Molecular B-cell clonality assay in minor salivary glands as a useful tool for the lymphoma risk assessment in Sjögren's syndrome.

OBJECTIVES: Non-Hodgkin's lymphoma (NHL) risk assessment is crucial in Sjögren's syndrome (SS). We studied the prevalence of clonal immunoglobulin gene rearrangements in minor salivary glands (MSG) and their correlations with lymphoma occurrence and with previously established NHL predictors. METHODS: Molecular B-cell expansion was studied in fresh-frozen MSG of 207 patients with either suspected SS or with suspected lymphoma during SS, using a standardised multiplex PCR assay combined with heteroduplex analysis by microcapillary electrophoresis. The assignation of clonal cases was based on EuroClonality consortium guidelines. RESULTS: Among 207 studied patients, 31 (15%) had MSG monoclonal B-cell infiltration. Monoclonality was significantly more frequent in patients with SS (28/123, 22.8%) compared with patients without SS (3/84, 3.6%, P<0.001). Monoclonal B-cell infiltration in MSG of SS patients correlated significantly with ongoing salivary gland NHL, salivary gland swelling, CD4+ T-cell lymphopenia, rheumatoid factor (RF) activity, low complement levels and type 2 mixed cryoglobulinemia. The accumulation of biological risk factors was associated with a higher rate of MSG B-cell monoclonality given that patients with only positive RF had no probability of MSG B-cell monoclonality, RF-positive patients with 1 or 2 other risk factors had a 25.0% and 85.7% probability of MSG B-cell monoclonality, respectively. CONCLUSION: The detection of MSG monoclonal B-cell expansion by this easy-to-perform molecular assay is useful, both at the time of diagnosis and during the course of SS. Monoclonal B-cell expansion is associated with a subset of SS patients presenting either ongoing lymphoma or other established lymphoma predictive factors.

Clinicopathologic and Molecular Study of Hybrid Nerve Sheath Tumors Reveals Their Common Association With Fusions Involving VGLL3.

A subset of benign peripheral nerve sheath tumors are "hybrid" combining several lines of differentiation, most often schwannian and perineurial features. The pathogenesis of these tumors was poorly described until the recent discovery of recurrent VGLL3 rearrangements in hybrid schwannoma/perineuriomas, supporting the hypothesis that this entity represents a distinct subgroup of tumors and not only a morphologic variation of other peripheral nerve sheath tumors. Following this finding, we investigated 10 cases of hybrid peripheral nerve sheath tumors with immunohistochemistry, RNA sequencing, and array comparative genomic hybridization. By light microscopy, 7 tumors were hybrid schwannoma/perineurioma tumors, and 3 were hybrid schwannoma/neurofibroma. Most cases of hybrid schwannoma/perineuriomas displayed VGLL3 rearrangements fused in 5' either to CHD7 or CHD9 (n=6/7) and had simple diploid genetic profiles with few copy number alterations. Compared with a control group composed of 28 tumors associated with varied neural phenotypes, all VGLL3-fused tumors clustered together by transcriptomic analysis. In contrast, 1 case of hybrid schwannoma/perineurioma tumor harbored a CDH9-ZFHX3 fusion, a prominent perineurial component identified by immunohistochemistry and clustered with perineuriomas. No recurrent genetic alteration was seen in the 3 hybrid schwannoma/neurofibromas. To summarize, this study confirms and expands the recent findings on hybrid schwannoma/perineurioma, highlighting the predominance of VGLL3 fusions in these tumors.

[Soft tissue tumours with FN1 (Fibronectin 1) fusion gene]. / Tumeurs des tissus mous avec fusion du gène FN1 (Fibronectine 1).

Translocations involving FN1 gene have been described in several tumours, which share the presence of a cartilaginous matrix with or without calcifications and a good prognosis. They encompass: soft tissue chondroma, synovial chondromatosis, calcifying aponeurotic fibroma, phosphaturic mesenchymal tumour and a new spectrum of tumours: "the calcified chondroid mesenchymal neoplasms". We review all the clinical, histopathological and molecular data of these tumours and discuss the differential diagnoses.

Acral FibroChondroMyxoid tumor: imaging features of a new entity.

"Acral FibroChondroMyxoid tumor" (AFCMT) is a recently described distinctive subtype of acral soft tissue tumor that typically arises on the fingers and toes. We herein present the unreported imaging features of AFCMT in a 44-year-old woman. This otherwise healthy patient was referred for a painful, slow-growing, soft tissue mass in the middle finger of her right hand. Initial radiographs and computed tomography showed a small lesion centered in the soft tissue of the ulnar aspect of the proximal phalanx, associated with scalloping of the underlying bone. Magnetic resonance imaging confirmed the presence of a well-circumscribed soft tissue tumor that exhibited relatively high T2-weighted signal intensity and marked enhancement after contrast administration. Subsequent excisional biopsy was performed. Histologically, the tumor was characterized by an abundant stroma displaying fibrous, chondroid, and myxoid areas. By immunohistochemistry, tumor cells stained for CD34, ERG, and focally S100 protein. RNA-sequencing allowed detection of THBS1-ADGFR5 gene fusion which confirmed the diagnosis of AFCMT. At 2-year follow-up, the patient remains free of recurrence. AFCMT is a previously unrecognized entity that may mimic chondroma and should be considered in the differential diagnosis of soft tissue tumors with cartilaginous or myxoid stroma in the extremities.

Genetic variant of SRF-rearranged myofibroma with a misleading nuclear expression of STAT6 and STAT6 involvement as 3' fusion partner.

Pediatric neoplasms with a myofibroblastic differentiation are frequent in children, in particular myofibroma. Recently, a novel deep soft tissue myofibroblastic neoplasm has been described with high cellularity, a smooth muscle phenotype and SRF-RELA fusion. We report the case of a 15-year-old boy who presented with a tumor of the deep soft tissue of the arm, with overlapping histological features with the recently described SRF-RELA group of myofibromas but differing by the presence of calcifications, a novel SRF-STAT6 fusion transcript and nuclear expression of STAT6. No local recurrence nor distant metastasis was detected at the current follow-up of 29 months. The clinical relevance of this novel fusion requires further investigations.