A clinical and histomorphologic comparison of the central giant cell granuloma and the giant cell tumor

doi:10.1016/0030-4220(88)90094-1

Oral Surgery, Oral Medicine, Oral Pathology

Volume 66, Issue 2, August 1988, Pages 197-208

Oral Surgery, Oral M...

https://doi.org/10.1016/0030-4220(88)90094-1 Get rights and content

Abstract

The clinical, histologic, and histomorphometric features of 42 giant cell tumors (GCT) of long bones and 49 central giant cell granulomas (CGCG) of the jaws were compared. These findings were also correlated with the clinical behavior of 25 cases of CGCG for which follow-up information was available. There was a female predilection for both lesions. The mean ages of patients with CGCG and GCT were 21 and 25 years, respectively. In contrast to CGCG, GCT rarely occurred in persons below the age of 10 years. The only statistically significant quantitative difference between the lesions at the histologic level was the greater number of nuclei in the giant cells of the GCT. There were four significant histologic differences between the two lesions, but 26% of the GCTs were histologically similar to most of the CGCGs and 10% of the CGCGs were histologically similar to most of the GCTs. Five of the 25 patients with CGCG for whom follow-up information was available had recurrences. The average age of those five patients was 11 years, compared to 29 years for those patients without recurrence. All five patients with recurrence were under 17 years of age, and they constituted 45% of the patients in this age group with follow-up. There were no quantitative or histologic differences between the recurrent and nonrecurrent CGCGs that were useful in predicting the likelihood of recurrence. Our findings suggest that the GCT and the CGCG represent a spectrum of a single disease process modified by the age of the patient and the site of occurrence.

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Reparative giant cell granuloma (RGCG) is a benign lesion with common gnathic expression in young patients. It is divided into aggressive and non-aggressive forms based on clinical and radiological features.
This is a case report of reparative granuloma of the maxilla in a six-year-old child who presented with asymptomatic gingival overgrowth in the maxillary teeth region which was surgically excised. An aggressive recurrence was noted eight months after excision, which was then excised with wider margins under general anesthesia. The case was finally diagnosed as the central type of RGCG with no further recurrence up till 36 months follow up.
Early recognition of RGCG is key to avoiding eventual demolitive outcomes. The complete wide excision of such lesions minimizes the chances of recurrence.
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The distinction between giant cell tumors and giant cell granulomas is challenging, as both entities have overlapping diagnostic criteria, especially in oral locations. The two entities have similar clinical and radiological presentations, but they differ in their prognoses.
The main objective of this study was to list the clinical, radiological, histological, and prognostic features of maxillomandibular giant cell tumors and giant cell granulomas cases n order to assess their value as a diagnostic referral factor that may allow the distinction between maxillo-mandibular giant cell granuloma and giant cell tumor.
Data of maxillomandibular giant cell granulomas and giant cell tumors were assessed through a scoping review and a pre-existing systematic review of literature. We have also realized a bicentric retrospective study.
Various criteria facilitate the differential diagnosis like age, size, locularity and presence of necrosis zone but not the gender. The most discriminating factors was symptomatology (reported in 72% of GCTs while only 15% of GCGs) and the distribution pattern of giant cells in the stroma (homogeneously dispersed in 80% of GCTs versus grouped in clusters in 86.7% of GCGs). Recurrences were most described for giant cell tumors than giant cell granulomas. Malignant transformation and pulmonary metastasis were exclusively reported for giant cell tumors.
As clinical and radiological elements are not sufficient to distinguish between these two entities, immunohistochemistry and molecular genetics can be represent diagnostic biomarkers to distinguish giant cell granulomas and giant cell tumors in oral cavity. We have attempted to define the main criteria for the differentiation of giant cell tumor and giant cell granuloma and propose a decision tree for the management of single maxillomandibular giant cell lesions.
RANKL inhibition for giant cell lesions of the jaw: A retrospective cohort analysis
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In all giant-cell-rich lesions (GCRL) occurring in bone, a common underlying excessive RANKL expression is held responsible for the osteolytic activity. Apart from giant cell tumour of bone (GCTB), systematic outcome analysis of RANKL inhibition in other GCRL is unavailable. The aim of this study is to assess the efficacy and safety of a 1-year denosumab protocol in giant cell lesions of the jaw (GCLJ).
A retrospective cohort study was conducted compromising patients treated with a 1-year protocol of monthly subcutaneously administered 120 mg denosumab. Objective tumour response based on histology and imaging was used to calculate objective tumour response rate, progression-free survival (PFS) and time to progression. Type, severity and frequency of adverse events were recorded in a standardised way to assess safety.
Twenty patients, predominantly female (90%), were included. Fifty-five per cent of lesions were located in the mandible; most classified as aggressive lesions (90%). Thirty-five per cent (7/20) of cases were either recurrent after prior treatment or progressive, while on other drug treatment. Objective tumour response rate was 100% after 12 months of treatment. Median PFS was 50.4 months (95% CI 38.0–62.8) with a cumulative PFS rate of 22.6% (95% CI 1.8–43.4) at 5 years follow-up. Median time to progression was 38.4 months (95% CI 26.0–50.8). Treatment was well tolerated, and none of the patients had to interrupt therapy for toxicity.
High-dose denosumab is effective and safe in achieving a complete response in GCLJ within 12 months. The high long-term relapse rate after treatment cessation is the main obstacle for denosumab to become standard treatment for GCLJ.
Denosumab for central giant cell granuloma in an Australian tertiary paediatric centre
2022, Bone
Central giant cell granulomas (CGCG) are rare osteolytic, benign but often locally aggressive tumours of bone. Surgical curettage may not be possible in extensive lesions and resection carries high morbidity, especially in growing children, and previous medical therapies have had variable efficacy and high recurrence rates. Interruption of receptor activator of nuclear factor-kappa B ligand (RANKL) signalling holds promise as an effective therapeutic strategy for these tumours.
To evaluate the efficacy and safety of our protocol for denosumab treatment of CGCG in children.
Retrospective review of 4 patients treated with denosumab using a standardised protocol for CGCG in a tertiary paediatric centre. Denosumab 70 mg/m² was given 4-weekly, followed by 2 doses of zoledronate 0.025 mg/kg, aimed at preventing rebound hypercalcaemia.
Treatment of CGCG resulted in metabolic remission in all patients, but recurrence, detected by positron emission tomography (PET), occurred at 6 months in three patients and 12 months in one patient. Three patients developed symptomatic hypercalcaemia 4–5 months and one patient asymptomatic hypercalcaemia 7 months after cessation of denosumab, with 3 requiring additional bisphosphonate treatment.
Denosumab produced a radiological and metabolic response in our patients, but metabolic recurrence occurred in all patients. PET imaging was effective for monitoring treatment response and early detection of recurrence. Incidence of rebound hypercalcaemia in this paediatric cohort was high. We present proposed changes to our protocol with the aim of producing sustained remission and preventing rebound hypercalcaemia.
Multiple versus solitary giant cell lesions of the jaw: Similar or distinct entities?
2021, Bone
The majority of giant cell lesions of the jaw present as a solitary focus of disease in bones of the maxillofacial skeleton. Less frequently they occur as multifocal lesions. This raises the clinical dilemma if these should be considered distinct entities and therefore each need a specific therapeutic approach.
Solitary giant cell lesions of the jaw present with a great diversity of symptoms. Recent molecular analysis revealed that these are associated with somatic gain-of-function mutations in KRAS, FGFR1 or TRPV4 in a large component of the mononuclear stromal cells which all act on the RAS/MAPK pathway.
For multifocal lesions, a small group of neoplastic multifocal giant cell lesions of the jaw remain after ruling out hyperparathyroidism. Strikingly, most of these patients are diagnosed with jaw lesions before the age of 20 years, thus before the completion of dental and jaw development. These multifocal lesions are often accompanied by a diagnosis or strong clinical suspicion of a syndrome. Many of the frequently reported syndromes belong to the so-called RASopathies, with germline or mosaic mutations leading to downstream upregulation of the RAS/MAPK pathway. The other frequently reported syndrome is cherubism, with gain-of-function mutations in the SH3BP2 gene leading through assumed and unknown signaling to an autoinflammatory bone disorder with hyperactive osteoclasts and defective osteoblastogenesis.
Based on this extensive literature review, a RAS/MAPK pathway activation is hypothesized in all giant cell lesions of the jaw. The different interaction between and contribution of deregulated signaling in individual cell lineages and crosstalk with other pathways among the different germline- and non-germline-based alterations causing giant cell lesions of the jaw can be explanatory for the characteristic clinical features. As such, this might also aid in the understanding of the age-dependent symptomatology of syndrome associated giant cell lesions of the jaw; hopefully guiding ideal timing when installing treatment strategies in the future.
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^☆: This paper was presented in part at the meeting of the American Academy of Oral Pathology, May 20, 1987, in Phoenix, Arizona. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the view of the Department of the Navy, the Department of the Army, the Department of the Air Force, the Department of Defense, or the Veterans Administration.

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A clinical and histomorphologic comparison of the central giant cell granuloma and the giant cell tumor☆

Abstract

Oral Surg Oral Med Oral Pathol

Oral Surg Oral Med Oral Pathol

Oral Surg Oral Med Oral Pathol

Hum Pathol

Oral Surg Oral Med Oral Pathol

J Oral Maxillofac Surg

J Hand Surg

The central giant cell reparative granuloma of the jaws

Am J Clin Pathol

A histological comparison of the giant cells in the central giant cell granuloma of the jaws and the giant cell tumor of long bone

J Oral Pathol

Tumors of the head and neck: Clinical and pathological considerations

A symposium on the pathology of bone tumors

Giant-cell lesions of the facial skeleton

Arch Otolaryngol

“Giant-cell tumors” of the mandible and facial bones

Arch Otolaryngol

Bone tumors

Giant cell tumor of bone: highlights of 407 cases

AJR

Giant-cell tumours of bone: a study of 209 cases with long-term follow-up in 130

Ital J Orthop Traumatol

Giant-cell tumor of bone

J Bone Joint Surg [Am]

Giant-cell tumor of bone: a demographic, clinical, and histopathological study of all cases recorded in the Swedish Cancer Registry for the years 1958 through 1968

J Bone Joint Surg [Am]

Giant-cell tumor of bone: analysis of two hundred and eight cases in Chinese patients

J Bone Joint Surg [Am]