Aggressive Intraosseous Myofibroma of the Maxilla: Report of a Rare Case and Literature Review

Abstract

Myofibroma (MF) is a benign mesenchymal myofibroblast-derived tumor, which occurs most frequently in children, and rarely affects the maxilla. We reported a case of an aggressive intraosseous lesion found in the maxilla of a 9-year-old female child. Intraorally, the swelling extended from tooth 12 to 16, causing displacement of teeth 13, 14, and 15. Computed tomography revealed a large osteolytic lesion causing thinning and cortical erosion. Microscopically, the lesion showed a proliferation of spindle-shaped cells, with elongated nuclei and eosinophilic cytoplasm, arranged in interlaced fascicles. The immunohistochemical analysis revealed cytoplasmic positivity for α-SMA and HHF-35, and negativity for desmin, laminin, S-100, β-catenin, and CD34. Ki-67 was positive in 8% of tumor cells. The diagnosis was MF. Herein, we describe an additional case of central MF arising in the maxilla, including clinical, imaging, microscopical, and immunohistochemical features, as well as a review of the literature.

Introduction

Myofibromas (MF) are rare benign mesenchymal neoplasms. Although considered a childhood neoplasm, MF can occur at any age and is the solitary counterpart of myofibromatosis [1, 2]. MF involve more frequently the subcutaneous tissues of the head and neck (approximately one-third of all cases) [2, 3], and involvement of the oral cavity is uncommon, particularly centrally in the maxilla [3, 4]. When they occur in oral tissues, the mandible (intraosseous) is the most affected anatomic site, followed by the buccal mucosa, posterior mandible alveolar mucosa/retromolar region, tongue, and labial mucosa [4].

To the best of our knowledge, only six cases of central myofibromas affecting the maxilla have been reported in the English-language literature, including the current case (Table 1) [5–9]. In view of the rarity of these lesions in maxilla, the diagnosis may cause confusion with other benign mesenchymal lesions, or even with low-grade malignant spindle cell neoplasms [10, 11]. Therefore, the establishment of a correct diagnosis is crucial for a proper treatment approach [11]. Herein, we describe a case of central MF in the maxilla, including clinical, imaging, microscopical, and immunohistochemical features, as well as a review of the literature.

Table 1.

Summary of previous cases of solitary intraosseous myofibromas affecting the maxilla

Case	Author	Age (years)b	Gender	Localization	Size (cm)	Symptoms	Treatment	Follow up time (months)	Recurrence	Trauma	Immunohistochemistry performed
1	Fushimi et al. [5]	57	F	Anterior Maxilla	2,0 × 1,0 × 1,5	No	Resection and extraction of resorbed teeth associated with the lesion	24	No	NR	α-SMA + , Vimentin + , S-100 − , Desmin -
2	Damera et al. [6]	13	F	A–P Maxilla	NR	No	NR	24	No	NR	α-SMA + , Vimentin + , S-100 − , Desmin − , HHF-35 +
3	Tabrizi et al. [7]	1	M	Posterior Maxilla	4,5 × 3,0	NR	Enucleation	18	No	Yes	α-SMA + , HHF-35 + , Desmin −
4	Nashef et al. [9]	9	F	A–P Maxilla	2,0 × 3,0	No	Partial maxillectomy and peripheral ostectomy	8	No	NR	α-SMA + , Desmin − , CD34 -, CD39 − , H-caldesmon − , Factor XIIIa -
5	Kaur et al. [8]a	12	F	A–P Maxilla	5,0 × 6,0	No	Enucleation	NR	No	NR	α-SMA + , Vimentin + , S-100 − , Ki-67 − , Focal positivity for desmin
6	Present case	9	F	A–P Maxilla	3,5 × 2,0	No	Enucleation and curettage	36	No	No	α-SMA + , Desmin -, β-catenin -, Laminin − , S-100 − , CD34 − , Ki-67 < 10%

NR not reported, F female, M male, A-P anterior and posterior region

^aDoes not provide histological images of the case

^bAge at time of diagnosis

Case Report

An otherwise healthy 9-year-old female was referred to the oral medicine service of the School of Dentistry at the Federal University of Sergipe, with a chief complaint of a painless swelling in the right maxilla with a duration of approximately 4 months. There was no history of previous trauma in the region, and the past medical history was not contributory. The extraoral examination showed a slight swelling on the right side of the face and cervical lymph node alterations were not observed. The intraoral examination revealed a swelling in the right maxillary region covered by normal-colored mucosa with focal ulceration, measuring approximately 3 cm in diameter, extending from tooth 12 to 16, and causing displacement of teeth 13, 14 and 15 (Fig. 1). The lesion had a rubbery consistency on palpation and was asymptomatic, except for slight discomfort due to tumor growth.

Fig. 1.

Clinical appearance of the lesion

Cone-beam computed tomography (CT) (Fig. 2) demonstrated, in a panoramic reconstruction, the presence of a hypodense lesion with poorly defined limits, located in the right posterior maxilla, causing perforation of buccal and lingual cortical plates. A provisional diagnosis of osteosarcoma was established, and an incisional biopsy was performed. The biopsy specimen was submitted to histopathological analysis.

Fig. 2.

Cone-beam computed tomography (CT). A and B. Presence of an ill-defined hypodense lesion in the right posterior maxilla (axial sections). C. 3D reconstruction showing loss of lingual and vestibular cortical continuity

Gross examination revealed a soft tissue fragment with a firm and rubbery consistency and a yellowish surface, measuring 1.3 × 1.1 × 0.5 cm (Fig. 3). On a cross-section, the surgical specimen showed a glistening white surface with patchy areas of hemorrhage. Morphological analysis revealed spindle-cell proliferation, forming intersecting fascicles of variable length, or in a haphazard arrangement. In a low-power view, a slight biphasic pattern of lighter-stained and darker-stained areas (zoning phenomenon) was observed. Tumor cells exhibited elongated vesicular nuclei with two or more inconspicuous nucleoli and eosinophilic cytoplasm of indistinct boundaries, compatible with myofibroblast morphology. In focal peripheral regions, associated with ulceration, a mixed inflammatory infiltrate was observed; however, it was not present in the rest of the tumor. In the central areas of the sample, large thin-walled vessels with “stag-horn” morphology were noted. Although some neoplastic cells presented slightly hyperchromatic nuclei, the mitotic index was low, and tumor necrosis was not observed (Fig. 4).

Fig. 3.

Macroscopic appearance of the biopsy specimen

Fig. 4.

Histopathologic features of MF (hematoxylin and eosin stain). a and b Proliferation of spindle-shaped cells arranged in intersecting fascicles or in a haphazard pattern (original magnification a × 100, b × 200). c Detail of thin-walled blood vessels with a hemangiopericytoma-like pattern original magnification × 400). d Myofibroblasts with a characteristic spindle or stellate shape, pale or vesicular nuclei, small nucleoli, and eosinophilic cytoplasm. Occasional mitoses are observed (arrowhead) (original magnification × 400)

Immunohistochemical analysis was performed for confirmation of the myofibroblastic phenotype of tumor cells. The tumor cells were strongly positive for α-SMA and HHF35, and negative for desmin, laminin, S-100, and β-catenin. Positivity for CD34 was limited to the vascular network, and the positivity for Ki-67 was seen in approximately 8% of parenchymal cells (Fig. 5). Based on clinical, histopathological, and immunohistochemical findings, a diagnosis of MF was established.

Fig. 5.

Immunohistochemical features of MF. a Tumor cells showing strong positivity for a-smooth muscle actin (original magnification × 200). b Positive immunohistochemical staining for HHF-35 (original magnification × 200). c Ki-67 (MIB-1) labeling index is approximately 8% (original magnification × 200)

The patient was referred for enucleation and curettage of the lesion, and no recurrence was observed after 3 years of follow-up. Prosthetic rehabilitation with implants will be performed after the maxillofacial bones attained complete growth. The patient is currently undergoing routine follow-up.

Discussion

To date, only six cases of intraosseous myofibromas affecting the maxilla have been reported in the English-language literature, including the current case. The overall information for the 6 cases is displayed in Table 1. According to these cases [5–9], most of the patients were children or adolescents and females, which is an agreement with our case. However, a well-documented case has been reported in a 57-year-old patient [5], which suggests that the diagnosis of MF must also be considered in cases of neoplasms of the maxilla even in older patients. In addition, racial predisposition was not observed. Abramowicz et al. (2012) reported 2 intraosseous MF in the maxilla. However, accurate information on individual cases has not been provided and for this reason were not included in the present study [12].

When the jaws are involved, MF present as a painless destructive osteolytic lesion, with well-defined borders, and slow growth [4, 13–15] (Table 2). Extensive lesions may cause expansion, thinning, and perforation of the cortical plates, mimicking the biological behavior of a wide range of intraosseous diseases, from odontogenic tumors to malignant neoplasms [1, 13, 14, 16]. Clinical signs and symptoms mainly depend on the affected anatomical site and vary considerably. The typical clinical presentation in the head and neck region is a painless swelling [4, 14, 16]; however, it may present ulceration, and sometimes, display a rapid growth mimicking malignant tumors and thus becoming alarming [13, 15]. However, most of these cases did not show rapid growth, as observed in the present case. The spectrum of clinical presentation suggests that MF may present variation in biological behavior [13]. Furthermore, other signs and symptoms have been reported, such as proptosis, nasal obstruction, and nasal discharge [16].

Table 2.

Imaging features of the previously reported myofibromas affecting the maxilla

Case	Author	Imaging	Borders	Internal structure	Locularity	Effects on teeth	Expansion	Cortical perforation	Periosteal reaction
1	Fushimi et al. [5]	Panoramic X-ray, CT, MR, BC	WD	RL, LA, T2S	U	D, R	Y	NV	NR
2	Damera et al. [6]	Panoramic X-ray, CT (n/a)	ID	RL, LA, Ca	U	D, R	Y	Y	NR
3	Tabrizi et al., 2013	CT	WD	LA	U	NR	Y	Y	NR
4	Nashef et al. [7]	Panoramic X-ray, CT	WD	RL, LA	U	D	Y	Y	NR
5	Kaur et al. [8]	Panoramic X-ray, CT	WD	RL, LA	U	D	Y	Y	NR
6	Present case	Panoramic X-ray, CT	ID	RL, LA	U	D	Y	Y	NV

NR not reported, BC bone scintigraphy, CT computed tomography, MR magnetic resonance Imaging, WD well-defined, ID ill-defined, RL radiolucent, LA low-attenuation, Ca calcification, T2S hyperintense T2 MR Signal, U unilocular, M multilocular, D root displacement, R root resorption, Y yes, NV not visualized

The rare occurrence of MF in the oral cavity, particularly in the maxilla, and the morphological similarity with other malignant or benign mesenchymal lesions can make the diagnosis challenging [7, 14]. In addition, misdiagnosis may occur, leading to an improper therapeutic approach [5, 7, 14–16]. In fact, several cases published in the literature were initially diagnosed as other diseases [12, 14, 15, 17]. Early diagnosis and surgery are important for preventing subsequent deformity and eventual destruction of anatomic structures in children and adolescents [7]. Thus, careful histological and immunohistochemical evaluation is mandatory to avoid incorrect diagnosis and unnecessary radical surgery [10, 14].

Other fibromatoses, particularly desmoid fibromatosis (DF), nodular fasciitis (NF), inflammatory myofibroblastic tumor, solitary fibrous tumor (SFT), neurofibroma, and smooth muscle tumors should be considered in the differential microscopical diagnosis [3, 4, 14]. Moreover, some low-grade spindle cell sarcomas such as low-grade myofibroblastic sarcoma (LGMS), infantile fibrosarcoma, and leiomyosarcoma might also be confused with MF [18]. Thus, immunohistochemical analysis is helpful to confirm the myofibroblastic phenotype of the neoplastic cells and the benign nature of the tumor [11, 14, 15].

A panel of antibodies for desmin, h-caldesmon, s-100, and α-SMA antigen detection has been suggested to distinguish MF from neural and smooth-muscle tumors [4, 15]. In addition, the use of vascular markers, such as CD31 and CD34, may be used to exclude SFT [14]. On the other hand, β-catenin and Ki-67 immunoexpression could be helpful to perform the differential diagnosis with some aggressive fibromatosis (desmoid tumors) and malignant tumors of the connective tissue [3, 11, 18].

Nodular fasciitis was considered in our case; however, NF is a self-limiting disease considered by many to be a reactive process and rarely observed in newborns and children [19]. In addition, oral lesions are uncommon, especially in intraosseous sites. Also, the lesion did not exhibit a prominent myxoid matrix, dispersed chronic inflammatory infiltrate, extravasated red blood cells, findings often described in these lesions [14, 15, 18]. The tumor also presented a hemangiopericytoma-like vascular pattern, which is not observed in NF [14]. However, recent studies have identified recurrent USP6 gene rearrangements in most cases, often with MYH9 as the fusion partner (~ 70%) [20–22], firmly establishing its neoplastic nature [11, 18].

Differentiation from SFT may also be difficult because of the hemangiopericytoma-like vascular appearance shared by both lesions; nevertheless, MF exhibiting this prominent vascular pattern can be distinguished from SFT by the denser spindle-cell component, biphasic pattern, and immunohistochemical positivity for α-SMA [14, 15]. In addition, recent studies have identified recurrent NAB2-STAT6 gene fusions in nearly all SFTs [23–26]; subsequent multiple researchers have confirmed that nuclear STAT6 immunohistochemical reactivity is highly specific for SFT [26–32] and is a reliable marker to differentiate SFT from MF and other histologic mimics [18, 26, 31]. Smooth muscle-derived tumors, such as leiomyomas, may also resemble MF [14, 15]; however, intraosseous leiomyomas are extremely rare [15] and exhibit immunopositivity for desmin and/or laminin [14], which has not been described in MF, as observed in the current case. In addition, h-caldesmon has been a useful immunohistochemical marker to differentiate between leiomyomas and MF [4, 33].

Differentiation of desmoid fibromatosis can also be a challenge, especially because both lesions show positive staining for vimentin and variable expression for smooth muscle actin [14]. However, DF is usually more collagenous and less cellular than MF, exhibit slender fibroblasts in long fascicles and infiltrative growth pattern [11, 18]. In addition, about 85% of cases of fibromatoses show positive nuclear staining for the β-catenin result of mutations in the gene encoding β-catenin (CTNNB1) [10, 11, 18], unlike our case that was β-catenin negative. Thus, nuclear immunostaining for β-catenin is useful in distinguishing fibromatoses from other similar spindle cell lesions [11].

On the other hand, interestingly, some MF may exhibit infiltrative margins, cytologic atypia, and increased mitotic activity, which may lead to a misdiagnosis of malignancy [4, 14]. Leiomyosarcoma and low-grade myofibroblastic sarcoma, in particular, may show a similar infiltrative pattern, but differently of MF, present a less uniform morphology, exhibiting cytological atypia and frequently shows positivity for desmin [14]. Congenital/infantile fibrosarcoma (IF) may also resemble MF; however, fibrosarcomas are uncommon tumors of the oral cavity and exhibit well-organized fusiform cells in a herringbone pattern, moderate to high cellularity and nuclear atypia, increased mitotic figures, hemorrhage, necrosis, and infiltrates adjacent soft tissue with irregular margins [16], features not commonly observed in MF. Also, IF are tumors of infancy traditionally associated with the ETV6–NTRK3 gene fusion [34].

In the present case, discrete areas of cell atypia were observed, which raised the suspicion of a possible LGMS, especially when correlating with the clinical characteristics and short evolution time of the lesion. LGMS is a rare relatively indolent myofibroblastic neoplasm that tends to arise in the head and neck region and extremities and occasionally metastasizes [11, 18]. Most of the cases arise between the fourth and fifth decades of life, and rarely are intraosseous. In the oral cavity, the tongue is the most affected site [18]. Histologically, LGMS consist of atypical spindle-shaped tumor cells with fusiform nuclei and eosinophilic cytoplasm arranged in fascicles or storiform architecture with an infiltrative growth pattern, the stroma shows variable grades of collagenization/hyalinization [11, 18]. Although LGMS has been included in our differential diagnosis, the low rate of cell proliferation (assessed by Ki-67), low mitotic index, absence of necrosis, and negativity for desmin were valuable information to rule out this possibility. In addition, the typical biphasic pattern of the myofibroma (zoning phenomenon) is not observed in LGMS. Although genetic analyses were not performed in this case, it must be considered that between both tumors, the genetic alterations differ (myofibroma: recurrent somatic PDGFRB mutations; LGMS: cytogenetic or molecular genetic alterations have not been described so far) [18, 35, 36].

In summary, solitary intraosseous MF present a benign clinical course, with slow growth and cure after complete conservative surgical excision [3, 4, 37]. Although some cases presented rapid growth [3], as observed in the present case, some lesions showed spontaneous regression [38], and some remained stable after partial excision [39]. In the previous cases [5–9] and the present case involving maxilla, the follow-up time ranged from 8 to 36 months (17.2 ± 7.15, mean ± SD), and no recurrences were reported. Although most published cases have a short follow‐up, recurrences are rarely observed in solitary MF affecting other anatomical sites [14], even when only curettage was the treatment used. However, newborns with multiple tumors (congenital infantile myofibromatosis) have a mortality rate of more than 70% [4], and often die at birth or soon after birth due to complications associated with tumor growth [3], by which, is considered a different entity from solitary MF. Thus, it is important to exclude multifocal or multicentric disease, since the prognosis for multicentric disease is much worse than for isolated cases [40].

Conclusions

In conclusion, solitary intraosseous MF involving the maxilla are very rare. The correlation of the clinical, histopathological, and immunohistochemical features are necessary for the correct diagnosis and avoid radical surgical interventions with associated morbidity. Although rare, the MF of maxilla should be considered in the differential diagnosis of unilocular radiolucent lesions presenting undefined limits in children and adolescents.

Funding

No funding sources to disclose.

Compliance with Ethical Standards

Conflict of interest

No conflicts of interest to disclose.

Ethical Approval

For this type of retrospective case report, formal consent is not required.

Informed Consent

No identifier information is included in the case report, and the study meets the waiver criteria for the institutional review board of School of Dentistry of Piracicaba.