ABSTRACT
In 2011, the American Dental Association Council on Scientific Affairs released an update by their expert panel on managing the care of patients receiving antiresorptive therapy for the prevention and treatment of osteoporosis. In this report, the panel found no study results that confirmed the effectiveness of drug holidays to prevent antiresorptive agent-induced osteonecrosis of the jaws without increasing the risks of low bone mass. The purpose of this article is to provide suggestions for a pattern of patient care for individuals who desire or require an invasive surgical procedure of the jaws, but who also have a skeleton that is at risk for osteoporotic fracture. The authors reviewed pertinent literature related to basic bone histology, the pharmacokinetics of the aminobisphosphonates (nBP), diagnostic criteria for osteopenia/osteoporosis, and clinical applications of the antiresorptive agents. The skeletal system demonstrates a mixture of resting surfaces (osteocytes, 85%), resorbing surfaces (osteoclasts, 2%), and forming surfaces (osteoblasts, 10%-12%). Deposition of nBP is not uniform, and is highly concentrated in areas of bone remodeling. A full understanding of bone remodeling and the pharmacokinetics of nBP allow for the modification of the antiresorptive therapy and the timing of the oral surgical procedure in a manner that minimizes the prevalence of osteonecrosis while at the same time continuing to protect the patient's skeleton from osteoporotic fracture. The lack of support for drug holidays by the ADA's expert panel is strongly consistent with the science behind bone remodeling and nBP pharmacokinetics. In spite of this, creative interdisciplinary patient care has the potential to dramatically reduce the prevalence of bisphosphonate-related osteonecrosis (BRON), while at the same time continuing to protect the skeleton of the osteoporotic patient. Creative interdisciplinary patient care may prove to be an effective intervention to reduce the prevalence of BRON of the jaws.
Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Bone Density Conservation Agents/therapeutic use , Dental Care for Chronically Ill , Diphosphonates/therapeutic use , Aged , Bisphosphonate-Associated Osteonecrosis of the Jaw/diagnosis , Bone Density Conservation Agents/pharmacokinetics , Bone Diseases, Metabolic/drug therapy , Bone Remodeling/physiology , Dental Pulp Diseases/therapy , Denture, Partial, Fixed/adverse effects , Diphosphonates/pharmacokinetics , Etidronic Acid/analogs & derivatives , Etidronic Acid/therapeutic use , Female , Follow-Up Studies , Humans , Mandibular Diseases/diagnosis , Oral Surgical Procedures/methods , Osteoblasts/physiology , Osteoclasts/physiology , Osteocytes/physiology , Osteoporosis/drug therapy , Patient Care Planning , Patient Care Team , Risedronic Acid , Root Caries/therapy , Tooth ExtractionSubject(s)
Adenocarcinoma/diagnosis , Carcinoma/diagnosis , Oropharyngeal Neoplasms/diagnosis , Palatal Neoplasms/diagnosis , Adenocarcinoma/pathology , Adult , Carcinoma/pathology , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Oropharyngeal Neoplasms/pathology , Palatal Neoplasms/pathology , Palate/pathologySubject(s)
Carcinoma, Mucoepidermoid/diagnosis , Carcinoma, Squamous Cell/diagnosis , Gingival Neoplasms/diagnosis , Palatal Neoplasms/diagnosis , Aged , Carcinoma, Mucoepidermoid/pathology , Carcinoma, Squamous Cell/pathology , Diagnosis, Differential , Gingiva/pathology , Gingival Neoplasms/pathology , Humans , Male , Middle Aged , Palatal Neoplasms/pathology , Palate/pathologyABSTRACT
BACKGROUND: GLI1 is a transcription factor protein that has recently gained recognition in a morphologically distinct group of epithelioid soft tissue tumors characterized by GLI1 fusions or amplifications. The head and neck region, particularly the tongue, is a common location for GLI1-altered tumors. DDIT3 break apart fluorescence in situ hybridization (FISH), commonly used to identify translocations in myxoid/round cell liposarcoma, has been used as a surrogate test to detect both fusions and amplifications of the 12q13.3 region encompassing DDIT3 and GLI1 gene loci. METHODS: We herein report 5 cases of GLI1-altered soft tissue tumors. Three arose in the oropharynx (base of tongue/vallecula, tonsil) and two arose in the tongue. Given the frequent oropharyngeal location and epithelioid morphology, p16 immunohistochemistry was performed on cases with available material. Commercially available DDIT3 break apart FISH, custom GLI1 specific FISH, and RNA sequencing were performed on select cases. RESULTS: Two cases showed amplification using DDIT3 FISH which was confirmed using GLI1 specific FISH. The remaining cases harbored ACTB::GLI1, one of which showed rearrangement of the 12q13.3 region by DDIT3 FISH with absence of amplification by GLI1 specific FISH. STAT6 immunoexpression was positive in the GLI1-amplified cases and negative in the GLI1-rearranged cases while MDM2 expression was positive in the 4 cases tested. CDK4 expression was strong and diffuse in the GLI1-amplified cases. p16 immunohistochemistry showed strong nuclear and cytoplasmic staining in 50-70% of tumor cells in all four tested cases. CONCLUSION: Here we show that GLI1-altered soft tissue tumors are frequently positive for p16 and can occur in tonsillar regions of the oropharynx. As such, positive p16 immunohistochemistry alone cannot be used as evidence for the diagnosis of HPV-related squamous cell carcinoma as strong and diffuse p16 expression may also occur in GLI1-altered soft tissue tumors. Commercially available DDIT3 break apart FISH, which is readily available in many cytogenetic laboratories, may be useful as a sensitive surrogate test for GLI1 fusions and amplifications.