Factors affecting the accuracy of anti-BRAF V600E immunohistochemistry results in ameloblastomas.

BACKGROUND: There are still some controversies about the results of anti-BRAF V600E-specific antibody immunohistochemistry in ameloblastomas. This study aimed to examine the accuracy of V600E-specific antibody immunohistochemistry in detection of BRAF V600E mutation in ameloblastoma tissue sections of different ages. METHODS: The BRAF V600E status of 64 ameloblastoma specimens was assessed using both Sanger sequencing and V600E-specific antibody immunohistochemistry, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. The difference in V600E-specific antibody immunohistochemistry staining intensity among the three groups of ameloblastoma tissue blocks of different ages was evaluated by chi-square test. The consistency between V600E-specific antibody immunohistochemistry and DNA sequencing results and the V600E-specific antibody immunohistochemistry staining intensity of 15 paired newly-cut and 3-month storage sections of the same 15 ameloblastomas were also compared. RESULTS: For detection of BRAF V600E mutation, the V600E-specific antibody immunohistochemistry had high sensitivity (98.21% 55/56), specificity (87.5% 7/8), positive predictive value (98.21% 55/56), and negative predictive value (87.5% 7/8). Heterogeneity of the staining intensity was observed in the same tissue section, but all or none expression pattern was noticed in the solid tumor nests. The storage time of paraffin tissue blocks ranging from 2 to 14 years did not affect the V600E-specific antibody-positive staining intensity. However, the three-month storage sections showed a significant diminishment of V600E-specific antibody-positive staining signals. CONCLUSIONS: The BRAF V600E-specific antibody immunohistochemistry is suitable for routine detection of BRAF V600E mutation in ameloblastomas. The all or none expression pattern suggests the BRAF V600E mutation may be an early event in the pathogenesis of ameloblastoma.

Enrichment of SOX2-Positive Cells in BRAF V600E Mutated and Recurrent Ameloblastoma.

Ameloblastoma is the most common benign odontogenic neoplasm, but with an aggressive behavior and a high recurrence rate. Nowadays wide surgical resection is the current recommended treatment, which can cause further loss of function and esthetics. Recent studies point to the stem/progenitor cells as both initiators and propagators of the tumors. Elucidation of the cellular and molecular mechanisms underlying the tumor stem cells is of broad interest for understanding tumorigenesis and for developing effective targeted therapies. SRY related HMG box gene 2 (SOX2) is a transcription factor that plays important roles in development, stem cell renewal, and cancer formation. Few studies have revealed increased SOX2 expression in atypical ameloblastoma and ameloblastic carcinoma. For the development of personalized medicine for ameloblastoma, biomarkers that provide prognostic or predictive information regarding a tumor's nature or its response to treatment are essential. Thus, in this study, we aimed to study if SOX2-positive cells exist in ameloblastomas and their correlation with the clinicopathologic parameters. Our data suggested BRAF(V600E) mutation might contribute to the expansion of SOX2-positive cells. The identification of BRAF(V600E) mutation and the amplification of SOX2-positive cells in ameloblastomas imply the possible benefit of applying BRAF and SOX2 inhibitors in recurrent and un-resectable ameloblastomas.

Retrospective analysis of primary intraosseous malignancies in mandible and maxilla in a population of Taiwanese patients.

BACKGROUND/PURPOSE: Due to the rarity and diversity of primary intraosseous malignancies in jawbones, we aimed to evaluate the clinicopathological features and discuss the findings of our collected cases with the literatures. METHODS: Twenty-nine patients (2000-2020) diagnosed with primary central malignancies of jawbones were selected from the database of Oral Pathology Department in our institution. Clinical features, radiographic appearance, and histopathological diagnosis of the 29 cases were analyzed. RESULTS: Twenty-nine patients aged between 19 and 84 years (average, 57.4 years) with a male to female ratio of 1.2:1 were included. The most frequent site was the mandibular body and ramus, followed by the posterior maxilla and mandibular symphysis. The most common diagnosis was osteogenic sarcoma (n = 13), followed by odontogenic carcinoma (n = 7), hematologic malignancies (n = 5), salivary gland malignancies (n = 2), and neurogenic sarcomas (n = 2). The most frequent symptoms were swelling, pain, paresthesia of lower lip, and mobile tooth. Radiographically, they usually presented as ill-defined osteolytic to osteoblastic lesions depending on the amount of ossification. Wide excision comprising partial maxillectomy and segmental mandibulectomy were the most common therapeutic methods. CONCLUSION: Despite the rarity of primary central malignancies in jawbones, the clinical features may mimic infectious process or benign lesions. Detailed history-taking, clinical and imaging examination and awareness of the patient's signs and symptoms combining with the histopathological inspection are important for early diagnosis and improved prognosis. The current data contributes a useful basis for clinical investigation regarding intraosseous malignancies occurring in the jawbones.

Clinical manifestations of oral lymphomas - Retrospective study of 15 cases in a Taiwanese population and a review of 592 cases from the literature.

BACKGROUND/PURPOSE: Due to the rarity of oral lymphoma (OL), we aimed to evaluate the clinical features of OL and discuss these findings in light of the literature. METHODS: English language literature (1980-2019) related to OL was searched in two electronic databases. Patients (2000-2019) diagnosed with OL were also selected from the database of the Oral Pathology Department in our institution. The clinical features, radiographic appearance, and histopathological diagnosis in these selected cases from publications and our institution were then analyzed. RESULTS: 607 cases of OL (15 in our institution and 592 from literature) in patients aged between 0 and 92 years (average, 51.8 years) with a male to female ratio of 1.6:1 were included. The most common diagnosis was diffuse large B-cell lymphoma (n = 205), followed by Burkitt lymphoma (n = 72) and T-cell lymphoma (n = 37). The most frequent site was the gingiva, followed by palate, maxilla, mandible, tongue and buccal mucosa. The most frequent symptoms were swelling, ulceration, paresthesia, mobile tooth and pain. Radiographic findings included ill-defined osteolytic lesion, thickening of the periodontal ligament, loss of lamina dura and tooth displacement. CONCLUSION: Despite the rarity of extranodal lymphomas in oral cavity, their occurrence may be part of disseminated disease. Detailed history-taking, clinical and imaging examination and awareness of the patient's signs and symptoms are important for early diagnosis and an improved prognosis. The current data form a useful basis for clinical investigation and teaching regarding lymphoma occurring in the oral cavity.

Non-calcifying Langerhans Cell Rich Variant of Calcifying Epithelial Odontogenic Tumor and Amyloid Rich Variant of Central Odontogenic Fibroma: A Unique Entity or a Spectrum?

Overlapping clinicopathological features of non-calcifying Langerhans cell rich variant of calcifying epithelial odontogenic tumor (NCLC-CEOT) and the amyloid rich variant of the central odontogenic fibroma (AR-COF) have been recognized recently. It is still under debate whether these two diseases are indeed one unique disease entity or belong to CEOT and COF, respectively. To clarify this issue, we have performed a literature review to compare the similarities and differences in clinicopathological features among NCLC-CEOT, AR-COF, classic CEOT, and classic COF. We aimed to investigate whether NCLC-CEOT and AR-COF might be the same and one distinctive disease entity, or a variant (or variants) of either CEOT or COF; or whether COF, NCLC-CEOT/AR-COF, and CEOT represented a histopathological spectrum of one disease. Our results indicate that NCLC-CEOT and AR-COF cases share many similar clinicopathological features. Thus, we suggest that they are the same disease entity. Due to nearly no reported recurrence of NCLC-CEOT/AR-COF cases, the conservative surgical treatment is appropriate. The NCLC-CEOT/AR-COF cases show some overlapping clinicopathological features with COF rather than the CEOT cases. However, differences in the clinicopathological features are still recognized among the NCLC-CEOT/AR-COF, COF, and CEOT cases. Future research, particularly molecular biological studies, may further elucidate their relationships and assist proper classification of the NCLC-CEOT/AR-COF cases.

Contemporary Molecular Analyses of Malignant Tumors for Precision Treatment and the Implication in Oral Squamous Cell Carcinoma.

New molecular tests and methods, in addition to morphology-based diagnosis, are widely used as a new standard of care in many tumors. "One-size-fits-all medicine" is now shifting to precision medicine. This review is intended to discuss the key steps toward to development of precision medicine and its implication in oral squamous cell carcinoma. The challenges and opportunities of precision medicine in oral cancer will be sequentially discussed based on the four steps of precision medicine: identification/detection, diagnosis, treatment and monitoring.

Clinicopathological study of 13 cases of intraoral soft tissue metastatic carcinomas.

BACKGROUND/PURPOSE: Oral metastatic carcinomas are rarely found in oral soft tissues. This study reported the clinicopathological features of 13 intraoral soft tissue metastatic carcinomas. MATERIALS AND METHODS: A total of 13 intraoral soft tissue metastatic carcinomas were included in this study. The clinicopathological features of the 13 cases including the primary cancer site, metastatic intraoral soft tissue region, clinical presentation, and histopathological diagnoses were examined and reported. RESULTS: The 13 intraoral soft tissue metastatic carcinomas occurred in 13 patients (11 males and 2 females) with a mean age of 59.4 (range, 39-78) years. Nine cases originated from the liver (69.2%), and one each from the colon (7.7%), pancreas (7.7%), thyroid (7.7%), and kidney (7.7%). The histopathological diagnoses of the metastatic lesions were hepatocellular carcinoma in 9 cases, adenocarcinomas in 2 cases (one each from the colon and pancreas), clear cell carcinoma of the kidney in one case, and follicular thyroid carcinoma in one case. The gingiva and alveolar mucosa were the major metastatic sites (10 cases, 76.9%), followed by the buccal mucosa (two cases, 15.4%), and soft palate (one case, 7.7%). Twelve metastatic lesions manifested as ulcerated, easy-bleeding, and pyogenic granuloma-like lesions. CONCLUSION: The results of our series of 13 cases indicate that intraoral soft tissue metastatic carcinomas have a male predilection with a male to female ratio of 11:2, are commonly found in the gingiva and alveolar mucosa (76.9%), present frequently as an easy-bleeding pyogenic granuloma-like lesion (92.3%). In addition, the most common primary cancer site is the liver.