Neurogenic tumours of the posterior mediastinum and differential diagnosis considerations.

The mediastinal compartment harbours vital organs and structures, including the heart, great vessels, major airways, and thymus. These structures are embedded in and associated with soft-tissue elements consisting of adipose and fibro-collagenous tissue in which soft-tissue tumours may develop. A detailed inventory of soft-tissue tumours that may be encountered in the mediastinum based on the WHO 2013 classification was published in 2015. In addition, several comprehensive reviews on mediastinal soft-tissue pathology are available, including reviews focusing specifically on a single tumour type. This review will focus on primary neurogenic and spindle cell tumours of the somatic soft tissue of the posterior mediastinum and provide a discussion of the pertinent differential diagnoses.

Dataset for reporting of thymic epithelial tumours: recommendations from the International Collaboration on Cancer Reporting (ICCR).

AIMS: Thymic epithelial tumours (TET), including thymomas and thymic carcinomas and thymic neuroendocrine neoplasms, are malignant neoplasms that can be associated with morbidity and mortality. Recently, an updated version of the World Health Organization (WHO) Classification of Thoracic Tumours 5th Edition, 2021 has been released, which included various changes to the classification of these neoplasms. In addition, in 2017 the Union for International Cancer Control (UICC) / American Joint Committee on Cancer (AJCC) published the 8th Edition Staging Manual which, for the first time, includes a TNM staging that is applicable to thymomas, thymic carcinomas, and thymic neuroendocrine neoplasms. METHODS AND RESULTS: To standardize reporting of resected TET and thymic neuroendocrine neoplasms the accrediting bodies updated their reporting protocols. The International Collaboration on Cancer Reporting (ICCR), which represents a collaboration between various National Associations of Pathology, updated its 2017 histopathology reporting guide on TET and thymic neuroendocrine neoplasms accordingly. This report will highlight important changes in the reporting of TET and thymic neuroendocrine neoplasms based on the 2021 WHO, emphasize the 2017 TNM staging, and also comment on the rigour and various uncertainties for the pathologist when trying to follow that staging. CONCLUSION: The ICCR dataset provides a comprehensive, standardized template for reporting of resected TET and thymic neuroendocrine neoplasms.

Asymptomatic lipofibroadenoma in a 17-year-old male: a case report and literature review of a rare entity.

Background: The most common thymic tumours, thymomas, are derived from thymic epithelium and are generally low-grade neoplasm. Frankly malignant tumours, thymic carcinomas are rarer still. Exceedingly rare thymic tumours contain a mesenchymal tissue component such as fibrous connective tissue and/or mature fat. Lipofibroadenoma (LFA) is a very rare mixed epithelial-mesenchymal thymic tumour, included in the category of thymic epithelial tumors. LFA in addition to a mature adipocytic component, contains variable epithelial and mesenchymal tissue components. Owing to the presence of an epithelial component in LFA, this entity, in contrast to thymolipoma, is included in the World Health Organization (WHO) category of thymic epithelial neoplasm. Currently only 12 LFA cases have been described. The 12 previously reported cases all behaved in a benign fashion, although four cases were associated with a conventional type of thymoma. We here present a new, 13th, case of LFA. Case Description: The LFA was discovered incidentally in a previously healthy 17-year-old male after investigations for suspected pneumonia. On imaging a mass was discovered in the anterior mediastinum which was subsequently surgically removed. The resected tumour was extensively investigated, including the first instance of full molecular analysis of this rare entity and all available literature on LFA was sourced to provide a comprehensive overview. The histology of this LFA was similar to previously described cases. No gene mutations or rearrangements were identified. The patient made an uneventful recovery and after 13 months of follow-up remained well. Conclusions: An additional, 13th case of LFA is presented. Based on the available literature it appears that LFA may be considered a benign composite thymic tumour, although the combination of an additional conventional thymoma component may warrant closer follow-up.

Biopsy prostate cancer perineural invasion and tumour load are associated with positive posterolateral margins at radical prostatectomy: implications for planning of nerve-sparing surgery.

AIMS: Radical prostatectomy (RP) for prostate cancer is frequently complicated by erectile dysfunction and urinary incontinence. However, sparing of the nerve bundles adjacent to the posterolateral sides of the prostate reduces the number of complications at the risk of positive surgical margins. Preoperative selection of men eligible for safe, nerve-sparing surgery is therefore needed. Our aim was to identify pathological factors associated with positive posterolateral surgical margins in men undergoing bilateral nerve-sparing RP. METHODS AND RESULTS: Prostate cancer patients undergoing RP with standardised intra-operative surgical margin assessment according to the NeuroSAFE technique were included. Preoperative biopsies were reviewed for grade group (GG), cribriform and/or intraductal carcinoma (CR/IDC), perineural invasion (PNI), cumulative tumour length and extraprostatic extension (EPE). Of 624 included patients, 573 (91.8%) received NeuroSAFE bilaterally and 51 (8.2%) unilaterally, resulting in a total of 1197 intraoperative posterolateral surgical margin assessments. Side-specific biopsy findings were correlated to ipsilateral NeuroSAFE outcome. Higher biopsy GG, CR/IDC, PNI, EPE, number of positive biopsies and cumulative tumour length were all associated with positive posterolateral margins. In multivariable bivariate logistic regression, ipsilateral PNI [odds ratio (OR) = 2.98, 95% confidence interval (CI) = 1.62-5.48; P < 0.001] and percentage of positive cores (OR = 1.18, 95% CI = 1.08-1.29; P < 0.001) were significant predictors for a positive posterolateral margin, while GG and CR/IDC were not. CONCLUSIONS: Ipsilateral PNI and percentage of positive cores were significant predictors for a positive posterolateral surgical margin at RP. Biopsy PNI and tumour volume can therefore support clinical decision-making on the level of nerve-sparing surgery in prostate cancer patients.

Urinary Incontinence and Sexual Function After the Introduction of NeuroSAFE in Radical Prostatectomy for Prostate Cancer.

BACKGROUND: Nerve-sparing (NS) radical prostatectomy (RP) results in better functional outcomes. Intraoperative neurovascular structure-adjacent frozen section examination (NeuroSAFE) significantly increases the frequency of NS surgery. The effect of NeuroSAFE on postoperative erectile function (EF) and continence is not yet clear. OBJECTIVE: To describe EF and continence outcomes for men undergoing RP with the NeuroSAFE technique. DESIGN, SETTING, AND PARTICIPANTS: Between September 2018 and February 2021, 1034 men underwent robot-assisted RP. Data for patient-reported outcomes were collected via validated questionnaires. INTERVENTION: NeuroSAFE technique for RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Continence was assessed using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) or Expanded Prostate Cancer Index Composite short form (EPIC-26) and defined as use of 0-1 pads/d. EF was evaluated using EPIC-26 or the International Index of Erectile Function short form (IIEF-5), with data converted according to the Vertosick method and categorized. Descriptive statistics were used to asses and describe tumor characteristics and continence and EF outcomes. RESULTS AND LIMITATIONS: Of the 1034 men who underwent RP after introduction of the NeuroSAFE technique, 63% and 60% completed a preoperative and at least one postoperative questionnaire on continence and EF, respectively. Of the men who underwent unilateral or bilateral NS surgery, use of 0-1 pads/d was reported by 93% after 1 yr and 96% after 2 yr; the corresponding rates for men who underwent non-NS surgery were 86% and 78%. Overall, use of 0-1 pads/d was reported by 92% of the men at 1 yr and by 94% at 2 yr after RP. Men in the NS group had a good or intermediate Vertosick score after RP more often than the non-NS group. Overall, 44% of the men had a good or intermediate Vertosick score at 1 and 2 yr after RP. CONCLUSIONS: After introduction of the NeuroSAFE technique, the continence rate was 92% at 1 yr and 94% at 2 yr after RP. The NS group had a greater percentage of men with an intermediate or good Vertosick score and a higher continence rate after RP in comparison to the non-NS group. PATIENT SUMMARY: Our study shows that after introduction of the NeuroSAFE technique during removal of the prostate, the continence rate among patients was 92% at 1 year and 94% at 2 years after surgery. Some 44% of the men had a good or intermediate score for erectile function 1 and 2 years after surgery.

Development and verification of new monoclonal orthopedia homeobox (OTP) specific antibodies for pulmonary carcinoid diagnostics.

Background: Orthopedia homeobox (OTP) has shown to be a useful prognostic marker to predict outcome in pulmonary carcinoids, which is also supported by the World Health Organization. However, the discontinuation of the initially used polyclonal antibody and absence of a reliable routinely applicable monoclonal OTP antibody hampers implementation in routine diagnostics. Here, new monoclonal antibodies directed against OTP were developed and verified on formalin-fixed paraffin-embedded tissue of pulmonary neuroendocrine tumors (NETs) for clinical diagnostics. Methods: OTP specific monoclonal antibodies were produced from mice immunised with a recombinant human OTP protein fragment. Enzyme-linked immunosorbent assay (ELISA) positive hybridomas were evaluated using immunohistochemistry (IHC). Following epitope-mapping and isotyping, purified monoclonal antibodies were validated for IHC in formalin-fixed paraffin-embedded tissues, the optimal dilution was determined, and results were cross validated with the OTP polyclonal antibody (HPA039365, Atlas Antibodies). Staining protocols were optimized on two automated staining platforms and performance was harmonized using a tissue microarray (TMA). Results: Two clones (CL11222 and CL11225) were selected for purified monoclonal antibody (mAb) production. Intratumor heterogeneity assessment revealed similar performance for both clones. While clone CL11225 displayed a unique epitope compared to those present in the polyclonal antibody, this clone performed most similar to the polyclonal antibody. Cross-platform assessment revealed an excellent agreement for clone CL11225 while clone CL11222 showed somewhat discordant results on Dako. Conclusions: New monoclonal OTP specific antibodies have been developed and verified on different automated immunohistochemical staining platforms. The OTP specific monoclonal antibodies showed excellent agreement with the often-used polyclonal antibody allowing application in routine diagnostics.

Percentage Gleason pattern 4 and PI-RADS score predict upgrading in biopsy Grade Group 2 prostate cancer patients without cribriform pattern.

PURPOSE: To identify parameters to predict upgrading in biopsy Grade Group (GG) 2 prostate cancer patients without cribriform and intraductal carcinoma (CR/IDC) on biopsy. METHODS: Preoperative biopsies from 657 men undergoing radical prostatectomy (RP) for prostate cancer were reviewed for GG, presence of CR/IDC, percentage Gleason pattern 4, and tumor length. In men with biopsy GG2 without CR/IDC (n = 196), clinicopathologic features were compared between those with GG1 or GG2 without CR/IDC on RP (GG ≤ 2-) and those with GG2 with CR/IDC or any GG > 2 (GG ≥ 2+). Logistic regression analysis was used to predict upgrading in the biopsy cohort. RESULTS: In total 283 men had biopsy GG2 of whom 87 (30.7%) had CR/IDC and 196 (69.3%) did not. CR/IDC status in matched biopsy and RP specimens was concordant in 179 (63.3%) and discordant in 79 (27.9%) cases (sensitivity 45.1%; specificity 92.6%). Of 196 biopsy GG2 men without CR/IDC, 106 (54.1%) had GG ≥ 2+ on RP. Multivariable logistic regression analysis showed that age [odds ratio (OR): 1.85, 95% confidence interval (CI)1.09-3.20; p = 0.025], percentage Gleason pattern 4 (OR 1.54, 95% CI 1.17-2.07; p = 0.003), PI-RADS 5 lesion (OR 2.17, 95% CI 1.03-4.70; p = 0.045) and clinical stage T3 (OR 3.60; 95% CI 1.08-14.50; p = 0.049) were independent parameters to predict upgrading to GG ≥ 2+ on RP in these men. CONCLUSIONS: Age, clinical stage T3, percentage Gleason pattern 4 and presence of PI-RADS 5 lesions are independent predictors for upgrading in men with biopsy GG2 without CR/IDC. These findings allow for improved clinical decision-making on surveillance eligibility in intermediate-risk prostate cancer patients.

Sex Differences in Neoplastic Progression in Barrett's Esophagus: A Multicenter Prospective Cohort Study.

Recommendations in Barrett's esophagus (BE) guidelines are mainly based on male patients. We aimed to evaluate sex differences in BE patients in (1) probability of and (2) time to neoplastic progression, and (3) differences in the stage distribution of neoplasia. We conducted a multicenter prospective cohort study including 868 BE patients. Cox regression modeling and accelerated failure time modeling were used to estimate the sex differences. Neoplastic progression was defined as high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC). Among the 639 (74%) males and 229 females that were included (median follow-up 7.1 years), 61 (7.0%) developed HGD/EAC. Neoplastic progression risk was estimated to be twice as high among males (HR 2.26, 95% CI 1.11-4.62) than females. The risk of HGD was found to be higher in males (HR 3.76, 95% CI 1.33-10.6). Time to HGD/EAC (AR 0.52, 95% CI 0.29-0.95) and HGD (AR 0.40, 95% CI 0.19-0.86) was shorter in males. Females had proportionally more EAC than HGD and tended to have higher stages of neoplasia at diagnosis. In conclusion, both the risk of and time to neoplastic progression were higher in males. However, females were proportionally more often diagnosed with (advanced) EAC. We should strive for improved neoplastic risk stratification per individual BE patient, incorporating sex disparities into new prediction models.

NeuroSAFE in radical prostatectomy increases the rate of nerve-sparing surgery without affecting oncological outcome.

OBJECTIVES: To investigate the impact of intra-operative neurovascular structure-adjacent frozen-section examination (NeuroSAFE) on the rate of nerve-sparing surgery (NSS) and oncological outcome in a large radical prostatectomy (RP) cohort. PATIENTS AND METHODS: Between January 2016 and December 2020, 1756 prostate cancer patients underwent robot-assisted RP, of whom 959 (55%) underwent this with NeuroSAFE and 797 (45%) without (control cohort). In cases where NeuroSAFE showed tumour in the margin, a secondary resection was performed. The effect of NeuroSAFE on NSS and positive surgical margin (PSM) status was analysed using logistic regression. Cox regression was used to identify predictors of biochemical recurrence-free survival (BCRFS). RESULTS AND LIMITATIONS: Patients in the NeuroSAFE cohort had a higher tumour grade (P < 0.001) and clinical stage (P < 0.001) than those in the control cohort. NeuroSAFE enabled more frequent NSS for both pT2 (93% vs 76%; P < 0.001) and pT3 disease (83% vs 55%; P < 0.001). In adjusted analysis, NeuroSAFE resulted in more frequent unilateral (odds ratio [OR] 3.90, 95% confidence interval (CI) 2.90-5.30; P < 0.001) and bilateral (OR 5.22, 95% CI 3.90-6.98; P < 0.001) NSS. While the PSM rate decreased from 51% to 42% in patients with pT3 stage disease (P = 0.031), NeuroSAFE was not an independent predictor of PSM status (OR 0.85, 95% CI 0.68-1.06; P = 0.2) in the entire cohort. Patients who underwent NeuroSAFE had better BCRFS compared to the control cohort (hazard ratio 0.62, 95% CI 0.45-0.84; P = 0.002). This study is limited by its comparison with a historical cohort and lack of functional outcomes. CONCLUSIONS: NeuroSAFE enables more unilateral and bilateral NSS without negatively affecting surgical margin status and biochemical recurrence. This validation study provides a comprehensive overview of the implementation, evaluation and intra-operative decision making associated with NeuroSAFE in clinical practice.

Functional Ex Vivo Tissue-Based Chemotherapy Sensitivity Testing for Breast Cancer.

Background chemotherapy is part of most breast cancer (BC) treatment schedules. However, a substantial fraction of BC tumors does not respond to the treatment. Unfortunately, no standard biomarkers exist for response prediction. Therefore, we aim to develop ex vivo sensitivity assays for two types of commonly used cytostatics (i.e., platinum derivates and taxanes) on organotypic BC tissue slices. METHODS: Ex vivo cisplatin sensitivity assays were established using organotypic tissue slices derived from the surgical resection material of 13 primary BCs and 20 fresh histological biopsies obtained from various metastatic sites. Furthermore, tissue slices of 10 primary BCs were used to establish a docetaxel ex vivo sensitivity assay. RESULTS: Cisplatin sensitivity was assessed by tissue morphology, proliferation and apoptosis, while the relative increase in the mitotic index was discriminative for docetaxel sensitivity. Based on these read-outs, a scoring system was proposed to discriminate sensitive from resistant tumors for each cytostatic. We successful completed the cisplatin sensitivity assay on 12/16 (75%) biopsies as well. CONCLUSIONS: We developed an ex vivo cisplatin and docetaxel assay on BC slices. We also adapted the assay for biopsy-sized specimens as the next step towards the correlation of ex vivo test results and in vivo responses.

Clinical-Pathologic Challenges in the Classification of Pulmonary Neuroendocrine Neoplasms and Targets on the Horizon for Future Clinical Practice.

Diagnosing a pulmonary neuroendocrine neoplasm (NEN) may be difficult, challenging clinical decision making. In this review, the following key clinical and pathologic issues and informative molecular markers are being discussed: (1) What is the preferred outcome parameter for curatively resected low-grade NENs (carcinoid), for example, overall survival or recurrence-free interval? (2) Does the WHO classification combined with a Ki-67 proliferation index and molecular markers, such as OTP and CD44, offer improved prognostication in low-grade NENs? (3) What is the value of a typical versus atypical carcinoid diagnosis on a biopsy specimen in local and metastatic disease? Diagnosis is difficult in biopsy specimens and recent observations of an increased mitotic rate in metastatic carcinoid from typical to atypical and high-grade NEN can further complicate diagnosis. (4) What is the (ir)relevance of morphologically separating large cell neuroendocrine carcinoma (LCNEC) SCLC and the value of molecular markers (RB1 gene and pRb protein or transcription factors NEUROD1, ASCL1, POU2F3, or YAP1 [NAPY]) to predict systemic treatment outcome? (5) Are additional diagnostic criteria required to accurately separate LCNEC from NSCLC in biopsy specimens? Neuroendocrine morphology can be absent owing to limited sample size leading to missed LCNEC diagnoses. Evaluation of genomic studies on LCNEC and marker studies have identified that a combination of napsin A and neuroendocrine markers could be helpful. Hence, to improve clinical practice, we should consider to adjust our NEN classification incorporating prognostic and predictive markers applicable on biopsy specimens to inform a treatment outcome-driven classification.

Inter-observer variability of cribriform architecture and percent Gleason pattern 4 in prostate cancer: relation to clinical outcome.

The Grade group is an important parameter for clinical decision-making in prostate cancer. Recently, percent Gleason pattern 4 and presence of invasive cribriform and/or intraductal carcinoma (CR/IDC) have been recognized for their independent predictive value for prostate cancer outcome. There is sparse data on the inter-observer agreement for these pathologic features in practice. Our objectives were to investigate inter-observer variability of percent Gleason pattern and CR/IDC and to relate individual tumour scores to clinical outcome. Our cohort included 80 consecutive radical prostatectomies with a median follow-up 87.1 months (interquartile range 43.3-119.2), of which the slide with largest tumour volume was scored by six pathologists for Grade group (four tiers: 1, 2, 3 and 4/5), percent Gleason pattern 4 (four tiers: 0-25%, 26-50%, 51-75% and 76-100%) and presence of CR/IDC (two tiers: absent, present). The individual assignments were related to post-operative biochemical recurrence (20/80). Inter-observer agreement was substantial (Krippendorff's α 0.626) for assessment of Grade group and moderate for CR/IDC (α 0.507) and percent Gleason pattern 4 (α 0.551). For each individual pathologist, biochemical recurrence rates incremented by Grade group and presence of CR/IDC, although such relation was less clear for percent Gleason pattern 4. In conclusion, inter-observer agreement for CR/IDC and percent Gleason pattern 4 is lower than for Grade groups, indicating awareness of these features needs further improvement. Grade group and CR/IDC, but not percent Gleason pattern 4 was related to biochemical recurrence for each pathologist, indicating overall validity of individual grade assignments despite inter-observer variability.

Preoperative Biopsy Diagnosis in Pulmonary Carcinoids, a Shot in the Dark.

INTRODUCTION: The preferred treatment for pulmonary carcinoids (PCs) is lobectomy, and parenchyma-sparing approaches might be considered for typical carcinoids (TCs). Treatment decisions are based on a preoperative biopsy diagnosis. Following the WHO criteria (2015), definitive diagnosis is only feasible postoperatively, thereby hampering preoperative treatment decisions. Here, we determined whether the final carcinoid classification on a resection specimen can be predicted by a preoperative biopsy. METHODS: We searched all stage I to III patients with a final carcinoid diagnosis who underwent a curative resection and of whom both a preoperative biopsy and paired resection specimen were available (2003-2012) using the Dutch Pathology Registry (PALGA) and the Netherlands Cancer Registry (IKNL). Pathology report conclusions of the biopsy-resection specimen were compared. RESULTS: Paired biopsy-resection specimens in combination with clinical data were available from 330 patients. 57% (189 of 330) of the patients exhibited discordance between the preoperative biopsy and paired resection diagnosis, including 36% (44 of 121) preoperatively diagnosed TC, 40% (six of 15) atypical carcinoid (AC), and 65% (103 of 158) not-otherwise-specified (NOS) carcinoids. A quarter of preoperatively diagnosed TC and NOS was reclassified as AC on the resection specimen. Preoperatively diagnosed ACs exhibited the highest relapse rates (40%, 6 of 15). Preoperatively diagnosed TC and NOS patients who were reclassified as ACs exhibited higher relapse rates as compared to nonreclassified TCs and NOS (3% versus 1%, and 16% versus 6%). CONCLUSIONS: We provide evidence that carcinoid classification on preoperative biopsies is imprecise, as is also stated by the current WHO classification. We advise clinicians to interpret the preoperative biopsy diagnosis with caution in deciding the extent of surgery (e.g., parenchyma-sparing versus non-parenchyma-sparing).

Interobserver variation in the classification of thymic lesions including biopsies and resection specimens in an international digital microscopy panel.

AIMS: Thymic tumours are rare in routine pathology practice. Although the World Health Organization (WHO) classification describes a number of well-defined categories, the classification remains challenging. The aim of this study was to investigate the reproducibility of the WHO classification among a large group of international pathologists with expertise in thymic pathology and by using whole slide imaging to facilitate rapid diagnostic turnover. METHODS AND RESULTS: Three hundred and five tumours, consisting of 90 biopsies and 215 resection specimens, were reviewed with a panel-based virtual microscopy approach by a group of 13 pathologists with expertise in thymic tumours over a period of 6 years. The specimens were classified according to the WHO 2015 classification. The data were subjected to statistical analysis, and interobserver concordance (Fleiss kappa) was calculated. All cases were diagnosed within a time frame of 2 weeks. The overall level of agreement was substantial (κ = 0.6762), and differed slightly between resection specimens (κ = 0.7281) and biopsies (κ = 0.5955). When analysis was limited to thymomas only, and they were grouped according to the European Society for Medical Oncology Clinical Practice Guidelines into B2, B3 versus A, AB, B1 and B3 versus A, AB, B1, B2, the level of agreement decreased slightly (κ = 0.5506 and κ = 0.4929, respectively). Difficulties arose in distinguishing thymoma from thymic carcinoma. Within the thymoma subgroup, difficulties in distinction were seen within the B group. CONCLUSIONS: Agreement in diagnosing thymic lesions is substantial when they are assessed by pathologists with experience of these rare tumours. Digital pathology decreases the turnaround time and facilitates access to what is essentially a multinational resource. This platform provides a template for dealing with rare tumours for which expertise is sparse.

Intraoperative assessment and reporting of radical prostatectomy specimens to guide nerve-sparing surgery in prostate cancer patients (NeuroSAFE).

AIMS: Radical prostatectomy for prostate cancer is frequently complicated by urinary incontinence and erectile dysfunction. Nerve-sparing surgery reduces the risk of postoperative complications and can be optimised by the use of intraoperative frozen sections of the adjacent neurovascular structure (NeuroSAFE). The aims of this study were to evaluate the pathological outcomes of the NeuroSAFE technique and to develop a comprehensive algorithm for intraoperative clinical decision-making. METHODS AND RESULTS: Between September 2018 and May 2019, 491 NeuroSAFE procedures were performed in 258 patients undergoing radical prostatectomy; 74 of 491 (15.1%) NeuroSAFE specimens had positive surgical margins. As compared with the corresponding paraffin sections, NeuroSAFE had a positive predictive value and negative predictive value of 85.1% and 95.4%, respectively. In 72.2% of secondary neurovascular bundle resections prompted by a NeuroSAFE positive surgical margin, no tumour was present. These cases more often had a positive surgical margin of ≤1 mm (48.7% versus 20.0%; P = 0.001) and only one positive slide (69.2% versus 33.3%; P = 0.008). None of the nine patients with Gleason pattern 3 at the surgical margin, a positive surgical margin length of ≤1 mm and one positive slide had tumour in the secondary resection. CONCLUSIONS: This study provides a systematic reporting template for pathological intraoperative NeuroSAFE evaluation, supporting intraoperative clinical decision-making and comparison between prostate cancer operation centres.

[A woman with a progressive skin tumor during immunotherapy]. / Een snelgroeiende huidtumor tijdens immuuntherapie.

A 62-year-old woman who was treated with daratumumab, bortezomib and dexamethasone for multiple myeloma, developed a skin tumor on her back. Histologic examination of a biopsy from the nodule revealed cutaneous plasmacytoma. Secondary plasmacytoma is an indicator of poor prognosis.

Anisometric Cell and Dysplastic Lipomas in a Retinoblastoma Patient.

Anisometric cell lipoma (ACL) and dysplastic lipoma (DL) are underrecognized subtypes of benign lipomatous tumors, with wide variation in cell size, microscopic fat necrosis, and no or mild nuclear changes (DL). ACL/DL appear more commonly in retinoblastoma patients, in whom an increased incidence of lipomas has been established. The occurrence of ACL/DL in retinoblastoma patients suggests that RB1 aberrations play a role in its pathogenesis, similar to spindle cell/pleomorphic lipoma. In this article, we present a patient with a history of retinoblastoma with multiple lipomas histologically consistent with ACL/DL. Analysis of the lipomas supports involvement of RB1 in the development of ACL/DL. Dysplastic changes were only seen in a single lipoma, which harbored an additional TP53 mutation. While providing further support for the occurrence of ACL/DL in retinoblastoma patients, we also suggest that DL is an ACL with TP53 mutation.

Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial.

BACKGROUND: There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers. METHODS: A total of 13,195 men (primary analysis) and 2594 women (subgroup analyses) between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3, and year 5.5 or no screening. We obtained data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium, and a review committee confirmed lung cancer as the cause of death when possible. A minimum follow-up of 10 years until December 31, 2015, was completed for all participants. RESULTS: Among men, the average adherence to CT screening was 90.0%. On average, 9.2% of the screened participants underwent at least one additional CT scan (initially indeterminate). The overall referral rate for suspicious nodules was 2.1%. At 10 years of follow-up, the incidence of lung cancer was 5.58 cases per 1000 person-years in the screening group and 4.91 cases per 1000 person-years in the control group; lung-cancer mortality was 2.50 deaths per 1000 person-years and 3.30 deaths per 1000 person-years, respectively. The cumulative rate ratio for death from lung cancer at 10 years was 0.76 (95% confidence interval [CI], 0.61 to 0.94; P = 0.01) in the screening group as compared with the control group, similar to the values at years 8 and 9. Among women, the rate ratio was 0.67 (95% CI, 0.38 to 1.14) at 10 years of follow-up, with values of 0.41 to 0.52 in years 7 through 9. CONCLUSIONS: In this trial involving high-risk persons, lung-cancer mortality was significantly lower among those who underwent volume CT screening than among those who underwent no screening. There were low rates of follow-up procedures for results suggestive of lung cancer. (Funded by the Netherlands Organization of Health Research and Development and others; NELSON Netherlands Trial Register number, NL580.).