Case of metastatic clear cell odontogenic carcinoma with response to chemoimmunotherapy.

Our patient initially presented with 6 months of left jaw pain and gingival bleeding, leading to the discovery of a radiolucent left maxillary mass on dental evaluation. A biopsy confirmed clear cell odontogenic carcinoma, and the patient was treated with definitive surgery and radiation for localised disease. Unfortunately, the patient was found to have pulmonary metastases 3 months after initial management and was subsequently treated with a combination of cytotoxic chemotherapy and immunotherapy with a partial response. To our knowledge, this is the first case demonstrating the successful use of chemoimmunotherapy in metastatic clear cell odontogenic carcinoma.

Feasibility and clinical value of CT-guided 125I brachytherapy for metastatic soft tissue sarcoma after first-line chemotherapy failure.

PURPOSE: To evaluate the feasibility and usefulness of computed tomography (CT)-guided iodine125 (125I) brachytherapy for patients with metastatic soft tissue sarcoma (STS) after first-line chemotherapy failure. METHODS: We recruited 93 patients with metastatic STS who had received first-line chemotherapy 4-6 times but developed progressive disease, from January 2010 to July 2015; 45 patients who had combined 125I brachytherapy and second-line chemotherapy (Group A), and 48 patients who received second-line CT only (Group B). RESULT: In Group A, 49 125I seed implantation procedures were performed in 45 patients with 116 metastatic lesions; the primary success rate was 91.1% (41/45), without life-threatening complications. Local control rates at 3, 6, 12, 24 and 36 months were 71.1%, 62.2%, 46.7%, 28.9% and 11.1% for Group A, and 72.9%, 54.2%, 18.8%, 6.3% and 0% for Group B. Mean progression-free survival differed significantly (Group A: 7.1±1.3 months; Group B: 3.6 ±1.1 months; P<0.001; Cox proportional hazards regression analysis), but overall survival did not significantly differ (Group A: 16.9 ±5.1 months; Group B: 12.1 ± 4.8 months). Group A showed better symptom relief and quality of life than Group B. CONCLUSION: CT-guided 125I brachytherapy is a feasible and valuable treatment for patients with metastatic STS. KEY POINTS: • 125 I brachytherapy is feasible and valuable for treating metastatic soft tissue sarcoma. • 125 I brachytherapy represents a prominent activity in disease control. • 125 I brachytherapy can achieve better symptom relief and quality of life.

Pharmacological and surgical therapy for the central giant cell granuloma: A long-term retrospective cohort study.

PURPOSE: This is a retrospective cohort study of patients with a central giant cell granuloma (CGCG) treated at a single center to assess and compare the different surgical and non-surgical approaches. MATERIAL AND METHODS: A cohort with a single histologically proven non-syndrome-related CGCG was selected and reviewed. Patients were allocated to group I (surgery), group II (pharmacotherapy), and group III (pharmacotherapy and surgery). The primary outcome was long-term radiologic response using computed tomography. Secondary outcomes were intermediate radiologic responses and occurrence and severity of side effects. RESULTS: Thirty-three subjects were included in the study. The surgical group (n = 4) included 1 patient with progression during follow-up and a relatively high post-surgical morbidity. Twenty-nine patients started on various pharmacological treatment regimens (groups II and III). Fourteen patients could be managed without additional surgery. One of these lesions showed progression during follow-up. The other 15 lesions underwent additional surgery, and none showed progression during follow-up. Interferon treatment was associated with the most side effects. CONCLUSION: Pharmacological agents have a role in the treatment of aggressive and non-aggressive CGCGs by limiting the renewed progression during long-term follow up and the extent and morbidity of surgical treatment.

Adjuvant Antiangiogenic Treatment for Aggressive Giant Cell Lesions of the Jaw: A 20-Year Experience at Massachusetts General Hospital.

PURPOSE: To document long-term outcomes using a standardized treatment protocol of enucleation with preservation of vital structures and adjuvant subcutaneous interferon for aggressive giant cell lesions (GCLs) of the jaws. MATERIALS AND METHODS: A retrospective cohort study was designed. We evaluated all patients treated at Massachusetts General Hospital from April 1995 through September 2015 by enucleation with preservation of vital structures and adjuvant daily subcutaneous interferon for aggressive GCLs. The sample included patients with complete medical records consisting of clinical, radiographic, histopathologic, and follow-up data. The exclusion criteria included patients with incomplete records, contraindications to interferon therapy, non-aggressive GCLs, and GCLs associated with syndromes or with hyperparathyroidism. The primary outcome variable was long-term progression-free survival (PFS). The secondary outcome variables were adverse effects and laboratory abnormalities classified by type, frequency, and severity. Predictor variables for recurrence or failure included age, gender, location and features of lesion, type of procedure, duration of interferon treatment, amount of bone fill at end of treatment, and adverse effects. Descriptive statistics, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis were computed. RESULTS: Of a total of 77 patients, 45 (mean age, 18.8 ± 12.5 years; 29 female patients; 36 in whom the mandible was affected) met the inclusion criteria. The mean duration of interferon therapy was 7.9 ± 2.3 months. After follow-up of 4.8 ± 3.9 years, 6 patients showed progression of the lesion, considered recurrence (13.3% failure rate, 82.6% PFS rate). Most patients had mild (n = 42; 93.3%) and/or moderate (n = 31; 68.8%) side effects, which were readily managed. Adverse effects required stoppage of interferon in 7 patients, whereas no patients had long-term toxicity. No variable was significantly associated with PFS. CONCLUSIONS: The results of this study indicate that enucleation with preservation of vital structures in combination with adjuvant interferon alfa is a reliable treatment for aggressive GCLs of the jaws associated with a low recurrence rate.

Unusual maxillary osteoblastic and osteolytic lesions presenting as an initial manifestation of childhood acute myeloid leukemia: A case report.

Changes in facial bones may represent a manifestation of systemic disease. Dentists play an important role in the early detection of these manifestations of complex systemic diseases. A case of unusual maxillary mixed (osteoblastic and osteolytic) lesions as an initial manifestation of childhood acute myeloid leukemia (AML) is presented. A 12-year-old male patient was referred to the Department of Oral Medicine complaining of severe swelling in the right buccal region. 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) showed enhanced FDG uptake in the right maxillary sinus. In addition, PET maximum intensity projection image showed diffused FDG uptake in the entire bone marrow. Bone marrow aspiration was performed on the lumbar vertebra, and fluorescence in situ hybridization (FISH) demonstrated AML. The patient was diagnosed with AML (M5a) and treated with chemotherapy by the pediatric department. Six months later, the patient achieved complete remission. After chemotherapy, the disappearance of the osteoblastic and osteolytic lesion and 18F-FDG accumulation were confirmed by PET/CT. Dentists should be familiar with oral manifestations of leukemia because early detection of oral lesions would increase the life span of the patients and reduce the severity of complications.

Tumor-induced Osteomalacia in a 3-Year-Old With Unresectable Central Giant Cell Lesions.

Tumor-induced osteomalacia (TIO) is a rare cause of hypophosphatemia involving overproduction of fibroblast growth factor 23. TIO has been described largely in adults with small mesenchymal tumors. We report a case of TIO in a child who presented with knee pain and radiographic findings concerning for rickets, and was found to have maxillomandibular giant cell lesions. The patient was treated with oral phosphorus and calcitriol, surgical debulking, and intralesional corticosteroids, which resulted in tumor regression and normalization of serum fibroblast growth factor 23 and phosphorus. This case illustrates the occurrence of this rare paraneoplastic syndrome in children and adds to our knowledge about clinical manifestations and pathologic findings associated with pediatric TIO.

Clinical diagnostic dilemma in an uncharacteristic rapidly enlarging swelling of the anterior maxilla: extranodal diffuse large B cell lymphoma.

Extranodal non-Hodgkin lymphoma (NHL) is infrequent in the oral cavity and constitutes 3.5% of oral cancers, and less than 2.2% of maxillofacial lymphomas. Diffuse large B cell lymphoma (DLBCL) accounts for 40% of NHL and has a 5-year survival rate of less than 30%. Early detection of extranodal NHL by dental personnel is extremely important as a delay in diagnosis can result in the cancer being diagnosed at an advanced stage and a poor prognosis. A 60-year-old male presented with an uncharacteristic asymptomatic rapidly enlarging swelling of the anterior maxilla, which on histopathological and immunohistochemical analysis was diagnosed as DLBCL. Imaging studies showed bone invasion and lymph node metastasis with poor prognosis. The patient received radiotherapy and chemotherapy but died within 3 months of diagnosis. A literature search revealed one another case with anterior maxilla occurrence, as the few oral DLBCL so far reported have appeared on the posterior palate or other intraoral sites.

Results of the treatment of keratocystic odontogenic tumours using enucleation and treatment of the residual bony defect with Carnoy's solution.

This retrospective study aimed to investigate the recurrence rate of keratocystic odontogenic tumours (KCOTs) treated by enucleation and the application of Carnoy's solution, and to assess the surgical morbidities associated with this treatment. KCOTs treated using a standard protocol of enucleation and the application of Carnoy's solution between 1990 and 2013 were evaluated. One hundred and five KCOTS in 105 patients (54 male, 51 female) were analysed. The mean follow-up period was 86.6 months (range 24-313 months). The recurrence rate was 11.4%. A postoperative inferior alveolar nerve neurosensory deficit occurred in 30.1% of the mandibular cases, with 16% of these being permanent. The postoperative infection and fracture rates were 1.9% and 0.9%, respectively. Younger age, multilocular KCOTs, larger tumour size, and longer antero-posterior lesion length on the radiograph were found to be risk factors for recurrence. It is concluded that enucleation and the application of Carnoy's solution to treat KCOTs results in a relatively low recurrence rate and a low rate of surgical morbidities.

Melanotic neuroectodermal tumour of infancy: surgical and chemotherapeutic management.

Melanotic neuroectodermal tumour of infancy (MNTI) is a rare pigmented neoplasm of neural crest origin. It usually presents in the first year of life in the maxilla as a fast growing lesion. We describe the case of a 3-month-old boy who presented with an enlarging swelling of left maxillary alveolus. He was treated with combined surgical and chemotherapy modalities. MNTI is complicated by high recurrence rate, local invasion and malignancy has been reported. This report describes the diagnosis, treatment and follow-up of recurrent MNTI.

Suppression of Poly(rC)-Binding Protein 4 (PCBP4) reduced cisplatin resistance in human maxillary cancer cells.

Cisplatin plays an important role in the therapy for human head and neck cancers. However, cancer cells develop cisplatin resistance, leading to difficulty in treatment and poor prognosis. To analyze cisplatin-resistant mechanisms, a cisplatin-resistant cell line, IMC-3CR, was established from the IMC-3 human maxillary cancer cell line. Flow cytometry revealed that, compared with IMC-3 cells, cisplatin more dominantly induced cell cycle G2/M arrest rather than apoptosis in IMC-3CR cells. That fact suggests that IMC-3CR cells avoid cisplatin-induced apoptosis through induction of G2/M arrest, which allows cancer cells to repair damaged DNA and survive. In the present study, we specifically examined Poly(rC)-Binding Protein 4 (PCBP4), which reportedly induces G2/M arrest. Results showed that suppression of PCBP4 by RNAi reduced cisplatin-induced G2/M arrest and enhanced apoptosis in IMC-3CR cells, resulting in the reduction of cisplatin resistance. In contrast, overexpression of PCBP4 in IMC-3 cells induced G2/M arrest after cisplatin treatment and enhanced cisplatin resistance. We revealed that PCBP4 combined with Cdc25A and suppressed the expression of Cdc25A, resulting in G2/M arrest. PCBP4 plays important roles in the induction of cisplatin resistance in human maxillary cancers. PCBP4 is a novel molecular target for the therapy of head and neck cancers, especially cisplatin-resistant cancers.

Activated cytotoxic T-lymphocyte immunotherapy is effective for advanced oral and maxillofacial cancers.

Conventional cancer treatments are surgery, radiotherapy, and chemotherapy, but treatment efficiency is insufficient and cancer recurrence is common. Immunotherapy has been added as an important cancer treatment component, but no reports on its efficacy in oral and maxillofacial cancers exist. We evaluated the clinical efficacy of adoptive immunotherapy using ex vivo-activated cytotoxic T lymphocytes (CTL) in the treatment of 7 patients with advanced oral and maxillofacial cancers with stage IV disease at diagnosis. The mean follow-up period was 26.2 months. Phenotype of the lymphocyte assay revealed that the percentage of CD4(+) T cells decreased and that of CD8(+) T cells increased among infused lymphocytes compared to that in unstimulated peripheral blood mononuclear cells (PBMCs), and infused lymphocytes produced a significantly higher level of IFN-γ than PBMCs or tumor cells alone. In a representative patient who refused surgery tumor regression was confirmed after CTL infusion. Computed tomography clearly indicated a significant reduction in tumor size followed by the complete disappearance of the tumor. Histological examination showed that the cancers in patients receiving CTL therapy were heavily infiltrated with lymphocytes. The other 2 patients who received CTL therapy as adjuvant therapy showed neither recurrent disease nor new disease lesions. The 1-year survival rates showing response and those with progressive disease were 100 and 25%, respectively. Moreover, no significant adverse reactions were reported during the study period. CTL therapy remains in the early stages of treatment options, but it has potential as a valuable treatment and improvement of quality of life for patients with otherwise incurable cancers.

Primary non-metastatic Ewing sarcoma of the jaw in children: results of surgical resection and primary reconstruction.

BACKGROUND AND OBJECTIVE: The rarity of Ewing sarcoma (ES) of the jaw coupled with the technical challenge of resection and associated functional and cosmetic impairment has resulted in deficient data on surgical management of these tumors. The purpose of this study is to describe the results of surgical excision and reconstruction of primary non-metastatic ES of the mandible and maxilla in children. METHODS: Consecutive patients (mandible = 6, maxilla = 5) treated with surgery from August 2005 to January 2013 were selected. All patients received induction chemotherapy and were selected for surgical resection based on the presence of specific criteria for operability. RESULTS: The median age was 11.5 years (range 5-16 years). Free fibular osteocutaneous flap was commonly used for reconstruction. There were no complications related to microvascular anastomosis or flap loss. Five patients had 100% tumor necrosis and did not receive radiotherapy. Teeth alignment, chewing, swallowing, and speech were normal in all and donor site morbidity occurred in one. The 5-year overall, event-free survival, and local control are 87.5%, 72.9%, and 90%, respectively. CONCLUSION: In eligible patients, surgery with contemporary reconstruction results in optimal oncological and functional outcome. Surgery also has the added advantage of identifying patients who may not need radiotherapy.

Managing local swelling following intratumoral electro-chemo-gene therapy.

Delivering genes and other materials directly into the tumor tissue causes specifically localized and powerfully enhanced efficacy of treatments; however, these specific effects can cause rapid, drastic changes in the appearance, texture, and consistency of the tumor. These changes complicate clinical response measurements which can confound the results and render recurring treatments difficult to perform and clinical response measurements nearly impossible to obtain accurately. One of the complicating issues is local swelling. Here, we demonstrate how swelling caused by intratumoral gene treatments can confound the clinical results and impede further treatments, and we demonstrate an easy technique to help overcome this potential hurdle.

Plasmablastic lymphoma of the oral cavity in a human immunodeficiency virus-negative patient: a case report with literature review.

Plasmablastic lymphoma (PBL) is an aggressive diffuse large B-cell lymphoma variant that is most frequently observed in the oral cavity of human immunodeficiency virus (HIV)-infected individuals. However, in recent years, some cases have emerged in patients without HIV infection and involve other sites like stomach, lung, nasal cavity, and jejunum. We report a rare case of PBL in the maxillary anterior area of a 62-year-old man without HIV infection. The tumor cells were characterized by non-cohesive round or oval shape cells with eccentrically-placed nuclei with a prominent perinuclear halo. Immunohistochemical studies showed that the tumor cells were strongly positive for MUM1, VS38c, VMT, and κ light chain, focally positive for LCA and CD79a, and negative for CD3, CD20, CD56, λ light chain, CK-pan, EMA, and HMB45. The patient was treated with chemotherapy using cyclophosphamide, doxorubicin, vincristine, and prednisone. The lesion showed partial remission.

Maxillary solitary recurrent plasmacytoma: a case report.

Solitary plasmacytoma is a very rare form of neoplasia, part of the monoclonal gammopathies. It represents a tumoral proliferation of plasma cells in the form of a solitary mass which can be located in the bone marrow or extramedullary.Initial symptoms are vague and nonspecific. Being such a rare affliction, there is little information in the literature. Early diagnosis is difficult but very important due to therapy outcome.A high risk of progression towards a multiple myeloma has been reported. We present a rare case of a 52-year-old patient diagnosed with multiple solitary plasmacytomas. The tumours were separated from one another in time, over a 14 years period. The various medullograms did not show any sign of medullary plasma cell infiltrate. Initially, the affliction responded to chemotherapy, but later the haematologist recommended surgical resections followed by reconstruction.The maxillary localization required excision of the tumour with the preservation of the eye bulb despite the destruction of the orbital floor and with the regain of ocular functionality as well as aesthetic rehabilitation. This evolution highlights the benefits of surgical treatment in conjunction with chemotherapy in the treatment of this entity.

Primary extranodal B-cell non-Hodgkin lymphoma mimicking an endodontic lesion: report of 2 cases.

Intrabony oral non-Hodgkin lymphoma (NHL) is rare. We report 2 cases of NHL of the maxilla that initially presented as apical abscesses in endodontically treated teeth. Radiographic findings were nondescript, but tissue biopsy revealed diffuse large B-cell NHL in both instances. No other sites of disease were found. Both patients were treated by chemotherapy and radiation with good results. As primary NHL of the maxilla can mimic a dental inflammatory lesion, tissue biopsy is mandatory in cases where symptoms do not resolve after specific treatment.

Aseptic meningitis: a rare side effect of cetuximab therapy.

Cetuximab, a chimeric IgG1 monoclonal antibody against the epidermal growth factor receptor, is indicated for the treatment of epidermal growth factor receptor-expressing metastatic colorectal cancer and recurrent or metastatic squamous cell cancer of the head and neck after failure of platinum-based therapy. The commonly reported side effects of cetuximab are infusion-related reactions, skin rash, fatigue, malaise and nausea. We report a case of aseptic meningitis developing as a rare side effect in a patient of stage IVB squamous maxillary cancer treated with cetuximab. To our knowledge, there have been very few cases of cetuximab-induced aseptic meningitis reported in literature. Clinicians should recognize that self-limiting aseptic meningitis can occur with administration of cetuximab. Our case report may serve as an additional reference for clinicians encountered with aseptic meningitis in the setting of using cetuximab.