PMC5168862_01
Imaging at Time of Diagnosis Before Treatment. a Scout PET scan showing cervical/mediastinal/inguinal adenopathy and vertebral lesions. b Cross section of mediastinum with increased update in mediastinal nodes (SUVmax 10 in subcarinal node). c Cross section of knees with no increased uptake. d MRI brain with two right cerebellar metastases with vasogenic edema
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Fig1
Diagnostic imaging with PET/CT and brain MRI demonstrated brain metastases, pulmonary nodules, left hilar and subcarinal lymphadenopathy, liver metastases, and several bone and soft tissue lesions (Figs. 1 and 2).
PET-CT of Hepatic Metastases Before and After Combination Immunotherapy. a PET-CT scan at times of diagnosis of with several hypermetabolic hepatic lesions consistent with metastases. b PET-CT scan after 4 cycles of nivolumab plus ipilimumab and 3 cycles of nivolumab maintenance
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Fig2
Diagnostic imaging with PET/CT and brain MRI demonstrated brain metastases, pulmonary nodules, left hilar and subcarinal lymphadenopathy, liver metastases, and several bone and soft tissue lesions (Figs. 1 and 2).
PET-CT scan after Nivolumab + Ipilimumab Induction and on Maintenance Nivolumab. a Scout PET scan showing cervical/mediastinal/inguinal adenopathy and vertebral lesions. b Cross section of mediastinum with increased uptake in mediastinal nodes (SUVmax 16 in paratracheal node). c Cross section of knees with increased uptake in left soft tissue nodule (SUVmax 2.7). d MRI brain with interval improvement of right cerebellar metastases
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Fig3
The left pretibial lesion was FDG-avid, and the scans also revealed new supraclavicular, mediastinal, right hilar and left iliac adenopathy, as well as subcutaneous left pretibial and right calf nodules (Fig. 3). The baseline subcarinal and left hilar lymphadenopathy had increased in size, but the hepatic, soft tissue, and brain lesions had resolved (Fig. 3). 
Hematoxylin and Eosin Staining of Pre-Tibial Soft Tissue Nodule. Microscopic hematoxylin and eosin (H&E) section showing (A) large, deep dermal collections of non-caseating granulomas (a, 2x) extending into the subcutaneous tissue (b, 2x). Higher magnification shows tightly formed granulomas containing multinucleated giant cells separated by fibrous connective tissue (c, 4x). Scattered mature appearing lymphocytes are seen surrounding the granulomatous inflammation (d, 10x)
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Fig4
Given the mixed clinical and radiographic results, excisional biopsy of the left pretibial lesion was performed and revealed non-necrotizing granulomatous inflammation consistent with tumefactive sarcoidal granulomas (Fig. 4).
PD-L1 Staining of Pre-Tibial Soft Tissue Nodule. PD-L1 antibody stained section of the granulomatous inflammation shows strong membranous staining of the histiocytes within the granulomas and scattered positive lymphocytes (a, 4x; b, 20x)
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Fig5
To obtain preliminary information on the mechanism for growth of sarcoid lesions in the setting of PD-1 blockade, the skin biopsy tissue was stained for PD-L1 expression, and demonstrated strong PD-L1 staining of the histiocytes and lymphocytes within the granulomas (Fig. 5).  