Publications by authors named "Fumi Kawakami"

45 Publications

Microsecretory Adenocarcinoma of Salivary Glands: An Expanded Series of 24 Cases.

Head Neck Pathol 2021 May 12. Epub 2021 May 12.

Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA.

Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor with a characteristic histologic and immunophenotypic profile and recurrent MEF2C-SS18 fusions. Because only six cases of MSA have been published, its complete clinicopathologic spectrum is unclear, and its biologic behavior has not been documented. Here, we present an updated and expanded experience of 24 MSA cases. All cases of MSA were obtained from the authors' files. Immunohistochemistry for S100, SOX10, p63, p40, SMA, calponin, and mammaglobin was performed. Molecular analysis was performed by targeted RNA sequencing, SS18 break apart fluorescence in situ hybridization, and/or reverse transcriptase polymerase chain reaction for MEF2C-SS18 fusion. Clinical follow-up was obtained from medical records. A total of 24 MSA cases were collected, from 13 women and 11 men, ranging from 17 to 83 years (mean 49.5 years). The vast majority (23 of 24) arose in the oral cavity, with the palate (n = 14) and buccal mucosa (n = 6) as the most frequent subsites. Tumors showed consistent histologic features including: (1) microcystic tubules, (2) flattened intercalated duct-like cells, (3) monotonous oval hyperchromatic nuclei, (4) abundant basophilic luminal secretions, (5) fibromyxoid stroma, and (6) circumscribed borders with subtle infiltration. The tumors were very consistently positive for S100 (24 of 24), p63 (24 of 24), and SOX10 (14 of 14) and negative for p40 (0 of 21), calponin (0 of 12) and mammaglobin (0 of 16), while SMA (4 of 20) was variable. MEF2C-SS18 fusion was demonstrated in 21 of 24 cases; in the remaining 3 cases with insufficient RNA, SS18 break apart FISH was positive. Treatment information was available in 17 cases, all of which were managed with surgery only. In 14 cases with follow-up (1-216 months, mean 30), no cases recurred or metastasized. MSA is a distinct salivary gland neoplasm with remarkably consistent clinical, histologic, immunophenotypic, and genetic features that generally behaves in an indolent manner following surgery alone. These observations solidify MSA as a unique, low-grade salivary gland carcinoma that warrants inclusion in the next version of the WHO classification of head and neck tumors.
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http://dx.doi.org/10.1007/s12105-021-01331-7DOI Listing
May 2021

Extramammary Paget's disease of the hard palate: A case report and review of the literature.

Pathol Int 2021 Mar 6;71(3):216-218. Epub 2021 Jan 6.

Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan.

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http://dx.doi.org/10.1111/pin.13062DOI Listing
March 2021

Microsecretory adenocarcinoma of the hard palate: A case report of a recently described entity.

Pathol Int 2020 Oct 20;70(10):781-785. Epub 2020 Jul 20.

Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan.

We report a case of microsecretory adenocarcinoma of the hard palate. The patient is a 37-year-old woman with a 15 mm submucosal tumor, which was incidentally found by her primary care dentist, in her hard palate. Preoperative magnetic resonance imaging revealed a tumor exhibiting high signal on T2-weighted image, which was gradually enhanced on dynamic study. Histologically, the tumor border was ill-defined without fibrous capsule and adjoined minor salivary gland with permeative infiltration at the tumor periphery. The tumor comprised intercalated duct-like cells with polygonal narrow eosinophilic to clear cytoplasm and small, uniform oval nuclei. These cells formed small infiltrative microcysts, tubules and fascicular cords collecting pale basophilic secretions and small vacuoles setting in an abundant fibromyxoid stroma. The tumor cells were positive for CK AE1+AE3, S-100 protein, and p63, while are completely negative for p40, alpha-SMA, and calponin. The MEF2C-SS18 fusion was identified by reverse transcriptase-polymerase chain reaction followed by Sanger sequencing. The combination of characteristic histology, immunophenotype, and presence of MEF2C-SS18 fusion indicated the diagnosis of microsecretory adenocarcinoma of the hard palate, an entity described only recently. Post-operative course was uneventful and there was no evidence of disease at 4 months after surgery.
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http://dx.doi.org/10.1111/pin.12987DOI Listing
October 2020

Hybrid oncocytic/chromophobe renal tumors are molecularly distinct from oncocytoma and chromophobe renal cell carcinoma.

Mod Pathol 2019 11 23;32(11):1698-1707. Epub 2019 Jun 23.

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

Hybrid oncocytic/chromophobe tumor (HOCT) of the kidney represents a poorly understood clinicopathologic entity with pathologic features that overlap between benign renal oncocytoma (RO) and malignant chromophobe renal cell carcinoma (ChRCC). Consequently, characterization of HOCT and its separation from the foregoing entities are clinically important. The aim of this study was to describe the pathologic and molecular features of HOCT and to compare them with those of RO and ChRCC. We retrospectively identified a cohort of 73 cases with renal oncocytic tumors (19 RO, 27 HOCT, and 27 ChRCC) for whom clinical follow-up data were available by 2 tertiary care hospitals. All cases were sporadic except for 2 HOCTs that were associated with Birt-Hogg-Dubé syndrome. Lesional tissues were retrieved for molecular analysis. We performed targeted gene sequencing of all exons of 261 cancer related genes on a subset of HOCT samples (n = 16). Gene expression profiling of a customized codeset was conducted on 19 RO, 24 HOCT, and 27 ChRCC samples. Clinicopathologic characteristics as well as DNA copy number alterations, mutational and transcriptional features of HOCT derived from sequencing and expression profiling data are described and compared to those in RO and ChRCC. HOCTs were more frequently multifocal and did not exhibit mutations in genes that are recurrently mutated in RO or ChRCC but showed copy number alterations primarily involving losses in chromosomes 1 and X/Y. The mRNA transcript data show that HOCT can be separated from RO and ChRCC. Hence, HOCT appears to represent a distinct renal tumor entity with genomic features that are intermediate between those of RO and ChRCC.
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http://dx.doi.org/10.1038/s41379-019-0304-yDOI Listing
November 2019

Clinicopathological analysis of clinically occult extrapulmonary lymphangioleiomyomatosis in intra-pelvic and para-aortic lymph nodes associated with pelvic malignant tumors: A study of nine patients.

Pathol Int 2019 Jan;69(1):29-36

Department of Pathology, Kobe City Medical Center General Hospital, Kobe, Japan.

The clinicopathological and immunohistochemical characteristics of clinically occult extrapulmonary lymphangioleiomyomatosis in lymph nodes (LN-LAM) being dissected during surgical staging of pelvic malignancy have not been well investigated. We assessed samples from nine female patients (median age, 61). None had past or familial history of tuberous sclerosis and had LAM lesions other than LN such as lung. The primary malignancies included four endometrial endometrioid carcinomas, one endometrial carcinosarcoma, three ovarian serous carcinomas and one urothelial carcinoma. Median follow-up was 43 months. The number of affected LNs ranged from 1 to 15 (median, 2) with sizes ranging from 1 to 13 mm (median, 3.0). Six cases had clinically occult LN-LAM only within the pelvic LNs, two only within para-aortic LNs, and one within both pelvic and para-aortic lymph nodes. Immunohistochemically, LAM cells exhibited a strong diffuse positivity for β-catenin and E-cadherin in all nine cases. Clinically occult LN-LAM mainly affects peri- or post-menopausal women. On rare occasions, occult LN-LAM may manifest as systemic LAM, including in the lung. β-catenin and E-cadherin carry potential utility as additional diagnostic markers.
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http://dx.doi.org/10.1111/pin.12749DOI Listing
January 2019

Uc.416 + A promotes epithelial-to-mesenchymal transition through miR-153 in renal cell carcinoma.

BMC Cancer 2018 Oct 4;18(1):952. Epub 2018 Oct 4.

Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Background: The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis in some cancers. However, the expression and biological role of T-UCRs in renal cell carcinoma (RCC) remain poorly understood. This study aimed to examine the expression and functional role of Uc.416 + A and analyze the association between Uc.416 + A and epithelial-to-mesenchymal transition in RCC.

Methods: Expression of Uc.416 + A in 35 RCC tissues, corresponding normal kidney tissues and 13 types of normal tissue samples was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). We performed a cell growth and migration assay in RCC cell line 786-O transfected with negative control and siRNA for Uc.416 + A. We evaluated the relation between Uc.416 + A and miR-153, which has a complimentary site of Uc.416 + A.

Results: qRT-PCR analysis revealed that the expression of Uc.416 + A was higher in RCC tissues than that in corresponding normal kidney tissues. Inhibition of Uc.416 + A reduced cell growth and cell migration activity. There was an inverse correlation between Uc.416 + A and miR-153. Western blot analysis showed Uc.416 + A modulated E-cadherin, vimentin and snail. The expression of Uc.416 + A was positively associated with the expression of SNAI1, VIM and inversely associated with the expression of CDH1.

Conclusions: The expression of Uc.416 + A was upregulated in RCC and especially in RCC tissues with sarcomatoid change. Uc.416 + A promoted epithelial-to-mesenchymal transition through miR-153. These results suggest that Uc.416 + A may be a promising therapeutic target.
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http://dx.doi.org/10.1186/s12885-018-4863-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172711PMC
October 2018

Transformed Follicular Lymphoma (TFL) Predicts Outcome in Advanced Endometrial Cancer.

Cancer Epidemiol Biomarkers Prev 2018 08 21;27(8):963-969. Epub 2018 May 21.

Section of Translational Research, Hyogo Cancer Center, Akashi, Japan.

Transformed follicular lymphoma () was identified as a candidate tumor suppressor gene that contributes to cell-cycle arrest through regulation of Rb phosphorylation, but the clinical impact of TFL is unknown. The goal of this study was to evaluate the prognostic significance of TFL expression in advanced endometrial cancer. Tissue samples were obtained from 103 patients with Federation Internationale des Gynaecologistes et Obstetristes stage III-IV endometrial cancer. Associations between TFL expression and outcomes were evaluated using the Kaplan-Meier method and multivariate Cox proportional hazards regression models. There were 24 TFL-low cases (23.3%) and the 10-year progression-free survival (PFS) and overall survival (OS) in these cases were lower than those for patients with normal TFL expression in univariate analysis (PFS, = 0.003; OS, = 0.106). In multivariate analysis, TFL status was a significant predictor for PFS [HR = 2.76; 95% confidence interval (CI), 1.45-5.28; = 0.002] and OS (HR = 1.94; 95% CI, 0.91-4.11; = 0.085), adjusted for covariates. The gene maps to human chromosome 6q25.1, where estrogen receptor alpha (ERα) gene is also located. Lack of ERα expression is a poor prognostic factor in early endometrial cancer. Among 41 ERα-low patients, 10-year PFS was significantly lower in 15 TFL-low cases (univariate analysis, = 0.055; multivariate analysis, HR = 4.70; 95% CI, 1.68-13.20; = 0.003). We identified TFL as a strong independent prognostic factor, regardless of ERα status. An investigation of the mechanism underlying tumor suppression by TFL may lead to new therapies for patients with advanced endometrial cancer. .
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http://dx.doi.org/10.1158/1055-9965.EPI-17-0762DOI Listing
August 2018

Programmed cell death ligand 1 and tumor-infiltrating lymphocyte status in patients with renal cell carcinoma and sarcomatoid dedifferentiation.

Cancer 2017 Dec 22;123(24):4823-4831. Epub 2017 Aug 22.

Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: The immune profile of sarcomatoid renal cell carcinoma (sRCC), including the programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) status, has not been well characterized.

Methods: An immunohistochemical digital analysis of PD-L1, PD-1, CD4, and CD8 was performed on nephrectomy specimens from 118 sRCC patients and 92 nonsarcomatoid clear cell renal cell carcinoma (ccRCC) patients. The clinical characteristics of the population were compared between sRCC and ccRCC. Overall survival was estimated, and comparisons were made between PD-L1-positive and PD-L1-negative groups as well as tumor-infiltrating lymphocyte (TIL)-high and TIL-low groups.

Results: The PD-L1 H-score of sRCC (mean, 3.7; range, 0-192.1) was significantly higher than the score of grade 4 ccRCC (P = .001), and 41.3% of sRCC cases showed a PD-L1 H-score ≥ 10. The PD-1-positive cell density was significantly higher in sRCC versus ccRCC within the tumor and at the invasive front. The intratumoral CD8-positive cell density was significantly higher in sRCC versus ccRCC. Forty-one percent in the sarcomatoid component of sRCC and 8% in the epithelioid component of sRCC had an adaptive immune resistance phenotype (PD-L1-positive and TIL-positive), whereas only 1% in ccRCC had the type I phenotype.

Conclusions: sRCC showed higher PD-L1 expression and higher PD-1- and CD8-positive cell density than grade 4 ccRCC. The results indicate a notable immunosuppressive environment in sRCC. Despite advances in the treatment of advanced-stage renal cell carcinoma, sRCC still has a poor prognosis. This work describes highly immunosuppressive characteristics of sRCC in comparison with an appropriate ccRCC control. The results suggest PD-1/PD-L1 blockade therapy as a potential therapeutic approach for sRCC. Cancer 2017;123:4823-31. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731248PMC
December 2017

Sarcomatoid Renal Cell Carcinoma Has a Distinct Molecular Pathogenesis, Driver Mutation Profile, and Transcriptional Landscape.

Clin Cancer Res 2017 Nov 14;23(21):6686-6696. Epub 2017 Jul 14.

Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Sarcomatoid renal cell carcinoma (SRCC) ranks among the most aggressive clinicopathologic phenotypes of RCC. However, the paucity of high-quality, genome-wide molecular examinations of SRCC has hindered our understanding of this entity. We interrogated the mutational, copy number, and transcriptional characteristics of SRCC and compared these data with those of nonsarcomatoid RCC (RCC). We evaluated whole-exome sequencing, single-nucleotide polymorphism, and RNA sequencing data from patients with SRCC ( = 65) and RCC ( = 598) across different parent RCC subtypes, including clear-cell RCC, papillary RCC, and chromophobe RCC subtypes. SRCC was molecularly discrete from RCC and clustered according to its parent RCC subtype, though with upregulation of TGFβ signaling across all subtypes. The epithelioid (E-) and spindled (S-) histologic components of SRCC did not show differences in mutational load among cancer-related genes despite a higher mutational burden in S-. Notably, sarcomatoid clear-cell RCC (SccRCC) showed significantly fewer deletions at 3p21-25, a lower rate of two-hit loss for and , and more mutations in , , and compared with ccRCC. A two-hit loss involving predicted for ccRCC and a better prognosis, whereas mutations in , , or predicted for SccRCC and worse prognosis. SRCC segregates by parent subtype, and SccRCC has a fundamentally different early molecular pathogenesis, usually lacking the classic 3p21-25 deletion and showing distinctive mutational and transcriptional profiles. These features prompt a more precise molecular classification of RCC, with diagnostic, prognostic, and therapeutic implications. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-1057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683086PMC
November 2017

Study of the Kidney Tumor-Parenchymal Interface after Neoadjuvant Treatment with Axitinib for Locally Advanced Clear Cell Renal Cell Carcinoma: Matched Analysis from a Phase II Trial.

J Urol 2017 03 25;197(3 Pt 1):559-565. Epub 2016 Sep 25.

Department of Urology, University of Texas M.D. Anderson Cancer Center, Houston, Texas. Electronic address:

Purpose: The aim of this study was to evaluate histological changes in the tumor-parenchymal interface in clear cell renal cell carcinoma after neoadjuvant axitinib treatment.

Materials And Methods: We obtained clinical and pathology materials from 23 patients with clear cell renal cell carcinoma treated with neoadjuvant axitinib in a phase II clinical trial and from 23 matched patients with clear cell renal cell carcinoma who underwent upfront surgery. Histology of the tumor pseudocapsule and the peritumor kidney parenchymal change was evaluated and compared between the 2 cohorts.

Results: A tumor pseudocapsule was noted in all 23 patients who received neoadjuvant axitinib and in all 23 control patients. Most pseudocapsules were noncontinuous and only partially covered the tumor, including in 17 of 23 axitinib cases (74%) and 19 of 23 controls (83%). In axitinib cases the median thickness of the intrarenal and extrarenal pseudocapsule was 1.4 and 2.4 mm, respectively, which was significantly thicker than in control cases (intrarenal p = 0.0008 and extrarenal p <0.0001). The thickness of the pseudocapsule in axitinib treated cases was more frequently irregular compared to that in controls (16 of 23 or 70% and 9 of 23 or 39%, respectively, p = 0.0746). Inflammation, nephrosclerosis, glomerulosclerosis and arteriosclerosis decreased with increasing distance from the tumor edge in the neoadjuvant axitinib and control groups.

Conclusions: The tumor pseudocapsule becomes irregularly thick after neoadjuvant axitinib therapy. Although axitinib likely evokes a strong fibrous reaction in the tumor-parenchymal interface, it does not affect the frequency of infiltrative tumor invasion to the outside of the pseudocapsule or the degree of atrophic/inflammatory change in tissue surrounding the tumor. These findings support the notion that partial nephrectomy could be safely done in well selected patients after neoadjuvant axitinib.
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http://dx.doi.org/10.1016/j.juro.2016.09.081DOI Listing
March 2017

Expression of Epithelial-Mesenchymal Transition-related Factors in Adherent Placenta.

Int J Gynecol Pathol 2015 Nov;34(6):584-9

Department of Obstetrics and Gynecology (T.S., Y.M., K.T., H.M., H.Y.), Kobe University Graduate School of Medicine Department of Diagnostic Pathology (F.K., T.I.), Kobe University Hospital, Kobe, Japan.

Epithelial-mesenchymal transition is a key process influencing cancer progression and metastasis. The purpose of this study was to investigate the expression of epithelial-mesenchymal transition-related factors in chorionic villi and decidual cells in adherent placenta. The current study included 19 patients diagnosed with adherent placenta after hysterectomy. The expression of E-cadherin, Vimentin, Snail, and transforming growth factor-β in placental tissues was analyzed by immunohistochemical staining. Immunostaining intensity was semiquantitatively evaluated using the HSCORE algorithm. In the chorionic villi of the invasive part (placenta with invasion into myometrium), E-cadherin expression was significantly lower than that in the noninvasive part (placenta with no invasion). In the decidual cells of the invasive part, expression of transforming growth factor-β and Snail significantly increased. These results suggest that epithelial-mesenchymal transition may contribute to excessive trophoblast invasion into the myometrium in adherent placenta.
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http://dx.doi.org/10.1097/PGP.0000000000000190DOI Listing
November 2015

Cytologic features of gastric-type adenocarcinoma of the uterine cervix.

Diagn Cytopathol 2015 Oct 14;43(10):791-6. Epub 2015 Jul 14.

Department of Diagnostic Pathology, Kobe University Hospital, Kobe, Japan.

Background: Gastric-type mucinous carcinoma (GAS) is a clinically aggressive variant of cervical adenocarcinoma. This study sought to describe the cytologic features of GAS.

Methods: We reviewed the cervical and endometrial smears of 14 patients with a histopathologic diagnosis of GAS. All slides were conventionally smeared. We included 20 controls with usual-type endocervical adenocarcinoma (UEA).

Results: Monolayered and honeycomb sheets were observed in 78.6% (11/14) of patients with GAS, and were prominent in seven patients. Three-dimensional clusters were more prominent in the UEA group. Vacuolar and/or foamy cytoplasm was observed in 71.4% (10/14) of patients with GAS, whereas this finding was rare among those with UEA (2/18). Marked intracytoplasmic neutrophil entrapment was more common in the GAS group (7/14) than in the UEA group (2/18). Intracytoplasmic mucin was present in eight patients with GAS. Nuclei were vesicular in eight patients with GAS, but were homogenous and hyperchromatic in UEA patients. Conspicuous nucleoli were present in nine patients with GAS. Conversely, this finding was rarely observed in UEA patients.

Conclusions: The characteristic cytologic findings of GAS include (1) monolayered and honeycomb sheets, (2) vacuolar and/or foamy cytoplasm, (3) intracytoplasmic neutrophil entrapment, and (4) vesicular nuclei with prominent nucleoli.
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http://dx.doi.org/10.1002/dc.23304DOI Listing
October 2015

Triexponential function analysis of diffusion-weighted MRI for diagnosing prostate cancer.

J Magn Reson Imaging 2016 Jan 27;43(1):138-48. Epub 2015 Jun 27.

Department of Radiology, Kobe University Hospital, Chuo-ku Kobe, Hyogo, Japan.

Background: To evaluate more detailed information noninvasively through on diffusion and perfusion in prostate cancer (PCa) using triexponential analysis of diffusion-weighted imaging (DWI).

Methods: Sixty-three prostate cancer patients underwent preoperative 3.0 Tesla MRI including eight b-values DWI. Triexponential analysis was performed to obtain three diffusion coefficients (Dp , Df , Ds ), as well as fractions (Fp , Ff , Fs ). Each diffusion parameter for cancerous lesions and normal tissues was compared and the relationship between diffusion parameters and Gleason score (GS) was assessed. K(trans) , Ve , and the ratios of intracellular components measured in histopathological specimens were compared with diffusion parameters.

Results: Dp was significantly greater for cancerous lesions than normal peripheral zone (PZ) (P < 0.001), whereas Dp in transition zone (TZ) showed no significant difference (P = 0.74, 95% confidence interval (CI) = -4.69-6.48). Ds was significantly smaller for each cancerous lesions in PZ and TZ (P < 0.001, respectively). There was no significant difference in Df between cancerous lesions and normal tissues in PZ and TZ (P = 0.07, 95% CI = -0.29-0.12 and P = 0.53, 95% CI = -3.51-2.29, respectively). D obtained with biexponential analysis were significantly smaller in cancerous lesions than in normal tissue in PZ and TZ (P < 0.001 for both), while D* in PZ and TZ showed no significant difference (P = 0.14, 95% CI = -1.60-0.24 and P = 0.31, 95% CI = -3.43-1.16, respectively). Dp in PZ and TZ showed significant correlation with K(trans) (R = 0.85, P < 0.001; R = 0.81, P < 0.001, respectively), while D(*) in PZ obtained with biexponential analysis showed no such correlation (P = 0.08, 95% CI = -0.14-0.30). Fs was significantly correlated with intracellular space fraction evaluated in histopathological specimens in PZ and TZ cancer (R = 0.41, P < 0.05; R = 0.59, P < 0.001, respectively). Ff and Fs correlated significantly with GS in PZ and TZ cancer (PZ: R = -0.44, P < 0.05; R = 0.37, P < 0.05, TZ: R = -0.59, P < 0.05; R = 0.57, P < 0.05, respectively).

Conclusion: Triexponential analysis is a noninvasive approach that can provide more detailed information regarding diffusion and perfusion of PCa than biexponential analysis.
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http://dx.doi.org/10.1002/jmri.24974DOI Listing
January 2016

Review of renal cell carcinoma with rhabdoid features with focus on clinical and pathobiological aspects.

Pol J Pathol 2015 Mar;66(1):3-8

Naoto Kuroda MD, Department of Pathology, Kochi Red Cross Hospital, Shin-honmachi 2-13-51, Kochi City,, Kochi 780-8562, Japan, tel. +81-88-822-1201, fax +81-88-822-1056, e-mail:

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.
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http://dx.doi.org/10.5114/pjp.2015.51147DOI Listing
March 2015

IgG4-related disease manifesting as pericarditis with elevated adenosine deaminase and IL-10 levels in pericardial fluid.

Mod Rheumatol 2017 Sep 28;27(5):894-897. Epub 2015 May 28.

a Department of Rheumatology and Clinical Immunology , Kobe University Graduate School of Medicine , Chuo-ku, Kobe , Japan.

A 78-year-old female with massive pericardial effusion fulfilled diagnostic criteria for immunoglobulin G4 (IgG4)-related disease. Although her adenosine deaminase (ADA) level in the pericardial effusion was high, all the tests for tuberculosis infection were negative. Immunostaining of the pericardium biopsy specimen revealed remarkably increased IgG4-positive cells. This is the first report describing IgG4-related pericarditis with elevated ADA level. We also demonstrate the elevated interleukin-10 (IL-10) level in pericardial fluid and IL-10-producing T-cells in the pericardium.
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http://dx.doi.org/10.3109/14397595.2015.1039628DOI Listing
September 2017

Pathogenesis of combined high-grade squamous intraepithelial lesion and adenocarcinoma in situ of the uterine cervix: human papillomavirus genotype and methylation status and immunohistochemical study.

Kobe J Med Sci 2014 Nov 6;60(3):E66-73. Epub 2014 Nov 6.

Department of Diagnostic Pathology, Kobe University Hospital, Kobe, Japan.

To determine the etiology of combined high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS) of the uterine cervix, we examined human papillomavirus (HPV) subtypes, methylation status of the HPV-16 L1 gene, and immunohistochemical staining pattern of Krt7 in 8 cases of combined HSIL and AIS. Overall, 6 (75%) of 8 patients with combined HSIL and AIS were infected by the same subtype of HPV in both HSIL and AIS (cases 1-5, HPV-16; and case 6, HPV-18), whereas 2 (25%) patients showed infection with different subtypes of HPV (case 7, HPV-31 and -18; and case 8, HPV-52 and -16, in HSIL and AIS, respectively). The degrees of methylation at CpG islands within the HPV-16 L1 gene were almost equivalent between HSIL and AIS in cases 1-4, whereas a great difference in CpG methylation patterns between two was seen in only 1 case (case 5). In addition, both patients infected with different subtypes of HPV between HSIL and AIS were positive for Krt7 only within the AIS component. Based on these results, we propose two distinct developmental pathways of combined HSIL and AIS of the uterine cervix, the common pathway and the individual pathway.
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November 2014

Immunohistochemical characterization of renal tumors in patients with Birt-Hogg-Dubé syndrome.

Pathol Int 2015 Mar 19;65(3):126-32. Epub 2015 Jan 19.

Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder associated with a germline mutation of folliculin (FLCN). The affected families are at a high risk for developing multiple renal cell carcinomas (RCC). Little is known about the immunostaining patterns of mutant FLCN-associated RCCs. We investigated 32 RCCs obtained from 17 BHD patients. The studied tumors included chromophobe RCCs (n = 15), hybrid oncocytic/chromophobe tumors (HOCT) (n = 14) and clear cell RCCs (n = 3). Almost all chromophobe RCCs and HOCTs revealed positive staining for S100A1, Ksp-cadherin and CD82. They stained either focally or diffusely for CK7, and were negative for CA-IX. All clear cell RCCs were positively stained for CA-IX and negative for CK7. These data confirmed that mutant FLCN-associated oncocytic and clear cell RCCs exhibited generally similar immunostaining patterns compared to their sporadic counterparts. Frequent positive staining for S100A1, Ksp-cadherin and CD82 in chromophobe RCCs and HOCTs indicated that these two types were relatively similar rather than distinctively different in their patterns of immunoreactivity. Characteristic peri-nuclear halos and polygonal cells with clear cytoplasm, which often misleads pathologists into the diagnosis of clear cell RCC, should be carefully examined using an immunohistochemical panel including CA-IX, Ksp-cadherin, CD82 and CK7.
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http://dx.doi.org/10.1111/pin.12254DOI Listing
March 2015

Clear cell papillary renal cell carcinoma: a review.

Int J Clin Exp Pathol 2014 15;7(11):7312-8. Epub 2014 Oct 15.

Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center Los Angeles, CA, USA.

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270541PMC
April 2017

Central neurocytoma with ependymoma-like glial component.

Brain Tumor Pathol 2015 Apr 28;32(2):119-23. Epub 2014 Oct 28.

Department of Diagnostic Pathology, Kobe University Hospital, 7-5-2, Kusunoki cho, Chuou-ku, Kobe, Hyogo, 650-0017, Japan,

We present the first case of central neurocytoma with a component suggesting ependymal-like differentiation as an unclassified glioneuronal tumor. The patient was a 26-year-old Japanese man with a brain tumor extending from the frontal wall of the bilateral lateral ventricles to the corpus callosum. Histologically, the tumor's neuronal component consisted of small bland looking cells with fine, delicate, neuropil-like processes forming a rosette structure; its glial component consisted of tumor cells with thick processes arranged around the thinly walled vessels, resulting in a perivascular pseudo-rosette formation and indicating ependymal-like differentiation. Immunohistochemically, the cytoplasm of the tumor cells with ependymal-like features was positive for glial fibrillary acidic protein and negative for synaptophysin, while the tumor component with neuronal features showed the opposite immunohistochemical staining pattern. Most of the tumor cells were positive for Olig2, but EMA, D2-40, CD99, p53, and mutant IDH-1 (R132H) were totally negative. Its Ki-67 labeling index was less than 1 %. Histologically, this tumor was diagnosed as a central neurocytoma with an ependymoma-like glial component, and its tumor grade was estimated at grade II. The tumor location, infiltrating the corpus callosum, and histology were distinctive and might represent a peculiar subtype of glioneuronal tumor.
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http://dx.doi.org/10.1007/s10014-014-0204-2DOI Listing
April 2015

Intratumoral peripheral small papillary tufts: a diagnostic clue of renal tumors associated with Birt-Hogg-Dubé syndrome.

Ann Diagn Pathol 2014 Jun 29;18(3):171-6. Epub 2014 Mar 29.

Department of Diagnostic Pathology, Chiba University Graduate School of Medicine, Chiba, Japan.

In this article, we searched for the common histologic characteristic of renal tumors in patients with Birt-Hogg-Dubé syndrome (BHDS). We selected 6 patients with histologically confirmed renal tumor in BHDS. Germline FLCN gene mutation has been identified in 5 patients. Multifocality and bilaterality of the renal tumors were pathologically or radiologically confirmed in 5 and 2 cases, respectively. Histologic subtypes of the dominant tumor included 3 previously described hybrid oncocytic tumors, one composite chromophobe/papillary/clear cell renal cell carcinoma (RCC) and one unclassified RCC resembling hybrid chromophobe/clear cell RCC. In one case, chromophobe RCC and clear cell RCC were separately observed. Small papillary lesions located in the peripheral area of the tumor, which we designated as intratumoral peripheral small papillary tufts, were identified in all patients. In conclusion, multifocality/bilaterality of renal tumors, discordance of histologic subtypes, and the presence of intratumoral peripheral small papillary tufts may be important clues to identify BHDS-associated renal tumors.
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http://dx.doi.org/10.1016/j.anndiagpath.2014.03.002DOI Listing
June 2014

Severe post-transplant lymphoproliferative disorder after living donor liver transplantation.

Hepatol Res 2015 Mar 13;45(3):356-62. Epub 2014 May 13.

Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Hyogo, Japan.

Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication after transplantation. A living donor liver transplantation was performed on a 31-year-old man for fulminant hepatitis. He again developed liver dysfunction after 7 months. He was diagnosed as having acute cellular rejection and the steroid pulse therapy introduced resulted in little improvement. He gradually developed a high fever and right axillary lymphadenopathy appeared. Chest computed tomography (CT) was performed revealing small lung nodules and axillary lymphadenopathy. Because his serological status for Epstein-Barr virus was positive, PTLD was highly suspected and immunosuppression treatment was withdrawn with little improvement. One week later, he developed tachycardia. Chest CT was re-performed revealing an infiltration to the left cardiac chamber. For diagnosis, axillary lymph node biopsy was performed and during the procedure, he developed ventricular tachycardia (VT). Immunohistological staining revealed PTLD of T lymphocytes, and chemotherapy was introduced on the same day he developed VT. After two cycles of tetrahydropyranyl, adriamycin, cyclophosphamide, vincristine, prednisolone and etoposide treatment, he completely recovered. This is a first case report of severe PTLD with VT, and our case implies the feasibility of chemotherapy after the appearance of dissemination symptoms.
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http://dx.doi.org/10.1111/hepr.12345DOI Listing
March 2015

Surgical treatment for recurrent solitary fibrous tumor invading atlas.

Head Neck 2014 Nov 9;36(11):E121-4. Epub 2014 Apr 9.

Department of Otolaryngology-Head and Neck Surgery, Kobe University Hospital, Kobe, Japan.

Background: Solitary fibrous tumor (SFT), a rare neoplasm, usually originates in the pleura. Extrapleural SFTs occasionally occur in the head and neck.

Methods: In this study, the extirpation of a rare case of recurrent SFT invading the atlas is discussed.

Results: Ten years after surgical resection of an SFT in the right parapharyngeal space, the patient returned with a complaint of swelling sensation in the right neck. MRI and CT showed an enhanced lobulated mass invading the right lateral C1 vertebral body and canal and encasing the right vertebral artery. Extirpation of the recurrent tumor with a combined transcervical and midline posterior approach was successful. The surgical margin was negative for cancer and the postoperative course was uneventful.

Conclusion: Although an SFT is generally benign, recurrence can occur even after several years, therefore, careful long-term follow-up is essential for early detection. A combined transcervical and midline posterior approach proved useful for resection of the atlas body.
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http://dx.doi.org/10.1002/hed.23628DOI Listing
November 2014

In situ total aortic arch replacement for infected distal aortic arch aneurysms with penetrating atherosclerotic ulcer.

J Thorac Cardiovasc Surg 2014 Nov 8;148(5):2096-100. Epub 2014 Feb 8.

Division of Cardiovascular Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address:

Background: We present a series of patients who underwent in situ total aortic arch replacement for infected distal aortic arch aneurysms.

Methods: Between 2002 and 2013, 9 patients with infected distal aortic arch aneurysms underwent total aortic arch replacement using antegrade selective cerebral perfusion. There were 4 male and 5 female patients with a mean age of 72.7±9.0 years. All patients had penetrating atherosclerotic ulcer in the distal aortic arch, which formed saccular aneurysms. Four patients had preoperative hoarseness. Maximum preoperative white blood cell count was 10,211±4375/μL, and mean serum C-reactive protein concentration was 12.7±7.2 mg/dL. Causative microorganisms were identified by blood culture or aortic wall culture and were as follows: Candida albicans, Pseudomonas aeruginosa, Edwardsiella tarda, Streptococcus dysgalactiae, Listeria monocytogenes, Staphylococcus aureus (2 cases), and unknown (2 cases). Radical debridement with in situ total aortic arch replacement was performed in all patients, followed by the omental flap grafting in 7 patients. All surgery was performed on an urgent or emergency basis.

Results: Average cardiopulmonary bypass time and lower body circulatory arrest time were 199.7±50.7 minutes and 66.6±13.8 minutes, respectively. There was no in-hospital mortality, but 1 patient died of asphyxia 5 months after hospital discharge. Freedom from recurrence of infection was 100%.

Conclusions: Surgical treatment with the combination of radical debridement with in situ total aortic arch replacement using antegrade selective cerebral perfusion and omental flap grafting was a reliable procedure for the treatment of infected distal aortic arch aneurysms.
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http://dx.doi.org/10.1016/j.jtcvs.2014.02.015DOI Listing
November 2014

Angiosarcoma arising in schwannoma of cerebellopontine angle and later associating with meningioma in a patient with neurofibromatosis type 2.

Brain Tumor Pathol 2014 Oct 6;31(4):293-8. Epub 2014 Mar 6.

Department of Diagnostic Pathology, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe-shi, Hyogo, 650-0017, Japan,

Here, we describe an extremely rare case of angiosarcoma arising in schwannoma of the cerebellopontine angle and later associating with meningioma in a patient with neurofibromatosis type 2. A 33-year-old disabled Japanese man with right drop foot after surgery for an unspecified tumor demonstrated multiple tumors, suspected to be schwannoma, in the bilateral cerebellopontine angles, the cervical and lumbar spinal cord, and on the right nuchal skin. Also present were several tumors in the medulla and thoracic spinal cord suspected to be ependymoma or astrocytoma. The patient was diagnosed with neurofibromatosis type 2 according to the diagnostic criteria by the U.S. National Institutes of Health. The bilateral tumors in the cerebellopontine angle were resected to reduce symptoms and brain stem compression. Histopathological analysis revealed angiosarcoma arising in schwannoma of the bilateral tumors, and angiosarcoma was proportionally larger in the right tumor than in the left. At age 36, the patient underwent a second resection of the regrown tumor in the left cerebellopontine angle, and histopathology demonstrated mixed angiosarcoma and meningioma. That angiosarcoma arises in schwannoma is a pathogenesis within the realm of conjecture, especially that the phenomenon of mixed meningioma and angiosarcoma has not been reported to date.
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http://dx.doi.org/10.1007/s10014-014-0180-6DOI Listing
October 2014

Novel MRI finding for diagnosis of invasive placenta praevia: evaluation of findings for 65 patients using clinical and histopathological correlations.

Eur Radiol 2014 Apr 22;24(4):881-8. Epub 2013 Nov 22.

Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan,

Objective: To review established magnetic resonance (MR) criteria and describe a new MR finding for the diagnosis of invasive placenta praevia.

Methods: A retrospective review of prenatal MRI examinations of 65 patients (median age: 35 years) who underwent MR for the screening of invasive placenta praevia. All MRIs were performed on a 1.5-T unit, including axial, coronal and sagittal T2-weighted half-Fourier single-shot turbo spin echo imaging. Fifteen patients were diagnosed with invasive placenta praevia. Two experienced radiologists reviewed the MR images and evaluated a total of six MRI features of the placenta, including our novel finding of the placental protrusion into the internal os (placental protrusion sign). Inter-rater reliability was assessed by using kappa statistics. Features with a kappa statistic >0.40 were evaluated using Fisher's two-sided exact test for comparison of their capabilities for placental invasion assessment.

Results: Interobserver reliability was moderate or better for the intraplacental T2 dark band, intraplacental abnormal vascularity, uterine bulging, heterogeneous placenta and placental protrusion sign. Fisher's two-sided exact test results showed all these features were significantly associated with invasive placenta praevia.

Conclusion: The novel MRI finding of a placental protrusion sign is a useful addition to the established MRI findings for the diagnosis of invasive placenta praevia.

Key Points: • Prenatal diagnosis for an invasive placenta is essential for perinatal planning. • Magnetic resonance imaging provides useful information for the diagnosis of invasive placenta. • The placental protrusion sign is a useful novel MRI finding for predicting invasive placenta.
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http://dx.doi.org/10.1007/s00330-013-3076-7DOI Listing
April 2014

Tumefactive fibroinflammatory lesion presenting with head and neck fibrosclerosing lesions and orbital pseudotumors: a case report.

J Med Case Rep 2013 Nov 14;7:260. Epub 2013 Nov 14.

Division of Infectious Diseases, Kobe University Hospital, Kusunokicho 7-5-2, Chuoku, Kobe, Hyogo 650-0017, Japan.

Introduction: Tumefactive fibroinflammatory lesion is an idiopathic fibrosclerosing disorder occurring in the head and neck region. It is one of a broad spectrum of entities named inflammatory pseudotumors and, as the name suggests, it mimics a lot of diseases such as malignancies or infections. Combined with its rarity, tumefactive fibroinflammatory lesion can be a tremendous diagnostic challenge. This case report describes a case of tumefactive fibroinflammatory lesion, which was initially thought to be peri-orbital and mandibular osteomyelitis caused by Aspergillus. A lengthy work up ensued and was required to reach the final diagnosis.

Case Presentation: A 64-year-old Asian man with a history of diabetes mellitus and chronic kidney disease who was on hemodialysis presented with worsening exophthalmos and relapsing trismus. He was diagnosed as "mandibular osteomyelitis" about 20 years ago. Since then he had suffered chronic relapsing exophthalmos and jaw pain with numerous medical treatments. In 2011 he was diagnosed as peri-orbital and intramandibular aspergillosis because a serum Aspergillus galactomannan assay was positive. He was treated with multiple antifungal medications to no avail. A biopsy of his orbital lesions was not revealing. After repeated biopsies, we finally concluded that the patient was suffering from tumefactive fibroinflammatory lesion. Corticosteroid therapy was initiated with prompt response.

Conclusions: Tumefactive fibroinflammatory lesion is a rare inflammatory benign tumor, which mimics many inflammatory and neoplastic disorders. Conventional work up including biopsy may not lead to the diagnosis without understanding this entity. Awareness of this disorder will aid early diagnosis and treatment.
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http://dx.doi.org/10.1186/1752-1947-7-260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225680PMC
November 2013

Unusual hepatic involvement with significant fibrosis in adult T cell leukemia.

Ann Hematol 2014 May 13;93(5):897-8. Epub 2013 Aug 13.

Hematology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan,

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http://dx.doi.org/10.1007/s00277-013-1875-1DOI Listing
May 2014

Computed diffusion-weighted imaging using 3-T magnetic resonance imaging for prostate cancer diagnosis.

Eur Radiol 2013 Dec 25;23(12):3509-16. Epub 2013 Jul 25.

Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan,

Objective: To assess the efficacy of computed diffusion-weighted images (cDWIs) of b = 2000 s/mm(2) (cDWI2000) generated from DWIs of b = 0 and 1000 for prostate cancer (PCa) diagnosis in comparison with that of measured original DWIs of b = 1000 (mDWI1000) and b = 2000(mDWI2000) using 3-T MRI.

Methods: Eighty patients who underwent a preoperative MRI examination, including T2WI and DWI (b = 0, 1000, 2000 s/mm(2)), were enrolled in this study. Four combinations of images, protocol A (T2WI alone), B (T2WI + mDWI1000), C (T2WI + mDWI2000) and D (T2WI + cDWI2000), were assessed for their diagnostic capability. Areas under the receiver operating characteristic curve (Az) and diagnostic performance were evaluated, as well as contrast ratios (CR) between cancerous and non-cancerous lesions for each DWI.

Results: The highest CR was obtained with cDWI2000 (0.29 ± 0.16). Sensitivity, specificity, accuracy, and Az of the protocols were: A: 66.3 %, 59.4 %, 63.0 %, 0.67; B: 82.6 %, 62.0 %, 72.5 %, 0.80; C: 84.1 %, 66.5 %, 75.5 %, 0.86; D: 83.2 %, 70.0 %, 76.6 %, and 0.84, respectively The specificities and accuracies of protocol C and D were significantly higher than those of protocol B (P < 0.05).

Conclusion: cDWI2000 appears to be more effective than mDWI1000, and at least as effective as mDWI2000 for PCa diagnosis.
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http://dx.doi.org/10.1007/s00330-013-2958-zDOI Listing
December 2013

Distinctive histopathologic findings of pancreatic hamartomas suggesting their "hamartomatous" nature: a study of 9 cases.

Am J Surg Pathol 2013 Jul;37(7):1006-13

Department of Pathology, Saitama International Medical Center, Saitama Medical University, Hidaka, Japan.

Pancreatic hamartoma is a rare tumor, and its characteristic histopathologic features have not yet been fully evaluated. In this study, we collected 9 cases of pancreatic hamartoma to elucidate distinctive histopathologic features that can serve to establish this tumor as a clear disease entity and thus formulate useful histopathologic criteria for this tumor. The cases comprised 4 men and 5 women with a mean age of 62.7 years. The average tumor diameter was 3.3 cm. All patients underwent surgical treatment, and none showed any recurrence postoperatively. Macroscopically, pancreatic hamartomas were well-demarcated tumors with a solid or solid and cystic appearance. Microscopically, these tumors comprised mature acini and small-sized to medium-sized ducts showing a distorted architecture with various amounts of fibrous stroma. Strikingly, the tumors consistently lacked concentric elastic fibers in their duct walls, peripheral nerves, and well-formed islets of Langerhans, all of which exist in both the normal and atrophic pancreas. Immunohistochemically, scattered chromogranin A-positive neuroendocrine cells were observed in the acinar and ductal components. Ductal components were positive for S-100 protein. Spindle-shaped stromal cells expressed CD34 and/or c-kit. These histopathologic features were distinct from those of 5 cases of pancreatic ductal adenocarcinoma, 3 cases of type 1 autoimmune pancreatitis (lymphoplasmacytic sclerosing pancreatitis), 3 cases of alcoholic chronic pancreatitis, and 5 cases of normal pancreas. In conclusion, pancreatic hamartomas share some distinctive histopathologic features and clinical outcomes (neither recurrence nor metastasis) that allow them to be interpreted as malformative lesions. The term "hamartoma" is appropriate for these unique lesions.
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http://dx.doi.org/10.1097/PAS.0b013e318283ce4cDOI Listing
July 2013

Do apparent diffusion coefficient (ADC) values obtained using high b-values with a 3-T MRI correlate better than a transrectal ultrasound (TRUS)-guided biopsy with true Gleason scores obtained from radical prostatectomy specimens for patients with prostate cancer?

Eur J Radiol 2013 Aug 19;82(8):1219-26. Epub 2013 Mar 19.

Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan.

Objective: To investigate the usefulness of apparent diffusion coefficient (ADC) values in predicting true Gleason scores from radical prostatectomy specimen (tGS), compared with systematic transrectal ultrasound (TRUS)-guided biopsy GS (bGS).

Materials And Methods: One hundred and five patients with biopsy-proven prostate cancer underwent preoperative DWI (b-values of 0, 1000, and 2000s/mm(2)) of 3-T MRI. The mean and minimum ADCs of visible tumors were calculated for either of a pair of b-values: 0 and 1000s/mm(2) (ADC1000), or 0 and 2000s/mm(2) (ADC2000), and relationships between the four ADC parameters and tGS evaluated for the peripheral zone (PZ) and transition zone (TZ). For multiple tumors, the dominant tumor's GS and ADCs were estimated for cancer aggressiveness assessment by computing ROC curves.

Results: Significant negative correlations were observed between tGS and mean ADC1000, mean ADC2000, minimum ADC1000, and minimum ADC2000 (r=-0.41, -0.39, -0.39, and -0.37, respectively) of 100 visible PZ tumors and 66 visible TZ tumors (r=-0.40, -0.42, -0.29, and -0.21, respectively). For distinguishing high-grade from low/intermediate-grade PZ lesions, the areas under the curve (AUCs) of mean ADC1000 (0.751), mean ADC2000 (0.710), minimum ADC1000 (0.768), and minimum ADC2000 (0.752) were similar to that of the highest bGS (0.708) (p=0.61, p=0.98, p=0.47, and p=0.60, respectively). For distinguishing high-grade from low/intermediate-grade TZ lesions, AUCs of mean ADC1000 (0.779), and mean ADC2000 (0.811) were similar to that of the highest bGS (0.805) (p=0.83 and p=0.97).

Conclusion: Tumor ADCs obtained with high b-values could predict prostate cancer aggressiveness as effectively as systematic TRUS-guided biopsy.
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http://dx.doi.org/10.1016/j.ejrad.2013.02.021DOI Listing
August 2013