Primordial odontogenic tumor : an immunohistochemical profile

Primordial Odontogenic Tumor (POT) is a recently described odontogenic tumor characterized by a variably cellular loose fibrous tissue with areas similar to the dental papilla, covered by cuboidal to columnar epithelium that resembles the internal epithelium of the enamel organ, surrounded at least partly by a delicate fibrous capsule. The purpose of this study was to investigate the possible histogenesis and biological behavior of this rare tumor by means of a wide immunohistochemical analysis of its epithelial and mesenchymal components. The immunoexpression of twenty-three different antibodies were evaluated in four cases of POT. The epithelial cells that cover the periphery of the tumor showed immunopositivity for Cytokeratins 14 and 19, while Amelogenin, Glut-1, MOC-31, Caveolin-1. Galectin-3, PITX2, p53, Bax, Bcl-2, Survivin and PTEN were variably expressed in focal areas. The mesenchymal component of the tumor was positive for Vimentin, Syndecan-1, PITX2, Endoglin (CD105), CD 34, Cyclin D1, Bax, Bcl-2, Survivin and p53. PTEN and CD 90 showed a moderate positivity. BRAF V600E and Calretinin were negative in all samples. Cell proliferation markers (Ki-67, MCM-7) were expressed in <5% of the tumor cells. According to these immunohistochemical findings, we may conclude that POT is a benign odontogenic tumor in which there is both epithelial and mesenchymal activity during its histogenesis, as there is expression of certain components in particular zones in both tissues that suggests this tumor develops during the immature (primordial) stage of tooth development, leading to its inclusion within the group of benign mixed epithelial and mesenchymal odontogenic tumours in the current World Health Organization classification of these lesions

Expression of hMLH1 and hMSH2 proteins in ameloblastomas and tooth germs

Mismatch repair proteins (MMRPs) are a group of nuclear enzymes that participate in the repair of base mismatches that occur during DNA replication in all proliferating cells. The most studied MMRPs are hMSH2 and hMLH1, which are known to be highly expressed in normal tissues. A loss of MMRPs leads to the accumulation of DNA replication errors in proliferating cells. Ki-67 is a biomarker regarded to be the gold-standard tool for determining cell proliferation by immunohistochemical methods. The aim of this study was to investigate the immunohistochemical expression of hMLH1, hMSH2 and Ki-67 proteins in ameloblastomas and tooth germs, to contribute to the understanding of the development of this odontogenic neoplasm. Immunohistochemical assays to determine the presence of proteins hMSH2, hMLH1 and Ki-67 were performed in 80 ameloblastomas (40 solid and 40 unicystic) and five tooth germs. Unicystic ameloblastomas showed higher MMRP expression (hMLH1: 62.5 ± 43.4; hMSH2: 83.3 ± 47.8) than did solid ameloblastomas (hMLH1: 59.4 ± 13.5; hMSH2: 75.8 ± 40.2). Additionally, the cell proliferation index assessed by Ki-67 was inversely proportional to the expression of MMRP. Comparison between tooth germs and ameloblastoma revealed significantly higher expression of hMLH1, hMSH2 and Ki-67 in tooth germs (p=0.02). The differences of MMRP and Ki-67 immunoexpression between ameloblastomas and tooth germ suggest that alterations in the MMRP mechanisms could participate in the biological behavior of ameloblastomas

Analysis of mTOR Inhibition-Involved Pathway in Ovarian Clear Cell Adenocarcinoma

This study was designed to clarify the mechanism of the mammalian target of rapamycin (mTOR)-hypoxia inducible factor-1 (HIF-1) pathway using the cultured cell strain derived from human ovarian clear cell adenocarcinoma (CCA). Everolimus (a derivative of rapamycin)-treated cells and non-treated cells did not show any difference in mTOR expression. But, phosphorylated-mTOR (p-mTOR) expression significantly decreased in the treated cells, and mTOR-related factors such as phosphorylated-4E-BP1 (p-4E-BP1), HIF-1α, and vascular endothelial growth factor (VEGF) in the downstream region of mTOR revealed a marked decrease in expression. The analysis of influences of the drug on the HIF-1α degradation system showed an increase in von-Hippel Lindau (VHL) expression in the treated cells. Increase of cleaved caspase-3, one of key factors involved in apoptosis, was also shown in the treated cells. In the next step, using nude mice implanted with RMG-1 cells, a decrease in tumor size was demonstrated in 4 of the 7 mice which were orally administered with everolimus. As a result, it was suggested that everolimus administration would be helpful as an anti-tumor therapy for CCA not only via down-regulation of p-mTOR but also degradation of HIF-1α by VHL and induction of apoptosis by cleaved caspase-3

Treatment Strategy for Recurrent and Refractory Epithelial Ovarian Cancer: Efficacy of High-Dose Chemotherapy with Hematopoietic Stem Cell Transplantation

According to population statistics in Japan, approximately 3,800 women die of ovarian ­cancer annually, and approximately 6,000 are affected by this disease. Ovarian cancer is ­referred to as a “silent tumor”, since patients have few subjective symptoms and by the time symptoms are observed, the cancer has progressed to Stage III or IV in about half of the patients. The basic treatment for advanced epithelial ovarian cancer is to remove as much of the tumor as possible, and subsequently to perform anticancer therapy using drugs such as cisplatin, carboplatin and paclitaxel, all of which have been shown to be effective for epi­thelial ovarian cancer. However, the 5-year survival rate in advanced ovarian cancer patients is still only about 20%, and a treatment that leads to long-term survival has yet to be developed. Here, we review the available treatments for ovarian cancer, and present the results of high-dose chemotherapy (HDC) performed in our hospital for recurrent and refractory ­ovarian cancer

Alterations in Mucin Expression in Ovarian Mucinous Tumors: Immunohistochemical Analysis of MUC2, MUC5AC, MUC6, and CD10 Expression

The aim of this study was to evaluate the immunohistochemical expression of MUC2, MUC5AC, MUC6, and CD10 in ovarian mucinous adenoma (MA), mucinous borderline tumor (MB), and mucinous adenocarcinoma (MC), and to analyze the relationship between prognosis and these expressions. The expression of MUC2, MUC5AC, MUC6, and CD10 was evaluated by immunohistochemical analysis in 29 cases of MA, 29 cases of MB, and 26 cases of MC and scored based on the percentage of positive cells. Moreover, the ovarian mucinous tumors were classified into 4 phenotypes based on the staining patterns: intestinal, gastrointestinal, gastric, and unclassified patterns. The gastrointestinal pattern and the expression of MUC2 and CD10 increased from MA to MC. Conversely, the gastric pattern and MUC5AC expression decreased from MA to MC. Low MUC2 expression in MC was correlated with a better long-term survival rate. MUC2 expression in MC may be a useful predictor of the clinical outcome. The expression patterns of MUC2, MUC5AC, MUC6, and CD10 indicated that intestinal metaplasia may arise from the gastric-like epithelium in MA and that a close association exists between carcinogenesis and intestinal metaplasia in major ovarian mucinous tumors

Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of vulvar cancer and vaginal cancer

BackgroundVulvar cancer and vaginal cancer are relatively rare tumors, and there had been no established treatment principles or guidelines to treat these rare tumors in Japan. The first version of the Japan Society of Gynecologic Oncology (JSGO) guidelines for the treatment of vulvar cancer and vaginal cancer was published in 2015 in Japanese.ObjectiveThe JSGO committee decided to publish the English version of the JSGO guidelines worldwide, and hope it will be a useful guide to physicians in a similar situation as in Japan.MethodsThe guideline was created according to the basic principles in creating the guidelines of JSGO.ResultsThe guidelines consist of five chapters and five algorithms. Prior to the first chapter, basic items are described including staging classification and history, classification of histology, and definition of the methods of surgery, radiation, and chemotherapy to give the reader a better understanding of the contents of the guidelines for these rare tumors. The first chapter gives an overview of the guidelines, including the basic policy of the guidelines. The second chapter discusses vulvar cancer, the third chapter discusses vaginal cancer, and the fourth chapter discusses vulvar Paget’s disease and malignant melanoma. Each chapter includes clinical questions, recommendations, backgrounds, objectives, explanations, and references. The fifth chapter provides supplemental data for the drugs that are mentioned in the explanation of clinical questions.ConclusionOverall, the objective of these guidelines is to clearly delineate the standard of care for vulvar and vaginal cancer with the goal of ensuring a high standard of care for all women diagnosed with these rare diseases

Reliability of clinical diagnosis and DIAGNOdent^<TM> measurement value for dental caries comparing with results of contact microradiographic examinations

齲蝕の治療を行うにあたり,齲蝕部位の病理組織学的診断を行うことは実際に不可能である。そのため,実際に行われている臨床診断の精度は明らかでない。本研究の目的は,ふだん行われている診査方法による臨床診断の信頼性,および術者間における診断の変動についてin vitroで調べることである。臨床診断にはエアーシリンジを用いた視診,探針による触診,それにエックス線診が使われた。試験には抜去歯が用いられ,臨床診断とコンタクトマイクロラジオグラム(CMR)による最終診断が比較された。レーザー型齲蝕検出装置であるDIAGNOdent^も客観的に臨床診断を行う方法として検討を行った。その結果,臨床診断のうち81%がCMRによる最終診断と一致した。4名の歯科医師の特異度はC_1で0.8から1.0,C_2で0.63から0.88だった。敏感度はC_1で0.5から0.83,C_2で0.88から1.0だった。Kappa係数は0.45から0.66だった。DIAGNOdent^と最終診断の一致率は50%だった。結論として,術者間の再現性は必ずしも高くはなく,共通の診断方法を使った場合でも術者によって臨床診断は変化するように思われた。したがって,臨床診断と最終診断は81%が一致したが,より正確な臨床診断を行うためにはさらなる研究が必要と思われる。一方,単独のDIAGNOdent^計測値は現在のところ,臨床診断ほどには信頼できないものだった。The histopathological diagnosis cannot be performed in the dental caries, and thus, accuracy of clinical diagnosis is uncertain. The purpose of this study is to examine the reliability of clinical diagnosis by conventional methods and to examine the diagnostic variation among examiners in vitro. Visual inspections using an air syringe, probing using a dental explorer and radiographic examinations were all used for clinical diagnosis. Clinical diagnosis and final diagnosis by the contact microradiography (CMR) were compared using extracted carious teeth. DIAGNOdent^, a laser fluorescence device for caries detection was also examined as an objective method for clinical diagnosis. As a result, 81% of the clinical diagnosis matched those from the CMR diagnosis. Specificity for clinical diagnosis of four dentists ranged between 0.8 and 1.0 (C_1) and between 0.63 and 0.88 (C_2). Sensitivity ranged between 0.5 and 0.83 (C_1) and between 0.88 and 1.0 (C_2). The Kappa values varied from 0.45 to 0.66. The results of DIAGNOdent^ measurements correlated with the final diagnoses at the rate of 50%. In conclusion, inter-examiner reproducibility was not always high and clinical diagnosis seemed to vary by examiners even when common conventional methods were used. Thus, in order to provide a more accurate clinical diagnosis more investigation seems to be necessary, though 81% of clinical diagnosis matched final diagnosis. On the other hand, DIAGNOdent^ measurement value alone was not as dependable as clinical diagnosis at present

複数の埋伏過剰歯を伴った石灰化嚢胞性歯原性腫瘍の1例

石灰化嚢胞性歯原性腫瘍(以下CCOT)は病理組織学的に,裏装上皮内にghost cellの出現とそれらの石灰化を特徴とし,また,歯牙腫をはじめとする歯原性腫瘍を合併することがある.さらに,CCOT症例の半数前後は埋伏歯を伴うことが知られているが,複数の埋伏過剰歯を伴うことは稀である。今回われわれは,歯牙腫と8本の埋伏過剰歯を伴ったCCOTの1例を経験したので,その概要を報告する.症例は40歳代の男性で,近歯科医院を受診した際にX線検査にて右側上顎洞部に嚢胞様透過像が認められ,精査・加療目的に当科紹介となった.初診時,上顎右側側切歯から右側第一大臼歯部の頬側歯肉に弾性軟の腫脹を認め,波動が触知された.CTにて,右側上顎洞および鼻腔の下部に境界明瞭で単胞性の嚢胞様病変を認め,病変内部に大小の石灰化像および歯牙様石灰化像を認めた.全身麻酔下にて摘出術および対孔形成術を施行した.摘出組織ではCCOTとともに歯牙腫ならびに8本の埋伏歯を認めた.病理組織学的に上皮層内にghost cellとその石灰化がみられた.文献的に本症例のように複数の埋伏過剰歯を伴ったCCOTはきわめてまれであった.It is well known that an associated impacted tooth is seen in about half of cases with calcifying cystic odontogenic tumor (CCOT), but CCOT with two or more impacted teeth is extremely rare. This paper reports a case of CCOT with 8 impacted, supernumerary teeth. The patient is an adult male with swelling of right maxilla. X-ray examination showed a cystic lesion with calcification and with numerous impacted, supernumerary teeth. A clinical diagnosis of CCOT with odontoma was made. And surgical excised of the lesion was performed. Macroscopically, surgically excised specimen showed eight supernumerary teeth with formal and/or unformal shape were involved in the lesion, but these teeth were not enclosed by fibrous capsule. The lesion was diagnosed finally as CCOT with odontoma and with eight impacted, supernumerary teeth by pathological examination. The review of the literature yielded CCOT with more than 3 associated supernumerary has not been documental

チタンメッシュトレーとPCBMによる下顎骨再建を施行した類腱型エナメル上皮腫の1例

類腱型のエナメル上皮腫(desmoplastic ameloblastoma:DA)は,エナメル上皮腫の一亜型で,豊富な膠原線維の増生からなる間質と石鹸泡状のエックス線透過像を特徴とする.DAは,X線学的に境界不明瞭で,腫瘍周囲の被膜がないため切除範囲の設定が困難で,典型的なエナメル上皮腫と比較して,再発の割合が高いと考えられている.2006年9月,58歳の男性が,下顎右側臼歯部歯肉の腫脹と顎骨の膨隆にて近医より当科を紹介受診した.画像所見において,腫瘍の境界は不明瞭で,腫瘍は下顎骨下縁にまで及んでいた.生検の結果,組織学的に類腱型のエナメル上皮腫と診断された.下顎区域切除術ならびにチタンメッシュトレーと腸骨からのPCBMによる下顎骨再建を施行した.術後4年経過した現在,再発はみられていない.Desmoplastic ameloblastoma (DA) is a variant of ameloblastoma, characterized by foamy radiolucency and desmoplastic stroma. The recurrence rate of DA is thought to be higher than that of usual ameloblastoma because the fibrous capsule surrounding the tumour is not present and decision of the resection area is difficult, corresponding to the radiographically poorly-defined tumour margin. A 58-year-old man was referred to our clinic in September 2006 because of swelling of the mandible on the right side. Radiography indicated a poorly-defined lesion that expanded to the inferior border of the mandible. We carried out a biopsy and a diagnosis of DA was made histopathologically. Then, we carried out segmental mandibulectomy and mandibular reconstruction using a titanium mesh tray and PCBM from iliac bone. No signs of recurrence have been seen for 4 years after surgery