Discussion and conclusions
OFM is a rare mucosal disease of unknown etiology. While the pathophysiology of OFM is not clearly understood, it is characterized by the local deposition of mucin in connective tissue in which there has been mucoid degeneration [
1]. To the best of our knowledge, there have been 65 reported cases of this disease in the English literature [
1‐
23] (Table
1). The age of the patients ranged from 2 to 68 years, with a mean age of 38.4 years. Twenty-one cases involved male patients (32.3%), while 44 involved female patients (67.7%), yielding a male:female ratio of 1:2.1. Cases of gingival origin were the most prevalent (65.6%), followed by cases with origins in the hard palate, buccal mucosa, tongue, retromolar region, and lip.
Table 1
Classification of the 65 reported cases of oral focal mucinosis identified in the literature [
1‐
23]
Age (years) | Mean 38.4, range 2–68 |
Male:female ratio | 21:44 |
Region of origin |
gingiva | 44 (65.6%)a |
palate | 9 (13.4%)b |
buccal mucosa | 5 (7.5%) |
tongue | 4 (6.0%) |
retromolar | 3 (4.5%)a |
lip | 1 (1.5%) |
unknown | 1 (1.5%) |
Clinical diagnosis |
fibroma | 22 (32.8%) |
epulis | 7 (10.4%) |
papilloma | 2 (3.0%) |
mucocele | 2 (3.0%) |
periodontal abscess | 1 (1.5%) |
giant cell granuloma | 1 (1.5%) |
pleomorphic adenoma | 1 (1.5%) |
benign tumor | 1 (1.5%) |
unknown | 30 (44.8%) |
Treatment method |
surgical resection | 67 (100%) |
Recurrence | 1 (1.5%) |
OFM is reportedly most likely to occur on keratinized mucosa attached to the bone [
1]; cases of gingival and palatal origin together comprise 79.0% of the reported cases. Occurrence in the retromolar region, as in Case 1 of our report, is rare. The overproduction of hyaluronic acid by fibroblasts and consequent formation of myxoid lesion due to its accumulation has been hypothesized as a mechanism involved in this condition [
1]. While the etiology is unknown, Neto
et al. [
15] have proposed traumatic stimulation as an eliciting factor in the disease mechanism. Moreover, Joshi
et al. [
18] suggested that traumatic stimulation may be involved in the increase in size of soft tissue lesions. However, we were unable to identify any obvious involvement of traumatic stimuli in the current cases.
The clinical findings of OFM include a painless nodular mass of elastic hardness with a similar color as that of the surrounding mucosa. However, there are no characteristic clinical and radiological features; accidental findings during dental treatment over a period of 10 years (from the first presentation of symptoms to diagnosis) have been reported [
1,
4,
7].
The clinical diagnosis of OFM is particularly difficult, and the diagnoses in previous reports have included fibroma (32.8%), epulis (10.4%), papilloma (3.0%), mucocele (3.0%), benign tumor (1.5%), periodontal abscess (1.5%), and giant cell granuloma (1.5%), as well as pleomorphic adenomas in cases of lesions of palatal origin [
23] (Table
1). A large number of cases (44.8%) were unidentified, with unrecorded clinical diagnoses at the first medical visit. None of these cases were diagnosed as OFM based on the clinical findings. Among the present cases, the first patient presented with no oral symptoms. Clearly delineated bone resorption in the right retromolar region was incidentally observed on the panoramic radiograph and diagnosed as a suspected retromolar tumor. Diagnoses of epulis were made in Cases 2 and 3, based on the presence of localized tissue masses on the buccal gingiva at the maxillary right canine and first premolar regions. Although it is difficult to tentatively diagnose OFM based on clinical symptoms and radiological findings, this disease should be considered in a differential diagnosis for benign oral tumors.
Pathological examination, including immunostaining, is essential for the definitive diagnosis of OFM. Histopathological findings include lack of encapsulation of the neoplastic tissue mass, a myxomatous stroma, and—in cases where a myxomatous stroma is absent—localized fibrous connective tissue [
1]. Therefore, histopathological distinction from diseases with a myxomatous stroma, including myxoma, mucocele, nerve sheath myxoma, neurofibroma accompanied by mucus degeneration, focal myxedema, and mucoid degeneration of fibrotic lesions, is important [
1].
In the present cases, Alcian blue and PAS staining revealed the deposition of a myxomatous substance between fibrous tissues. While positive for Alcian blue, the negative response for PAS was suggestive of the presence of acidic mucin. Furthermore, the possibility of mucoid degeneration of a peripheral nerve-derived lesion, such as nerve sheath myxoma, was eliminated based on the negative result for S-100 protein, which is an immunohistochemical marker of neural tissues or lesions. In addition, sparse fibrous connective tissue was observed in the present lesions, but reticular fibers were barely visible on silver staining.
In Case 1, bone resorption in the right retromolar region was observed, consistent with the tissue mass, and odontogenic myxoma was identified as a differential diagnosis based on the biopsy findings. However, a definitive diagnosis was not reached. Odontogenic myxoma is a true neoplasm of mesenchymal origin. It mainly consists of spindle-shaped cells and scattered collagen fibers distributed through a loose, mucoid material. Unlike OFM, odontogenic myxoma invariably presents as an intraosseous expansile lesion causing slow-growing enlargement of the jaw bone. Odontogenic myxoma and OFM are differentiated based on the arrangement and course of reticular fibers [
3,
11]. Silver staining identified very sparse reticular fibers in this case. Hence, myxoma, which shows abundant reticular fiber formation, was ruled out. These findings pertaining to the present soft tissue mass were congruent with those described by Tomich [
1], with an additional lack of invasion of the surrounding bone. There is no clear encapsulation in OFM, unlike tumors, and OFM lesions consist of a localized area of relatively thick myxomatous tissue surrounded by normal collagenous tissue; this histological feature is thought to be important in the differentiation of OFM and other diseases. Thus, a definitive diagnosis of OFM was established. However, in Case 1, resorption of the jaw bone, which is unusual for OFM, was also seen, which made an accurate clinical diagnosis difficult. There was only one case other than our case report that reported bone resorption in the radiological findings [
23]. Even though radiographic findings have typically shown the mandibular cases of odontogenic myxoma to be multilocular [
24], in these cases, the masses were unilocular on radiography; we presume that bone absorption was caused by compression with increasing size of the lesion.
Systemic diseases indicating mucinosis include pretibial myxedema occurring with hyperthyroidism, myxedema diffusum with hypothyroidism, scleredema and multiple myeloma due to diabetes, and lichen myxedematosus due to diabetes or collagenosis. In the present cases, these systemic diseases were not observed; in addition, because mucinosis was limited to the oral region, the possibility of systemic mucinosis was excluded. We believe it may be worthwhile to consider performing blood tests to eliminate endocrinological diseases after pathological diagnosis of OFM.
Thus far, treatment for all reported cases of OFM has been surgical resection. Of all the reported cases, there has been only one recurrence (1.5%) due to incomplete resection [
16]; progress was satisfactory in the remaining reported cases. The current series showed no recurrence; however, a certain period of follow-up observation may be necessary in most cases.
Here we present three cases of OFM along with a review of the literature. Although OFM is difficult to diagnose on the basis of clinical findings and its frequency is low, the disease should be considered when diagnosing benign oral tumors.