Consolidation of Tumorous Mandibular Ramus Defect During Denosumab Treatment for Rapidly Progressive Metastatic Breast Cancer.

BACKGROUND: Pharmacological inhibition of osteoclast activity is an essential component of oncological therapy for patients with bone metastases. In rare cases, medication-related osteonecrosis of the jaws (MRONJ) is observed. MRONJ can cause bone defects not inferior to primary or metastatic jaw neoplasms. Oral examination of patients on osteoclast-inhibiting medication aims to identify risk factors at an early stage and to initiate therapy. The current focus on osteoclast-inhibiting drugs in the maxillofacial region is MRONJ. Effects of the substances other than MRONJ are rarely reported. CASE REPORT: The female patient with metastatic breast cancer had developed extensive osteolysis of the mandibular ramus at the time of initial diagnosis. The patient was treated with denosumab. Seven months later, a significant reduction in the mandibular osteolytic zone was recorded. However, known bone metastases from other sites had increased in size during multimodal therapy, and further metastases were recorded. CONCLUSION: Jaw metastasis can shrink under denosumab therapy.

Osteosarcoma as a second neoplasm after chemotherapeutic treatment of hereditary retinoblastoma: a case report.

Osteosarcoma is the most common second neoplasm in patients with retinoblastoma. The risk of occurrence of second neoplasm after retinoblastoma increases after radiotherapy and chemotherapy. A case is presented of an 11-year-old girl who had painless swelling on the left side of her face for 8 days. The patient was asymptomatic before the onset of the swelling. Biopsy of the lesion revealed tumor cells forming trabeculae of osteoid and woven bone interspersed with myxoid and cartilaginous areas. The tumor cells showed pleomorphism and hyperchromatism with increased and abnormal mitotic figures consistent with the diagnosis of osteosarcoma. Further investigations revealed no history of retinoblastoma in the family. (This case was considered hereditary, however, because of the occurrence of the second neoplasm.) To the best of our knowledge, this is the first case of mandibular osteosarcoma occurring after unilateral retinoblastoma treated with chemotherapy.

Morphological changes of epithelial rests of Malassez in rat molars induced by local administration of N-methylnitrosourea.

The objective was to examine the possibility that epithelial rests of Malassez can give origin to odontogenic tumours. A mixture of N-methylnitrosourea (MNU) and alginate impression material for dental use was injected onto the periosteum of the buccal side of the left mandible of 5-week-old, male Wistar rats (300 mg/kg body wt). The mixture was left at the site for several months. The rats were killed 1, 3, 5, and 8 months after the injection. After 5 and 8 months, the epithelial rests of Malassez in the cervical and bifurcational regions of the first, second, and third left mandibular molars were significantly enlarged and the alveolar bone around the lesion was resorbed by multinucleated cells in all rats. The epithelial masses were characterized by enamel organ-like structures, deposition of eosinophilic amorphous material, duct-like structures, and squamous metaplasia. In addition to these masses in the molar regions, odontogenic tumours were induced in the incisal region and carcinomas and sarcomas in the buccal region, knee, bladder, and skin. Local administration of a mixture of MNU and alginate impression material can induce odontogenic tumours from the epithelial rests of Malassez at high incidence.

Experimental odontogenic tumors produced by ethylnitrosourea injections and mechanical injuries.

The present study was carried out to investigate odontogenic tumor induction in the rats by injections of carcinogen N-ethyl-N-nitrosourea (ENU) coupled with incisional wounds. The animals which received local injections of ENU in the region of incisor tooth germ of the right mandible every other day for 19 days after birth coupled with incisional wounding in the same region at 2 and 8 days, developed odontogenic carcinomas. However, the animals which were given local injections of ENU in the region of incisor tooth germ but did not receive incisional wounds, showed no pathologic changes. The animals which received both local injections of physiologic salt solution and incisional wounds in the same manner as mentioned above, did not exhibit any pathologic changes. The present results indicate that local administration of carcinogen ENU coupled with mechanical injuries, namely incisional wounding, caused the production of odontogenic carcinomas in the incisor region of the mandible in rats.

Evaluation of the carcinogenic risk of the phenoxyherbicide MCPA to an urodele amphibian.

To evaluate the carcinogenic potential of the phenoxyherbicide 2-methyl-4-chlorophenoxy-acetic acid (MCPA) in the crested newt, Triturus cristatus carnifex, a long-term study has been carried out exposing the animals by the percutaneous route. Two hundred adult newts were divided into one control and three experimental groups of 20 females and 30 males each. The control group was kept in tap water and the experimental groups were kept for 4 days a week in an aqueous solution of Agroxone 3, a commercial formulation of MCPA, at concentrations equivalent to 100, 200, and 400 ppm of the active ingredient. Treatment was continued for 1 year, after which all the animals were kept under observation for approximately another year. Surviving female newts were killed 22-24 months after the beginning of experimentation, whereas the male newts were killed after 28 months, at the end of 18 weeks of exposure to the tumour promoter 12-O-tetradecanoylphorbol-13-acetate. Under experimental conditions, there was no carcinogenic activity of MCPA. Putative preneoplastic nodules of the liver and tumor-like lesions of the lower jaw were occasionally observed among the animals that survived more than 22 months after the beginning of experimentation. However, no significant differences in frequency between control and experimental groups were found.

Experimentally-induced jaw sarcoma in the rat.

Jaw bones differ embryologically from limb bones and the axial skeleton as they are derived from migrating neural crest cells and are not preformed in cartilage as are the latter bone types. The purpose of the present study was to determine whether this embryologically different nature implied a different response to a locally applied carcinogenic compound, 4-hydroxyamino-quinoline-1-oxide; this within the context of elucidating why human jaw osteo- and fibrosarcomas behave differently from identical tumours elsewhere in the skeleton. Rat mandibles were exposed to the carcinogen. Of the 5 rats used, 3 developed tumours which were however histologically identical to the tumours experimentally induced in the limb bones by the same carcinogenic agent. As a consequence, it is concluded that the embryologically different nature of the jaw bone does not imply that local exposure to a carcinogenic agent induces other kinds of tumours as are seen in the extragnathic skeleton.

Difference in the induction of osteosarcoma in rabbit bone with single administration of three kinds of chemical carcinogens.

A single intramedullary administration of each dose (15 approximately 20 mg) of 4-nitroquinoline 1-oxide, 3-methylcholanthrene, or 7,12-dimethylbenz[alpha]anthracene was applied to the mandible, diaphysis, or distal metaphysis of the femur of rabbits. The highest incidence in production of osteosarcoma was obtained from the group in which 4-nitroquinoline 1-oxide was applied to the distal metaphysis (75%, including one case of chondrosarcoma). Tumors hardly appeared in any of the groups when given 3-methylcholanthrene or 7,12-dimethylbenz[alpha]anthracene. Histologically, three kinds of entities were recognized from the quantitative difference of the reactive tissues which appeared around carcinogens. It is estimated that the condition of entity III induces the highest incidence of osteosarcoma if chemical carcinogens are given into the bone marrow of experimental animals.

Ameloblastic odontoma in rats induced by N-butylnitrosourea.

Four cases of ameloblastic odontomas were found in the Long-Evans rats treated with multiple oral administration of a heavy dose of N-butylnitrosourea. The tumor was found as an expansive enlargement over the mandible and was roentgen-opaque. The tumor was histologically characterized by various elements such as odontogenic epithelium, stellated reticulum tissue, enamel, and/or dentine, and was classified as ameloblastic odontoma.

Experimental production of osteogenic sarcoma of the mandible in rabbits with 4-nitroquinoline 1-oxide.

A single intramedullary administration of 4-nitroquinoline 1-oxide (4-NQO) into the mandible in 32 rabbits induced 21 cases of osteogenic sarcoma (65.6%), 5 chondrosarcoma (15.6%), 2 fibrosarcomas, and 3 cementoblastomas. None of the tumors appeared until the 3rd month after the treatment. From the 4th to 6th month, early stages of osteogenic tumors were seen. In the late stadium, from 7th to 12th month, tumors showed prominent proliferation and invasion to the oral cavity and surrounding areas. Metastasis to the lung and liver was found in 2 cases of osteogenic sarcoma.