Abstract
BACKGROUND: Primary ileal squamous cell carcinoma (PISCC) is a rare malignant tumor of the ileum. Its development is an exceptional phenomenon, as the ileal mucosa is lined exclusively by simple columnar epithelium, with no native squamous epithelium under physiological conditions. PISCC accounts for fewer than 0.001% of all intestinal malignancies. As of 2025, only 12 confirmed cases have been documented in the global literature, predominantly as isolated case reports. CASE SUMMARY: A 47-year-old female developed abdominal pain two years after chemotherapy for ovarian low-grade serous carcinoma (International Federation of Gynecology and Obstetrics stage IC1). Positron emission tomography/computed tomography showed localized thickening of the small intestinal wall in the right pelvic region with increased metabolic activity, suggesting implantation metastasis. The patient underwent partial ileal resection, intestinal anastomosis, appendectomy, omentectomy, and pericolic lymphadenectomy. Histopathological and immunohistochemical analyses confirmed a primary ileal low-grade squamous cell carcinoma. Postoperatively, the patient received intravenous doxorubicin plus carboplatin combined with anti-angiogenic targeted therapy. After six cycles, the regimen was changed to paclitaxel plus carboplatin with bevacizumab. Following five cycles, maintenance therapy with intravenous bevacizumab monotherapy was initiated, supplemented with adjunctive hepatoprotective agents. At the 30-month postoperative follow-up, the patient remained progression-free with no clinical or radiologic evidence of recurrence or distant metastasis. CONCLUSION: Accurate diagnosis of PISCC requires integration of clinical history, systemic examination, histopathology, and immunohistochemical profiling to reduce misdiagnosis and missed diagnosis.