Final Diagnosis
Low-grade fibromyxoid sarcoma with prominent collagen rosettes and osseous metaplasia
Discussion
Low-grade fibromyxoid sarcoma (LGFS), also known as Evan’s tumor, is a neoplasm of fibroblastic or myofibroblastic origin characterized by a tendency for local recurrence and distant metastasis. It typically occurs in young adults, with a slight male predominance, and predominantly affects the proximal extremities and trunk, usually within the subfacial plane.
Histologically, LGFS is composed of areas that range from hypocellular to cellular, featuring bland spindle cell proliferation interspersed with small blood vessels, all set against a prominent myxoid to collagenous background. Mitotic activity is generally minimal, and a significant subset of cases displays rosettes composed of a hyalinized collagen center lined peripherally by tumor cells.
The majority of LGFS cases exhibit the characteristic translocation (7;16)(q33;p11), present in approximately two-thirds of cases, with supernumerary ring chromosomes noted in most of the remaining cases. This results in the fusion of the 5' part of the FUS gene (16p11) with the 3' part of CREB3L2 (7q33) in over 90% of cases, although rare instances of FUS::CREB3L1 and EWSR1::CREB3L1 fusions have been reported. The resulting chimeric protein functions as a transcription factor, leading to the dysregulation of genes such as MUC4 and CD24. Strong cytoplasmic expression of MUC4 in immunohistochemistry is a highly specific and sensitive marker for LGFS and is frequently observed in most cases of sclerosing epithelioid fibrosarcoma, as both tumors share similar molecular alterations. Additionally, a minor subset of other tumors, including certain carcinomas, synovial sarcoma, ossifying fibromyxoid tumors, epithelioid gastrointestinal stromal tumors, and myoepithelial carcinoma, has been reported to exhibit MUC4 staining.
Osseous metaplasia in LGFS is exceedingly rare, with only a handful of cases reported in the literature. The nearly complete rim of mature bone observed in our case is characteristic of ossifying fibromyxoid tumor (OFMT), another translocation-associated tumor. OFMT is composed of monomorphic round to ovoid cells arranged in cords and trabeculae within a variably fibromyxoid stroma. OFMT typically expresses S100 and desmin. Recurrent rearrangements of the PHF1 gene are characteristic of OFMT and can be found in its typical, atypical, and malignant variants.
In conclusion, our case highlights the classic features of LGFS, such as collagen rosettes, while also presenting a rarely described histologic feature of a nearly complete rim of mature bone.
References
Leona A. Doyle, Fredrik Mertens. Low-grade fibromyxoid sarcoma. In: WHO Classification of Tumours Editorial Board. Soft tissue and bone tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2020 [2024 Aug 26]. (WHO classification of tumours series, 5th ed.; vol. 3). Available from: https://tumourclassification.iarc.who.int/chapters/33.
Mertens F, Fletcher CD, Antonescu CR, et al. Clinicopathologic and molecular genetic characterization of low-grade fibromyxoid sarcoma, and cloning of a novel FUS/CREB3L1 fusion gene. Lab Invest. 2005; 85: 408–415.
Doyle LA, Möller E, Dal Cin P, et al. MUC4 is a highly sensitive and specific marker for low-grade fibromyxoid sarcoma. Am J Surg Pathol. 2011;35:733–741.
Serinelli S, Mookerjee GG, Stock H, et al. Low-grade Fibromyxoid Sarcoma With Heterotopic Bone Formation: Case Report and Review of the Literature. Appl Immunohistochem Mol Morphol. 2022 Oct 1;30(9):640-646
Thway K, Chisholm J, Hayes A, Swansbury J, Fisher C. Pediatric low-grade fibromyxoid sarcoma mimicking ossifying fibromyxoid tumor: adding to the diagnostic spectrum of soft tissue tumors with a bony shell. Hum Pathol. 2015 Mar;46(3):461-6.