Case report
A 76-year-old man with cancer of the right side of the tongue (cT3N2bM0) underwent hemiglossectomy of the right side and dissection of the right side of the neck followed by reconstruction using anterolateral thigh flap. Postoperative pathological examination showed pT3N2b and negative surgical margins and extranodal invasion. The patient was treated with 60 Gy/30 Fr postoperative radiation therapy, because a vertical margin of only 4 mm could be obtained. Five months after surgery, multiple cavitatory lesions were detected in the lungs in the computed tomography (CT) scans. Bronchoscopic biopsy revealed that the tongue cancer had metastasized to the lungs (Fig 1). Six months after the surgery, chemotherapy with cisplatin plus 5-FU (PF, CDDP 60 mg/m2, 5-FU 750 mg/m2, a reduced dosage was used due to renal dysfunction) was initiated. Considering the possibility of chronic obstructive pulmonary disease and cavitatory lesions in the lung, cetuximab was not administered. He developed febrile neutropenia 13 days after the initiation of PF treatment and was urgently hospitalized. CT scans showed the progression of the lung metastases. Considering the possibility of platinum resistance, the first dose of nivolumab (240 mg/body) was administered 7 months after the surgery and the second dose was administered 2 weeks later. A rash appeared on the trunk region on the 27th day after the administration of the first dose of Nivolumab. Since fever of more than 38°C also developed on the 28th day, we suspected drug eruption and antihistamines were administered to the patient. Due to the exacerbation of the skin rash and fever, he was hospitalized on the 29th day. On the 31st day, a dermatologist diagnosed the patient with Stevens-Johnson syndrome (SJS) (Fig 2a). Pathological examination of a skin specimen showed the presence of necrotic keratinocytes and vacuolar degeneration in the epidermis (Fig 2b). There was no history of usage of any drug other than Nivolumab. Hence, nivolumab was suspected to be the cause of SJS. On the same day, steroid pulse therapy with 1000 mg methylprednisolone was initiated, and cefepime was administered to prevent secondary infection. Steroid pulse therapy was continued for 3 days, after which it was transferred to oral administration with 50 mg prednisolone. On the 35th day, the dermatologist diagnosed the patient with TEN considering the spread of erythema and erosion (Fig 2c). According to the diagnostic criteria for TEN, the presence of three major items ( (i) Blisters and erosions exceeding 10% of the body surface area, (ii) Fever, (iii) Staphylococcal scalded skin syndrome, toxic shock syndrome, contagious impetigo, acute generalized exanthematous pustulosis, or autoimmune blistering) and of four sub-items ( (i) Flat, atypical target legions initially, (ii) Mucosal lesions at the skin mucosa transition, (iii) Objective generalized symptoms, subjective malaise, or eating disorders, (iv) Histopathological changes in the epidermis such as necrosis 200 times more than 10 epidermal cell necrosis in a visual field) was confirmed. From the 37th day, intravenous immunoglobulin 40 mg/kg/day was administered for 5 days. From the 43rd day, symptoms improved. On the 49th day, the reduction in dose of predonin was initiated, and on the 66th day, treatment with predonin was completed. All skin eruptions had epithelialized, and only pigmentations were evident. However, his respiratory condition worsened from the 42nd day, and treatment with morphine was initiated from the 44th day to relieve the respiratory distress. CT scan advised on the 44th day showed increased lung metastatic lesions and pleural effusion (Fig 3). We believed that the deterioration of respiratory function occurred due to increase in cancerous lesions. Hence, a ventilator was not used. His respiratory condition continued to worsen, and he died on the 67th day. The clinical course of the case is depicted in Fig 4.