Low-grade Fibromyxoid Sarcoma With Massive Degeneration: A Case of Unusual Gross and Histological Features

Abstract

Background: Low-grade fibromyxoid sarcoma (LGFMS) is a rare type of sarcoma which is observed in the soft tissue of proximal extremities, typically in young and middle-aged adults. It consists of a solid proliferation of bland spindle cells within collagenous and myxoid stroma.

Case report: Herein, we report a case of LGFMS with massive degeneration and hyalinization. A 30-year-old man presented with a well-circumscribed mass measuring 15 cm in diameter in his left biceps femoris muscle. Marginal tumor resection was performed under the clinical diagnosis of an ancient schwannoma or chronic expanding hematoma (CEH). The resected tissue revealed a well-demarcated tumor mass with massive degeneration and hyalinization with focal calcification. Proliferation of spindle tumor cells with abundant collagenous stroma, which resembled the fibrous capsule of CEH, was observed exclusively in a small area of the periphery of the tumor. No nuclear palisading, myxoid stroma, or collagen rosettes were identified. Immunohistochemical analysis demonstrated that the spindle tumor cells expressed mucin 4 and epithelial membrane antigen. Reverse transcriptase-polymerase chain reaction analysis detected mRNA expression of fused in sarcoma::CAMP-responsive element binding protein 3-like protein 2 (FUS::CREB3L2) fusion gene. Thus, a final diagnosis of LGFMS with massive degeneration and FUS::CREB3L2 fusion was made.

Conclusion: The recognition of massive degeneration and hyalinization as unusual features of LGFMS might be helpful to differentiate it from CEH and other benign spindle-cell tumors.

Keywords: FUS::CREB3L2 fusion; Low-grade fibromyxoid sarcoma; MUC4; massive necrosis.

Figure 1. Diagnostic imaging. Coronal (A) and axial (B) contrast-enhanced computed tomography of the tumor revealed low density in most areas, suggesting cystic degeneration or a hematoma. The peripheral area showed mild contrast enhancement (arrowheads) and calcification (arrow). 18F-Fluorodeoxyglucose positron-emission tomography/computed tomography showed an increased uptake in the peripheral area (arrowheads). On T1-weighted (D) and T2-weighted (E) magnetic resonance imaging, the central area of the tumor exhibited high intensity, while the peripheral area (arrowheads) showed low intensity. On post-contrast T1-weighted magnetic resonance imaging (F), the peripheral area demonstrated moderate contrast enhancement (arrowheads), indicating a cellular area of a fibrous capsule or tumor proliferation.

Figure 2. Macroscopic and microscopic tumor findings. A: Macroscopic examination of the resected tumor, showing a yellow-brown cyst-like cavitation area and peripheral greyish-white solid area (arrowheads). B: Histological examination with a low-power scanning view of the areas of massive necrosis and hyalinization (left side of the dashed line) [hematoxylin and eosin (HE), 40×]. C: Medium-power view of the tumor periphery, showing a fascicular proliferation of spindle cells with collagenous stroma. (HE, 100×). D: High-power view of the tumor, showing spindle cells with bland-looking nuclei and inconspicuous nucleoli. No myxoid stroma or collagen rosettes were observed. (HE, 400×). Immunohistochemical study revealed that spindle cells were positive for mucin 4 (E) and epithelial membrane antigen (F). (400×).

Figure 3. Reverse transcriptase-polymerase chain reaction analysis for the detection of fused in sarcoma–CAMP-responsive element binding protein 3-like protein 2 (FUS::CREB3L2) fusion gene. A: Reverse transcriptase-polymerase chain reaction using mRNAs extracted from formalin-fixed paraffin-embedded tumor tissue. Using F-C3 primers, a specific PCR product (149 bp) of FUS::CREB3L2 fusion gene was detected. F-C5 primers for FUS::CREB3L1 did not amplify any genes. B: Sanger sequencing of the PCR product revealed a fusion point generating FUS::CREB3L2 fusion, in exon 6 of FUS and exon 5 of CREB3L2. F-C1, -2, -3, -4: FUS::CREB3L2 primers (F-C3: 149 bp); F-C5: FUS::CREB3L1 primer; M: molecular size marker; N: negative control (distilled water); PBGD: porphobilinogen deaminase (127 bp); PGK: phosphoglycerate kinase (247 bp).