PMC8526861_01
Magnetic resonance imaging of the left knee (A, B), white arrows indicate a mass measuring 2.8 x 3.8 cm violating the cruciate ligaments; positron emission tomography-computed tomography (PET-CT) (C), the fluorodeoxyglucose-avid tumour is seen within the left knee, indicating tumour recurrence; PET-CT (D), the fluorodeoxyglucose-avid tumour is presented on maximum intensity projection image as increased uptake around the left knee, indicating a second tumour recurrence.
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Positron emission tomography-computed tomography (PET-CT) indicated tumour recurrence with a maximum 8.4 SUV activity in areas of prior radiation therapy, whereas, no distant metastasis was detected ( Figure 1C ). PET-CT demonstrated a second local recurrence with a maximum 7.6 SUV activity, and multiple metastatic lesions in the lungs and left inguinal lymph nodes ( Figures 1D ,  2C ), maximum SUV activity in 4.8.
Pathological features of the local lesions. (A) Sheets of epithelioid and spindle-shaped large atypical cells and moderate nuclear pleomorphism (Haematoxylin and eosin stain, 200x); CT of the chest, (B) Immunohistochemical loss of integrase interactor 1 (INI-1) (400x); (C) white arrows indicate multiple pulmonary metastases (D) five months after camrelizumab therapy, pulmonary metastases completely disappeared; (E) Timeline of treatments from diagnosis to date.
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INI-1 ( Figures 2A, B ). In May 2017, the patient underwent wide resection of the lesion, followed by endo-prosthetic reconstruction. PET-CT demonstrated a second local recurrence with a maximum 7.6 SUV activity, and multiple metastatic lesions in the lungs and left inguinal lymph nodes ( Figures 1D ,  2C ), maximum SUV activity in 4.8. In August 2020, that 5 months after commencing camrelizumab, pulmonary metastases demonstrated a complete response (CR) ( Figure 2D ). The patient was asymptomatic and had a normal physical examination with an ECOG performance status of 0 at the time of writing ( Figure 2E ).
(A, B) Tumour immune microenvironment (TIME) analysis indicates that TILs including CD3+, CD4+, CD8+ cells and TAMs including CD68+, CD163+ cells are enriched in TIME. Granzyme B also was detected foci positive in TIME (immunohistochemical staining, Scar bar 50 muM, 400x); (C) High expression of PD-L1 as assessed by 30% (immunohistochemical staining, Scar bar 50 muM, 400x); (D), PCR-based microsatellite instability testing using five microsatellite markers (BAT25, BAT26, NR-21, NR-24, NR-27), revealed microsatellite status of stable.
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Immunohistochemical (IHC) staining of the resected recurrent tumour with 22C3 pharmDx assay (Agilent Technologies, Santa Clara, California, USA) revealed over 30% of PD-L1 positivity ( Figure 3C ). Moreover, CD3+ and CD8+ lymphocytes were enriched in TIME ( Figure 3A ). In addition, Granzyme B, which is secreted by cytotoxic T cells or NK cells, also detected foci positive in TIME ( Figure 3A ). Macrophages related markers including CD163 and CD68 were also detected ( Figure 3B ). MSI testing revealed the microsatellite status of stable (MSS) ( Figure 3D ).