Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.

The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors characterized by early fixation of multiple mutational and copy number drivers and rapid metastases to highly branched tumors with >10 subclonal drivers and extensive parallel evolution associated with attenuated progression. We identify genetic diversity and chromosomal complexity as determinants of patient outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance.

Prognostic implications of histological tumor regression (Böhm's score) in patients receiving neoadjuvant chemotherapy for high grade serous tubal & ovarian carcinoma.

OBJECTIVE: Primary objective of this study was to determine prognostic significance of Bohm's histopathological regression score in patients who received neoadjuvant chemotherapy (NACT) for treatment of high grade serous (HGS) tubal & ovarian carcinoma. METHODS: This was a retrospective cohort study of patients who received NACT between 2010 and 2015. The 3 point histopathological regression score of Böhm was used to classify chemotherapy response. Survival outcomes between the 3 different subgroups was analysed and compared with standard clinico-pathological variables using the Cox proportional hazards model and log-rank test. RESULTS: Study cohort comprised 111 patients. Chemotherapy response score (CRS) 3 was observed in 47 (42.4%) and CRS 1and CRS 2 in 22 (19.8%) and 42 (37.8%) women respectively. Women with CRS score of 1 and 2 combined showed a three-fold increased risk of progression on both univariate and multivariate assessment (HR 3.54; C.I 2.19-5.72, p < 0.001). The median overall survival for patients with CRS 1 was 34 months, CRS 2 was 30 months and 47 months for CRS 3. CRS 1 and 2 combined was the only variable that held significance in prediction of reduced overall survival on multivariate assessment (HR 3.26, C.I 1.91-5.54, p 0.0006). CRS 1 and 2 were also associated with 5.15-fold increased risk of relapse within 6 months of completion of chemotherapy (Odds ratio OR 5.15, C.I 0.07-0.47, p - 0.002). CONCLUSION: CRS is an independent prognosticator of survival and reliable predictor of relapse within 6 months in advanced high grade serous tubal and ovarian carcinoma patients receiving NACT.

Pathological Concordance between Prostate Biopsies and Radical Prostatectomy Using Transperineal Sector Mapping Biopsies: Validation and Comparison with Transrectal Biopsies.

Background/Aims/Objectives: Our aim was to evaluate the accuracy of systematic transperineal sector mapping biopsy (TPSMB) in predicting Gleason score (GS) at radical prostatectomy (RP), to compare its accuracy with standard transrectal ultrasound-guided biopsies (TRUS) and to establish the clinical impact of discordance between biopsies and RP on subsequent surgical management. METHODS: Two hundred fifty-five patients from 2008 to 2013 who underwent RP following TPSMB (n = 204) or TRUS (n = 51), were included in this retrospective multi-institutional study. Concordance between biopsies and RPs GS was assessed both as percentages and with Cohen's Kappa coefficient. All mismatches between biopsies and RP were assessed for significance by 3 urologists using the Delphi method. RESULTS: No differences were present among the groups. Concordance between biopsy and RP GS was 75.49% for TPSMB and 64.70% for TRUS. Kappa coefficient was 0.42 and 0.39 respectively. The Delphi method showed lower clinical impact of GS discordances for TPSMB with 7.8% of patients having significant change, thus being potentially more suitable for other treatment modalities, compared to TRUS (13.7%). CONCLUSIONS: TPSMB had a higher accuracy for predicting the GS grade at RP showing superior GS concordance compared with standard TRUS. TPSMB provides an effective technique for systematic prostate biopsy to evaluate overall prostate cancer GS.

Definitions of terms, processes and a minimum dataset for transperineal prostate biopsies: a standardization approach of the Ginsburg Study Group for Enhanced Prostate Diagnostics.

OBJECTIVES: To define terms and processes and agree on a minimum dataset in relation to transperineal prostate biopsy procedures and enhanced prostate diagnostics. To identify the need for further evaluation and establish a collaborative research practice. PATIENTS AND METHODS: A 19-member multidisciplinary panel rated 66 items for their appropriateness and their definition to be incorporated into the international databank using the Research and Development/University of California Los Angeles Appropriateness Method. The item list was developed from interviews conducted with healthcare professionals from urology, radiology, pathology and engineering. RESULTS: The panel agreed on 56 items that were appropriate to be incorporated into a prospective database. In total, 10 items were uncertain and were omitted. These items were within the categories: definitions (n = 2), imaging (n = 1), surgical protocols (n = 2) and histology (n = 5). CONCLUSIONS: The components of a minimum dataset for transperineal prostate biopsy have been defined. This provides an opportunity for multicentre collaborative data analysis and technique development. The findings of the present study will facilitate prospective studies into the application and outcome of transperineal prostate biopsies.

Leprosy-an unusual cause of a suspicious nodule on mammography.

A routine mammogram identified changes thought to be due to a lymph node, which was confirmed on biopsy. The lymph node was infiltrated with macrophages and showed fragmented acid-fast bacilli. The patient had been treated for leprosy some years before and was still taking thalidomide for erythema nodosum leprosum. Leprosy-associated lymphadenopathy may be identified on routine breast screening.

Primary Retroperitoneal Mucinous Tumours Diagnosed in Pregnancy: A Case Report and Literature Review.

We present the case of a pregnant patient who was found to have a primary retroperitoneal mucinous tumour (PMRT). An abdominal mass measuring 11.5 × 9.8 × 8.8cm, initially thought to be of ovarian origin, was found incidentally on ultrasound in a 36-year-old patient at 20 weeks' gestation. Tumour markers were normal. She underwent an elective Caesarean section at 34 weeks, but the uterus, fallopian tubes and ovaries were normal. The mass was found to be retroperitoneal. A clinical decision was made to avoid further surgical exploration at the time. Following further surgical planning, the patient underwent open resection of the retroperitoneal mass, 6 weeks after her Caesarean section. Histology confirmed a moderately differentiated adenocarcinoma suggestive of a primary retroperitoneal mucinous adenocarcinoma. A literature review following this identified five case reports of PMRT in pregnancy in the last decade. In all cases, the patients underwent tumour resection without adverse pregnancy outcomes. While our patient had an uncomplicated pregnancy, she developed a 2cm lesion suggestive of disease recurrence 15 months post-operatively. A plan was made for surgical resection. PMRT are rare, but can occur in pregnant patients and patients of childbearing age. Tumour resection should be carried out, but where there is no concrete evidence of tumour invasion, the uterus and ovaries should be spared to avoid infertility and menopause. We would recommend early tumour resection, given its potentially aggressive nature.

Extramammary Paget disease in a retrorectal dermoid cyst: report of a unique case.

Retrorectal (presacral) dermoid cysts are rare entities, also described as mature cystic or monodermal teratomas. We present a unique case arising in a 64-year-old man, in which the lining squamous epithelium showed marked expansion by Paget disease of extramammary type, and discuss the clinical, radiologic, and pathologic findings.

The Use of Transperineal Sector Biopsy as A First-Line Biopsy Strategy: A Multi-Institutional Analysis of Clinical Outcomes and Complications.

PURPOSE: Systematic transrectal ultrasound biopsies have been the first-line biopsy strategy in men with suspected prostate cancer for over 30 years. Transperineal biopsy is an alternative approach but has been predominately reserved as a repeat biopsy strategy and not widely used as a first-line approach. This study evaluates the diagnostic and clinical outcomes of transperineal sector biopsy (TPSB) as a first-line biopsy strategy in the diagnosis and management of prostate cancer. MATERIALS AND METHODS: A multi-institutional review of 402 consecutive patients who underwent primary transperineal sector biopsy. All patients had no prior history of prostate biopsy. TPSB was carried out as a day-case procedure under general or regional anaesthesia. The cancer detection rate, location and complications for all cases were evaluated. RESULTS: Prostate cancer was identified in 249 patients (61.9%) and was comparably sited across anterior, middle and posterior sectors. The disease was clinically significant (Gleason 3+4 or > 4mm maximum cancer length) in 187 patients (47%). Post biopsy urinary retention occurred in 6 patients (1.5%). Hematuria requiring overnight hospital admission occurred in 4 patients (1.0%). There were no cases of urosepsis. CONCLUSIONS: As a primary diagnostic strategy, TPSB is a safe and effective technique with high cancer detection rates. It also offers an attractive compromise to more extensive transperineal protocols, which can be more time-consuming and associated with higher morbidity. .

Recurrent chromosomal gains and heterogeneous driver mutations characterise papillary renal cancer evolution.

Papillary renal cell carcinoma (pRCC) is an important subtype of kidney cancer with a problematic pathological classification and highly variable clinical behaviour. Here we sequence the genomes or exomes of 31 pRCCs, and in four tumours, multi-region sequencing is undertaken. We identify BAP1, SETD2, ARID2 and Nrf2 pathway genes (KEAP1, NHE2L2 and CUL3) as probable drivers, together with at least eight other possible drivers. However, only ~10% of tumours harbour detectable pathogenic changes in any one driver gene, and where present, the mutations are often predicted to be present within cancer sub-clones. We specifically detect parallel evolution of multiple SETD2 mutations within different sub-regions of the same tumour. By contrast, large copy number gains of chromosomes 7, 12, 16 and 17 are usually early, monoclonal changes in pRCC evolution. The predominance of large copy number variants as the major drivers for pRCC highlights an unusual mode of tumorigenesis that may challenge precision medicine approaches.

Giant atypical ossifying fibromyxoid tumour of the calf.

We present a case of giant atypical ossifying fibromyxoid tumour (OFMT) of soft tissue, occurring in the calf, in a 77-year-old woman. The patient presented with a history of bleeding ulcer over a calf lump that had been present for over 4 years. Clinical presentation, radiological features and histopathologic findings are described, and the relevant literature is reviewed.