Abstract
INTRODUCTION AND IMPORTANCE: Primary tracheal squamous cell carcinoma (SCC) is exceedingly rare and may present with acute airway obstruction, posing diagnostic and therapeutic challenges. Aberrant CK20 expression in SCC is uncommon and may mimic metastatic disease, complicating diagnosis. CASE PRESENTATION: A 43-year-old male presented with sudden respiratory distress, stridor, and right supraclavicular swelling. MRI revealed a 7.9 × 6 × 6 cm tracheal wall mass with nodal involvement. Biopsy confirmed poorly differentiated SCC positive for AE1/AE3, CK5/6, p63, p40, and aberrant CK20, with PD-L1 CPS <1. lactate dehydrogenase was elevated. Urgent systemic chemotherapy (nanoparticle paclitaxel, carboplatin, 5-FU) was initiated, followed by addition of toripalimab. Marked regression was observed on fluorodeoxyglucose positron emission tomography/computed tomography, and tracheal stenting was avoided as the airway was stabilized with noninvasive ventilation. Concurrent chemoradiotherapy was subsequently administered. Despite initial response, follow up imaging revealed hepatic, pleural, and skeletal metastases. CLINICAL DISCUSSION: Primary tracheal SCC remains a rare and aggressive malignancy. Aberrant CK20 expression can create diagnostic pitfalls, emphasizing the importance of broad immunohistochemical profiling. Rapid response to chemo-immunotherapy, even in PD-L1 low tumors, suggests its potential role in emergent airway compromise. Nonetheless, disease progression highlights the need for vigilant surveillance and possible molecularly guided therapy. CONCLUSION: Early recognition and prompt initiation of chemo-immunotherapy can stabilize airway compromise and induce rapid response in tracheal SCC. However, aggressive biology mandates close follow-up and individualized, multidisciplinary management.