TY - JOUR
T1 - Histopathologic and Molecular Insights Following the Management of Ameloblastomas via Targeted Therapies – Pathological and Clinical Perspectives
AU - Hirschhorn, Ariel
AU - Grynberg, Shirly
AU - Campino, Gadi Abebe
AU - Dobriyan, Alex
AU - Patel, Vinod
AU - Greenberg, Gahl
AU - Yacobi, Rinat
AU - Barshack, Iris
AU - Yahalom, Ran
AU - Toren, Amos
AU - Vered, Marilena
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Purpose: Current standard of care for ameloblastoma (conventional/unicystic - mural type) usually mandates extensive bone resection that frequently necessitates immediate reconstruction with serious sequelae, especially among young patients. BRAF-mutated ameloblastomas can be targeted by BRAF inhibitors to markedly reduce their size, enabling conservative removal of residual tumor. We aimed to characterize the effect of post-treatment histomorphologic changes. Methods: Study included 14 patients, 11 mandibular and three maxillary tumors. Cases with very minimal residual tumor were defined as near-complete response, while those with mostly vital residual tumor as partial response. The epithelium component was scored for architectural and cellular changes, stroma - for fibrosis, inflammation and new bone formation, on a 3-tired score system: 0–no, 1–focal and 3–frequent changes. The mean scores of each parameter, total epithelium and total stroma were calculated and related to duration of treatment. Differences in the mean scores were investigated for mandibular tumors with near-complete response (n = 3) and partial response (n = 8). Results: There were no significant differences in mean epithelium or stroma scores between tumors with near-complete and those with partial response (2.22 ± 0.68 versus 2.08 ± 0.43, p = 0.55; 1.41 ± 1.04 versus 1.43 ± 0.44, p = 0.27), suggesting that ameloblastomas have potential to undergo complete response to targeted treatment. This is probably dependent upon tumor/patient/treatment-related factors. Response to treatment appears to be predictable with neoplastic epithelium being first, while the stromal response increases during treatment, the entire process expanding over weeks-to-months. Conclusion: Albeit preliminary, these are the first comprehensive histomorphologic findings on BRAF-treated ameloblastomas. Analyzing the suggested parameters in tumors with partial response, should highlight which tumor component has responded/failed to respond. This could serve as a basis for decision-taking toward subsequent steps in adjuvant treatment (e.g., follow-up, conservative surgery, modifications/changes in treatment regimen, combinations of approaches), with a prime aim of jaw preservation and minimal risk of sequelae.
AB - Purpose: Current standard of care for ameloblastoma (conventional/unicystic - mural type) usually mandates extensive bone resection that frequently necessitates immediate reconstruction with serious sequelae, especially among young patients. BRAF-mutated ameloblastomas can be targeted by BRAF inhibitors to markedly reduce their size, enabling conservative removal of residual tumor. We aimed to characterize the effect of post-treatment histomorphologic changes. Methods: Study included 14 patients, 11 mandibular and three maxillary tumors. Cases with very minimal residual tumor were defined as near-complete response, while those with mostly vital residual tumor as partial response. The epithelium component was scored for architectural and cellular changes, stroma - for fibrosis, inflammation and new bone formation, on a 3-tired score system: 0–no, 1–focal and 3–frequent changes. The mean scores of each parameter, total epithelium and total stroma were calculated and related to duration of treatment. Differences in the mean scores were investigated for mandibular tumors with near-complete response (n = 3) and partial response (n = 8). Results: There were no significant differences in mean epithelium or stroma scores between tumors with near-complete and those with partial response (2.22 ± 0.68 versus 2.08 ± 0.43, p = 0.55; 1.41 ± 1.04 versus 1.43 ± 0.44, p = 0.27), suggesting that ameloblastomas have potential to undergo complete response to targeted treatment. This is probably dependent upon tumor/patient/treatment-related factors. Response to treatment appears to be predictable with neoplastic epithelium being first, while the stromal response increases during treatment, the entire process expanding over weeks-to-months. Conclusion: Albeit preliminary, these are the first comprehensive histomorphologic findings on BRAF-treated ameloblastomas. Analyzing the suggested parameters in tumors with partial response, should highlight which tumor component has responded/failed to respond. This could serve as a basis for decision-taking toward subsequent steps in adjuvant treatment (e.g., follow-up, conservative surgery, modifications/changes in treatment regimen, combinations of approaches), with a prime aim of jaw preservation and minimal risk of sequelae.
KW - Ameloblastoma
KW - BRAF mutation
KW - Epithelium
KW - Response
KW - Stroma
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85211122890&partnerID=8YFLogxK
U2 - 10.1007/s12105-024-01734-2
DO - 10.1007/s12105-024-01734-2
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C2 - 39621130
AN - SCOPUS:85211122890
SN - 1936-055X
VL - 18
JO - Head and Neck Pathology
JF - Head and Neck Pathology
IS - 1
M1 - 129
ER -