Sporadic giant cell granulomas (GCGs) of the jaws and cherubism-associated giant cell lesions share histopathological features and microscopic diagnosis alone can be challenging. Additionally, GCG can morphologically closely resemble other giant cell-rich lesions, including non-ossifying fibroma (NOF), aneurysmal bone cyst (ABC), giant cell tumour of bone (GCTB), and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and DNA methylation profiling has been shown to be clinically useful for the diagnosis of other tumour types. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic GCG and cherubism to test whether DNA methylation patterns can help to distinguish them. Additionally, we compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. DNA methylation analysis was performed for central (n = 10) and peripheral (n = 10) GCG, cherubism (n = 6), NOF (n = 10), ABC (n = 16), GCTB (n = 9), and chondroblastoma (n = 10) using the Infinium Human Methylation EPIC Chip. Central and peripheral sporadic GCG and cherubism share a related DNA methylation pattern, with those of peripheral GCG and cherubism appearing slightly distinct, while central GCG shows overlap with both of the former. NOF, ABC, GCTB, and chondroblastoma, on the other hand, have distinct methylation patterns. The global and enhancer-associated CpG DNA methylation values showed a similar distribution pattern among central and peripheral GCG and cherubism, with cherubism showing the lowest and peripheral GCG having the highest median values. By contrast, promoter regions showed a different methylation distribution pattern, with cherubism showing the highest median values. In conclusion, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions. Conversely, it could discriminate sporadic GCG of the jaws from their giant cell-rich mimics (NOF, ABC, GCTB, and chondroblastoma).

UNASSIGNED: To evaluate and compare the clinicopathological features of giant cell tumour (GCT), central giant cell granuloma (CGCG) and peripheral giant cell granuloma (PGCG).
UNASSIGNED: From 2006 to 2016, all histopathologically diagnosed cases of GCT were retrieved from the Department of Pathology, T.N.M.C, Mumbai and CGCG and PGCG were retrieved from the Department of Oral Pathology, Nair Hospital Dental College, Mumbai. Statistical analysis of the clinicopathological features was done using SPSS v 21.0, IBM. Intergroup comparison of all variables was done using t test for two groups, whereas, Kruskal-Wallis test and one-way ANOVA were done for more than two groups.
UNASSIGNED: Twelve cases of GCT, 31 cases of CGCG and 39 cases of PGCG were reported over 11 years. The mean age of occurrence for GCT, CGCG and PGCG was 30.41 years, 27.69 years and 34.03 years, respectively. GCT was seen in long bones and CGCG and PGCG showed mandible predilection. Histologically, GCT showed evenly distributed giant cells with aggregated nuclei, whereas CGCG and PGCG showed aggregated giant cells with evenly distributed nuclei. The mean value of the number of giant cells and nuclei within giant cells was maximum in GCT (27.33, 33.50) followed by CGCG (23.56, 15.51) and PGCG (21.45, 11.32).
UNASSIGNED: The clinicopathological differences between GCT, CGCG and PGCG suggest that each one of these entities represent biologically different lesions.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s12663-022-01724-3.

Giant cell tumour (GCT) is locally aggressive benign neoplasm of long bones whereas giant cell granulomas; central giant cell granuloma (CGCG) and peripheral giant cell granuloma (PGCG); are tumour-like conditions of the oral cavity. This study aimed to evaluate and compare the immunohistochemical expression of p63 in GCT, CGCG, PGCG and determine whether p63 can be used as a diagnostic, prognostic and differential biomarker between these entities. Histopathologically diagnosed 10 cases of GCT, 20 cases of CGCG and 20 cases of PGCG were subjected to p63 immunohistochemical staining. The percentage of p63-positive cells was semi-quantitatively assessed on the whole section. Intergroup comparison was done using Kruskal-Wallis test and one-way ANOVA. The value p < 0.05 was considered to be statistically significant and value p < 0.01 was considered to be statistically highly significant. p63 immunoexpression was seen in 100% (10/10) cases of GCT whereas CGCG and PGCG revealed the complete absence of p63 immunopositivity. These results showed a highly significant difference in p63 expression between GCT, CGCG and PGCG (p < 0.01). No difference was noted between CGCG and PGCG. GCT is a distinct entity when compared with CGCG and PGCG. Even aggressive CGCG also did not show p63 immunopositivity, so it is not a prognostic marker. Also, p63 cannot differentiate between CGCG and PGCG.