CIC-DUX4 Sarcoma Involving the Skull Base: A Rare Presentation and Review of the Literature

Objective: The finding of a progressively enlarging lateral neck mass in the adult patient is always concerning for malignancy. While most neoplastic cervical adenopathy represents metastatic squamous cell carcinoma, less common tumors remain on the differential. CIC-DUX4 sarcomas are one such rare tumor. Though closely related to Ewing's sarcoma, CIC-DUX4 sarcomas are their own distinct pathologic entity. These aggressive, poorly differentiated sarcomas have been reported in the skin, lymph nodes, and viscera. We report the first description of CIC-DUX4 involving the middle cranial fossa and review the unique symptomatology, morphology, immunoprofile and genetic signature that distinguish this rare tumor.

Case Report: A 32-year-old man with morbid obesity presented with an enlarging right lateral neck mass, progressive hoarseness, and orofacial pain. Prior to our evaluation, biopsy revealed a high-grade undifferentiated malignant neoplasm suggestive of Ewing's sarcoma. CT imaging demonstrated an 8-cm mass in the right neck extending to the middle cranial fossa and abutting the carotid sheath, pulmonary nodules, and pelvic lymphadenopathy ([Fig. 1]). Despite initial response to chemotherapy, he experienced disease progression. His body habitus precluded standard-of-care external beam radiation; thus, surgical resection, radical neck dissection, and brachytherapy were performed ([Fig. 2]). Intraoperatively, the tumor involved the superior laryngeal nerve, vagus nerve, and occipital artery. Preservation of the vagus was attempted; however, the lesion was completely adherent to the nerve at the carotid bifurcation. The superior portion of the vagus was transected, producing notable bradycardia. Despite concern for residual disease, there was reluctance to chase tumor along the skull base given his lung metastasis and cardiac response to nerve sacrifice. Within 8 weeks of treatment, he developed diplopia, dysphagia, and dyspnea reflecting progression of disease involving the neck, middle cranial fossa, and lung. CT head venogram showed soft tissue lesions in the right neck with encasement of the hypoglossal nerve and carotid space, thrombus in the upper internal jugular vein, and dural sinus thrombosis extending into the sigmoid sinus ([Fig. 3]). Additional cranial neuropathies including right anisocoria, right-sided hearing loss, and central facial nerve palsy raised concern for leptomeningeal disease. Definitive pathologic diagnosis was achieved with next-generation sequencing. Adjuvant chemotherapy was planned, but the patient succumbed to his disease prior to initiation of further therapy.

Discussion: CIC-DUX4 sarcomas are rare, aggressive tumors that are difficult to diagnose. With a propensity for rapid growth, disease progression can quickly become locally destructive, even after attempted tumor debulking. Diagnosis requires either fluorescence in-situ hybridization or next generation sequencing. Resection, radiation therapy, and chemotherapy have all been employed with some success, however, prognosis remains poor with a 2-year survival rate around 50%. Due to its rarity, there is no standard-of-care treatment for this tumor and further study is needed to understand disease behavior and develop targeted therapeutic modalities.

Fig. 1 CT of the head and neck with axial view demonstrating 8-cm mass in right neck.

Fig. 2 Brachytherapy catheters in place.

Fig. 3 CT venogram demonstrating cavernous sinus thrombosis in axial (L) and coronal (R) view.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
15 February 2022