Conclusion:We expand the current knowledge on PRDM10-STT and SCD34FT and provide additional evidence for considering them as overlapping entities.

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Gene mutation status assessment of tumors has become standard practice in diagnostic pathology. This is done using samples comprising tumor cells but also non-tumor cells, which may dramatically dilute the proportion of tumor DNA and induce false negative results. Increasing sensitivity of molecular tests presently allows detection of a targeted mutation in a sample with a small percentage of tumor cells, but assessment of tumor cellularity remains essential to adequately interpret the results of molecular tests. Comprehensive tumor cell counting would provide the most reliable approach but is time consuming, and therefore rough global estimations are used, the reliability of which has been questioned in view of their potential clinical impact. The French association for quality assurance in pathology (AFAQAP) conducted two external quality assurance schemes, partly in partnership with the French group of oncology cytogenomics (GFCO). The purpose of the schemes was to (1) evaluate how tumor cellularity is assessed on tissue samples, (2) identify reasons for discrepancies, and (3) provide recommendations for standardization and improvement. Tumor cell percentages in tissue samples of lung and colon cancer were estimated by 40-50 participants, on 10 H&E virtual slides and 20 H&E conventional slides. The average difference between lowest and highest estimated percentage was 66. This was largely due to inadequate definition of cellularity, reflecting confusion between the percentage of tumor cells and the percentage of the area occupied by tumor in the assessed region. The widest range of interobserver variation was observed for samples with dense or scattered lymphocytic infiltrates or with mucinous stroma. Estimations were more accurate in cases with a low percentage of tumor cells. Macrodissection of the most homogeneous area in the tissue reduced inter-laboratory variation. We developed a rating system indicating potential clinical impact of a discrepancy. Fewer discrepancies were clinically relevant since the study was conducted. Although semi-quantitative estimations remain somewhat subjective, their reliability improves when tumor cellularity is adequately defined and heterogeneous tissue samples are macrodissected for molecular analysis.

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Pediatric high grade glioma (pHGGs), including sus-tentorial and diffuse intrinsic pontine gliomas, are known to have a very dismal prognosis. For instance, even an increased knowledge on molecular biology driving this brain tumor entity, there is no treatment able to cure those patients. Therefore, we were focusing on a translational pathway able to increase the cell resistance to treatment and to reprogram metabolically tumor cells, which are, then, adapting easily to a hypoxic microenvironment. To establish, the crucial role of the hypoxic pathways in pHGGs, we, first, assessed their protein and transcriptomic deregulations in a pediatric cohort of pHGGs and in pHGG's cell lines, cultured in both normoxic and hypoxic conditions. Secondly, based on the concept of a bi-therapy targeting in pHGGs mTORC1 (rapamycin) and HIF-1α (irinotecan), we hypothesized that the balanced expressions between RAS/ERK, PI3K/AKT and HIF-1α/HIF-2α/MYC proteins or genes may provide a modulation of the cell response to this double targeting. Finally, we could evidence three protein, genomic and metabolomic profiles of response to rapamycin combined with irinotecan. The pattern of highly sensitive cells to mTOR/HIF-1α targeting was linked to a MYC/ERK/HIF-1α over-expression and the cell resistance to a major hyper-expression of HIF-2α.

OBJECTIVES:The management of pIIIA-N2 non-small-cell lung cancer (NSCLC) is still controversial. In particular, there are wide variations in overall survival (OS), suggesting the existence of subgroups among N2 patients. We aimed to evaluate the prognostic value of microscopic pN2 in NSCLC. METHODS:Between 1996 and 2015, the data from all 982 pathologically stage IIIA-N2 patients who underwent surgery with curative intent for NSCLC were retrospectively reviewed. Microscopic pN2 disease was defined as a nodal metastasis ranging from 0.2 to 2 mm in size. RESULTS:With a median follow-up of 17 months (2-101), the 5-year OS for the whole cohort was 31%. Microscopic N2 was observed in 309 (31.5%) patients. Microscopic N2 was associated with better median OS compared with macroscopic N2 [42 months (95% CI 36.85-47.15) vs 23 months (95% CI 19.7-26.29), P < 0.0001, with a corresponding 5-year OS rate of 39 and 21%, respectively]. In multivariate analysis, microscopic N2 remained a favourable independent prognostic factor [HR 0.681 (95% CI 0.481-0.967), P = 0.03]. The median OS of microscopic N2 patients who benefitted from simple follow-up was significantly better than those who underwent chemotherapy, radiation therapy or both ) vs 31 months (95% CI 27.66-34.34) vs 16 months (95% CI 14.6-17.4), P = 0.008].CONCLUSION: Microscopic N2 seems to be associated with better prognosis in patients with pIIIA-N2 NSCLC and these could benefit from a simple follow-up. Prospective cohort studies are necessary to confirm these preliminary results.

The clinical spectrum of coronavirus disease 2019 is getting wider with the exponential increase of patients worldwide. Initially described with flu-like symptoms, variable cutaneous manifestations have been reported, with only few histopathological descriptions. Detection of the virus in cutaneous samples has been assessed in very few cases until now, and the causative role of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been proven for every type of cutaneous manifestations yet. We aimed to describe histological features of cutaneous eruptions occurring concomitantly to SARS-CoV-2 infection and assess by immunochemistry and in situ hybridization using RNAscope validation techniques the presence of the virus in skin lesions. We retrieved all skin biopsies received in the departments of pathology and dermatopathology, University Hospital of Strasbourg, performed in hospitalized SARS-CoV-2–infected patients presenting concomitant cutaneous manifestations since March 2020. In situ hybridization and immunostaining using a polyclonal SARS nucleocapsid protein antibody were performed on each sample. Skin biopsies from six patients presenting morbilliform eruption concomitant to SARS-CoV-2 infection were available for evaluation. All six samples showed varying degrees of spongiosis, perivascular inflammatory infiltrates of the dermis, and, for some of them, discrete interface dermatitis. In situ hybridization and immunohistochemistry were negative in all cutaneous samples. Morbilliform rash concomitant to SARS-CoV-2 infection is characterized by mild and unspecific histopathological features with no detectable viral RNA and protein and appears then not to be directly caused by the virus. Even if, at least for a few cases, the differential diagnosis with drug hypersensitivity reaction can be difficult, these cutaneous eruptions seem to rather correspond to paraviral rashes.