Abstract
The oral mucosal calcified nodule (OMCN) is a rare soft tissue lesion with only 7 cases reported in the English literature. It typically presents in the pediatric population as an asymptomatic submucosal nodule of less than 2 cm size affecting the maxillary ridge or palate, though other sites are reported. The histopathology displays stratified squamous epithelium overlying fibrous connective tissue with embedded calcified aggregates bordered by variable numbers of multinucleated giant cells. Surgical excision is curative. In this report, we present a new case of OMCN, outline the characteristic histopathologic features and review the cases reported in the English literature.
Introduction
Calcifications may manifest in the human body upon precipitation of calcium salts and clinically present in a myriad of ways. Calcinosis cutis is the broad term for this pathologic process of calcification in the subepithelial tissues. 1 The 5 main categories of calcinosis cutis include: dystrophic, idiopathic, metastatic, iatrogenic, and calciphylaxis.1,2
Dystrophic calcinosis cutis, the most common type of calcinosis cutis, is the result of calcium salt deposition due to tissue damage in the setting of normal serum calcium and phosphorus levels. 2 Metastatic calcinosis cutis presents with abnormal serum levels of phosphorus and calcium as a result of defects in metabolism or in cases such as malignancy leading to destruction of bone (breast and prostate cancer). 2 Iatrogenic calcification occurs when patients receive an exogenous source of substances which contain calcium or phosphate such as during a medical procedure which pierces the skin. 2 Calciphylaxis is more commonly noted in patients with abnormal serum calcium due to renal failure but since it has been reported in patients with normal serum calcium levels, it is categorized accordingly as a distinct subtype. 2
Parenthetically, other examples of pathologic accumulation of calcifications in soft tissues include but are not limited to rare processes such as gout, pseudogout, hydroxyapatite deposition disease, and heterotopic lesions like choristomas.
In this case report, we are presenting a pediatric patient with the rare manifestation of an oral mucosal calcified nodule. The purpose of this case report is to provide a description of a rare lesion, the oral mucosal calcified nodule, in an infant and to review the literature to present the consistencies with and variation from past reports of this unique entity.
Case Report
A 1-year-old female child presented with parents to the oral and maxillofacial surgeon with the chief complaint of a growing lesion on the mandibular anterior gingiva. The parents reported the child displayed no discernible issues with discomfort during feeding or failure to thrive in conjunction with the lesion.
Intraoral examination revealed a solitary, slightly white, sessile, exophytic nodule located on the mandibular anterior gingival ridge right of the midline (Figure 1). The mucosa overlying the nodule was normal in appearance. No observation of a painful reaction was elicited upon firm palpation. Other findings from the intraoral evaluation included the absence of erupted incisors in the anterior mandibular region. The intraoral absence of the primary teeth indicates a possible discrepancy between dental and chronologic age. Attempts to obtain an intraoral radiograph were unsuccessful. Based on the clinical presentation of the lesion, consent was obtained from the parents for an excisional biopsy under local anaesthesia using a scalpel.
Solitary nodule on the anterior mandibular gingiva.
The specimen was submitted in total to the pathology lab in 10% formalin. The gross description indicated the specimen was irregularly-shaped, smooth-surfaced, and measured 0.5 × 0.3 × 0.3 cm. Histopathological examination revealed stratified squamous epithelium covering fibrous connective tissue containing masses of crystalline calcified material (Figure 2(A)). The fibrous connective tissue contained variously sized and shaped aggregates of basophilic crystalline particles. The collections of crystalline fragments were noted to be associated with clusters of multinucleated giant cells (Figure 2(B and C)).
(A) Intact stratified squamous epithelium overlying fibrous connective tissue with embedded calcified masses (40×). (B) Well-vascularized stroma and central aggregates of deep purple calcified matter (100×). (C) Calcified fragments bordered by multinucleated giant cells (black arrows) (200×). (D) Von Kossa stain with Nuclear Fast Red counterstain highlights the calcium deposits visualized as metallic silver (brown-black fragments).
The tissue was subsequently stained using the Von Kossa histochemical stain to confirm the presence of calcium deposits. In this process, the calcium salts transform into silver salts which ultimately display the metallic silver deposits as black or dark brown brittle deposits (Figure 2(D)). The definitive diagnosis of oral mucosal calcified nodule was rendered.
In follow-up communication with the oral and maxillofacial surgeon, he reported discussing the case with the child’s pediatrician to rule out an underlying systemic etiology. All bloodwork was normal and no underlying metabolic issues with calcium were present. There was no sign of recurrence at the 6 month follow up.
Discussion
The oral mucosal calcified nodule (OMCN) is a rare pathological entity noted in the oral cavity of pediatric patients. A review of the English language literature revealed a paucity of cases. Prior to this case report, only 7 cases of OMCN have been reported (Table 1).3,5-9 In the reported cases, children were noted to be of varying ages. The youngest child was 3 months old, 9 and the oldest child was 6 years old. 6 The average age for the OMCN is 2 years.3,5-9 In our case report, the child was a 1 year old, which coincides with the typical occurrence in the pediatric population.
Reported Cases of Oral Mucosal Calcified Nodule.
In previous reports, authors have claimed a male predilection for the OMCN. 7 Of the 7 cases where gender was reported, there are 4 males3,5-7 and 3 females, including the current case.3,8 The presentation of a female in this case lessens support of a male predilection for the OMCN. The analogous subepidermal calcified nodule of the skin in fact has a male predilection. 10 The authors feel that due to the low number of reports of this entity, the predilection for sex remains unclear at this time, it may indeed occur equally amongst females and males. We will not be sure until more cases are reported to clarify this.
The most common location for the OMCN is maxillary in orientation, specifically the palatal region. The location on the palate ranges from the junction of the hard and soft palate to palatal gingiva.3,5-7,9 Notably, there is 1 case reported to be from the dorsal tongue 3 and another from the lower lip vermilion. 8 Another observation is the more anterior presentation of 6 out of the 8 cases, including the current case.3,6-8 A proximity to the midline was also seen in the majority of the cases, including our case.3,5-7,9 which may be attributed to possible dysgenesis when tissue planes are fusing during embryogenesis. 4 This median presentation is also observed in soft tissue oral hamartomas noted in the pediatric cohort, 11 however the histopathologic finding in this case completely precludes the diagnosis of a hamartoma. Only 1 case was noted on the transition between the skin of face and the oral mucosa, namely the vermilion zone. 8 This aforementioned case was also further from the midline in position. The sizes of the lesion, including our case, ranged from 0.5 to 2 cm in greatest dimension.3,5,7,9 The descriptive terminology used in the reports of OMCN in a majority of cases was a variably hard or soft, spongy and occasionally sessile, solitary nodule.3,5,7,8 The clinical appearance varied from pink to yellow to white.7,8 One case was verrucous in nature with visible punctate calcifications and redness. 9 According to the report in Case 5, the swelling was described as painful, although the majority of OMCN lesions are described as asymptomatic, as was noted in the current case. 7
Several unique features have been reported including displacement or delayed eruption of incisors, as seen in our case,3,7 discharge of calcified masses before or during surgery,3,7 difficulty with feeding or teething,7,9 and a congenital presentation. 8 The absence of antecedent trauma was only explicitly stated in 2 cases5,8 and there was no such report of trauma in the current case. In 5 cases with reported details, including our case, patients and their caregivers were compliant with care and completed lab tests such as alkaline phosphatase, inorganic phosphate and serum calcium levels.3,7,8 The blood tests were done in conjunction with the histopathological evaluation in order to confirm the idiopathic nature of the OMCN.
With respect to the plausible clinical differential diagnoses for the OMCN, there was variability in the cases due to disparity in location of the lesions, clinical appearance, and prevalence of the lesions. The clinical differential diagnosis in our case included congenital epulis, Bohn’s nodules, dental lamina cyst, and potentially peripheral ossifying fibroma. In 1 case, a detailed clinical differential for the maxillary gingiva case included gingival abscess (prior to radiograph), infected eruption cyst with dystrophic calcification, calcifying odontogenic cyst, developing odontoma, and adenomatoid odontogenic tumor. 7 Case 5 was the only case with a diagnostic occlusal radiograph displaying fine granular radiopacities less radiodense than tooth structure. 7 The lack of radiographs in other gingival cases may possibly be due to patient cooperation and the absence of a perceived necessity for radiographs of mucosal lesions. Case 7 considered a squamous papilloma, foreign body reaction, minor salivary gland lesion, and reactive or developmental lesions as part of the clinical differential diagnosis. 9 Consideration should also be given to entities forming hard tissue in the soft tissue such as a choristoma. The choristoma, a proliferation of normal tissues in an abnormal location, is one such hard tissue lesion which was ultimately ruled out upon histopathologic evaluation. 12 A similarity which ties all of the clinical differential diagnoses together is the benign clinical nature of the OMCN. This appears to have led to the identical conservative treatment of an excision in all reports including the current case.3,5-9 In one case, the surgery resulted in a defect which healed post-operatively. 9 This surgical management is further supported by the absence of reported recurrences in all cases including the current case.3,5-9.
It has been suggested that the extrusion of calcified particles possibly from recurrent trauma, coupled with the presence of a progressive foreign body reaction, are evidence the OMCN may spontaneously resolve over time. 3 This was also cited as the prime reason for no cases in adulthood. 3 This theory has not been formally confirmed however as most reported cases are excised. Trauma has been proposed as a possible etiology. The subepidermal calcified nodule is theorized to arise in sites of injury. 10 More data will be needed to prove this, however in the current case there was no reported trauma to the area prior to development of the nodule.
In our literature review, there were distinct similarities observed in the histopathologic findings. For example, all of the cases in Table 1 demonstrated aggregates or pools of a basophilic granular matrix composed of calcified matter.3,5-9 Foreign body reactions composed of multinucleated foreign body giant cells and macrophages were a consistent finding.3,5-9 Cases also had an associated inflammatory infiltrate present. Von Kossa stain was used in 3 cases, including the current case, to support the diagnosis.3,5 Hyperplasia of the overlying epithelium was seen on occasion.5,9
In the published literature, a case of a 34-year-old male with a calcified inflammatory nodule in the buccal mucosa was documented. 13 This was thought to represent the first reported adult case of the oral mucosal calcified nodule. We have chosen not to include this case in our literature review after observing the histopathology which appears dissimilar to the cases found in children. The microscopic findings of a peripheral wall with minimal calcifications and internal nodules with hyalinization and scattered calcifications is dissimilar to the features present in the pediatric cases. These findings appear more consistent with the histopathologic characteristics of a phlebolith rather than an oral mucosal calcified nodule. 13 Another separate case presenting as idiopathic calcinosis of the tongue was also excluded based on histopathologic criteria. 14
Although the OMCN has been presented as the oral variant of the subepidermal calcified nodule(SCN), the theories regarding the pathogenic mechanism of the OMCN have not been extensively explored, likely a result of the rarity of cases. Winer who first described the SCN in 1952, postulated the skin nodule represents a calcified hamartoma of sweat duct origin. 15 Other authors have theorized that the basophilic matrix of calcification may be produced by fibroblasts in the area or degranulation of mast cells.5,16 Specific theories have yet to be confirmed for the derivation of the OMCN. However, consideration may be given to the comparable embryologic derivation of both skin and oral mucosa and theories of origin of SCN may be cross-referenced. 4
Another proposed etiology for OMCN is a process homologous to dystrophic calcinosis cutis or the development of acne calcifications but in the setting of the oral cavity as a result of submucosal localized inflammation during embryogenesis/early formative years. 17 The clinical presentation in the pediatric population and predominantly near the midline where fusion planes exist in current and past cases3,5-7,9 is supportive of this theory, however since the initial tissue insult/trauma is difficult to correlate with lesion progression in these cases, it is not possible to categorize OMCN as dystrophic at this time.
Sialoliths, tonsilloliths, or aggregates of various calcium phosphates are seen in the oral cavity, most commonly in the submandibular gland duct region. 12 These calcified phenomena are typically not found within the connective tissue but rather “outside” of the epithelium such as within the lumen of a duct or within the crypt of a tonsil. The formation of the OMCN does not appear to recapitulate these entities.
Conclusion
Although the OMCN is a rare lesion, there are some characteristic clinical features such as a distinct prevalence in the pediatric population and a mucosal nodule clinical appearance. Our case is the 8th reported case of an OMCN. Due to the scarcity of this lesion, we propose there is no confirmed male predilection at this time and more reported cases are needed to confirm this. The pathophysiological mechanism of the OMCN remains largely unknown and requires further investigation. Many dentists and physicians may be unaware of the OMCN and would therefore not include this entity in the differential diagnosis of calcified lesions of the oral cavity. It is important to increase awareness of this lesion and to consider the OMCN for any solitary nodule of the oral cavity in a pediatric patient.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
