Low-grade Myofibroblastic sarcoma: clinical and imaging findings

Low-grade myofibroblastic sarcoma (LGMS) is a rare type of malignant myofibroblastic tumor. Though it may occur to any body part, the most common location is the limbs, head and neck region, particularly the tongue and mouth [1]. Previously published literature mainly focused on reporting pathological analyses of LGMS, while only few systematic clinical and/or radiological studies of this disease have been conducted.

This study recruited 14 cases of LGMS from two hospitals (one of the 14 participants had converted to LGMS from multiple relapses of an inflammatory myofibroblastic tumor). The imaging findings and biological characteristics were different from those of previous studies. Therefore, we report them in this article, hoping to provide further insights into LGMS.

Myofibroblastic tumor cell is a type of contractible fusiform mesenchymal cell. It integrates the morphologic features of fibroblasts and those of smooth muscle cells into itself [2]. It was firstly discovered in granulation tissues. Mentzel et al. [2] reported 18 cases of low-grade myofibroblastic sarcoma in 1998. This type of tumor was recognized as a new category by the World Health Organization’s (WHO) in “Pathology and Genetics of Tumors of Soft Tissue and Bone” in 2002, and characterized by intermediate grade (occasionally transferable) malignancy. Tumor cells were considered as the origin of myofibroblasts. The WHO 2013 document maintained the classification of this disease [3]. Accurate categorization of myofibroblastic tumors and inflammatory myofibroblastic tumors (IMT) on oncology may provide further insights into pseudo-tumoral lesions and myofibroblastic tumors.

To the best of our knowledge, only a few studies about LGMS have been conducted, reporting 65 cases of this disease [4‐9]. Tumors occurred to 24 cases in the head and neck region (24/65, 38.7%), including the lower jaw, jawbone, nasal sinus, oral cavity, etc. Among the other 41 cases, tumors were found in the upper and lower limbs, ileums, bones, etc. In these patients with an average age of 40 years old (age range: 9–75 years), most of the tumors were solitary with a maximum diameter of 1.5 to 22 cm. Only 3 cases of them were reported to develop tumors in the abdomen, pelvis and upper extremities [2, 10]. All of our participants (average age: 45.5 years old) developed solitary tumors, with the largest maximum diameter being 13.5 cm. Five out of these tumors were located in bones (35.7%), and most of the 5 were in the distal femur. Another five participants’ tumors were located in the musculoskeletal groups of the extremities (35.7%). The other four cases developed tumors in the pyriform sinus, epiglottis, breast and liver (7.1%), respectively. Overall, the tumor locations in our studies were different from those reported previously.

Although LGMS is classified as an intermediate grade tumor, high recurrence and metastasis rate highlight the need for more pathological analyses. Among the 65 cases mentioned above [5‐9] and the 14 cases in our study, overall 23 cases suffered local recurrence (23/79, 29.1%), among which 3 were from our study (3/14, 21.4%). The recurrence period varied from 6 months to 7 years, with a maximal recurrence frequency of 4 times. After 3 recurrences of inflammatory myofibroblastic tumor, one participant in our study (Case 14) developed LGMS and the following 4 recurrences were all LGMS, indicating an increase in tumor grade due to recurrence. Theoretically, recurrence of LGMS can lead to escalation to intermediate-grade and high-grade myofibroblastic sarcoma. However, to the best of our knowledge, no such escalation has yet been reported. Fourteen cases experienced distal metastases (14/79, 17.7%), among which 5 were from our study (5/14, 35.7%). This means that the overall metastasis rate among our 14 participants is obviously higher than that among the 65 cases previously reported. Metastasis and the primary tumor were found at the same time in only 1 case (Case 1), while in the other 13 cases of our study, metastases were found within 4 months to 9 years after surgical procedures. The most common sites of metastasis include the lungs (7/14) and bones (5/14). Metastasis was also found in the heart, gastrocnemius, and tongue. Multiple metastases may occur to any of these body parts. There was one patient who underwent extensive resection and radiotherapy, and did not experience any recurrence or metastasis within 12-year follow-up. Other 6 patients who underwent extensive resection suffered no recurrence within 18 to 59 months of the follow-up. Our findings demonstrate that extensive resection of LGMS contributes to a good prognosis. Only a few tumors (especially those in deep locations) recur after local excision (mostly within 2 years, including small tumors), and some of these tumors may metastasize to distal locations 5 years later. After a series of evaluation and grading, we come to a conclusion: patients suffering metastasis but expecting to live longer can undergo extensive resection, joint replacement and adjuvant chemotherapy or radiotherapy, while palliative therapy can be prescribed to those who are intolerable to these therapies. So far, 2 patients have died of multiple organ failures. Previous studies [10] have reported that intermediate grade myofibroblastic sarcomas have a high rate of recurrence and metastasis, compared with fibrosarcoma and leiomyosarcoma.

Scarcity of imaging studies of LGMS makes imaging characteristics of this disease still poorly understood. To our knowledge, imaging findings about 4 LGMS cases have been reported so far [5, 7‐9], and the tumors were found in the wall of the right atrium, abdomen, epiglottis, and distal femur, respectively. The tumor located in the right atrium was a result of metastasis. It was more hyperintense than that in the myocardium on T1WI images, and the signal was enhanced on delayed contrast-enhanced images [8]. Another case of a large abdominal LGMS was characterized by a low signal solid mass with significant signal enhancement in the early phase and concentric filling during the late phase. MRI of this tumor located in abdomen displayed homogeneous and hypointense signal on T1WI, hyperintense signal on T2WI, and homogeneous signal enhancement on contrast-enhanced images. Enhanced CT scan of the tumor located in the epiglottis revealed inhomogeneous enhancement [5]. The patient whose tumor was located in the distal femur presented extensive multi-cystic bone destruction with clearly sharp margins and without significant hardened edges. Parts of the cortical bone were invaded and a soft tissue mass developed. In all four cases described above, no calcification or ossification of the lesions was observed, and there was no CT number change before and after enhanced CT scans. Some tumors in our study were located in bones (5/14,35.7%) with 3 of the 5 in the distal femur (3/5, 60%). Imaging results in our study are different from those previously reported [9]. The 3 tumors located in the femur were in high-grade malignancy, and with permeant tumor tissues and osteolytic bone destruction. In addition, the bone interval boundary was not clear, and transitional zone and cortical bone erosion were present. In the other 2 cases whose tumor were located in the right shoulder blade and right lower pubic region, the huge mass damaged the bone cortex and a significant soft tissue mass formed. Massive ossification was observed in the primary tumor and the lung metastasis (Case 1). X-ray or CT scan of 2 LGMS cases revealed significant ossification masses within bones, indicating a higher rate of LGMS ossification than that reported in previous studies. LGMS ossification is presumably attributed to multiple differentiations of intratumoral myofibroblasts into metaplasia-induced osteoblasts. There have been no reports about osteoblastic metastases from LGMS. It is important to distinguish bone LGMS from osteosarcoma, fibrosarcoma, malignant fibrous histiocytoma or malignant cartilaginous tumor.

Breast LGMS is very rare. To our knowledge, 1 of our 14 cases represents the fourth reported case [11‐13]. It is necessary to differentiate breast LGMS from breast cancer. Most breast sarcomas of mesenchymal origins are prone to blood metastasis, while breast cancer of epithelial origins are prone to lymphatic metastasis. Therefore, mammography of advanced-stage breast cancers usually reveals interstitial edema, increased trabecular thickening, opacity of the subcutaneous fat layer and thickening of the skin because of the clogged lymphatic drainage from the cancer cells. However, these and axillary lymph node enlargement are not observed in the mammographs of stromal breast sarcoma. Breast LGMS in our study is characterized by a certain level of aggressiveness (indicated by an irregular shape, and multiple angular and poorly-circumscribed margins), or precisely, a lack of encapsulation.

LGMS is a rare type of tumor. Only few systematic studies of its diagnostic and radiological features have been conducted. In this study, we find that LGMS is characterized by several imaging features: invasiveness, metastasis and calcification. Inflammatory myofibroblastic tumors are likely to progress into LGMS after several recurrences. A large portion of the tumors in our study were located in bones. This study has two limitations. Only small amounts of patients were recruited. And more imaging examinations should have been performed on each patient. Therefore, further exploration is need to understand imaging features of LGMS better, for example, the most preferred site. Although it is classified as an intermediate grade tumor, LGMS has high rate of recurrence, metastasis and calcification, which also highlights the need for further clinical and pathological analysis. With accurate diagnosis comes effective treatment.