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When evaluating mediastinal/hilar lymphadenopathy (LAD) or masses, guidelines recommend endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) as an initial technique for tissue analysis and diagnosis. However, owing to the small sample size obtained by needle aspiration, its diagnostic yield (DY) is limited. EBUS transbronchial forceps biopsy (TBFB) used as a complimentary technique to EBUS-TBNA might allow for better histopathological evaluation, thus improving DY. In this retrospective bicentric study, we assessed the DY and safety of an EBUS-guided 1.5 mm mini-forceps biopsy combined with EBUS-TBNA for the diagnosis of mediastinal/hilar LAD or masses compared to EBUS-TBNA alone. In total, 105 patients were enrolled. The overall DY was 61.9% and 85.7% for TBNA alone and EBUS-TBNA combined with EBUS-TBFB, respectively (p < 0.001). While the combined approach was associated with a significantly higher DY for lung cancer diagnosis (97.1% vs. 76.5%, p = 0.016) and sarcoidosis (85.2% vs. 44.4%, p = 0.001), no significant differences in DY were calculated for subgroups with smaller sample sizes such as lymphoma. No major adverse events were observed. Using a 1.5 mm mini-forceps is a safe and feasible technique for biopsy of mediastinal or hilar LAD or masses with superior overall DY compared to EBUS-TBNA as a standalone technique.

Rearrangements of the transcription factors FOS and FOSB have recently been identified as the genetic driver event underlying osteoid osteoma and osteoblastoma. Nuclear overexpression of FOS and FOSB have since then emerged as a reliable surrogate marker despite limitations in specificity and sensitivity. Indeed, osteosarcoma can infrequently show nuclear FOS expression and a small fraction of osteoblastomas seem to arise independent of FOS/FOSB rearrangements. Acid decalcification and tissue preservation are additional factors that can negatively influence immunohistochemical testing and make diagnostic decision-making challenging in individual cases. Particularly aggressive appearing osteoblastomas, also referred to as epithelioid osteoblastomas, and osteoblastoma-like osteosarcoma can be difficult to distinguish, underlining the need for additional markers to support the diagnosis. Methylation and copy number profiling, a technique well established for the classification of brain tumors, might fill this gap. Here, we set out to comprehensively characterize a series of 77 osteoblastomas by immunohistochemistry, fluorescence in-situ hybridization as well as copy number and methylation profiling and compared our findings to histologic mimics. Our results show that osteoblastomas are uniformly characterized by flat copy number profiles that can add certainty in reaching the correct diagnosis. The methylation cluster formed by osteoblastomas, however, so far lacks specificity and can be misleading in individual cases.

Highlights • SalvGlandDx includes 27 genes known to be involved in salivary gland neoplasms • Can be applied to FFPE histological and cytological (cell block) specimen • Solely RNA extraction is needed • Gene fusions, hotspot mutations and gene expression levels can be detected • Guides diagnosis in uncertain cases and can detect therapeutically relevant fusions, Diagnosis of salivary gland neoplasms is often challenging due to their high morphological diversity and overlaps. Several recurrent molecular alterations have been described recently, which can serve as powerful diagnostic tools and potential therapeutic targets (e.g. NTRK or RET fusions). However, current sequential molecular testing can be expensive and time consuming. In order to facilitate the diagnosis of salivary gland neoplasms, we designed an all-in-one RNA-based next generation sequencing panel suitable for the detection of mutations, fusions and gene expression levels (including NR4A3) of 27 genes involved in salivary gland neoplasms. Here we present the validation of the “SalvGlandDx” panel on FFPE histological specimen including fine needle aspiration (FNA) cell block material, against the standard methods currently used at our institution. In a second part we describe selected unique cases in which the SalvGlandDx panel allowed proper diagnosis and new insights into special molecular characteristics of selected salivary gland tumors. We characterize a unique salivary gland adenocarcinoma harboring a ZCCHC7-NTRK2 fusion, a highly uncommon spindle cell and pseudoangiomatoid adenoid-cystic carcinoma with MYBL1-NFIB fusion, and a purely oncocytic mucoepidermoid carcinoma, whereas diagnosis could be made by detection of a CRTC3-MAML2 rearrangement on the cell block specimen of the FNA. Further, a rare case of a SS18-ZBTB7A rearranged low-grade adenocarcinoma previously described as potential spectrum of microsecretory adenocarcinoma, is reported. In addition, features of six cases within the spectrum of polymorphous adenocarcinoma / cribriform adenocarcinoma of salivary gland including PRKD1 p.E710D mutations and novel fusions involving PRKAR2A-PRKD1, SNX9-PRKD1 and ATL2-PRKD3, are described.

Non‐ossifying fibroma (NOF) has been an intriguing entity since its first description. It is the most common bone tumour, is usually asymptomatic affecting children and adolescents, is composed of a heterogeneous cell population, and undergoes spontaneous regression after puberty. In a recent article in The Journal of Pathology, Baumhoer and colleagues demonstrate mutations activating the RAS‐MAPK pathway (KRAS, FGFR1 and NF1) in ∼80% of the tumours. Activation of the RAS‐MAPK pathway by somatic mutations is found in a plethora of tumour types, both benign and malignant, while germline mutations cause a wide range of syndromes collectively termed the RASopathies. Their findings indicate that NOF, for long thought to be reactive, should be considered a true neoplasm. Moreover, their data suggest that only a subset of cells in the lesion contain the mutation. A second cell population consisting of histiocytes and osteoclast‐like giant cells appears to be reactive. This intimate relation between WT and mutant cells is also frequently encountered in other benign and locally aggressive bone tumours and seems essential for tumourigenesis. The spontaneous regression remains enigmatic and it is tempting to speculate that pubertal hormonal signalling, especially increased oestrogen levels, affect the balance between mutant and WT cells. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Background: Mesenchymal chondrosarcoma (MCS) is a distinct, very rare sarcoma with little evidence supporting treatment recommendations.Patients and methods: Specialist centres collaborated to report prognostic factors and outcome for 113 patients.Results: Median age was 30 years (range: 11-80), male/female ratio 1.1. Primary sites were extremities (40%), trunk (47%) and head and neck (13%), 41 arising primarily in soft tissue. Seventeen patients had metastases at diagnosis. Mean follow-up was 14.9 years (range: 1-34), median overall survival (OS) 17 years (95% confidence interval (CI): 10.3-28.6). Ninety-five of 96 patients with localised disease underwent surgery, 54 additionally received combination chemotherapy. Sixty-five of 95 patients are alive and 45 progression-free (5 local recurrence, 34 distant metastases, 11 combined). Median progression-free survival (PFS) and OS were 7 (95% CI: 3.03-10.96) and 20 (95% CI: 12.63-27.36) years respectively. Chemotherapy administration in patients with localised disease was associated with reduced risk of recurrence (P = 0.046; hazard ratio (HR) = 0.482 95% CI: 0.213-0.996) and death (P = 0.004; HR = 0.445 95% CI: 0.256-0.774). Clear resection margins predicted less frequent local recurrence (2% versus 27%; P = 0.002). Primary site and origin did not influence survival. The absence of metastases at diagnosis was associated with a significantly better outcome (P Conclusions: Prognosis in MCS varies considerably. Metastatic disease at diagnosis has the strongest impact on survival. Complete resection and adjuvant chemotherapy should be considered as standard of care for localised disease. (C) 2014 Elsevier Ltd. All rights reserved.