SMARCB1 (INI-1)-deficient carcinoma with eosinophilia and cervical lymph node metastasis of unknown primary: a case report and literature review

Background: Cancer of unknown primary (CUP) represents a heterogeneous group of metastatic malignancies in which the primary site remains unidentified despite comprehensive clinical, laboratory, radiological, and pathological evaluation. CUP is generally characterized by aggressive biological behavior, poor prognosis, and the absence of standardized treatment strategies. Tumor-associated blood eosinophilia (TABE) is relatively uncommon and typically occurs after tumor dissemination, often indicating an unfavorable prognosis. SMARCB1 (INI-1) is a core subunit of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex, and its functional loss can drive tumorigenesis through epigenetic dysregulation. However, cases of SMARCB1-deficient carcinoma presenting as CUP with marked TABE are exceedingly rare, posing significant diagnostic and therapeutic challenges. Case report: A 71-year-old man presented with a painless mass in the left side of the neck accompanied by generalized pruritus. Laboratory evaluation revealed persistent peripheral blood eosinophilia, and imaging studies demonstrated multiple enlarged lymph nodes in the left supraclavicular region and abdominal cavity. Histopathological examination of a lymph node biopsy showed poorly differentiated carcinoma. Immunohistochemistry revealed loss of nuclear SMARCB1 expression. A final diagnosis of SMARCB1-deficient undifferentiated carcinoma was established, and comprehensive systemic evaluation failed to identify a primary tumor. The patient received paclitaxel combined with cisplatin and a programmed cell death protein 1 (PD-1) inhibitor. Immunotherapy was discontinued due to the development of immune-related cutaneous adverse events. Despite subsequent management, the disease progressed rapidly, with the development of brainstem metastasis, and the patient ultimately died. Conclusion: We report a case of SMARCB1-deficient undifferentiated carcinoma presenting as CUP, predominantly with cervical lymph node metastases, accompanied by marked TABE. The benefit of current empirical treatment strategies appears limited. Future prospective clinical studies targeting the epigenetic vulnerabilities of this entity are warranted to improve patient outcomes.