reported this disease entity as a special type of ductal carcinoma in situ with several characteristic histopathological features, including low-grade cellular atypia, intracellular or extracellular mucin deposition, and solid papillary growth pattern, as well as neuroendocrine differentiation. The present paper describes a case of SPC with bcl-2 expression, which is known as a marker for malignancy of neuroendocrine tumors. Interestingly, despite bcl-2 expression being a poor prognostic indicator of neuroendocrine tumors, the patient with this tumor has achieved long-term survival (approximately 6 years) at the time of writing this report. Because previous investigators reported that bcl-2 expression might play a role in the inhibition of the development of breast cancer, we suggest that bcl-2 expression might reflect a good prognosis in patients with SPC, rather than being a poor prognostic indicator, as it is in several types of neuroendocrine tumor. However, to confirm this hypothesis, further investigation is required.

Intraosseous Schwannoma of Rib With Severe Back Pain and Characteristic Pathological Findings.

A 44-year-old man was admitted to our hospital with severe back pain continuing for 12 years. Computed tomography of the chest revealed a 14 mm diameter tumor with calcification located in the right seventh rib. We performed right seventh rib and sixth to seventh intercostal muscle partial resection. Microscopically, the tumor showed typical features of a schwannoma composed of Antoni A and Antoni B tissues. The tumor had positive immunohistochemical staining for S-100 protein. The pathological diagnosis was intraosseous schwannoma. The patient's severe back pain disappeared and there was no recurrence or metastasis of the tumor during a 1-year follow up.

Investigation of ossification in the posterior longitudinal ligament using micro-focus X-ray CT scanning and histological examination.

BACKGROUND: Ossification in the posterior longitudinal ligament (PLL) correlates with changes of enthesis during the early stages of development, but this issue remains controversial, as little is known regarding the details of this process. The aim of the present study was to elucidate part of the ossification mechanism. Thus, in the present study, we observed and evaluated minute ossifications in the PLL that did not exhibit symptoms of ossification of the posterior longitudinal ligament (OPLL). METHODS: The subjects in the present study were derived from serial autopsy cases from January 2009 to December 2013 at Toho University Omori Medical Center, Japan. Minute ossifications in the PLL from autopsy subjects without any history of OPLL were screened as high-density areas using micro-focus X-ray CT, and the foci were histologically examined. Subsequently, we conducted both micro-focus X-ray CT image analysis and histological examination, and evaluated the correlation between these findings and putative predictive factors reported in previous studies. RESULTS: A total of 103 individuals among the 267 subjects involved in the present study were analyzed within the study period. There were no cases involving OPLL identification prior to death, and no subjects presented with neurological symptoms of myelopathy. The incidence of cases involving high-density areas greater than 0.1 mm(2) in the PLL was 46.6 %, half of which revealed mature bone structures inside this area. Thus, the high-density areas comprised three types: a continuous posterior-annular fibrosus type (23 cases), an isolated posterior-annular fibrosus type (11 cases), and a posterior-vertebral type (29 cases). However, a positive correlation was observed between the proportion of high-density areas, age (Pearson r = 0.265, p < 0.01), and HbA1c (Pearson r = 0.294, p < 0.01). Histological examination confirmed that these high-density areas involved calcification with or without mature bone formation. CONCLUSIONS: We evaluated minute foci of calcification with and without ossification in the PLL from 103 cadavers, generating the following observations: 1. Minute calcification foci greater than 0.1 mm(2) were observed in the PLL of 48 cases (46.6 %), half of which revealed mature bone structures inside this area (23.3 %). 2. The proportion of minute calcification foci observed in the present study was correlated with age and glucose tolerance, suggesting changes in the OPLL in the early stage. 3. Three different mechanisms of ossification were suggested: The two structures developed behind the disc might reflect the elongation of enthesis or rupture of annular fibrosus, while the remaining structure developed behind the vertebral body might reflect a dystrophic calcification-based bony metaplasia sequence.

A case of postoperative hepatic granuloma presumptively caused by surgical staples/clipping materials.

A 66-year-old man with postsigmoidectomy status for colon cancer received laparoscopic partial hepatectomy due to a hepatic mass with employing titanium clips were for a vascular clamp. Histological examination showed liver metastasis from sigmoid colon cancer. Twenty-nine months after the partial hepatectomy, a mass developed on the stump at the hepatic resection. Laparoscopic left lateral segmentectomy was conducted under suspicion of cancer recurrence and an automatic titanium stapling device was used. The macroscopically cut surface of the liver showed a grey-white solid nodule measuring 23 x 20 mm and involving metal clips. The nodule was consistent with granuloma microscopically. Twenty-three months after the segmentectomy, a mass reappeared on the hepatic radial margin and an open left lateral hepatic lobectomy was performed because of its growth tendency. Histopathological examination revealed granuloma similar to the previous instance. Since these nodules formed a granulomatous lesion surrounding metal staples/clips and evidence of caseous necrosis was lacking, granuloma due to surgical staples/clips was suspected. Sporadic case reports of postoperative pulmonary granuloma at the staple line have been published previously, but there are no articles detailing a case involving hepatic granuloma. We present our case as the first report of postoperative staple-line hepatic granuloma.

Genomic Analysis of Single Nucleotide Polymorphisms Asp299Gly and Thr399Ile in Japanese Patients with Invasive Aspergillosis.

Single nucleotide polymorphisms (SNPs) 1063A/G (Asp299Gly) and 1363C/T (Thr399Ile) in the gene encoding Toll-like receptor 4 (TLR4) increase susceptibility to invasive aspergillosis. However, limited information is available on the prevalence of these SNPs in Japan. Therefore, we surveyed these TLR4 SNPs by using formalin-fixed and paraffin-embedded tissue blocks obtained from autopsies of patients with invasive pulmonary aspergillosis. Tissue samples of approximately 30% patients were included in genomic analysis. However, none of these samples showed the presence of TLR4 Asp299Gly and Thr399Ile polymorphisms. Thus, the present study provided information on the prevalence of TLR4 SNPs in Japanese patients with invasive aspergillosis and indicated that these SNPs played a minor role in increasing the susceptibility of Japanese individuals to invasive aspergillosis.

Histological study of chronic pulmonary aspergillosis.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) has been accepted the criteria for the diagnosis of pulmonary Aspergillus infection. Whereas, either pathophysiology or signs of CPA remains still controversial. METHODS: In this study, we histopathologically investigated 25 specimens of CPA, surgically resected. RESULTS: 21 (84 %) of that comprised male. There were 21 cases with mild impairment of the immune system and/or a scar mostly due to old tuberculosis. There is a tendency for a negative correlation between peripheral blood white cell numbers and value level of beta-(1,3)-D-glucan. Four cases showed a granular fluorescent signal in granulation tissue surrounding the cavity without the fungal aspects itself. CONCLUSIONS: In conclusion, acute inflammatory exudate along the terminal respiratory tract is most significant pathophysiolocial complication of the CPA, caused to organizing pneumonia, which derives fatal respiratory failure. In addition, the viability of fungus does not concern extension of exudative inflammation at the site of erosion along terminal airway.

Comparison between the location and the histomorphological/immunohistochemical characteristics of noninvasive neoplasms of the ampulla of Vater.

To determine useful factors when selecting an appropriate procedure for noninvasive ampullary neoplasia, we investigated the relationship between the location and the histomorphological/immunohistochemical characteristics of 56 noninvasive ampullary neoplasms obtained by endoscopic papillectomy (EP). All subjects were classified according to histomorphology and location of neoplasms, and we evaluated the characteristics of each classified group using complementary immunohistochemical procedures. The CK20-positive rates of each location type were also evaluated. Subjects presented with 52 intestinal-type adenomas (low/high grade, 32:20) and 4 noninvasive pancreatobiliary papillary neoplasms (low/high grade, 1:3). Twenty-seven periampullary (peri-AMP)-type tumors and 23 extended-type tumors comprised the intestinal type, and the intra-ampullary (intra-AMP) type was composed of 4 pancreatobiliary and 2 intestinal histomorphological types. The CK20-positive rates of these 3 location types differed significantly (peri-AMP type, 50.6% ± 21.0%; extended type, 35.4% ± 18.6%; intra-AMP type, 6.9% ± 6.3%). The CK20-positive rate for intestinal-type tumors of the intra-AMP location type was lower than that of the peri-AMP location type. Intestinal-type tumors without CDX2 expression included extended and intra-AMP types, which are tumors that may show positive vertical margins when EP is performed. In this study, we found that an understanding of pancreatobiliary-type histology is an important aspect for the investigation of tumors involving the common channel of the ampulla. Furthermore, immunostaining of CDX2 and CK20 provides beneficial information if considering whether to perform an EP.

Applied gene histopathology: identification of Fusarium species in FFPE tissue sections by in situ hybridization.

Although accurate and rapid diagnosis of fusariosis is now required, morphological similarities among molds make it difficult to histologically differentiate Fusarium spp. from other molds. In this chapter, we present our in situ hybridization (ISH) technique as a valuable tool to identify Fusarium spp. and emphasize the usefulness of the technique.

Histopathological evaluation of the efficacy of antifungals for experimental Trichosporon bloodstream infection.

The efficacy of polyene macrolides to treat experimental Trichosporon bloodstream infection was evaluated by histopathological examination and viable cell counts in the kidneys of infected mice. Viable cell counts on the 5th day after infection confirmed that liposomal amphotericin B (L-AMB) is a more effective treatment than fluconazole (FLC) for mice infected with an azole-resistant strain of Trichosporon. Histological examination revealed that the administration of L-AMB induced a transformation from acute purulent inflammation caused by both azole-susceptible and -resistant strain infections to a chronic and subsiding form, whereas FLC failed to convert the acute inflammation induced by the azole-resistant strain to a subsiding form. Our results demonstrate that polyene macrolides can be used as an alternative therapy for infection of azole-resistant strains of Trichosporon and that histopathological evaluation is useful for elucidating the pathophysiology of an experimental Trichosporon infection.