PMC6826182_01
Histologic and radiographic findings, and immunohistochemical staining for CD3+ TILs, PD-L1, and MLH1, MSH2, MSH6 and PMS2 expression in cervical small cell carcinoma tissue before PD-1 inhibitor treatment. (A) Clinical course of the patient. (B) Immunohistochemical staining of excisional tumor tissue demonstrated small cell cervical carcinoma, infiltrating the full-thickness cervix. (C) FDG-PET/CT overview showed multiple lesions of increased FDG metabolism in the field of operation, left lateral psoas muscle, right groin district lymph nodes, and multiple bones throughout the body. (D) Abundant CD3+ TILs infiltrated in cervical small cell carcinoma tissue. (E) Missing immunohistochemical staining for PD-L1 in tumor cells. (F) Representative immunohistochemical staining for MLH1 in tumor cells, and missing immunohistochemical staining of MSH2 (G), MSH6 (H), and PMS2 (I) in tumor cells. Original magnification x400.. Abbreviations: PD-1, programmed death-receptor 1; TILs, tumor-infiltrating lymphocytes; PD-L1, programmed death ligand 1; FDG-PET/CT, 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT).
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The schematic course of diagnosis and treatment of the patient was shown in Figure 1A. Postoperative pathological examination demonstrated small cell carcinoma infiltrating the full thickness of the cervix and involving the full layer of vaginal fornix (Figure 1B). On September 14, 2016, radiological examination with positron emission tomography-computed tomography (PET-CT) scan indicated multiple lesions of increased FDG metabolism, including the field of operation (residual tumor), the sites of multiple bones, the left lateral psoas muscle and the right groin district (bone and lymph node metastases) (Figure 1C). Although PD-L1 IHC (SP 142, Roche) in tumor tissue was negative (< 1%), but PD-L1 mRNA in tumor tissue was 33.9% (Figure 1D-I).
Radiographic changes pre- and post-immunotherapy and variation tendency of immunity indexes and tumor markers during immunotherapy. (A) MRI of pelvic cavity pre- and post-immunotherapy: The target tumor volume increased, and new metastases appeared. Arrows indicate the tumor lesions pre- (yellow arrows) and post-immunotherapy (green arrows). (B) The mutation abundance of ctDNA in peripheral blood and the amount of CTCs increased successively. (C) Variation tendency of tumor markers was observed during process of diagnosis and treatment: tumor markers gradually decreased after surgery, and then returned to normal; after the start of immunotherapy, tumor markers continued to rise above the normal.. Abbreviations: ctDNA, circulating tumor DNA; CTCs, circulating tumor cells.
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Chest computer tomography (CT) revealed pulmonary nodules, indicating tumor pulmonary metastases (Figure 2).