掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/ctd2.158

その他URL： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ctd2.158

担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

担当区分：筆頭著者,　責任著者   掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

The prognostic significance of an architectural grading system for clear cell renal cell carcinoma (ccRCC) has recently been demonstrated. The present study aimed to establish a vascularity-based architectural classification using the cohort of 436 patients with localized ccRCC who underwent extirpative surgery and correlated the findings with conventional pathologic factors, gene expression, and prognosis. First, we assessed architectural patterns in the highest-grade area on hematoxylin and eosin-stained slides, then separately evaluated our surrogate score for vascularity. We grouped nine architectural patterns into three categories based on the vascular network score. "Vascularity-based architectural classification" was defined: category 1: characterized by enrichment of the vascular network, including compact/small nested, macrocyst/microcystic, and tubular/acinar patterns; category 2: characterized by a widely spaced-out vascular network, including alveolar/large nested, thick trabecular/insular, papillary/pseudopapillary patterns; category 3: characterized by scattered vascularity without a vascular network, including solid sheets, rhabdoid and sarcomatoid patterns. Adverse pathological prognostic factors such as TNM stage, WHO/ISUP grade, and necrosis were significantly associated with category 3, followed by category 2 (all p < 0.001). We successfully validated the classification using The Cancer Genome Atlas (TCGA) cohort (n = 162), and RNA-sequencing data available from TCGA showed that the angiogenesis gene signature was significantly enriched in category 1 compared to categories 2 and 3, whereas the immune gene signature was significantly enriched in category 3 compared to categories 1 and 2. In univariate analysis, vascularity-based architectural classification showed the best accuracy in pathological prognostic factors for predicting recurrence-free survival (c-index = 0.786). The predictive accuracy of our model which integrated WHO/ISUP grade, necrosis, TNM stage, and vascularity-based architectural classification was greater than conventional risk models (c-index = 0.871 vs. 0.755-0.843). Our findings suggest that the vascularity-based architectural classification is prognostically useful and may help stratify patients appropriately for management based on their likelihood of post-surgical recurrence.

DOI： 10.1038/s41379-021-00982-9

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1007/s00262-022-03204-6

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1016/j.urology.2021.11.006

担当区分：筆頭著者,　責任著者   掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.3390/cancers14041062

PubMed

担当区分：筆頭著者,　責任著者   掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.3390/biomedicines10020323

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1002/cjp2.232

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1111/iju.14648

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1136/jitc-2021-002922

国際・国内誌：国際誌  

組織学的に前立腺導内管癌(IDC-P)が認められた、前立腺神経内分泌癌(NEPC)発症の3症例について報告した。症例1は76歳男性で、アンドロゲン除去療法(ADT)開始から8年後に前立腺特異抗原が高値であったため再生検を行ったところ、NEPCであることが確認された。症例2は70歳男性で、ADT開始から3年後に多発性骨転移が認められ、その際に神経特異性エノラーゼの増加に伴い、NEPCが認められた。症例3は70歳男性で、初回の経尿道的切除標本の組織学的検査により、NEPCと確定診断された。また、NEPCの組織学的所見では、3症例ともに神経内分泌癌と腺房腺癌が多様な比率で混合して観察され、神経内分泌癌の構成成分ではシナプトフィジンとクロモグラニンAに陽性で、腺癌構成成分ではPSAとNKX3.1に陽性が認められた。さらに、3例の初回に行われたHE染色スライドを調べたところ、全3例からIDC-Pが検出され、過去に当院で前立腺生検を行い、初期生検標本が得られたNEPC患者全6例からも、IDC-P構成成分が同様に検出されていたことが確認された。本例により、前立腺初期の組織学的標本によるIDC-Pの検出から、NEPCへの形質転換が予測可能であることが示唆された。

担当区分：筆頭著者,　責任著者   掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.21873/anticanres.15271

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1016/j.euros.2021.03.009

担当区分：筆頭著者  

担当区分：責任著者   掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1111/pin.13060

PubMed

国際・国内誌：国際誌  

DOI： 10.1111/cup.13838

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1136/jclinpath-2020-206548

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1245/s10434-020-09075-4

PubMed

国際・国内誌：国際誌  

DOI： 10.1002/iju5.12157

担当区分：責任著者   掲載種別：研究論文（学術雑誌）   国際・国内誌：国内誌  

DOI： 10.1007/s10147-019-01543-6.

PubMed

国際・国内誌：国際誌  

DOI： 10.21037/atm.2019.09.77

PubMed

掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00428-019-02710-w

PubMed

その他URL： http://link.springer.com/article/10.1007/s00428-019-02710-w/fulltext.html

掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/cancers11101492

PubMed

国際・国内誌：国際誌  

DOI： 10.1111/papr.12782

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.juro.2018.08.046

掲載種別：研究論文（学術雑誌）  

Aims: Stratified mucin-producing intra-epithelial lesion (SMILE) and invasive stratified mucin-producing carcinoma (ISMC) are recently described cervical and penile lesions. We report an unusual case of mixed variant of penile squamous cell carcinomas with warty, usual and mucoepidermoid SMILE/ISMC features. Methods and results: A 62-year-old Japanese man had a glans penis lesion of one-and-a-half years’ duration, suggesting malignancy. Partial penectomy and left inguinal lymphadenectomy were performed. Pathological evaluation revealed a mixed squamous cell carcinoma with warty, mucinous and usual features. The mucinous component resembled mucoepidermoid carcinoma (MEC) and SMILE/ISMC. Glandular differentiation was absent. All the diverse tumour components were negative for p16, which was confirmed by negative human papillomavirus (HPV) genotyping. The mucinous component was diffusely positive for cytokeratin 7 and largely negative for cytokeratin 5 and p63. Fluorescence in-situ hybridisation did not detect rearrangement in the MAML2 or EWSR1 genes. The tumour was pathological stage pT2, pN1 (AJCC prognostic stage group IIIA) and was disease-free 26 months after surgery. Conclusions: The lack of glands in the mucinous areas suggested that MEC should be separated from adenosquamous carcinoma (ASC). Penile SMILE/ISMC may occur without dependence upon HPV status. Further studies will be necessary to determine the pathogenesis and definition of penile SMILE/ISMC, the presence of true MEC arising from the glans penis and the clinicopathological differences of penile ASC, MEC and SMILE/ISMC. Herein, we refer to the SMILE-like penile lesion as ‘mucinous penile intra-epithelial neoplasia’.

DOI： 10.1111/his.13438

掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/pin.12628

PubMed

担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

掲載種別：研究論文（学術雑誌）  

Objective: To evaluate the accuracy of a magnetic resonance imaging (MRI)-based Likert scoring system in the detection of clinically significant prostate cancer (CSPC), using MRI/ultrasonography (US) image-fusion targeted biopsy (FTB) as a reference standard. Patients and Methods: We retrospectively reviewed 1218 MRI-detected lesions in 629 patients who underwent subsequent MRI/US FTB between October 2012 and August 2015. 3-Tesla MRI was independently reported by one of eight radiologists with varying levels of experience and scored on a five-point Likert scale. All lesions with Likert scores 1–5 were prospectively defined as targets for MRI/US FTB. CSPC was defined as Gleason score ≥7. Results: The median patient age was 64 years, PSA level 6.97 ng/mL and estimated prostate volume 52.2 mL. Of 1218 lesions, 48% (n = 581) were rated as Likert 1–2, 35% (n = 428) were Likert 3 and 17% (n = 209) were Likert 4–5. For Likert scores 1–5, the overall cancer detection rates were 12%, 13%, 22%, 50% and 59%, respectively, and the CSPC detection rates were 4%, 4%, 12%, 33% and 48%, respectively. Grading using the five-point scale showed strong positive correlation with overall cancer detection rate (r = 0.949, P = 0.05) and CSPC detection rate (r = 0.944, P = 0.05). By comparison, in Likert 4–5 lesions, significant differences were noted in overall cancer detection rate (63% vs 35%
P = 0.001) and CSPC detection rate (47% vs 29%
P = 0.027) for the more experienced vs the less experienced radiologists. Conclusions: The detection rates of overall cancer and CSPC strongly correlated with the five-point grading of the Likert scale. Among radiologists with different levels of experience, there were significant differences in these cancer detection rates.

DOI： 10.1111/bju.13972

PubMed

掲載種別：研究論文（学術雑誌）  

Primary thymic adenocarcinoma is an extremely rare tumor, and thymic enteric type adenocarcinoma has recently been proposed as a distinct pathological entity. Herein, we report the first cytological description of thymic enteric type adenocarcinoma. A 29-year-old Japanese female without a significant past medical history was found to have an abnormal chest shadow. Chest computed tomography demonstrated a well-circumscribed tumor in the anterior mediastinum, and thymectomy was performed. The Papanicolaou staining of the touch smear of the resected tumor demonstrated tightly cohesive epithelial cell clusters in a necrotic background. These cells were cuboidal to columnar in shape and had large round to oval nuclei with conspicuous nucleoli. Some of these neoplastic cells had intracytoplasmic mucin. Immunocytochemically, the neoplastic cells were positive for cytokeratin 20 and CDX-2. Histopathological study revealed tubular and papillotubular neoplastic growth composed of cuboidal to columnar neoplastic cells that contained large round to oval nuclei. Some of the neoplastic cells had intracytoplasmic mucin. Immunohistochemical study confirmed the expression of cytokeratin 20 and CDX-2. The final diagnosis of thymic enteric type adenocarcinoma was made. The cytological and immunocytochemical features of this case led to a diagnosis of enteric type adenocarcinoma. However, these features alone cannot be differentiated from a metastatic adenocarcinoma arising from the gastrointestinal tract. Cytological examination of a fine-needle aspiration of the mediastinal tumor has been reported to be useful in making a diagnosis. Therefore, an awareness of this new pathological entity is important for differentiating a thymic tumor from a metastatic carcinoma in the thymus.

DOI： 10.1002/dc.23806

PubMed

掲載種別：研究論文（学術雑誌）  

Gene expression signatures are commonly used as predictive biomarkers, but do not capture structural features within the tissue architecture. Here we apply a 2-step machine learning framework for quantitative imaging of tumor vasculature to derive a spatially informed, prognostic gene signature. The trained algorithms classify endothelial cells and generate a vascular area mask (VAM) in H&E micrographs of clear cell renal cell carcinoma (ccRCC) cases from The Cancer Genome Atlas (TCGA). Quantification of VAMs led to the discovery of 9 vascular features (9VF) that predicted disease-free-survival in a discovery cohort (n = 64, HR = 2.3). Correlation analysis and information gain identified a 14 gene expression signature related to the 9VF's. Two generalized linear models with elastic net regularization (14VF and 14GT), based on the 14 genes, separated independent cohorts of up to 301 cases into good and poor disease-free survival groups (14VF HR = 2.4, 14GT HR = 3.33). For the first time, we successfully applied digital image analysis and targeted machine learning to develop prognostic, morphology-based, gene expression signatures from the vascular architecture. This novel morphogenomic approach has the potential to improve previous methods for biomarker development.

DOI： 10.1038/s41598-017-13196-4

掲載種別：研究論文（学術雑誌）  

Renal medullary carcinoma (RMC) is a highly aggressive renal cell carcinoma arising in the collecting system and requiring careful correlation with status of sickle cell trait. A panel of international experts has recently proposed provisional diagnostic terminology, renal cell carcinoma, unclassified, with medullary phenotype, based on encountering an extraordinarily rare tumor with RMC morphology and immunophenotype in an individual proven not to have a hemoglobinopathy. Herein, we extend this observation to a cohort of 5 such tumors, morphologically similar to RMC, lacking SMARCB1 expression by immunohistochemistry, but each without evidence of a hemoglobinopathy. The tumors arose in 4 men and 1 woman with a mean age of 44 years, occurring in 3 left and 2 right kidneys. Clinically, aggression was apparent with involvement of perinephric adipose tissue in all 5 cases, nodal metastasis in 4 of 5 cases, and death of disease in 4 of 5 cases within 3-27 months. Histologic sections showed poorly differentiated adenocarcinoma, often with solid and nested growth patterns, as well as infiltrative glandular, tubulopapillary, cribriform, or reticular growth. Rhabdoid and sarcomatoid cytomorphology was seen in a subset. All tumors showed PAX8 nuclear positivity and SMARCB1 loss, with OCT3/4 expression in 4 of 5 cases. In summary, this first series of renal cell carcinoma, unclassified, with medullary phenotype documents tumors with morphologic, immunophenotypic, and prognostic features of RMC occurring in individuals without sickle cell trait. Although greater biologic and molecular understanding is needed, the available evidence points to these cases representing a sporadic counterpart to sickle cell trait-associated RMC. (C) 2017 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.humpath.2017.07.006

PubMed

掲載種別：研究論文（学術雑誌）  

Aims: Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a high-grade, aggressive tubulopapillary carcinoma, arising predominantly in the setting of the hereditary leiomyomatosis-RCC syndrome of familial uterocutaneous leiomyomatosis and deficiency of FH. In contrast, succinate dehydrogenase (SDH)-deficient RCC is a lower-grade oncocytic carcinoma with cytoplasmic flocculence/vacuolation and inclusions, arising mostly in individuals harbouring germline mutations of subunit B of the SDH complex (SDHB). Herein we aim to report the clinicopathologic features of a novel form of FH-deficient RCC showing a low grade oncocytic morphology, reminiscent of SDH-deficient RCC.
Methods and results: These distinctive, low-grade oncocytic neoplasms, with solid, nested and focally tubular architecture (2-90 mm), arose in four males (aged 11-41 years). Uniform cytology of polygonal cells, with flocculent, vacuolated eosinophilic cytoplasm with scattered inclusions, fine chromatin, and inconspicuous nucleoli, was apparent. Despite these features suggestive of SDH-deficient RCC, each tumour was confirmed as an FH-deficient carcinoma with retained SDHB expression. One case showed a synchronous, anatomically separate, typical highgrade FH-deficient RCC; one other showed such a tumour at nephrectomy 4 years later. No progression has been noted at 3 and 7 years in the cases with only the SDH-like lesions; the two cases with separate, typical FH-deficient RCCs progressed.
Conclusions: In summary, we characterize a novel oncocytic type of FH-deficient RCC with a striking resemblance to SDH-deficient RCC, posing a diagnostic challenge and raising concerns about sampling and multifocality for syndrome-associated cases under surveillance protocols.

DOI： 10.1111/his.13183

掲載種別：研究論文（学術雑誌）  

We compared the clinical outcomes of pancreatic ductal adenocarcinoma (PDAC) resection after neoadjuvant chemoradiation therapy (NACRT) vs. chemotherapy (NAC).
The study population comprised 81 patients with UICC stage T3/4 PDAC, treated initially by NACRT with S-1 in 40 and by NAC with gemcitabine + S-1 in 41. This was followed by pancreatectomy with routine nerve plexus resection in 35 of the patients who had received NACRT and 32 of those who had received NAC. We compared the survival curves and clinical outcomes of these two groups.
The rates of clinical response, surgical resectability, and margin-negative resection were similar. The NACRT group patients had significantly higher rates of Evans stage &gt;= IIB tumors (29 vs. 0 %, respectively, p = 0.010) and negative lymph nodes (49 vs. 16 %, respectively, p = 0.021) than the NAC group patients. There was no difference in disease-free survival between the groups, but the disease-specific survival of the NAC group patients was better than that of the NACRT group patients (p = 0.034). Patients undergoing pancreatectomy with nerve plexus resection following NACRT had significantly higher rates of intractable diarrhea and ascites but consequently received significantly less adjuvant chemotherapy and therapeutic chemotherapy for relapse.
NACRT followed by pancreatectomy with nerve plexus resection is superior for achieving local control, but postoperative diarrhea and ascites may prohibit continuation of adjuvant chemotherapy or chemotherapy for relapse (UMIN4148).

DOI： 10.1007/s00595-016-1358-9

掲載種別：研究論文（学術雑誌）  

The patient was a 76-year-old woman who had noticed slight difficulty in swallowing in the 3 years prior to this presentation. Her dysphagia progressed while she was hospitalized following cervical cancer surgery. Esophagogastroduodenoscopy and an esophagram showed circumferential erosion and a stricture of the thoracic esophagus. Esophageal resection was performed; the resected specimens showed a stricture and wall thickening. Histologically, transmural hyperplasia, which consisted of inflammatory granulation tissue with the abundant infiltration of IgG4-positive plasma cells and lymphocytes, was observed. The patient was diagnosed with probable IgG4-related disease. IgG4-related esophageal disease presenting as esophageal lesions alone is a very rare condition.

DOI： 10.2169/internalmedicine.8095-16

PubMed

掲載種別：研究論文（学術雑誌）  

An emerging group of high-grade renal cell carcinomas (RCCs), particularly carcinomas arising in the hereditary leiomyomatosis renal cell carcinoma syndrome (HLRCC), show fumarate hydratase (FH) gene mutation and loss of function. On the basis of similar cytomorphology and clinicopathologic features between these tumors and cases described as tubulocystic carcinomas with poorly differentiated foci (TC-PD) of infiltrative adenocarcinoma, we hypothesized a relationship be-tween these entities. First, 29 RCCs with morphology of TC-PD were identified retrospectively and assessed for FH expression and aberrant succination (2SC) by immunohistochemistry (IHC), with targeted next-generation sequencing of 409 genes-including FH-performed on a subset. The 29 TC-PD RCCs included 21 males and 8 females, aged 16 to 86 years (median, 46), with tumors measuring 3 to 21 cm (median, 9) arising in the right (n = 16) and left (n = 13) kidneys. Family history or stigmata of HLRCC were identifiable only retrospectively in 3 (12%). These tumors were aggressive, with 79% showing perinephric extension, nodal involvement in 41%, and metastasis in 86%. Of these, 16 (55%) demonstrated loss of FH by IHC (14/14 with positive 2SC). In contrast, 5 (17%) showed a wild-type immunoprofile of FH+/2SC-. An intriguing group of 8 (28%) showed variable FH+ positivity, but with strong/diffuse 2SC+. Next-generation sequencing revealed 8 cases with FH mutations, including 5 FH-/2SC+ and 3 FH-/2SC+ cases, but none in FH+/2SC- cases. Secondly, we retrospectively reviewed the morphology of 2 well-characterized cohorts of RCCs with FH-deficiency determined by IHC or sequencing (n = 23 and n = 9), unselected for TC-PD pattern, identifying the TC-PD morphology in 10 (31%). We conclude that RCCs with TC-PD morphology are enriched for FH deficiency, and we recommend additional workup, including referral to genetic counseling, for prospective cases. In addition, based on these and other observations, we propose the term "FH-deficient RCC" as a provisional term for tumors with a combination of suggestive morphology and immunopheno-type but where genetic confirmation is unavailable upon diagnosis. This term will serve as a provisional nomenclature that will enable triage of individual cases for genetic counseling and testing, while designating these cases for prospective studies of their relationship to HLRCC.

掲載種別：研究論文（学術雑誌）  

AimsMost thymic carcinomas express the lymphocyte marker CD5 aberrantly. This study was performed to examine the role of the self-reactive CD5 antigen in thymic carcinoma.
Methods and resultsWe examined CD5 expression in thymic carcinoma in relation to the lymphoid stroma. All cases of thymic carcinoma examined expressed CD5. A number of CD5(+) lymphocytes were also present in the stroma of thymic carcinoma. The CD5(+) tumour areas were predominantly in contact with the lymphoid stroma, and the expression level was significantly lower in tumour cells than lymphocytes. Although p53 and Bcl-2 expression levels were significantly higher in thymic carcinoma than normal thymic epithelial cells (TECs), they did not differ between CD5(+) and CD5(-) areas. E-cadherin expression in thymic carcinoma was comparable with that of normal TECs, and it also did not differ between these areas. In contrast, both Ki-67 index and mitotic activity were significantly higher in thymic carcinoma than normal TECs, and they were significantly higher in CD5(+) than CD5(-) areas.
ConclusionsCD5 may be induced by interaction with CD5(+) lymphoid stroma, and may be related to tumour proliferation. CD5 induction may also be a significant and/or specific effect of the tumour microenvironment of the thymus.

DOI： 10.1111/his.12742

掲載種別：研究論文（学術雑誌）  

Renal anastomosing hemangiomas (RAH) has been recently proposed as a new entity. In this article, we summarize the clinicopathologic features of this tumor. RAH usually develops on a background of end-stage renal disease. Macroscopically, tumors are well-defined and their cut surface shows mahogany brown spongy tissue with epicenter in the renal medulla. Tumors are usually small, but larger lesions are reported. On microscopic examination, the tumor consists of sinusoid-like vascular channels lined by cuboidal endothelial cells with occasional hobnail-like appearance of endothelial cells closely mimicking splenic sinusoids. Eosinophilic hyaline globules may be present in the cytoplasm of neoplastic endothelial cells. Extramedullary hematopoiesis containing erythroid precursor and megakaryocytes may be present in the vascular lumens. Immunohistochemically, endothelial cells are positive for CD31 and CD34, but negative for D2-40, GLUT-1 and HHV8. The surrounding stroma around endothelial cells demonstrates positivity for a smooth muscle action. To date, there are no studies on molecular genetic aspects of RAH. This tumor is indolent based on site and size of the lesion, partial or nephrectomy is sufficient as a therapeutic modality.

DOI： 10.5114/pjp.2016.61443

PubMed

掲載種別：研究論文（学術雑誌）  

Chromophobe renal cell carcinoma (CRCC) with neuroendocrine differentiation (CRCCND) has only recently been described. Eighteen cases of CRCC with morphologic features suggestive of neuroendocrine differentiation were selected from among 624 CRCCs in our registry. The tissues were fixed in neutral formalin, embedded in paraffin, cut into 4- to 5-mu m-thick sections, and stained with hematoxylin and eosin. As CRCC with neuroendocrine features, tumors with following morphology were suggested: (1) trabecular/palisading/ribbon-like, gyriform, insular, glandular, and solid pattern; (2) uniform polygonal cells formed in small islets; and (3) cribriform pattern in combination with palisading. Selected cases were further analyzed using immunohistochemistry, electron microscopy, array comparative genomic hybridization, and fluorescence in situ hybridization. Cases were classified as CRCCND or CRCC with neuroendocrine-like features (CRCCND-L) based on the immunohistochemical expression of neuroendocrine markers: CRCCND, 4 cases, age range 49 to 79 years, size ranged from 2.2 to 22 cm, and CRCCND-L, 14 cases, age range 34 to 74 years, size range 3.8 to 16.5 cm. Follow-up information was available for 11 of 18 patients aged 0.5 to 12 years. Two of 4 CRCCNDs showed aggressive clinical course with metastatic spreading. Chromophobe renal cell carcinomas with neuroendocrine differentiation were focally positive for CD56 (4/4), synaptophysin (4/4), chromogranin A (1/4), and neuron-specific enolase (3/4). All 14 CRCCND-Ls were mostly negative or very weakly focally positive for some of the aforementioned markers. All 18 tumors were positive for cytokeratin 7 and CD117. Ultrastructural analysis showed poorly preserved neuroendocrine granules only in 2 of 4 analyzed CRCCNDs. Losses of chromosomes 1, 2, 6, and 10 were found in all analyzable CRCCNDs, whereas multiple losses (chromosomes 1, 2, 6, 10, 13, 17, and 21) and gains (chromosomes 4, 11, 12, 14, 15, 16, 19, and 20) were found in CRCCND-L. (c) 2015 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.anndiagpath.2015.05.001

掲載種別：研究論文（学術雑誌）  

Background: EUS-guided FNA (EUS-FNA) has been increasingly performed to obtain specimens for the pathological evaluation of patients with GI and pancreaticobiliary masses as well as lymphadenopathies of unknown origin. Photodynamic diagnosis by using 5-aminolebulinic acid (ALA) has been reported to be useful for enabling the visual differentiation between malignant and normal tissue in various cancers.
Objective: To evaluate the diagnostic accuracy of fluorescence cytology with ALA in EUS-FNA.
Design: A prospective study.
Setting: A single center.
Patients: A total of 28 consecutive patients who underwent EUS-FNA for the pathological diagnosis of a pancreaticobiliary mass lesion or intra-abdominal lymphadenopathy of unknown origin.
Interventions: Patients were orally administered ALA 3 to 6 hours before EUS-FNA. The sample was obtained via EUS-FNA for fluorescence cytology and conventional cytology. A single gastroenterologist performed the fluorescence cytology by using fluorescence microscopy after the procedure, independently of the conventional cytology by pathologists.
Main Outcome Measurements: The accuracy of fluorescence cytology with ALA in the differentiation between benign and malignant lesions by comparing the results of fluorescence cytology with the final diagnosis.
Results: Of the 28 patients included in the study, 22 were considered as having malignant lesions and 6 patients as having benign lesions. Fluorescence cytology could correctly discriminate between benign and malignant lesions in all patients. Therefore, both the sensitivity and specificity of fluorescence cytology were 100% in our study.
Limitations: Fluorescence cytology was performed by only 1 gastroenterologist with a small number of patients.
Conclusion: Fluorescence cytology with ALA in EUS-FNA may be an effective and simple method for differentiating between benign and malignant lesions.

DOI： 10.1016/j.gie.2015.01.031

掲載種別：研究論文（学術雑誌）  

Infantile malignant osteopetrosis (IMO) is a rare and fatal autosomal recessive condition characterized by a generalized increased in bone density. Hematopoietic stem cell transplantation (HSCT) is the only effective and rational therapy with achieving long-term disease-free survival. However, complications with HSCT for IMO remain unclear. Here we describe a male infant with IMO, carrying two novel mutations in the T-cell immune regulator 1 (TCIRG1) gene. The TCIRG1 gene encodes the a3 subunit of vacuolar H+-ATPase that plays an essential role in the resorptive function of osteoclasts. Direct sequencing of all 20 exons of the TCIRG1 gene revealed a single nucleotide change in exon 11 (c1305 G &gt; T), which causes the substitution of Asp (GAT) for Glu (GAG) at position 435, and a two-nucleotide deletion in exon 16 (c19521953 del CA), causing a frame-shift mutation. However, the functional consequence of each mutation remains to be determined. Allogeneic HSCT was performed in the patient at the age of nine months. Donor engraftment was achieved, and abnormal bone metabolism and extramedullary hematopoiesis were corrected. Graft-versus-host disease was mild (grade I). However, the patient died of complication of pulmonary arterial hypertension at seven months after the HSCT. Postmortem examination revealed prominent vascular wall thickening of the pulmonary artery and macrophage infiltration to alveoli. It should be noted that a patient with IMO has a risk for pulmonary arterial hypertension, and the evaluation of pulmonary arterial flow should be included in the assessment of each patient with IMO even after HSCT.

DOI： 10.1620/tjem.234.309

掲載種別：研究論文（学術雑誌）  

The aim of this study was to analyze the pathological features of prostatectomy specimens from patients with low-risk prostate cancer eligible for active surveillance (AS) and evaluate preoperative data suitable for predicting upstaged (a parts per thousand yenpT3) or upgraded disease (Gleason score of a parts per thousand yen7), defined as 'reclassification'.
A retrospective analysis of 521 consecutive radical prostatectomy procedures (January 2005 through to December 2011) performed at our institution without neoadjuvant hormonal therapy was performed. Eighty-four patients fulfilled the following criteria-clinical T1 or T2 disease, prostate-specific antigen (PSA) level of a parts per thousand currency sign10 ng/ml, one or two positive biopsies, and Gleason score of &lt; 7. Clinicopathological features at diagnosis were compared between patients with and without reclassification after radical prostatectomy.
Forty of 84 patients (47.6 %) had a Gleason score of a parts per thousand yen7, and 8 (9.5 %) had upstaged disease (a parts per thousand yenpT3). Seven patients with upstaged disease also showed upgraded reclassification. Two patients with reclassification showed biochemical recurrence at 59 and 89 months after surgery, respectively. Preoperative parameters evaluated included age, PSA level, PSA density (PSAD), clinical T stage, and number and percentage of positive prostate cores. Among 82 patients with complete data, univariate analysis showed that PSAD (ng/ml(2)) was a significant parameter to discriminate patients with reclassified disease and those without reclassified disease (p &lt; 0.001). Multivariate analysis revealed that PSAD was the only independent variable to predict disease with reclassification (p = 0.006).
Preoperative PSAD may be a good indicator for selecting patients eligible for AS in the Japanese population.

DOI： 10.1007/s10147-013-0553-6

掲載種別：研究論文（学術雑誌）  

Small cell carcinoma (SmCC) of the kidney is extremely rare. In this article, we present a review of SmCC of the kidney with the focus on clinical and pathobiological aspects. Macroscopically, this tumor often shows a bulky mass extensively replacing the renal parenchyma with vascular invasion and metastasis to lymph nodes. Histologically, the tumor is composed of small cells with scant cytoplasm, round to oval nuclei, finely granular chromatin and inconspicuous nucleoli. Rosette or tubular formation may be present Immunohistochemically, neoplastic cells show variable positivity for neuron-specific enolase, chromogranin A, synaptophysin, CD57 (Leu7) and CD56. A dot-like staining pattern for cytokeratin may also be observed. An electron microscopic examination may identify electron-dense neurosecretory granules in the cytoplasm. As a therapeutic option, nephrectomy and systemic chemotherapy should be considered. However, despite multimodal therapy, most patients have a dismal outcome and die of widely metastatic disease within one to two years. As there are limited genetic data on SmCC of the kidney, a large series studying this will be needed in the future.

DOI： 10.5114/PJP.2014.42664

担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）  

Chromophobe renal cell carcinoma (ChRCC) with neuroendocrine differentiation/ morphology (NED/NEM) is exceedingly rare. We present three cases of ChRCC with NED/NEM, two of which showed positivity for neuroendocrine markers on immunohistochemical analysis. Patients ranged in age from 49 to 79 years (mean: 64.3 years). One of the three patients died of metastatic disease to multiple organs. Of the remaining two patients, one is currently alive without disease and the other is alive with disease. Histologically, all three tumors were composed of conventional ChRCC and NEM showed glandular and rosette formation. Immunohistochemically, tumor cells were positive for CK7, KAI1, E-cadherin, and c-kit in both ChRCC and neuroendocrine areas in three cases. CD56 and synaptophysin immunoreactivity were detected in two cases
in only the neuroendocrine area in one case and in both components in the other. Neuroendocrine granules were ultrastructurally observed at both neuroendocrine and conventional areas of ChRCC. Array comparative genomic hybridization (CGH) study indicated losses of chromosomes 1, 2, 6, 10, 17, 21, and Y in both conventional ChRCC and NED in one case. In addition, losses of chromosomes 1, 2, 4, 6, 9, 10, 13, 16p, 17, and 21 were observed in both components of the remaining one tumor. Furthermore, loss of chromosome 5 was identified only in the neuroendocrine area in this case. We concluded that the neuroendocrine area may reflect dedifferentiation within ChRCC. It is possible that losses of chromosomes 4, 5, and 16p may be involved in the neuroendocrine differentiation or progression of ChRCC.

DOI： 10.1016/j.ehpc.2014.08.003

担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）  

We present a case of renal epithelioid angiomyolipoma (eAML)/perivascular epithelioid cell tumor (PEComa) with a TFE3 gene break visible by fluorescence in situ hybridization (FISH). Histologically, the tumor was composed of mainly epithelioid cells forming solid arrangements with small foci of spindle cells. In a small portion of the tumor, neoplastic cells displayed nuclear pleomorphism, such as polygonal and enlarged vesicular nuclei with prominent nucleoli. Marked vascularity was noticeable in the background, and perivascular hyaline sclerosis was also seen. Immunohistochemically, neoplastic cells were diffusely positive for alpha-smooth muscle actin and melanosome in the cytoplasm. Nuclei of many neoplastic cells were positive for TFE3. FISH analysis of the TFE3 gene break using the Poseidon TFE3 (Xp11) Break probe revealed positive results. Reverse transcriptase-polymerase chain reactions (RT-PCR) for ASPL/TFE3, PRCC/TFE3, CLTC/TFE3, PSF/TFE3, and NonO/TFE3 gene fusions all revealed negative results. This is the first reported case of renal eAML/PEComa with a TFE3 gene break, and it has unique histological findings as compared to previously reported TFE3 gene fusion-positive PEComas. Pathologists should recognize that PEComa with TFE3 gene fusion can arise even in the kidney.

DOI： 10.1007/s00795-012-0584-5

担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）  

Distinction of renal oncocytoma (RO) from chromophobe renal cell carcinoma (ChRCC) is important because their clinical behavior is different. As part of a search for the best available immunohistochemical markers to distinguish ChRCC from RO, we investigated the immunohistochemical profiles of these tumors. We selected 30 renal tumors consisting of ChRCC, typical variant (n = 14), ChRCC, eosinophilic variant (n = 6), and RO (n = 10). Their expression of cytokeratin (CK) 7, KAI1, epithelial-specific antigen (ESA), epithelial-related antigen (ERA), Claudin- 7, and Claudin-8 was studied using an autostainer. Immunoreactivity was assessed based on a combined score of the extent and intensity of staining. Compared to RO, a significantly higher percentage of the total ChRCCs stained positive for CK7 (85% vs. 10%, respectively), KAI1 (90% vs. 10%), ESA (95% vs. 10%), ERA (95% vs. 10%), and Claudin-7 (95% vs. 20%) (P &lt; 0.001). Additionally, there was a significant difference between the percentage of ChRCC eosinophilic variant (ChRCC-E) and RO that stained positive for KAI1 (100% vs. 10%, respectively), ESA (83% vs. 10%), and ERA (83% vs. 10%) (P &lt; 0.001). We recommend immunohistochemical analysis of KAI1, ESA, and ERA to distinguish ChRCC-E from RO.

DOI： 10.1007/s00795-011-0546-3

掲載種別：研究論文（学術雑誌）  

The aim of this study was to compare short-term surgical results in pancreatic cancer patients who underwent surgical resection after neo-adjuvant chemoradiation therapy (NACRT) using S-1.
The study population comprised 77 patients with pancreatic cancer between 2006 and 2010. Out of 34 patients who underwent staging laparoscopy between 2008 and 2010, 31 patients without occult distant organ metastasis underwent chemoradiation and of whom 30 underwent pancreatectomy (NACRT group). Of the other 43 patients, 36 underwent surgical resection in 2006-2008, followed by adjuvant therapy (adjuvant group). The primary endpoint was frequency of pathological curative resection (R0).
The new regimen of NACRT was feasible and safe. Twenty-eight of 30 (93%) patients in the NACRT group had R0 resection, which was significantly higher than in the adjuvant group (21 of 36 patients, 58%, p = 0.005). The number and extent of metastatic lymph nodes in the NACRT group (1 (0-25), N0/1; 18 of 38) was significantly lower than in the adjuvant group (2 (0-19), N0/1; 23 of 30), p = 0.0363). The frequency of intractable ascites in the NACRT group (eight of 30) was significantly higher than in the adjuvant group (two of 36, p = 0.035).
Neo-adjuvant chemoradiation therapy using S-1 followed by pancreatectomy can improve the rate of pathologically curative resection and reduces the number and extent of lymph node metastasis.

DOI： 10.1007/s11605-011-1795-0

掲載種別：研究論文（学術雑誌）  

Recent histological and clinical studies have suggested the existence of 2 distinct types of autoimmune pancreatitis (AIP): type 1 AIP related to IgG4, exhibiting lymphoplasmacytic sclerosing pancreatitis (LPSP), and type 2 AIP related to granulocyte epithelial lesions (GELs), exhibiting idiopathic duct-centric chronic pancreatitis (IDCP). We herein present a case of type 1 AIP with histologically proven LPSP with GELs. This patient had neither serum IgG4 elevation nor MPD narrowing. In this case, the clinically and histologically atypical findings for type 1 AIP are intriguing.

DOI： 10.2169/internalmedicine.51.6859

掲載種別：研究論文（学術雑誌）  

Clear cell papillary renal cell carcinoma (RCC) is a recently established disease entity. However, there are few reports on genetic study of this entity. We report such a case with focus on genetic study. A 57-year-old Japanese man was found to have 3 renal tumors. Histologically, two tumors showed findings of clear cell RCC; and the other tumor showed findings of clear cell papillary RCC that was characterized by papillary growth pattern of neoplastic cells in cystic space with purely clear cell cytology. Immunohistochemically, tumor cells of clear cell papillary RCC were diffusely positive for PAX2 and cytokeratin 7, but negative for CD 10, RCC Ma, and AMACR. In fluorescence in situ hybridization study for one clear cell papillary RCC, we detected polysomy for chromosome 7 and monosomy for chromosomes 17, 16, and 20. In addition, we detected mutation of VHL gene in clear cell RCC, but found no VHL gene mutation in clear cell papillary RCC. Finally, our results provide further evidence that clear cell papillary RCC may be both morphologically and genetically distinct entity from clear cell RCC and papillary RCC. (C) 2011 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.anndiagpath.2010.03.007

掲載種別：研究論文（学術雑誌）  

Recently, renal angiomyoadenomatous tumor (RAT) has been identified. However, there are no descriptions about clear cell renal cell carcinoma (RCC) with focal RAT-like features. A 33-year-old Japanese man was found to have a tumor in the left kidney. Macroscopically, the tumor extended into the perinephric fat tissue, and the cut surface showed the yellowish color. The histologic examination of the tumor consisted of 2 components of clear cell RCC and RAT-like area. The RAT-like area showed the admixture of epithelial cells with basophilic or clear cytoplasm and stromal component containing leiomyomatous stroma, fine capillary network, and pericytic network. Immunohistochemically, epithelial neoplastic cells in RAT-like area were diffusely positive for CD10 and RCC Ma. G-band karyotype showed the structural abnormality of chromosome 3 and both components of clear cell RCC and RAT-like area revealed the identical VHL gene mutation. Finally, pathologists should pay attention to the presence of clear cell RCC focally resembling RAT. (C) 2011 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.anndiagpath.2010.03.003

掲載種別：研究論文（学術雑誌）  

S100A1 is a calcium-binding protein and a member of the S100 family. Recently, S100A1 immunohistochemistry may be an available marker in the differential diagnosis between renal oncocytoma and chromophobe renal cell carcinoma (RCC). However, there are no reports on S100A1 expression in oncocytic papillary RCC that has been recently identified. In this article, we immunohistochemically examined the expression of S100A1 protein in 18 renal tumors including 4 renal oncocytoma, 10 chromophobe RCCs, and 4 oncocytic papillary RCCs. All the cases of renal oncocytoma and oncocytic papillary RCC showed a positive reaction for S100A1 with cytoplasmic pattern. In chromophobe RCC, 3 of 4 tumors with typical variant and 4 of 6 tumors in eosinophilic variant were completely negative for S100A1. Finally, S100A1 immunohistochemistry may be useful in distinguishing renal oncocytoma from chromophobe RCC, but it may be of no use in the differential diagnosis between renal oncocytoma and oncocytic papillary RCC.

DOI： 10.1007/s00795-009-0461-z

担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）  

Primary splenic mucinous cystadenocarcinoma (MCCa) is extremely rare, and only six cases appear to have been reported previously. We present herein a case of primary splenic MCCa resulting in pseudomyxoma peritonei (PMP). A 66-year-old Japanese woman presented to a hospital with a chief complaint of upper abdominal pain and a 7-year history of splenic cyst. Cyst rupture was noted on computed tomography, and splenectomy was performed. The abdominal cavity was filled with a large amount of gelatinous ascites, with the appearance of PMP. On the cut surface, multiple cysts containing mucinous material were found within and outside the spleen. Microscopically, splenic parenchyma was occupied by large mucinous pools focally lined with mucinous epithelial cells and mesothelial cell-like cells, which were considered benign. Outside the spleen, a low-grade MCCa component was found. No ectopic pancreatic or intestinal tissue was identified. Although most PMP cases are known to be caused by low-grade mucinous appendiceal tumor, the present case represents the first report of a splenic MCCa resulting in PMP.

DOI： 10.1007/s00795-010-0507-2

担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1365-2559.2010.03631.x

掲載種別：研究論文（学術雑誌）  

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is extremely rare; only four cases have been reported. Herein are presented the case reports of two Japanese male patients with thyroid-like LGNPPA. Macroscopically, these tumors were pedunculated polypoid masses on the roof of the nasopharynx. Microscopically, they were characterized by papillary and glandular epithelial proliferation. The papillae were complex and tightly packed with hyalinized fibrovascular cores and lined by columnar and pseudostratified cells with intervening spindle-shaped cells. Both cell types had round to oval vesicular nuclei with tiny nucleoli and mildly eosinophilic cytoplasm. Mitotic figures were not evident and necrosis was not observed. Psammoma bodies were seen focally in one of the patients. Transition from normal surface epithelium to tumor cells was identified in both cases. On immunohistochemistry the tumor cells were positive for cytokeratin (CK) 7, CK19, thyroid transcription factor-1 (TTF-1) and vimentin. They were negative for CK5/6, CK20, thyroglobulin, S-100 protein and CD15. In situ hybridization for EBV was negative. Nasopharyngeal tumors with similar morphological appearance should be examined for TTF-1 immunoreactivity, and patients should be clinically followed to determine the course of this unusual disease and the significance of TTF-1 expression.

DOI： 10.1111/j.1440-1827.2009.02480.x

掲載種別：研究論文（学術雑誌）  

Few genetic studies of renal carcinoid tumor have been conducted thus far We performed immunohistochemical and genetic examinations on four renal carcinoid tumors Histologically, the tumors consisted of neoplasm cells with round to oval nuclei Various growth patterns such as tightly packed cords and trabeculae, ribbon-like, trabecular, sheet-like or solid growth were observed Nuclear chromatin showed a coarse and granular pattern Immunohistochemically, tumors were positive for chromogranin A and synaptophysin In the fluorescence in situ hybridization study, three of four tumors revealed monosomy of chromosome 3 (D3Z1), but one tumor showed monosomy of chromosome 13 (D13S319/13q34) Using PCR amplification and fragment analysis of three microsatellite markers (D3S1300, D3S666 and D3S1768) of chromosome arm 3p, one tumor showed loss of heterozygosity at D3S1300 and D3S1768, one tumor was not informative and the analysis of two tumors failed due to low DNA quality In three cases, the VHL gene status was tested Two tumors showed wild-type but the analysis of one tumor failed to provide adequate results In conclusion, we suggest that the abnormality of chromosome 3 is involved in the pathogenesis of renal carcinoid tumor

DOI： 10.3892/ol_00000015

掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1440-1827.2009.02429.x

掲載種別：研究論文（学術雑誌）  

We present a series of a distinct tumorous entity named renal angiomyoadenomatous tumor (RAT). Five cases were retrieved from the consultation files of the authors. Histologic and immunohistochemical features were evaluated. Sequencing analysis of coding region of the VHL gene was carried out in all cases. The tumors were composed of admixture of an epithelial clear cell component and prominent leiomyomatous stroma. Epithelial cells formed adenomatous tubular formations endowed with blister-like apical snouts. All tubular/glandular structures were lined by a fine capillary network. The epithelial component was positive for epithelial membrane antigen, CK7, CK20, AE1-AE3, CAM5.2, and vimentin in all cases. In all analyzed samples, no mutation of the VHL gene was found. RAT is a distinct morphologic entity, being different morphologically, immunohistochemically, and genetically from all renal tumors including conventional clear cell carcinoma and mixed epithelial and stromal tumor of kidney.

DOI： 10.1007/s00428-008-0697-3

担当ページ：154-161   著書種別：学術書  

担当ページ：138-141   著書種別：学術書  

担当ページ：17-26   著書種別：学術書  

現在,様々な臓器においてWHO分類第5版シリーズが発刊されているが,その改訂コンセプトとしては,最新の分子生物学的成果を含めた治療効果予測に繋がる分類の採用,全世界で使用できるよう形態像を重視した分類に基づく必須の診断基準,画像診断の重要性の強調などが挙げられる。本総説では,尿路上皮癌に焦点を当ててWHO分類第5版の改訂点を概説する。主な改訂点は1)非浸潤性尿路上皮腫瘍の用語の改訂,2)細胞診におけるThe Paris Systemの使用の推奨,3)浸潤性尿路上皮癌における分子生物学的分類の位置づけ,4)pTステージの評価におけるVesical Imaging Reporting and Data System(VI-RADS)の併用の推奨であり,各項目について解説する。(著者抄録)

＜文献概要＞ポイント　・淡明細胞型腎細胞癌はVHL遺伝子異常を反映した組織形態を示し,繊細で豊富な血管網を背景に淡明や好酸性の腫瘍細胞が増殖する.・CA9はVHL/HIF経路に関連する蛋白で,細胞膜にびまん性に陽性を示すと淡明細胞型腎細胞癌としての診断的価値が高い.・血管網が消失する組織構築では免疫系の遺伝子発現が高く,予後不良と関連する.

オンコサイトーマと嫌色素性腎細胞癌を代表組織型とするoncocytic and chromophobe renal tumorの鑑別診断は広範囲に及び,日常診断でしばしば難渋する。本総説ではWHO泌尿生殖器腫瘍分類第5版(以下,WHO2022)におけるオンコサイトーマと嫌色素性腎細胞癌の診断基準の改定点と,両者の鑑別診断について解説する。また,WHO2022では新たにother oncocytic tumors of the kidneyという項目が加わった。そのあらましと,本項目に含まれる腫瘍群の特徴について紹介する。(著者抄録)

DOI： 10.1186/s12920-022-01155-6

その他URL： https://link.springer.com/article/10.1186/s12920-022-01155-6/fulltext.html

DOI： 10.3390/cimb44010010

PubMed

掲載種別：記事・総説・解説・論説等（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1053/j.semdp.2021.03.007

掲載種別：記事・総説・解説・論説等（学術雑誌）   国際・国内誌：国内誌  

掲載種別：記事・総説・解説・論説等（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.5114/pjp.2021.111769

PubMed

掲載種別：記事・総説・解説・論説等（学術雑誌）  

Collecting duct carcinoma was described over 30 years ago as a renal tumor, based in the medullary collecting system, with tubulopapillary morphology, prominent infiltrative growth, and stromal desmoplasia. While diagnostic workup has always emphasized exclusion of upper tract urothelial carcinoma and metastatic adenocarcinoma to the kidney, the molecular era of renal cell carcinoma classification has enabled recognition of and provided tools for diagnosis of new entities in this morphologic differential. In this review, we consider these developments, with emphasis on renal medullary carcinoma, closely related renal cell carcinoma, unclassified with medullary phenotype, and fumarate hydratase-deficient renal cell carcinoma. Integration of ancillary studies with suggestive patterns of morphology is emphasized for practical implementation in contemporary diagnosis, and several emerging tumor types in the morphologic differential are presented.

DOI： 10.1111/pin.12667

担当区分：筆頭著者   掲載種別：記事・総説・解説・論説等（学術雑誌）   国際・国内誌：国内誌  

担当区分：筆頭著者   掲載種別：記事・総説・解説・論説等（学術雑誌）   国際・国内誌：国内誌  

掲載種別：記事・総説・解説・論説等（学術雑誌）   国際・国内誌：国内誌  

担当区分：筆頭著者   掲載種別：記事・総説・解説・論説等（学術雑誌）   国際・国内誌：国内誌  

掲載種別：記事・総説・解説・論説等（学術雑誌）  

S100P, or placental S100, is a member of a large family of S100 proteins and considered to be a promising immunohistochemical marker to support urothelial differentiation. This review synthesizes published data regarding the expression of S100P in urothelial carcinoma across histological grade and variant patterns, and in other malignancies, in an effort to summarize the state of understanding of this marker and evaluate its potential. We provide also a broad comparison of S100P with other contemporary and traditional urothelial markers and outline the potential utility of S100P in various diagnostically challenging scenarios. Taken in context, we recommend that to provide immunohistochemical support for consideration of urothelial differentiation, S100P may be included in a panel of markers (due to its high sensitivity), with better established (GATA3) and more specific (uroplakin 2) markers, for comparison with corresponding markers of other primary sites under consideration, depending on the clinical context. We emphasize that the overall most appropriate panel for any given case depends on the differential diagnosis engendered by the morphology encountered, and the constellation of clinical findings. As always with immunohistochemical panels, expected positive and negative markers for each diagnostic consideration should be included. Finally, since as of date there are no optimally sensitive or specific markers of urothelial differentiation, all final diagnoses relying on immunohistochemical support should be made in the appropriate clinical and histological context.

DOI： 10.1097/PAP.0000000000000150

掲載種別：記事・総説・解説・論説等（学術雑誌）  

The entity of hereditary leiomyomatosis renal cell carcinoma (HLRCC)-associated RCC has been proposed and integrated into the recent International Society of Urologic Pathology (ISUP) of renal tumors. This tumor is characterized by presence of cutaneous and/or uterine leiomyomas and RCC and autosomal dominant hereditary form. Grossly, HLRCC arising in the kidney show the solid tumor with frequent partial cystic area. Microscopically, the tumor typically shows papillary RCC, type 2, with eosinophilic large nucleoli reminiscent of cytomegaloviral inclusion and perinuclear clearing/haloes. Immunohistochemically, tumor cells show the overexpression for 2SC and reduced expression of FH. Germline mutation of fumarate hydratase (FH) gene, the HLRCC responsible gene mapped to chromosome 1q43, has been identified in patients with HLRCC. As the renal cancer in patients with HLRCC generally behave aggressively even in a small size, complete surgical resection and retroperitoneal lymph node resection should be performed promptly when the tumor is discovered. The surveillance of renal tumor in FH gene germline mutation-positive patients should be started from the early age using ultrasound sonography or magnetic resonance imaging.

DOI： 10.5114/pjp.2017.73920

PubMed

掲載種別：記事・総説・解説・論説等（学術雑誌）  

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) was first identified in 2004 and has been integrated into the 2016 WHO classification of RCC. Succinate dehydrogenase (SDH) is an enzyme complex composed of four protein subunits (SDHA, SDHB, SDHC and SDHD). The tumor which presents this enzyme mutation accounts for 0.05 to 0.2% of all renal carcinomas. Multiple tumors may occur in approximately 30% of affected patients. SDHB-deficient RCC is the most frequent, and the tumor histologically consists of cuboidal cells with eosinophilic cytoplasm, vacuolization, flocculent intracytoplasmic inclusion and indistinct cell borders. Ultrastructurally, the tumor contains abundant mitochondria. Immunohistochemically, tumor cells are positive for SDHA, but negative for SDHB in SDHB-, SDHC- and SDHD-deficient RCCs. However, SDHA-deficient RCC shows negativity for both SDHA and SDHB. In molecular genetic analyses, a germline mutation in the SDHB, SDHC or SDHD gene (in keeping with most patients having germline mutations in an SDH gene) has been identified in patients with or without a family history of renal tumors, paraganglioma/pheochromocytoma or gastrointestinal stromal tumor. While most tumors are low grade, some tumors may behave in an aggressive fashion, particularly if they are high nuclear grade, and have coagulative necrosis or sarcomatoid differentiation.

DOI： 10.5114/PJP.2016.59227

掲載種別：記事・総説・解説・論説等（学術雑誌）  

Rhabdoid morphology in renal cell carcinoma (RCC) may, like sarcomatoid change, be perceived as a type of dedifferentiation, and is a poor prognostic factor. Histologically, rhabdoid neoplastic cells are round to polygonal cells with globular eosinophilic cytoplasmic inclusions and eccentric vesicular nuclei and enlarged nucleoli. All types of RCC, including clear cell, papillary, chromophobe, collecting duct carcinoma, renal medullary carcinoma, acquired cystic disease-associated RCC, ALK-positive renal cancer and unclassified RCC, may display a variably prominent rhabdoid phenotype. Immunohistochemically, the cytoplasm of rhabdoid cells shows positivity for vimentin and/or cytokeratin. Ultrastructurally, cytoplasmic whorls/aggregates of intermediate filaments correspond to light microscopically observed inclusions. Genetically, a previous report suggests that combined loss of BAP1 and PBRM1 may be associated with rhabdoid morphology. As with sarcomatoid change, pathologists should describe, estimate and state the proportion of tumor cells with a rhabdoid phenotype in the routine pathology report of RCC.

DOI： 10.5114/PJP.2015.51147

担当区分：筆頭著者   掲載種別：記事・総説・解説・論説等（学術雑誌）  

掲載種別：記事・総説・解説・論説等（学術雑誌）  

The disease concept of clear cell (tubulo) papillary renal cell carcinoma (CCP-RCC) as a distinct subtype of renal cell carcinoma has been recently established. First described in the setting of end stage renal disease, this tumor type is more frequently recognized and encountered in a sporadic setting. In this article, we provide an overview of the recent understanding of this tumor. Macroscopically, tumors are well circumscribed with well-developed tumor capsule. Histologically, the tumor cells are cuboidal to low columnar cell with clear cytoplasm and papillary and tubulo-papillary configuration. Immunohistochemically, tumor cells generally show diffuse expression for cytokeratin 7, CA9 (cup-shaped pattern), HIF-1, GLUT-1 and high molecular weight cytokeratin, but negative for AMACR, RCC Ma and TFE3. CD10 is negative or focally positive in most tumors. Genetically, this tumor has no characteristics of clear cell RCC or papillary RCC. Prognostically, patients with CCP-RCC behave in an indolent fashion in all previously reported cases. In conclusion, although this tumor has been integrated into recent International Society of Urologic Pathology Classification of renal neoplasia, both aspects of disease concept and clinical behavior are yet to be fully elucidated. Further publications of large cohorts of patients will truly help understand the biologic potential and the molecular underpinnings of this tumor type.

掲載種別：記事・総説・解説・論説等（学術雑誌）  

Renal solitary fibrous tumor (SFT) is a rare, and a large scale study on this topic is lacking to date. In this article, we summarize the previously reported cases. The symptoms and signs resemble those of renal cell carcinoma, including hematuria, flank/abdominal/lumbar pain and palpable abdominal mass. Grossly, the tumor demonstrates a well-circumscribed solid mass. Microscopically, the tumor consists of fusiform or ovoid spindle cells and a various amounts of collagen bundles with patternless, storiform, or fascicular arrangements with an occasional hemangiopericytomatous pattern. Immunohistochemically, CD34, CD99 and bcl-2 are often detected. Ultrastructurally, tumor cells contain irregular nuclei, prominent Golgi apparatus, branching rough endoplasmic reticulum, variable numbers of mitochondria. Surgical resection is considered to be the gold standard therapy. Most of renal SFT are benign, but cases of approximately 10 to 15% behave in an aggressive fashion. All patients need to be on long-term follow-up because clinical behavior is rather unpredictable. As the molecular genetic study of renal SFTs is lacking, a large scale study will be desirable in the future.

掲載種別：記事・総説・解説・論説等（学術雑誌）  

Tubulocystic carcinoma of the kidney (TCK) is a recently established entity in renal neoplastic pathology. This review aims to give an overview of the clinical and pathobiological aspects of TCK. Grossly, the TCKs are well-demarcated multicystic lesions giving a "wrapped bubble" or "spongy" appearance. Microscopically, the tumors are composed of multiple, variably sized cysts separated by thin fibrous septa lacking ovarian stroma or desmoplastic reaction. The cysts are lined by tumor cells with eosinophilic cytoplasm and nuclear atypia of variable, but not infrequently of high grade corresponding to Fuhrman grade 3. A frequent association with papillary tumors has been reported. Recent molecular genetic studies of TCK have revealed distinct features separating this subset of renal cell carcinomas (RCCs) from other types of renal tumors including collecting duct carcinoma of Bellini and renal medullary carcinoma as well as pointing towards a close kinship with papillary RCC. Tubulocystic carcinoma of the kidney generally pursues an indolent clinical course. However, several cases with aggressive clinical behavior have been reported. We strongly feel that there is enough clinicopathological evidence to corroborate TCK as a separate entity and that it should be incorporated into the next WHO classification of renal tumors as a separate neoplastic category.

DOI： 10.5114/PJP.2013.39329

掲載種別：記事・総説・解説・論説等（学術雑誌）  

The recent classification of renal tumors has been proposed according to genetic characteristics as well as morphological difference. In this review, we summarize the immunohistochemical characteristics of each entity of renal tumors. Regarding translocation renal cell carcinoma (RCC), TFE3, TFEB and ALK protein expression is crucial in establishing the diagnosis of Xp11.2 RCC, renal carcinoma with t(6
11)(p21
q12), and renal carcinoma with ALK rearrangement, respectively. In dialysis-related RCC, neoplastic cells of acquired cystic disease-associated RCC are positive for alpha-methylacyl-CoA racemase (AMACR), but negative for cytokeratin (CK) 7, whereas clear cell papillary RCC shows the inverse pattern. The diffuse positivity for carbonic anhydrase 9 (CA9) is diagnostic for clear cell RCC. Co-expression of CK7 and CA9 is characteristic of multilocular cystic RCC. CK7 and AMACR are excellent markers for papillary RCC and mucinous tubular and spindle cell carcinoma. CD82 and epithelial-related antigen (MOC31) may be helpful in the distinction between chromophobe RCC and renal oncocytoma. WT1 and CD57 highlights the diagnosis of metanephric adenoma. The combined panel of PAX2 and PAX8 may be useful in the diagnosis of metastatic RCC. © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

DOI： 10.1111/pin.12080

PubMed

掲載種別：記事・総説・解説・論説等（学術雑誌）  

Renal carcinoid tumor is a rare neoplasm. In this article, we review this neoplasm with a focus on clinical and pathobiological aspects. The majority of patients present in the fourth to seventh decades, but there is no gender predilection. Clinically, patients with renal carcinoid tumor frequently present with abdominal, back or flank pain. This tumor is occasionally associated with horseshoe kidney and/or mature cystic teratoma located in the kidney. Macroscopically, these tumors are well demarcated with a lobulated appearance and yellow or tan-brown color cut surface. Microscopically, these tumors are composed of monomorphic round to polygonal cells with granular amphophilic to eosinophilic cytoplasm. Tumor cells are arranged in trabecular, ribbon-like, gyriform, insular, glandular and solid patterns. The nuclei are round to oval and with evenly distributed nuclear chromatin, frequently with a "salt and pepper"-pattern. Immunohistochemically, tumor cells demonstrate immunolabeling for chromogranin A and synaptophysin. Ultrastructurally, the neoplastic cells contain abundant dense core neurosecretory granules. In previous genetic studies, abnormalities of chromosomes 3 or 13 have been reported. The clinical behavior of renal carcinoid tumors is variable, but is more indolent than most renal cell carcinomas. Further investigations are warranted in order to elucidate the critical genetic abnormalities responsible for the pathogenesis of this rare entity in renal neoplastic pathology.

PubMed

掲載種別：記事・総説・解説・論説等（学術雑誌）  

Renal oncocytosis is a recently established disease entity characterized by numerous oncocytic tumors and diffuse involvement of oncocytic changes in renal parenchymal epithelia. In this article, we review this disease with a focus on its clinical and pathobiological aspects. Clinically, renal oncocytosis may occur in a sporadic form without any underlying disease or may be associated with chronic renal failure/long-term hemodialysis. However, Birt-Hogg-Dube syndrome, characterized by skin tumors such as fibrofolliculoma or trichodiscoma, pulmonary lesions including bullae and spontaneous pneumothorax, and renal tumors should be evaluated in the differential diagnosis. The disease can develop either unilaterally or bilaterally. The involved renal parenchyma contains several to multiple brownish-colored nodules of varying size and is entirely replaced by lesions at the overt stage. Histologically, oncocytic tumors in both the dominant mass and smaller lesions encompass so-called hybrid tumor, chromophobe renal cell carcinoma (RCC), and renal oncocytoma (RO). Regarding renal parenchymal abnormalities, infiltrative growth of oncocytic cells, cortical cysts with oncocytic features, or extensive oncocytic change in non-neoplastic tubules can also be observed. Histochemical, immunohistochemical, and molecular genetic features of chromophobe RCC and RO arising in the setting of renal oncocytosis are generally identical to those in the sporadic type. However, hybrid tumors seem to be histologically distinct from chromophobe RCC and RO. In FISH analyses of some hybrid tumors, a gain of chromosomes 1, 2, 6, 10, and 17 was identified. In one tumor, no germ line mutation of folliculin gene was identified. Published data show that tumors follow a benign course. Further studies will be necessary to clarify the pathogenesis of renal oncocytosis.

掲載種別：記事・総説・解説・論説等（学術雑誌）  

Multilocular cystic renal cell carcinoma (MCRCC) accounts for approximately 1 to 2% of all renal tumors. This tumor is currently classified as a subtype of clear cell RCC. Clinically, the majority of these tumors are incidentally found. Macroscopically, the tumor is well demarcated and consists of various-sized cysts. The fibrous septa are generally thin and there is no discernible expansile nodule. Microscopically, the cyst walls are lined with tumor cells with clear to occasionally slightly eosinophilic cytoplasm. The Fuhrman nuclear grade is generally low and usually corresponds to grade 1. The deletion of chromosome 3p was identified in most tumors using FISH analysis and VHL gene mutation was identified in 25% of MCRCC. As MCRCC generally exhibits a low stage of TNM classification, the great majority of these tumors have a favorable clinical course. To date, there are no reports of metastasis, vascular invasion or sarcomatoid change in MCRCC. Accordingly, nephron sparing surgery is first recommended as a therapeutic strategy.

掲載種別：記事・総説・解説・論説等（学術雑誌）  

Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) is a recently established entity. In this article, we introduce the general view of this new entity. Macroscopically, the disease exclusively occurs in ACD and may arise as a dominant mass or non-dominant masses. Histologically, the tumor is characterized by a microcystic pattern, neoplastic cells with an eosinophilic or oncocytic cytoplasm and frequent intratumoral oxalate crystal deposition. Prominent nucleoli of tumor cells are often observed. Immunohistochemically, neoplastic cells are generally positive for AMACR but negative for cytokeratin 7. Ultrastructurally, neoplastic cells contain abundant mitochondria in the cytoplasm. Genetically, the gain of chromosomes 3, 7, 17 and abnormality of the sex chromosome were frequently observed in several studies. In conclusion, ACD-associated RCC may be widely recognized as a distinct entity in the near future because this tumor is morphologically and genetically different from other renal tumor entities that have been previously established.

掲載種別：記事・総説・解説・論説等（学術雑誌）  

Juxtaglomerular cell tumor (JGCT) generally affects adolescents and young adults. The patients experience symptoms related to hypertension and hypokalemia due to renin-secretion by the tumor. Grossly, the tumor is well circumscribed with fibrous capsule and the cut surface shows yellow or gray-tan color with frequent hemorrhage. Histologically, the tumor is composed of monotonous polygonal cells with entrapped normal tubules. Immunohistochemically, tumor cells exhibit a positive reactivity for renin, vimentin and CD34. Ultrastructurally, neoplastic cells contain rhomboid-shaped renin protogranules. Genetically, losses of chromosomes 9 and 11 were frequently observed. Clinically, the majority of tumors showed a benign course, but rare tumors with vascular invasion or metastasis were reported. JGCT is a curable cause of hypertensive disease if it is discovered early and surgically removed, but may cause a fatal outcome usually by a cerebrovascular attack or may cause fetal demise in pregnancy. Additionally, pathologists and urologists need to recognize that this neoplasm in most cases pursues a benign course, but aggressive forms may develop in some cases.

DOI： 10.1186/1746-1596-6-80

掲載種別：記事・総説・解説・論説等（学術雑誌）  

CiNii Article

担当区分：筆頭著者   掲載種別：記事・総説・解説・論説等（学術雑誌）  

CiNii Article

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