Primary gastric squamous cell carcinoma (SCC) is extremely rare and can resemble adenocarcinoma or submucosal tumors such as GIST, making diagnosis difficult. We report a case that began with isolated back pain and progressed to massive upper GI bleeding, ultimately revealing a primary gastric SCC.

A 66-year-old man presented with several months of thoracolumbar back pain. A CT scan performed for musculoskeletal evaluation incidentally revealed a large gastric mass at the lesser curvature. Upper endoscopy showed an extensive infiltrative, exulcerated lesion with deep ulcerations and a small active bleed. Biopsy was deferred due to dual antiplatelet therapy. Endoscopic ultrasound demonstrated a large heterogeneous lesion arising from the muscularis propria, suggesting a GIST-like submucosal tumor. EUS-guided sampling was performed. After cessation of antiplatelet therapy, repeat endoscopy showed an infiltrating carcinoma, and biopsies confirmed poorly differentiated SCC (CK5/6 positive, p63 positive, CK7 negative). The esophagus appeared normal.

The clinical course was marked by recurrent malignant bleeding requiring several urgent endoscopies. One procedure showed interval tumor progression without active hemorrhage, whereas later examinations revealed large amounts of hematin and multiple arterial bleeding points. Injection therapy, coagulation and hemostatic powder (TC-325/HaemoSpray) achieved only temporary control. The final endoscopy, performed under intubation, showed the stomach filled with a large volume of blood and a deep necrotic cavity with persistent arterial bleeding. The patient died from hemorrhagic shock.

Further staging with PET-CT showed no evidence of another SCC primary and no esophageal involvement. Together with the extra-cardiac location of the tumor, these findings fulfilled Parks’ criteria and supported the diagnosis of primary gastric SCC. The multidisciplinary tumor board classified the tumor as unresectable, and palliative systemic chemotherapy was initiated, but recurrent bleeding ultimately led to a fatal outcome.

This case highlights how primary gastric SCC may present with atypical symptoms and a deceptive GIST-like EUS appearance. It underscores the importance of multimodal evaluation including EGD, EUS, imaging and targeted biopsy in diagnosing rare gastric tumors. The case also demonstrates the limited durability of endoscopic hemostasis in advanced malignant bleeding and the need to consider gastric SCC in ulcerated, subepithelial-appearing lesions when endoscopic, imaging and histologic findings are discordant.