Ipilimumab-induced cutaneous reactions.

*<p>case is detailed in the result section.</p>a<p>listed treatments are systemic treatments unless otherwise specified.</p>b<p>tumor free high-risk stage III melanoma (AJCC 2009); adjuvant administration of ipilimumab.</p>c<p>stage IV metastatic disease (AJCC 2009).</p>d<p>MelanA-specific vaccination.</p><p>M indicates male; F, female; LN, lymph nodes; IFN-α, interferon-α; DTIC, dacarbazine; TKI, tyrosine kinase inhibitor; PR, partial response; SD, stable disease; PD, progressive disease; MR, mixed response; CR, complete response; MAH, melanoma-associated hypopigmentation.</p

Ipilimumab-induced skin reactions and nephritis.

<p>Melanoma-associated hypopigmentation (MAH) in a patient exhibiting a partial clinical response (A). Masson’s trichome staining showed lymphocytic nephritis in a patient with an ipilimumab-induced drug rash with eosinophilia and systemic symptoms (DRESS) (B). Skin toxicity with the formation of blisters upon induction of treatment with ipilimumab in an area that had been radiated, five weeks earlier, in a patient with previous resection of the distal part of digit II due to an acrolentiginous melanoma (C).</p

Ipilimumab-induced miscellaneous reactions.

*<p>case is detailed in the result section.</p>a<p>listed treatments are systemic treatments unless otherwise specified.</p>b<p>tumor-free high-risk stage III melanoma (AJCC 2009); adjuvant administration of ipilimumab melanoma.</p>c<p>stage IV metastatic disease (AJCC 2009).</p>d<p>sinusitis.</p>e<p>VZV-infection.</p>f<p>limb perfusion with melphalan.</p>g<p>MAGE-A3 vaccination by GSK; NCT 00796445.</p>h<p>PRAME; vaccination with GSK2302025A.</p><p>M indicates male; F, female; LN, lymph nodes; IFN-α, interferon-α; DTIC, dacarbazine; VZV, varicella-zoster virus; SD, stable disease; MR, mixed response; PD, progression of disease.</p

Ipilimumab-induced myocardial fibrosis in conjunction with hepatotoxicity.

<p>Hematoxillin eosin staining at 50× magnification (A), 200× magnification (B) and 400× magnification (C) and chloracetate esterase staining at 50× magnification (D), 200× magnification (E) and 400× magnification (F) revealed neutrophilic granulocytes (black arrow) mostly around the central vein (asterisk). Portal fields were almost normal (white arrows). Some necrotic hepatocytes (black arrow heads panel C) and cholestasis of hepatocytes (white arrow heads panel C) indicating liver insufficiency, were detected pericentrally. Slightly elevated myocardial fibrosis (white arrow heads panel F) surrounded by structural changes of cardiomyocytes were detected (black arrow heads panel F).</p

Ipilimumab-induced reactions of the respiratory tract and renal system.

*<p>case is detailed in the result section.</p>a<p>listed treatments are systemic treatments unless otherwise specified.</p>b<p>tumor-free high-risk stage III melanoma (AJCC 2009); adjuvant administration of ipilimumab.</p>c<p>stage IV metastatic disease (AJCC 2009).</p>d<p>PRAME study; vaccination with GSK2302025A.</p>e<p>atypical pneumonia.</p>f<p>acute renal failure.</p>g<p>renal failure/atypical pneumonia.</p>h<p>iridocyclitis/keratitis, deafness.</p>I<p>renal failure/atypical pneumonia/iridocyclitis/keratitis.</p>j<p>deafness.</p><p>M indicates male; F, female; LN, lymph nodes; IFN-α, interferon-α; DTIC, dacarbazine; DVP; polychemotherapy with dacarbazine/vindesine/paclitaxel; GIT, gastrointestinal tract; PR, partial response; SD, stable disease; MR, mixed response; PD, progressive disease.</p

Ipilimumab-induced gastrointestinal, pancreatic and hepatic reactions.

*<p>case is detailed in the result section.</p>a<p>listed treatments are systemic treatments unless otherwise specified.</p>b<p>tumor free high-risk stage III melanoma (AJCC 2009); adjuvant administration of ipilimumab.</p>c<p>stage IV metastatic disease (AJCC 2009).</p><p>M indicates male; F, female; TVP, polychemotherapy with temozolomide+vinblastin+carboplatin; TKI, tyrosine kinase inhibitor RAF265; ALT, alanine transaminase; AST, aspartate transaminase; GGT, gamma-glutamyl transferase; LN, lymph nodes; IFN-α, interferon-α; DTIC, dacarbazine; PR, partial response; SD, stable disease; PD, progressive disease.</p

Ipilimumab-induced ischemic gastritis.

<p>Hematoxillin eosin staining showed edematous hypervascularized lamina propria mucosae, foveolar hyperplasia and regenerative basal crypts at 10× magnification (A) and 50× magnification (B). Endoscopic narrow band imaging (NBI) showed signs of reactive chronic inflammation of the gastric corpus mucosa with prominent vascular pattern consistent with an ischemic gastritis (C). Positron emission tomography (PET) scan illustrated high level tracer uptake in the gastric wall consistent with inflammation (D) and its spontaneous resolution after four months with a remaining thickening of the gastric wall (E).</p

Ipilimumab-induced side effects of the endrocrine system.

*<p>case is detailed in the result section.</p>a<p>listed treatments are systemic treatments unless otherwise specified.</p>b<p>tumor-free high-risk stage III melanoma (AJCC 2009); adjuvant administration of ipilimumab.</p>c<p>stage IV metastatic disease (AJCC 2009).</p>d<p>limb perfusion with melphalan.</p><p>M indicates male; F, female; LN, lymph nodes; IFN-α, interferon-α; DTIC, dacarbazine; GIT, gastrointestinal tract; IGF-1, insulin-like growth factor-1; TSH, thyroid-stimulating hormone; PR, partial response; SD, stable disease; PD, progressive disease; MR, mixed response.</p

Ipilimumab-induced reactions of the nervous system.

*<p>case is detailed in the result section.</p>a<p>listed treatments are systemic treatments unless otherwise specified.</p>b<p>tumor-free high-risk stage III melanoma (AJCC 2009); adjuvant administration of ipilimumab.</p>c<p>stage IV metastatic disease (AJCC 2009).</p><p>M indicates male; F, female; LN, lymph nodes; IFN-α, interferon-α; DTIC, dacarbazine; TKI, tyrosine kinase inhibitor RAF265; GIT, gastrointestinal tract; PR, partial response; SD, stable disease; PD, progressive disease.</p