大城 久

A 54-year-old man was admitted with obstructive jaundice. Computed tomography showed common bile duct stricture and a tumor around the celiac artery. Repeated endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic retrograde cholangiopancreatography (ERCP) as well as a laparotomic biopsy around the celiac artery were diagnostically unsuccessful. Since the bile duct stricture progressed, EUS-FNA and ERCP were performed a third time, finally leading to the diagnosis of diffuse large B-cell lymphoma. The treatment plan and prognosis of obstructive jaundice differ greatly depending on the disease. It is important to conduct careful follow-up and repeated histological examinations with appropriate modifications until a diagnosis is made.

【背景】膵神経内分泌腫瘍の細胞診断の際には,その特徴的な細胞所見を把握することが重要である.今回,典型的な膵神経内分泌腫瘍の1例を経験したので,その細胞所見を報告する.【症例】40歳代,男性.発熱と上腹部痛を主訴に近医を受診し,腹部造影CTで膵頭部に2cm大の腫瘤を認めたため,精査加療目的で当院に紹介受診となり,超音波内視鏡下膵穿刺吸引細胞診が施行された.そのPapanicolaou染色標本では,類円形核を呈する異型上皮様細胞が結合性の緩い充実性集塊～孤立性に出現しており,ロゼット配列や索状配列を呈していた.異型上皮様細胞の核はやや偏在性で,顆粒状の核クロマチンパターンを呈し,核小体を1～数個有していた.これらの細胞所見より膵神経内分泌腫瘍を推定した.その後,膵頭十二指腸切除術が施行され,病理組織学的に膵神経内分泌腫瘍,G1と診断が確定された.【結論】膵神経内分泌腫瘍の細胞診では,上述した特徴的な細胞所見を捉えることにより,組織型を推定することが十分に可能であると考える.(著者抄録)

【背景】体腔液中に出現する反応性中皮細胞は,ときに悪性細胞との鑑別を要する.今回,卵巣癌の術中腹水細胞診で腺癌細胞との鑑別を要した反応性中皮細胞の1例を経験したので,その所見を報告する.【症例】患者は40歳代女性で,下腹部痛と腰痛を主訴に当センターを紹介受診した.CT・MRI検査にて腹膜転移を伴う卵巣癌が疑われた.入院後,子宮および両側付属器,腹膜結節,大網切除術を施行し,術中腹水細胞診検査を行った.その腹水細胞診標本では,炎症性背景に,多空胞状でライトグリーン淡好性の細胞質を有するやや大型の細胞集塊が少量認められた.明細胞癌を含めた腺癌細胞との鑑別を要したが,核の腫大や核クロマチンの濃染性,核形不整,核・細胞質比の増高はいずれも軽度で,細胞質は小空胞状を示し,細胞の重積性は目立たなかった.よって,細胞判定は陰性とし,中皮細胞の反応性変化と報告した.最終的な病理診断は右付属器原発の高異型度漿液性癌,骨盤外腹膜転移あり,大網転移なし,FIGO Stage IIIC期となった.【結論】腹水の細胞診断において中皮細胞の形態学的多様性を理解することは,腺癌を含めた悪性細胞との鑑別に有用と考えられる.(著者抄録)

Chronic active Epstein-Bar virus infection (CAEBV) is known to cause various symptoms. Although pulmonary artery hypertension (PAH) has been reported as a cardiovascular complication of CAEBV, the mechanisms of PAH and the effects of treatment have not been fully elucidated. We experienced 4 adult patients with CAEBV complicated by PAH. All of them received treatment for PAH with a vasodilator followed by chemotherapy with or without allogeneic hematopoietic cell transplantation for CAEBV. In all of these patients, the transtricuspid pressure gradient improved under treatment with vasodilator, and further improvement was observed under treatment for CAEBV in 3 patients. Autopsy was performed in 2 patients, which revealed EBER-positive cells and a change in the pulmonary artery at each stage in the pathology. In conclusion, EBV-infected cells can cause vasculitis and finally PAH. However, PAH complicated with CAEBV can be improved by PAH medication and treatment of CAEBV.

Immunoglobulin G4 (IgG4)-related disease is established as a new clinical entity, characterized by high levels of plasma IgG4 and IgG4-positive plasma cell infiltration. However, the elevation of plasma IgG4 and infiltration of IgG4-positive cells have been observed in other diseases, including malignancy. We experienced a case of prominent IgG4-positive lymphadenopathy, which was diagnosed as a reactive lesion in response to lung cancer. The cancerous lesion was so small in size that it was difficult to reveal the coexisting lung cancer. Surgical lymph node biopsy and endobronchial ultrasound-guided transbronchial needle aspiration did not reveal lymph node metastasis of cancer. Mediastinal lymph node dissection finally revealed it. After the right upper lobectomy, the patient underwent postoperative chemotherapy and remains cancer-free after 1 year. Our case suggests that close examination and careful follow-up are necessary when IgG4-positive lymphadenopathy is observed.

Cytological detection of chordoma cells in the serosal cavity is challenging because of its rare presentation. Herein, we report a case of chordoma showing malignant pleural effusion accompanied by pleuropulmonary metastases in a 68-year-old woman. Cytological analysis was performed using pleural fluid obtained following thoracentesis. Conventional cytological staining demonstrated few clusters of large, atypical cells characterized by epithelial cell-like connectivity and rich cytoplasm with foamy and/or multivacuolar changes. The nuclei of these atypical cells were large and either round or oval with no conspicuous irregularities in the nuclear membrane. Periodic acid-Schiff staining of these atypical cells revealed fine granules in the cytoplasm. Giemsa staining showed foamy and/or multivacuolar cytoplasm in these cells, with metachromatic mucoid stroma in the surroundings. Immunocytochemistry analysis using cellblock showed these cells to be positive for broad cytokeratins, epithelial membrane antigen, S100 protein, vimentin, and Brachyury. To the best of our knowledge, this is the first case report in which chordoma cells were cytologically detected in pleural effusions. Our findings also suggest that conventional cytology combined with cellblock immunocytochemistry can increase the accuracy of chordoma cell detection in the serosal cavity.

Background Nonalcoholic fatty liver disease (NAFLD) is common in the general population but identifying patients with high-risk -nonalcoholic steatohepatitis (NASH) who are candidates for pharmacologic therapy remains a challenge. Purpose To develop a score to identify patients with high-risk NASH, defined as NASH with an NAFLD activity score (NAS) of 4 or greater and clinically significant fibrosis (stage 2 [F2] or higher). Materials and Methods This was a cross-sectional secondary analysis of data prospectively collected between April 2017 and March 2019 for a group of patients with NAFLD in Japan (Japan NAFLD, the derivation data set) with contemporaneous two-dimensional shear-wave elastography and biopsy-proven NAFLD (age range, 20-89 years). Three US markers (liver stiffness [LS, measured in kilopascals], attenuation coefficient [AC, measured in decibels per centimeter per megahertz], and dispersion slope [DS, measured in meters per second per kilohertz]) were determined, together with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and the AST-to-ALT ratio. The best-fit multivariate logistic regression model for identifying patients with high-risk NASH was determined. Diagnostic performance was assessed by using the area under the receiver operating characteristic curve (AUC). The findings were validated in an independent data set (Korea NAFLD; age range, 20-78 years). Results The Japan NAFLD data set included 111 patients (mean age, 53 years ± 18 [standard deviation]; 57 men), 84 (76%) with NASH. The Korea NAFLD data set included 102 patients (mean age, 48 years ± 18; 43 men), 55 (36%) with NASH. The most predictive model (LAD NASH score) combined LS, AC, and DS. Performance was satisfactory in both the derivation sample (AUC, 0.86; 95% CI: 0.79, 0.93) and the validation sample (AUC, 0.88; 95% CI: 0.80, 0.95). The LAD NASH score showed a positive predictive value of 86.5% and a negative predictive value of 87.5% for high-risk NASH in the derivation sample. Conclusion A score combining three US markers may be useful for noninvasive identification of patients with high-risk nonalcoholic steatohepatitis for inclusion in clinical trials and pharmacologic therapy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lockhart in this issue.

PURPOSE: Attenuation imaging (ATI) is a new noninvasive ultrasound technique for assessing steatosis grade (S). However, validated region-of-interest (ROI) sampling strategies are not currently available. We investigated the diagnostic performance of various ATI-ROI positions for determining histopathologic S in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: This retrospective study included 105 patients with biopsy-proven NAFLD. All attenuation coefficient (AC, dB/cm/MHz) measurements were obtained by the same hepatologist using a commercially available ultrasound system on the same day as liver biopsy. Mean (± standard deviation) age and body mass index of the patients were 53 (± 18) years and 27.1 (± 4.1) kg/m2, respectively. The numbers of patients with steatosis affecting < 5%, 5-33%, 33-66%, and > 66% of hepatocytes were 8, 50, 29, and 18, respectively. The ATI-ROI was placed at three different positions for AC measurement using a dedicated workstation: the upper edge of the area ROI, twice the depth of the liver capsule, and the lower edge of the area ROI. Diagnostic performance was evaluated using the area under the receiver-operating characteristic curve (AUC). RESULTS: The AUCs of AC at the three ATI-ROI positions were 0.734 (95% confidence interval [CI]: 0.470-0.998), 0.750 (0.639-0.861), and 0.878 (0.788-0.968) for S ≥ 1; 0.503 (0.392-0.615), 0.824 (0.741-0.907), and 0.809 (0.724-0.895) for S ≥ 2; and 0.606 (0.486-0.726), 0.849 (0.767-0.932), and 0.737 (0.626-0.848) for S = 3, respectively. CONCLUSION: For accurate steatosis grade assessment, the ATI-ROI should not be placed at the upper edge of the area ROI.

A 52-year-old man underwent pneumonectomy of the left lung for previously diagnosed primary spindle cell carcinoma (pT4aN1M0, stage III B) with programmed death-ligand 1 expression (tumor proportion score ≥95%) and without epidermal growth factor receptor gene mutation and anaplastic lymphoma kinase fusion gene. However, brain metastasis and chest wall tumor relapse occurred. Considering insufficient improvement with gamma knife treatment for brain metastasis and combination chemotherapy (paclitaxel, carboplatin, and bevacizumab), pembrolizumab monotherapy and palliative irradiation therapy for chest metastases were started after brain tumor volume reduction using craniotomy. Brain edema and chest wall metastases markedly improved following a pseudoprogression of the brain edema accompanied by a performance status decline; this effect continued until 11 cycles of pembrolizumab administration.

PURPOSE: Measurement of spleen stiffness (SS) using ultrasound (US) elastography is useful for predicting portal hypertension. However, the mechanism leading to increased SS remains unclear. We jointly developed a new US elastography system (Aplio i-series, Canon Medical Systems) that can easily measure organ viscosity (dispersion slope: DS). We analyzed the cause of increased SS by calculating the shear wave speed (SWs, which reflects fibrosis) and DS of the spleen in carbon tetrachloride (CCL4) rat liver cirrhosis models. METHODS: A total of 13 Sprague-Dawley rats were randomly divided into four groups (C group: 3 rats as control, 2D group: 3 rats injected with CCL4 twice in 1 week, 4D group: 4 rats injected 4 times in 1 week, 6W group: 3 rats injected twice a week for 6 weeks). The SWs and the DS of each group were calculated, and histopathological analysis was performed. RESULTS: The spleen SWs of the 6W group was significantly higher than that of the C group (p = 0.044). The spleen DS did not change after CCL4. The liver SWs of the 4D and 6W groups was significantly higher than that of the C group (p = 0.012 and 0.007, respectively) with fibrosis change on histopathology, and the DS of the 4D group was significantly higher than that of the C group (p = 0.033). Splenic fibrosis was confirmed in the 6W group, but inflammation and necrosis were not seen. CONCLUSION: SS increased due to fibrosis and can be predicted based on SWs and DS values.

症例は67歳,女性.乳癌検診異常で受診した.左乳房に低エコー腫瘤を認め,針生検の結果,腺様嚢胞癌が疑われた.左乳房温存術およびセンチネルリンパ節生検を施行し,病理組織学的診断はpT1N0M0 StageIA,腺様嚢胞癌(ER-,PgR-,HER2-,Ki-67 5%)であった.補助化学療法を考慮する症例であったが,予後良好と考えられたため,化学療法は省略し放射線治療のみ施行した.術後2年6ヵ月でCTにて左肺結節を指摘されたが,原発か転移性かの鑑別が困難であったため,胸腔鏡下左肺上葉切除およびリンパ節郭清を施行した.病理組織学的診断では腺様嚢胞癌の肺転移と診断された.他の特殊型乳癌が通常の浸潤性乳管癌に準じて補助化学療法を行うことが推奨されているが,乳腺腺様嚢胞癌は多くがtriple negative症例にも関わらず予後良好と言われ,腋窩リンパ節転移が陰性ならば補助化学療法は必要としないことが多い.今回,乳腺腺様嚢胞癌で術後肺転移を認めた症例を経験したので,若干の文献的考察を加え報告する.(著者抄録)

目的:Shear wave elastography(SWE)は,B型およびC型慢性肝炎で有効性が実証されているが,非アルコール性脂肪肝疾患(non-alcoholic fatty liver disease:NAFLD)の場合には有効性は限定的である.本研究は,肝生検によりNAFLDの確定診断を受けた患者に対し,SWEおよびFIB4 indexの精度を評価し,SWE測定に関するその他の組織学的パラメーターの影響を評価することを目的とした.方法:本研究は当施設の倫理委員会の承認を受けて行った.組織学的にNAFLDと診断された71名の患者(平均年齢50.8歳±15.7歳)を対象に調査した.患者全員にSWE(Aixplorer;SuperSonic Imagine)を用いて肝硬度測定を行い,FIB4 index(年齢,AST,ALT,血小板数に基づく)の測定を行った.SWE測定値は,NAFLD activity score(NAS)とFIB4 indexに基づいて組織学的特性と比較を行った.結果:肝線維化stage 3以上の診断で見られるROC曲線下の面積は,SWEの場合0.821(最適Cut off値13.1kPa,感度62.5%,特異度57.4%)で,FIB4 index(最適Cut off値1.41,感度71.9%,特異度53.9%)の場合は0.822であった.SWEを使用して測定した肝硬度の中央値は,肝線維化stage(P<0.001),炎症grade(P=0.018),風船様腫大grade(P<0.001)が上昇するにつれて,段階的に上昇し,肝脂肪化gradeが上がるにつれて段階的に上昇した(P=0.046).結論:SWEおよびFIB4 indexは,NAFLD患者の肝線維化stageを推定するのに役立つ非侵襲的方法である.しかし,重度の肝脂肪化の存在下では肝硬度測定に影響を及ぼし,肝線維化stageが過小評価される場合がある.(著者抄録)

INTRODUCTION: Breast adenomyoepithelioma (AME) is a rare tumor composed of myoepithelial cells and ductal or luminal cells. Most cases of AME are benign, but rare cases in which either or both cell types exhibited malignant features have been reported. Due to its rarity, no diagnostic criteria for malignancy have been established for AME. PATIENT CONCERNS: A 64-year-old woman presented with a mass in her right breast. Fine-needle aspiration cytology and biopsy examinations revealed lesions composed of spindle-shaped cells and round epithelial cells. AME was suspected, and partial mastectomy was performed. DIAGNOSIS: The tumor specimen showed AME, which mainly consisted of spindle-shaped myoepithelial cells with slight atypia, admixed with tubular luminal cells and small areas of atypical intraductal proliferative lesions. No apparent features of malignancy, such as necrosis or invasion, were seen in the myoepithelial cells or the luminal or intraductal component. However, the atypical intraductal component exhibited focal nuclear atypia, a cribriform pattern, and moderate to strong membranous human epidermal growth factor receptor 2 (HER2) immunoreactivity. HER2 amplification was detected in focal regions of the atypical intraductal component by fluorescence in situ hybridization (FISH), which resulted in a diagnosis of AME with ductal carcinoma in situ. OUTCOMES: The patient did not receive further therapy and was free from tumor recurrence at 23 months after the operation. CONCLUSION: HER2 FISH might be useful for evaluating suspected AME tumors for malignancy when an atypical ductal lesion that lacks definitive features of malignancy is encountered.

AIMS: Proliferative activity, evaluated from the Ki-67 index, is a strong prognostic factor in lung adenocarcinoma (LADC). Here, we optimized a procedure to measure the Ki-67 index and establish the best cut-off value. METHODS AND RESULTS: We examined 342 LADCs at stage I for the immunohistochemical expression of Ki-67 using different antibodies, MIB1 and SP6. The results revealed the superior specificity of SP6; therefore, SP6 was used in subsequent analyses. Slides were scanned with a virtual slide system. Using software, tumor cells were counted in a whole tumor. Thereafter, the tumor was evenly subdivided into 0.25-mm2 tiles. The frequency of positive cells was counted in each tile of an invasive area or the whole tumor. We calculated the number of tumor cells required to produce a 95% confidential interval (CI) <0.05. Additionally, we calculated coverage probabilities (CP) using two different methods, counting any number or 200 cells per tile. The results showed that we could meet our goal by counting 2000 cells from 10 random tiles (200 cells each) in invasive areas. CONCLUSIONS: We successfully developed an optimal procedure using an SP6 antibody, which provided CP >70% and CI of <0.05 in more than 90% of cases. Furthermore, we identified an optimal cut-off value of 0.12 with an alternative of 0.15, based on disease recurrence. This procedure and the cut-off values may be used in the routine pathological diagnosis of LADC.

Background Nonalcoholic steatohepatitis (NASH) is diagnosed with histopathologic testing, but noninvasive surrogate markers are desirable for screening patients who are at high risk of NASH. Purpose To investigate the diagnostic performance of dispersion slope, attenuation coefficient, and shear-wave speed measurements obtained using two-dimensional (2D) shear-wave elastography (SWE) in assessing inflammation, steatosis, and fibrosis and in the noninvasive diagnosis of NASH in patients suspected of having nonalcoholic fatty liver disease (NAFLD). Materials and Methods This prospective study collected data from 120 consecutive adults who underwent liver biopsy for suspected NAFLD and were enrolled between April 2017 and March 2019. Three US parameters (dispersion slope [(m/sec)/kHz], attenuation coefficient [dB/cm/MHz], and shear-wave speed [in meters per second]) were measured using a 2D SWE system immediately before biopsy. The biopsy specimens were scored by one expert pathologist according to the Nonalcoholic Steatohepatitis Clinical Research Network criteria (119 participants underwent a histologic examination). Diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUC) for the categories of inflammation, steatosis, and fibrosis. Results One hundred eleven adults (mean age, 53 years ± 18 [standard deviation]; 57 men) underwent a US examination. Dispersion slope enabled the identification of lobular inflammation, with an AUC of 0.95 (95% confidence interval [CI]: 0.91, 0.10) for an inflammation grade greater than or equal to A1 (mild), 0.81 (95% CI: 0.72, 0.89) for an inflammation grade greater than or equal to A2 (moderate), and 0.85 (95% CI: 0.74, 0.97) for an inflammation grade equal to A3 (marked). Attenuation coefficient enabled the identification of steatosis, with an AUC of 0.88 (95% CI: 0.80, 0.97) for steatosis grade greater than or equal to S1 (mild), 0.86 (95% CI: 0.79, 0.93) for steatosis grade greater than or equal to S2 (moderate), and 0.79 (95% CI: 0.68, 0.89) for steatosis grade equal to S3 (severe). Shear-wave speed enabled the identification of fibrosis, with an AUC of 0.79 (95% CI: 0.69, 0.88) for fibrosis stage greater than or equal to F1 (portal fibrosis), 0.88 (95% CI: 0.82, 0.94) for fibrosis stage greater than or equal to F2 (periportal fibrosis), 0.90 (95% CI: 0.84, 0.96) for fibrosis stage greater than or equal to F3 (septal fibrosis), and 0.95 (95% CI: 0.91, 0.99) for fibrosis stage equal to F4 (cirrhosis). The combination of dispersion slope, attenuation coefficient, and shear-wave speed showed an AUC of 0.81 (95% CI: 0.71, 0.91) for the diagnosis of NASH. Conclusion Dispersion slope, attenuation coefficient, and shear-wave speed were found to be useful for assessing lobular inflammation, steatosis, and fibrosis, respectively, in participants with biopsy-proven nonalcoholic fatty liver disease. © RSNA, 2020 Online supplemental material is available for this article.

We encountered a patient with multiple myeloma treated with autologous hematopoietic stem cell transplantation (HSCT) who developed repeated episodes of enteritis but regressed spontaneously. An endoscopic examination revealed no abnormalities, but biopsy specimens showed massive infiltration of CD4+ and EBER+ abnormal lymphocytes in which a high copy number of Epstein Barr virus (EBV) genomes was detected by quantitative polymerase chain reaction (qPCR). EBV infection was exclusively detected in CD4+ T-cells, leading to a diagnosis of EBV-positive CD4+ T-cell LPD. This case suggests that an immediate biopsy and examinations, including qPCR for EBV DNA, should be considered for patients with recurrent enteritis after autologous HSCT, regardless of endoscopic findings.

BACKGROUND: Capicua transcriptional repressor (CIC) -rearranged sarcoma is characterized by small round cells, histologically similar to Ewing sarcoma. However, CIC-rearranged sarcoma has different clinical, histological, and immunohistochemical features from Ewing sarcoma. It is important to differentiate between these tumors. CASE PRESENTATION: The patient is a 44-year-old man with a duodenal tumor diagnosed in another hospital who presented with a history of melena. Laboratory studies showed anemia with a serum hemoglobin of 6.0 g/dL. He was hospitalized and gastrointestinal bleeding was controlled successfully with endoscopy. However, he suffered from appetite loss and vomiting and progression of anemia a few weeks after presentation. Upper gastrointestinal endoscopy showed a circumferential soft tumor in the second portion of the duodenum and the endoscope could not pass distally. Computed tomography scan showed a greater than 10 cm tumor in the duodenum, with compression of the inferior vena cava and infiltrating the ascending colon. A definitive pathologic diagnosis could not be established despite four biopsies from the tumor edge. Due to gastrointestinal obstruction and progression of anemia, a pylorus-preserving pancreaticoduodenectomy with partial resection of the inferior vena cava and right hemicolectomy was performed as a complete tumor resection. The tumor was diagnosed as a CIC-rearranged sarcoma, but 2 months postoperatively local recurrence and distant metastases to the liver and lung were found. The patient died 3 months after surgery. CONCLUSIONS: Although the only definitive treatment for CIC-rearranged sarcoma is surgical resection, the CIC-rearranged sarcoma is highly malignant with a poor prognosis even after radical resection. More research is needed to establish optimal treatment strategies.

Shear wave (SW) dispersion imaging is a newly developed imaging technology for assessing the dispersion slope of SWs, which is related to tissue viscosity in diffuse liver disease. Our preclinical and preliminary clinical studies have shown that SW speed is more useful than dispersion slope for predicting the degree of fibrosis and that dispersion slope is more useful than SW speed for predicting the degree of necroinflammation. Thus, dispersion slope, which reflects viscosity, may provide additional pathophysiological insight into diffuse liver disease.

RATIONALE: Primary carcinosarcoma of the upper urinary tract is rare. Ureteral duplication is one of the most common urinary tract malformations. Additionally, the association between ureteral duplication and malignancy is unknown. To the best of our knowledge, no cases of malignant tumors diagnosed as carcinosarcoma with ureteral duplication have been reported. We herein report the case of a patient with carcinosarcoma of the ureteropelvic junction associated with incomplete ureteral duplication. PATIENT CONCERNS: A 60-year-old Japanese woman presented with painless gross hematuria. She had a history of total hysterectomy and chemotherapy for endometrioid carcinoma 5 years before. She had no history of occupational chemical exposure. DIAGNOSES: Radiographic imaging revealed right incomplete ureteral duplication, hydronephrosis, and a polypoid tumor in the ureteropelvic junction of the lower moiety of the right kidney. Urine cytology showed a small amount of degenerated atypical epithelial and nonepithelial cells. The transureteral biopsy specimen showed dysplastic urothelial cells and atypical myoid spindle cells. These findings were indefinite for malignancy. INTERVENTIONS: The patient underwent right nephroureterectomy. Pathological examination of the resected tumor showed a biphasic neoplasm composed of carcinomatous and sarcomatous components. The sarcomatous component was immunohistochemically positive for vimentin, desmin, h-caldesmon, and α-SMA and negative for pancytokeratin (AE1/AE3), low molecular weight cytokeratin (CAM 5.2), EMA, E-cadherin, GATA3, uroplakin 2, and p63. Based on these findings, we diagnosed the tumor as carcinosarcoma. OUTCOMES: The postoperative course was uneventful. No additional therapy was administered. The patient has remained alive without recurrence for 21 months since surgery. LESSONS: Carcinosarcoma can arise from ureteral duplication. Although the majority of carcinosarcomas of the upper urinary tract are diagnosed at an advanced stage and have a poor prognosis, some can have a less aggressive course. Further studies are needed to determine the association between ureteral duplication and malignancy.

口腔領域の細胞診は、ブラシや綿棒などで粘膜を擦過して細胞を採取するので、侵襲性が少なく、繰り返し実施可能である。そのため、口腔癌検診や初診時のスクリーニング目的に実施されることが多い。口腔粘膜疾患細胞診の判定区分について解説し、口腔潜在的悪性疾患(紅板症、白板症、口腔扁平苔癬)、口腔上皮性異形成、扁平上皮癌(上皮内癌含む)における病理学的および細胞学的な項目を中心に概説した。

Bile duct cancer is known to contain numerous fibroblasts, and reported to recruit cancer- associated fibroblasts by secreting platelet-derived growth factor-D (PDGF-D) which needs serine proteases, such as matriptase, to behave as a ligand. However, their expression pattern, and prognostic value have not been clarified. In this study, we investigated the clinicopathological significance of PDGF-D and matriptase expression in patients with extrahepatic bile duct cancer. The samples were obtained from 256 patients who underwent the surgical resection between 1991 and 2015, and the expression levels of PDGF-D and matriptase were evaluated immunohistochemically. Staining intensities and distribution were scored, and finally classified into low and high expression groups in cancer cells and stroma respectively. High expression of matriptase in the cancer stroma was detected in 91 tumors (40%). The high stromal matriptase expression was significantly associated with shorter recurrence-free survival (RFS) and overall survival (OS) (P = 0.0027 and 0.0023, respectively). Multivariate analyses also demonstrated that the stromal matriptase expression level was an independent influential factor in RFS (P = 0.0050) and OS (P = 0.0093). Our findings suggest that the high stromal matriptase expression was strongly associated with tumor progression, recurrence and poor outcomes in patients with extrahepatic bile duct cancer.

RATIONALE: Liver heterotopia associated with congenital diaphragmatic hernia (CDH) is a rare condition; to the best of our knowledge, only 17 cases have been reported to date. The histogenesis and clinicopathological features are largely unknown. We herein report 2 cases of liver heterotopia associated with CDH along with 17 cases described in the literature to shed light on their clinicopathological characteristics. PATIENT CONCERNS: Case 1 was a vaginally delivered male newborn who presented with respiratory distress immediately after birth. Case 2 was a female fetus who was found to have left-sided CDH during gestation. DIAGNOSIS: In case 1, a chest X-ray revealed left-sided CDH. In case 2, magnetic resonance imaging performed at 33 weeks of gestation revealed left-sided CDH. INTERVENTIONS: Case 1 underwent diaphragmatic patch repair surgery 3 days after birth. Histopathological examination following surgery in case 1 revealed the presence of ectopic liver tissue in the hernia sac. Case 2 was delivered by Cesarean section, and diaphragmatic patch surgery was performed 3 days after birth. During surgery, an isolated nodule was identified on the peritoneal side of the border of the defective foramen of the diaphragm. Histopathological examination following surgery in case 2 confirmed the presence of an epidermal cyst in the hernia sac. In addition, the isolated nodule was histopathologically found to be ectopic liver tissue. OUTCOMES: In Case 1, CDH recurred at 6 months after surgery, and a second patch repair surgery was performed. The surgically removed hernia sac was found to contain microscopic ectopic liver tissue on histopathology. Case 1 recovered well after surgery, and there was no critical change during the 10-month postoperative period. Case 2 recovered well after surgery, and there was no critical change during the 20-month postoperative period. LESSONS: There were no secondary pathological conditions associated with the presence of ectopic liver in CDH, such as torsion, infarction, rupture, intra-abdominal bleeding, or tumorization. Our observations suggest that liver heterotopia is a rare but asymptomatic condition in patients with CDH.

Little is known concerning the prognostic significance of the degree of lymphatic vessel invasion in pancreatic head cancer. To address this gap in knowledge, we retrospectively examined 60 patients with locally advanced, surgically resectable pancreatic head cancer who underwent pancreaticoduodenectomy and lymph node (LN) dissection.All cases were histopathologically diagnosed as ductal adenocarcinoma, stage II (25 pT3N0 cases, 35 pT3N1 cases). The following variables were investigated: age; sex; neoadjuvant therapy; adjuvant therapy; tumor size; tumor grade; invasion into the serosa, retropancreatic tissue, duodenum, bile duct, portal venous system and perineural area; cut margins; LN metastasis; and the number of invaded lymphatic vessels (LVI-score).Univariate analysis demonstrated that LN metastasis and an LVI-score ≥5 were significantly associated with poor disease-free survival. Multivariate Cox regression analysis confirmed that LN metastasis and an LVI-score ≥7 were significantly associated with poor disease-free survival. Additionally, LVI-scores ≥9 and ≥10 were comparable to or surpassed the significance of LN metastasis based on the hazard ratio. Univariate analysis demonstrated that tumor size >30 mm, duodenal invasion, LN metastasis and an LVI-score ≥2 were significantly associated with poor overall survival. Multivariate Cox regression analysis confirmed that LN metastasis and LVI-scores ≥9 and ≥10 were significantly associated with poor overall survival, and an LVI-score ≥10 was comparable to or surpassed the significance of LN metastasis based on the hazard ratio.Our study strongly suggests that a high degree of lymphatic vessel invasion is associated with a poor prognosis in patients with locally advanced, surgically resectable pancreatic head cancer.

To investigate the usefulness of shear-wave speed and dispersion slope measurements obtained, using an ultrasound elastography system in rat livers with various degrees of necroinflammation and fibrosis. A total of 25 male Sprague Dawley rats were randomly divided into 5 groups of 5 rats each: G0 (control), G1 (CCl4 injected twice a week for 1 wk), G2 (CCl4 injected four times a wk for 1 wk), G3 (CCl4 injected twice a wk for 6 wk) and G4 (CCl4 injected twice a wk for 10 wk). The shear-wave speed (m/s) and the dispersion slope ([m/s]/kHz) were measured. Histologic features (inflammation, necrosis and fibrosis) were used as reference standards. In multivariable analysis with histologic features as independent variables, the fibrosis grade was significantly related to shear-wave speed (p < 0.05) and the necrosis grade was significantly related to dispersion slope (p < 0.05). Dispersion slope is more useful than shear-wave speed for predicting the degree of necroinflammation.

組織学的に診断した非アルコール性肝疾患(NAFLD)24症例を対象として、超音波エラストグラフィによる画像パラメータと肝生検による組織学的パラメータの相関性を評価した。その結果、粘弾性に関連するshear wave(SW)speedと粘性に関連するdispersion slope、脂肪化の程度を反映する減衰値とAlanine aminotransferase、SW speedと線維化の指標であるFIB4、dispersion slopeとFIB4との間にそれぞれ有意な相関関係を認めた。また、SW speedは線維化を反映し、dispersion slopeは小葉内炎症を反映しており、減衰値は組織学的肝脂肪化と関連する傾向を認めた。SW speedとdispersion slopeはNAFLDの病態評価において有用な指標と考えられた。

PURPOSE: Shear wave elastography (SWE) has been validated in chronic hepatitis C and B; however, limited data are available in non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the accuracy of SWE and FIB4 index for the diagnosis of fibrosis in a cohort of consecutive patients with biopsy-proven NAFLD, and to evaluate the effects of other histologic parameters on SWE measurement. METHODS: Written informed consent was obtained from all patients, and this study was approved by our internal review board and ethics committee. Seventy-one patients with histologically proven NAFLD (mean age 50.8 years ± 15.7) were examined. All patients underwent SWE (Aixplorer™; SuperSonic Imagine) and FIB4 index (based on age, aspartate aminotransferase and alanine aminotransferase levels, and platelet counts) measurements. SWE measurements were compared with the histologic features based on the NAFLD activity score and FIB4 index. RESULTS: The area under the ROC curve for the diagnosis of hepatic fibrosis stage 3 or higher was 0.821 (optimal cut-off value 13.1 kPa, sensitivity 62.5%, specificity 57.4%) for SWE and 0.822 (optimal cut-off value 1.41, sensitivity 71.9%, specificity 53.9%) for FIB4 index. The median liver stiffness values measured using SWE showed a stepwise increase with increasing hepatic fibrosis stage (P < 0.001), inflammation score (P = 0.018), and ballooning score (P < 0.001), and showed a stepwise decrease with increasing hepatic steatosis stage (P = 0.046). CONCLUSIONS: SWE and FIB4 index are useful noninvasive tools for estimating the severity of fibrosis in NAFLD patients. However, the presence of severe steatosis may affect the liver stiffness measurement, resulting in underestimations of liver fibrosis.

Rationale: Solitary fibrous tumors are mesenchymal tumors presenting as fibroblastic neoplasms with prominent branching vascular patterns, which are often generated from the pleura. Most solitary fibrous tumors are benign however, some can turn malignant. High-grade sarcomas from solitary fibrous tumors include multidirectional histopathological components. Patient concerns: We describe our experience of a giant high-grade sarcoma with mixed components generated from a solitary fibrous tumor of the pleura in a 67-year-old female patient presenting with cough and left-sided chest pain. The patient had been diagnosed with a pleural mass in the left chest by X-ray about 30 years earlier. However, the tumor was allowed to grow, without surgical intervention, for a long time. Interventions: Thoracic surgeons performed the removal of the giant pleural tumor the tumor measured 18.0 × 14.5 × 10 cm in size, and was considered a giant tumor generated from the pleura of the left chest cavity. Diagnoses: The surgically removed tumor was solid and light brownish, and included myxoid and arabesque pattern lesions. The tumor also showed hemorrhagic and necrotic lesions. Moreover, spindle cells with less atypia, resembling fibroblasts, were noted. These spindle tumor cells were CD34- and Stat6-positive, suggesting a solitary fibrous tumor. Some of the spindle tumor cells were surrounded by thick collagenous fibers. Considering that the tumor originated from the parietal pleura, the tumor was defined as a solitary fibrous tumor in origin. The tumor also comprised high-grade sarcomatous components these included lipid-rich, rhabdomyosarcomatous, and pleomorphic components. The high-grade sarcoma component included bizarre tumor cells with severe atypia. Outcomes: Tumor recurrence occurred in the left chest about 4 months after the surgery, and the patient died 8 months postoperatively. Lessons: The present case clearly demonstrates that a solitary fibrous tumor can develop into high-grade sarcomatous overgrowth, including lipid-rich, rhabdomyosarcoma, and pleomorphic sarcoma components, if left untreated for a prolonged period. This case provides profound insights about the natural history, histogenesis, differentiation, and malignant transformation of solitary fibrous tumors.

四塩化炭素(CCL)投与にて急性肝障害モデルと肝繊維化モデルを作製し、各種病態における粘性と弾性との関係について考察した。5週齢の雄性SDラット25匹を用い、20匹にCCLを投与して急性肝障害モデルと肝繊維化モデルを作製し、残りの5匹は正常コントロール(G0)とした。CCL2回隔日投与群急性肝障害モデルG1群(n=5)、CCL4回連日投与急性肝障害モデルG2群(n=5)、CCL週2回6週間投与肝繊維化モデルG3群、CCL週2回10週間投与肝繊維化モデルG4群とした。実験の結果より、粘弾性に関連するSW伝搬速度と、粘性のみと関連するdispersion slopeとの間には弱い相関があるものの、dispersion slopeは弾性率とは独立した指標と捉えることができた。弾性は主に肝繊維化を反映し、粘性は主に肝臓の壊死・炎症を反映することが示唆された。粘性と関連する指標であるdispersion slopeは弾性率とは独立した指標であり、肝臓の病態を評価する上で有用であると考えられた。

Unilateral multiple adrenocortical micronodules (UMNs) constitute a rare subset of primary aldosteronism (PA) characterized by the hypersecretion of aldosterone derived from multiple small nodules in the zona glomerulosa of the unilateral adrenal grand. This case study describes a 49-year-old man with PA and UMNs who presented with muscle cramps at rest due to hypokalemia. The patient had a 6-year history of hypertension treated with antihypertensive drugs. Imaging studies revealed bilateral adrenal nodules as large as 5mm. Adrenal venous sampling confirmed unilateral PA; therefore, the patient underwent the removal of the affected adrenal gland. Macroscopically, the removed adrenal gland exhibited irregular adrenocortical thickening accompanied by ill-defined, adrenocortical macronodules as large as 6mm. The zona glomerulosa was histologically hyperplastic. However, an immunohistochemistry test of the steroidogenic enzymes revealed that these macronodules and the hyperplastic glomerular layer tested negative for CYB11B2. Moreover, we observed adrenocortical micronodules as large as 0.5mm that tested immunohistochemically positive for CYP11B2 and HSD3B2 but negative for CYP17A1 and CYP11B1. Thus, UMNs were diagnosed. This case instructively indicates that a grossly or histologically detectable nodular lesion is not necessarily a culprit lesion for PA. Therefore, functional histopathology is indispensable for the correct subclassification of PA.

<p>症例は39歳男性．37歳時に食道静脈瘤破裂で他院入院の際，両側肺門リンパ節腫脹および肺野粒状影を認め，リンパ節生検で非乾酪性肉芽腫を認めたため，肺サルコイドーシスの診断となった．食道静脈瘤のフォローアップと門脈圧亢進症の原因精査目的に当科紹介となった．腹腔鏡検査では肝表面は広範に凹凸不整で辺縁は鈍であった．また肝表面には粒状の白色結節が多数見られ，肝辺縁で一部癒合し斑状であった．同時に施行した肝生検では，非乾酪性肉芽腫を認め，肝表面の所見と合わせて，肝サルコイドーシスの診断に至った．肉芽腫は門脈域に認めており，門脈の壁外性圧迫や閉塞により門脈圧亢進症を来したと推定された．ステロイドによる加療を開始し，1年近く経過しているが，肝障害は軽度改善し，食道静脈瘤は増悪なく経過している．肝サルコイドーシスに門脈圧亢進症を合併することは稀であり，腹腔鏡検査にて合併症なく診断できたので報告する．</p>

Background and Aims: A side-port needle has been developed to improve diagnostic accuracy by obtaining more cellular material during EUS-guided FNA (EUS-FNA). We compared the accuracy rate of histology and the quality of histologic specimens from 22-gauge (G) side-port and standard needles for EUS-FNA of a solid pancreatic mass in a multicenter, prospective, randomized control trial. Methods: Between January 2013 and September 2013, 160 consecutive patients with a suspected solid pancreatic mass at 5 tertiary referral centers were enrolled. Patients were randomized to the 22G side-port needle or 22G standard needle group. The primary endpoint was the diagnostic accuracy of histology. Secondary endpoints were the quality of the histologic specimen (quantity of tissue, degree of GI contamination, and amount of blood). Results: An analysis of 154 patients (side-port, 76, vs standard, 78) was performed. Six patients were excluded because of no pancreatic mass on EUS. There was no significant difference in the rate of diagnostic accuracy of histology (side-port, 87% [66/76], vs standard, 82% [64/78]; P = .51). Samples that enabled histologic interpretation were obtained in 64% (47/73) and 43% (33/77) of patients from the side-port and standard groups, respectively (P = .009). No significant difference was seen in the degree of GI contamination and amount of blood between groups. Conclusions: There was no significant difference in the accuracy rate of histology between needle types. The side-port needle was superior to the standard needle in terms of obtaining samples that enabled histologic interpretation.

Recent tissue microarray (TMA)-based studies have shown that cell proliferation- and apoptosis-related biomarkers are associated with clinical outcomes in patients with bladder urothelial carcinoma. However, little is known about the differences in these biomarker measurements between whole mount tissue preparations and TMAs. This study aimed to elucidate the discrepancy in the measurements of Ki-67 indices (KIs) and apoptosis indices (AIs) between whole mount tissue preparations and TMAs of bladder urothelial carcinoma samples.Whole mount tissue preparations for Ki-67 immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling were made from 30 patients who underwent transurethral resection of bladder urothelial carcinoma. Digital microscopy-assisted virtual TMAs, consisting of 3 small round areas (1 or 0.6 mm in diameter), were generated from the same whole mount tissue preparations. The measurement results in highly reactive areas of biomarkers were compared between the whole mount tissue preparation- and the TMA-based methods. Bland-Altman plot analysis, regression analysis, and Kendall τ were performed to investigate differences in the measurement results, systematic biases, and correlations between biomarkers.Although the Bland-Altman plot analysis demonstrated that almost all the plots were within the limits of agreement, fixed biases were detected in the 1- and 0.6-mm TMAs for the KI (0.181 and 0.222, respectively) and the AI (0.055 and 0.063, respectively). Proportional biases were also detected in the 1- and 0.6-mm TMAs for the AI (P < 0.001 and P < 0.001, respectively). Furthermore, positive correlations between KIs and AIs were observed in whole mount tissue preparations (r = 0.260, P = 0.044) and in the 1 mm TMAs (r = 0.375, P = 0.004); however, no such correlation was observed in the 0.6 mm TMAs.Our study suggests that the measurement results for certain biomarkers of bladder urothelial carcinoma obtained from TMA-based samples can be susceptible to systematic bias, and the lack of correlation between biomarkers cannot be avoided as it is in whole mount tissue preparations. Virtual TMAs can help identify systematic bias and establish a better sampling strategy prior to performing high-throughput TMAs for biomarker studies.

The aim of the present study was to investigate two methods of determining liver stiffness in rats with various degrees of non-alcoholic steatohepatitis induced by a methionine- and choline-deficient (MCD) diet by comparing each finding with reference to histopathological liver findings. Twenty male Wister rats were fed an MCD diet for up to 32 weeks, and four were fed a normal diet. Ultrasound-based shear wave elastography (SWE) and mechanical compression testing using an Instron Universal Testing machine were performed on each rat at designated time points. After each examination, liver histopathology was analyzed to evaluate the degrees of steatosis, inflammation, and fibrosis based on non-alcoholic fatty liver disease (NAFLD) activity score, and each finding was compared with reference to liver histopathologic findings. Median liver stiffness values measured using SWE showed a stepwise increase with increasing histological inflammation score (P = 0.002), hepatic fibrosis stage (P = 0.029), ballooning score (P = 0.012), and steatosis grade (P = 0.030). Median liver stiffness measured using an Instron machine showed a stepwise increase only with increasing histological fibrosis stage (P = 0.033). Degree of liver stiffness measured by SWE and the Instron machine differed. SWE reflected mainly inflammation, whereas Instron machine-derived values primarily reflected fibrosis. This is the main source of discrepancies between measurements made with these two modalities.

We previously investigated the utility of mu-oxo N,N'-bis(salicylidene) ethylenediamine iron (Fe(Salen)) nanoparticles as a new anti-cancer agent for magnet-guided delivery with anti-cancer activity. Fe(Salen) nanoparticles should rapidly heat up in an alternating magnetic field (AMF), and we hypothesized that these single-drug nanoparticles would be effective for combined hyperthermia-chemotherapy. Conventional hyperthermic particles are usually made of iron oxide, and thus cannot exhibit anticancer activity in the absence of an AMF. We found that Fe(Salen) nanoparticles induced apoptosis in cultured cancer cells, and that AMF exposure enhanced the apoptotic effect. Therefore, we evaluated the combined three-fold strategy, i.e., chemotherapy with Fe(Salen) nanoparticles, magnetically guided delivery of the nanoparticles to the tumor, and AMF-induced heating of the nanoparticles to induce local hyperthermia, in a rabbit model of tongue cancer. Intravenous administration of Fe(Salen) nanoparticles per se inhibited tumor growth before the other two modalities were applied. This inhibition was enhanced when a magnet was used to accumulate Fe(Salen) nanoparticles at the tongue. When an AMF was further applied (magnet-guided chemotherapy plus hyperthermia), the tumor masses were dramatically reduced. These results indicate that our strategy of combined hyperthermia-chemotherapy using Fe(Salen) nanoparticles specifically delivered with magnetic guidance represents a powerful new approach for cancer treatment.