A 50-year-old male presented in 2024 with dysphagia of unknown cause. While the symptom initially manifested as an obstruction sensation during rapid eating, it gradually progressed to difficulty with solid foods. He denied B symptoms such as fever, night sweats, or weight loss. Although he had no nausea or vomiting, he suffered from severe coughing with dark red blood-tinged sputum and experienced intermittent abdominal discomfort. Physical examination was unremarkable. The patient had a history of smoking (20 cigarettes/day for over 20 years, ceased 5 years prior) and occasional alcohol consumption. His past medical history included surgery for a left ankle fracture and perianal abscess resection six years ago. He denied any history of hypertension, diabetes, coronary heart disease, tuberculosis, or hepatitis. The Karnofsky Performance Status (KPS) score at admission was 80.

The clinical course and treatment timeline of the patient are summarized in Table 1.

On June 12, 2024, computed tomography (CT) scans of the upper chest and abdomen showed significant thickening of the esophageal wall in the lower thorax, with possible invasion into the right posterior mediastinum and adjacent lower lobe of the right lung. Multiple lymphadenopathies in the mediastinum, right hilar region, and hepatogastric space suggested metastasis (Figures 1A–C). Upper gastrointestinal endoscopy revealed an extrinsic bulge on the posterior wall, 34–38 cm from the incisors, with an irregular mucosal surface (Figures 1D, E). The lesion’s nature is uncertain, though chronic non-atrophic gastritis was noted. Ultrasound gastroscopy demonstrated marked esophageal wall thickening at 34–38 cm, with the thickest portion measuring about 35.6 mm, indicating invasion into the extra-adventitia. Scattered lymph nodes around the lesion had a maximum diameter of 12.5 mm (Figures 1F–H). Biopsy confirmed squamous cell carcinoma, with immunohistochemical analysis showing P40 (+), P53 (+, 100%), P16 (-), P63 (+), CK5/6 (+), CK (+), and KI-67 (+, 30%) (Figure 1I). Following departmental discussions, the patient was diagnosed with squamous cell carcinoma of the lower thoracic esophagus, with suspected lung invasion, mediastinum and hepatogastric space lymph node metastasis (clinical T4N2M0, Stage IVA).

Considering that the patient has an esophageal fistula, a nasogastric tube was inserted. With the implementation of optimal supportive measures, including nutritional support and anti-infective therapy, the patient’s overall health status demonstrated marked improvement. Given the advanced disease stage, the focus shifted to systemic therapy. The patient underwent the first and second cycles of chemoimmunotherapy on June 20, 2024, and July 12, 2024, respectively. The treatment regimen included paclitaxel 135 mg/m² d1, carboplatin at an AUC of 4 d1, and tislelizumab (an programmed death receptor-1 [PD-1] blockade) 200 mg d1, once every three weeks. A follow-up CT scan on August 2, 2024 showed uneven thickening of the lower thoracic esophagus wall, with possible invasion into the right posterior mediastinum and lower lobe of the right lung. The local right lateral wall was incompletely continuous, suggesting potential fistula formation. Although the tumor size decreased compared to the previous scan, an esophageal fistula had developed. A re-examination of the upper gastrointestinal endoscopy revealed a localized depression at 36 cm from the incisors and evidence of bubble overflow. Due to pressure from the nasogastric tube on the pharyngeal mucous membrane, the patient’s coughing and sore throat symptoms worsened. Given the upcoming chemoradiotherapy and the need for adequate nutrition while managing pain, a gastrostomy was deemed necessary. An endoscopic percutaneous gastrostomy was performed on August 6, 2024. The patient then completed the third and fourth cycles of chemoimmunotherapy on August 14 and September 6, 2024, respectively, with a regimen of paclitaxel 135 mg/m² d1, carboplatin at an AUC of 4 d1, and tislelizumab 200 mg d1. The patient failed to present at the hospital on the scheduled date, resulting in a longer-than-usual interval between the second and third cycles of chemotherapy. Concurrently, from August 16 to September 20, 2024, the patient received intensity-modulated radiation therapy (IMRT) targeting the primary esophageal tumor and mediastinal lymph nodes, delivering a dose of 1.8 Gy over 23 fractions. A follow-up CT scan conducted on October 8, 2024, showed uneven thickening of the lower thoracic esophageal wall, reduced in size from previous scans. Enlarged lymph nodes in the mediastinum, right hilar region, hepatogastric ligament, and retroperitoneum were noted, with some showing size reduction (Figures 2A–C). After multidisciplinary discussion, the patient is considered for potential surgical treatment.

On October 10, 2024, the patient underwent radical esophagectomy with three-incision approach (neck, thorax, and abdomen), along with thoracic duct ligation, esophageal reconstruction, and wedge resection of the right lower lung lobe. Postoperative pathological: 1. Lymph node summary: Total lymph nodes examined: 22; Total positive lymph nodes: 0 (all 22 nodes were negative); Station-wise breakdown: Right recurrent laryngeal nerve LN: 0/1; Station 8 LN: 0/1; Station 7 LN: 0/2; Station 15 LN: 0/1; Left recurrent laryngeal nerve LN: 0/1; Periesophageal LN: 0/2; Perigastric LN: 0/2; Station 16 LN: 0/4; Station 17 LN: 0/9; 2. Primary tumor bed and regression: The primary esophageal tumor bed showed fibrous tissue proliferation with chronic inflammatory cell infiltration, consistent with a complete pathological response (ypT0) following neoadjuvant therapy; no residual tumor cells were identified. All surgical margins (esophageal, gastric, and radial margins) were negative for carcinoma. No lymphovascular invasion or perineural invasion was detected. 3. Upper esophageal stump and right lower lung wedge resection findings: Upper esophageal stump: A spindle cell tumor was identified, confirmed as a leiomyoma by immunohistochemistry (stains: SMA (+), Desmin (+), S100 (-), CD34 (-), CD117 (-), Dog-1 (-), SDHB (+), Ki-67 (~1%)). This is a benign lesion unrelated to the esophageal squamous cell carcinoma. Right lower lung wedge resection: No tumor metastasis or neoplastic lesions were present; only inflammatory changes were noted. Overall, the pathology suggests ypT0N0M0 stage, indicating pCR.

A follow-up CT scan on November 19, 2024, showed postoperative changes in the esophagus, with slightly thickened anastomotic soft tissue and blurred surrounding fat planes. There was a slight accumulation of fluid in the mediastinum, consistent with prior findings. Changes were also noted in the lower lobe of the right lung, along with a trace of pleural effusion on the left side, which had significantly decreased compared to earlier scans (Figures 2D–F). One year later, during a follow-up visit, the CT scan showed no signs of tumor recurrence, and pulmonary inflammation had improved. The patient’s postoperative recovery was satisfactory. Throughout treatment, the primary adverse events included grade 1 nausea, grade 1 vomiting, and grade 3 leukopenia and neutropenia (CTCAE v5.0). The nadir occurred on September 14, 2024, with a white blood cell count of 1.1 × 10⁹/L and an absolute neutrophil count of 0.6 × 10⁹/L. All toxicities resolved following symptomatic treatment. No other toxic side effects were reported, indicating the treatment’s safety. Currently, the patient’s condition is stable, with occasional shortness of breath and cough. The patient reports no weight loss, with a KPS score of 90 and a good appetite.

The PD-L1 immunohistochemistry (IHC) was performed using the 22C3 clone on the Dako Autostainer Link 48 platform. Tissue sections were deparaffinized and rehydrated through a graded alcohol series, followed by antigen retrieval in sodium citrate buffer. The sections were then blocked with 5% goat serum for 30 minutes at room temperature and incubated with primary antibodies overnight at 4°C. IHC staining was carried out using horseradish peroxidase (HRP)-conjugated secondary antibodies (anti-rabbit IgG, ZSGB-BIO, Cat# PV-6001; anti-mouse IgG, ZSGB-BIO, Cat# PV-6002) with DAB as the chromogen. Finally, the stained images were scanned and captured using Image Viewer (version 3.2) and analyzed with ImageJ software (National Institutes of Health, USA). The scoring criterion was based on the Combined Positive Score (CPS).

CD8 was quantitatively analyzed using a digital quantification platform. The density was calculated as 71 cells/mm², which is significantly higher than that in the adjacent normal tissue (used as a control reference).