PMC9256999_01
Imaging and pathological data of the patient at diagnosis and after initial immuno-chemotherapy. (A) Representative chest CT before (upper) and after treatment (lower): abnormal lymph node in supraclavicular and mediastinum disappeared after two cycles of immuno-chemotherapy. (B) Representative PET-CT before (upper) and after treatment (lower): lesions with increased FDG uptake completely disappeared, and new bone generated after two cycles of immuno-chemotherapy. (C) Representative images of bone marrow aspiration cell smear: diffusely proliferative malignant tumor cells completely disappeared after two cycles of immuno-chemotherapy. (D) Pathological analysis (HE staining) of resected left supraclavicular lumps. (E) The protein expression of PD-L1 analyzed by IHC test (antibody clone number: 22C3).
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Cooperative Oncology Group performance status (ECOG-PS) score was 2. Chest CT showed multiple enlarged lymph nodes in the mediastinum with some nodules in both lung fields (Figure 1A, upper). PET-CT showed that FDG uptake significantly increased in multiple enlarged lymph nodes (bilateral clavicle area, left armpit, and mediastinum) and multiple bones (thoracic spine, lumbar spine, sacral spine, pelvis, scapula, sternum, and ribs), implying extensive lymph node metastases and bone destruction (Figure 1B, upper). A bone marrow biopsy showed diffusely proliferative malignant tumor cells of epithelial origin (Figure 1C, left). Lymph node pathology implied metastatic poorly differentiated cancer (Figure 1D) and a large series of IHC markers (AE1/AE3+, EMA+, CK7-, CK5/6-, CK20-, HMB45-, S-100-, CD138-, CD38-, CD20-, CD3-, P40-, NapsinA-, TTF1-, PAX8-, CD30-, EBER-, CDX2-, Syn-, CgA-, CD56-, Ki-67: 80%+) were unable to identify the tissue source. Fortunately, the tumor proportion score (TPS) of programmed death-ligand 1 (PD-L1) (Figure 1E) and tumor mutation burden (TMB) was 16.7 per million bases. Chest CT was used and showed no obvious lesions (Figure 1A, lower). Amazingly, the original FDG metabolism increased focus completely disappeared and enlarged lymph nodes disappeared (Figure 1B, lower). A bone marrow biopsy showed no proliferative malignant tumor cells (Figure 1C, right). A color doppler ultrasound showed an enlarged lymph node (Figure S1A) and a biopsy with a coarse needle was applied. The pathological result was still metastatic poorly differentiated carcinoma (Figure S1B).
The timeline of the treatment process for the patient. The patient has experienced immunotherapy, the combination of immunotherapy and chemotherapy, and the combination of immunotherapy and radiotherapy. At initial treatment and after two recurrences, the patient achieved clinical benefits.
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However, on 5 April 2021, retroperitoneal lymph nodes showed new metastasis, and the sequential treatment with radiotherapy (dose unknown outside our hospital) and pembrolizumab 200 mg D1 (q3w) exhibited encouraging efficacy, and efficacy evaluation reached PR (Figure S2). The treatment process is shown in Figure 2.
Blood test results during the treatment process for the patient. (A) NLR value and its dynamic changes during the treatment process. (B) Tumor marker levels and their dynamic changes during the treatment process, including CEA, AFP, CA199, CA125, NSE, and CYFRA21-1.
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Additionally, we also summarized the changes of several significant blood test results, including NLR and tumor markers (CEA, AFP, CA199, CA125, NSE, and CYFRA21-1), but no significant clinical importance was observed (Figure 3).