High frequency of concomitant squamous metaplasia in bulbar urethral stricture and its association with reconstructive delay and urethral rest.

PURPOSE: To determine the prevalence of concomitant squamous metaplasia (SM), the initial histological change from normal urethra to urethral stricture, in bulbar urethral strictures and to investigate the associated clinical factors. METHODS: A retrospective review was conducted on 165 male patients with bulbar urethral strictures who underwent excision and primary anastomosis (EPA) between 2010 and 2020, for whom complete clinical data and excised urethral specimens were available. An experienced pathologist histologically evaluated concomitant SM in paraffin sections of the proximal end of the excised urethra blinded to the clinical data. Disease duration was calculated as the period from the initial diagnosis of urethral stricture to the date of EPA. The association between concomitant SM and clinical background was investigated. RESULTS: SM was identified in 86 (52.1%) patients. The median disease duration in patients with SM (38 months) was significantly longer than that in patients without SM (9 months, p < 0.0001). In multivariate analysis, the longer disease duration, non-traumatic stricture etiology, and failure to maintain urethral rest with urinary diversion via a suprapubic tube for more than 90 days were independent factors predicting concomitant SM. No significant difference was observed in success rates of EPA between patients with SM (93.2%) and those without SM (97.5%, p = 0.18). CONCLUSIONS: Reconstructive urologists need to be aware that concomitant SM is frequent in patients with bulbar urethral stricture, especially in those with long disease duration and those who were voiding volitionally during the period of urethral rest.

Histological parameters and stromal desmoplastic status affecting accurate diagnosis of extraprostatic extension of prostate cancer using multi-parametric magnetic resonance imaging.

OBJECTIVE: To investigate the clinicopathological factors affecting discrepancies between multi-parametric magnetic resonance imaging (mpMRI) and histopathological evaluation for diagnosis of extraprostatic extension (EPE) of prostate cancer. METHODS: One hundred-and-three lesions from 96 cases with suspected EPE on preoperative mpMRI, of which 60 and 43 showed bulging and frank capsular breach, respectively, were grouped according to pathological (p)EPE in radical prostatectomy specimens. Additionally, clinicopathological/immunohistochemical findings for periostin reflecting a desmoplastic stromal reaction were compared between these groups. RESULTS: pEPE was detected in 49 (48%) of the 103 lesions. Of these, 25 (42%) showed bulging and 24 (56%) showed frank capsular breach on MRI. In the total cohort, the absence of pEPE was significantly associated with a lower Gleason Grade Group (GG) (p < 0.0001), anterior location (p = 0.003), absence of intraductal carcinoma of the prostate (IDC-P) (p = 0.026), and high stromal periostin expression (p < 0.0001). These trends were preserved in subgroups defined by MRI findings, except for anterior location/IDC-P in the bulging subgroup. CONCLUSIONS: GG, anterior location, and periostin expression may cause mpMRI-pathological discrepancies regarding EPE. Periostin expression was a significant pEPE-negative factor in all subgroup analyses. Our results indicate that patients with suspected EPE on MRI, regardless of their pEPE results, should be followed as carefully as those with definite pEPE.

Copy number gain of ACTN4 is associated with poor prognosis in patients with upper urinary tract urothelial carcinoma.

α-Actinin4 (ACTN4), an isoform of non-muscular α-actinin, is involved in enhancing cell motility and promoting cancer infiltration and metastasis in various cancers. However, information remains limited regarding the pathological significance of ACTN4 expression in upper urinary tract urothelial carcinomas (UUTUCs). We obtained tumor samples from 168 consecutive patients with newly diagnosed UUTUCs (92 with renal pelvic cancers and 76 with ureteral cancers), who were treated with nephroureterectomy or partial ureterectomy, and analyzed the expression of the ACTN4 protein and the amplification of ACTN4 using immunohistochemistry and fluorescence in situ hybridization (FISH), respectively. The median follow-up duration was 65 months. Among 168 cases, 49 (29%) showed ACTN4 protein overexpression and 25 (15%) showed copy number gain (≥4 copies per cell) of ACTN4. The copy number gain of ACTN4 detected using FISH significantly correlated with ACTN4 protein overexpression and several adverse clinicopathological factors, including higher pathological T stage, lymphovascular invasion, lymph node metastasis, positive surgical margin, concomitant subtype histology, and non-papillary gross finding. Cox univariate regression analyses revealed that both copy number gain of ACTN4 and ACTN4 protein overexpression were significant risk factors for extraurothelial recurrence and death (each p < 0.0001), but multivariate analysis revealed that only copy number gain of ACTN4 was an independent risk factor for extraurothelial recurrence and death (p = 0.038 and 0.027, hazard ratio = 2.16 and 2.17, respectively). This is the first study demonstrating the aberrant expression status of ACTN4 in UUTUC and indicating its putative usefulness as a prognostic indicator in patients with UUTUC.

Myofibroblast-dominant proliferation associated with severe fibrosis in bulbar urethral strictures.

OBJECTIVES: Myofibroblast-dominant proliferation (relative to fibroblast proliferation) is the key process in urethral fibrosis, but its association with clinical features is not understood. We conducted a histological analysis of urethral strictures and examined the association between myofibroblast proliferation and stricture characteristics. METHODS: Formalin-fixed, paraffin-embedded urethral sections sliced axially from 175 male patients with bulbar urethral strictures were retrospectively analyzed. All patients underwent excision and primary anastomosis between September 2008 and January 2021 by a surgeon (AH). Masson's trichrome stain was used to estimate the area of fibrosis. Corresponding unstained slides with the largest area of fibrosis were selected and double-immunostained with anti-smooth muscle actin (SMA) and anti-TE-7 mouse monoclonal antibodies for the assessment of myofibroblasts and fibroblasts, respectively. The ratio of the number of SMA-positive cells to the number of TE-7-positive cells (SMA/TE-7 ratio) was calculated. RESULTS: The area of fibrosis in strictures due to perineal trauma (n = 85, median 108.9 mm2 ) was significantly larger than that in non-traumatic strictures (n = 90, median 42.9 mm2 , p < 0.0001). The area of fibrosis positively correlated with SMA expression (r = 0.35, p < 0.0001) and the SMA/TE-7 ratio (r = 0.36, p < 0.0001), but not with TE-7 expression (r = -0.01, p = 0.75). In a multivariate linear regression model, traumatic etiology (standard coefficient 0.37, t value 3.9, p < 0.0001) and increased SMA expression (standard coefficient 0.17, t value 2.1, p = 0.03) were the predictors of wide fibrosis area. CONCLUSIONS: Myofibroblast-dominant proliferation may contribute to the pathogenesis of severe urethral fibrosis.

MRI-detectability and histological factors of prostate cancer including intraductal carcinoma and cribriform pattern.

BACKGROUND: Histopathological characteristics affecting the detectability of clinically significant prostate cancer (csPCa) on magnetic resonance imaging (MRI) remain unclear. This study aimed to compare the histopathology between MRI-detectable and MRI-undetectable cancers, emphasizing intraductal carcinoma of the prostate (IDC-P) and predominant Gleason pattern 4 subtype. METHODS: This single-center retrospective study enrolled 153 consecutive patients with 191 lesions who underwent preoperative multiparametric MRI and subsequent radical prostatectomy. MRI/histopathological findings and area fractions of histological components (cancer cells, stroma, and luminal spaces) of MRI-detectable and MRI-undetectable cancers were compared. Data were analyzed using Fisher's exact, independent t, or Mann-Whitney U tests. RESULTS: Overall, 148 (77%) and 43 (23%) cancers were MRI-detectable and MRI-undetectable, respectively. MRI-detectable cancers were significantly larger than MRI-undetectable cancers (p = 0.03). The percentage of lesions in Grade Group 3 or higher was significantly higher among MRI-detectable cancers than among MRI-undetectable cancers (p = 0.02). MRI detectability of csPCa was associated with increases in relative area fractions of cancer cells (p < 0.001) and decreases in those of stroma (p < 0.001) and luminal spaces (p < 0.001) in prostate cancer (PCa) than the percentage of Gleason pattern 4 (p = 0.09). The percentage of lesions containing IDC-P was similar for MRI-detectable and MRI-undetectable cancers (40% vs. 33%; p = 0.48). The distribution of cribriform gland subtypes was not significantly different between MRI-detectable and MRI-undetectable Gleason pattern 4 subtype cancers (p > 0.99). Contrarily, the ratio of fused gland subtype was significantly higher in MRI-detectable than in MRI-undetectable cancers (p = 0.03). Furthermore, the ratio of poorly-formed gland subtype was significantly higher in MRI-undetectable than in MRI-detectable cancers (p = 0.01). CONCLUSIONS: MRI detectability of csPCa is strongly associated with the relative area fractions of cancer cells, stroma, and luminal spaces in PCa rather than conventional histopathological parameters. Neither the presence nor the percentage of IDC-P affected MRI detectability.

Prognostic impact of stromal periostin expression in upper urinary tract urothelial carcinoma.

BACKGROUND: Periostin is an extracellular matrix protein that has been known to be implicated in fibrillogenesis and cell migration, including cancer metastasis. Periostin overexpression in cancer cells and/or intervening stroma is usually related to tumor progression and poor patient outcomes in various human cancers; however, its role in urothelial carcinoma, especially upper urinary tract urothelial carcinomas (UTUCs), remains inconclusive. METHODS: Samples from 126 consecutive cases of invasive UTUC (69 renal pelvic cancers and 57 ureteral cancers) were histologically reviewed and analyzed for periostin expression using immunohistochemistry. The intensities of immunoreactivity and the fraction of positive cancer cells and stroma (i.e., epithelial and stromal expression, respectively) were classified into four categories each (intensity, 0-3; fraction, 0-25% = 1; 26-50% = 2; 51-75% = 3; and > 75% = 4). The overall score was determined by multiplying both scores, and overall scores ≥ 6 were considered to indicate high periostin expression. RESULTS: Among 126 UTUCs, 55 (44%; 27 renal pelvic and 28 ureteral cancers) showed high stromal periostin expression. None of the cases were considered to have high epithelial periostin expression. High stromal periostin expression was associated with non-papillary gross findings, higher pathological T category, lymphovascular invasion, concomitant carcinoma in situ, subtype histology, lymph node metastasis, positive surgical margins, high tumor budding, and high tumor-associated immune cell status. Multivariate analysis revealed that high stromal periostin expression was an independent predictor of overall survival (p = 0.00072, hazard ratio = 3.62), and lymphovascular invasion and high stromal periostin expression were independent predictors of cancer-specific survival (p = 0.032 and 0.020, hazard ratio = 2.61 and 3.07, respectively). CONCLUSIONS: Stromal periostin expression was often observed in invasive UTUCs with adverse clinicopathological factors and may be a useful predictor of patient outcomes.

Intraepithelial lymphocytes are indicators of better prognosis in surgically resected endometrioid-type endometrial carcinomas at early and advanced stages.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) may be useful prognostic indicators in endometrial cancer. However, standardized assessment methods and the prognostic roles of these cells in different stage groups are unclear. METHODS: Formalin-fixed paraffin-embedded tissue samples of 107 endometrioid-type endometrial carcinomas (EECs) comprising 60 stage IB and 47 stage IIIC or IVB cases were evaluated. CD3+ TILs, CD8+ TILs, CD68+ TAMs, and CD163+ TAMs were detected by immunohistochemistry, and their densities were evaluated by semiquantitative and quantitative methods. TILs within tumor epithelial cell nests (E-TILs) and those within the stroma at the invasive front (S-TILs) were evaluated separately for CD3+ and CD8+ cells. The "TIL score" was defined as the sum of semiquantitative scores of CD3+ E-TILs, CD3+ S-TILs, CD8+ E-TILs, and CD8+ S-TILs. For TAMs, the area of CD68+ and CD163+ cells in the invasive margin were semiquantitatively and quantitatively evaluated. Clinicopathological and prognostic implications of TILs and TAMs in stage IB and IIIC/IVB EECs were examined by Cox univariate and multivariate analyses. RESULTS: By Cox univariate analyses, semiquantitatively low CD3+ E-TILs, low CD8+ E-TILs, and low "TIL score" were significantly correlated with worse prognosis in stage IB patients (P = 0.011, 0.040, and 0.039, respectively). Likewise, low CD3+ E-TILs and low CD8+ E-TILs, by both semiquantitative (P = 0.011 and 0.0051) and quantitative evaluations (P < 0.0001, and P = 0.0015) and low "TIL score" (P = 0.020) were significantly correlated with worse prognosis in stage IIIC/IVB patients. By Cox multivariate analyses, semiquantitatively low CD3+ E-TILs and low CD8+ E-TILs, low "TIL score", and quantitatively low CD3+ E-TILs and low CD8+ E-TILs were independent worse prognostic factors in stage IIIC/IVB (P = 0.0011, 0.0053, 0.012, < 0.0001, and < 0.0001, respectively). CD68+ or CD163+ TAMs were not correlated with prognosis in any patients. CONCLUSIONS: Both semiquantitatively and quantitatively low E-TILs, are correlated with worse prognosis in both early and advanced stage patients with EECs. In particular, CD3+ E-TILs and CD8+ E-TILs are potentially useful prognostic markers in patients with EEC regardless of the stage.

Risk assessment of femoral pathological fracture in prostate cancer patients by computed tomography analysis.

INTRODUCTION: Prostate cancer often forms osteoblastic lesions that appear as a high-dense shadow upon X-ray. Although the lesions may seem to increase bone strength, pathological fracture occurs in one in four patients with prostate cancer. The aim of this study is to elucidate the factors that may increase the risk of pathological fracture in patients with prostate cancer metastases in the proximal femur by analyzing computed tomography data. MATERIALS AND METHODS: Computed tomography data of the femur of 62 prostate cancer patients were retrospectively analyzed. The patients were divided into three groups based on the presence or absence of femoral metastatic lesions and pathological fracture. Surgical specimens of the proximal femur collected from patients who had a pathological fracture were histologically analyzed. RESULTS: Bone density in the marrow area was increased in all cases with metastases compared with those with no metastases. Contrarily, the cortical bone density at the medial trochanter region was significantly lower in patients who had pathological fractures in the proximal femur than those who did not. Accordingly, histological analysis of the surgical specimens revealed that the affected cortical bone was osteopenic without any apparent new bone formation. CONCLUSION: These results indicate that prostate cancer is less effective in inducing bone formation in the cortex than in the marrow and that the decrease in the cortical bone density at the medial trochanter region leads to an increased risk of pathological fracture. Therefore, a previously undocumented risk factor for pathological fracture in prostate cancer patients is presented.

Ability of photocurable gelatin to prevent stricture recurrence after urethral dilation in rabbits.

OBJECTIVES: To evaluate the ability of photocurable gelatin to prevent stricture recurrence after urethral dilation in a rabbit urethral stricture model. METHODS: We created urethral strictures in the bulbar urethras of 10 male Japanese white rabbits using electrocoagulation. After 1 month, the rabbits were randomly divided into Group A (n = 5; urethral stricture dilation and the local application of photocurable gelatin using a ruthenium photoinitiator and irradiation with a light-emitting diode light [λ = 455 nm, 50 mW/cm2 ] for 1 min) and Group B (n = 5; dilation only). Urethral stricture status was evaluated 1-2 months later by retrograde urethrography and urethroscopy. The lumen ratio (urethral width at the stricture site to the normal urethral width on retrograde urethrography) was calculated. Urethral patency was considered to be improved when the urethral lumen could accommodate a 10-Fr urethroscope without resistance. Urethral specimens were harvested for histopathological examination. RESULTS: The mean lumen ratio did not differ significantly between Groups A and B before dilation (25.8% vs 23.4%; P = 0.40), but differed significantly after dilation (65.5% vs 27.3%, respectively; P = 0.03). Urethral patency improved in all rabbits in Group A (100%) versus one rabbit in Group B (20%; P = 0.02). The mean circumference of the regenerated urethral epithelium at the stricture site was larger in Group A than in Group B (14 mm vs 6.6 mm; P = 0.06). CONCLUSIONS: Photocurable gelatin can reduce urethral stricture recurrence after dilation in a rabbit model.

Fluvastatin potentiates anticancer activity of vorinostat in renal cancer cells.

Drug repositioning is an emerging approach to developing novel cancer treatments. Vorinostat is a histone deacetylase inhibitor approved for cancer treatment, but it could attenuate its anticancer activity by activating the mTOR pathway. The HMG-CoA reductase inhibitor fluvastatin reportedly activates the mTOR inhibitor AMP-activated protein kinase (AMPK), and we thought that it would potentiate vorinostat's anticancer activity in renal cancer cells. The combination of vorinostat and fluvastatin induced robust apoptosis and inhibited renal cancer growth effectively both in vitro and in vivo. Vorinostat activated the mTOR pathway, as evidenced by the phosphorylation of ribosomal protein S6, and fluvastatin inhibited this phosphorylation by activating AMPK. Fluvastatin also enhanced vorinostat-induced histone acetylation. Furthermore, the combination induced endoplasmic reticulum (ER) stress that was accompanied by aggresome formation. We also found that there was a positive feedback cycle among AMPK activation, histone acetylation, and ER stress induction. This is the first study to report the beneficial combined effect of vorinostat and fluvastatin in cancer cells.

Frequent EGFR expression/EGFR amplification and lack of activating mutation in testicular choriocarcinoma.

Choriocarcinoma (CC) is the rarest but most aggressive histological component of adult testicular germ cell tumor (TGCT). Although we previously reported a putative role of epidermal growth factor receptor (EGFR) alterations in the progression of CC, little is known about the kinase-activating mutation status of EGFR, which predicts the response to EGFR-tyrosine kinase inhibitors. In this study, we clinicopathologically reviewed a total of 12 cases of mixed TGCTs with CC components. Immunohistochemistry, fluorescence in situ hybridization, and direct sequencing was performed to investigate EGFR expression, EGFR copy number alterations, and functional mutation of EGFR in these CC components, respectively. Four (33%) of 12 cases exhibited predominant CC components (>50%), and all these patients died due to disease within 62 months. Overexpression of EGFR, higher copy number of EGFR, and amplification of EGFR was observed in 12 (100%), 10 (83%), and 9 (75%) of 12 CC components, respectively. None of the cases showed any mutational events in exons 18 to 24, which encode the tyrosine kinase domain of EGFR. These results confirm an important role of EGFR in the tumor aggressiveness of testicular CCs and may suggest its possible innate resistance against conventional anti-EGFR therapies.

Histological differences in cancer cells, stroma, and luminal spaces strongly correlate with in vivo MRI-detectability of prostate cancer.

The current study aimed to investigate the plausible histopathological factors that affect the detectability of prostate cancers on multiparametric magnetic resonance imaging (MP-MRI). This retrospective study included 59 consecutive patients who had undergone MP-MRI and subsequent radical prostatectomy. The cases were standardized according to the tumor size ranging from 10 to 20 mm on the final pathological diagnosis. Histopathological review and semi-automated imaging analysis were performed to evaluate the relative area fractions of the histological components, including cancer cells, stroma, and luminal spaces. Among the 59 prostatectomy specimens, no case showed two or more foci of cancer that matched the size criteria. Of the 59 lesions, 35 were MRI-detectable [Prostate Imaging Reporting and Data System (PIRADS) score of 3 or greater] and 24 were MRI-undetectable (PIRADS score of 2 or less). No significant differences were observed in Gleason Grade Group, percentage of Gleason pattern 4, and predominant subtype of Gleason pattern 4 between MRI-detectable and MRI-undetectable cancers. On the other hand, significantly higher mean area fraction of cancer cells (60.9% vs. 42.7%, P < 0.0001) and lower mean area fractions of stroma (33.8% vs. 45.1%, P = 0.00089) and luminal spaces (5.2% vs. 12.2%, P < 0.0001) were observed in MRI-detectable cancers than in MRI-undetectable cancers. In a multivariable analysis performed upon exclusion of area fraction of stroma due to its multicollinearity with that of cancer cells, area fractions of cancer cells (P = 0.0031) and luminal space (P = 0.0035) demonstrated strong positive and negative correlation with MRI-detectability, respectively. Changes in cancer cells, stroma, and luminal spaces, rather than conventional histological parameters, could be considered one of the best predictors to clinical, in vivo MRI-detectability of prostate cancer.

Invasive form of ciliated muconodular papillary tumor of the lung: A case report and review of the literature.

We report a case of a 67-year-old woman with an invasive ciliated muconodular papillary tumor (CMPT) that developed in her right middle lobe. The current tumor was incidentally detected during a follow-up imaging examination for a large cell carcinoma that was resected 10 years previously. Partial removal of the middle lobe showed a 2 cm-sized, solid and myxoid tumor located in the peripheral region. Histologically, this tumor primarily consisted of ciliated columnar cells, mucous cells, and basal cells, all of which had relatively swollen nuclei and were proliferating in a lepidic or papillary/micropapillary manner. These features were consistent with those of previously reported CMPT. In addition, atypical spindle tumor cells with more swollen nuclei, which were partly continuous to less atypical basal tumor cells, were focally found and invaded fibrous stroma in a reticular fashion. Immunohistochemically, both basal cells and atypical spindle tumor cells were positive for pancytokeratin, cytokeratin 5/6, and p40. Increased p53 positivity was found in these invading spindle cells compared with basal tumor cells. Neither BRAF V600E nor V600K mutation was detected. We concluded that this tumor was an extremely rare invasive case of CMPT, possibly representing malignant transformation of basal tumor cell components of CMPT.

Erratum: Increased fatty acid synthase expression in prostate biopsy cores predicts higher Gleason score in radical prostatectomy specimen.

[This corrects the article DOI: 10.1186/1472-6890-14-3.].

Elevated fatty acid synthase expression in prostate needle biopsy cores predicts upgraded Gleason score in radical prostatectomy specimens.

BACKGROUND: We examined whether fatty acid synthase (FAS) expression in prostate biopsy cores had valuable information and could predict a Gleason score (GS) upgraded from biopsy to radical prostatectomy (RP) specimens. METHODS: Immunostaining with a FAS antibody was performed on paraffin-embedded prostate biopsy cores with GS 5-6 obtained from 80 patients who subsequently underwent RP. The correlations between FAS expression and clinicopathological parameters, upgrading group, and clinicopathological parameters including FAS expression were analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for upgrading GS. RESULTS: A total of 46 patients (57.5%) with biopsy GS 5-6 were upgraded to GS ≥7 at RP. FAS expression was significantly associated with clinical T stage (P = 0.0232) and positive core rate (P = 0.0245). Upgrading from biopsy GS 5-6 to GS ≥7 at RP was significantly associated with clinical T stage (P = 0.0337), positive core rate (P = 0.0262), and FAS expression (P < 0.0001). FAS expression was a significant predictor for upgrading from biopsy GS 5-6 to GS ≥7 at RP in multivariate analysis (P < 0.0001; odds ratio, 12.35). FAS scores showed the largest area under the receiver-operating characteristic curve (AUC) in preoperative parameters (AUC = 0.753). CONCLUSIONS: Increased FAS expression in prostate biopsy cores could be a novel parameter for upgrading from biopsy GS 5-6 to GS ≥7 at RP. If a biopsy GS is low, the treatment strategy for patients with high FAS expression in prostate biopsy cores should be carefully determined.

Prognostic impact of fatty acid synthase expression in upper urinary tract urothelial carcinoma.

OBJECTIVE: Fatty acid synthase has been shown to be highly expressed in various types of cancers with increased tumour aggressiveness. In this study we examined the level of fatty acid synthase expression in surgically resected upper urinary tract urothelial carcinoma specimens and evaluated the relations between fatty acid synthase expression and the patients' pathological features and clinical outcomes. METHODS: Sections of paraffin-embedded tumour specimens from 113 patients who underwent surgical treatment for upper urinary tract urothelial carcinoma were immunostained with a polyclonal fatty acid synthase antibody, and a tumour was considered to have high fatty acid synthase expression if >50% of the cancer cells stained with moderate-to-strong intensity. Associations between fatty acid synthase expression and the patients' pathological parameters and survival were analyzed statistically. RESULTS: During the follow-up time (median: 46.8 months), 61 patients (54.0%) had recurrence and 17 (15.0%) died of upper urinary tract urothelial carcinoma. High fatty acid synthase expression was significantly associated with high tumour grade (P = 0.0273). Patients with high fatty acid synthase expression had significantly worse recurrence-free survival and extravesical-recurrence-free survival than those with low fatty acid synthase expression (P = 0.0171, P = 0.0228, respectively). In multivariate analysis, high fatty acid synthase expression was an independent predictor of shortened recurrence-free survival (P = 0.0220, hazard ratio (HR) = 1.970). CONCLUSIONS: Fatty acid synthase expression in upper urinary tract urothelial carcinoma is an independent predictor for tumour recurrence. Patients with high fatty acid synthase expression in upper urinary tract urothelial carcinoma should be followed carefully and adjuvant therapy for them should be considered.

Community-acquired lobar pneumonia caused by Pseudomonas aeruginosa infection in Japan: a case report with histological and immunohistochemical examination.

Pseudomonas aeruginosa is a common pathogen in nosocomial and/or healthcare-associated pneumonia, but is rare in community-acquired pneumonia. A 50-year-old previously healthy woman was taken to the emergency department because of rapidly progressing dyspnea. Chest radiograph showed consolidation of the entire right upper lobe, a finding suggestive of lobar pneumonia. The patient died of respiratory failure with bronchial bleeding, on the same day of admission. Autopsy revealed that the alveoli throughout the upper right lobe were filled with dense inflammatory cells mainly consisting of macrophages and neutrophils. Immunoreactive bacilli by using an anti-P. aeruginosa antibody were localized within macrophages accumulated in the alveoli as well in the vessel walls. Lobar pneumonia composed of dense neutrophils and bacteria-laden macrophages with total lung congestion and edema may be characteristic for community-acquired P. aeruginosa pneumonia in a healthy adult.

Increased fatty acid synthase expression in prostate biopsy cores predicts higher Gleason score in radical prostatectomy specimen.

BACKGROUND: Fatty acid synthase (FAS) is highly expressed in various types of cancer, and elevated expression of FAS has been suggested to be a predictor of tumor aggressiveness and poor prognosis. We examined whether FAS expression in prostate biopsy cores could predict the pathological characteristics of radical prostatectomy (RP) specimens. METHODS: Paraffin-embedded prostate biopsy cores, obtained from 102 patients who subsequently underwent RP, were immunostained with polyclonal anti-FAS antibody. The staining intensity was categorized into non-staining, weak, moderate, and strong. Tumors with moderate or strong immunostaining were considered to show high FAS expression, and other tumors were considered to show low FAS expression. The relation between the FAS expression status in biopsy cores and pathological parameters in RP specimens was analyzed. RESULTS: The FAS expression in the biopsy cores of 64 of the 102 tumors (63%) was high, whereas it was low in the biopsy cores of the other 38 tumors (37%). High FAS expression was significantly associated with Gleason Score (GS) ≥ 7 in RP specimens (p< 0.0001). In multivariable logistic regression analyses, GS ≥7 in biopsy cores (p <0.0001), higher preoperative PSA (p = 0.0194), and high FAS expression (p = 0.0004) were independent predictors of GS ≥ 7 in the RP specimen. CONCLUSIONS: Increased FAS expression in prostate biopsy cores could be a novel parameter for predicting higher GS in RP specimens. The treatment strategy for patients with high FAS expression in prostate biopsy cores should be carefully determined.

Implementation of The Paris System for Reporting Urine Cytology improves diagnostic accuracy of selective upper urinary tract cytology.

BACKGROUND: The Paris System for Reporting Urine Cytology (TPS) recommends diagnostic criteria for urinary tract cytology, focusing primarily on the detection of high-grade urothelial carcinoma (HGUC) in the lower urinary tract. The second edition of TPS (TPS 2.0), published in 2022, extends these recommendations to the upper urinary tract (UUT); however, there is a lack of comprehensive data on this subject. METHODS: In total, 223 consecutive UUT cytology specimens from 137 patients were retrieved and reclassified according to TPS 2.0 criteria and were compared with the original diagnosis based on the conventional system (CS). Histologic follow-up within a 3-month period was conducted for 43 patients. RESULTS: Histologic follow-up revealed 30 HGUCs, five low-grade urothelial carcinomas (LGUCs), and eight nonneoplastic fibrotic tissues. The risk of high-grade malignancy for each TPS diagnostic category was 16.7% for nondiagnostic/unsatisfactory, 2.3% for negative for HGUC (NHGUC), 42.1% for atypical urothelial cells, 50.0% for suspicious for HGUC (SHGUC), and 81.8% for HGUC. In all five cases of histologically diagnosed LGUC, the cytologic diagnosis was NHGUC. When SHGUC/HGUC was considered positive, the diagnostic accuracy of TPS had 63% sensitivity, 95% specificity, a 90% negative predictive value, and a 79% positive predictive value, which were better than those of CS. In addition, the TPS indices did not differ significantly between the specimens obtained before and after the application of contrast reagents. CONCLUSIONS: TPS implementation improved the accuracy of UUT cytology in predicting histologic HGUC, which was unaffected by the application of contrast reagents. These data indicate the usefulness of TPS for UUT cytology in routine clinical settings.