Patient B is a 76-year-old white male who presented with microscopic hematuria in 1986 on a routine urinalysis and a diagnosis of left RCC was made by imaging. He then underwent nephrectomy for a 7 × 6 × 5.5 cm tumor extending though the fascia into the perinephric fat. He did well until March of 2006 when he had a routine chest X-ray that showed new lung nodules and a CT scan was ordered. A large retroperitoneal mass posterior to the stomach measuring 10 × 9 × 8 cm was also found along with bilateral lung nodules, with the largest lung lesion measuring 2 cm. Biopsy of the retroperitoneal mass confirmed RCC. MRI of the brain and bone scan was negative. He was seen for the first time at our institution in April of 2006. He was determined to be a candidate for high-dose IL-2 (600,000 IU/kg). After 8 weeks, he did show some response, but was only able to tolerate half of cycle 2 and he declined further IL-2. He was then started on sorafenib and had a minor response at all disease sites until CT scan in January 2007 after 24 weeks showed progression. He was then switched to sunitinib 50 mg daily for 4 weeks of a 6 weeks cycles, and after 12 weeks on therapy had a significant response which he enjoyed until week 54 when CT scanning showed marked disease progression. Sunitinib was discontinued and in January of 2008 he was started on temsirolimus 25 mg IV weekly. He required a 20% dose reduction for thrombocytopenia and oral ulcers. He remained on temsirolimus until April of 2008 when he developed symptomatic mTOR interstitial pneumonitis, so temsirolimus was discontinued. His disease continued to progress off therapy and in October of 2008, bevacizumab 10 mg/m2 given every 2 weeks was started as fifth line therapy. After 24 weeks of treatment the patient was found to have a pulmonary embolus. Lovenox was started and bevacizumab was continued without incident. At the time of submission, the patient's disease has remained stable after 72 weeks of bevacizumab. He has continued to work full time as a maintenance man.
A 79-year-old male patient was referred on December 2015 to the Turin Oral Health Department (Dental School) for a baseline exam before starting therapy with bisphosphonates; clinical examination revealed an already present bone exposition approximately 3 mm × 1 mm in the left posterior mandible, in correspondence of the mylohyoid line, asymptomatic ().\nThe history from the patient included colon adenocarcinoma that was diagnosed and treated surgically on October 2008 (stage pT2 pN1 G3). Subsequently the patient underwent adjuvant chemotherapy with the XELOX scheme (capecitabine and oxaliplatin).\nHe also suffered from hypertension and prostatic hyperplasia, and had been submitted for coronary angioplasty due to cardiac ischemia in 2007.\nOn September 2010, the patient underwent surgery of lung nodules (pathology revealed a lung hamartoma and some metastases of carcinoma of colorectal origin). From November 2010 to April 2011, he received postoperative chemotherapy with the FOLFIRI scheme (irinotecan, fluorouracil, folinic acid).\nAfter the lung progression of the disease, from January 2012 to March 2012 he underwent FOLFOX chemotherapy (oxaliplatin, fluouracil, folinic acid) which was stopped for an allergic reaction to oxaliplatin. In April 2012, he started chemotherapy with irinotecan together with bevacizumab (7.5 mg/kg every 14 days) for seven cycles (until June 2012). After a drug holiday, on October 2013 the patient restarted chemotherapy (without bevacizumab) for five other cycles. On March 2014, he underwent stereotactic radiation therapy of two residual lung nodules.\nDue to a new lung progression, on October 2014 he started irinotecan and bevacizumab again (same doses) for 12 cycles, until April 2015. He continued bevacizumab only (maintenance therapy) until October 2015 for 10 courses, until reaching a total of 22 bevacizumab administrations in this second course.\nOn October 2015, bone metastases were diagnosed and he started therapy with mitomycin and fluorouracil.\nOn 1 October 2015, the patient had undergone tooth extraction of the two mandible canines and of the second left mandible molar due to excessive mobility at a private dentist office. Tooth extractions were conducted under antibiotic coverage (amoxicilline plus clavulanic acid 1 g every 12 h for six days).\nOn December 2015, the patient was referred to the Turin Oral Health Department (Dental School) for a baseline evaluation in order to start intravenous bisphosphonate therapy, after diagnosis of bone metastases. At the time of the visit the patient was completely edentulous, and he was a wearer of two dentures. As written before, intraoral examination showed a bone exposition approximately 3 mm × 1 mm in the left posterior mandible, in correspondence of the mylohyoid line, asymptomatic (). Trauma from the dentures was excluded. The surrounding soft tissue appeared ulcerated and necrotic, with no evidence of infection, so a cone-beam computer tomography (CBCT) was requested in order to investigate the real dimensions of the necrosis and to exclude metastatic lesions. CBCT revealed a minor cortical sclerotic bone lesion and a residual of the post-extraction socket without images of bone sequestra (a–c).\nThe patient underwent six administrations of low level laser therapy (LLLT), twice a week, and then he was re-evaluated. At the end of January 2016, the patient underwent a contrast-enhanced computer tomography (CT) scan, which excluded definitively the hypothesis of a metastatic lesion. At that date, the lesion was still asymptomatic, but an oral fistula appeared in the second left molar region (). The diagnosis of MRONJ was confirmed.\nA new antibiotic therapy was prescribed (amoxicilline plus clavulanic acid 1 g every 8 h for six days and metronidazole 500 mg every 8 h for six days) in combination with a chlorhexidine 0.2% oral rinse. After a week the patient expelled a bone sequestrum approximately 4 mm × 2 mm large as well as referred mucosal healing at the bone exposure site and disappearance of the oral fistula.\nOn 3 March 2016, the patient was re-evaluated and at intraoral examination both the bone exposure and the oral fistula were completely healed ().\nAt six months from the event, there were no recurrences. Further follow-up visits are planned.