Low-Grade Myofibroblastic Sarcoma in the Oral Cavity: Case Report and Clinical Insights

Abstract

Background/Objectives: Low-grade myofibroblastic sarcoma is a rare malignant myofibroblastic tumor, first described by Gabbiani et al. in 1971. It predominantly affects adult males and is uncommon in children. The tumor can occur anywhere in the body, with a preference for the limbs and head and neck regions, including the oral cavity. Methods: A case report of a 22-year-old male patient with no systemic conditions who presented with a painless, red, firm swelling between teeth 34 and 35 was examined. Panoramic radiography was unremarkable. The lesion measured 19 × 8 mm. Histological analysis revealed a spindle cell proliferation with atypia. Immunohistochemical staining was positive for SMA and showed a low Ki-67 proliferative index, while negative for Desmin, CD34, and beta-catenin. The final diagnosis was low-grade myofibroblastic sarcoma. Results: After surgical excision, the lesion recurred within one month. The patient was referred to the Portuguese Institute of Oncology for further treatment. Conclusions: Low-grade myofibroblastic sarcoma is a rare tumor with a tendency for local recurrence and metastasis. Accurate diagnosis, which includes histological examination and immunohistochemistry, is essential to differentiate it from other benign and malignant lesions. This case highlights the importance of an incisional biopsy to confirm diagnosis prior to surgical excision, thereby reducing the risk of relapse and enabling appropriate treatment planning.

1. Introduction

Low-grade myofibroblastic sarcoma (LGMS) is an atypical malignant tumor composed of myofibroblasts, first described by Gabbiani et al. in 1971 [1,2]. This rare tumor affects adult males slightly more frequently (51%), and is uncommon in children [3]. Although it can develop anywhere in the body, the extremities and the head and neck region are the most frequent sites [4,5]. Within the head and neck, it is most often found in the tongue, gingiva, and maxilla [6,7].

Clinically, LGMS usually appears as a painless lump or a gradually enlarging mass. Despite its slow growth, it is prone to frequent local recurrences and metastasis [1,2,8]. Macroscopically, the majority of cases present as firm masses with well-defined fibrous cut surfaces, but their margins are typically ill-defined [4], blending into the surrounding tissues. Only a small proportion of these neoplasms are sharply circumscribed, featuring distinct and easily recognizable borders [8]. Radiologically, these lesions are characterized as irregular, destructive, and radiolucent abnormalities [9].

Given the rarity of these tumors and the limited number of reported cases, this case report aims to provide valuable insights and enhance our understanding of these tumors.

2. Case Report

A 22-year-old male patient, with no systemic conditions, attended a consultation reporting the appearance of a “lump” in the premolar area (teeth 34–35) without being able to specify when it first developed. A panoramic X-ray (Figure 1A) was performed, revealing no abnormalities. Panoramic radiography was unremarkable, and advanced imaging techniques such as MRI or second-level imaging were not utilized, which may have provided further insights into the lesion’s characteristics. Clinically, a firm red lesion resembling a blister was observed between the attached and free gingiva in the area between teeth 34 and 35 (Figure 1B). The lesion had a smooth surface, a pedunculated base, and measured 19 × 8 mm.

The lesion was exercised with a 15 blade under local anesthesia (articaine—artinibsa^® 40 mg/mL + 0.01 mg/mL, Inibsa^®, Llissá De Vall, Spain) (Figure 2A–C) and sent for histopathological examination. The following prescription was recommended: ibuprofen 600 mg, 12/12 h for two days, chlorhexidine mouthwash 0,12%, 3 times/day for 10 days.

On histological examination, a fragment of mucosa (Figure 3) with a nodular configuration was observed, circumferentially lined by stratified squamous epithelium, focally ulcerated, and without dysplasia. In the submucosa, there was a high cellular proliferation of spindle-shaped cells arranged in short to intermediate interwoven bundles, showing mild nuclear atypia with six mitotic figures per 2 mm². No atypical mitotic figures or necrosis were identified. In the stroma, focally, more hyalinized collagen was also noted. No significant inflammatory infiltrate or mineralized tissue was observed. The morphological aspects suggested a spindle-cell proliferation with atypia. Immunohistochemical analysis revealed stromal cell immunoreactivity for SMA and a low proliferative index assessed with Ki67 antibody, while showing no immunoreactivity for Desmin, CD34, or beta-catenin. The observed morphological features, along with the immunohistochemical profile, pointed towards a low-grade myofibroblastic sarcoma.

The post-operative follow-up assessments were conducted on days 10 and 28. At the one-month follow-up, the lesion showed signs of reappearance (Figure 4). Considering this diagnosis, the patient was referred to his general practitioner, who then directed him to the Portuguese Oncology Institute in Porto. The timeline of the case report is illustrated in Figure 5.

3. Discussion

The literature on low-grade myofibroblastic sarcoma (LGMS) reveals a relatively high incidence of tumors occurring in the oral cavity [1,6,8,10,11]. However, most studies have analyzed LGMS in the head and neck region, which encompasses tumors of the oral cavity [3,6,8,11,12]. This complicates the establishment of specific characteristics of oral LGMS. LGMS is a rare tumor that requires further characterization [3]. Although the term suggests it is a “low-grade tumor,” some myofibroblastic sarcomas have demonstrated high-grade features and behavior [5].

Low-grade myofibroblastic sarcoma presents features that can overlap with several benign and malignant lesions. Clinically, the differential diagnoses include benign fibrous lesions such as fibromas or peripheral ossifying fibromas, given their firm consistency and localized swelling. Malignant tumors such as leiomyosarcoma, fibrosarcoma, and other spindle cell neoplasms should also be considered due to their shared histopathological characteristics [2,5,13].

Radiologically, the lack of significant findings on panoramic imaging can make it challenging to distinguish these from benign lesions or inflammatory processes. Advanced imaging techniques, such as MRI, could aid in assessing the lesion’s extent, the involvement of adjacent structures, and potential infiltration, which are critical for differentiating it from aggressive benign tumors or other low-grade sarcomas [6,7,8].

Until 2019, only 65 cases of myofibroblastic sarcoma had been reported in the literature, with 24 of these cases located in the head and neck region and the remaining 41 cases in the upper and lower limbs and other areas [2].

Myofibroblasts are fusiform mesenchymal cells with contractile functions that exhibit characteristics of both fibroblasts and smooth muscle cells from an ultrastructural perspective [4,13]. The cytomorphological and functional heterogeneity of myofibroblasts, combined with the fact that they share features with both fibroblasts and smooth muscle cells, makes the concept of myofibroblastic sarcomas controversial [13].

These myofibroblastic cells are key components of the connective tissue, found in soft tissues and nearly all organs. Although their role within the spectrum of proliferative and neoplastic cell lesions has been widely studied over the past three decades, defining their exact function remains challenging, particularly when dealing with myofibroblastic neoplasms—tumors primarily composed of myofibroblasts, or mesenchymal neoplasms with a myofibroblastic differentiation lineage [2,13].

Some researchers advocate ultrastructural studies as essential for classifying these tumors, emphasizing that positive immunohistochemical staining for at least one myogenic marker can confirm a diagnosis of LGMS [8]. Others argue that diagnosis should not rely solely on ultrastructural features, and instead recommend a combination of morphology observed in hematoxylin–eosin stained sections and immunohistochemistry [1]. Additionally, some authors note the challenges in identifying myofibroblastic differentiation without electron microscopy but acknowledge that the neoplastic cells often exhibit poorly developed ultrastructural characteristics, making them difficult to detect consistently [14].

Furthermore, since LGMS shares histological features with other malignant neoplasms (such as fibrosarcoma), conventional microscopy is often insufficient for a definitive diagnosis [8]. Therefore, techniques such as immunohistochemical analysis or electron microscopy may be necessary for accurate confirmation [8]. Despite advances in immunohistochemical techniques, diagnosis remains challenging as myofibroblasts lack specific immunohistochemical markers [15]. Smooth muscle actin (SMA) is commonly used to identify myofibroblasts, but it also marks tumors of smooth muscle origin, while desmin is used to identify tumors of skeletal muscle origin [16].

Histologically, most cases of LGMS are characterized by a diffusely infiltrative growth pattern, with fusiform or stellate cells organized into fascicles. In rare cases, a prominent collagenous matrix with focal hyalinization and numerous thin-walled capillaries or inflammatory cells may be observed [8]. Neoplastic cells typically exhibit contractile elements and produce collagen, fibronectin, and laminin, along with nuclear atypia and enlarged, hyperchromatic, and irregular nuclei [17]. Proliferative activity may be slightly increased, and mitoses can be observed, though necrosis is rare [18].

Immunohistochemically, the immunophenotype of LGMS cells is variable. Common markers include smooth muscle actin (SMA), desmin, muscle actin (HHF35), and calponin. Most cells show immunoreactivity for SMA, as observed in the clinical case described, while fewer than half are positive for desmin—desmin was not detected in this case. Although calponin is generally positive, it is considered a non-specific marker. Other markers, such as fibronectin, vimentin, CD34, and CD99, may be positive in some cases; however, in the clinical case presented, CD34 immunoreactivity was not observed. Studies indicate that LGMS rarely shows immunoreactivity for CD34 [19]. Although this tumor was diagnosed as a “low-grade” myofibroblastic sarcoma, close monitoring is essential, as high-grade features may emerge. The Ki-67 (MIB-1) activity, for example, was elevated, suggesting high-grade behavior [5].

Regarding therapeutic approaches, there is no established consensus, but complete resection is considered the ideal treatment for LGMS, as it is for other types of sarcomas. The primary goal of treatment is to remove the mass at the primary site, with postoperative radiotherapy and chemotherapy remaining controversial [20]. Most clinicians advocate for wide local excision and regular follow-ups [8].

Predicting the outcome of LGMS is challenging, as most published cases have only short follow-up periods [3]. The lack of long-term data is significant, underscoring the need for future studies with extended follow-up. Despite the limited follow-up periods, approximately 30% of LGMS lesions have recurred [21], as observed in our patient, who experienced a recurrence after only one month of follow-up.

4. Conclusions

This case report emphasizes the critical role dentists play in diagnosing neoplastic lesions, particularly given the indolent nature of these tumors, which often leads to delayed diagnosis. Additionally, it underscores the value of considering an incisional biopsy in cases of suspected neoplasia to establish a definitive diagnosis before surgical excision, thereby reducing the risk of recurrence. Further research is needed to fully understand the biological behavior of these tumors.