Ver Berne Jonas, Jacobs Reinhilde, Hauben Esther
Department of Pathology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
Department of Imaging and Pathology, OMFS-IMPATH, Catholic University Leuven, Kapucijnenvoer 7, 3000, Leuven, Belgium.
Head Neck Pathol. 2025 Jun 25;19(1):77. doi: 10.1007/s12105-025-01818-7.
The classification of mixed odontogenic tumors-specifically ameloblastic fibroma (AF), ameloblastic fibro-odontoma (AFO), and odontoma-remains controversial. The current WHO classification emphasizes the presence of dental hard tissues but overlooks the distinction between aberrant inductive activity and maturation resembling normal odontogenesis. This has led to diagnostic ambiguity and inconsistent management strategies. This study aims to propose a biologically grounded reclassification based on histological, developmental, and molecular criteria.
We conducted a conceptual reassessment of AF, AFO, and odontoma, using six cases from our pathology archives. Histological slides were reviewed with focus on the type and organization of mineralized tissue (tubular dentin, osteodentine, enamel) and its epithelial-mesenchymal context. Clinical and radiological data were evaluated, and BRAF V600E mutation status was retrieved when available. A targeted literature review was performed to integrate findings on histology, genetic alterations, and malignant transformation risk.
Two distinct lesion types were identified: (1) Ameloblastic fibroma with aberrant inductive activity, showing irregular osteodentine and enameloid deposits without odontoblast differentiation, harboring BRAF mutations; and (2) odontomas, characterized by mature tubular dentin and enamel formation, indicating a hamartomatous nature, despite significant clinical growth. Historical descriptions support this biological dichotomy, emphasizing the difference between aberrant inductive activity and processes resembling normal odontogenesis.
We propose abandoning AFO as a distinct diagnostic entity. Instead, lesions could be classified based on the presence of organized, mature dental hard tissues. AF with aberrant inductive activity represents a benign neoplasm with low malignant potential, while odontoma is a hamartomatous lesion sometimes with large growth capacity but no malignant risk. This binary classification would align histological criteria with biological behavior, integrate molecular data, and restore diagnostic clarity. The validity of this framework should be investigated in future cohorts.
混合性牙源性肿瘤——特别是成釉细胞纤维瘤（AF）、成釉细胞纤维牙瘤（AFO）和牙瘤——的分类仍存在争议。当前的世界卫生组织分类强调牙硬组织的存在，但忽略了异常诱导活性与类似正常牙发生的成熟之间的区别。这导致了诊断的模糊性和不一致的管理策略。本研究旨在基于组织学、发育学和分子标准提出一种基于生物学的重新分类方法。
我们利用病理学档案中的6个病例对AF、AFO和牙瘤进行了概念性重新评估。对组织学切片进行了复查，重点关注矿化组织（管状牙本质、骨样牙本质、釉质）的类型和组织结构及其上皮-间充质背景。评估了临床和放射学数据，并在可行时获取BRAF V600E突变状态。进行了有针对性的文献综述，以整合组织学、基因改变和恶性转化风险方面的研究结果。
确定了两种不同的病变类型：（1）具有异常诱导活性的成釉细胞纤维瘤，表现为不规则的骨样牙本质和类釉质沉积，无成牙本质细胞分化，存在BRAF突变；（2）牙瘤，其特征为成熟的管状牙本质和釉质形成，表明具有错构瘤性质，尽管临床上有明显生长。历史描述支持这种生物学二分法，强调异常诱导活性与类似正常牙发生过程之间的差异。
我们建议放弃将AFO作为一个独立的诊断实体。相反，病变可根据有组织的成熟牙硬组织的存在进行分类。具有异常诱导活性的AF代表一种恶性潜能低的良性肿瘤，而牙瘤是一种错构瘤性病变，有时生长能力较大但无恶性风险。这种二元分类将使组织学标准与生物学行为相一致，整合分子数据，并恢复诊断的清晰度。该框架的有效性应在未来的队列研究中进行调查。
