Thomas Le Corroller
email: thomas.lecorroller@ap-hm.fr

Nicolas Macagno

Hugo Nihous

Pierre Champsaur

Corinne Bouvier

Acral FibroChondroMyxoid tumor: imaging features of a new entity

Keywords: Extremity, Tumor, Soft tissue

come

Introduction

"Acral FibroChondroMyxoid tumor" (AFCMT) is a recently described soft tissue tumor that occurs electively in the hands and feet and may involve the underlying bone in half of cases [START_REF] Bouvier | Recurrent novel THBS1-ADGRF5 gene fusion in a new tumor subtype "acral FibroChondroMyxoid tumors[END_REF]. Histologically, this tumor presents a multinodular growth pattern composed of a proliferation of small monotonous ovoid to spindle cells. AFCMT is characterized by an abundant fibrous or chondromyxoid stroma which may account for the previous misclassification of this entity as chondroma. Immunohistochemistry is of limited help with tumor cells usually expressing CD34, ERG, SOX 9, and S100, hinting at a partial cartilaginous differentiation [START_REF] Bouvier | Recurrent novel THBS1-ADGRF5 gene fusion in a new tumor subtype "acral FibroChondroMyxoid tumors[END_REF][START_REF] Shon | ERG expression in chondrogenic bone and soft tissue tumours[END_REF]. Yet, RNA-sequencing recently led to the identification of a recurrent THBS1-ADGFR5 gene fusion in all cases of AFCMT allowing better delineation of this entity [START_REF] Bouvier | Recurrent novel THBS1-ADGRF5 gene fusion in a new tumor subtype "acral FibroChondroMyxoid tumors[END_REF].

Thus far, the imaging features of this tumor have not been described. Here, we describe the imaging appearances, including radiography, computed tomography (CT) and magnetic resonance (MR) imaging, and histological features of AFCMT arising from the soft tissue of the proximal phalanx of the middle finger in a 44-year-old patient.

Case report

An otherwise healthy 44-year-old woman was evaluated for a slow-growing soft tissue mass present for 5 years in the middle finger of her right hand, associated with increasing pain. There was no history of trauma or prior surgery. Physical examination revealed a tender prominence just proximal to the ulnar aspect of the proximal interphalangeal (PIP) joint of the right medius. Plain radiographs showed a focal soft tissue fullness immediately medial to the proximal phalanx head of the third digit. There was associated saucerization of the underlying proximal phalanx cortex (Fig. 1). Computed tomography (CT) demonstrated a small soft tissue tumor at the ulnar aspect of the head of the proximal phalanx (Fig. 2). Subtle cortical buttressing at the proximal and dorsal aspects of the lesion indicated chronic pressure erosion. The tumor exhibited attenuation similar to that of water. There was no mineralization within the lesion. At MR imaging, the lesion exhibited intermediate signal on T1-weighted images and markedly hyperintense signal on T2-weighted images (Fig. 3). After intravenous contrast medium injection, the tumor displayed marked heterogeneous enhancement (Fig. 4). The lesion was well-circumscribed and did not extend into the PIP joint. As also seen on radiograph and CT, there was smooth scalloping of the underlying cortex of the proximal phalanx head. There was no associated perilesional bone marrow or soft tissue edema. At this point, a periosteal or soft tissue chondroma was thought likely, and the patient underwent an excisional biopsy.

Histological examination of the curettage specimens revealed a multilobulated tumor with fibrovascular septa (Fig. 5). The tumor was composed of round cells with scant eosinophilic cytoplasm arranged in small clusters or in columns within an abundant myxoid stroma. Neoplastic cells displayed round monotonous nuclei, without nucleoli. No mitosis was found. Immunochemistry study revealed diffuse expression of ERG and CD34, and focal expression of PS100, while SOX9, AE1-AE3, EMA, P63, and smooth muscle actin alpha were negative. Ki67 labeling index was 2%. A provisional diagnosis of chondroma was done, and IDH gene mutations were searched but not found. Because the microscopic features of this tumor were unusual, the molecular study was carried on. RNA-sequencing identified a THBS1-ADGFR5 gene fusion confirmed by RT-PCR. Finally, the histomorphologic findings combined with immunohistochemical and molecular findings led to the diagnostic of Acral FibroChondroMyxoid tumor.

The patient made complete recovery and remains free of recurrence at 2-year follow-up.

Discussion

Our case belongs to the recently published series reporting ten cases of a new mesenchymal acral tumor named Acral FibroChondroMyxoid tumor [START_REF] Bouvier | Recurrent novel THBS1-ADGRF5 gene fusion in a new tumor subtype "acral FibroChondroMyxoid tumors[END_REF]. In this series, AFCMT typically arose in the hands and feet, affecting mostly the fingers and phalanges, but also sometimes the metacarpophalangeal joint of adult patients with a median age of 42 years. The tumor appeared to be more common in males, with an apparent male to female ratio of 2/1. Clinically, the tumor presented as a painless nodule of the extremity, although moderate pain was reported in a minority of cases. Although AFCMT was not associated with aggressive clinical or morphological features, the tumor involved the adjacent cortical bone in half of cases. In all patients, AFCMT was surgically treated with marginal resection. Tumor recurrence was reported in two cases of this series, likely related to incomplete primary excision. Because prior radiological work-up was not available in most cases, the imaging features of this new entity have not been described yet.

Radiologically, the tumor presented in our case as a focal soft tissue fullness adjacent to the proximal phalanx head of the third digit, with saucerization of the underlying cortical bone. CT confirmed a small, well-circumscribed mass centered in the soft tissue of the ulnar aspect of the proximal phalanx. The tumor exhibited attenuation similar to that of water. On MR imaging, the lesion was slightly hyperintense to skeletal muscle on T1-weighted images and markedly hyperintense on T2-weighted images. As previously seen on radiograph and CT, there was smooth scalloping of the underlying cortex of the proximal phalanx head, and interestingly subtle cortical buttressing from a chronic pressure erosion. After intravenous contrast administration, the enhancement pattern was marked and peripheral. The tumor did not exhibit locally aggressive features. At the time of imaging, the diagnosis of juxtacortical chondroma was favored.

Radiologically, the differential diagnosis of a wellcircumscribed tumor in the soft tissue of a finger with pressure erosion of the underlying bone includes periosteal chondroma, giant cell tumor of tendon sheath, glomus tumor, inclusion cyst, and periosteal ganglion [START_REF] Varikatt | Superficial acral fibromyxoma: a report of two cases with radiological findings[END_REF][START_REF] Douis | The imaging of cartilaginous bone tumours. I. Benign lesions[END_REF][START_REF] Kwee | Calcified or ossified benign soft tissue lesions that may simulate malignancy[END_REF]. Based on imaging, however, the major differential diagnoses in our case were matrixrich mesenchymal tumors such as soft tissue chondroma, superficial acral fibromyxoma, and myoepithelioma [START_REF] Kwee | Calcified or ossified benign soft tissue lesions that may simulate malignancy[END_REF].

Indeed, in our patient, it was difficult to determine the exact nature of the neoplasm on preoperative imaging as well as on microscopy. The advent of next-generation sequencing has enabled the identification of novel recurrent gene fusion that can help redefine the classification of many previously unclassified mesenchymal tumors. The identification of a recurrent THBS1-ADGRF5 gene fusion in a group of acral soft tissue tumors associated with an abundant chondromyxoid matrix allowed the description of a new distinctive subtype of acral mesenchymal tumor called Acral FibroChondroMyxoid tumor [START_REF] Bouvier | Recurrent novel THBS1-ADGRF5 gene fusion in a new tumor subtype "acral FibroChondroMyxoid tumors[END_REF]. This neoplasm is characterized by a lobular pattern with fibrovascular septa, chondromyxoid stroma, and round or spindle cells, with immunophenotype that highlights a partial cartilaginous differentiation. Histologically, it has to be distinguished from periosteal or soft tissue chondroma, synovial chondromatosis, superficial acral fibromyxoma, and myoepithelial neoplasms. Periosteal and soft tissue chondromas exhibit a more hyaline cartilaginous matrix though myxoid features could focally be present. Molecular studies have respectively found IDH gene mutations in periosteal chondromas and FN1 fusions in soft tissue chondromas [START_REF] Amary | IDH1 and IDH2 mutations are frequent events in central chondrosarcomas and central and periosteal chondromas but not in other mesenchymal tumors[END_REF][START_REF] Amary | Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement[END_REF]. Synovial chondromatosis is characterized by mature cartilage formation and is connected to the synovium. FN1-ACVR2A fusions have been reported in half of cases [START_REF] Amary | Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement[END_REF]. Superficial acral fibromyxoma is a made of hypocellular myxoid nodules with bland spindle cells arranged in a storiform pattern. Exceptional cases with cartilaginous metaplasia have been reported [START_REF] Moulonguet | Superficial acral fi bromyxoma w ith carti laginous metaplas ia[END_REF][START_REF] Hollmann | Digital fibromyxoma (superficial acral fibromyxoma): a detailed characterization of 124 cases[END_REF]. Myoepithelial soft tissue tumors are usually multinodular as AFCMT and have a variable myxoid or chondroid stroma. However, tumor cells coexpress epithelial markers and Sox10 and/or S100 protein, and often also present EWSR1 or FUS fusions [START_REF] Antonescu | EWSR1-POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of sixty-six cases, including soft tissue, bone, and visceral lesions, showing common involvement of the EWSR1 gene[END_REF].

In summary, we reported the exhaustive radiographic, CT, MR imaging, and histological appearances of a case of AFCMT at the hand in a middle-aged woman. In our patient, this neoplasm exhibited overall non-specific imaging features and did not display aggressive behavior, supporting its benign Compliance with ethical standards

Fig. 1

 1 Fig. 1 Frontal radiographic view of the third digit showing a focal soft tissue fullness medial to the proximal phalanx head with saucerization of the underlying cortex and subtle cortical buttressing at the proximal aspect of the lesion (arrowhead)

Fig. 2

 2 Fig. 2 Frontal (a, b) and axial (c) CT reformatted images demonstrating a small soft tissue tumor at the ulnar aspect of the head of the proximal phalanx (thick arrows) and subtle cortical buttressing from a chronic periosteal reaction at the proximal and dorsal aspects of the lesion (arrowheads)

Fig. 3

 3 Fig. 3 Frontal T1-weighted (a) and fat-suppressed T2 (b) SE MR images showing a wellcircumscribed tumor (thick arrows) at the ulnar aspect of the proximal phalanx head of the third digit that does not extend into the PIP joint or medulla

Conflict of interest

The authors declare that they have no conflict of interest.

Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.