Nosologic reappraisal of the recently proposed calcified chondroid mesenchymal neoplasm concept in a series of 20 cases.

Abstract

"Calcified chondroid mesenchymal neoplasm (CCMN)" is a recently proposed term for tumors with hypercellular chondroid histology and fusion genes. However, its impact on the present classification framework has not been extensively investigated. In this study, we analyzed 20 tumors with histology that would fit with that reported as "CCMN." With the combined use of RNA sequencing and fluorescence in situ hybridization, 15 tumors were found to have gene fusions, including FN1::FGFR2 (N=4), FN1::TEK (N=1), FN1::MERTK (N=1), PDGFRA::USP8 (N=2), FN1 rearrangements with undetermined non-FGFR2 partners (N=4), and PDGFRA rearrangements with undetermined partners (N=3). FN1 or PDGFRA rearrangement signals were restricted to epithelioid/polygonal cells, indicating that these were neoplastic elements mixed with abundant reactive cells. The fusion-positive tumors were found in 7 men and 8 women aged 29-82 years (median, 57 years), and most involved the temporomandibular joints (TMJ) or digits. Tumors showed a chondroid matrix with grungy calcification and cellular components with epithelioid/polygonal cells and were divided into 2 groups whose histology corresponded to chondroid tenosynovial giant cell tumor or soft-tissue chondroma. Three fusion-positive tumors harbored calcium pyrophosphate dihydrate crystals. Nuclear atypia was frequent. Gene fusions were not detected in the remaining 5 tumors with abundant crystal/calcium deposition, and some may represent reactive conditions. All 20 tumors followed an indolent clinical course, and 4 patients with TMJ tumors were successfully followed up without surgery for 9-60 months. Using "CCMN" as an entity would entail mixed repercussions in diagnostic practice, and how and whether it should be used in diagnosis requires deliberate discussion. The concept might bring some benefits, but it may cause more confusion because it would substantially restructure the conventional framework by drawing a boundary within the chondroma and conflating the chondroma with chondroid tenosynovial giant cell tumor.