Primary Intraosseous Carcinoma Arising in an Odontogenic Cyst: A Case Report

IntroductionThe prognosis of metastatic ameloblastoma (METAM), now defined as a benign tumor, and malignant odontogenic tumors (MOT) is poorly studied in the literature. The aim of this study was to determine the prognosis and factors influencing the survival of these patients. Material and methodsUsing the SEER database, we retrieved clinical data of patients with malignant tumors of dental origin between 1975 and 2020. They include 3 histological groups: metastatic ameloblastoma (METAM), malignant odontogenic tumors (MOT, including odontogenic carcinoma, odontogenic sarcoma, primary intraosseous carcinoma, and ameloblastic carcinoma) and ameloblastic fibrosarcoma (AFS). ResultsOn 251 patients, we observed no significant difference in disease-specific survival (DSS) between the three histological groups, with 5-year DSS of 77.4% (59.9 – 100), 84.0% (78.7 – 89.7) and 71.1% (50.7 – 99.7) for METAM, MOT and AFS respectively (p = 0.460). In the MOT group, using a multivariate analysis, surgical treatment appeared to be a protective factor for DSS (HR = 0.483 [0.243 - 0.960], p = 0.038) after taking into account the potential confounding factors mentioned above. No variable significantly influenced DSS in the METAM and AFS group in univariate analysis. DiscussionWe found no difference in specific survival between the three histological groups. Although metastatic ameloblastoma was reclassified as a benign tumor by the WHO in 2017, the vital risk for patients remains consequent, and statistically similar to malignant odontogenic tumors.

Primary intraosseous carcinoma(IOC)is a rare malignancy originating from the epithelial lining of odontogenic cysts. We present a case of IOC arising from an odontogenic cyst in the mandible. A 51-year-old man presented to a general hospital with limited mouth opening. Initial anti-inflammatory treatment was administered for a presumed secondary infected mandibular odontogenic cyst;however, symptoms persisted. Subsequent biopsy revealed squamous cell carcinoma, prompting referred to our department for multidisciplinary management. Various examinations were performed, and the patient was diagnosed with a primary intraosseous carcinoma arising from a mandibular odontogenic cyst. Chemoradiotherapy was planned for this patient with unresectable locally advanced cancer. Three courses of induction chemotherapy were administered, followed by radiation therapy to the primary tumor and bilateral cervical areas(total 72 Gy)with cetuximab(Cmab). Cmab was continued post-radiation;however, the patient failed to respond to treatment and died 1 year and 2 months post-treatment initiation. Primary IOCs are challenging to distinguish from odontogenic cysts. This highlights the importance of definitive diagnosis and early intervention.

Unilateral primary intraosseous carcinoma arising from odontogenic cyst associated with an impacted maxillary third molar in a patient with multifocal jaw lesions: A rare case report

A case of primary intraosseous carcinoma in the mandible associated with anti-transcription intermediary factor 1 gamma (TIF1-γ) antibody-positive dermatomyositis

Proposal of staging system and treatment guideline for diagnostically challenging primary intra-osseous carcinoma: A retrospective single-center case series and literature review.

The recent World Health Organization (WHO) classification of odontogenic tumours defines Sclerosing Odontogenic Carcinoma (SOC) as a rare primary intraosseous carcinoma (PIOC) of the jaws. With the exception of one case, there have been no cases of SOC with metastatic disease. We report a unique case of SOC with neck node metastases, further expanding the clinical, radiological and histological spectrum of this rare intriguing tumour. A 52-year-old female presented with a destructive radiolucent lesion of right mandible. Incisional biopsy was interpreted as desmoplastic ameloblastoma. The segmental mandibulectomy specimen was histologically consistent with SOC with positive anterior margin. Further resection with neck dissection revealed positive right levels IB and IIA nodes. Immunohistochemistry and Fluroscent In Situ Hybridization (FISH) were performed to confirm the diagnosis. The tumour was positive for CK5, p63, p40 and negative for CK19, CK20, CK7, SOX-10, S100, ER, PR, BRAFV600E, and EWSR1 gene rearrangements. Ki67 was 15%. To avoid confusion with PIOC, a high grade squamous cell carcinoma of the jaws with poor prognosis, SOC may be best defined as a rare infiltrative and locally aggressive odontogenic carcinoma with metastatic potential but with a reasonably favourable outcome. SOC shares similar histologic features with many benign and malignant tumours. An appropriate panel of immunohistochemical markers, in conjunction with special stains and molecular studies can help refine the differential diagnosis. It appears that a Ki67 proliferation index of more than 10%, may pose a risk for nodal metastasis and may assist in planning the clinical management. To achieve lower rates of positive margins and tumour recurrence, a wider resection margin (more than a centimetre) is recommended.

To date, pagetoid spread-the proliferation of pagetoid cells in intraepidermal lesions, as observed in secondary extramammary Paget's disease-has not been reported in squamous epithelium derived from the extension of head and neck carcinomas. Herein, we report a case of pagetoid squamous cell proliferation associated with a primary intraosseous carcinoma (PIOC) arising in the periapical lesion of the maxilla, a finding not reported previously. A 60-year-old man presented with prostate adenocarcinoma and bilateral pubic bone, ilium bone, and sacral bone metastases. Radiological examination revealed a cyst that enveloped the apices of the left maxillary first molar roots. Histopathological examination of the cyst specimen indicated squamous cell carcinoma; hence, PIOC was suspected and partial left maxillectomy was performed. Histopathology results showed distant epitheliotrophic spread of atypical clear cells regarding the tumor. The epitheliotrophic cells were positive for cytokeratin (CK)19 and CK7 as odontogenic markers. These phenotypes were similar to those of tumor cells, suggesting pagetoid squamous cell proliferation associated with a PIOC arising. Although diagnosis of this condition is challenging, early detection is vital to ensure prompt treatment and improve patient prognosis.

Navigating controversies in primary intraosseous carcinoma: A comprehensive literature review concerning the odontogenic origin and diagnostic challenges.

Background: Primary intraosseous carcinoma is a rare neoplasm of odontogenic origin. The World Health Organization defines it as a squamous cell carcinoma (SCC), usually arises inside the jaw bones and having no connection with the oral mucosa. This lesion is documented with low incidence and unfavourable prognosis. PIOC occurred mainly in older age group with potent preference to males. In this study we presented this case to add that unusual clinical presentation of this lesion to the current literature. This case showed this malignant tumour commonly known for its unfavourable behaviour and aggressiveness documented with in unusual radiographic presentation that mimics periapical cyst.Case Presentation: An old-aged heavy smoker male patient was admitted to Cairo University dental hospital with a complaint of painful swelling in his right posterior area of the mandible, started 4 months ago. Intra-oral examination revealed a swelling in the lower right posterior area in relation to the non-vital lower molars. A panoramic x-ray showed a well-defined radiolucent lesion apically to roots of lower right posterior teeth. An incisional biopsy was performed and the microscopic examination was done. The final diagnosis was confirmed to be primary intraosseous carcinoma.Conclusion: Reporting this case could add to the existing literature about adding primary intraosseous carcinoma in list of D.D of any intrabony lesion regardless its size, extension and radiographic margins. This would help clinicians to early detection and improve survival rate of such affected patients.

Imaging findings in a case of primary intraosseous carcinoma arising from a mandibular cyst.

BackgroundDespite their rarity, malignant odontogenic tumors (MOT) represent an important group of oral lesions characterized by their variable clinical presentations and sometimes unexpected biological behavior.ObjectivesThe purpose of this retrospective cross-sectional study was to evaluate the number, types, and frequency of MOT and to investigate the relative rate of malignant transformation in recurrent odontogenic tumors (OT).MethodologyThe records of patients diagnosed with OT in the hospital of the Faculty of Dentistry, Cairo University, were reviewed over 10 years (2013-2022). The OT were investigated for frequency, age, gender, site, and recurrence. The data were recorded and then analyzed using SPSS software version 25.ResultsAmong 5543 oral excisions, 357 cases of them were OT, including 336 benign (94.1%) and 21 malignant neoplasms (5.9%). Among the odontogenic malignancies, 18 lesions (85.7%) appeared de novo, and 3 lesions (14.3%) developed as recurrent of previously classified benign tumors. A high incidence was observed in the middle and old age groups (90.4%) with a median age being 42. Slight male predilection (1.3:1) was noticed. The mandible was the highly affected site but all recurrent cases were diagnosed in the maxilla as ghost cell odontogenic carcinoma (n = 2, 66.6%) and primary intraosseous carcinoma (n = 1, 33.3%).ConclusionRetrospective analysis of the relative frequency of MOT and the documentation of the unusual recurrence of benign OT as a malignancy enhances our understanding of OT behavior and the need for appropriate therapy and clinical follow-up.

Primary Intraosseous Carcinoma (PIOC), NOS: Origin from cyst lining, immunohistochemical profile and review of the literature

Odontogenic tumors (OGTs), which originate from cells of odontogenic apparatus and their remnants, are rare entities. Primary intraosseous carcinoma NOS (PIOC), is one of the OGTs, but it is even rarer and has a worse prognosis. The precise characteristics of PIOC, especially in immunohistochemical features and its pathogenesis, remain unclear. We characterized a case of PIOC arising from the left mandible, in which histopathological findings showed a transition from the odontogenic keratocyst to the carcinoma. Remarkably, the tumor lesion of this PIOC prominently exhibits malignant attributes, including invasive growth of carcinoma cell infiltration into the bone tissue, an elevated Ki-67 index, and lower signal for CK13 and higher signal for CK17 compared with the non-tumor region, histopathologically and immunohistopathologically. Further immunohistochemical analyses demonstrated increased expression of ADP-ribosylation factor (ARF)-like 4c (ARL4C) (accompanying expression of β-catenin in the nucleus) and yes-associated protein (YAP) in the tumor lesion. On the other hand, YAP was expressed and the expression of ARL4C was hardly detected in the non-tumor region. In addition, quantitative RT-PCR analysis using RNAs and dot blot analysis using genomic DNA showed the activation of Wnt/β-catenin signaling and epigenetic alterations, such as an increase of 5mC levels and a decrease of 5hmC levels, in the tumor lesion. A DNA microarray and a gene set enrichment analysis demonstrated that various types of intracellular signaling would be activated and several kinds of cellular functions would be altered in the pathogenesis of PIOC. Experiments with the GSK-3 inhibitor revealed that β-catenin pathway increased not only mRNA levels of ankyrin repeat domain1 (ANKRD1) but also protein levels of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) in oral squamous cell carcinoma cell lines. These results suggested that further activation of YAP signaling by Wnt/β-catenin signaling may be associated with the pathogenesis of PIOC deriving from odontogenic keratocyst in which YAP signaling is activated.

This study aimed to determine the patterns of invasion of oral squamous cell carcinoma (OSCC) into the bucco-mandibular space (BMS) using detailed histopathological analysis and to assess clinical outcomes. Patients with OSCC who underwent segmental mandibulectomy or hemi-mandibulectomy combined with resection of the BMS between 2012 and 2021 were included. The invasions of the BMS were classified into three patterns. Pattern A was defined as a horizontal invasion, Pattern B as a vertical invasion, and Pattern C as an expansive invasion. In total, 109 patients were reviewed. Of these 109 patients, the primary tumor affected the lower gingiva in 78 patients, the buccal mucosa in 18 patients, and was a primary intraosseous carcinoma of the mandible in 13 patients. Invasion of the BMS was significantly associated with a higher pathological T stage, positive/close margins, and lower disease-free survival (DFS) rates. The DFS rates were 86.7% and 66.0% in the BMS non-invasion and invasion groups, respectively. The DFS rates for each type of invasion were 82.1% for Pattern A, 67.4% for Pattern B, and 48.0% for Pattern C (P=0.277). Patients with BMS invasion have a poorer prognosis than those without invasion of the BMS. Therefore, adjuvant therapy is necessary, especially in Patterns B and C. Evaluation of preoperative BMS invasion patterns is important for predicting the prognosis of OSCC.

Abstract Dentigerous cysts are among the most common cysts of the jaw. They are attached to the crown of an unerupted tooth, most frequently third molars and maxillary canines. They are often asymptomatic and may therefore be diagnosed late. We report a case of a primary intraosseous carcinoma arising from the wall of a dentigerous cyst and describe the expression of typical genes associated with tumour growth and prognosis. The tumour expressed cytokeratins (CK) 5/6, 8, 14 and 19, but not CK7. Ki‐67 and P53 were upregulated in dysplastic epithelium and tumour tissue. Although rare, the possibility for tumour development in the wall of a common cyst should be considered. The case emphasizes the importance of histopathological examination of surgical specimens, even if the clinical diagnosis seems obvious.

PRIMARY INTRAOSEOUS CARCINOMA - CASE REPORT

A rare case of primary intraosseous carcinoma of the mandible with perineural extension mimicking neurolymphomatosis on [18F]-FDG PET/CT.

To investigate the comparison of maximum and mean standardized uptake values (SUVs) of jaw pathologies with bone Single-photon emission computed tomography/computed tomography (SPECT/CT), and a special focus on medication-related osteonecrosis of the jaw (MRONJ). Eighty-nine patients with jaw pathologies (63 MRONJ, 13 chronic osteomyelitis, 11 osteoradionecrosis and 2 primary intraosseous carcinoma) underwent bone SPECT/CT scans acquisition at 4 h after intravenous injection of Tc-99m hydroxymethylene diphosphonate in this prospective study. The evaluation of mean and maximum SUVs of jaw pathologies were performed using Q. Metrix and Xeleris workstation and defined the data automatically. Statistical analyses were performed by Pearson's correlation coefficient for comparison of maximum and mean SUVs and Mann-Whitney U-test for SUVs of MRONJ. A P value lower than 0.05 was considered to indicate statistical significance. Maximum SUVs of MRONJ, chronic osteomyelitis, osteoradionecrosis and primary intraosseous carcinoma were 17.6 ± 8.4, 21.7 ± 7.1, 11.9 ± 4.8 and 26.6 ± 7.0, respectively. Mean SUVs of MRONJ, chronic osteomyelitis, osteoradionecrosis and primary intraosseous carcinoma were 10.1 ± 4.9, 11.9 ± 3.3, 7.0 ± 2.8 and 10.1 ± 4.5, respectively. The maximum SUV of jaw pathologies was significantly correlated with the mean SUV (Y = 0.494X + 1.228; R2 = 0.786; P < 0.001). Furthermore, maximum and mean SUVs of MRONJ had significant differences in underlying diseases, medication and staging. The maximum and mean SUVs with bone SPECT/CT can be an effective tool for the quantitative evaluation of jaw pathologies, especially MRONJ.

Malignant odontogenic tumors. A report of a series of 30 cases and review of the literature