A 56-year-old never smoking woman was admitted to our Lung Cancer Center with no symptoms, but a big mass was found in the left lower lobe (Computed tomography (CT) of the chest) through annual healthy check-up. She denied hepatitis, tuberculosis, or other infectious disease, and had no history of smoking, drinking, allergies, or surgery. There was no obvious change in body weight.
An enhanced CT of the chest, whole abdomen, brain, and nasopharyngeal and a whole body bone scan were arranged. The enhanced CT of the chest showed a bulky soft tissue mass in the left lower lobe with lobulated, burr sign, and the largest cross-section size was about 6.4x6.0 cm. Furthermore, the left lung door and mediastinal lymph nodes showed enlargement. There were no trachea bronchial stenosis and no pericardial or pleural effusion (Figures 1A1, A2, B1, and B2). The enhanced CT of the whole abdomen showed a kind of circular low density shadow of 4.1x3.6 cm in the liver (Figure 1C). The brain and nasopharyngeal enhanced CT and the whole body bone scan were roughly normal except some focal ischemia, deputy nose, and hypertrophy of bilateral inferior turbinate (Figures 1D-F). Serum tumor markers indicated cell keratin fragments antigen 21-1 (CYFRA21-1) and neural specificity enolase (NSE) were higher than the normal values (10.38 ng/mL vs <3 ng/mL and 22.62 ng/mL vs <15 ng/mL, respectively). Carcinoembryonic antigen (CEA), serum carbohydrate antigen 125, 19-9, 15-3, and 72-4 (CA125, CA19-9, CA15-3, and CA72-4) were all negative. Other abnormal blood test results including heat shock protein 90alpha (HSP90alpha) and erythrocyte sedimentation (ESR), especially EBV-EA-IgG was 158.14 RU/mL which was almost eight times higher than normal value.
In order to define the diagnosis, fiber optic bronchoscope (FOB) and percutaneous lung biopsy were performed. All levels of the bronchial lumen were normal through the FOB, and the biopsy showed only chronic inflammation. However, percutaneous lung biopsy prompted lymphoepithelioma-like carcinoma combined with the results of hematoxylin-eosin (HE) and immunohistochemical (IHC) staining. IHC staining demonstrated PCK (+), P40 (+), CK5/6 (+), EBER1/2-ISH (+), CK7 (-), TTF-1 (-), and PD-L1 (+, positive proportion about 80%, antibody SP142, ZSGB-BIO Company) (Figure 2). The findings from next generation sequencing (NGS) were negative for mutations in EGFR, KRAS, and BRAF and negative for rearrangements in ALK and ROS1. Then we diagnosed left lower lobe lymphoepithelioma-like carcinoma invading the pericardium and descending aorta, with metastasis of mediastinal lymph nodes and liver (cT4N2M1b, stage IVA).
The first treatment regimen was paclitaxel (190 mg) plus carboplatin (550 mg). After two cycles, we evaluated the curative effect according to enhanced CT of the chest and whole abdomen, and we found the size of tumor became larger (Figures 3A1 and A2) and the lesions of liver became more broader than before (Figures 3B1-B4, evaluation result was SD (according to RECIST 1.1)). We evaluated again after four cycles of chemotherapy, and found the CT imaging demonstrated significant progression of disease (Figure 4, evaluation result was PD). After consulting with the patient and considering the high expression of PD-L1, we decided to stop the chemotherapy and began to use nivolumab (Opdivo; Bristol-Myers Squibb, New York, NY). Subsequently, the patient was administered nivolumab 3 mg/kg every 14 days. After two cycles, we evaluated the curative effect again, and to our surprise the size of the mass had reduced significantly (Figures 5A1 and A2, evaluation result was PR), and there was no metastasis in the brain (Figure 5B). After five cycles of nivolumab, the size of the tumor and the lesions of the liver became even smaller (Figure 6, evaluation result was PR). At the same time, we performed the blood tests again and found that the values of CYFRA21-1 and NSE dramatically decreased compared to before, especially the CYFRA21-1 (Figure 7). So far, this patient has finished six cycles of treatment of nivolumab and there have been no obvious side-effects during the treatment process except an occasional mild cough. Meantime, the hormone level of the thyroid and cortisol have remained roughly normal.
The images of enhanced CT of chest and whole abdomen after two cycles of chemotherapy. (A1, A2) A bulky soft tissue mass in the left lower lobe, which was larger than before. (B1-B4) Multiple classes of circular low density shadows in the liver, and the lesions of liver had become broader than before (October 29, 2018).