Quite a few lesions of the oral cavity specifically of the gingiva have a greater inclination towards women and mostly occur during the first four decades of life, the cause of which may be credited to the changing levels of sex hormones. Out of all such lesions, one lesion whose aetiology is still unclear and which originats from the periosteum or periodontal ligament is central giant cell granuloma. Repeatedly, it is has been described as a reactive lesion, the cause of which may be secondary to local irritants or trauma, specifically plaque or calculus, which is not considered to be a true neoplasm. Here we present a case of a 51-year-old female patient with aggressive gingival growth within 10–13 months of hormonal replacement therapy. The aetiology, histological features and appropriate treatment are discussed in the light of current literature.
- dentistry and oral medicine
- endocrine system
Statistics from Altmetric.com
WHO defined central giant cell granuloma (CGCG) as an intraosseous lesion consisting of more or less fibrous tissue containing multiple foci of haemorrhage, aggregates of multinucleated giant cells, some amount of trabaculae of woven bone forming within the septa of more mature fibrous tissue that may traverse the lesion.1 It is a disease with an unknown aetiology seen mostly in young adults and mostly prevalent in females than males.2 3 It is more often seen in mandible than maxilla with a ratio of 2:1. The most common location includes anterior mandible up to first molar with a tendency to cross the midline.4
Clinically, CGCG presents as an asymptomatic lesion, which is slowly growing and attains a rampant form, like expansion followed by root resorption and pain.3
When observed radiographically CGCG occasionally shows ‘saucerisation’ or ‘cup-shaped’ resorption of the subjacent alveolar bone.5 A radiographic examination is must to differentiate the origin of the lesion between gingival (peripheral) or bone (central). Also, root resorption of the teeth adjacent to the lesion is rare.6
The aim of reporting this case report is to illustrate an example of an aggressive CGCG in a patient on hormonal replacement therapy and to discuss a reasonable aetiology, differential diagnosis, based on the age of the patient, history and clinical features
A 51-year-old female patient reported with a complaint of pain in lower right side of jaw since 2 weeks, which was related to carious premolar tooth in the same region. But upon intraoral examination other than carious lesion there was presence of a sessile gingival growth over the right alveolar ridge extending from distal aspect of 45 to distal aspect of 47 encircling the teeth in a collar like manner. The growth was not associated with the premolar teeth of the pain associated with them. On enquiring about the history of growth, the patient revealed that it had a gradual onset and was progressive in size. It was not associated with any pain, which was the reason patient did not seek any treatment for the same. Medical history of the patient revealed that she had menopause at the age of 49 years and was currently on hormone replacement therapy for the same. Although, rest of the oral cavity was healthy. On palpation the growth was firm, lobulated and non-tender. No lymph node enlargement was seen.
On radiographic examination bone loss was evident between tooth 47 and 48, involving the furcation are of tooth 47 (figure 1).
Haematological investigations included complete haemogram (including red blood cell count, white blood cell count, haematocrit, haemoglobin, platelet count and so on) and biochemical evaluation along with hormonal assay (oestorgen). Haematological evaluation revealed that the patient was aneamic. Hormonal assay revealed oestrogen levels to be 75 pg/mL as the patient was on hormonal replacement therapy.
Further, the patient was advised excisional biopsy. The growth was excised in toto and sent for histopathological evaluation. Further, the patient was advised to regularly visit the hospital for follow-up.
On macroscopic examination, the excised tissue was creamish brown in colour, irregular in shape, lobulated surface, firm in consistency and measured 2.6 x 3.2 x 2.0 cm in maximum dimensions (figure 2). Histopathological evaluation of biopsied specimen revealed the presence of multinucleated giant cell proliferation within a background of spindle-shaped and ovoid mesenchymal cells. Presence of dense fibrous connective tissue seen separating the proliferating giant cell from the mucosal surface (figure 3). Numerous giant cells varying in shape and size, containing 10–12 nuclei were well appreciated (figure 4). Areas of haemorrhage with extravasated RBCs and chronic inflammatory cells were also noticed (figure 5). The histopathological features were suggestive of giant cell granuloma.
Pyogenic granuloma: usually a long standing lesion, seen in female patients more often with overlying mucosa being reddish blue in colour.
Peripheral ossifying fibroma: asymptomatic growth and the overlying mucosa appears normal.
Fibrous hyperplasia: asymptomatic growth, can be related to any irritation to gingival or interdental papilla.
Fibrolipoma: growth appears smooth, overlying mucosa is asymptomatic.
Neurofibroma: is a firm, oval, smooth and asymptomatic lesion.
Central giant cell granuloma: the lesion is asymptomatic, aggressive type perforates the cortical plates and appear as exophytic lesion.
Peripheral odontogenic fibroma: slow growing gingival mass, firmly attached, seen in dentulous areas.
Outcome and follow-up
As there was absence of any local factor as a cause of CGCG, the patient was informed that the condition might have occurred secondary to the medication of hormomal replacement. Also, she was well-educated about the chances of recurrence, owing to which she was put on subsequent follow-up, which revelead no signs of recurrence up to 1 years.
CGCG is a benign hyperplastic reactive lesions but are not a true neoplasm and are related to local irritation or trauma.7 CGCGs are predominantly reported in maxilla and mandible.8 9 The most preferred site for occurrence of CGCG is the mandible.2 The etiopathogenesis of CGCG is still unknown and remains questionable. In the past, several hypotheses have been proposed that define the presence of multinucleated giant cells, among which the most accepted is that, the osteoclasts seen in CGCG are the remnants of the physiological resorption of teeth or a reaction from a probable periosteum injury. At present, reports suggest presence of receptors for calcitonin, which are capable of excavating bone in vitro.10 Another opinion is that giant cells may simply represent a reactionary component and are derived from blood stream in bone marrow.11
Giant cells present in the lesional tissue are of two types: type I cells consisting of multiple large, ovoid cells with vesicular nuclei, ranging in number from 5 to 15 having prominent nucleoli with the nuclear chromatin seen on the nuclear membrane peripherally with different sizes mostly greater than 100 μm in diameter and representing metabolically active cells. Type II cells are less in number, tiny and more irregular than type I cells, which makes detection of nucleoli difficult, also the cytoplasm stains deeply eosinophilic and granular representing dying cells.12
Giant cells can be classified morphologically into three types13: type I: containing clusters of vesicular nuclei with prominent nucleoli; type II: majority of cells are with deeply staining eosinophilic cytoplasm and nuclei clustered in one part of the cell along with clear round vacuoles with central dark areas in the cytoplasm; type III: these were less in number and represented dying cells.
Although, in the present case no evident cause for occurrence of CGCG was evident. Thus, here a hormonal assay was carried out along with the haematological investigations, to check the level of oestrogen, weather or not its levels were under normal range irrespective of the patient being on hormonal replacement therapy. Also, the test was an attempt to correlate the outcome of the lesion with the hormonal replacement therapy.
Studies have suggested that CGCG is propagated by pregnancy, and is not at all dependent on pregnancy. The lesion entirely is not hormone dependent, rather it is believed to be an outcome of a combination of various factors including immunosuppressive action of hormones which in turn causes a hyper responsiveness to gingiva. This hyper responsiveness of gingival can be attributed to the fact that the metabolism of oestrogen is thrice more in unhealthy gingiva when compared with normal gingiva. Hence, they concluded that this lesion is result of influence of ovarian hormones.14 Clinically CGCG may be enlarged during pregnancy, again due to increase in levels of oestrogen and may atrophy and desquamate during menopause. This observation regarded the gingiva as another ‘target organ’ as action site for oestrogen, by some investigators.12
Steroid hormone act by forming a hormone-receptor complex. This is aided by uptake of hormone by target cell and its interaction with cytoplasmic receptor protein. The hormone-receptor complex is transported to the nucleus thus activating the genome and stimulating protein synthesis. Oestrogen and progesterone being hydrophobic steroid hormones follow the similar mechanism of action. These molecules bind to intracellular receptor proteins in the cytoplasm and nuclear membrane. Metabolic condition further regulates the transcription of specific genes.15 Thus, the summation leads to the fact that oestrogen and progesterone may stimulate the proliferation and maturation of gingival connective tissue and epithelium.12
In the present case since the patient is menopausal woman and on hormone replacement therapy, the occurrence and pathogenesis can be attributed to the role of replacement hormones, as there was no other local factor or contributing history which would suggest a reason for the occurrence of this lesion.
This case is an attempt to find a corelation between central giant cell granuloma and patients on hormonal replacement therapy, in an otherwise health oral cavity without any local irritants.
Histopathology along with hormonal assay in menopausal patients is the diagnostic tool for differentiating similar lesions.
Surgical excision is a successful treatment of choice in minimising the recurrence of lesion.
Marked female predilection of central giant cell granuloma suggests a possible hormonal influence.
Contributors SG was responsible for concept, design, contents, literature, histopathological diagnosis, manuscript preparation. MG was responsible for design, contents, literature review, histopathological analysis and manuscript editing. NS was responsible for literature search, data analysis, data compilation, manuscript drafting. KSA was responsible for evaluation of radiographs, literature search, manuscript editing, manuscript reviewing. All the authors had approved the final draft of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Patient consent for publication Obtained.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.