Ⅰ. INTRODUCTION
Intramuscular myxoma is a type of mesenchymal myxoid tumor manifesting predominantly in the large muscles, including thighs, shoulders and buttocks. However, their occurrence in the soft tissues of the head and neck is extremely uncommon1,2,3), with the masseter muscle being the most common site reported in the literature4). Intramuscular myxoma usually affects adults aged > 40 years with a female predominance. It manifests as a round, firm, and immovable mass covered with normal oral mucosa and is not associated with clinical symptoms5). In some cases, patients with Carney complex or Mazabraud’s syndrome presented with such types of myxoid tumors6,7). Intramuscular myxomas typically demonstrate a benign behavior with slow growth. Although these tumors are usually well-demarcated, they demonstrate a potential for infiltration2,8).
Myxomatous tumors have a wide range of characteristics, varying from completely benign tumors to those resembling malignant neoplasms, according to histological variances. Intramuscular myxoid tumors comprise a diverse array of lesions, which exhibit variations in cellularity and vascularity, thus making it necessary to classify them into distinct categories9). Histologically, fibroblast-like or stellate-shaped cells and blood vessels with abundant extracellular myxoid stroma are rarely observed. Among these myxomas, cellular myxoma, a subtype of intramuscular myxomas, is distinguished from typical intramuscular myxomas through exhibiting focal or diffuse hypercellularity and vascularity. Moreover, these lesions are not accompanied by hyperchromatic and atypical nuclei or curvilinear vascular structures, which are characteristic of myxoid sarcoma10). These peculiarities are related to the characteristics reported on magnetic resonance (MR) scans, including homogeneous low signal intensity on T1‐weighted MR sequences and high-signal intensity on T2‐weighted sequences. Most lesions display sharp margins with hypointense rims, and heterogeneous contrast enhancement has been observed in many lesions11). In addition, GNAS (Guanine Nucleotide binding protein, Alpha Stimulating activity polypeptide) mutations can be considered a diagnostic tool to differentiate a cellular myxoma from clinically similar myxoid fibrosarcomas 5).
Nevertheless, the prognostic value of these features for cellular myxomas is limited owing to the absence of key indicators, such as atypical cell morphology, necrosis, mitotic activity within cells, and specific histopathological categorizations. Moreover, clinical pathology reports on this specific type of myxoid tumors are scarce, posing challenges in accurate diagnosis establishment and recurrence prediction.
This case study aims to present a rare occurrence of a cellular myxoma in the buccal mucosa of the oral cavity and to identify its diagnostic characteristics through a comparative analysis with relevant studies on myxoid tumors.
Ⅱ. CASE REPORT
Clinical examinations
A 38-year-old woman was referred to the Department of Oral and Maxillofacial Surgery, Kyung Hee University Medical Center, with a round mass located in the buccal mucosa of the oral cavity. The patient first noticed the presence of the lesion approximately 4 years ago, and since then, its size has gradually increased. Clinical examination revealed a solid and immobile mass measuring 2 × 2 cm, palpated in the buccal mucosa. The overlying oral mucosa had an intact, smooth surface. Although the lesion showed a linear alba, the patient did not report any subjective symptoms. Considering the slow growth and immobility of the lesion, the possibility of malignancy was considered low.
Radiological examinations
Radiological examinations, including panorama and cone-beam computed tomography (CBCT), were performed and did not show any involvement of the surrounding hard tissues. However, MR scans revealed a well-demarcated, oval-shaped mass measuring approximately 2.0 x 1.6 x 1.9 cm in the left buccal mucosa. The mass appeared isointense on T1-weighted images, with intermediate to bright high-signal intensity on T2-weighted images, and showed multiple septal structures. On contrast enhancement, the mass displayed clear and homogeneous enhancement without any internal fatty components. Abnormalities in the lymphatic system and the parotid and submandibular glands were not observed. Based on the imaging findings, a hemangioma was suspected, and it was necessary to differentiate it from a pleomorphic adenoma (PA) of the minor salivary glands. Based on the tumor size and the preservation of the adjacent anatomical structures, we decided to perform surgical excision with biopsy under general anesthesia.
Treatment
An incision was made in the overlying buccal mucosa. Subsequently, the tumor enclosed within a thin fibrous capsule was undermined and excised from the surrounding structures. The surgical wound healed without any complications, and no postoperative complications were observed. No recurrence of the lesion was detected within 1 year postoperatively.
Histopathological and immunohistochemical findings
The excised mass showed as a spherical, lobulated, and solid structure with a light yellowish hue and comprised several capillaries on the surface.
After gross confirmation of the lobulated shape on the microscopic view of the excised mass, the pattern of separation of the myxoid components by the fibrous septa was found to be consistent with that on the MR images. Spindle-shaped and stellate fibroblast-like cells were diffusely increased within a collagenous stroma; however, small cell clusters were focally distributed surrounding myxoid extracellular substrates. The cells were relatively uniform and did not exhibit any significant atypical pleomorphisms. Excessive hyperchromatic patterns were not observed in the cell nuclei, which had a relatively constant shape. Small vessel fragments were confirmed to be locally present in the myxoid backgrounds. A fibrous pseudocapsule surrounding the mass was identified; however, its thickness was irregular. An immunohistochemical analysis revealed local positivity for SMA, while CD34 demonstrated diffuse positivity. The desmin test did not reveal positive results.
Ⅲ. DISCUSSION
Three primary hypotheses have been proposed regarding the etiology of myxoma: (1) excessive synthesis of mucosal matrix and glycosaminoglycans by immature fibroblasts or myofibroblasts, (2) tumors originating from primary mesenchymal elements derived from the dental papilla, dental fol-licles, or periodontal tissues, and (3) concomitant systemic disorders such as mucopolysaccharidoses, Carney complex, and Mazabraud’s syndrome6,7,8,12).
Cellular myxomas are uncommon benign tumors. According to a comprehensive study, a cellular myxoma is best regarded as a variant of myxoid lesions, representing an intermediate stage between an intramuscular myxoma and a low-grade myxofibrosarcoma. Consequently, it has been definitively classified as a low-grade myxoid neoplasm with a potential for recurrence9). Therefore, cellular myxomas are assumed to have characteristics related to the first aforementioned hypothesis.
It is challenging to distinguish tumors that have a myxoid matrix, thus misdiagnosing them as malignancies. In clinical practice, it is crucial to differentiate myxoid tumors that occur in the soft tissues of the oral cavity from traumatic fibromas, oral focal mucinosis, hemangiomas, PAs, low-grade fibromyxoid sarcomas, and low-grade myxofibrosarcomas8). In the present case, the absence of any changes in the location or size of the lesion over an extended period or any traumatic events during the initial examination excluded the possibility of local oral mucinosis and traumatic fibromas.
Most soft-tissue tumors are difficult to distinguish based on individual diagnoses using only radiologic evaluation. If the lesions are isointense to the muscle on T1- weighted MR images, they should be assessed on T2-weighted MR images. If a T2 hyperintense mass demonstrates internal enhancement, myxomatous tumors (e.g., intramuscular myxomas and myxoid sarcomas) should be considered. The characteristic MR features of cellular myxoma include homogenous low-signal intensity on T1‐weighted MR sequences and high-signal intensity on T2‐weighted sequences. Most lesions are well-circumscribed, and heterogeneous contrast enhancement has been observed in many reported lesions 11). In the present case, the lesion exhibited the adjacent muscle tissue and was isointense on T1-weighted images, indicating lower myxoid characteristics and higher cellularity than those of typical intramuscular myxomas. In addition, a mass presenting with intermediate to bright high SI with a hypointense thin rim and multiple septa-like structures on T2-weighted signals can be considered as the typical feature of cellular myxomas and is consistent with the lobulated pattern of collagenous septa observed microscopically. According to this result, we excluded hemangioma that presents with poorly defined margins with hyperintense T1-weighted signals as a radiological differential diagnosis13,14). Contrast enhancement is useful for differentiating soft-tissue myxoid tumors from fluid-like lesions. If an internal enhancement is shown, a solid myxoid tumor such as intramuscular myxoma should be considered. Referring to the degree of enhancement, we can consider the vascularity of the lesion14).
Moreover, distinguishing low-grade myxofibrosarcomas from PAs is challenging owing to their morphological characteristics and clinical similarities. Based on the MR findings of our patient, it is necessary to consider a PA in the minor salivary gland as a differential diagnosis. In general, intramuscular or cellular myxomas in the head and neck region exhibit imaging patterns similar to those of cysts owing to the abundance of myxoid substances within the lesion, resulting in homogeneously low signal intensity on T1-weighted MR images and high signal intensity on T2-weighted MR images 11,15). In cases of PA requiring a differential diagnosis, the diagnostic criteria for PA have been established based on the following five factors: (1) bright T2-signal, (2) well-defined margins, (3) heterogeneous nodular enhancement, (4) lobulated appearance, and (5) T2-dark-rim. However, based on the relative quantities of components (each group of epithelial cells, myoepithelial cells, and matrix) that constitute PA, it often does not match the criteria. Regarding the imaging findings of our patient, all the criteria presented were met except for the heterogeneous nodular enhancement. Therefore, it may be difficult to clearly distinguish a PA from a cellular myxoma depending only on MR images16).
Distinctive histopathological features of cellular myxomas include the presence of fibroblast-like or stellate-shaped cells densely concentrated within a collagenous matrix and the presence of capillary blood vessels in curved or smaller segments17). In our patient, small groups of cells were distributed throughout the myxoid substrate. Moreover, distinct areas with relatively abundant myxoid components and regions that exhibited a high tendency for cellular clustering were included. It is crucial to differentiate cellular myxoma from other conditions, such as myxoid liposarcoma, low-grade fibromyxoid sarcoma, low-grade myxofibrosarcoma, myxoid neurofibroma, and schwannoma, which exhibit varying degrees of myxoid degeneration to establish an accurate diagnosis based on histopathological findings. In particular, distinguishing low-grade myxofibrosarcomas from cellular myxomas often poses a significant challenge.
Low-grade myxofibrosarcomas exhibit greater heterogeneity in their gross appearance than that of typical cellular myxomas, as they have higher cellularity in whorled patterns, mild cellular atypicality, and solid areas with increased collagen content interspersed with the myxoid matrix. In addition, from a macroscopic perspective, low-grade myxofibrosarcomas often display greater heterogeneity than that of cellular myxomas, as they commonly develop in areas characterized by firm collagen deposition. Nevertheless, the cellular components of myxofibrosarcomas consistently exhibit higher nuclear variability and pleomorphism than those of cellular myxomas10).
Moreover, immunohistochemically differentiating cellular myxomas from low-grade myxoid tumors is challenging due to the absence of specific immunohistochemical markers. Given the absence of systemic diseases or a family history in our patient, the previously proposed epigenetic hypothesis can guide the selection of markers, such as S100, CD34, SMA, and Desmin, which may be associated with the histological features. Thus, we used the SMA, CD34, and Desmin markers. The presence of local SMA positivity, diffuse CD34 positivity, and negative desmin on immunohistochemistry indicated a predominant association with undifferentiated fibroblast- like cells. CD34 can indicate both cellular myxomas and low-grade myxofibrosarcomas, and the use of GNAS mutations as a diagnostic tool for limited specimens from fine-needle aspiration is a reasonable option. This gene is translated to a G protein involved in cell signaling to activate the cell cycle5). The clinically benign tendency of intramuscular myxomas accompanied by hypercellularity is consistent with the fact that intramuscular myxomas are probably either reactive soft tissue lesions or benign tumors. The fibroblast-like or stellate-shaped cells in intramuscular myxomas; this changes the cell cycle into a secretory phase and produces vast amounts of extracellular myxoid substances and occasional collagenous fibers10). Accordingly, a local recurrence may occur in the primary region if complete resection is not performed for highly cellular lesions. In certain cases, when the lesion is located in an anatomically challenging area that threatens complete resection or when complete resection poses a risk of functional impairment, a longer follow-up duration without complete resection may be considered. Although high cellularity indicates potential invasion, previous studies have suggested that the complete resection of the lesion can lead to complete recovery. Therefore, surgical resection should be considered the primary treatment approach. Given the possibility of infiltration into the adjacent tissues based on histological characteristics and insufficient encapsulation, postoperative management should be established to prevent the potential recurrence 9,11,17).
Ⅳ. CONCLUSION
Cellular myxomas of the head and neck are rare benign myxoid tumors that are difficult to distinguish from low-grade myxofibrosarcomas or other benign myxoid tumors. Owing to the degree of cellularity of the cellular myxoma and the incomplete surgical excision, the potential for local recurrence should be considered during the postoperative care period. Therefore, following clinical and radiological evaluations, the entire excised specimen should be examined via histopathological and immunohistochemical methods for establishing a precise diagnosis. In this case report, we identified a cellular myxoma of the oral cavity and achieved proper treatment and postoperative care without recurrence.
