Hirschhorn Ariel, Grynberg Shirly, Campino Gadi Abebe, Dobriyan Alex, Patel Vinod, Greenberg Gahl, Yacobi Rinat, Barshack Iris, Yahalom Ran, Toren Amos, Vered Marilena
Department of Cranio-Maxillofacial Surgery, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Ella Lemelbaum Institute for Immuno-Oncology, and Melanoma, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Head Neck Pathol. 2024 Dec 2;18(1):129. doi: 10.1007/s12105-024-01734-2.
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.
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).
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.
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.
成釉细胞瘤（传统型/单囊性 - 壁型）当前的治疗标准通常要求进行广泛的骨切除，这常常需要立即进行重建，且会带来严重的后遗症，尤其是在年轻患者中。BRAF 突变的成釉细胞瘤可通过 BRAF 抑制剂进行靶向治疗，以显著缩小其大小，从而能够保守切除残留肿瘤。我们旨在描述治疗后组织形态学变化的影响。
研究纳入了 14 例患者，其中下颌肿瘤 11 例，上颌肿瘤 3 例。残留肿瘤极少的病例被定义为接近完全缓解，而残留肿瘤大多仍有活性的病例为部分缓解。上皮成分根据结构和细胞变化进行评分，基质根据纤维化、炎症和新骨形成进行评分，采用三级评分系统：0 - 无，1 - 局灶性，3 - 频繁变化。计算每个参数、上皮总分和基质总分的平均得分，并与治疗持续时间相关。对接近完全缓解（n = 3）和部分缓解（n = 8）的下颌肿瘤的平均得分差异进行了研究。
接近完全缓解的肿瘤与部分缓解的肿瘤在上皮或基质平均得分上无显著差异（分别为 2.22 ± 0.68 与 2.08 ± 0.43，p = 0.55；1.41 ± 1.04 与 1.43 ± 0.44，p = 0.27），这表明成釉细胞瘤有可能对靶向治疗产生完全缓解。这可能取决于肿瘤/患者/治疗相关因素。对治疗的反应似乎是可预测的——肿瘤上皮首先出现反应，而基质反应在治疗过程中增加，整个过程持续数周至数月。
尽管是初步研究，但这些是关于 BRAF 治疗的成釉细胞瘤的首批全面组织形态学发现。分析部分缓解肿瘤中的建议参数，应能突出哪些肿瘤成分有反应/无反应。这可为辅助治疗后续步骤（如随访、保守手术、治疗方案的调整/改变、联合治疗方法）的决策提供依据，主要目标是保留颌骨并使后遗症风险降至最低。
