Superficial acral calcified chondroid mesenchymal neoplasm harboring an FN1::FGFR2 fusion and review of the literature

Abstract

Calcified chondroid mesenchymal neoplasm is a recently recognized bone and soft tissue entity primarily found in the extremities and the temporomandibular joint. This neoplasm is typically driven by the fusion of the FN1 gene with a kinase. In this case report, we provide a detailed account of a rare superficial calcified chondroid mesenchymal neoplasm located on the left big toe, characterized by an FN1::FGFR2 fusion. The tumor exhibited a peripheral collarette and consisted of large intradermal histiocytoid to epithelioid cells with no mitotic activity. These cells displayed fine chromatin and abundant pale eosinophilic cytoplasm, forming a swirling syncytium. They were interspersed with localized areas of glassy chondromyxoid matrix containing randomly mineralized calcific material and isolated osteoclast-like giant cells. RNA sequencing confirmed the presence of an FN1 (exon 29)::FGFR2 (exon 7) gene fusion. Our report emphasizes the importance for dermatopathologists to consider this entity when evaluating superficial lesions displaying mesenchymal, chondroid, and calcified attributes.

Keywords: FGFR2; FN1; acral; calcified chondroid mesenchymal neoplasm; superficial.

Figure 1:

A. Subungual and superficial location on the left hallux. B. Foot X-ray examination reveals no bone abnormalities. C and D. Hematoxylin and eosin (H&E) sections demonstrate a multinodular and zonated architecture, which can be appreciated at low power (100x). The lesion is centered in the dermis and is surrounded by a peripheral collarette that directly abuts the overlying attenuated epidermis.

Figure 2:

A & B. The tumor displays a multilobulated growth pattern with lobules composed of neoplastic cells embedded in chondromyxoid stromal tissue separated by fibrous septa of variable thickness (H&E 200x and 400x, respectively). C. Grungy calcification with isolated osteoclast-like multinucleated giant cells at the periphery of the lobules (arrow) (H&E 400x). D. Intercellular lacings with grungy calcification and large histiocytoid to epithelioid cells, exhibiting fine chromatin and voluminous pale eosinophilic cytoplasm (H&E 400x). E. Strong and diffuse nuclear ERG positivity in tumor cells (400x). F. Moderate S100 immunoreactivity in the neoplastic cells (200x).

Figure 3:

A. screenshot of RNA sequencing showing an in-frame fusion between exon 29 of FN1 at the 5’ end with exon 7 of FGFR2 at the 3’end producing a chimeric fusion. The fusion passed all quality control metrics including total number of unique RNA reads supporting the fusion (14171, above the validated cutoff of 5 reads), unique RNA reads with unique start sites (357, above the validated cutoff of 3 reads) and a unique RNA percentage of 77.7% above the validated cutoff of 40%. Red arrow designates the gene specific primer targeting FGFR2 that generated the reads mapping to the FN1::FGFR2 fusion.