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.