Abstract
Phenotypic heterogeneity has been a complex phenomenon lately, fetching attention in tumour pathology. Myofibroblastic differentiation is one such example and, besides, functional heterogeneity contributes to the biological behaviour of the tumours. Myofibroma is a distinctive neoplasm of myofibroblasts with a low incidence rate in the oral cavity. A case of myofibroma in mandibular alveolus in an adult patient is reported here for its rarity and diagnostic dilemma.
Keywords: Myofibroblast, myofibroma, spindle cell tumour
INTRODUCTION
The profile of myofibroblast is fascinating for dual reasons. Firstly, it is not a normal cell and is not easy to define. Secondly, it harbours within itself two phenotypic (fibrous and smooth muscle cell) properties.[1] Myofibroblasts are unique cells and contractile in nature which play a role in inflammation, fibrosis, and tumour progression.[2] Hence, myofibroblastic differentiation can occur in a wide range of events from repair to neoplasms.
History:
The term myofibroblast was coined by Gibbiani.[2]
Myofibromatosis was first described by Stout as congenital generalized fibromatosis in 1954.[3]
Renamed as infantile myofibromatosis by Chung et al. in 1981.
The term ‘Myofibroma’ was introduced by Smith et al. in 1989.[4]
Myofibroma (MF) is a mysterious spindle cell lesion which is considered to be a benign tumour of myofibroblasts which exists in three forms; infantile/adult, multicentric, and solitary forms.[5] About 1/3rd of all myofibromas are reported in the head and neck region and the incidence and prevalence of solitary myofibroma in the oral cavity are very low with very few cases described in oral soft tissues.[4]
CASE REPORT
A 67-year-old male reported swelling in the lower right back teeth region of 1-month duration. The swelling was sudden in onset and was smaller in size about 1 × 1 cm initially and gradually progressed to the present size of 6 × 5 cm. The swelling was huge, non-tender, and caused difficulty with eating and swallowing. The patient had a history of smoking bidi for 25 years and gutka chewing for 2 years. No history of similar swellings elsewhere in the body.
On oral examination, a soft pedunculated mass on the mandibular alveolus, extending anteroposteriorly from the mesial aspect of 43 to retromolar area and mesio-laterally from the buccal vestibule to lingual vestibule was noted [Figure 1]. The overlying mucosa appeared pink and normal with focal areas of ulceration due to trauma. It was firm in consistency on palpation.
Figure 1.
Firm mass on the mandibular alveolus
No significant radiographic changes were observed in the mandible.
Considering the histopathological findings of an incisional biopsy which was suggested to be a benign reactive growth, the mass was excised under local anaesthesia with electrocautery and the specimen was submitted for histopathological examination.
Grossly, the mass was irregular, having two nodules attached together resembling a butterfly shape, measuring 6 × 5 cm [Figure 2].
Figure 2.
Gross appearance of the excised mass
Microscopic examination of H&E-stained sections revealed surface ulceration and granulation tissue response with an underlying spindle cell lesion composed of cells arranged in intersecting long fascicles with bland nuclei, inconspicuous nucleoli, and indistinct cytoplasmic membranes [Figure 3]. The mitotic count activity was <1 per 10 high-power fields. The surrounding stroma was fibro collagenous with scattered congested vessels with focal areas exhibiting staghorn vessel morphology [Figure 4]. Basophilic calcifications were noted focally with no evidence of necrosis and atypia [Figure 5].
Figure 3.
Spindle cells arranged in fascicles, H&E stain (20×)
Figure 4.
Staghorn vessels, H&E stain (20×)
Figure 5.
Calcification H&E stain (40×)
An immunohistochemical panel of markers was considered and spindle cells showed cytoplasmic positivity for smooth muscle actin [Figure 6]. Negative expressions for CD 34, desmin, S-100, beta-catenin, Pan CK, and P63 were observed in the spindle cells and Ki-67 expression was <1%.
Figure 6.
SMA positivity –IHC (40×)
The final diagnosis of myofibroma was rendered taking into consideration the morphological and immunohistochemical profile. Recovery of the patient is uneventful one year after surgery with no recurrence.
DISCUSSION
Myofibroblasts have the ability to repair, differentiate and invade the tissues by producing an extracellular matrix (ECM).[6] The fibronexus is a cell–to–matrix junction which ensures a degree of adhesion to ECM and therefore procures special importance as a myofibroblast marker.[1]
Myofibroma is a tumour of spindle cell morphology which can involve any age group. It is common in children, where 89% of cases occur before 2 years of age and 54% out of these are congenital.[7] Tumour shows slight female predilection (F/M ratio—1.6:1).[8]
The etiopathogenesis is unclear and trauma has been implicated in pathogenesis. Fibroblasts are stimulated due to trauma and are differentiated into proto myofibroblasts under the influence of platelet-derived growth factor. Further, these cells are differentiated into myofibroblasts under the influence of transforming growth factors—beta and EDA—fibronectin.[7] The possibility of a familial pattern of inheritance (autosomal-dominant and -recessive patterns) in MF is reported.[8]
There is no site predilection for MF and the tumour tends to involve both soft tissues and bone in the head and neck region. In the oral cavity, the tongue (30%) is the most commonly affected tissue followed by buccal mucosa (20%).[9] In our case, the site involved was the mandibular alveolus, which obliterated both the buccal and lingual vestibules, and is a rare site for myofibromas.
Morphologically, myofibromas are presented as a well-circumscribed, unencapsulated tumour comprising of haphazardly arranged sweeping fascicles of plump spindle cells. The zonation phenomenon is characteristically evident where there are alternating fascicular and cellular areas and cells exhibit a biphasic appearance. Spindle cells with eosinophilic cytoplasm with tapered ends and oval nuclei are seen in the centre. Cellular areas consisting of the small dark spindle or polygonal cells with rich vascularity are evidently seen in the periphery.[5]
Myofibroma needs to be differentiated from leiomyoma, inflammatory myofibroblastic tumour, and nodular fasciitis. Due to the clinical presentation and invasive nature, sarcomas are also listed in the differentials [Table 1].[10]
Table 1.
Morphological Differentials for Myofibroma
| MF | Leiomyoma | Nodular fasciitis | IMT |
|---|---|---|---|
| Zonation pattern Fascicular and cellular components | Well-formed, long fascicles that intersect at right angles. Cigar-shaped nuclei in spindle cells |
No zonation and HPC-like areas. Tissue culture-like growth pattern Myxoid areas Keloid-like collagen |
Storiform to fascicular patterns with associated chronic inflammation. |
MF: Myofibroma, IMT: Inflammatory myofibroblastic tumor
Immunohistochemistry is a significant aid in differentiating tumours of spindle cell morphology which display morphological overlapping features.
SMA is considered to be the most reliable marker for myofibroblast identification. Foss et al. in their study verified 100% positivity for SMA protein.[4]
Surgical excision is the treatment of choice for MF. Multiple lesions, familial history, tumour location and cortical involvement are some of the influencing factors for treatment planning. Myofibromas, despite rapid enlargement, may regress or spontaneously involute over time with a low recurrence rate. MF does not show any tendency for malignant transformation or metastasis.[11]
CONCLUSION
Myofibroma is a rarity in the oral cavity with regard to its occurrence. With the varied clinical presentation, an uncommon site along with overlapping morphological features, it can pose diagnostic dilemmas and is challenging for 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 initial s 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.
REFERENCES
- 1.Eyden E. The myofibroblast in health and disease. Rev Esp Patol. 2008;41:3–10. [Google Scholar]
- 2.Bagul N, Ganjre A, Goryawala SN, Kathariya R, Dusane S. Dynamic role of myofibroblasts in oral lesions. World J Clin Oncol. 2015;10:264–71. doi: 10.5306/wjco.v6.i6.264. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Beck JC, Devaney KO, Weatherly RA, Koopmann CF, Jr, Lesperance MM. Pediatric myofibromatosis of the head and neck. Arch Otolaryngol Head Neck Surg. 1999;125:39–44. doi: 10.1001/archotol.125.1.39. [DOI] [PubMed] [Google Scholar]
- 4.Brasileiro BF, Martins-Filho PR, Piva MR, da Silva LC, Nonaka CF, Miguel MC. Myofibroma of the oral cavity. A rare spindle cell neoplasm. Med Oral Patol Oral Cir Bucal. 2010;15:e596–600. doi: 10.4317/medoral.15.e596. [DOI] [PubMed] [Google Scholar]
- 5.Foss RD, Ellis GL. Myofibromas and myofibromatosis of the oral region: A clinicopathologic analysis of 79 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;89:57–65. doi: 10.1067/moe.2000.102569. [DOI] [PubMed] [Google Scholar]
- 6.Micallef L, Vedrenne N, Billet F, Coulomb B, Darby IA, Desmoulière A. The myofibroblast, multiple origins for major roles in normal and pathological tissue repair. Fibrogenesis Tissue Repair. 2012;5(Suppl 1):S5. doi: 10.1186/1755-1536-5-S1-S5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Rodrigues EDR, Oliveira EMF, Ribeiro R, Passador-Santos F, Matos FR, Almeida Souza G. Myofibroma of the oral cavity mimicking a non-neoplastic inflammatory process: An unusual report. J Oral Diag. 2020;05:e20200002. [Google Scholar]
- 8.Tajima N, Shiraishi T, Ohba S, Fujita S, Asahina I. Myofibroma of the tongue: A case suggesting autosomal dominant inheritance. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117:e92–6. doi: 10.1016/j.oooo.2013.05.010. [DOI] [PubMed] [Google Scholar]
- 9.Andreadis D, Epivatianos A, Samara A, Kirili T, Iordanidis F, Poulopoulos A. Myofibroma of the oral mucosa: A case report. Med Princ Pract. 2012;21:288–91. doi: 10.1159/000334587. [DOI] [PubMed] [Google Scholar]
- 10.Beham A, Badve S, Suster S, Fletcher CD. Solitary myofibroma in adults: Clinicopathological analysis of a series. Histopathology. 1993;22:335–41. doi: 10.1111/j.1365-2559.1993.tb00132.x. [DOI] [PubMed] [Google Scholar]
- 11.Smith MH, Reith JD, Cohen DM, Islam NM, Sibille KT, Bhattacharyya I. An update on myofibromas and myofibromatosis affecting the oral regions with report of 24 new cases. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;124:62–75. doi: 10.1016/j.oooo.2017.03.051. [DOI] [PubMed] [Google Scholar]