Prolonged Hypophosphatemia and Intensive Care After Curative Surgery of Tumor Induced Osteomalacia: A Case Report.

Introduction: Rare FGF23-producing mesenchymal tumors lead to paraneoplastic tumor-induced osteomalacia (TIO) presenting with phosphate wasting, hypophosphatemia, chronic hypomineralization of the bone, fragility fractures and muscle weakness. Diagnosis of TIO requires exclusion of other etiologies and careful search for a mesenchymal tumor that often is very small and can appear anywhere in the body. Surgical removal of the tumor is the only definitive treatment of TIO. Surgical complications due to chronic hypophosphatemia are not well recognized. Case Description: The current case describes severe fragility fractures in a 58-year-old woman, who lost her ability to walk and was bedridden for two years. First, the initial diagnostic laboratory work-up did not include serum phosphorus measurements, second, the suspicion of adverse effects of pioglitazone as an underlying cause delayed correct diagnosis for at least two years. After biochemical discovery of hyperphosphaturic hypophosphatemia at a tertiary referral centre, a FGF23-producing tumor of the mandible was discovered on physical examination, and then surgically removed. Postoperatively, severe hypophosphatemia and muscle weakness prolonged the need for ventilation support, intensive care and phosphate supplementation. After two years of rehabilitation, the patient was able to walk short distances. The tumor has not recurred, and serum phosphate concentration has remained within normal limits during 3.5 years of follow-up. Conclusions: The case report illustrates knowledge gaps in the diagnostic work-up of rare causes of low bone mass and fragility fractures. Compared to other low phosphate conditions, surgical recovery from TIO-induced hypophosphatemia warrants special attention. Increased alkaline phosphatase concentration may indicate impaired postsurgical recovery due to prolonged hypophosphatemia, underlining the need for proactive perioperative correction of hypophosphatemia.

Gene polymorphism of interleukin-1 alpha and beta in keratocystic odontogenic tumors.

AIM AND BACKGROUND: Odontogenic keratocysts have a different growth mechanism and biologic behavior in comparison with more common dentigerous and radicular cysts. It was reclassified as keratocystic odontogenic tumor (KCOT). The proliferative activity of the epithelial cells of KCOT has a close relationship with tissue levels of interleukin-1 (IL-1). Moreover, IL-1 increases the expression of several matrix metalloproteinases in the fibroblasts of adjacent stroma and activates the osteoclastogenesis process. So it plays an important role in the activity, spread, and local aggressiveness of this tumor. Therefore, it seems that the gene polymorphism of the cytokines of the IL-1 family is influential in the pathogenesis of KCOT and the patients' susceptibility to disease. METHOD: A total of 38 blood samples of patients suffering from KCOT and 150 blood samples of healthy patients were assessed using PCR-SSP. The blood samples were assessed for the following polymorphisms: interleukin-1 alpha (-889) and interleukin-1 beta (-511). Following up the patients, we found six recurrent and one syndromic cases. FINDINGS: By comparing the case and control groups, we observed the significant dominance of allele T over C, and genotype TT over CC and CT in IL-1α, although no significant difference was seen in the allele frequency and genotypes regarding IL-1ß. CONCLUSION: The function of IL-1α has a significant relationship with KCOT. Its effective genotype associated with pathogenesis, growth, local invasion, and recurrence is TT.

[Maxilla-mandibular brown tumors as a first sign of parathyroid adenoma]. / Tumeurs brunes maxillomandibulaires révélant un adénome parathyroïdien.

OBJECTIVES: Through a novel observation of parathyroid adenoma revealed by brown tumors of the jaws and a review of the literature, the authors describe this rare mode of primary hyperparathyroidism discovery. MATERIAL AND METHODS: The patient was a 23-year-old woman who consulted for a recurrent tumefaction of the maxillary; histology showed reparative giant cell granuloma. RESULTS: The clinical examination found an osseous tumefaction in continuity with the zygomatic bone and a gingival tumefaction on the mandible symphysis. The radiological findings showed two osteophytic lesions: mandibular and maxillary. The phosphocalcic metabolism was disturbed and the parathormone rate was high. The etiologic search consisted of a MRI of the neck, which showed a mass behind the thyroid gland, suggesting a parathyroid adenoma. The diagnosis was confirmed at surgical exploration. After removal of this tumor, the blood calcium rate dropped sharply and the bone tumefaction progressively regressed. CONCLUSION: Brown tumors are a rare mode of parathyroid adenoma discovery, and the jaw location is exceptional. The diagnosis is based on the parathormone rate, and radiological exams generally find the etiology. Treatment is based on surgery of the parathyroid adenoma.

Tumor-induced osteomalacia: lessons learned.

Tumor-induced osteomalacia is a rare acquired metabolic disorder characterized by hypophosphatemia and inappropriately low serum levels of 1,25-dihydroxyvitamin D. Symptoms include chronic muscle and bone pain, weakness, and fatigue in association with a high risk of fragility fractures due to osteomalacia. The diagnosis is commonly delayed for years due to the nonspecific nature of the presenting symptoms, failure to include determination of serum phosphorus levels in blood chemistry testing, and difficulty in identifying the responsible tumor. The pathogenesis of tumor-induced osteomalacia involves tumor expression of fibroblast growth factor 23, a hormone that inhibits proximal renal tubular reabsorption of phosphate and down-regulates renal conversion of 25-hydroxyvitamin D to its active form, 1,25-dihydroxyvitamin D. The metabolic abnormalities may be partially or completely corrected with phosphate supplementation and calcitriol. A definitive diagnosis and treatment require excision of the responsible tumor.

Brown tumor of the mandible associated with secondary hyperparathyroidism: a case report and review of the literature.

Brown tumors are rare lesions that can develop in persistent cases of hyperparathyroidism (HPT). Therefore, identification of these lesions by diagnostic imaging is important during the follow-up of patients with HPT. This report describes a 45-year-old woman who developed HPT-induced brown tumors that appeared initially as an oral lesion. The diagnosis, treatment, and control of the disease--as well as the histopathological characteristics--are emphasized.

[Ampicillin and sulbactam concentrations in the irradiated mandible after oral squamous cell cancer]. / Untersuchungen zum Ampicillin/Sulbactam-Spiegel im bestrahlten Unterkieferknochen bei Patienten mit oralen Plattenepithelkarzinomen.

INTRODUCTION: Radiation therapy of the oral and maxillo-facial region increases the risk of an infected osteoradionecrosis (IORN) which is a severe complication. Therefore, perioperative antibiotics for the prophylaxis of ORN is a standard in clinical oncology. The combination therapy of ampicillin and sulbactam (Unacid) promises a good therapeutic and prophylactic outcome. PATIENTS: We compared the concentration of Unacid in bone and blood specimens of 22 irradiated patients. All patients were irradiated with 39.6 Gy prior to surgery. The specimens were obtained during the operation 3 weeks after the end of the radiation therapy. RESULTS: The concentration of ampicillin/sulbactam in the blood was 124.9/64.5 microg/ml. The bone specimens showed a concentration of ampicillin/sulbactam of 5.54/1.21 microg/g. The concentration of the antibiotic in the bone was three to four times lower than in non-irradiated patients. Nevertheless, this concentration exceeds the minimum inhibitory concentration for bacteria in the oral cavity such as streptcoccae (MHK90<0.25 microg/ml) or staphylococcae (MHK90=0.12-2.0 microg/ml). CONCLUSIONS: The results of this study suggest, that Unacid is an effective antibiotic in the prophylaxis of ORN in irradiated patients with head and neck tumors.

Ameloblastic carcinoma ex ameloblastoma of the mandible with malignancy-associated hypercalcemia.

Ameloblastoma is a rare, locally destructive, benign neoplasm of the jawbones, which arises from epithelium derived from the epithelial components of the developing tooth. Ameloblastic carcinoma is the term used to designate any ameloblastoma in which there is histologic evidence of malignancy in the primary tumor, regardless of whether it has metastasized. Most ameloblastic carcinomas are presumed to have arisen de novo, with few cases of malignant transformation of ameloblastoma being apparent. Hypercalcemia is the most common metabolic complication of malignancy. Although malignancy-associated hypercalcemia is often reported in association with other malignancies, it is exceedingly unusual in association with ameloblastoma, malignant ameloblastoma, or ameloblastic carcinoma. We describe a patient with multiple recurrences of ameloblastoma, with subsequent malignant transformation presenting with malignancy-associated hypercalcemia.

[Solitary plasmacytomas in the head area. Diagnostic and therapeutic considerations]. / Solitäre Plasmozytome im Kopfbereich. Diagnostische und therapeutische Erwägungen.

Based on two case reports the inherent problems of diagnosis and treatment of this rare tumor are discussed. The importance of a complex immunohistologic and immunochemical analysis of the monoclonal immunoglobulin produced by the tumor is emphasized. Determining the serum level of the immunoglobulin is decisive for establishing the necessary treatment strategy. Apart from the tumor-specific aftercare by a specialist, these patients always require additional treatment at an immunology clinic.

Vitamin D resistant hypophosphatemic osteomalacia associated with osteosarcoma of the mandible: report of a case.

A case of vitamin D resistant hypophosphatemic osteomalacia associated with osteosarcoma of the mandible is presented. The patient complained of lumbar, knee and foot pain and muscle weakness of two years' duration. Serum phosphorous was 1.0-1.6 mg/dl, tubular reabsorption of phosphorus was 47 to 58%, TmPO4/GFR was o.7-1.2 mg/dl. Aminoaciduria was noted. Bone biopsy confirmed the diagnosis of osteomalacia. He partially responded to the treatment with 1 alpha()H) D3 and sodium phosphate. After removal of sarcoma of the mandible, symptoms remitted and pertinent laboratory data became normal except serum alkaline phosphatase for more than one year without treatment. It is suggested that an impaired response of the tubule and bone to active vitamin D3, caused in some way by the osteosarcoma might be one of the causes of osteomalacia in this case.