In June 2019, a 56-year-old woman without a relevant medical history underwent right renal tumourectomy. Histology findings demonstrated clear cell renal cell carcinoma (RCC), sarcomatoid type, grade 4 (Fuhrman), free margins, pT1b Nx M0. On 26 July after a multidisciplinary team discussion (MTD), follow-up with chest and abdominal CT scans within 1 month was scheduled.
In August 2019, the patient was admitted to the emergency department for neurological symptoms. A brain CT scan showed a left frontal lesion. She was admitted to the neurology department and started steroid treatment. A whole-body CT scan confirmed progressive disease with mediastinal node involvement and two enlarged abdominal nodes (one perirenal and one close to the right iliac vessels).
Steroid therapy during hospitalization resulted in improvement.
In August 2019, the MTD advised radical single brain metastasis excision followed by systemic therapy. The patient underwent brain surgery. Histology showed epithelial neoplasia with clear cell aspects and large necrotic areas, immuno-morphologically consistent with secondary RCC.
In October 2019, the patient started combination immunotherapy with ipilimumab and nivolumab. After 1 week, liver toxicity was reported (grade 2 on aspartate aminotransferase (AST) and alanine transaminase (ALT), and grade 3 on total bilirubin (TB) and direct bilirubin (DB)). The patient then underwent a liver ultrasound (Fig. 1) which was negative for metastasis. She was started on oral prednisone 25 mg (1 capsule) three times a day.
On 4 November, due to progressive liver impairment, the patient started methylprednisolone at 2 mg/kg. Alternative causes for the liver impairment were investigated and excluded. Tests for hepatitis A, B and C infection, cytomegalovirus and immune hepatitis were performed and resulted negative.
Budd-Chiari syndrome was excluded because neither imaging or coagulation status were suggestive for the disease.
Blood analysis demonstrated worsening liver toxicity. We considered the liver failure was due to immune-related toxicity and increased the steroid dose. The patient was admitted to the oncology ward to start intravenous high-dose steroids according to international guideline . The patient's medication included 2 mg/kg methylprednisolone (daily dose 80 mgx2), euthyrox 125 mug, levetiracetam 500 mgx2, furosemide 20 mg x 2, omeprazole 20 mg x2 in the evening, delorazepam 8 mg in the evening, and cetirizine 10 mg (1 capsule)x2. The blood results during treatment are given in Table 1.
In November 2019, the patient underwent an abdominal CT scan (Fig. 2A) which showed a slightly enlarged liver without focal lesions. Liver enzymes continued to increase without impairment in coagulation function. The patient maintained a fair general condition until the beginning of December 2019.
At the end of November, the patient started mycophenolate 100 mg twice daily and underwent liver ultrasound plus-guided biopsy (Fig. 3). Liver enzyme trends are shown in Fig. 4. The histology report noted hepatic tissue with cytoplasmic and intracanalicular cholestasis, sinusoid ectasia and histiocytosis, tissue macrophage or dendritic cell aggregation, and microfoci of liver necrosis in single or a few cells.
There was no evidence of endotheliosis.
On 11 December, the patient started the third-line immunosuppressive therapy with tacrolimus 2 mg daily. On 17 December, she underwent an abdominal CT scan (Fig. 2B) which showed progressive disease but no liver involvement. The patient's condition deteriorated and she died on 27 December. Her relatives did not consent to an autopsy.