The odontogenic keratocyst (OKC, currently designated by the World Health Organization as a keratocystic odontogenic tumor) is a locally aggressive, cystic jaw lesion with a putative high growth potential and a propensity for recurrence. Although it is generally agreed that some features of OKCs are those of a neoplasia, notably the relatively high proliferative rate of epithelial cells, controversies over the behavior and management of OKCs still exist. This article is intended to review this intriguing entity and to summarize the findings of recent studies related to the nature of OKCs and their clinical and therapeutic implications. Recent advances in genetic and molecular research, i.e., PTCH1 mutations and involvement of the Hedgehog signaling pathway, have led to increased knowledge of OKC pathogenesis which hints at potential new treatment options, although the question of whether the OKC is a cyst or a cystic neoplasm is yet to be answered with certainty. Since some advocate a more conservative treatment for OKCs, notably marsupialization and decompression, future treatment strategies may focus on molecular approaches and eventually reduce or eliminate the need for aggressive surgeries.

Context. —Orthokeratinized odontogenic cyst (OOC) is a relatively uncommon developmental cyst comprising about 10% of cases that had been previously coded as odontogenic keratocysts. Odontogenic keratocyst was designated as keratocystic odontogenic tumor (KCOT) in the new World Health Organization classification and OOC should be distinguished from KCOT for differences in histologic features and biologic behavior. Objective. —To analyze the clinicopathologic features of 61 cases of OOC in a Chinese population. Design. —Clinicopathologic analysis was performed on 61 cases of OOC. Immunohistochemical expression of Ki-67 and p63 was evaluated in 15 OOCs and 15 typical KCOTs. Results. —The 61 patients with OOC ranged from 13 to 75 years (average, 38.93 years). The lesions developed mainly in the third and fourth decades (57.38%) with a distinct predilection for males (72.13%). Six (9.84%) lesions were found in the maxilla and 55 (90.16%) in the mandible. The most common sites were in the mandibular molar and ramus region. Of the 54 cases with radiographic record, 47 (87.04%) were unilocular and 7 (12.96%) were multilocular radiolucencies. Twenty-seven of the 54 cysts were associated with an impacted tooth. Follow-up of 42 patients revealed no recurrence during an average period of 76.8 months after surgery. Compared with KCOTs, expression level of Ki-67 and p63 was significantly lower in OOCs, suggesting a lower proliferative activity. Conclusion. —Orthokeratinized odontogenic cyst is clinicopathologically distinct from KCOT and should constitute its own clinical entity.

Tooth development undergoes a series of complex reciprocal interactions between dental epithelium and the underlying mesenchymal cells. Compared with the study in tooth crown formation, little is known about the molecular mechanism underlying the development of tooth roots. In the present study, we conditionally knock out β-catenin gene (Ctnnb1) within developing odontoblasts and cementoblasts during the development of tooth roots, and observed rootless molars as well as incomplete incisors. Histological analyses revealed intact structure of molar crown and labial side of incisor, however, as for the molar roots and the lingual portion of incisor, the formation of dentin and periodontal tissues were greatly hampered. In situ hybridization experiments using probes of odontoblastic marker genes collagen type I, alpha 1 (Col1a1), osteocalcin (OC) and dentin sialophosphoprotein (Dspp) manifested striking undifferentiation of root odontoblasts in which Ctnnb1 was eliminated. Bromodeoxyuridine (BrdU) labeling and proliferating cell nuclear antigen (PCNA) immunohistochemical experiments also showed retarded proliferation of pre-odontoblasts in mutant mice. However, cell apoptosis was not affected. Additionally, a disrupted formation of cementoblasts, suggested by the absence of transcripts of bone sialoprotein (Bsp) in follicle mesenchyme, was also evident in mutant mice. Our study provides strong in vivo evidence to confirm that Wnt/β-catenin signaling is functionally significant to root odontogenesis and cementogenesis during the tooth root development.

Context. —Odontogenic myxoma is an uncommon tumor that has the potential for extensive destruction of the jaws. Objective. —To document the clinical, pathologic, and behavioral features of odontogenic myxomas. Design. —Histologic and immunocytochemical examinations were performed on odontogenic myxomas from 25 Chinese patients. Clinical and available follow-up data were analyzed. Results. —In the present series, 13 were male and 12 female. The age at diagnosis ranged from 6 to 66 years, with a mean age of 28.8 years. Twelve tumors involved the mandible and 13 occurred in the maxilla, with a predilection for posterior areas. The posterior maxillary tumors frequently (9/10) involved the maxillary sinus. Of the 23 cases with radiographic records, 22 lesions presented with a multilocular appearance. Although 80% of the mandibular lesions showed a well-defined border, only 33.3% of the maxillary tumors were well-defined. Histologically, odontogenic myxomas were mainly composed of spindled or stellate-shaped cells in a mucoid-rich intercellular matrix. Tumors containing noticeable fibrous components were evident in 13 cases. Apart from 5 cases treated conservatively by enucleation, the remaining 20 cases were treated by relatively radical procedures, including block/segmental resection and partial or total maxillectomy or mandibulectomy. Follow-up data were available on 22 patients and only 1 patient initially treated by enucleation had a recurrence. Conclusions. —Odontogenic myxomas have a very bland histologic appearance that lacks atypia and may easily lead to misdiagnosis. The tumors are infiltrative with no capsulation and may recur after inadequate surgery.

Context. —Primary intraosseous squamous cell carcinoma is a rare form of squamous cell carcinoma, arising within the jaws. Objective. —To clarify the clinicopathologic and behavioral spectrum of primary intraosseous squamous cell carcinoma. Design. —The clinical and pathologic findings, treatment, and follow-up data of 39 cases of primary intraosseous squamous cell carcinoma were collected and analyzed. Results. —Of the 39 patients, 26 (67%) were men and 13 (33%) were women. The age at diagnosis ranged from 24 to 82 years (mean, 54 years). The tumors occurred predominantly (84.6%) in the posterior mandible. Microscopically, all tumors demonstrated general features of a squamous cell carcinoma; 19 of which (49%) also showed features suggestive of an odontogenic origin. The overall survival rates were 69.8% at 2 years and 36.3% at 5 years. Univariate analysis showed that tumors with or without odontogenic features, tumor grading, lymph node metastasis, and treatment modalities were significant prognostic factors for survival, but multivariate analysis showed that only histologic grading (relative risk, 4.43; P = .03) remained a significant prognostic factor. The cumulative probabilities of recurrence were 55.7% at 2 years and 75.9% at 5 years. Univariate analysis showed that lymph node metastasis and treatment modalities were significant prognostic factors for recurrence. On multivariate analysis, however, only lymph node metastasis remained a significant prognostic factor (relative risk, 2.54; P = .05). Conclusions. —Primary intraosseous squamous cell carcinoma is a high-grade malignancy with frequent, regional lymph node metastasis and high rates of recurrence and mortality. The tumor grading and regional lymph node metastasis may serve as useful indicators for prognosis.