Contributors
Author
University of Debrecen
Keywords
Ameloblastoma (AM) is a locally aggressive benign expansible odontogenic tumor that shows a variety of clinicopathological features. AM reveals a slight preference for affecting males near their third decades with a high rate of local recurrence after resection [1]. Histologically, there are four phenotypes of AM: solid/multicystic, peripheral, desmoplastic and unicystic types. Solid/multicystic shows diverse subtypes. Although evidence on the molecular involvement of BRAF V600E mutant gene in the oncogenesis of mandibular AM and SMO in maxillary AM can be accepted now, surgical resection is the standard treatment because molecular-based therapy is still lagging [2–4]. Synchronous association of AM with other syndromes were observed in Gorlin syndrome, Gardner syndromes, epidermal nevus syndrome, Simpson-Golabi-Behmel Syndrome and Williams’ syndrome[5, 6].
Malignant transformation of AM into primary intraosseous carcinoma, squamous cell carcinoma has been reported. There are high hopes for finding a molecular signature malignant ameloblastoma (either metastasizing ameloblastoma or ameloblastic carcinoma) or an immunohistochemical marker that would be of high sensitivity and specificity to distinguish the diverse ameloblastomatous lesions (with intraoral and extraoral onsets). The absence of any distinguishing histological features or immunohistochemical markers for malignant AM, when compared to benign AM, challenges its early detection[3, 7].
The controversy on the best surgical treatment approach for managing AM is attributed to several factors. First, the solid/multicystic, peripheral, desmoplastic and unicystic types demonstrate a different clinical behavior in terms of aggressiveness, response to conservative treatment (e.g., enucleation with Carnoy's solution) and recurrence. However, the many phenotypes solid/multicystic reveals, including follicular, plexiform, acanthomatous, hemangiomatous, adenoid, granular, basal, mucinous, keratoameloblastoma, adenoid and hybrid AMs do not demonstrate any significant clinicopathological behavior [3]. Second, several clinical parameters, such as the age of the patient, date of diagnosis, quality of bone, concomitant systematic disease, syndromic association with other lesions, and general health of the patient are reported to affect the invasiveness of AM. The most recent systematic review on the surgical management of AM recommends the radical treatment for both unicystic and solid or multicystic AM, although the included studies do not consider any of the clinical parameters mentioned above[8]. Third, Although recent molecular pathogenetic discoveries have proven promising in mitigating the aggressiveness of several cases when used as adjunctive therapy to reduce the size of AM, maxillofacial surgeons tend to treat the tumor by surgical resection [7].
Approximately 1,800 research articles and reviews were published about AM over the past ten years. Most of these publications delve into discussing the histological nuance of the subtypes of the conventional AM and call for new pathological taxonomies. However, only 10-20 % of these articles contribute to the effective treatment of AM [2, 9–12]. The genomic findings that may explain the molecular oncogenesis is shown in Table 1.
Table 1. Genes commonly involved in the pathogenesis of ameloblastoma
|
Gene |
Chromosome |
Aliases |
|
PTGS2 |
1 |
COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2, hCox-2 |
|
CDC42 |
1 |
CDC42Hs, G25K, TKS |
|
HSPG2 |
1 |
HSPG, PLC, PRCAN, SJA, SJS, SJS1 |
|
SDC1 |
2 |
CD138, SDC, SYND1, syndecan |
|
IL1A |
2 |
IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1 |
|
HSPD1 |
2 |
CPN60, GROEL, HLD4, HSP-60, HSP60, HSP65, HuCHA60, SPG13 |
|
BMPR2 |
2 |
BMPR-II, BMPR3, BMR2, BRK-3, POVD1, PPH1, T-ALK |
|
RHOB |
2 |
ARH6, ARHB, MST081, MSTP081, RHOH6 |
|
WIPF1 |
2 |
PRPL-2, WAS2, WASPIP, WIP |
|
RHOA |
3 |
ARH12, ARHA, EDFAOB, RHO12, RHOH12 |
|
MME |
3 |
CALLA, CD10, CMT2T, NEP, SCA43, SFE |
|
BAP1 |
3 |
HUCEP-13, UCHL2, hucep-6 |
|
PIK3CB |
3 |
P110BETA, PI3K, PI3KBETA, PIK3C1 |
|
DAG1 |
3 |
156DAG, A3a, AGRNR, DAG, LGMDR16, MDDGA9, MDDGC7, MDDGC9 |
|
GNL3 |
3 |
C77032, E2IG3, NNP47, NS |
|
CXCL8 |
4 |
GCP-1, GCP1, IL8, LECT, LUCT, LYNAP, MDNCF, MONAP, NAF, NAP-1, NAP1, SCYB8 |
|
SPARC |
5 |
BM-40, OI17, ON, ONT |
|
PPP2CA |
5 |
NEDLBA, PP2Ac, PP2CA, PP2Calpha, RP-C |
|
TERT |
5 |
CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1, TP2, TRT, hEST2, hTRT |
|
FGF10 |
5 |
|
|
CDKN1A |
6 |
CAP20, CDKN1, CIP1, MDA-6, P21, SDI1, WAF1, p21CIP1 |
|
BRAF |
7 |
B-RAF1, B-raf1, NS7, RAFB1, BRAF |
|
EGFR |
7 |
ERBB, ERBB1, ERRP, HER1, NISBD2, PIG61, mENA |
|
IL6 |
7 |
BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2, IFNB2, IL-6 |
|
SHH |
7 |
HHG1, HLP3, HPE3, MCOPCB5, SMMCI, ShhNC, TPT, TPTPS |
|
SMO |
7 |
CRJS, FZD11, Gx, PHLSH, SMO |
|
TWIST1 |
7 |
ACS3, BPES2, BPES3, CRS, CRS1, CSO, SCS, SWCOS, TWIST, bHLHa38 |
|
WASL |
7 |
N-WASP, NWASP, WASPB |
|
PTK2 |
8 |
FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71, p125FAK, pp125FAK |
|
SNAI2 |
8 |
SLUG, SLUGH, SLUGH1, SNAIL2, WS2D |
|
PTCH1 |
9 |
BCNS, NBCCS, PTC, PTC1, PTCH |
|
NOTCH1 |
9 |
AOS5, AOVD1, TAN1, hN1 |
|
RECK |
9 |
ST15 |
|
IL33 |
9 |
C9orf26, DVS27, IL1F11, NF-HEV, NFEHEV |
|
ENG |
9 |
END, HHT1, ORW1 |
|
PLIN2 |
9 |
ADFP, ADRP |
|
PTEN |
10 |
10q23del, BZS, CWS1, DEC, GLM2, MHAM, MMAC11, PTENbeta, TEP1, PTEN |
|
MKI67 |
10 |
KIA, MIB-, MIB-1, PPP1R105 |
|
ITGB1 |
10 |
CD29, FNRB, GPIIA, MDF2, MSK12, VLA-BETA, VLAB |
|
FGFR2 |
10 |
BBDS, BEK, BFR-1, CD332, CEK3, CFD1, ECT1, JWS, K-SAM, KGFR, TK14, TK25 |
|
BMPR1A |
10 |
10q23del, ACVRLK3, ALK3, CD292, SKR5 |
|
YAP1 |
11 |
COB1, YAP, YAP2, YAP65, YKI |
|
NCAM1 |
11 |
CD56, MSK39, NCAM |
|
CTTN |
11 |
EMS1 |
|
MAML2 |
11 |
MAM-3, MAM2, MAM3, MLL-MAML2 |
|
MDM2 |
12 |
ACTFS, HDMX, LSKB, hdm2 |
|
KRAS |
12 |
'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A, K-RAS4B, K-Ras, K-Ras 2, KI-RAS1, KRAS2, NS, NS3, OES, RALD, RASK2, c-Ki-ras, c-Ki-ras2, KRAS |
|
CDKN1B |
12 |
CDKN4, KIP1, MEN1B, MEN4, P27KIP1 |
|
TNFRSF1A |
12 |
CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55, TNFAR, TNFR1, TNFR55, TNFR60, p55, p55-R, p60 |
|
GLI1 |
12 |
GLI, PAPA8, PPD1 |
|
HOXC13 |
12 |
ECTD9, HOX3, HOX3G |
|
HOXC13-AS |
12 |
HOXC-AS5 |
|
TNFSF11 |
13 |
CD254, ODF, OPGL, OPTB2, RANKL, TNLG6B, TRANCE, hRANKL2, sOdf |
|
POSTN |
13 |
OSF-2, OSF2, PDLPOSTN, PN |
|
MMP14 |
14 |
MMP-14, MMP-X1, MT-MMP, MT-MMP 1, MT1-MMP, MT1MMP, MTMMP1, WNCHRS |
|
FAM30A |
14 |
C14orf110, HSPC053, KIAA0125 |
|
HIF1A |
14 |
HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1, PASD8, bHLHe78 |
|
BMP4 |
14 |
BMP2B, BMP2B1, MCOPS6, OFC11, ZYME |
|
FOS |
14 |
AP-1, C-FOS, p55 |
|
FGF7 |
15 |
HBGF-7, KGF |
|
PLIN1 |
15 |
FPLD4, PERI, PLIN |
|
CDH1 |
16 |
Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM, UVO |
|
MMP2 |
16 |
CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1 |
|
CALB2 |
16 |
CAB29, CAL2, CR |
|
TP53 |
17 |
BCC7, BMFS5, LFS1, P53, TRP53 |
|
TIMP2 |
17 |
CSC-21K, DDC8 |
|
FASN |
17 |
FAS, OA-519, SDR27X1 |
|
BCL2 |
18 |
Bcl-2, PPP1R50 |
|
HRAS |
18 |
H-RAS |
|
XRCC1 |
19 |
RCC, SCAR26 |
|
TGFB1 |
19 |
CED, DPD1, IBDIMDE, LAP, TGF-beta1, TGFB, TGFbeta |
|
CCNE1 |
19 |
CCNE, pCCNE1 |
|
MIR524 |
19 |
MIRN524, hsa-mir-524, mir-524 |
|
MMP9 |
20 |
CLG4B, GELB, MANDP2, MMP-9 |
|
BMP2 |
20 |
BDA2A, SSFSC, SSFSC1, BMP2 |
|
SNAI1 |
20 |
SLUGH2, SNA, SNAH, SNAIL, SNAIL1, dJ710H13.1 |
|
JAG1 |
20 |
AGS, AGS1, AHD, AWS, CD339, DCHE, HJ1, JAGL1 |
|
MCM5 |
22 |
CDC46, MGORS8, P1-CDC46 |
|
TMSB4X |
X |
FX, PTMB4, TB4X, TMSB4 |
To conclude, the clinicopathological profile of AM has differed as regards its malignant transformation, extra-oral incidence, synchronous occurrence with other systematic syndromes, and response to conservative and adjunctive therapeutics.
Notes: None
Acknowledgements: None
Funding resources: None
Conflict of interest: The author declares that there is no conflict of interest to be reported.
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