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Updated: Mar 24, 2026
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Systemic inflammation in a melanoma patient treated with immune checkpoint inhibitors-an autopsy study
Viktor H Koelzer1, Sacha I Rothschild2, Deborah Zihler3
1Institute of Pathology, Cantonal Hospital Baselland, Mühlemattstrasse 11, CH-4410 Liestal, Switzerland ; Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstrasse 31, CH-3010 Bern, Switzerland.
Background:
Immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) have been recently approved for treatment of patients with metastatic melanoma and non-small cell lung cancer (NSCLC). Despite important clinical benefits, these therapies are associated with a diverse spectrum of immune-related adverse events (irAEs) that are typically transient, but occasionally severe or even fatal.
Case Presentation:
This autopsy case illustrates that clinically overt irAEs may represent only a fraction of the total spectrum of immune-related organ pathology in patients treated with immune checkpoint inhibitors. We report a comprehensive analysis of systemic irAE pathology based on the autopsy of a 35-year-old female patient with metastatic melanoma treated first with ipilimumab and then nivolumab. The clinical course was characterized by a mixed tumor response with regression of skin and lung metastases and fatal progression of metastatic disease in the small bowel, peritoneum and brain. During therapy with ipilimumab, radiographic features of immune-related pneumonitis were noted. The autopsy examination established a sarcoid-like granulomatous reaction of the lung, pulmonary fibrosis and diffuse alveolar damage. Importantly, a clinically unapparent but histologically striking systemic inflammation involving the heart, central nervous system, liver and bone marrow was identified. Severe immune-related end-organ damage due to lymphocytic myocarditis was found.
Conclusions:
Autopsy studies are an important measure of quality control and may identify clinically unapparent irAEs in patients treated with immunotherapy. Pathologists and clinicians need to be aware of the broad spectrum of irAEs for timely management of treatment-related morbidity.
Insights
Autopsy revealed significant immune-related organ damage beyond clinical symptoms in a patient treated with immune checkpoint inhibitors for metastatic melanoma. This highlights the need for awareness of broader immune-related adverse events (irAEs).
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Immune checkpoint inhibitors (ICIs) targeting CTLA-4 and PD-1 offer benefits for metastatic melanoma and NSCLC.
- However, ICIs can cause diverse immune-related adverse events (irAEs), which are sometimes severe or fatal.
Purpose of the Study:
- To illustrate that clinically apparent irAEs may only represent a fraction of the total immune-related organ pathology.
- To report a comprehensive analysis of systemic irAE pathology via autopsy.
Main Methods:
- Autopsy of a 35-year-old female patient with metastatic melanoma treated with ipilimumab and nivolumab.
- Analysis of systemic immune-related organ pathology, including clinically unapparent inflammation.
Main Results:
- The patient experienced mixed tumor response but fatal progression in the small bowel, peritoneum, and brain.
- Autopsy revealed sarcoid-like granulomatous reaction, pulmonary fibrosis, and diffuse alveolar damage.
- Clinically unapparent but severe systemic inflammation was identified in the heart, CNS, liver, and bone marrow, including lymphocytic myocarditis.
Conclusions:
- Autopsy studies are crucial for identifying clinically unapparent irAEs in patients receiving immunotherapy.
- Pathologists and clinicians must recognize the wide spectrum of irAEs for effective management of treatment-related morbidity.
