Non-familial paediatric oral myofibroma - A masquerade. Case report with a brief literature review

Spoorti Kulkarni; Adarsh Kudva; Srikanth Gadicherla; Sunitha Carnelio

doi:10.4103/jomfp.jomfp_141_22



CASE REPORT

Year : 2023 \| Volume : 27 \| Issue : 5 \| Page : 1-5

Non-familial paediatric oral myofibroma - A masquerade. Case report with a brief literature review

Spoorti Kulkarni¹, Adarsh Kudva², Srikanth Gadicherla², Sunitha Carnelio¹
¹ Department of Oral Pathology and Microbiology, Manipal College of Dental Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India
² Department of Oral and Maxillofacial Surgery, Manipal College of Dental Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India

Date of Submission	24-Mar-2022
Date of Acceptance	19-May-2022
Date of Web Publication	04-Feb-2023

Correspondence Address:
Sunitha Carnelio
Professor and Head, Department of Oral Pathology and Microbiology, Manipal College of Dental Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jomfp.jomfp_141_22

Abstract

Myofibromas are fibrous tumours that could be of familial or non-familial origin, belonging to the fibroblastic and myofibroblastic subset with a wide spectrum of clinical behaviour. Oral myofibromas present with a broad range of differential diagnoses, including benign and malignant lesions. Histopathologically, these lesions may imitate many other soft tissue tumours of the oral cavity, such as spindle cell tumours of nerve, smooth muscle cell origin, and other myofibroblastic lesions, thus leading to misdiagnosis and mistreatment. In the present paper, we report a soft tissue lesion, which presented as a growth on the gingivobuccal sulcus in a 7-year-old child. We also emphasise the various differential diagnoses that need to be eliminated and the importance of immunohistochemistry to know the nature of tumour cells in establishing the accurate diagnosis.

Keywords: α-SMA, fibromatosis, immunohistochemistry, myofibroma, paediatrics

How to cite this article:
Kulkarni S, Kudva A, Gadicherla S, Carnelio S. Non-familial paediatric oral myofibroma - A masquerade. Case report with a brief literature review. J Oral Maxillofac Pathol 2023;27, Suppl S1:1-5

How to cite this URL:
Kulkarni S, Kudva A, Gadicherla S, Carnelio S. Non-familial paediatric oral myofibroma - A masquerade. Case report with a brief literature review. J Oral Maxillofac Pathol [serial online] 2023 [cited 2023 Apr 1];27, Suppl S1:1-5. Available from: https://www.jomfp.in/text.asp?2023/27/5/1/369166

Introduction

Myofibroma and myofibromatosis belong to myofibroblastic lineage, presenting as solitary or multiple tumours, though both the lesions have the same histopathological presentation. This spindle cell neoplasm occurs within the submucosal or intramuscular tissue in the oral cavity and the most common site is the tongue, followed by buccal mucosa and lips. The first case of solitary myofibroma was described by Smith et al. in 1989. The terms “myofibromatosis” and “myofibroma” were then adopted by the World Health Organization (WHO).^[1] The recent classification by WHO has included myofibromas, in a continuum of perivascular tumours in the intellect of morphologic spectrum of perivascular myoid cell neoplasms.^[2] The lesion is typically benign, but because of difficulty in diagnosis, it may lead to inappropriate therapy.

We report a case of soft tissue growth in a paediatric patient on the left gingivobuccal sulcus, which clinically presented as a pyogenic granuloma or a fibroma. The final diagnosis was made based on the histopathological features and immunohistochemical examination. This paper also emphasises the differential diagnosis of the spindle cell neoplasms and the panel of immunohistochemical markers that aid in confirming the diagnosis.

Case Report

A 7-year-old boy reported to the dental clinic with a complaint of growth with left buccal mucosa for 20 days. The patient gave no history of discharge, any halitosis, difficulty in swallowing, speaking, chewing, tongue movements, change in taste and salivation, or decrease in appetite and weight loss. On extra-oral examination, diffuse swelling with the left cheek, approximately 2 x 2 cm, was seen. There were no signs of erythema, sinus tract, and pus discharge. The skin over the swelling appeared normal in texture and colour [Figure 1]a. Mouth opening and mandibular movements were normal. On palpation, the swelling was soft, tender, and not attached to the underlying structures. On intra-oral examination, a growth in relation to the left gingivobuccal sulcus measuring approximately 2.5 x 2 cm in dimension extending posteriorly till the first molar, superiorly till the mid buccal mucosa, anteriorly till the deciduous canine, inferiorly involving the gingivobuccal sulcus, was seen [Figure 1]b. The Growth was reddish-white in colour and erythematous. The rest of the oral mucosa appeared normal. On palpation, the growth was smooth in consistency, non-pulsatile, and tender, and the base of the tongue and floor of the mouth were free. There were no sharp teeth associated. Complete hemogram, biochemical investigations, and Contrast Enhanced Computerized Tomography (CECT) of the head and neck were done. The blood reports were within the normal parameters. CECT report revealed a well-defined lobulated soft tissue density arising from the buccal surface of gingiva of the mandibular alveolus and inferior gingivobuccal sulcus, posteromedially abutting the alveolar process of the mandible with no obvious bony erosions and likely to be an infective/inflammatory etiology [Figure 1]c. Based on the clinical and radiographic features, the provisional diagnosis of pyogenic granuloma was given.

Figure 1: (a) Extra-oral picture showing diffuse swelling on the left cheek, (b) Intra-oral picture showing growth in relation to left gingivobuccal sulcus, (c) CECT report, showing a well-defined lobulated soft tissue density arising from the gingivobuccal sulcus area, with no bony involvement

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Surgical excision of the lesion was done and sent to the department of oral pathology and microbiology for histopathological examination. On gross examination, the lesion was whitish in colour, soft in consistency, and approximately 2.5 x 2 cm in size.

Histopathological examination revealed multinodular growth with biphasic patterns owing to the alteration of light and dark staining areas. The light staining areas consisted of plump spindle cells arranged in fascicles. The dark staining areas were composed of round cells with slightly pleomorphic hyperchromatic nuclei around a distinct hemangiopericytoma-like vascular pattern. Few chronic inflammatory cells, numerous blood vessels with endothelial lining, and haemorrhagic areas were also evident in the section. The histopathological features were suggestive of a spindle cell neoplasm [Figure 2]a and [Figure 2]b. However, to confirm the diagnosis, immunohistochemical analysis with α-SMA (Dako, clone 1A4, 1:200), desmin (Dako, clone D33, 1:250), and Beta Catenin (Dako, clone 14, 1:500) was done to differentiate between myofibroma and fibromatosis. Immunopositivity of tumour cells was seen for α-SMA [Figure 2]c, and negative for Beta-catenin [Figure 2]d and desmin, indicating a myofibroblastic lineage of the lesion. Thus, based on histopathologic features and immunohistochemical findings, a diagnosis of myofibroma involving the left gingivobuccal sulcus was made.

Figure 2: (a and b) Biphasic growth pattern with round cells and spindle cells arranged in fascicles [H&E, 100X (a), 400X (b)], (c) Diffuse immunopositivity of cells to α-SMA. (100X), (d) Negative immune-reactivity of cells to β-catenin

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Discussion

Myofibroma is a benign tumour of uncertain histogenesis, with a wide range of clinical presentations from aggressive multicentric to benign localised forms, found commonly in the dermis or subcutaneous tissue.^[3] In the head and neck region, the most frequent site is bone (mandible), followed by tongue and buccal mucosa. According to the study done by Jordan and Regezi,^[4] the incidence of solitary myofibroma was low in the oral cavity; eight cases in a total of 307 non-odontogenic spindle cell neoplasms were positive. In a recent review done by Vered et al.,^[5] only 41 cases of oral soft tissue myofibroma were reported.

Myofibroblasts are the specialised fibroblasts or intermediate cells, exhibiting the features of smooth muscle, fibroblasts, and undifferentiated cells, which play an important role in wound healing. Prostaglandins derived from myofibroblasts promote the healing process by resorting to the epithelium and also the contractile properties, which are essential during wound healing due to the presence of α-SMA filaments. These myofibroblasts also secrete collagen (Type I, III, IV, VIII), fibronectin, tenascin, and matrix metalloproteinases (MMPs), which are the mediators in tissue remodelling. Studies have shown that the myofibroblasts are few or devoid in the normal epithelium compared to a higher number of myofibroblasts in oral squamous cell carcinoma. The transdifferentiation of myofibroblasts is due to the inductive effect of malignant epithelial cells, which secrete numerous growth factors. The chemokines, growth factors, and matrix-degrading enzymes are secreted by myofibroblasts, which act along with the host immune cells to aid in angiogenesis, basement membrane breakdown, and metastasis. Thus myofibroblasts play a significant role in physiologic as well as pathologic processes like the healing of wounds and tumour progression.^[3] The exact cause of myofibroma is not clear; one of the factors associated with its pathogenesis is trauma. Trauma stimulates the proliferation of fibroblasts, which under the influence of PDGF (Platelet-derived growth factor), get differentiated into protomyofibroblasts. The cytoplasms of these cells show the excess amount of actin microfilaments (stress fibers). Further, under the influence of TGF-β (Transforming growth factor – Beta) and fibronectin, these protomyofibroblasts are differentiated into myofibroblastic cells. The proliferation of these myofibroblast cells could be responsible for myofibroma.^[6]

Regarding the molecular pathogenesis of myofibroma (pediatric/infantile), there are a lot of controversies. In familial cases of myofibroma, somatic mutation of PDGFRB ((Platelet-Derived Growth Factor Receptor Beta) and L1519P mutation in the NOTCH3 gene could be the molecular driver events. NOTCH3^L1519P upregulates PDGFRB expression in fibroblasts, which supports a functional link between Notch and PDGF dysregulation. PDGFRB binds to the ligand PDGF. The binding induces dimerisation and conformation changes. This, in turn, activates tyrosine kinase domain and receptor auto-phosphorylation. Receptor phosphorylation on tyrosine residues creates docking sites for signalling molecules (Mitogen activated protein kinase (MAPK) pathway, Signal transducer and activator of transcription (STAT) transcription factor). Thus this disease can be treated with tyrosine kinase inhibitors such as imatinib, which potently blocks the PDGF receptor kinase activity.^[7],[8]

However, controversies remain in distinguishing the familial and non-familial lesions. In a study done by Cheung et al. on the recurrent cases of myofibroma, they did not find PDGFRB mutation.^[7],[8] Similar types of studies on recurrent non-familial myofibromas have shown mutation in the same gene in various exon sites (besides those seen in familial type).Further studies with a larger sample size need to be done to throw light on the pathogenesis of non-familial cases of myofibroma.

These benign myofibroblastic tumours belong to pericytic lineage and develop in the soft tissue, bone, and internal organs. Patients commonly present with solitary, multiple, and generalised forms. The solitary myofibroma (unifocal) or multicentric myofibromatosis (multifocal) without visceral involvement has a better prognosis, in contrast to myofibromatosis with visceral involvement (generalized form), due to the involvement of the heart wall, pulmonary parenchyma, gastrointestinal tract, and rarely the central nervous system. In these patients, the lesion would be fatal within days or weeks of birth. Although a majority of myofibroma cases are common in infants, a few cases have been noted in older children and adults as well.^[9] The present case is of solitary myofibroma in a 7-year-old child on the gingivobuccal sulcus. Most of the cases of the myofibroma are seen in males, with the Male: Female ratio being 2:1, and more commonly, the intra-oral myofibromas are seen on the tongue, buccal mucosa, and lips.^[3] In the present case, the lesion was seen in a male child on the gingivobuccal sulcus. The lesion presented as a slow-growing, painless swelling, with approximately measuring 2.5 x 2 cm.

Histopathologically, the lesion exhibited multinodular growth with a biphasic pattern of light and dark-stained areas. The spindle-shaped fibroblasts comprise cigar-shaped nuclei arranged in fascicles, whorls, or nodules; in a few areas, the cells were haphazardly arranged without any definite pattern. The morphology of the cells was round to spindly shaped, intensely stained, having basophilic nuclei, eosinophilic cytoplasm, and indistinct cell borders. Hence, the present case was quite challenging to have a confirmative diagnosis of myofibroma on hematoxylin and eosin (H&E) sections. One of the differential diagnoses was fibromatosis, which had a similar histopathological presentation as myofibroma, comprising of fascicles of spindle-shaped cells with wavy collagen fibers, which overlapped with our case but generally, this tumour exhibited a monophasic pattern. It has been shown that in aggressive fibromatosis, there is deregulation of connective tissue growth, and the process is more neoplastic rather than reactive. Fibromatosis can be superficial or deep. In cases of deep fibromatosis, there is a mutation of somatic β-catenin or APC (Adenomatous Polyposis Coli) gene that results in increased intranuclear accumulation of β-catenin that may cause cellular proliferation and a reduction in retinoblastoma gene expression, it could lead to tumour progression, which can be confirmed by immunohistochemical expression to this protein,^[6],[7],[8] and was negative in our case.

The marker α-SMA is specific for lesions that originated from myofibroblastic lineage. In the present case, the cells exhibited diffuse immunopositivity for α-SMA [Figure 2]c Thus, the final diagnosis was in favour of myofibroma. Other differential diagnosis includes nodular fascitis, which is rare in children and shows prominent myxoid stroma and does not show hemangiopericytoma-like areas as seen in myofibroma. Leiomyoma and leiomyosarcoma were excluded as they show immunopositivity to desmin, whereas myofibroma stains were negative to desmin (in the present case, the slides were negative for desmin).Fibrous histiocytoma was considered in the differential diagnosis, which exhibits a storiform pattern of the polymorphous cells, showing positivity with α-SMA at areas, factor XIIIa and α1-antitrypsin, unlike in the present case with diffuse immunoreactivity to α-SMA. Since the lesion did not show features of nuclear atypia, abnormal mitosis, and mitotic figures, fibrosarcoma was ruled out.^{[3],[6],[7],[8],[9],[10]} The differential diagnosis with a panel of immunohistochemical markers used for identifying the nature of neoplastic cells in spindle cell lesions has been summarised in [Table 1].^{[3],[6],[7],[8],[9],[10]}

Table 1: Differential diagnosis with microscopic features and immunohistochemical markers^{[3],[6],[7],[8],[9],[10]}

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In the current case, a wide surgical excision, including the border of clinically normal tissue, was done under general anaesthesia since the lesion was benign and well circumscribed. The recurrence rate is found to be 7% to 31% and reported in cases where the lesion is multicentric, difficult to access, or incomplete removal of the lesional tissue.^[10] In our case, there was no evidence of recurrence, and the patient is under regular follow-up.

Conclusion

Oral myofibromas are uncommon benign spindle cell tumours that present as slow-growing, asymptomatic, firm submucosal swelling, and rarely ulcerated. As this tumour masquerades various non-neoplastic and neoplastic spindle cell tumours of nerve, smooth muscle, and other myofibroblastic lesions, which exhibit variable biologic behaviour ranging from irritable or a reactive lesion to benign aggressive and malignancy, the knowledge of this tumour is of utmost importance for diagnosis and treatment. Immunohistochemistry plays a vital role in establishing the final diagnosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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