Recurrent USP6 rearrangement in a subset of atypical myofibroblastic tumours of the soft tissues: low-grade myofibroblastic sarcoma or atypical/malignant nodular fasciitis?

AIMS: Low-grade myofibroblastic sarcoma (LGMS) is a rarely metastasizing myofibroblastic tumour mostly affecting extremities and the head and neck of adults. Histologically, it shows long infiltrative fascicles of spindle cells with moderate nuclear atypia. By immunohistochemistry, it stains positive for smooth muscle actin (SMA) and sometimes for desmin. To date, no recurrent genetic abnormalities have been described. Ubiquitin-specific peptidase 6 (USP6) gene rearrangement is typically found in some benign bone and soft-tissue tumours including nodular fasciitis (NF), among others. Nevertheless, rare cases of USP6-rearranged tumours resembling NF with atypical features have been reported. METHODS AND RESULTS: One index case of LGMS of the deltoid in a 56-year-old man presented the THBS2::USP6 translocation by RNA sequencing (Archer FusionPlex Sarcoma v2 panel). Further screening of 11 cases of LGMS using fluorescent in situ hybridization (FISH) analysis with a USP6 break-apart probe identified two additional cases. These cases were investigated with RNA-sequencing, and a RRBP1::USP6 translocation was detected in one. The other case was not assessable because of low-quality RNA. Noteworthy, rearranged LGMSs presented distinctive features including variable multinodular/plexiform architecture, prominent vasculature with occasional wall thickening, scattered osteoclast-like multinucleated giant cells, and peripheral lymphoid aggregates. CONCLUSION: Our findings support the notion that among soft-tissue neoplasms with fibroblastic/myofibroblastic phenotype, USP6 rearrangement is not limited to benign tumours, and warrants further investigation of genetic changes in myofibroblastic sarcomas.

Sinonasal nodular fasciitis: report of a case with USP6 rearrangement.

Nodular fasciitis (NF) is a benign myofibroblastic proliferation characterized by rapid growth, a self-limiting course, and USP6 gene rearrangement. Although it can arise in the head and neck region, very few cases of NF involving the sinonasal tract have been reported to date. Herein we report a case of NF involving the nasal cavity presenting as a polypoid well-defined mass causing obstructive symptoms in a male with a history of multiple local surgeries. Although the mass had an unusual clinical presentation, the histopathologic and immunohistochemical findings were consistent with NF. Fluorescent in situ hybridization performed with break-apart probes flanking the USP6 locus on chromosome 17p13 revealed the presence of USP6 gene rearrangement. The patient remained free of disease 124 months after surgical treatment. Considering its remarkably benign behavior despite its alarming clinical and histologic features, the distinction of NF from sinonasal malignant tumors is essential.

The Histological Background of Recurrence in Laryngeal Squamous Cell Carcinoma: An Insight into the Modifications of Tumor Microenvironment.

Recurrent laryngeal carcinoma presents differences from the primary tumor that largely depend on the treatment. In this article, we review the histologic and molecular treatment-induced changes that may affect the diagnosis of recurrent laryngeal carcinoma, the assessment of predictive markers, and the response to treatment with immune checkpoint inhibitors. Radiotherapy induces profound modifications that are strictly related to necrosis of different tissue components, fibrosis, and damage of the tumor vessels. Postradiotherapy recurrent/persistent laryngeal squamous cell carcinoma typically presents a discohesive growth pattern within a fibrotic background associated with significant changes of the tumor immune microenvironment, with both important immunosuppressive and immunostimulatory effects. Overall, the increase of immunoregulatory cells and immune checkpoints such as CTLA-4, TIM-3, PD-1, and PD-L1 induced by radiotherapy and chemotherapy strongly supports the use of immune checkpoint inhibitors in recurrent/persistent laryngeal carcinoma. Future studies aiming to identify predictive factors of the response to immune checkpoint inhibitors should consider such treatment-induced modifications.

Unusual Case of Pancreatic Adenocarcinoma with Bladder Metastasis.

Background: The pancreas can be the site of neoplasms of several histogenetic origins; in most cases, tumors derive from the exocrine component, and ductal adenocarcinoma certainly prevails over the others. This tumor displays remarkably aggressive behavior, and it is often diagnosed at a late stage of disease. Case presentation: We discuss the rare case of a 76-year-old male with locally advanced pancreatic head adenocarcinoma who developed uncommon metastatic disease. The bladder constitutes a very rare site of metastases, mostly deriving from melanoma, gastric, lung and breast cancers. The bladder's secondary involvement in pancreatic malignancies represents an extremely unusual occurrence, and there are very few cases described in the literature to date. Conclusions: The finding of pancreatic adenocarcinoma metastases leads to a poor prognosis, and patients who are diagnosed at this stage constitute 53% of cases, with a 5-year survival of 3%. Although rare, therefore, the diagnostic hypothesis of pancreatic ductal adenocarcinoma (DAC) metastases to the bladder must, in some cases, be considered, especially if accompanied by a clinical picture that may suggest it.