Exclusive Cutaneous and Subcutaneous Sarcoidal Granulomatous Inflammation due to Immune Checkpoint Inhibitors: Report of Two Cases with Unusual Manifestations and Review of the Literature

Table 1

Sarcoidal-type granulomatous reaction due to immune checkpoint inhibitors (anti-CTLA-4 and anti PD-1 antibodies), affecting skin, with and without other organ systems.

	Case	Age	Sex	Primary disease	Clinical manifestation	ICI therapy
1	Suozzi, 2016 [9]	60	F	Lung Adenocarcinoma	Cutaneous only	Ipilimumab & Nivolumab
2	Ogawa, 2018 [10]	63	F	Lung Adenocarcinoma	Cutaneous only	Nivolumab
3	Birnbaum, 2017 [11]	56	F	Melanoma	Cutaneous only	Nivolumab
4	Dimitriou, 2018 [12]	72	M	Melanoma	Cutaneous only	Pembrolizumab
5	Tetzlaff, 2017 [2]	57	F	Ovarian Cancer	Subcutaneous only (bilateral lower extremities, forearms)	Ipilimumab & Nivolumab
6	Tetzlaff, 2017 [2]	39	F	Melanoma	Subcutaneous only (bilateral lower extremities & buttocks)	Ipilimumab & Nivolumab
7	Current Report, 2019	49	F	Renal Cell Carcinoma	Cutaneous only (left forearm and elbow)	Ipilimumab & Nivolumab
8	Current Report, 2019	58	M	Melanoma	Cutaneous only (black tattoo on chest, shoulders, back, forearm, thigh)	Ipilimumab
9	Kim, 2016 [14]	52	M	Urothelial Carcinoma	Cutaneous (tattoo & face), Hilar Lymph Nodes (LN)	Ipilimumab & Nivolumab
10	Cotliar, 2016 [16]	72	F	Hodgkin Lymphoma	Subcutaneous (bilateral arms), Pulmonary, Hilar LN, Bone	Pembrolizumab
11	Tetzlaff, 2018 [13]	44	F	Melanoma	Subcutaneous (peripatellar), Hilar LN	Ipilimumab
12	Tetzlaff, 2018 [13]	79	M	Melanoma	Cutaneous (bilateral forearms, elbows, hands), Hilar LN	Pembrolizumab & Nivolumab
13	Le Burel, 2017 [17]	71	F	Melanoma	Cutaneous, Pulmonary Parenchyma	Nivolumab
14	Lomax, 2017 [18]	75	F	Melanoma	Cutaneous, Pulmonary	Nivolumab
15	Oommen, 2017 [19]	54	M	Melanoma	Cutaneous, Pulmonary	Ipilimumab
16	Reddy, 2017 [20]	57	F	Melanoma	Cutaneous, Pulmonary	Ipilimumab
17	Reddy, 2017 [20]	55	F	Melanoma	Cutaneous, Pulmonary	Ipilimumab & Nivolumab
18	Toumeh, 2016 [21]	26	F	Melanoma	Cutaneous, Pulmonary	Ipilimumab
19	Yatim, 2018 [22]	72	F	Melanoma	Subcutaneous (left flank, right leg, scar), Pulmonary, hilar LN, Eye	Pembrolizumab
20	Firwana, 2017 [23]	37	F	Melanoma	Cutaneous (right forearm, bilateral shins), Hilar LN & other LN	Ipilimumab & Pembrolizumab
21	Firwana, 2017 [23]	57	F	Melanoma	Cutaneous (bilateral lower extremities), Hilar LN	Ipilimumab
22	Danlos, 2016 [24]	57	M	Melanoma	Cutaneous (lip, scar), Hilar and Mediastinal LN	Nivolumab
23	Martinez, 2016 [25]	46	F	Melanoma	Cutaneous, Pulmonary	Ipilimumab
24	Tissot, 2013 [26]	57	M	Melanoma	Cutaneous (elbow, arm), Pulmonary, Hilar LN	Ipilimumab
25	Eckert, 2009 [8]	67	F	Melanoma	Cutaneous, Pulmonary	Ipilimumab
26	Reule, 2013 [27]	55	M	Melanoma	Cutaneous (finger, forearm, knee), Pulmonary, Hilar LN	Ipilimumab
27	Lomax, 2017 [18]	57	F	Melanoma	Subcutaneous & Cutaneous (elbows, wrists, thighs), Pulmonary, Hilar LN	Pembrolizumab
28	McKenna, 2018 [28]	69	F	Melanoma	Cutaneous, Pulmonary	Nivolumab
29	Jespersen, 2018 [29]	57	F	Melanoma	Cutaneous, Pulmonary, Bone	Pembrolizumab
30	Dimitriou, 2018 [12]	65	M	Melanoma	Cutaneous (elbow), Hilar LN	Pembrolizumab
31	Dimitriou, 2018 [12]	57	M	Melanoma	Cutaneous (scar), Hilar LN, Thyroid	Ipilimumab & Nivolumab
32	Burillo-Martinez, 2017 [30]	69	F	Melanoma	Subcutaneous (forearms, legs, blue nevus), Hilar LN	Pembrolizumab
33	Paolini, 2018 [31]	56	F	Non-small Cell Lung Cancer	Cutaneous, Pulmonary	Nivolumab
34	Wilgenhof, 2012 [32]	37	M	Melanoma	Cutaneous, Pulmonary, Lymph Nodes, Spleen	Ipilimumab
35	Lomax, 2017 [18]	44	M	Melanoma	Cutaneous (elbow and occipital region), Pulmonary, Hilar and Mediastinal LN, Colitis	Nivolumab
36	Lomax, 2017 [18]	65	F	Melanoma	Cutaneous (face, knees), Thyroiditis, Pulmonary, Hilar LN	Pembrolizumab