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Background The presence of osteoclast-like giant cells (OGC) in hepatocellular carcinoma (HCC) is rare and literature on this topic is scarce. In this article, we report on a case of a 77-year-old male patient with HCC with OGC and provide an overview of the current literature. Methods We conducted a systematic search to find all available literature on OGC in HCC. The electronic databases PubMed, Web of Science, Embase and CENTRAL were searched from inception until October 2020. Results Thirteen articles on this topic were identified and were included in this review. Data on 14 patients were available, described in twelve case reports, one patient in a patient series and the present case. Median age of included patients was 68 years. Two patients underwent neoadjuvant therapy prior to surgery. Of the 14 cases, eight tumours with OGC arose in a cirrhotic liver. Oncological outcome in this series was unfavourable, even after surgical resection, with a median disease-free survival of 75 d. Conclusions The presence of OGC in HCC is rare. Current literature is scarce, and suggests an unfavourable outcome in regard to overall survival of HCC.

BACKGROUND Small cell neuroendocrine (NE) carcinomas of the prostate classically lose androgen receptor (AR) expression, may harbor loss of the RB1, TP53, and PTEN tumor suppressor genes, and are associated with a poor prognosis. However usual-type adenocarcinomas may also contain areas of NE differentiation, and in this context the molecular features and biological significance are less certain. METHODS We examined the molecular phenotype and oncologic outcomes of primary prostate adenocarcinomas with ≥5% NE differentiation (≥5% chromogranin A-positive NE cells in any given tumor spot on tissue microarray) using three independent study sets: a set of tumors with paneth cell-like NE differentiation (n = 26), a retrospective case-cohort of intermediate- and high-risk patients enriched for adverse outcomes (n = 267), and primary tumors from a retrospective series of men with eventual castration-resistant metastatic prostate cancer (CRPC) treated with abiraterone or enzalutamide (n = 55). RESULTS Benign NE cells expressed significantly lower quantified AR levels compared with paired benign luminal cells (P

BK polyomavirus (BKPyV) has been associated with some high-grade and special urothelial cell carcinoma (UCC) subtypes in immunosuppressed patients. Here, we evaluated the relationship of BKPyV-positive urine cytology specimens (UCS) with UCC. A large single-institution database was retrospectively searched for UCS positive for decoy cells, suggesting BKPyV infection. These were tested for the presence of BKPyV by PCR and immunohistochemistry (IHC) in urine sediments and formalin-fixed paraffin-embedded (FFPE) tissue samples of UCC. Decoy cells were reported in 30 patients out of the database with 22.867 UCS. Of these 30 patients, 16 (53.3%) had no history of UCC. Six patients out of these 16 had a history of transplantation, 4 had a history of severe chronic medical conditions, and 6 had no chronic disease. The other fourteen patients were diagnosed with either in situ or invasive UCC of the urinary bladder (14/30, 46.6%) prior to the detection of decoy cells in the urine. Nine of these UCC patients received intravesical treatment (BCG or mitomycin) after the first presentation with UCC. However, the clinical data on the treatment of the other five UCC patients was lacking. IHC identified BKPyV-positivity in the urine samples of non-UCC and UCC patients, while no BKPyV positivity was found in FFPE tissues of primary UCCs and metastases. In addition, BKPyV-PCR results revealed the presence of BKPyV DNA in the urine of the UCC cases, yet none in the UCC tissues itself. These data strongly indicate that BKPyV reactivation is not restricted to immunosuppression. It can be found in UCS of the immunocompetent patients and may be related to the intravesical BCG or mitomycin treatment of the UCC patients.

The purpose of this report was to systematically review the radiation enhancement factor (REF) effects of immunotherapy on radiotherapy (RT) to the local tumor in comparison with other traditional radiation sensitizers such as cisplatin. PubMed and Medline databases were searched until February 2019. Reports with abscopal effect in the results were excluded. Graphs of the selected papers were digitized using Plot Digitizer (Sourceforge.net) in order to calculate the tumor growth delay (TGD) caused by immunotherapy. To enable comparison between different studies,the TGD were used to define the REF between RT versus the RT/immunotherapy combination. Thirty-two preclinical papers, and nine clinical series were selected. Different mouse models were exposed to RT doses ranging from 1 to 10 fractions of 1.8 to 20 Gray (Gy) per fraction. Endpoints were heterogeneous, ranging from regression to complete local response. No randomized clinical studies were identified. The median preclinical REF effect of different immunotherapy was varying from 1.7 to 9.1. There was no relationship observed either with subclasses of immunotherapy orRT doses. In the clinical studies, RT doses ranged from 1 to 37 fractions of 1.8 to 24 Gy per fraction. Most clinical trials used ipilimumab and interleukin-2. Local control rate in the clinical series ranged from 66% to 100%. A strong REF of immunotherapy (1.7 to 9.1) was observed, this being higher than traditionally sensitizers such as cisplatin (1.1). This result implies that for the same RT dose, a higher local control was achieved with a combination of immunotherapy and RT in preclinical settings. This study therefore supports the use of combined RT and immunotherapy to improve local tumor control in clinical settings without exacerbation of toxicities.

Condyloma acuminatum rarely occurs in the urinary bladder and is considered to be a risk factor for squamous cell carcinoma, although there are only a few publications with limited cases. We studied 51 cases of condyloma acuminatum of the urinary bladder from transurethral resections of the urinary bladder of 38 patients from the consult files of one of the authors. Transurethral resections of the urinary bladder were obtained from 25 males with a median age of 73 years (range: 41 to 87 y) and 13 females with a median age of 68 years (range: 30 to 86 y). The follow-up period ranged from 15 months to 20 years (median: 6 y). Bladder lesions were accompanied by urethral lesions in 4 men. Eight patients (8/38; 21.0%) had a history of immunosuppression. Seven patients (7/8; 87.5%) from this group had multiple and/or recurrent condylomas. One patient (1/38; 2.6%) with renal transplantation had 10 separate bladder condylomas over time. One patient (1/38; 2.6%) had extensive anogenital condylomas and anal intraepithelial neoplasia grade 3. One patient (1/8; 12.5%) with renal transplantation presented with a solitary condyloma with synchronous squamous cell carcinoma in situ. Three female patients (3/38; 7.9%) had a history of premalignant vagina/cervix lesions. In total, 17 patients (17/38; 44.7%) had squamous cell carcinoma of the bladder, either invasive or in situ. In all cases, the squamous cell carcinoma (either in situ or invasive) was diagnosed either concurrent with the diagnosis of bladder condyloma or within 1 year of the condyloma diagnosis). In total, 9 of 38 (23.7%) patients had invasive squamous cell carcinoma with or without in situ squamous cell carcinoma. Eight of 38 (21.0%) patients had squamous cell carcinoma in situ only (without a definitive invasive component-in 3 cases invasive squamous cell carcinoma could not be excluded with certainty). In total, 19 patients (19/38; 50%) were positive for either low-risk human papillomavirus (LR-HPV) or high-risk human papillomavirus (HR-HPV) or both (3 were positive for both LR-HPV and HR-HPV, 12 patients for only LR-HPV, and 4 for only HR-HPV). Of the 19 patients that were negative for both LR-HPV and HR-HPV, 9 of 19 (47.4%) patients had associated squamous cell carcinoma. Of the 12 patients with only LR-HPV, 4 (33.3%) had associated squamous cell carcinoma (either invasive or in situ). Of the 7 patients with HR-HPV (with or without LR-HPV), 4 (57.1%) has associated squamous cell carcinoma. In summary, condyloma acuminatum of the urinary bladder shows a strong association with squamous cell carcinoma of the bladder, regardless of the condyloma's HPV in situ hybridization results. Immunosuppression is associated with condylomas of the bladder. It is important to distinguish bladder condylomas from papillary urothelial carcinoma, given their different risks for panurothelial disease and risk of squamous cell carcinoma. Recognition of bladder condylomas histologically is often challenging given their rarity, and that they can be negative for both LR-HPV and HR-HPV. The lack of a history of other anogenital human papillomavirus-related lesions further increases the difficulty in establishing the correct diagnosis.

Carcinoma in situ (CIS) is difficult to visualize with white light cystoscopy (WLC), whereas blue light cystoscopy (BLC) using photosensitizing agents improves detection rates. We retrospectively reviewed transurethral biopsies of bladder tumors in which both WLC and BLC evaluations were performed (n = 135 samples from 79 patients). Biopsies were classified based on the presence/absence of fluorescence under BLC and the final pathological report (CIS/benign/atypical). Forty-one (30%) cases were diagnosed as CIS; of those, 38 (93%) were BLC(+), including 23 that were WLC(-). Conversely, 51 (38%) lesions were BLC(+) but classified as non-CIS. Eleven BLC(+) cases were diagnosed as "atypical." These cases were anonymized and reviewed by 7 pathologists for concordance and then immunostained for CK20, p53, and Ki-67. Immunohistochemistry results were interpreted as consistent with CIS if there was full thickness staining of CK20, more than 50% p53-positive cells, and more than 50% Ki-67 positive cells. Review of BLC(+)/atypical cases showed a mean agreement of 79%, and none of the cases showed staining pattern consistent with CIS. Therefore, all 11 cases of BLC(+)/atypical were considered non-CIS for the final analysis. All patients with BLC(+)/atypical lesions had a history of intravesical Bacillus Calmette-Guerin and/or mitomycin. Using final pathology as the reference, sensitivity, specificity, and negative predictive value of BLC were 93% (confidence interval [CI], 80.1%-98.5%), 46% (CI, 35.4%-56.3%), and 94% (CI, 82.5%-97.8%), respectively. The low specificity of BLC leads to BLC(+) lesions with atypical diagnosis. Morphological classification of these lesions is fairly consistent among different pathologists. Immunohistochemistry for p53/CK20/Ki-67 in this setting is only helpful to potentially avoid overcalling CIS. (C) 2019 Elsevier Inc. All rights reserved.

This cohort study examines the potential association of the use of immune checkpoint inhibitors with testicular histopathologic conditions.

Cholangiocarcinoma (CCA) is a rare biliary-duct malignancy with poor prognosis. Recently, the presence of the human polyomavirus 6 (HPyV6) has been reported in the bile of diverse hepatobiliary diseases, particularly in the bile of CCA patients. Here, we investigated the presence of novel HPyVs in CCA tissues using diverse molecular techniques to assess a possible role of HPyVs in CCA. Formalin-Fixed Paraffin-Embedded (FFPE) tissues of 42 CCA patients were included in this study. PCR-based screening for HPyVs was conducted using degenerated and HPyV-specific primers. Following that, we performed FISH, RNA in situ hybridization (RNA-ISH), and immunohistochemistry (IHC) to assess the presence of HPyVs in selected tissues. Of all 42 CCAs, 25 (59%) were positive for one HPyV, while 10 (24%) CCAs were positive for 2 HPyVs simultaneously, and 7 (17%) were negative for HPyVs. Of the total 35 positive CCAs, 19 (45%) were positive for HPyV7, 4 (9%) for HPyV6, 2 (5%) for Merkel cell polyomavirus (MCPyV), 8 (19%) for both HPyV7/MCPyV, and 2 (5%) for both HPyV6/HPyV7 as confirmed by sequencing. The presence of viral nucleic acids was confirmed by specific FISH, while the RNA-ISH confirmed the presence of HPyV6 on the single-cell level. In addition, expression of HPyV7, HPyV6, and MCPyV proteins were confirmed by IHC. Our results strongly indicate that HPyV7, HPyV6, and MCPyV infect bile duct epithelium, hepatocytes, and CCA cells, which possibly suggest an indirect role of these viruses in the etiopathogenesis of CCA. Furthermore, the observed hepatotropism of these novel HPyV, in particular HPyV7, might implicate a role of these viruses in other hepatobiliary diseases.

A new prostate cancer grading system was proposed in 2013 and endorsed by major journals and societies in 2014, in part because of anecdotal evidence that Gleason scores (GSs) were incorrectly combined in the literature.To examine how published studies categorized GSs in current practice.A PubMed search was conducted on articles published in 2016-2017 using the search terms "Gleason" and "prostate". This literature review included 1576 articles after exclusions.(1) Separating GS 7: pathology journals were more likely than non-pathology journals to grade GS 7 separately (56.9% vs 40.0%, p0.05). Articles co-authored by a pathologist separated GS 7 more than those without a pathologist (53.2% vs 32.9%, p0.001). North American and European studies separated GS 7 more than Asian studies (47.6% and 44.1% vs 24.1%, p0.001). Clinical articles separated GS 7 more than research articles (43.7% vs 32.9%, p0.001). (2) Separating GS 8 from GS 9-10: pathology journals separated GS 8 from GS 9-10 more than non-pathology journals (55.2% vs 34.4%, p=0.001). Articles co-authored by a pathologist separated GS 8 from GS 9-10 more often than those without a pathologist (44.9% vs 29.5%, p0.001). (3) Using grade groups as "ideal" with all other groupings "non-ideal": pathology journals used ideal more than non-pathology journals (32.2% vs 15.9%, p0.001). Ideal grouping is more likely in articles co-authored by a pathologist than in those without a pathologist (20.6% vs 11.0%, p0.001). North American and European studies used ideal grouping more than Asian studies (17.6% and 14.0% vs 9.1%, p0.05). (4) Arranging groupings in decreasing order from ideal to non-ideal: pathology journals were closer to ideal than non-pathology journals (p=0.002). Articles co-authored by a pathologist were classified closer to ideal than those without a pathologist (p0.001). North American (p0.001) and European (p=0.02) studies were closer to ideal than Asian studies.There is still wide variation in how GSs are grouped world-wide. Only a minority of published articles group GSs accurately.In this report, we looked at how GSs were grouped world-wide. We found that only a minority of published articles on prostate cancer were grouping GSs accurately, which could lead to inaccurate results and affect patient care with different prostate cancer grades. Our study calls for more widespread adoption of the new prostate cancer grading system composed of five grade groups to minimize incorrect grouping for future studies.