Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group

Background There is currently no Europe-wide consensus on the appropriate preanalytical measures and workflow to optimise procedures for tissue-based molecular testing of non-small-cell lung cancer (NSCLC). To address this, a group of lung cancer experts (see list of authors) convened to discuss and propose standard operating procedures (SOPs) for NSCLC. Methods Based on earlier meetings and scientific expertise on lung cancer, a multidisciplinary group meeting was aligned. The aim was to include all relevant aspects concerning NSCLC diagnosis. After careful consideration, the following topics were selected and each was reviewed by the experts: surgical resection and sampling; biopsy procedures for analysis; preanalytical and other variables affecting quality of tissue; tissue conservation; testing procedures for epidermal growth factor receptor, anaplastic lymphoma kinase and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) in lung tissue and cytological specimens; as well as standardised reporting and quality control (QC). Finally, an optimal workflow was described. Results Suggested optimal procedures and workflows are discussed in detail. The broad consensus was that the complex workflow presented can only be executed effectively by an interdisciplinary approach using a well-trained team. Conclusions To optimise diagnosis and treatment of patients with NSCLC, it is essential to establish SOPs that are adaptable to the local situation. In addition, a continuous QC system and a local multidisciplinary tumour-type-oriented board are essential

Increased Prevalence of Metabolic Syndrome in Patients with Acne Inversa

BACKGROUND: Acne inversa (AI; also designated as Hidradenitis suppurativa) is a common chronic inflammatory skin disease, localized in the axillary, inguinal and perianal skin areas that causes painful, fistulating sinuses with malodorous purulence and scars. Several chronic inflammatory diseases are associated with the metabolic syndrome and its consequences including arteriosclerosis, coronary heart disease, myocardial infraction, and stroke. So far, the association of AI with systemic metabolic alterations is largely unexplored. METHODS AND FINDINGS: A hospital-based case-control study in 80 AI patients and 100 age- and sex-matched control participants was carried out. The prevalence of central obesity (odds ratio 5.88), hypertriglyceridemia (odds ratio 2.24), hypo-HDL-cholesterolemia (odds ratio 4.56), and hyperglycemia (odds ratio 4.09) in AI patients was significantly higher than in controls. Furthermore, the metabolic syndrome, previously defined as the presence of at least three of the five alterations listed above, was more common in those patients compared to controls (40.0% versus 13.0%; odds ratio 4.46, 95% confidence interval 2.02 to 9.96; P<0.001). AI patients with metabolic syndrome also had more pronounced metabolic alterations than controls with metabolic syndrome. Interestingly, there was no correlation between the severity or duration of the disease and the levels of respective parameters or the number of criteria defining the metabolic syndrome. Rather, the metabolic syndrome was observed in a disproportionately high percentage of young AI patients. CONCLUSIONS: This study shows for the first time that AI patients have a high prevalence of the metabolic syndrome and all of its criteria. It further suggests that the inflammation present in AI patients does not have a major impact on the development of metabolic alterations. Instead, evidence is given for a role of metabolic alterations in the development of AI. We recommend monitoring of AI patients in order to correct their modifiable cardiovascular risk factors

Preliminary findings suggest hidradenitis suppurativa may be due to defective follicular support

Summary Background The initial pathology in hidradenitis suppurativa (HS) ⁄acne inversa takes place in the folliculopilosebaceous unit (FPSU) and its surrounding tissue. The process involves follicular hyperkeratosis, inflammation and perifolliculitis. Identification of the exact origin of inflammation may shed new light on the pathogenesis and aetiology of the disease. Objectives To study the morphology of the basement membrane zone (BMZ) in patients with HS. Methods In total, 65 operative specimens from 20 patients diagnosed with HS were cut stepwise. Within each specimen, the focus was set on heavily involved HS regions (centre) and clinically uninvolved regions (border). All specimens were stained with periodic acid-Schiff (PAS) to visualize the epithelial support structures of the FPSU (i.e. the BMZ), the sinus tracts (STs) and the interfollicular basement membrane (BM). The intensity of BMZ PAS staining was graded from 0 to 4+. Results Compared with the axillary skin of human controls, the sebofollicular junction in patients with HS was found to be almost devoid of PAS-positive material (grade 0 ⁄1+) in both the border and centre lesions of HS, whereas STs and BMs showed uniformly grade 2-3+ positivity irrespective of any inflammation present. The distribution of inflammatory cells around the sebofollicular junction occurred predominantly in areas of BMZ thinning. Conclusions The BMZ PAS positivity of clinically uninvolved FPSUs of patients with HS appears to be wispy or not present at all. It is speculated that this may explain the apparent fragility of the sebofollicular junction. There is an increased concentration of inflammatory cells adjacent to these areas, while inflammatory cells are scarce in areas where the PAS-positive material is intact. It is hypothesized that the PAS gap identifies (i) areas susceptible to leakage, trauma and rupture, leading to release of materials that trigger inflammatory mediators, and (ii) the seeding of the dermis with free-living stem cells generating benign but invasive epithelialized sinuses, spreading horizontally in and below the dermis

ALK IHC and FISH discordant results in patients with NSCLC and treatment response For discussion of the question - To treat or not to treat?

International audienceIntroduction Lung cancer is the most common cancer worldwide. Latest guidelines from the College of American Pathologist and the European society of medical oncologists indicate anaplastic lymphoma kinase (ALK) rearrangement testing is standard practice. Historically, diagnostics for ALK used fluorescence in situ hybridisation (FISH); however, immunohistochemical (IHC) assays are becoming common practice. Unfortunately, recent assessment of current practice indicated that not all patients who should be tested for ALK translocation are undergoing ALK testing. Methods From a series of European and Israeli labs, we collected patients with discordant IHC and FISH testing, which were subsequently treated with ALK-targeted therapy, for discussion of the question, to treat or not to treat? Results Our study may support ALK IHC testing as a better predictor of response to targeted therapy provided that the labs implement controlled preanalytical procedures, use correct clone, run protocols on automated staining platforms and validate using external quality assessments. © Author (s) (or their employer(s)) 2018