Perron E., Pissaloux D., Neub A., Hohl D., Tartar M. D., Mortier L., Alberti L., de la Fouchardiere A.   Unclassified sclerosing malignant melanomas with AKAP9-BRAF gene fusion: a report of two cases and review of BRAF fusions in melanocytic tumors.  Virchows Arch..  2018 ;472 :469-476

The current classification of melanocytic tumors includes clinical, pathological, and molecular data. A subset of lesions remains difficult to classify according to these complex multilayer schemes. We report two cases of deeply infiltrating melanomas with a sclerosing background. The first case occurred on the back of a middle-aged man appearing clinically as a dermatofibroma. The architectural and cytological aspects resembled those of a desmoplastic melanoma but the strong expression of both melanA and HMB45, two stainings usually reported as negative in this entity, raised the question of an alternate diagnosis. The second case was a large, slowly growing, perivulvar tumor in a middle-aged woman. The morphology was complex with a central junctional spitzoid pattern associating an epidermal hyperplasia with large nests of large spindled melanocytes. The dermal component was made of deeply invasive strands and nests of nevoid unpigmented melanocytes surrounded by fibrosis; a perineural invasion was present at the periphery of the lesion. In both cases, aCGH found, among many other anomalies, a chromosomal breakpoint at the BRAF locus. RNA sequencing identified in both an AKAP9-BRAF gene fusion. A complementary resection was performed and no relapses have been observed in the respectively 15 and 6 months of follow-up. Both of these melanomas remained unclassified. We further review the variety of melanocytic tumors associated with such BRAF fusions.

Orczyk C., Villers A., Rusinek H., Le Pennec V., Bazille C., Mikheev A., Bernaudin M., Fohlen A., Valable S.   PROSTATE CANCER HETEROGENEITY: TEXTURE ANALYSIS OF MULTIPLE MRI SEQUENCES FOR DETECTION AND SELECTION OF BIOPSY TARGETS.  J. Urol..  2018 ;199 :E183-E183
Olivier J., Kasivisvanathan V., Drumez E., Fantoni J. C., Leroy X., Puech P., Villers A.   Low-risk prostate cancer selected for active surveillance with negative MRI at entry: can repeat biopsies at 1 year be avoided? A pilot study.  World J Urol.  2018

PURPOSE: In patients considered for active surveillance (AS), the use of MRI and targeted biopsies (TB) at entry challenges the approach of routine "per protocol" repeat systematic biopsies (SB) at 1 year. This pilot study aimed to assess whether an approach of performing repeat biopsies only if PSA kinetics are abnormal would be safe and sufficient to detect progression. METHODS: Prospective single-centre study of 149 patients on AS with low-risk PCa, a negative MRI at entry, followed for a minimum of 12 months between 01/2007 and 12/2015. Group 1 (n = 78) patients had per-protocol 12-month repeat SB; group 2 (n = 71) patients did not. Surveillance tests for tumour progression were for both groups: for cause SB and MRI-TB biopsies if PSA velocity (PSA-V) > 0.75 ng/ml/year, or PSA doubling time (PSADT) < 3 years. The main objectives are to compare the 2-year rates of tumour progression and AS discontinuation between groups. The secondary objectives are to estimate the diagnostic power of PSA-V and PSA-DT, to predict the risk of tumour progression. RESULTS: Overall, 21 out of 149 patients (14.1%) showed tumour progression, 17.1% for group 1 and 12.3% for group 2, and 31 (21.2%) discontinued AS at 2 years. There was no difference between the 2 groups (p = 0.56). The area under the PSA-V and PSADT curves to predict tumour progression was 0.92 and 0.83, respectively. CONCLUSIONS: We did not find any significant difference for progression and AS discontinuation rate between the 2 groups. The PSA kinetic seems accurate as a marker of tumour progression. These results support the conduct of a multi-centre prospective trial to confirm these findings.

Meszaros T., Vogelin E., Mathys L., Leclere F. M.   Perilunate fracture-dislocations: clinical and radiological results of 21 cases.  Arch. Orthop. Trauma Surg..  2018 ;138 :287-297

BACKGROUND: Perilunate dislocations and fracture-dislocations are a subcategory of the carpal instability complex. Herein, we report our university hospital experience with this complex injury. The goal of our study was to find predictive factors and quantify the development of arthritis and lunate necrosis. We tried to measure the impact of arthritis on hand function. METHODS: Between January 2000 and December 2014, 21 patients underwent surgery for perilunate dislocations and perilunate fracture-dislocations of the wrist in our tertiary university center. Mean patient age was 29.3 +/- 10.0 years (range 18-49 years). All displacements were posterior. They were reviewed both clinically and radiologically. RESULTS: Complications included misdiagnosed Essex-Lopresti-like lesion in one case, insufficient reposition of the carpus in two cases (LT in one case, SL in one case), and iatrogenic injury to the radial artery immediately sutured in one case. All 3 cases underwent a second procedure with satisfactory outcome. After a mean follow-up of 112 +/- 60 months (range 12-210 months), the average Cooney score was 80 +/- 19 (range 50-125). The mean PRWE score was 10 +/- 8 (range 0-25). The mean DASH score was 40 +/- 13 (range 30-75 months). Mean pain on load, measured with VAS was 1.1 +/- 1.6; Clinical examination assessed a mean wrist extension/flexion of 42.4 degrees +/- 17.2 degrees /48.4 degrees +/- 15.2 degrees . Mean wrist ulnar/radial deviation was, respectively, 22.9 degrees +/- 11.3 degrees /15.3 degrees +/- 7.0 degrees . Mean pro/supination was, respectively, 75.2 degrees +/- 11.5 degrees /76.3 degrees +/- 8.1 degrees . Mean pinch strength was 9.4 +/- 2.2 kg (87.4 +/- 17.7% of the contralateral side). Mean power strength was 41.9 +/- 9.9 kg (76.2 +/- 19.2% of the contralateral side). Two patients had a scaphoid non-union identified on their most recent imaging. The mean carpal height ratio was 0.53 +/- 0.05 (range 0.44-0.65). All except one patient developed arthritis: Grade 1 in 11 patients, Grade 2 in 3 patients, and Grade 3 in the remaining 6 patients. Age, length of follow-up, and loss of reduction were significantly associated with wrist arthritis (p < 0.001). Lunate avascular necrosis assessed by magnetic resonance imaging was present in 6 patients: Stage 2 in 4 patients, Stage 3a in 1 patient, and Stage 3b in the remaining patient. All these patients' intraoperative findings showed lesion of the cartilage of the radial side of the lunate. However, the small number of patients who developed lunate necrosis did not allow satisfactory statistical analysis. CONCLUSIONS: This retrospective study demonstrates good functional results despite the high rate of radiological wrist arthritis. Age, length of follow-up, and loss of reduction were significantly associated with wrist arthritis in our series.

Merlot B., Ploteau S., Abergel A., Rubob C., Hocke C., Canis M., Fritel X., Roman H., Collinet P.   [Extragenital endometriosis: Parietal, thoracic, diaphragmatic and nervous lesions. CNGOF-HAS Endometriosis Guidelines].  Gynecol Obstet Fertil Senol.  2018 ;46 :319-325

According to some studies, extragenital endometriosis represents 5% of the localisations. Its prevalence seems to be underestimated. The extra pelvic localisation can make the diagnosis more difficult. Nevertheless, the recurrent and catamenial symptomatology can evoke this pathology. Surgery seems to be the unique efficient treatment for parietal lesions. Pain linked to nervous lesions (peripheric and sacral roots) seems to be underestimated and difficult to diagnose because of various localisations. Neurolysis seems to have encouraging results. Diaphragmatic lesions are often discovered either incidentally during laparoscopy, or by pulmonary symptomatology as recurrent catamenial pneumothorax or cyclic thoracic pain. Surgical treatment seems as well to be efficient.

Martin-Malburet A., Marcq G., Leroy X., Guiffart P., Fantoni J. C., Flamand V., Villers A., Puech P., Ouzzane A.   [Pathology findings after radical prostatectomy for prostate cancer in patients eligible for active surveillance: Contribution of multiparametric MRI to treatment decision].  Prog. Urol..  2018 ;28 :425-433

OBJECTIVES: To analyze, in patients with prostate cancer (PC) potentially eligible for active surveillance (AS), whether multiparametric-MRI (mp-MRI) predicts presence of clinically significant cancer on radical prostatectomy (RP) specimen. METHODS: We identified 77 men with PC eligible for AS (PSA/=7 and/or tumoral maximal diameter>10mm) were evaluated using logistic regression. RESULTS: Median age was 61 and median PSA was 6.7ng/mL. Overall, 49 (64%) patients had a positive mp-MRI (score>/=3). Clinically significant cancer on RP specimen was found in 45 (58%) patients (69% in MRI-positive patients vs 39% in MRI-negative patients). In multivariate analysis, a positive MRI was a predictive factor for the presence of significant cancer on the surgical specimen (OR=3.0; CI95% [1.01-8.88]; P=0.04), as was age (OR=1.17; CI95% [1.05-1.31]; P=0.004) and PSAD (OR=1.10; CI95% [1.01-1.20]; P=0.02). CONCLUSION: Mp-MRI is a useful exam for selecting patients eligible for AS even if the situation remains unclear after prostate biopsies including targeted biopsies. Upon confirmation by further studies, mp-MRI should be considered as an independent criterion before entering an AS program. LEVEL OF EVIDENCE: 4.

Maio M., Lewis K., Demidov L., Mandalà M., Bondarenko I., Ascierto P. A., Herbert C., Mackiewicz A., Rutkowski P., Guminski A., Goodman G. R., Simmons B., Ye C., Yan Y., Schadendorf D.   mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.  Lancet Oncol..  2018 ;19 :510-520

BACKGROUND: Systemic adjuvant treatment might mitigate the high risk of disease recurrence in patients with resected stage IIC-III melanoma. The BRIM8 study evaluated adjuvant vemurafenib monotherapy in patients with resected, BRAF(V600) mutation-positive melanoma. METHODS: BRIM8 was a phase 3, international, double-blind, randomised, placebo-controlled study that enrolled 498 adults (aged >/=18 years) with histologically confirmed stage IIC-IIIA-IIIB (cohort 1) or stage IIIC (cohort 2) BRAF(V600) mutation-positive melanoma that was fully resected. Patients were randomly assigned (1:1) by an interactive voice or web response system to receive twice-daily adjuvant oral vemurafenib 960 mg tablets or matching placebo for 52 weeks (13 x 28-day cycles). Randomisation was done by permuted blocks (block size 6) and was stratified by pathological stage and region in cohort 1 and by region in cohort 2. The investigators, patients, and sponsor were masked to treatment assignment. The primary endpoint was disease-free survival in the intention-to-treat population, evaluated separately in each cohort. Hierarchical analysis of cohort 2 before cohort 1 was prespecified. This trial is registered with, number NCT01667419. FINDINGS: The study enrolled 184 patients in cohort 2 (93 were assigned to vemurafenib and 91 to placebo) and 314 patients in cohort 1 (157 were assigned to vemurafenib and 157 to placebo). At the time of data cutoff (April 17, 2017), median study follow-up was 33.5 months (IQR 25.9-41.6) in cohort 2 and 30.8 months (25.5-40.7) in cohort 1. In cohort 2 (patients with stage IIIC disease), median disease-free survival was 23.1 months (95% CI 18.6-26.5) in the vemurafenib group versus 15.4 months (11.1-35.9) in the placebo group (hazard ratio [HR] 0.80, 95% CI 0.54-1.18; log-rank p=0.026). In cohort 1 (patients with stage IIC-IIIA-IIIB disease) median disease-free survival was not reached (95% CI not estimable) in the vemurafenib group versus 36.9 months (21.4-not estimable) in the placebo group (HR 0.54 [95% CI 0.37-0.78]; log-rank p=0.0010); however, the result was not significant because of the prespecified hierarchical prerequisite for the primary disease-free survival analysis of cohort 2 to show a significant disease-free survival benefit. Grade 3-4 adverse events occurred in 141 (57%) of 247 patients in the vemurafenib group and 37 (15%) of 247 patients in the placebo group. The most common grade 3-4 adverse events in the vemurafenib group were keratoacanthoma (24 [10%] of 247 patients), arthralgia (17 [7%]), squamous cell carcinoma (17 [7%]), rash (14 [6%]), and elevated alanine aminotransferase (14 [6%]), although all keratoacanthoma events and most squamous cell carcinoma events were by default graded as grade 3. In the placebo group, grade 3-4 adverse events did not exceed 2% for any of the reported terms. Serious adverse events were reported in 40 (16%) of 247 patients in the vemurafenib group and 25 (10%) of 247 patients in the placebo group. The most common serious adverse event was basal cell carcinoma, which was reported in eight (3%) patients in each group. One patient in the vemurafenib group of cohort 2 died 2 months after admission to hospital for grade 3 hypertension; however, this death was not considered to be related to the study drug. INTERPRETATION: The primary endpoint of disease-free survival was not met in cohort 2, and therefore the analysis of cohort 1 showing a numerical benefit in disease-free survival with vemurafenib versus placebo in patients with resected stage IIC-IIIA-IIIB BRAF(V600) mutation-positive melanoma must be considered exploratory only. 1 year of adjuvant vemurafenib was well tolerated, but might not be an optimal treatment regimen in this patient population. FUNDING: F Hoffman-La Roche Ltd.