Surgical Treatment of Intramuscular Myxoma

Abstract

Purpose

Intramuscular myxoma (IM) is a rare benign myxoid tumor that may be challenging to differentiate from sarcoma in small amounts of biopsied material. Although IM appears to be well-circumscribed macroscopically, it infiltrates the adjacent edematous muscle microscopically. The recommended treatment is resection, but there is controversy with regard to the appropriate surgical margin. This study aimed to clarify which surgical procedure that should be applied when the preoperative diagnosis is IM and how to manage treatment if the postoperative diagnosis turns out to be a sarcoma.

Methods

We retrospectively examined 55 IM patients treated from January 1982 to December 2014. Patient characteristics, tumor location, tumor size, radiograph, preoperative and postoperative pathological reports, surgical techniques, treatment outcome, and complications were reviewed. The patients were followed up on for at least 5 years. All patients were confirmed not to have Mazabraud syndrome.

Results

In the 55 IM patients examined, the mean patient age was 48 years and most were female. The most common tumor locations were in the muscles of the thighs (47%) and buttocks (20%). The mean tumor diameter was 5 cm. Wide resection and marginal resection were performed in 24 and 31 patients, respectively. The mean follow-up duration was 19 years. No local recurrence, malignant transformation, or complications were observed.

Conclusions

Marginal resection is suitable in patients whose preoperative diagnosis is IM, as it is able to prevent local recurrence and allows for the preservation of muscle and muscle fascia. If the postoperative diagnosis turns out to be myxoid sarcoma, minimum surgical contamination makes additional wide resection less invasive.

Introduction

Intramuscular myxoma (IM) is a rare benign mesenchymal soft tissue tumor with a reported incidence of 1:1,000,000 [1, 2]. Despite its low incidence, it is the most common benign myxoid neoplasm. The most frequently occurs in patients aged between 40 and 70 years and is more common in females than males. The clinical presentation is a painless, solitary, slow-growing mass that is mainly found in the muscles of the thighs and buttocks [3, 4]. Multiple lesions are rare but may be associated with fibrous dysplasia as part of Mazabraud syndrome [5]. Previous reports have shown that IM exhibits non-specific imaging characteristics on MRI, usually presenting with homogeneous hypointensity on T1-weighted images, marked hyperintensity on T2-weighted images, and variable contrast enhancement [6–8]. In terms of macroscopic findings, although IM appears well-circumscribed, closer examination often reveals an ill-defined border, where the tumor merges with the surrounding muscle. Histologically, IMs are typically hypocellular, hypovascular, and consist of an abundance of the non-collagenous mucinous stroma. However, in some cases, there are areas of hypercellularity and vascularity that are often initially misdiagnosed as sarcomas [9]. An accurate diagnosis before surgery is particularly challenging due to the clinical, radiological, and pathological overlap with myxoid sarcomas, such as low-grade myxofibrosarcoma (MFS), low-grade fibromyxoid sarcoma (FMS), and myxoid liposarcoma (MLS), as well as the small amount of material that is obtainable by preoperative needle biopsy [1, 9]. The recommended treatment is surgical resection, but there is no consensus with regard to the optimal surgical margins. This study aimed to clarify which surgical procedure should be applied when the preoperative diagnosis is IM and how to manage treatment if the postoperative diagnosis turns to be a sarcoma.

Materials and Methods

This study was approved by our institutional ethics committee. The medical records were evaluated based on hospital records of 55 patients with pathologically confirmed IM treated between January 1982 and December 2014. Clinical data were retrospectively reviewed from the medical records, including the patient characteristics, tumor location and size, radiography results, preoperative and postoperative pathological reports, surgical technique, margin status, outcomes, and postoperative complications. We followed-up on the patients for at least 5 years. All patients were confirmed not to have fibrous dysplasia or Mazabraud syndrome.

Wide resection involves the removal of the tumor along with at least 1 cm of normal tissue, covering the edematous area of the tumor with resection of muscle and fascia. In marginal resection, the surgical plane runs through the reactive zone, and only the core is resected, while the surrounding tissue, including muscle and muscle fascia, is preserved (Fig. 1).

Fig. 1.

Surgical technique of wide and marginal resection. a Wide resection is defined as the removal of tumor along with at least 1 cm of normal tissue. b Marginal resection is a surgical plane that runs through the reactive zone which only the core part is resected while preserving surrounding tissue included muscle and muscle fascia

Results

Data were reviewed from a total of 55 IM patients (11 male and 44 female [1:4]) treated between 1982 and 2014 (Table 1). The mean patient age was 48 years (range 18–73 years), and the typical age at presentation was 40–60 years (77%). The most frequently encountered clinical sign was a painless, solitary, slow-growing mass located in the thigh muscle (47%) or the buttock and groin (20%). The mean tumor size was 5.0 cm (range 1–13.8 cm). In all cases, preoperative radiography showed a non-specific soft-tissue mass with no evidence of calcification, bone involvement, or periosteal reaction. Forty-two patients underwent MRI examination preoperatively, which, in most cases, showed well-circumscribed intramuscular lesions, homogeneous hypointensity on T1-weighted images, hyperintensity with surrounding soft tissue edema on T2-weighted images, and mild contrast enhancement on T1-FS-Gadolinium (Fig. 2). Six patients, all female, presented with tumors larger than 9.0 cm, all of which occurred in the large muscle of the thighs and buttocks. Tumors had a cystic component in two cases (Fig. 3).

Table 1.

Patient characteristics (n = 55 cases)

Sex
Male	11 (20%)
Female	44 (80%)
Age (years); mean [SD]	48.16 (range 18–73)
Location
Thigh	26 (47%)
Buttock and groin	11 (20%)
Shoulder and arm	6 (11%)
Knee, leg, and foot	5 (9%)
Chest and back	4 (7%)
Elbow and forearm	3 (6%)
Size (cm); mean [SD]	5.0
Resection
Marginal	31 (56%)
Wide	24 (44%)
Follow-up period (years); mean [SD]	18.7 (range 5–37)

Fig. 2.

An intramuscular myxoma at vastus intermedius muscle. a, b Homogeneous hypointense mass with fat at the inferior pole and rim (arrows) in coronal-T1-w. c Inhomogeneous hyperintense and peripheral edema (arrows) in coronal-T2-FS. d Mild enhancement (arrow) in coronal-T1-FS-Gado. e–g Mass at axial-T1-w, T2-w, and T1-FS-Gado (arrow). h Grey-white mucoid mass with peripheral edema (arrows)

Fig. 3.

A 60-year-old male patient. a Homogeneous hypointense mass at adductor magnus muscle (arrow) in coronal-T1-w. b Inhomogeneous hyperintense (arrow) with septation (arrowhead) and cystic area (asterisk) in coronal-T2-FS. c Mild heterogeneous enhancement (arrow) in coronal-T1-FS-Gado. d, e Mass attaches to the bone and vascular structures (arrows) in axial-T2-w and T1-FS-Gado

Initial treatment consisted of wide resection of the tumor in 24 cases, two of which were tumors larger than 9.0 cm. Marginal resection was performed in 31 cases, four with tumors larger than 9.0 cm (Fig. 4). The mean follow-up period was 19 years (range 5–37 years). Patients underwent regular follow-up evaluations every 6 months during the first 2 years after surgery, consisting of physical examinations and local ultrasound or MRI. Subsequently, patients were followed-up on once per year. No local recurrence, malignant transformation, or complications were observed in patients who underwent either surgical technique.

Fig. 4.

Intra-operative appearance of a mass located in the adductor magnus muscle. a–c Mass at adductor magnus muscle, marginal resection, and preserved muscle fascia (arrow). d Pale yellow-white appearance (arrow) and bilocular cystic area (arrowheads). e Microscopic findings, spindle cells with normochromic nuclei in a myxoid stroma background (papanicolaou stain of cytology smear)

Discussion

IM typically presents as a soft tissue mass in patients between the ages of 40 and 70 years. Two-thirds of IM patients are female, and the most common tumor sites are the thighs and buttocks. The duration of symptoms ranges from a few days to years, and tumor diameter ranges from 2 to 15 cm [3, 4]. Patient characteristics and tumor size and location in our series were similar to those observed in previous studies, but ours had a slightly higher proportion of female patients (approximately 80%) [3, 9]. From our results, the patients’ characteristics of IM still be the same for over decades for instance, age, gender, tumor size, and tumor location. The youngest patient in our series was 18 years. According to the literature, the IM is relatively rare in patients younger than 10 years, there were 2 cases from 2- and 5-year-old girls [10, 11]. Age should be considered when diagnosing IM. To the best of our knowledge, this report is considered the longest and the 2nd largest series of IM. However, the largest series studied in 68 cases of intramuscular myxomas, which studied about karyotyping and analysis of GNAS gene [12].

Recent genetic studies have suggested that IM could be linked to post-zygotic mutations of the GNAS1 gene, located on chromosome 20q13.2-q13.3. Guanine nucleotide-binding protein-α stimulating (GNAS) mutation is used in the diagnosis of IM and in differentiating it from other myxoid lesions. However, the sensitivity of these assays ranges from 29 to 92.3%, depending on the assay platform used, and the tools necessary for this kind of molecular genetic analysis are not readily available in most laboratories [12–17].

The recommended treatment is surgical resection, but there is no consensus with regard to the optimal surgical margin. Although IM appears to be well-circumscribed macroscopically, it infiltrates the adjacent muscle microscopically, meaning that the tumor is composed of a core and a surrounding edematous area [6]. Local recurrence has been reported in a small number of patients undergoing incomplete resection with highly cellular lesions [9]. Because it is unknown whether the reactive zone should be resected with the main tumor and due to the possibility of misdiagnosis with low-grade myxoid sarcoma, some reports have recommended wide resection or simple excision with a small margin of a few muscle fibers [18–22]. However, wide resection has been reported to lead to complications such as longer incision, excessive muscle removal, injury to neurovascular structures, and the need for amputation [3, 23]. In this study, we found no difference between wide and marginal resection in terms of local recurrence. In marginal resection, only the core of the tumor is resected, while the surrounding tissue is preserved. In case a multidisciplinary team such as the surgeon, radiologist, and pathologist confirmed final diagnosis is IM, the marginal resection may also be an appropriate treatment option, as it can both prevent local recurrence and lead to fewer complications compared to wide excision. Initially, our surgical plan was wide resection procedure, which completely removes both the tumor and the surrounding reactive zone. As the number of operated cases increased, we found that no local recurrence was observed even in cases, where the pathological resection line extended into the reactive zone. From these results, we decided to use marginal resection that is less invasive than wide resection. The definition of our marginal resection is no changing over time, which we defined marginal margin is a margin passing through the reactive zone. However, the definition of wide resection based on the pathological and surgical study was an evolution, which described in wide (inadequate and adequate) and curative resection in 1989 [24]. The reactive zone and barrier used in this evaluation system are strictly defined. Initially, the resection plan of our IM cases was wide-1 cm or inadequate wide margin, which means surgical line runs less than 1 cm outside the reactive zone.

It can be challenging to differentiate between IM and myxoid sarcoma preoperatively, especially when using small amounts of biopsied material [1, 9]. The final diagnosis is thus determined when the whole tumor is examined. There are some rare cases in which the final diagnosis turns out to be low-grade myxoid sarcoma. In such cases, additional resection is necessary [25]. The previous marginal resection preserves the muscle and muscle fascia and provides an effective barrier for containing the tumor. The quality of the margin (fascia) is more important than the size (length). If the scar from the previous operation, hemorrhage, or edema are determined to be contaminated with tumor material, resection with an adequately wide margin is recommended [26].

This study has some limitations. Its observational nature prohibited direct causal interpretation of margin status influence on outcomes. Also, inherent selection bias is present in all retrospective studies, but with a relatively rare disease such as IM, there are no randomized data available. All patients were treated at a single institution under a uniform surgical margin evaluation system [24], but our experience spans decades during which imaging, pathology, and surgical methods have undoubtedly evolved. Some of the strengths of this study include the large number of patients, length of follow‐up, and consistent data reporting of the institutions.

Conclusions

Marginal resection is suitable in patients whose preoperative diagnosis is myxoma, as it can prevent local recurrence and allow for the preservation of the muscle and muscle fascia. If the postoperative diagnosis turns out to be myxoid sarcoma, minimal surgical contamination makes additional wide resection less invasive.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Standard statement

This study received approval from the institutional review board (IRB) of the Cancer Institute Hospital of the Japanese Foundation for Cancer Research.

Informed Consent

For this type of study informed consent is not required.