PMC8489402_01
Clinical presentation of NEC and SCC. Esophagogastroduodenoscopy and CT findings in NEC (A,B). (A) A large ulcerated mass was found in the esophagogastric junction. (B) CT imaging reveals para-aortic lymph node swelling (yellow arrow). Esophagogastroduodenoscopy and CT findings in SCC (C,D). (C) A tiny, red-colored mucosal area in the center of the cicatrized lesion (white arrow). (D) CT imaging shows no distant metastasis after the chemotherapy for NEC. (E) Macroscopic findings for the resected specimen. No other regional/distant metastasis can be seen in the resected specimen. (F) An ulcerated mass at the esophagogastric junction can be observed in the resected specimen (white arrow). NEC, neuroendocrine carcinoma; SCC, squamous cell carcinoma; CT, computed tomography.
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F1
Esophagogastroduodenoscopy (EGD) revealed a large, ulcerated mass, 7 cm in diameter (Figure 1A). Subsequently, contrast-enhanced computed tomography (CT) imaging showed enlarged para-aortic lymph nodes, which was suggestive of lymph node metastasis from the primary lesion (Figure 1B). Thereafter, we switched the regimen to S-1 (tegafur/gimeracil/oteracil potassium) monotherapy. Three months after starting S-1 therapy, a follow-up EGD revealed a focal area of tiny, red-colored mucosal lesions at the center of the cicatrized lesion (Figure 1C), with no evidence of lymph node metastasis (Figure 1D). Additionally, ~60% of the entire SCC field was negative for SMAD4 staining (Supplementary Figure 1). The patient finally opted for total gastrectomy with lymph node dissection (Figures 1E,F).
Histological evaluation of NEC and SCC. Hematoxylin and eosin, and immunohistochemical staining of the biopsy (NEC; A-E) and surgically resected specimen (SCC; F-I). (A,F) H-E staining; (B,G) synaptophysin; (C,H) CD56; (D) MIB-1; (E,I) p53; (J) CK5/6. Scale bars; 50 mum. NEC, neuroendocrine carcinoma; SCC, squamous cell carcinoma; H-E, hematoxylin and eosin.
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F2
Biopsy of the primary tumor demonstrated round-shaped neoplastic cells with a high nucleus/cytoplasm ratio, consistent with pleomorphic, poorly differentiated carcinoma (Figure 2A). Immunohistochemistry (IHC) analysis revealed that cancer cells were positive for synaptophysin and negative for CD56, chromogranin A, and p53 (Figures 2B-E). Re-biopsy of the tumor revealed keratinizing SCC, with no NEC components (Figure 2F). IHC was positive for Cytokeratin 5/6 (CK5/6) and negative for synaptophysin (Figures 2G-J).
Timeline of the patient's clinical course. Following the diagnosis of NEC, CDDP+VP-16, and S-1 single-agent therapy was administered. CRT and surgical resection were performed after detecting SCC. NEC, neuroendocrine carcinoma; SCC, squamous cell carcinoma, CDDP+VP-16, cisplatin+etoposide therapy; S-1, tegafur/gimeracil/oteracil potassium; CRT, chemoradiotherapy.
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F3
Pathological staging was IIA (T3, N0, M0), and the patient survived without recurrence for >3 years after the initial presentation (Figure 3).