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In this study, a 76-year-old man initially diagnosed with branch-duct pancreatic intraductal papillary mucinous tumor is presented. During follow-up, stenosis was discovered in the main pancreatic duct of the tail. A nodular lesion was found in the pancreatic duct consistent with the stenosis. Distal pancreatectomy was performed since it was suspected to be malignant. Histopathology revealed polymorphic mononuclear cells proliferated with osteoclast-like giant cells in the nodule. The patient was finally diagnosed with anaplastic pancreatic cancer with osteoclast-like giant cells, a relatively rare tumor. It is reported herein with a review of the literature.

We report a very rare case of an ectopic thyroid in the superior mediastinum, which was detected incidentally using imaging. The case was a 50-year-old woman patient. She had an orthotopic thyroid and normal thyroid function. This superior mediastinum mass obviously lacked continuity with the orthotopic thyroid. Its computed tomography density was lower than that of the orthotopic thyroid, and an enhancement was heterogeneously observed. In the cytodiagnosis, only large and small lymphocytes were observed, and malignant diseases such as malignant lymphoma could not be ruled out, so surgical resection was performed through a cervical incision. Combined resection of the thyroid was unnecessary, and ligation of the feeding vessels from the thorax side was able to be carried out without incident.

Hypopharyngeal cancer is a head and neck cancer with a poor prognosis, and most cases show metastases on diagnosis. Cervical lymph node (LN) metastasis is a poor prognostic factor in hypopharyngeal cancer patients. The identification of risk factors for LN metastasis can help guide surgical treatment strategies for these patients.This retrospective study included 93 superficial hypopharyngeal cancer patients with 109 histopathologically examined lesions treated by endoscopic resection between January 2007 and December 2017. Tumor thickness quantification, quantification of budding nests, immunostaining and other histopathological analyses in paraffin-embedded, formalin-fixed tissue sections (3-μm) of surgical specimens were performed by a certified pathologist.Cervical LN metastasis was positive in 18 out of 93 cases (19.3%) and 18 out of 109 lesions (16.5%). No differences were detected in patient characteristics between LN-positive and LN-negative cases, except for tumor thickness, which was significantly larger in LN-positive cases (3119.4±602.2μm vs. 1015.5±129.6μm, respectively; p0.0001). Univariate analysis showed that tumor thickness ≥1000μm (odds ratio: 5.559, p=0.003), lesions with high budding grade (odds ratio: 5.188, p=0.01) and vascular invasion (odds ratio: 12.710, p=0.007) were significantly associated with cervical LN metastasis. Multivariate analysis revealed tumor thickness≥1000μm as the most significant risk factor for cervical LN metastasis in superficial hypopharyngeal cancer (odds ratio: 3.639, p=0.04).We demonstrate for the first time that high budding grade may serve as powerful predictors of LN metastasis and tumor thickness ≥1000μm is a significant risk factor for LN metastasis of superficial hypopharyngeal cancer. These results should be further examined in future larger scale studies.

It is of current interest to target cancer metabolism as treatment for many malignancies, including ovarian cancer (OVC), in which few druggable driver mutations have been identified. Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in the NAD salvage pathway, is a potential therapeutic target in OVC. However, factors that determine responsiveness to NAMPT inhibition are not fully understood. Here, we report that OVC cell lines can be divided into subgroups exhibiting NAMPT-dependent or NAMPT-independent glycolysis, and these metabolic differences correlate with vulnerability to NAMPT inhibition. Interestingly, cells showing NAMPT-dependent glycolysis were enriched in a group of cells lacking BRCA1/2 gene mutations. Our findings suggest the importance of selecting appropriate patients for NAMPT-targeting therapy in OVC.

Introduction An extremely rare case of mixed squamous cell and glandular papilloma of the lung is reported. The correlation between the radiological and the pathological features as well as the clinical pitfall in making a diagnosis is discussed. Presentation of case An asymptomatic 68-year-old female with a cigarette smoking habit presented with a small nodule in her peripheral lung. A wedge resection was performed though it failed on-site diagnosis which was instead obtained following pathological scrutiny. The postsurgical course was excellent with no recurrence of disease. Discussion A small ground glass nodule gradually enlarged and transformed to a partially solid nodule a year and a half later. This transformation falsely made us suspect an early adenocarcinoma development. Eventually, the extremely rare subtype of pulmonary papilloma, with biphasic glandular and squamous cells, had been demonstrated to obstruct the peripheral bronchiole; and the adjoining alveoli had filled with a large volume of mucus. These pathological features seemed to have constituted the inner solid portion and the marginal ground glass portion respectively in the CT images, mimicking invasive lepidic adenocarcinoma. Conclusion Both pre- and intra-operative diagnoses are difficult mainly because of the rareness of the disease, however, mixed squamous cell and glandular papilloma may be considered in case the presence of primary adenocarcinoma is not validated., Highlights • Mixed squamous cell and glandular subtype is extremely rare pulmonary papilloma. • Initial presentation of this benign tumor had resembled early adenocarcinoma. • This disease should be taken into account in making a differential diagnosis.

Lung cancer is the most common cause of cancer mortality, however, efficient methods to culture, expand and transform lung epithelial (LE) cells have not been established. In the present study, an efficient ex vivo method was applied to recapitulate lung carcinogenesis using mouse LE cells. A Matrigel-assisted three-dimensional culture was used to isolate and selectively expand LE cells from mouse lungs. Purified LE cells were passaged and expanded for at least 2 to 3 months while maintaining epidermal growth factor-dependence. LE cells were also easily transformed by genetic manipulations using retroviral vectors. A SV40 large-T antigen, suppressing p53 and pRB, plus an activated oncogene, such as KrasG12V or EGFRex19del, were required to transform LE cells. Transformed cells formed tumors resembling non-small cell lung cancer (NSCLC) in allograft models and exhibited strong oncogene addiction. This experimental system provided a unique model system to study lung tumorigenesis and develop novel therapeutics against NSCLC.

In this report, unique endocervical glandular lesions exhibiting gastric differentiation were examined in a patient with Peutz-Jeghers syndrome. The result of the human papillomavirus (HPV) in situ hybridization (ISH) for the hysterectomy specimens was negative, but they demonstrated a papillary mucinous adenocarcinoma at the proximal endocervix continuous to atypical lobular endocervical glandular hyperplasia. Both contained MUC6-positive neutral mucin in cytoplasm, and showed different immunoreactivity to p16, Ki-67, and p53. Moreover, they harbored the identical K-RAS gene mutation suggesting that there was a common origin. Somatic K-RAS mutation and defective function of p16 may have been involved in the tumorigenesis of these unusual mucinous neoplasms.

Angiosarcoma arising in the pulmonary artery is extremely rare. We herein report a case of angiosarcoma arising in the pulmonary artery trunk of 71 year-old woman. This case was clinically diagnosed as pulmonary thromboembolism but angiosarcoma of the pulmonary artery should be considered as the differential diagnosis of unusual clinical manifestations of pulmonary thromboembolism because of the extremely poor prognosis of the lesion.

Mammary Analog Secretory Carcinoma (MASC) is a new entity of malignant salivary gland tumors that morphologically resembles mammary secretory carcinoma and carries the identical ETV6-NTRK3 fusion gene. We report our first case of MASC in Japan occurring in the parotid gland of a 37-year-old female patient with a t (12; 15) (p13; q25) translocation. Histologically, the tumor was composed of monomorphic cuboidal cells with low-grade vesicular nuclei and pale eosinophilic cytoplasm, and formed microcystic and tubular spaces with periodic acid-Schiff-positive secretion. Immunohistochemically, the tumor cells tested positive for cytokeratin, vimentin, and S-100 protein. MASC is a morphological mimicker of acinic cell carcinoma, but is a distinct neoplasm characterized by a specific chromosomal translocation. An accumulation of similar case studies is mandatory in order to clarify biological behaviors.

Summary Expression of PKM2, which diverts glucose-derived carbon from catabolic to biosynthetic pathways, is a hallmark of cancer. However, PKM2 function in tumorigenesis remains controversial. Here, we show that, when expressed rather than PKM2, the PKM isoform PKM1 exhibits a tumor-promoting function in KRAS G12D -induced or carcinogen-initiated mouse models or in some human cancers. Analysis of Pkm mutant mouse lines expressing specific PKM isoforms established that PKM1 boosts tumor growth cell intrinsically. PKM1 activated glucose catabolism and stimulated autophagy/mitophagy, favoring malignancy. Importantly, we observed that pulmonary neuroendocrine tumors (NETs), including small-cell lung cancer (SCLC), express PKM1, and that PKM1 expression is required for SCLC cell proliferation. Our findings provide a rationale for targeting PKM1 therapeutically in certain cancer subtypes, including pulmonary NETs.

We report an extremely rare case of primary clear cell carcinoma (CCC), not otherwise specified (NOS) of the nasal cavity. An 80-year-old woman was referred to our hospital with left nasal obstruction caused by a nasal cavity tumor. The tumor was resected completely with lateral rhinotomy approach. Histopathological examination revealed CCC. CCC metastasis from renal cell carcinoma (RCC), which is at the top of differential diagnosis, was ruled out by the absence of renal tumor at computed tomography (CT). Also, immunohistochemical results of the specimen with vimentin negative and CK7 focally positive excluded the possibility of RCC metastasis. The patient is free from recurrence 1 year after the surgery, and there is no evidence of RCC. In this report histopathological characteristics, especially immunohistochemical properties of primary CCC, NOS of the nasal cavity are presented together with some clinical features of this rare tumor. Also, we refer to histopathogenesis of primary CCC of nasal cavity in relation to myoepithelial carcinoma. Histopathological discussion is further extended to include other CCC and CCC-resembling histologies to confirm the uniqueness of the present case.

We previously reported that deficiency in the gene encoding the catalytic subunit of protein phosphatase 6 (Ppp6c) predisposes mouse skin tissue to papilloma formation initiated by DMBA. Here, we demonstrate that Ppp6c loss acts as a tumor promoter in UVB-induced squamous cell carcinogenesis. Following UVB irradiation, mice with Ppp6c-deficient keratinocytes showed a higher incidence of skin squamous cell carcinoma than did control mice. Time course experiments showed that following UVB irradiation, Ppp6c-deficient keratinocytes upregulated expression of p53, PUMA, BAX, and cleaved caspase-3 proteins. UVB-induced tumors in Ppp6c-deficient keratinocytes exhibited a high frequency of both p53- and γH2AX-positive cells, suggestive of DNA damage. Epidemiological and molecular data strongly suggest that UVB from sunlight induces p53 gene mutations in keratinocytes and is the primary causative agent of human skin cancers. Our analysis suggests that PP6 deficiency underlies molecular events that drive outgrowth of initiated keratinocytes harboring UVB-induced mutated p53. Understanding PP6 function in preventing UV-induced tumorigenesis could suggest strategies to prevent and treat this condition.

Case 1. A 48-year-old man with no history of hypertension was referred to our hospital with a 1 cm bladder tumor. According to cystoscopy, magnetic resonance imaging and 131I-MIBG scintigraphy, we diagnosed it as a paraganglioma of the bladder. Partial cystectomy was performed. The histological findings supported the diagnosis of paraganglioma of the bladder. Six years later, he was free of any evidence of recurrence. Case 2. A 64-year-old woman with hypertension was pointed out to have a 1cm bladder mass by ultrasound in a health examination. She was referred to our hospital for further examination. Cystoscopoy revealed a 1 cm intramural nodule covered by intact urothelium at the right posterior wall. Submucosal bladder tumor was not diagnosed as paraganglioma by cold punch biopsy. So, transurethral resection of the bladder tumor was performed for differential diagnosis. The tumor was hypervascular and involved the muscular layer of the bladder. Although a transient elevation of blood pressure occurred during the procedure, the tumor was resected as completely as possible. The histological diagnosis was paraganglioma of the bladder. She has been followed up for 27 months after operation without any evidence of recurrence.

Somatic mutations in the gene encoding the catalytic subunit of protein phosphatase 6 (Ppp6c) have been identified in malignant melanoma and are thought to function as a driver in B-raf- or N-ras-driven tumorigenesis. To assess the role of Ppp6c in carcinogenesis, we generated skin keratinocyte-specific Ppp6c conditional knockout mice and performed two-stage skin carcinogenesis analysis. Ppp6c deficiency induced papilloma formation with 7,12-dimethylbenz (a) anthracene (DMBA) only, and development of those papillomas was significantly accelerated compared with that seen following DMBA/TPA (12-O-tetradecanoylphorbol 13-acetate) treatment of wild-type mice. NF-κB activation either by tumor necrosis factor (TNF)-α or interleukin (IL)-1β was enhanced in Ppp6c-deficient keratinocytes. Overall, we conclude that Ppp6c deficiency predisposes mice to skin carcinogenesis initiated by DMBA. This is the first report showing that such deficiency promotes tumor formation in mice.

Mammary Analog Secretory Carcinoma (MASC) is a new entity of malignant salivary gland tumors that morphologically resembles mammary secretory carcinoma and carries the identical ETV6-NTRK3 fusion gene. We report our first case of MASC in Japan occurring in the parotid gland of a 37-year-old female patient with a t (12; 15) (p13; q25) translocation. Histologically, the tumor was composed of monomorphic cuboidal cells with low-grade vesicular nuclei and pale eosinophilic cytoplasm, and formed microcystic and tubular spaces with periodic acid-Schiff-positive secretion. Immunohistochemically, the tumor cells tested positive for cytokeratin, vimentin, and S-100 protein. MASC is a morphological mimicker of acinic cell carcinoma, but is a distinct neoplasm characterized by a specific chromosomal translocation. An accumulation of similar case studies is mandatory in order to clarify biological behaviors.

We reported a case of early cystic duct carcinoma concomitant with xanthogranulomatous cholecystitis (XGC). This case was a 72-year-old man in whom thickening of the gallbladder wall was pointed out an abdominal ultrasonography and elevation of the CA19-9 level was detected at a local clinic. Endoscopic ultrasonography and CT demonstrated a mass in the cystic duct. Mapping biopsy using peroral cholangioscopy (POCS) revealed a diagnosis of cystic carcinoma with superficial flat growth, therefore a pylorus-preserving pancreatoduodenectomy was performed. Histopathological diagnosis was well differentiated papillotubular adenocarcinoma with superficial flat spread and the thickening of the gallbladder wall was XGC. A case of early cystic duct carcinoma concomitant with XGC is extremely rare.

Cutaneous bronchogenic anomalies are rare. We report a 4-year-old boy who presented with a tumour and relapsing infection in the right scapular region. Histopathological examination of this tumour revealed a subcutaneous cystic legion formed by ciliated columnar epithelium with smooth muscle bundles and squamous epithelium with sebaceous glands.

Method for simultaneous determination of asulam, oxin-copper, thiuram, simazine (CAT), mecoprop, napropamide, iprodione, bensulide (SAP) and pencycuron in water was investigated by high performance liquid chromatograpy (HPLC) . Pesticides in waters were absorbed on polystyrene gel mini cartrige. And then the pesticides on cartrige were eluted with acetonitrile and determined by high performance liquid chromatograph equipped with a column of RS pak DE-613 or NOVAPAK C18. The recoveries of these pesticides in distilled water were more than 80% except asulam and oxin-copper. And those in river water were more than 89% except oxin-copper. But those in tap water were less than 36% except mecoprop, iprodione and pencycuron. These low recoveries were caused by residual chlorine in tap water.

Diniconazole の主成分である (R)-(E)-1-(2, 4-dichlorophenyl)-4, 4-dimethyl-2-(1, 2, 4-triazol-1-yl)-1-penten-3-ol〔以下(R)-Eと略す〕の反復投与時のラットにおける代謝を調べた. トリアゾール基を14Cで標識した (R)-Eを125mg/kgの割合で連続14日間 (第0日～第13日) 毎日1回経口投与すると, 14Cは, 最初の数日間比較的遅く, その後速く, 第20日までに実質上完全に尿および糞中に排泄された. 組織中の14C濃度は第1および第6日に高かったが, その後低下して第10日および第14日には一定値を示した. 第20日の組織中14C濃度は1μg (R)-E相当量/g組織あるいはそれ以下に低下し, 14Cの組織への顕著な蓄積や残留は認められなかった. 第0日～第3日の排泄物中の主要代謝物はメチル基の酸化物であり, 第11日～第14日と同様であった. Diniconazole を125mg/kgの割合で1回経口投与すると, 肝ミクロソームの cytochrome P-450含量は投与後3時間目には著しく低下したが, 8時間目には回復し, 24時間目には顕著に増加した. 同様な変化はミクロソームの薬物代謝酵素活性にも認められた. 肝ミトコンドリアの cytochrome 含量や電子伝達系酵素活性には影響を認めなかった. Diniconazole は, 肝ミクロソーム cytochrome P-450と結合して典型的なII型スペクトルを示し, アニリン水酸化を非拮抗的に阻害した.

14C標識 esfenvalerate [(S)-α-cyano-3-phenoxybenzyl (S)-2-(4-chlorophenyl) isovalerate] を雌雄ラットおよびマウスに2.5mg/kgまたは2.5mg/kg/dayで1回経口または10日間連続経口投与を行なった. 投与14Cは速やかにかつほぼ完全に尿糞中に排泄された. 14C組織残留量は脂肪以外で全般的に非常に低かった. 主要代謝反応は1) 酸側の2-, 3-位とアルコール側の2′-, 4′-位の酸化, 2) エステル結合の開裂および3) グルクロン酸, 硫酸, グリシンまたはタウリンとの抱合反応であった. 14C-esfenvalerate と fenvalerate [(RS)-α-cyano-3-phe-noxybenzyl (RS)-2-(4-chlorophenyl) isovalerate] の3非標識体 [(2S, αS), (2S, αR) および (2R, αR)] との等量混合物を1回または連続経口投与した. 14C-esfenvalerate の単独投与と比べて14C排泄率, 14C組織残留量および代謝物量に差異は認められなかった. このことは esfenvalerate の体内挙動は他異性体から独立していることを示唆している. また酸側14C標識 fenvalerate とesfenvalerate の代謝を比較すると fenvalerate が全般的に若干高い14C組織残留量を示した. これは fenvalerate だけから生成する cholesteryl (R)-2-(4-chlorophenyl) isovalerate によるもので, この生成以外には esfenvalerate と fenvalerate の生体内運命に大きな差異はなかった.

A 40-year-old man presented with acute scrotum. He was afebrile and had no other symptoms. Color Doppler sonography of the scrotum was performed at 24 hours after the onset of pain and demonstrated avascularity of the left testis. The right testis was normal. Under the diagnosis of testicular torsion the left testis was excised. Histopathological examination revealed testicular vasculitis (fig. 1). The patient was subsequently evaluated for evidence of systemic disease. Laboratory tests, including complete blood count, erythrocyte sedimentation rate, liver and renal function tests, C-reactive protein, complement levels, antineutrophil cytoplasmic antibodies and hepatitis B surface antigen, were normal except for increased antinuclear antibody (titer 1:320, diffuse pattern). However, findings on examination were unremarkable and the diagnosis was PAN isolated to the left testis. After surgery no treatment was offered. The patient remained well with no clinical evidence of disease activity until 16 months after diagnosis, when sudden pain developed in the right scrotum. Sonography of the scrotum was performed at 48 hours after onset and showed avascularity of the right testis. Acute scrotum was diagnosed and emergency exploration was performed. An old blood clot was contained within the tunica albuginea without bleeding, so the right testis was excised. Microscopic examination demonstrated recurrent vasculitis (fig. 2). Autoimmune markers were normal except for increased antinuclear antibody (titer 1:160), so the patient was discharged home without additional treatment. A regimen of intramuscular injections of testosterone was started. At 22-month followup the patient had no signs of systemic PAN. DISCUSSION

Background: The mitotic kinase-encoding gene STK15/BTAK/ AuroraA is associated with aneuploidy and transformation when overexpressed in mammalian cells. STK15 overexpression activates an unknown oncogenic pathway that involves centrosome amplification and results in missegregation of chromosomes. Because clinical prognosis and tumor aneuploidy are tightly linked in human bladder cancer, we examined whether increased STK15 copy number and protein levels are linked to aneuploidy in bladder cancers. Methods: STK15 protein was visualized by immunohistochemistry in 205 formalin-fixed, paraffin-embedded human bladder tumors. STK15 gene copy number was evaluated in 61 tumors by Southern blot hybridization and in 21 of these 61 tumors by fluorescence in situ hybridization (FISH). Copy numbers of chromosomes 3, 17, 20, and 21 were evaluated by FISH with chromosome-specific probes. STK15 expression levels were related to histologic grade, stage, and DNA ploidy of the tumors and to the patients’ follow-up data. The chisquare test for association was used to analyze the relationship between STK15 expression and pathologic features. All statistical tests were two-sided. Results: Tumors with low levels of STK15 amplification (3–4 copies) showed minimal deviation in their chromosome copy number and diploid or near-diploid total nuclear DNA content. Tumors with higher levels of STK15 amplification (>4 copies) had a major increase of chromosome copy number and of their total nuclear DNA content, i.e., exhibited pronounced aneuploidy. Elevated expression of STK15 was strongly associated with parameters of clinical aggressiveness including high histologic grade (P

Adult neuroblastoma (ANB) is a rare and poorly recognized entity among a histologically defined group of small, round-cell tumors arising in the retroperitoneum and abdomen. Eight cases of ANB were compared with seven cases of primitive neuroectodermal tumor (PNET) in these locations to identify clinicopathologic features that could be used to distinguish between the two lesions. The ANB study group included four men and four women 22-74 years of age (mean 38 years). Five patients with ANB presented with inflammatory symptoms or elevated levels of catecholamines and their metabolites. Five of the ANB tumors were classified as undifferentiated and three as poorly differentiated with a background of neuropil. These cases often showed immunoreactivity for multiple neural markers such as CD56, chromogranin A, synaptophysin, neurofilament, and neuron-specific enolase, but were negative for CD99, cytokeratins, desmin, myogenin, smooth muscle actin, muscle-specific actin, CD34, S-100 protein, and CD45. In contrast, all of the PNETs were positive for CD99, and four (57%) were also positive for cytokeratins. Two cases of ANB of the undifferentiated subtype had ultrastructural features characteristic of neuroblastoma and lacked a chimeric transcript (EWS-FLI1or ERG), which is specific for PNET. All five patients with the undifferentiated subtype of ANB and six of the seven patients with PNET died of their disease within 3 years of discovery of the lesion. Our results show that ANB, although rare, should be considered in the differential diagnosis of patients with small, round-cell tumors in the retroperitoneum and abdomen. Appropriate immunohistochemical studies and laboratory examination enable pathologists to distinguish ANB from other differential diagnoses, especially PNET.

5-メトキシ-3-(2-メトキシフェニル)-1,3,4-オキサジアゾール-2(3H)-オン, metoxadiazone (Elemic®) のべンビン環14C標識体をSD系雌雄ラットに1mg/kgの割合で1回経口または皮下投与すると, 14Cは速やかに主に尿中へ排泄された. 尿中への14C排泄量は, 投与後1日間に投与量の68～75%, 7日間に80～90%であった. 糞および呼気への14C回収率はそれぞれ7～18%および0.1%であった. 肝, 腎および他の組織の14C濃度は投与後0.5～1時間目に最高となり, それぞれ4.1, 2.0および