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Desmoid‐type fibromatosis (DF) is a rare mesenchymal lesion with high risk of local recurrence. Specific β‐catenin mutations (S45F) appeared to be related to this higher risk compared to T41A‐mutated or wild‐type (WT). We explored the influence of both mutations and WT on structure stability and affinity of β‐catenin for α‐catenin and the pattern of gene expression that may influence DF behavior. Using 33 surgically resected primary DFs harboring T41A (n = 14), S45F (n = 10), or WT (n = 9), we performed a comparative molecular analysis by protein/protein interaction modeling, gene expression by DASL microarrays, human inflammation gene panel, and assessment of immune system‐based biomarkers by immunohistochemistry. Mutated proteins were more stable than WT and formed a weaker complex with α‐catenin. Consensus unsupervised gene clustering revealed the presence of two DF group‐mutated (T41A + S45F) and WT (P = 0.0047). The gene sets ‘Inflammatory‐Defense‐Humoral Immune Response’ and ‘Antigen Binding’ were significantly enriched in T41A. The deregulation of 16 inflammation‐related genes was confirmed. Low numbers of T cells and tumor‐associated macrophages (TAM) infiltrating the tumors and low/absent PD‐1/PD‐L1 expression were also identified. We demonstrated that mutated DFs (T41A or S45F) and WT are two distinct molecular subgroups with regard to β‐catenin stability, α‐catenin affinity, and gene expression profiling. A different inflammation signature characterized the two mutated groups, suggesting mediation either by T41A or by S45F. Finally, all mutated cases showed a low number of TIL and TAM cells and a low or absent expression of PD‐1 and PD‐L1 consistent with β‐catenin activation insensitive to checkpoint blockade.

[Background] To report on long-term results of a phase 3 trial comparing three versus five cycles of adjuvant chemotherapy (CT) with full-dose epirubicin+ifosfamide in high-risk soft tissue sarcomas (STS)., [Methods] Patients (pts) were randomized to receive three preoperative cycles of epirubicin 120 mg/m2 and ifosfamide 9 g/m2 (Arm A) or to receive the same three preoperative cycles plus two postoperative cycles (Arm B). Radiotherapy could be either delivered in the preoperative or in the postoperative setting. Non-inferiority of the primary end point, OS, was assessed by the confidence interval of the hazard ratio (HR; Arm A/Arm B) derived from Cox model., [Results] Between January 2002 and April 2007, 164 pts were assigned to arm A and 164 to arm B. At a median follow-up (FU) of 117 months (IQ range 103–135 months), 123 deaths were recorded: 58 in Arm A and 65 in Arm B. Ten-year OS was 61% for the entire group of patients: 64% in Arm A and 59% in Arm B. The intention-to-treat analysis confirmed that three cycles were not inferior to five cycles (one-sided 95% upper confidence limit was 1.24). A per protocol analysis was consistent with these results. Pts with leiomyosarcoma and undifferentiated pleomorphic sarcoma (UPS) had the lowest, and the highest response rates, respectively. Consistently, Leiomyosarcoma and UPS had the worse and the best prognosis, respectively., [Conclusions] At a longer FU, the non-inferiority of three cycles of a full-dose conventional CT in comparison to five is confirmed. Response to therapy is also confirmed to be associated with better survival. This regimen is currently tested within an ongoing international trial against three cycles of a neoadjuvant histology-tailored CT (ClinicalTrials.gov Identifier: NCT01710176).

An unclassified amicrobial pustular dermatosis particularly affecting the main cutaneous folds, external auditory canals and scalp and coexisting with systemic lupus erythematosus has been recently described.We studied 3 young females bearing such cutaneous manifestations in association with subacute cutaneous lupus erythematosus, celiac disease and various serum autoantibodies, respectively, in order to further characterize this possibly new entity.Various routine and immunological laboratory tests, histopathologic and direct immunofluorescence examinations and in vitro studies of neutrophil function were performed in each patient.We reported our findings and compared our cases with the few others appearing in the literature. We documented an impaired neutrophil chemotaxis in 2 subjects, but neutrophil dysfunction does not seem to be one of the verifying criteria.All of these cases may represent a distinctive form in the clinicopathological spectrum of neutrophilic dermatoses (ND) because of the typical distribution and the close link with different autoimmune disorders. Cimetidine in combination with ascorbic acid can be indicated as an effective and safe alternative to the classic medications of ND, although the action of both drugs remains unexplained.