Low-grade fibromyxoid sarcoma and myxofibrosarcoma are malignant soft tissue tumors, fibrosarcomas, of shared clinical and imaging appearances. We report sarcomatous lesions in soft tissue with deceptively benign clinical and imaging appearances, and correlate findings with those of histologic analysis. Two patients presented with a long history of painless swelling at the dorsum and upper extremity and denied any constitutional symptoms. Sonography and magnetic resonance imaging suggested the presence of benign soft tissue lesions of a predominant fluid-like consistency. Despite indolent clinical and imaging characteristics, in both cases, histopathology disclosed a diagnosis of spindle cell-type soft tissue sarcoma, designating an aggressive tumor. Knowledge of the seemingly benign clinical and imaging features of fibrosarcomas is required to raise the possibility of malignancy in soft tissue that may be underdiagnosed or misdiagnosed. The importance of a correct diagnosis and the implications of surgical resection, irradiation, and systemic oncological therapy are quite obvious.

low-grade fibromyxoid sarcoma, myxofibrosarcoma, soft tissue, sarcoma, ultrasound, magnetic resonance imaging

Soft tissue sarcomas constitute a diverse group of solid tumors with mesenchymal differentiation accounting for less than 1% of all adult malignancies.^[1] Low-grade fibromyxoid sarcoma (LGFMS) is a rare malignant soft tissue sarcoma that is recognized in the World Health Organization (WHO) classification as a variant of fibrosarcoma arising in skeletal muscle, or the subcutaneous tissue. More than 150 LGFMS cases have been reported so far, although it is postulated that this tumor is often misdiagnosed as myxofibrosarcoma, low-grade myxoid sarcoma, or other sarcomatous or non-sarcomatous fibrous or myxoid neoplasms.^{[1, 2]} LGFMS typically occurs in young adults and originates in the deep soft tissue of the trunk or the lower extremities. In addition to mild atypical symptoms, our case presentation, to our knowledge, is the first to describe LGFMS assuming a benign, cyst-like appearance on imaging, which proved a diagnostic challenge to the oncology team.

Another mesenchymal tumor, myxofibrosarcoma, is acknowledged as a distinct myxoid variant of malignant fibrous histiocytoma with fibroblastic differentiation. This fibrosarcoma usually originates in the dermal and subcutaneous tissue of the extremities and is more common in the elderly. Despite its indolent presentation as a slowly growing mass, myxofibrosarcoma is often highly infiltrative, rendering local recurrence frequent. Additional characteristics of this sarcoma that make it particularly noteworthy include the extension of the tumor along the fascial planes, following a route that virtually facilitates distant recurrence.^{[1, 3-5]}

Although both of these malignant fibrous neoplasms of soft tissue can have a silent clinical course and a fallacious bland histological appearance, recurrence after surgery and late distant metastasis have been reported at variable but significant rates. Because malicious biological characteristics substantiate early recognition and specialized oncology treatment^{[1, 3-7]}, consideration of this family of sarcomatous tumors arising in soft tissue is of fundamental clinical importance. We aimed to identify key features that might help characterize the nature of soft tissue sarcomas, assuming latent characteristics.

Low-grade fibromyxoid sarcoma is a rare malignant mesenchymal tumor, a spindle cell sarcoma that usually arises in the deep soft tissues - i.e., the skeletal muscle of the trunk or thigh of young to middle-aged adults. Additional sites of involvement may include the chest wall/axilla, the shoulder, and the inguinal region.^{[1, 2]} Another subtype of fibrosarcoma, termed myxofibrosarcoma, is predominantly myxoid and usually arises in the subcutaneous tissue of the lower extremities in older patients.^[1] Notably, patients with either type of sarcoma often have an initial presentation of a painless and slowly growing soft tissue mass that is already large at the time of diagnosis.^[8] Both of our cases feature a typical presentation of this family of malignancies with regard to age, location, and depth of involvement in soft tissue. Our two patients presented with an asymptomatic soft tissue mass, and virtually no clinical suggestion of malignancy.

Because of a deceptively bland histologic appearance, the fibrosarcoma variants may initially be misdiagnosed as benign processes. Distinction between the two fibrosarcomas on histology is difficult, and is usually made in conjunction with the evaluation of specific tumor characteristics including cellular atypia and potential for metastasis.^[1] In regard to the first criterion used for diagnosis, mitotic figures and nuclear pleomorphism are commonly absent or sparse in LGFMS, whereas cellular pleomorphism and nuclear atypia is prominent in myxofibrosarcoma.^[9] Further, both (fibro)-myxoid sarcomas may demonstrate an infiltrating growth pattern, although this is more typical of myxofibrosarcoma.^[1] Metastasis, the second confounding criterion used to differentiate these sarcomatous tumors, is usually to the lung. Indeed, metastasis tends to occur in up to 50% of the patients with LGFMS, which, in contrast, is relatively less in the myxofibrosarcoma variant, ranging from 20% to 25% of the cases.^{[1, 7]} The histologic grade, however, is directly correlated with the biological behavior in terms of tumor recurrences or metastases.^[1] Unlike myxofibrosarcoma, LGFMS reportedly shows a definite propensity for late recurrence or metastasis.^{[1, 2, 6, 10]} Interestingly, in the presence of metastases survival may be prolonged.^{[6, 11, 12]} The reason for this unique tumor biology is unknown at present. Finally, an additional diagnostic consideration of importance that proves useful in the differential diagnosis of the two fibrosarcoma variants appears to involve the FUS gene translocation that is merely confirmatory for LGFMS.‌^{[1, 9, 10, 12]} Both our patients showed histopathological findings corresponding to their respective individual fibrosarcoma subtypes.

Imaging plays a pivotal role in the identification and localization of a mass lesion residing in soft tissue. In the fibrosarcoma family of malignancies, the imaging characteristics reflect primarily the alternating fibrous and myxoid components of tumor.^[8] Despite nonspecific imaging appearances of sarcomatous soft tissue tumors, the variability in histologic findings holds as a pervasive theme the presence of fibrous tissue and myxoid components. For example, the LGFMS is of a predominant myxoid nature. Histopathology of this fibroblastic neoplasm is that of a spindle cell sarcoma harboring an admixture of collagenous and myxoid zones that are arranged in a fascicular or storiform pattern.^{[1, 2]} Macroscopic signs of malignancy, such as necrosis, hemorrhage, nodularity, and infiltrative border are quite rare. In our patient with LGFMS, non-infiltrative cyst-like appearance of tumor on imaging was clearly misleading and could have been mistaken for other, benign fluid-containing lesions. To our knowledge, LGFMS manifesting with merely fluid-like echogenicity on US images has not been reported previously. Similar to the US findings, MR images showed signal intensity alterations consistent with the predominant myxoid component of tumor. On histology, the single intralesional nodule that enhanced avidly on MR images represented hypervascular myxoid material.^{[11, 13]}

In our patient with myxofibrosarcoma, the matrix was of a mixed fibrous, but predominantly myxoid consistency. Tumor cells were mildly pleomorphic and were seen arranged in a fascicular pattern, exhibiting some mitotic figures. US revealed an inhomogeneous lesion, which on histology was found to correspond to abundant myxoid material. On MR images, the myxoid component of the tumor exhibited decreased signal intensity on the T1- and increased signal on the T2-weighted images. Fibrous tissue within tumor exhibited low signal intensity on both the T1- and T2-weighted images.

Although the imaging findings of the lesions could not be used to determine the aggressive or nonaggressive behavior of each individual process, the exact histologic composition, or the potential for complications, there is no doubt that the imaging studies offered us a window through which to view the histologic nature of abnormal tissue.^[13] The primary diagnostic considerations for soft tissue lesions with mixed fibrous and cyst-like elements are broad and besides LGFMS and low-grade myxofibrosarcoma include myxoliposarcoma, myxoid variant of dermatofibrosarcoma protuberans (DFSP), nodular fasciitis, desmoid fibromatosis, myxoid neurofibroma, and neurogenic tumors.^{[1, 13]} Myxoliposarcoma typically demonstrates a fatty component on imaging. Myxoid DFSP is a more cellular neoplasm infiltrating subcutaneous tissue in a lace-like fashion. Nodular fasciitis is situated in subcutaneous tissue and consists of bland myofibroblasts embedded in a prominent myxoid matrix, and chronic inflammatory cells. Desmoid fibromatosis is a less cellular and more collagen-forming process. Mild enhancement of hyperintense areas on corresponding T2-weighted MR images, and the presence of entering and exiting nerve favor neurogenic tumors versus LGFMS.^[13]

Because of a nonaggressive clinical course, soft tissue sarcomatous tumors can initially be misdiagnosed as lesions of a benign nature. Clinicians need to understand that a soft tissue mass exhibiting bland characteristics urges performance of diagnostic imaging and immediate biopsy to avoid misdiagnosis and to prevent delayed diagnosis and complications. The standard treatment for patients with localized disease is surgery with an intended wide margin. Patients with local recurrences are treated with repeat surgery and radiotherapy for local disease control. In those cases with metastatic fibrosarcomas, treatment includes multiagent palliative chemotherapy (doxorubicin, ifosfamide) for short-term stabilization of disease progression, and selective surgery of operable metastases.^[14]

We report the constellation of imaging findings, histologic analyses, and clinical follow-up favoring the diagnosis of soft tissue sarcoma containing both fibrous and fluid-like elements in two patients with slow-growing mass lesions. Our LGFMS case presentation as a simple cyst on US has not been described before, and as such, we believe this observation should be considered in the differential diagnosis of soft tissue mass lesions. These cases illustrate the difficulty in evaluating soft tissue sarcomas that may assume non-aggressive clinical, imaging, and histologic characteristics.

Authors are indebted to Dr. Kinta Hatakeyama, Department of Pathology, Miyazaki Medical College, for providing histologic slices.

The authors have no funding to report.

The authors have declared that no competing interests exist.