Oral myofibroma presenting as an aggressive gingival lesion

Abstract

Myofibromas are benign neoplasms of myofibroblastic origin and rarely encountered in the oral cavity. Myofibroma may frequently grow rapidly leading to suspicion of malignancy. This may lead to a tendency for aggressive management. The histopathology of this tumour has similarity with other spindle cell tumours and often requires immunohistochemical staining for diagnosis. Here, we present a case of myofibroma in a 15-year-old female patient who reported with an aggressive gingival swelling and discuss the various histopathological differential diagnosis.

BACKGROUND

Myofibromas (MF) are rare benign mesenchymal neoplasms.¹ These tumours can occur across a wide age range but are more common in the paediatric population. They, more commonly, involve the subcutaneous tissues of the head and neck.¹ Cases affecting the oral cavity are uncommon, and when they do occur, they tend to involve mandible, buccal mucosa, posterior alveolar mucosa/retromolar region, tongue and labial mucosa.¹ The histopathology of this tumour has similarity with other spindle cell tumours and often requires immunohistochemical staining for diagnosis. Here, we present a case of myofibroma in a 15-year-old female patient who reported with an aggressive gingival swelling.

Case presentation

A 15-year-old female patient came to our institution with a report of a swelling in relation to the left side of lower jaw for the past 1 month. On examination, a soft swelling of size 3×2 cm was seen in the lower lingual gingiva in relation to 37 with buccal displacement and mobility of the same tooth (figure 1). The swelling showed an erythematous surface with ulceration and indentation caused by the opposing maxillary teeth. There was no bleeding on probing but showed mild tenderness.

Figure 1.

Intra-oral photograph showing a lingual gingival swelling with buccally displaced 37.

Investigations

Orthopantomogram and CT showed only superficial bone loss in relation to 37 (figure 2A, B).

Figure 2.

Imaging studies. (A) Orthopantomogram showing mild alveolar bone loss between 36 and 37. (B) CT showing alveolar bone loss between 36 and 37 and distal to 37 above the developing 38.

Differential diagnosis

1. Reactive lesion like pyogenic granuloma, peripheral giant cell granuloma and fibromatosis due to the location though the latter is uncommon in gingiva.

2. Soft tissue neoplasms like inflammatory myofibroblastic tumour, schwannoma and low-grade fibrosarcoma due to the rapid development of the lesion.

Treatment

An incisional biopsy was taken and microscopically, proliferation of spindle cells of variable cellularity was seen below an ulcerated superficial epithelium (figure 3A–D). Cells showed elongated and plump nuclei with buckled end with some showing wavy nuclear contours. Cytoplasm was pale eosinophilic and moderate in amount. In some areas, the cells were tightly packed, while in other areas, myxoid loose matrix was seen. Mixed inflammatory infiltrate was seen in areas close to the ulcerated portion. Numerous endothelial lined capillaries engorged with red blood cells with some of them showing stag-horn morphology were also noted. There was no evidence of mitosis or necrosis. A diagnosis of benign spindle cell neoplasm with a differential diagnosis of schwannoma, inflammatory myofibroblastic tumour, myofibroma, solitary fibrous tumour and leiomyoma was considered. Immunohistochemical studies showed the tumour cells to be positive for vimentin and smooth muscle actin (SMA) and negative for S100, desmin, caldesmon, β-catenin, CD34 and anaplastic lymphoma kinase (ALK) with a Ki67 of 3%–5% (figure 4A–D). A final diagnosis of myofibroma was given.

Figure 3.

Histopathologic findings. (A) Superficial ulcerated epithelium with proliferation of spindle cells in a myxoid background (H&E). (B) Cellular connective tissue stroma showing proliferation of spindle cells with numerous slit-like vascular spaces (H&E). (C) Proliferating spindle cells forming a fascicular pattern along with vascular spaces (H&E). (D) High power showing some spindle cells with elongated, plump nuclei and others with wavy buckled nuclei with eosinophilic cytoplasm and vascular spaces sprinkled with inflammatory cells (H&E).

Figure 4.

Immunohistochemical staining. (A) Strong diffuse positivity with vimentin. (B) Strong positivity with SMA. (C) CD34 staining taken up by the vascular endothelial cells and not by the tumour cells. (D) Ki67 staining taken up by 3%–5% of cells. SMA, smooth muscle actin.

Outcome and follow-up

Wide local excision with alveolectomy was done. The excisional biopsy showed the same microscopic features as in the incisional biopsy, thus confirming the diagnosis. The patient is on regular follow-up for the previous 4 years without any recurrence.

Discussion

MF and myofibromatosis represent an enigmatic group of lesions that were originally described as a form of congenital multicentric fibroblastic proliferation by Stout.² They were subsequently characterised as phenotypically myofibroblastic tumours of infants and children by Chung and Enzinger, who noted the preponderance of solitary tumours compared with multicentric tumours.² In 1989, Smith et al proposed the term ‘myofibroma’ to describe the solitary form of these benign lesions and ‘myofibromatosis’ as the generalised form.³

Myofibroma can occur at any age group from newborn to old age.⁴ Clinically these lesions show a predilection for the head and neck, with the oral lesions typically presenting in the mandible, lips, cheek and tongue.⁵ Solitary MF have been reported in various sites in the oral cavity including gingiva. The majority of MF (41.3%) was found on movable mucosae, followed by intraosseous lesions (22.7%), alveolar mucosa (18.2%) and other sites (unspecified or palatal lesions (17.8%).³ Aiki M et al⁶, in 2014, compiled a review of MF reported in English language literature and reported a total of 22 cases occurring in the gingiva. Since then, 24 more cases have been added in the literature.^{3 7–13} Hence, a total of 47 cases including the present case have been reported to occur in the gingiva and this is given in table 1.

Table 1.

Summary of published cases of MF occurring in the gingiva

Sl number	Author (Year)	Number of cases	Age (in years)	Gender
1	Aiki et al (2014)6	22	8–70	12:10 (M:F)
2	Satomi et al (2014)7	1	18	F
3	Linos et al (2014)8	4	10–14	3:1(M:F)
4	Narayen et al (2015)9	1	7	F
5	Lopes et al (2015)10	1	2	F
6	Smith et al (2017)3	7	12–48	4:3(M:F)
7	Atarbashi-Moghadam et al (2018)11	1	4	M
8	Pereira de Oliveira et al (2019)12	8	NA	NA
9	Srinivasan et al (2019)13	1	15	F
10	Present case	1	15	F

MF, myofibromas; NA, Not available.;

In their study of 245 MFs, Smith et al³ reported that the age of the patients ranged from birth to 84 years while the average age was 23.1 years and the median age was 15 years. They also reported that men to women ratio was 1.2:1. Abramowicz et al,¹⁴ in their study, observed two patterns of clinical behaviour—exophytic and intraosseous. Exophytic MF showed rapid growth with tooth mobility, displacement and surface ulceration. Intraosseous ones were discovered incidentally on radiographs and often seen on lower border of mandible, ramus, condyle or palate and were less likely to cause cortical thinning, tooth resorption, displacement or periosteal reaction. However, there are reports of myofibroma causing palatal destruction.¹⁵ In our case, the clinical picture is similar to that of exophytic myofibroma with rapid growth, tooth mobility, displacement and surface ulceration, which could mimic a malignant lesion.

Radiographically, MF occurring intraosseously present with a well-defined radiolucent picture. Gingival lesions may present with no bone loss to evidence of alveolar bone erosion and destruction with floating teeth.^{6 11 16} Surface erosion of bone was seen in our case.

MF are tumours composed by the neoplastic proliferation of myofibroblasts. Myofibroblasts are fibroblasts with smooth muscle-like features characterised by the presence of a contractile apparatus and are found in the connective tissue stroma.¹⁷ Morphologically, they appear as spindle-shaped or stellate-shaped cells that contain elongated, oval or wavy nuclei with blunt ends and ill-defined pale eosinophilic cytoplasm with long processes arranged longitudinally.¹² Microscopically, these tumours are usually circumscribed but unencapsulated. They are composed of haphazardly arranged, interweaving bundles or short fascicles of plump myofibroblastic spindle cells.^{2 3} Often these tumours demonstrate a biphasic or zoning phenomenon.^{3 4} The periphery of these zones shows lighter stained areas composed of short fascicles or whorls of myofibroblasts with pale, pink cytoplasm and long, slender, tapered nuclei. The central zone shows darker stained, more cellular areas composed of more immature-appearing cells with less cytoplasm and larger, basophilic nuclei. This phenomenon is an important clue in distinguishing myofibroma from other similar spindle cell lesions. However, this zoning may not be present in all tumours and both may become intermingled. These tumours also show prominent vascularity and the spindle cell bundles may frequently be separated by slit-like or curvilinear vascular spaces. Though mitotic activity is usually low, these tumours may show some evidence of infiltrative growth pattern in between the connective tissue elements. In addition, scattered lymphocytes are seen in most of the tumours. The presence of osteoclast-like giant cells and degenerative changes in the form of hyalinisation, myxoid degeneration or necrosis have also been reported.² MF are positive for alpha-SMA, muscle-specific actin, calponin and vimentin and are negative for CD34, CD31, desmin, keratins and S-100 protein.³

The differential diagnosis to be considered includes inflammatory myofibroblastic tumour, fibromatosis, low-grade fibrosarcoma, schwannoma, leiomyoma and solitary fibrous tumour. MF can be differentiated from fibromatoses and low-grade fibrosarcomas by their zonation, myoid appearance and lack of mitotic activity. Immunohistochemical staining for β-catenin is positive only in fibromatosis and fibrosarcomas are negative for SMA. Both leiomyoma and myofibroma express SMA and show myofilaments ultrastructurally. Leiomyomas usually consist of perpendicularly oriented fascicles of homogeneous cells with blunt-ended nuclei, which is similar to myofibroma, but the latter also shows slit-like vascular pattern and zoning phenomenon.¹⁸ Also, leiomyomas are positive for desmin and caldesmon, which helps to differentiate them from myofibroma. MF with surface ulceration may be confused with inflammatory myofibroblastic tumour due to the presence of acquired inflammatory component. Inflammatory myofibroblastic tumours are positive for ALK unlike myofibroma, and examination of nonulcerated areas can help to differentiate between the two. The presence of slit-like vascular spaces resembling the staghorn pattern of solitary fibrous tumour requires careful microscopic evaluation for the zoning and immunohistochemical studies showing positivity for CD34 and CD99, which helps in differentiating it from myofibroma. STAT6 positive reactivity is also helpful in differentiating solitary fibrous tumour from myofibroma.¹⁹ Schwannomas usually have Antoni type A and Antoni type B and are positive for S100. Various studies4 7 12 14 have reported a low mitotic activity in myofibroma and this is reflected in its low Ki 67 staining, thus confirming the benign nature of the lesion.

The most common treatment done is wide local excision with or without removal of adjacent teeth depending on the involvement of bone. Recurrence is rare in oral lesions, and when it occurs, it may be due to incomplete removal of the primary lesion. A recurrence rate of 9.7% has been reported by Smith et al³ and when recurrences do occur, it was found that a second surgery is often curative. Our patient underwent a wide local excision with alveolectomy owing to the pressure resorption of the alveolar bone. She has reported no recurrences in the past 4 years following her surgery.

To conclude, MF may show an aggressive clinical course and, hence, mislead the clinician. Histologically, these lesions are challenging to diagnose due to its rarity and due to failure in identifying myofibroblasts as the lesional cell. Thus, the use of adjunctive aids like immunohistochemistry is essential in the diagnosis.

Learning points.

• Oral soft tissue myofibromas can occur anywhere in the oral cavity including gingiva.

• They frequently grow rapidly to raise suspicion of a malignancy.

• Final diagnosis is through histopathological examination and requires a thorough knowledge of spindle cell lesions as well as the judicious use of immunohistochemical stains.

• General practitioners as well as dental specialists need to have improved awareness regarding oral myofibromas for timely identification and diagnosis as well as to initiate early management of such lesions.