Mucinous adenocarcinoma derived from villous adenoma of the kidney with muconephrosis.

Upper respiratory tract villous adenoma (VA) with muconephrosis is rare and should be included in the differential diagnosis when pelvic dilatation with a solid component is detected. VA may transform into malignant mucinous adenocarcinoma, which should be suspected if contrast enhancement on computed tomography (CT)/magnetic resonance imaging (MRI) and restricted diffusion on MRI are observed.

En Bloc Resection Versus Conventional TURBT for T1HG Bladder Cancer: A Propensity Score-Matched Analysis.

BACKGROUND: We aimed to assess the clinical, oncological, and pathological impact of en bloc resection of bladder tumors (ERBT) compared with conventional transurethral resection of bladder tumors (cTURBT) for pT1 high-grade (HG) bladder cancer. PATIENTS AND METHODS: We retrospectively analyzed the record of 326 patients (cTURBT: n = 216, ERBT: n = 110) diagnosed with pT1 HG bladder cancer at multiple institutions. The cohorts were matched by one-to-one propensity scores based on patient and tumor demographics. Recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), and perioperative and pathologic outcomes were compared. The prognosticators of RFS and PFS were analyzed using the Cox proportional hazard model. RESULTS: After matching, 202 patients (cTURBT: n = 101, ERBT: n = 101) were retained. There were no differences in perioperative outcomes between the two procedures. The 3-year RFS, PFS, and CSS were not different between the two procedures (p = 0.7, 1, and 0.7, respectively). Among patients who underwent repeat transurethral resection (reTUR), the rate of any residue on reTUR was significantly lower in the ERBT group (cTURBT: 36% versus ERBT: 15%, p = 0.029). Adequate sampling of muscularis propria (83% versus 93%, p = 0.029) and diagnostic rates of pT1a/b substaging (90% versus 100%, p < 0.001) were significantly better in ERBT specimen compared with cTURBT specimen. On multivariable analyses, pT1a/b substaging was a prognosticator of disease progression. CONCLUSIONS: In patients with pT1HG bladder cancer, ERBT had similar perioperative and mid-term oncologic outcomes compared with cTURBT. However, ERBT improves the quality of resection and specimen, yielding less residue on reTUR and yielding superior histopathologic information such as substaging.

Vertical Lamina Propria Invasion Diagnosed by En Bloc Transurethral Resection is a Significant Predictor of Progression for pT1 Bladder Cancer.

PURPOSE: T1 bladder cancer is characterized by high recurrence and aggressive progression. Muscularis mucosae invasion may be a prognostic factor for progression, but the limitations of conventional transurethral resection of bladder tumors make diagnosis difficult. We correlated degree of invasion with oncologic outcome and evaluated the utility of pathological diagnosis following en bloc resection of bladder tumors. MATERIALS AND METHODS: We retrospectively analyzed the records of 123 consecutive patients diagnosed with pT1 bladder cancer between November 2013 and December 2018. Transurethral resection was conducted in 91 patients, and en bloc resection in 32 patients. All specimens were analyzed for invasion depth and pT1 substaging (T1a/b: invasion above or into/beyond muscularis mucosae, pT1m/e: microinvasive or extensively invasive). Primary end points were prognostic values of pT1 substaging and invasion depth. The secondary end point was the pathological diagnostic utility of en bloc resection. RESULTS: Median followup was 23 months. Three-year progression-free survival rate differed significantly depending on muscularis mucosae invasion (pT1a: 97.3%, pT1b: 72.8%; p=0.003) and invasion depth from basal membrane (<2 mm: 90.6%, ≥2 mm: 77.9%; p=0.03). Multivariate analysis showed that sessile tumor and invasion depth from basal membrane ≥2 mm were independent prognostic factors for progression. Diagnostic rates for pT1a/b and invasion depth were 77.6% and 85.9%, respectively, with transurethral resection, but 100% and 100% with en bloc resection (p=0.01 and p=0.03). CONCLUSIONS: Vertical lamina propria invasion is predictive of progression in T1 bladder cancer, underlining the importance of accurately diagnosing the degree of vertical lamina propria invasion with en bloc resection.

Feasibility and accuracy of pathological diagnosis in en-bloc transurethral resection specimens versus conventional transurethral resection specimens of bladder tumour: evaluation with pT1 substaging by 10 pathologists.

AIMS: En-bloc transurethral resection (TUR) of bladder tumour (ERBT) is designed to provide more accurate pathological diagnosis of specimens than conventional TUR of bladder tumour (cTURBT). Some studies have reported that T1 bladder cancer substage could be a prognostic factor in assessing tumour progression, but such substaging has not been widely adopted because of problems with pathological diagnosis using cTURBT specimens. The aim of this study was to evaluate the possible advantages of en-bloc TUR specimens in T1 substaging following assessment by a panel of 10 pathologists. METHODS AND RESULTS: We assessed the substages in 123 patients (cTURBT, n = 91; ERBT, n = 32) who were diagnosed with pT1 bladder cancer. We randomly selected 10 ERBT specimens and 10 cTURBT specimens with cancer invasion areas equivalent to those of their corresponding ERBT specimens. Ten pathologists performed pT1 substaging for pT1a/b/c and pT1m/e in 20 patients (cTURBT, n = 10; ERBT, n = 10). We evaluated diagnostic times and rates of diagnostic concordance among these pathologists, comparing cTURBT and ERBT. The median diagnostic times per slide were 87.7 s [interquartile range (IQR) 71.9-109.2 s) for cTURBT and 54.7 s (IQR 46.0-59.6 s) for ERBT (P = 0.009). The rate of diagnostic concordance was significantly better for ERBT specimens. For pT1a/b/c, the median concordance rates were 50% for cTURBT and 80% for ERBT (P = 0.02); for pT1m/e, the median concordance rates were 70% for cTURBT and 90% for ERBT (P = 0.05). For pT1a/b/c, the average κ-values between the pathologist and the standard diagnosis were 0.04 for cTURBT and 0.47 for ERBT. CONCLUSIONS: The use of ERBT specimens shortened the diagnostic time and minimised interobserver variability for T1 substaging compared with the use of cTURBT specimens.

HER2 Status in Molecular Subtypes of Urothelial Carcinoma of the Renal Pelvis and Ureter.

INTRODUCTION: Erb-b2 receptor tyrosine kinase 2 (ERBB2, also known as HER2) gene amplification or protein overexpression occurs in certain types of urothelial carcinomas. Molecular pathologic classification of urinary bladder cancer using immunohistochemistry has identified basal and luminal subtypes with differing prognoses, but the HER2 status of these subtypes has not been investigated. In addition, research on urothelial carcinoma of the renal pelvis and ureter (UCRPU) has not progressed because of its rarity, though its prognosis is worse than that of bladder cancer. In this study, we evaluated the clinical significance of HER2 status in molecular subtypes of UCRPU. MATERIALS AND METHODS: HER2 status (protein overexpression and/or gene amplification) and molecular subtyping were determined for 148 cases of UCRPU (83 and 65 cases in the renal pelvis and ureter, respectively), using immunohistochemistry and fluorescent in situ hybridization, and compared with clinicopathologic factors. RESULTS: Subtype analysis revealed that the cases were 46% basal and 54% luminal. HER2 protein overexpression and/or gene amplification was observed in 14% of UCRPU cases and was significantly more frequent in the luminal subtype than in the basal (22% vs. 4%; P = .0030). Univariate analysis showed that the overall survival of patients with HER2-positive UCRPU was significantly shorter than those with HER2-negative tumors. CONCLUSIONS: HER2 protein overexpression and gene amplification were specifically observed in the luminal subtype of UCRPU, suggesting that these cases may respond to HER2-targeted therapies like trastuzumab.

Cases Having a Gleason Score 3+4=7 With <5% of Gleason Pattern 4 in Prostate Needle Biopsy Show Similar Failure-free Survival and Adverse Pathology Prevalence to Gleason Score 6 Cases in a Radical Prostatectomy Cohort.

Recent discussions have suggested expanding the inclusion criteria for active prostate cancer surveillance to include cases with a Gleason score (GS) of 3+4=7. In this study, we examined this proposed use of a limited percent Gleason pattern 4 (%GP4) to identify candidates of active surveillance among 315 patients who underwent radical prostatectomy for prostate cancer with a GS of 6 or 3+4=7 via needle biopsy. The latter cases were divided into 4 groups using highest or overall %GP4 cut-off values of 5% and 10% as determined from prostate needle biopsies. The frequency of adverse pathology and risk of biochemical recurrence were compared between the GS 6 and both GS 3+4=7 groups. Adverse pathology was defined as a GS 4+3=7 or higher, pT3b staging or positive lymph node metastasis. Notably, the Gleason pattern 4 <5% and GS 6 groups did not differ significantly in terms of the frequency of adverse pathology and risk of biochemical recurrence by the highest method. However, other highest Gleason pattern 4 categories had significantly higher frequencies and risks. Using the overall method, even the Gleason pattern 4 <5% group had a significantly higher frequency of adverse pathology and risk of biochemical recurrence relative to the GS 6 group. In conclusion, our findings suggest that patients with a GS 3+4=7 on biopsy with a highest %GP4 <5% are similar candidates for active surveillance to men with GS 6 cancers.

Differential expression of androgen receptor variants in hormone-sensitive prostate cancer xenografts, castration-resistant sublines, and patient specimens according to the treatment sequence.

BACKGROUND: Androgen receptor variants (AR-vs), especially AR-v7 and AR-v 5, 6, and 7 exon-skipped (AR-v567es), are reportedly key players in the development of castration-resistant prostate cancer (CRPC). We previously established a mouse xenograft model (JDCaP) from a metastatic skin lesion from a Japanese patient with CRPC and that was revealed to exhibit androgen sensitivity. In the present study, we established multiple castration-resistant xenograft models from JDCaP mice to investigate the biological features of CRPC. METHODS: Tissue from JDCaP mice was transplanted into male and female nude mice, and after serial passaging, castration-resistant sublines (JDCaP-CR2M and JDCaP-CR4M in male mice, JDCaP-CR2F and JDCaP-CR4F in female mice) were established. We investigated anti-androgen and testosterone sensitivity and the messenger RNA expression pattern of full-length AR and AR-vs. In addition, we compared AR protein levels of patient specimens among primary, local-recurrent, and two skin-metastatic tumors. RESULTS: All JDCaP-CR sublines showed continuous growth following the administration of bicalutamide, although the effects of testosterone varied among sublines. Parental JDCaP and JDCaP-CR2M, JDCaP-CR4M, and JDCaP-CR4F sublines expressed AR-v7, whereas JDCaP-CR2F exhibited elevated AR-v567es expression resulting from genomic deletion, which was confirmed by DNA sequencing. Moreover, we confirmed AR-v7 expression in the tumor of the original patient after androgen-deprivation therapy. CONCLUSIONS: Each JDCaP-CR subline showed different AR-v-expression patterns, with JDCaP-CR2F expressing AR-v567es due to genomic deletion. Our results indicated that AR-vs emerged after androgen-deprivation therapy and appeared essential for acquisition of castration resistance.

Comparison of ERG and SPINK1 expression among incidental and metastatic prostate cancer in Japanese men.

BACKGROUND: TMPRSS2:ERG fusion is the most common genetic event in prostate cancer (PCa). However, its association with prognosis is controversial. Overexpression of serine protease inhibitor Kazal-type 1 (SPINK1) was almost exclusively defined in ERG-negative PCa in most studies. This study aimed to determine the association between ERG and SPINK1 expression and the biological aggressiveness of PCa by analyzing their expression in incidental and metastatic cohorts. METHODS: A total of 143 cystoprostatectomy specimens of invasive bladder cancer and 98 biopsy specimens from de novo metastatic PCa were analyzed. The prostate gland of cystoprostatectomy specimens was fixed and sliced in step sections. Immunohistochemistry of ERG and SPINK1 was conducted, and the results were correlated with the clinicopathological characteristics of the patients. RESULTS: The overall prevalence of incidental cancer was 32.2% (46/143). The frequencies of both ERG and SPINK1 expression were not significantly different between incidental and metastatic cohorts (15.2% and 14.3%; P = 1.00, and 6.5% and 12.2%; P = 0.38, respectively). In the metastatic cohort, any pre-treatment factors were not significantly associated with the frequencies of ERG and SPINK1 expression. However, SPINK1 expression was significantly associated with a shorter time to castration-resistant PCa (CRPC) (P = 0.048). Meanwhile, overall survival was not significantly associated with the expression status of ERG and SPINK1 (P = 0.71). CONCLUSIONS: ERG and SPINK1 expression may not have significant influence on the metastatic behavior of PCa. SPINK1 expression was significantly associated with a shorter time to CRPC in metastatic PCa. The expression profile of ERG and SPINK1 may be a useful predictor for effect of androgen deprivation therapy in patients with metastatic castration-sensitive PCa.

Anatomical localization and clinical impact of sentinel lymph nodes based on patterns of pelvic lymphatic drainage in clinically localized prostate cancer.

BACKGROUND: Although sentinel lymph node in prostate has been generating renewed interest, its significance remains controversial due to inadequate evidence. METHODS: We reviewed a prospective cohort of 50 consecutive patients with intermediate- to high-risk localized prostate cancer who had undergone laparoscopic radical prostatectomy. Sentinel lymph node biopsy by fluorescence detection using intraoperative imaging with indocyanine green and backup extended pelvic lymph node dissection were conducted prior to prostatectomy. Intraoperative and pathological findings were elaborated and compared for confirmation. RESULTS: Sentinel lymph nodes were successfully identified in 47 patients (94%). A median of four sentinel lymph nodes was detected per patient. Lymph node metastasis was confirmed in six patients (12%), all of whom had positive sentinel lymph nodes. Three typical pathways of lymphatic drainage related to sentinel lymph nodes from the prostate were recognized. Ninety-one percent of the positive sentinel lymph nodes (10/11) were located at two predominant sites along these characteristic lymphatic pathways. One site was the junctional nodes, located at the junction between internal and external iliac vessels. The other was the distal internal iliac nodes, located along the inferior vesical artery. CONCLUSIONS: Over 90% of positive sentinel lymph nodes were identified at two predominant sites. Priority should be given to the removal of these sentinel lymph nodes, which are located closer to the prostate, in pelvic lymph node dissection. Particular attention should be paid to identifying these nodes to reduce the possibility of overlooking lymph node metastasis.

[EXPRESSION OF PLAKIN FAMILY IN UROTHELIAL CARCINOMA OF THE UPPER URINARY TRACT].

(Objective) To determine whether the plakin family proteins periplakin, desmoplakin, plectin, and envoplakin could be markers of urothelial carcinoma of the upper urinary tract. (Materials and methods) Fifty-seven surgical specimens were obtained from patients with urothelial carcinoma of the upper urinary tract, who were admitted to the Jikei University Hospital between April 2000 and December 2005. The expression of plakin family proteins in cancerous and normal tissues was investigated using immunohistochemistry, and its association with clinicopathological parameters was analyzed. (Results) The expression of periplakin, envoplakin, and desmoplakin was significantly lower in cancerous tissue than in normal urothelium (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). Strong desmoplakin expression in cancerous tissue was significantly associated with poor cancer-specific survival and overall survival (P = 0.023 and P = 0.034, respectively, compared with cancerous tissue with slight or less desmoplakin expression). Furthermore, strong plectin expression was significantly associated with poor metastasis-free survival (P = 0.034, compared with cancerous tissue with slight or less plectin expression). (Conclusion) Plakin family, particularly desmoplakin was suggested to be a prognostic marker of urothelial carcinoma of the upper urinary tract.

Polypoid endometriosis of the ovary and müllerianosis of pelvic lymph nodes mimicking an ovarian carcinoma with lymph node metastasis.

Polypoid endometriosis is a distinctive variant of endometriosis with histological features simulating those of endometrial polyps. Müllerianosis is characterized by the presence of lesions at any site containing admixtures of endosalpingiosis, endometriosis, and endocervicosis. Here, we report a rare case of polypoid endometriosis of the ovary with müllerianosis of the pelvic lymph nodes in a 44-year-old woman without a past history of pelvic surgery. Magnetic resonance imaging revealed an ovarian tumor containing papillary nodules up to 3.0 cm in diameter and left pelvic lymph node enlargement. Nodules in ovarian tumor showed heterogeneous high intensity on T2-weighted image and high intensity on diffusion-weighted image and were mildly enhanced by gadolinium contrast material. Enlarged lymph node was markedly enhanced by gadolinium. We considered polypoid endometriosis in the differential diagnosis according to the results of the magnetic resonance imaging, and polypoid endometriosis was included in intraoperative consultation, however, ovarian carcinoma with lymph node metastasis could not be denied. According to histological examination, the final diagnosis was determined as polypoid endometriosis with glandular hyperplasia of the left ovary and müllerianosis in the obturator lymph nodes. To the best of our knowledge, this is the first report of polypoid endometriosis and müllerianosis of the pelvic lymph node.

Secondary osteosarcoma developing 10 years after chemoradiotherapy for non-small-cell lung cancer.

A 53-year-old female patient was admitted with pain and a progressively enlarging mass in the right upper chest. Chest computed tomography revealed a mass lesion in the region of the right upper ribs. Ten years prior to this admission, the patient had undergone right lobectomy for lung adenocarcinoma. One year after the surgery, follow-up computed tomography had revealed tumor recurrence in the mediastinal and supraclavicular lymph nodes, and the patient had been treated by chemoradiotherapy. Thereafter, regular follow-up had revealed no evidence of recurrence of the non-small-cell lung cancer. Histopathological findings revealed proliferation of spindle-shaped malignant tumor cells in a background of osteoid, consistent with the diagnosis of osteosarcoma. The location of the tumor was consistent with the radiation field. Based on the clinicopathological findings, the patient was diagnosed as having secondary osteosarcoma occurring as a result of the chemoradiotherapy administered previously for the recurrent non-small-cell lung cancer. Unfortunately, the patient died of rapid progression of the osteosarcoma within a week of admission to the hospital. The autopsy revealed contiguous invasion by the tumor of the heart, with massive thrombus formation. The peripheral pulmonary arteries were diffusely occluded by metastatic tumors. Our case serves to highlight the risk of development of secondary sarcoma as a life-threatening late complication after chemoradiotherapy for locally advanced non-small-cell lung cancer, even after complete cure of the primary tumor.