Reticular Myxoid Odontogenic Neoplasm with Novel STRN::ALK Fusion: Report of 2 Cases in 3-Year-Old Males.

Odontogenic tumors represent a collection of entities ranging from hamartomas to destructive benign and malignant neoplasms. Occasionally, pathologists encounter gnathic lesions which clearly exhibit an odontogenic origin but do not fit within the confines of established diagnoses. Here, we describe two such odontogenic tumors, both affecting 3-year-old males. Each case presented as a destructive, radiolucent mandibular lesion composed of mesenchymal cells, some with unique multi-lobed nuclei, frequently arranged in a reticular pattern and supported by a myxoid stroma with focal laminations. Production of odontogenic hard tissues was also seen. Because of their unique microscopic features, both cases were investigated by next-generation sequencing and found to harbor the same STRN::ALK oncogene fusion. To our knowledge, these cases represent the first report of an odontogenic tumor with a STRN::ALK gene rearrangement. We propose the possibility that this neoplasm could be separate from other known odontogenic tumors. Both patients were treated with surgical resection and reconstruction. The prognosis of patients with this entity is currently uncertain but shall become more apparent over time as more cases are identified and followed.

Oral cancer: enduring characteristics and emerging trends.

Oral cancer is arguably the most serious condition that dental providers may encounter in their practice. The relatively poor prognosis associated with oral cancer highlights the importance of the dental team's awareness of the disease. While many characteristics of oral cancer have endured over time, new research is revealing trends that are changing the way we approach its screening, diagnosis and treatment. In this report, we provide a translational overview of oral cancer, including risk factors, signs and symptoms, clinical management, as well as our recent findings on the role of chronic inflammation in the development of the disease. In addition, our recent genetic profiling approach in both cancer cell lines and in patients has identified potential biomarkers, molecular pathways and therapeutic drugs for oral squamous cell carcinomas. This comprehensive review should be of interest to all dental professionals.

Odontogenic keratocyst: a case report and review of an old lesion with new classification.

The odontogenic keratocyst (OKC) is distinctive among jaw cysts given its tendency toward recurrence and aggressive clinical behavior. This paper presents a well-documented case of OKC and a review of the diagnostic features, treatment modalities and new evidence supporting the reclassification and renaming of this unique pathologic process.

Mandibular abnormalities in a patient with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by the presence of cutaneous neurofibromas, multiple cafd-au-lait spots and pigmented nodules of the iris known as Lisch nodules. In some cases, the diagnosis can be made at birth while in others the diagnosis is made later in life based on the appearance of additional criteria. We describe radiographic abnormalities of the mandible in a young adult male with NF1.

Pro-inflammatory genes as biomarkers and therapeutic targets in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a major health problem worldwide, and patients have a particularly poor 5-year survival rate. Thus, identification of the molecular targets in OSCC and subsequent innovative therapies are greatly needed. Prolonged exposure to alcohol, tobacco, and pathogenic agents are known risk factors and have suggested that chronic inflammation may represent a potential common denominator in the development of OSCC. Microarray analysis of gene expression in OSCC cell lines with high basal NF-κB activity and OSCC patient samples identified dysregulation of many genes involved in inflammation, wound healing, angiogenesis, and growth regulation. In particular IL-8, CCL5, STAT1, and VEGF gene expression was up-regulated in OSCC. Moreover, IL-8 protein levels were significantly higher in OSCC cell lines as compared with normal human oral keratinocytes. Targeting IL-8 expression by siRNA significantly reduced the survival of OSCC cells, indicating that it plays an important role in OSCC development and/or progression. Inhibiting the inflammatory pathway by aspirin and the proteasome/NF-κB pathway by bortezomib resulted in marked reduction in cell viability in OSCC lines. Taken together our studies indicate a strong link between inflammation and OSCC development and reveal IL-8 as a potential mediator. Treatment based on prevention of general inflammation and/or the NF-κB pathway shows promise in OSCCs.

Oral cancer: enduring characteristics and emerging trends.

Oral cancer is arguably the most serious condition that dental providers may encounter in their practice. The relatively poor prognosis associated with oral cancer highlights the importance of the dental team's awareness of the disease. While many characteristics of oral cancer have endured over time, new research is revealing trends that are changing the way we approach its screening, diagnosis and treatment. In this report, we provide a translational overview of oral cancer, including risk factors, signs and symptoms, clinical management, as well as our recent findings on the role of chronic inflammation in the development of the disease. In addition, our recent genetic profiling approach in both cancer cell lines and in patients has identified potential biomarkers, molecular pathways and therapeutic drugs (Velcade and Aspirin) for oral squamous cell carcinomas. This comprehensive review should be of interest to all dental professionals.

Microsecretory Adenocarcinoma of Salivary Glands: An Expanded Series of 24 Cases.

Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor with a characteristic histologic and immunophenotypic profile and recurrent MEF2C-SS18 fusions. Because only six cases of MSA have been published, its complete clinicopathologic spectrum is unclear, and its biologic behavior has not been documented. Here, we present an updated and expanded experience of 24 MSA cases. All cases of MSA were obtained from the authors' files. Immunohistochemistry for S100, SOX10, p63, p40, SMA, calponin, and mammaglobin was performed. Molecular analysis was performed by targeted RNA sequencing, SS18 break apart fluorescence in situ hybridization, and/or reverse transcriptase polymerase chain reaction for MEF2C-SS18 fusion. Clinical follow-up was obtained from medical records. A total of 24 MSA cases were collected, from 13 women and 11 men, ranging from 17 to 83 years (mean 49.5 years). The vast majority (23 of 24) arose in the oral cavity, with the palate (n = 14) and buccal mucosa (n = 6) as the most frequent subsites. Tumors showed consistent histologic features including: (1) microcystic tubules, (2) flattened intercalated duct-like cells, (3) monotonous oval hyperchromatic nuclei, (4) abundant basophilic luminal secretions, (5) fibromyxoid stroma, and (6) circumscribed borders with subtle infiltration. The tumors were very consistently positive for S100 (24 of 24), p63 (24 of 24), and SOX10 (14 of 14) and negative for p40 (0 of 21), calponin (0 of 12) and mammaglobin (0 of 16), while SMA (4 of 20) was variable. MEF2C-SS18 fusion was demonstrated in 21 of 24 cases; in the remaining 3 cases with insufficient RNA, SS18 break apart FISH was positive. Treatment information was available in 17 cases, all of which were managed with surgery only. In 14 cases with follow-up (1-216 months, mean 30), no cases recurred or metastasized. MSA is a distinct salivary gland neoplasm with remarkably consistent clinical, histologic, immunophenotypic, and genetic features that generally behaves in an indolent manner following surgery alone. These observations solidify MSA as a unique, low-grade salivary gland carcinoma that warrants inclusion in the next version of the WHO classification of head and neck tumors.

Black and Brown: Non-neoplastic Pigmentation of the Oral Mucosa.

Black and brown pigmentation of the oral mucosa can occur due to a multitude of non-neoplastic causes. Endogenous or exogenous pigments may be responsible for oral discoloration which can range from innocuous to life-threatening in nature. Physiologic, reactive, and idiopathic melanin production seen in smoker's melanosis, drug-related discolorations, melanotic macule, melanoacanthoma and systemic diseases are presented. Exogenous sources of pigmentation such as amalgam tattoo and black hairy tongue are also discussed. Determining the significance of mucosal pigmented lesions may represent a diagnostic challenge for clinicians. Biopsy is indicated whenever the source of pigmentation cannot be definitively identified based on the clinical presentation.

Oral Mycosis Fungoides: A Report of Three Cases and Review of the Literature.

Mycosis fungoides (MF) and Sézary syndrome are clonal T-cell proliferations that exhibit skin homing and represent the majority of cutaneous T-cell lymphomas. Early MF is a diagnostic challenge as both the clinical and microscopic features often mimic benign inflammatory conditions. Oral MF is very rare and has been associated in the past with advanced disease and a poor prognosis. Skin lesions are present for an average of > 6 years before oral involvement occurs. The clinical appearance is highly variable with tongue, palate and gingiva most often affected. We report 3 additional cases of oral MF, including one in which oral lesions are the initial disease presentation. Survival in patients presenting with oral MF is improving and can be attributed to advances in therapy.

Detection of human papillomavirus DNA in formalin-fixed, paraffin-embedded squamous papillomas of the oral cavity.

BACKGROUND: Squamous papillomas are exophytic proliferations of surface oral epithelium. Human papillomavirus (HPV) infection is widely accepted as the etiology of squamous papillomas however the virus cannot be detected in a significant percentage of lesions. MATERIAL AND METHODS: Using polymerase chain reaction (PCR), we tested 35 formalin-fixed paraffin-embedded (FFPE) squamous papillomas for the presence of HPV DNA. RESULTS: Six papillomas (17%) tested positive for HPV DNA; four contained HPV-6 and two contained HPV-11. Given that ß-globin DNA was only identified in half of the samples, DNA degradation appears to have significantly impacted the results. CONCLUSIONS: The results likely represent an underestimation of the true number of HPV-positive specimens in our study. Potential explanations for HPV-negative squamous papillomas include transient HPV infection, failure of the experiment to detect HPV if present, or the possibility that some lesions may not result from HPV infection. Key words:HPV, PCR, FFPE, papilloma, oral.

AAOMP case challenge: a pigmented lesion of the mandibular facial gingiva.

A 55-year-old white male was referred by his dermatologist for evaluation of an asymptomatic dark brown lesion on the mandibular facial attached gingiva.

Peripheral giant cell granulomas: a series of 279 cases.

OBJECTIVE: This study investigated the demographic, clinicopathologic, and histopathologic findings of lesions diagnosed as peripheral giant cell granuloma (PGCG) by the Louisiana State University Oral Pathology Biopsy Service from 1974 to 2011. STUDY DESIGN: Clinical, demographic, and histopathologic evaluation was completed for 279 cases. A follow-up questionnaire was mailed to all surgeons who performed these biopsies from 1990 to 2011. RESULTS: Of the 279 lesions, 58% occurred in the mandible, 44% occurred in the anterior portion of the arches, 83% were adjacent to teeth, 14% occurred in edentulous areas, and 2% were adjacent to implants. Average duration was 10.5 months, and the average size was 12.7 mm. The recurrence rate was 17.5%. Histopathologically, 78% of lesions extended to the base of the specimen, 50% exhibited ulceration, 41% contained calcifications, and 6% exhibited features overlapping with another pathologic entity. CONCLUSIONS: PGCG is a well-defined pathologic entity among reactive gingival lesions. Recurrent lesions were more likely to contain calcifications.

Slow-growing gingival mass.

OBJECTIVES: A 33-year-old woman presented with a slow growing palatal gingival mass. The clinical differential diagnosis included benign tumors and tumor-like lesions, including the pyogenic granuloma, peripheral giant cell granuloma, peripheral ossifying fibroma, giant cell fibroma, peripheral odontogenic tumors, and oral focal mucinosis. STUDY DESIGN: The lesion was excised and histopathological examination followed by immunohistochemical staining was carried out. RESULTS: The microscopic findings and the immunohistochemical reactivity was diagnostic for a nerve sheath myxoma. CONCLUSIONS: The clinical features, microscopic findings, immunohistochemistry, and the differential diagnosis including the relationship to the neurothekeoma are discussed.