Osteosarcoma of the Mandible in a Patient with Florid Cemento-Osseous Dysplasia and Li-Fraumeni Syndrome: A Rare Coincidence.

Cemento-osseous dysplasia (COD) is the most common benign fibro-osseous lesion of the jaws and generally considered non-neoplastic and self-limited. Here, we present a 30-year old female who noticed a bilateral swelling of her posterior mandible with irregular periapical mineralization and incomplete root resorption on panoramic radiographs. A biopsy revealed florid COD and no further treatment was initiated. 9 years later, she presented with a progressive expansion of her left posterior mandible after being treated for bilateral breast cancer 4 and 8 years before. CT scans showed expansile and densely mineralized lesions in all four quadrants with the left posterior mandible showing a focal penetration of the buccal cortical bone. Biopsies revealed an osteoblastic high-grade osteosarcoma in the left and a COD in the right mandible, notably with cellular atypia in the spindle cell component. The patient underwent segmental resection of the left mandible with clear margins and adjuvant chemotherapy. Subsequent genetic testing identified a heterozygous germline TP53 mutation (p.V173G) which confirmed the clinically suspected Li-Fraumeni syndrome (LFS). 3 years after the resection, the patient is free of disease and the other foci of COD remained stable in size on follow-up imaging analyses. Our case illustrates LFS-related osteosarcoma developing within florid COD. Given the rarity of this coincidence, a causative relation between the two lesions seems unlikely but in patients with tumor predisposition syndromes it might be advisable to closely monitor even benign lesions like COD.

Macrophages and bisphosphonate-related osteonecrosis of the jaw (BRONJ): evidence of local immunosuppression of macrophages in contrast to other infectious jaw diseases.

OBJECTIVES: Bisphosphonates (BIP) are well established in bone diseases. A serious side effect is the bisphosphonate-related osteonecrosis of the jaw (BRONJ). Among different aetiology factors, local suppression of immune functions is gaining interest. The aim of this study was to analyze the function of macrophages in BRONJ in contrast to patients with osteoradionecrosis (ORN) and secondary chronic osteomyelitis (OM) of the jaws. Samples were also taken from patients with bisphosphonate medication (BP) without signs of infection, radiation therapy (RA), and osteoporosis (OP) as controls. MATERIAL AND METHODS: One hundred five patients with surgery to the jaw were included in this study: 33 patients with BRONJ, 17 with ORN, 11 with secondary chronic OM, 8 with RA, 25 with BP medication and 11 with OP. Samples were histologically analysed and monocytes/macrophages stained using CD14 and CD68. The number of positively marked cells was counted per view (pv), and the CD68/CD14 ratio was calculated. Statistically, the Naïve-Bayes and decision-tree classifier were used. RESULTS: The number of CD14 positive cells was 10.3 cells/pv in the BRONJ-group in as compared to 5 in the ORN- and 3.8 in the OM-group respectively. The number of CD68 positive cells was 11.4/pv (BRONJ-group) as compared to 14/pv (ORN-group) and 12.7/pv (OM-group). With 0.89, the BRONJ-group showed a statistically different CD68/CD14 ratio than ORN-group with 3.39 and OM-group with 3.03. CONCLUSIONS: Our results indicate a different expression of CD14 and CD68 markers of monocytes/macrophages in BRONJ as compared to other jaw infections. This could be a sign of macrophage immunosuppression by BPs. In contrast, patients receiving BP medication without BRONJ showed no differences to other controls. CLINICAL RELEVANCE: This is the first study that clinically indicates a compromised macrophage function at BRONJ sites in contrast to ORN or secondary OM sites. The BRONJ itself could be forwarded by this effect.

Relevance of a prolonged preoperative antibiotic regime in the treatment of bisphosphonate-related osteonecrosis of the jaw.

PURPOSE: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe and therapy-resistant disease. The present study was performed to evaluate the role of the duration of preoperative antibiotic therapy within an otherwise standardized treatment protocol of patients with BRONJ stages I and II. One group of patients received a short-term preoperative antibiotic regime (A-ST) and the other a long-term preoperative antibiotic regime (B-LT). PATIENTS AND METHODS: A retrospective chart review was used to analyze 46 patients with BRONJ from 2004 to 2009 who were treated with the same surgical technique and the same postoperative antibiotic treatment. Ten patients were classified as stage I, and 37 as stage II. All patients had intravenous bisphosphonate therapy in their case histories. Surgical treatment included an extended surgical procedure with sequestrectomy, bone smoothing, tension-free tissue covering, and drainage, with attention to neighboring teeth. After surgery, antibiotics were given (median) for 7 days intravenously and orally for another 10 to 12 days. Only patients who fulfilled these criteria were included in the retrospective chart review. In group A-ST 16 patients with 17 operations received antibiotics for 1 to 8 days before operation, whereas in group B-LT 30 patients had preoperative therapy of 23 to 54 days. Postoperative clinical examination followed a standardized protocol. Complete healing with intact soft tissue coverage was regarded as a success. RESULTS: The mean follow-up in both groups was 17.4 months (median, 11.5 months). Within the overall observation period, only 35% of patients in group A-ST and 70% in group B-LT showed complete healing, but at the time of the last clinical examination, 53% in group A-ST and 87% in group B-LT were free of soft tissue dehiscence. A certain number of soft tissue dehiscences within the observation period could clearly be related to later tooth extractions or pressure sores of dentures; excluding these interfering problems, 47% in group A-ST and 87% in group B-LT were treated successfully. Differences between these groups were significant. CONCLUSIONS: This study indicates that surgical treatment in patients with stage I BRONJ and especially in those with stage II BRONJ in combination with a long-term preoperative antibiotic treatment can lead to a complete healing in 70% to 87% of cases in contrast to 35% to 53% with a short-term regime. The higher success rate after prolonged preoperative antibiotic therapy may be linked to an infectious role in BRONJ etiology requiring adequate treatment. Antibiotics may effectively treat neighboring lightly infected bone, whereas surgery removes the irreversibly infected and necrotic bone. To achieve complete healing, an extended surgical procedure in combination with local mouth rinses and prolonged antibiotic therapy can be recommended for treatment of BRONJ.

Sunitinib may raise the risk of bisphosphonate-related osteonecrosis of the jaw: presentation of three cases.

OBJECTIVE: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of bisphosphonate (BP) medication. Tooth extractions are the most frequent causes for BRONJ. In some cases BRONJ is observed spontaneously, with some anatomic sites carrying a higher risk. Sunitinib, a tyrosine kinase inhibitor, is established in renal cell carcinoma and is known to lead to oral mucositis as a side effect, which in BP patients may additionally raise the risk of BRONJ. STUDY DESIGN: We present 3 patients with renal cell carcinoma under BP medication who developed BRONJ during and after sunitinib medication. RESULTS: In 2 patients, BRONJ was linked to the occurrence of mucositis after sunitinib intake. The third patient showed relapse of completely healed BRONJ lesions shortly after resumption of a sunitinib therapy. CONCLUSIONS: Oral mucositis during chemotherapy may raise the risk of BRONJ in cancer patients with BP medication. Especially in renal cell carcinoma patients under sunitinib therapy and intravenous BP medication, oral mucositis should be observed closely because it could be a risk factor for BRONJ.

Importance of microcracks in etiology of bisphosphonate-related osteonecrosis of the jaw: a possible pathogenetic model of symptomatic and non-symptomatic osteonecrosis of the jaw based on scanning electron microscopy findings.

The aim of this study was to evaluate a possible role of microcracks in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (ONJ) and to discuss an etiological model. Bone samples from 35 patients with ONJ were analyzed. Control samples were taken from five patients with osteomyelitis (OM), ten patients with osteoradionecrosis, seven patients with osteoporosis and bisphosphonate medication without signs of ONJ, and six osteoporotic elderly patients. Samples were examined using scanning electron microscopy. In 54% of the bone samples of patients with ONJ, microcracks were seen. Inflammatory and connective tissue reactions within the microcracks were evident in 82% of the cases, indicating that these cracks were not artificial. In contrast, only 29% of samples from patients with oral bisphosphonate medication without ONJ, no sample from patients with OM, none of the osteoradionecrosis group, and only 17% from patients with osteoporosis showed microcracks. Statistically significant differences could be found between the ONJ group and the group after irradiation and the group with OM, respectively. The evidence of microcracks could be a first step in the pathogenesis of bisphosphonate-related ONJ. The accumulation of these microcracks leads to a situation that could be named "non-symptomatic ONJ". Disruptions of the mucosal integrity may then allow bacterial invasion, leading to jawbone infection with exposed bone, fistulas, and pain. This state could be called "symptomatic ONJ". Furthermore, an assumed local immunosuppression as indicated by various studies could explain the severe courses of therapy-resistant ONJ as regularly observed.

Bilateral cystic pulmonary glial heterotopia and palatinal teratoma causing respiratory distress in an infant.

We report on a male infant with extensive, bilateral cystic and solid lung lesions who presented postnatally with respiratory distress caused by bilateral cystic lung lesions. Parenchyma-sparing resections were performed. Histology revealed the presence of neuroglial cell-lined cysts and glial nodules. In addition, a neural element containing palatinal teratoma was detected and excised. Based on previously published cases, the pathogenesis and clinical features of pulmonary neuroglial heterotopia are discussed.

The incidence of Frey's syndrome.

AIMS: The incidence of Frey's syndrome after parotidectomy greatly varies in the literature. The aim of this study was to analyse the incidence with the help of a new series of patients and to discuss and review the results. PATIENTS: 372 patients (age: 50.7+/-11.6 yrs) underwent unilateral parotidectomy. In 203 subjects the insertion of a sternocleidomastoideus flap in the parotid area was performed intraoperatively. METHODS: Patients were followed-up concerning the clinical presence of gustatory sweating and flushing after secretory stimulation, and were questioned about suffering in everyday life. RESULTS: 86 patients (23.5%) developed Frey's syndrome after an average of 12 months (12.3+/-9.9 months) following parotidectomy. Only 44% of the patients with Frey's syndrome were symptomatic. No benefit concerning Frey's syndrome following application of a sternocleidomastoideus flap was seen. CONCLUSION: Gustatory sweating after parotidectomy must still be regarded as an unpleasant and common complication. Nevertheless, it is more the subjective suffering of the patients than the incidence that makes prevention important.

[Rare case of an infiltration and invasion of a dental root by a mucosal melanoma of the oral cavity]. / Seltener Fall einer Zahnwurzelinfiltration durch ein metastasierendes malignes Melanom der Mundhöhle.

Malignant melanoma of the oral cavity is a rare disease with high lethality, rapid progression and frequently seen lymph node metastases. The clinical appearance of the mucosal melanoma is mostly irregular in shape and dark blue, brown or black in colour. During early stages the lesions are painless with a tendency to spontaneous bleeding. Mucosal melanoma shows expansive and infiltrative growth into neighbouring structures, with the result of bone destruction and loss of teeth. We present a case of a female patient with a primary mucosal melanoma. A local infiltration and invasion of a tooth could be seen. Although many publications deal with oral mucosal melanoma with local destruction of bone, there are no reports on an infiltration into dental roots. Aspects of this unusual infiltration of hard tissues are discussed.

Reconstruction of the temporal contour for traumatic tissue loss using a CAD/CAM-prefabricated titanium implant-case report.

INTRODUCTION: A 16-year-old Arab boy had suffered from a severe head injury including an intracranial haematoma. Despite replantation of the bone flap later on, the cosmetic result was very unfavourable due to partial resorption of the reinserted bone and atrophy of the right temporalis muscle. AIM: For contour reconstruction of both soft and hard tissues the boy was transferred from Saudi Arabia. METHOD: A spiral CT was obtained and the contour was reconstructed using a new algorithm for surface generation. RESULT: The resulting titanium implant was inserted without complications or the need for revision. The cosmetic result was good and corresponded to the preoperative digital planning. CONCLUSION: Techniques of computer-assisted implant prefabrication and surgery may include special algorithms for considering soft tissues including contour deficits of the temporalis muscle.

Performance of functionally graded implants of polylactides and calcium phosphate/calcium carbonate in an ovine model for computer assisted craniectomy and cranioplasty.

Biodegradable functionally graded skull implants on the basis of polylactides and calcium phosphate/calcium carbonate were prepared in an individual mould using a combination of different processing techniques. A geometrically corresponding resection template was designed to enable a craniectomy and cranioplasty with the prepared implant in the same operation. After various preliminary experiments concerning degradation kinetics, pH evolution during degradation, micromorphology, biocompatibility tests in human osteoblast cell cultures and surgery of cadaver heads, a new large-animal model was developed for long-term in vivo studies. In eight 12-months-old sheep, the surgical templates were used to create 4.5 x 5 cm(2) calvarial defects which were then filled with the corresponding degradable implants in the same operation. The animals were sacrificed after 2, 9, 12 and 18 months, and the implants and the surrounding tissues were analysed by computer tomography (CT), macroscopic examination and microscopy. The new animal model proved to be reliable and very suitable for large individual craniectomies and cranioplasties. The formation of new bone from the dural layer of the meninges corresponded well to the degradation of the porous inner layer of the implants whereas the skull contour was stabilised by the compact outer layer over the follow-up period.

Geometrically structured implants for cranial reconstruction made of biodegradable polyesters and calcium phosphate/calcium carbonate.

The aim of this study was the development of a processing pathway for manufacturing of biodegradable skull implants with individual geometry. The implants on the basis of polylactide and calcium phosphate/calcium carbonate were prepared by a combination of hot pressing and gas foaming. On the inside, the implant consists of a macroporous and faster degradable material (poly(D,L-lactide)+CaCO3) to allow the ingrowth of bone cells. The pore size is in the range of 200-400 microm. On the outside, the implant consists of a compact and slower biodegradable material (poly(L-lactide) and calcium phosphate) to ensure mechanical stability and protection. To overcome problems like inflammatory reactions caused by acidic degradation products of polylactide, the polyester was combined with basic filling materials (calcium salts). The filler neutralises the lactic acid produced during polymer degradation and increases the bioactivity of the material. The stabilised pH was demonstrated by long-term in vitro pH studies. Over a time period of 250 d in demineralised water, the pH was in the physiological range. The in vitro biocompatibility was shown by cell cultures with human osteoblasts. A good proliferation of the cells was observed over the whole test period of 4 weeks.

Intracerebral abscess after abutment change of a bone anchored hearing aid (BAHA).

OBJECTIVE: Brain abscesses are life-threatening and sometimes difficult to detect. A brain abscess after placement, manipulation of a bone anchored hearing aid, or a periauricular implant for fixation of an ear prosthesis has never been reported in the literature. PATIENT: A 42-year-old man suffered from a right-sided temporodorsal brain abscess after change of a bone anchored hearing aid abutment. The fixture itself had been inserted 8 years before without any complications in the peri- or postoperative period. A CT-guided puncture of the abscess could be performed via the screw-hole in the temporal bone after removal of the fixture, and the patient was treated with antibiotics. RESULTS: The outcome of the procedure was good without neurologic deficits for the patient. CONCLUSION: The insertion of periauricular screw implants bears the risk of meningeal lesions as well as a small risk of purulent intracranial and intracerebral complications perioperatively or in the context of later manipulations. Minimally invasive therapy of such brain abscesses can be performed by removal of the foreign body, CT-guided puncture, and antibiotic medication.

Microsurgical tissue transfer for rehabilitation of the patient with cleft lip and palate.

OBJECTIVE: Three case reports of microsurgically revascularized tissue transfer for secondary closure of complex oronasal fistulae in cleft lip and palate patients are reported. One scapular and two radial forearm flaps were used in that respect; the scapular flap was transferred without a skin paddle and was left for secondary epithelialization whereas iliac crest bone was transplanted in the two patients with the forearm flaps in a further surgical step. CONCLUSIONS: These microsurgical flaps represent solutions in selected cases of oronasal fistulae in patients with cleft lip and palate with extensive scarring, large defects, or both. Alternative free flaps of the vast spectrum available today, however, also deserve consideration.

Microsurgical tissue transfer and individual computer-aided designed and manufactured prefabricated titanium implants for complex craniofacial reconstruction.

From 1994 to 2000 187 individual computer-aided designed and manufactured (CAD/CAM) prefabricated titanium skull implants were inserted at 37 clinical centres. Since the processing chain of construction and fabrication of implants has become routine the clinical success totally depends on the condition of the soft tissues at the recipient site. In three patients in our own department with a history of up to 18 surgical interventions, and additional previous irradiation in one case, these conditions were so bad that a microsurgical tissue transfer had to be made before insertion of the implant. A latissimus dorsi free flap with submandibular microsurgical anastomosis had to be used in all three cases. However, the aetiology of the soft tissue deficits differed, and they were at a different tissue level in each case: anterior skull base, subcutaneous temporal area, and frontoparietotemporal skin. This series of patients therefore demonstrates the variability of possible combinations, which also require special timetables and principles of construction of the CAD of the implant. In all cases the cranioplasties were done three to five months after the transfer of the flaps and fulfilled the criteria of greatest precision and the best possible aesthetic outcome with minimal stress for the patients. These applications are surgical strategies for extreme cases but also illustrate the elaborate interdisciplinary approach in Computer Assisted Surgery.

Purulent pansinusitis, orbital cellulitis and rhinogenic intracranial complications.

Objectives: Acute pansinusitis is rarely seen in the maxillofacial surgery field, but often occurs in combination with orbital and intracranial involvement. Clinically this entity is of great importance, since it represents a severe disease with possibly disastrous consequences. Patients: Aetiology, diagnosis and therapy of acute pansinusitis and its complications were analysed in 36 patients treated surgically from 1987 to 1996. Results: Eighteen patients were aged between 3 and 21-years-old. Only eight suffered from pure pansinusitis, and three of an isolated purulent orbital infection. Of these 25 patients 20 had (pan-)sinusitis with orbital, three with intracranial, and two with both orbital and intracranial complications. Intracranial involvement included meningitis, empyema and brain abscess. Aetiology was rhinogenic in 26, odontogenic in six patients, and traumatic in two cases. Radiological work-up included conventional radiographs and CT in most cases, MRI was only used with special indications. Microbiological examination detected single or multiple species of micro-organisms with equal frequency. If multiple species were found, infection was mostly aerobic/anaerobic in combination. Conclusion: These purulent processes, frequently seen in young patients, require immediate surgical intervention and drainage with elimination of the cause of the disease if possible. Cooperation with other specialities is essential depending on the spread of the disease. In spite of the threatening acute symptoms, severe courses of disease or permanent defects should be avoidable. Copyright 2001 European Association for Cranio-Maxillofacial Surgery.