Extraskeletal Ewing sarcoma (EES) is a rare, highly aggressive malignant mesenchymal neoplasm belonging to the Ewing sarcoma family of tumors (ESFT). It accounts for approximately 15–20% of all Ewing sarcomas and shares the same histopathological, immunophenotypic, and molecular characteristics as conventional osseous Ewing sarcoma [1–3]. Although EES may occur at virtually any anatomical site, it predominantly arises in the deep soft tissues of the trunk, paravertebral region, pelvis, and lower extremities. Primary involvement of the head and neck is distinctly uncommon, representing only a small proportion of reported cases, while cervical localization remains exceptionally rare [2,4,5].

The rarity of cervical EES represents a major diagnostic challenge because its clinical presentation is usually nonspecific. Most patients present with a progressively enlarging painless cervical mass, whereas pain, neurological deficits, dysphagia, dysphonia, or respiratory symptoms generally occur only after compression of adjacent neurovascular or aerodigestive structures [4–7]. Our patient presented with an isolated rapidly enlarging cervical swelling without constitutional symptoms or neurological impairment despite the considerable tumor size. This relatively silent clinical course probably reflects the ability of the lesion to expand progressively along the cervical fascial planes before producing compressive manifestations.

Radiological assessment plays a central role in determining tumor extent and surgical planning but lacks sufficient specificity to establish a definitive diagnosis. In most published reports, cervical EES appears as a poorly or well-defined heterogeneous solid soft-tissue mass showing variable contrast enhancement with areas of necrosis or hemorrhage [2,5,8]. MRI usually demonstrates an isointense lesion on T1-weighted images and heterogeneous hyperintensity on T2-weighted sequences, with marked diffusion restriction owing to its high cellularity [8]. However, these findings overlap considerably with those observed in other malignant soft-tissue tumors, making imaging alone insufficient for diagnosis.

The radiological appearance observed in our patient was particularly unusual. CT demonstrated a giant multiloculated predominantly cystic lesion containing thick internal septa and only limited mural soft-tissue components. Moreover, surgical exploration confirmed multiple interconnected cystic cavities filled with abundant serous fluid, necessitating controlled aspiration before complete excision. Such a presentation has only exceptionally been reported in the literature and substantially broadened the differential diagnosis. Indeed, both the imaging and intraoperative findings strongly suggested a benign congenital cystic lesion rather than a malignant mesenchymal tumor. This observation emphasizes that EES should not be excluded solely because of a predominantly cystic appearance, particularly in young adults presenting with rapidly enlarging cervical masses [4–8].

The differential diagnosis of a multiloculated cystic lateral neck mass is broad and includes second branchial cleft cysts, cystic lymphatic malformations, infected congenital cysts, cystic schwannomas, abscesses, necrotic metastatic lymphadenopathy, and, less frequently, cystic salivary gland neoplasms [5,8]. Clinical history, patient age, imaging characteristics, and growth kinetics may orient the diagnosis; nevertheless, considerable overlap exists between these entities. In the present case, the rapid increase in tumor size over only two months together with the presence of mural soft-tissue nodules represented subtle imaging findings suggestive of an underlying malignant process despite the predominantly cystic morphology.

Histopathological examination remains the cornerstone of diagnosis. Microscopically, EES consists of sheets of uniform small round blue cells with hyperchromatic nuclei, finely dispersed chromatin, inconspicuous nucleoli, and scant cytoplasm rich in glycogen [1,9]. Because these features overlap with several other malignant small round cell tumors, including rhabdomyosarcoma, lymphoma, poorly differentiated synovial sarcoma, mesenchymal chondrosarcoma, desmoplastic small round cell tumor, and neuroblastoma, immunohistochemical and molecular analyses are indispensable [9–11]. Diffuse membranous expression of CD99 remains the most sensitive immunohistochemical marker, while NKX2.2 and FLI-1 significantly improve diagnostic specificity. Whenever feasible, demonstration of an EWSR1 rearrangement by FISH or RT-PCR remains the diagnostic gold standard [10,11]. In our patient, the diagnosis was established only after complete surgical excision, highlighting the limitations of clinical and radiological evaluation in atypical presentations.

Current treatment recommendations advocate multimodal therapy combining systemic chemotherapy with complete surgical excision whenever feasible, followed by radiotherapy according to surgical margins, histological response, and tumor stage [12–15]. Neoadjuvant chemotherapy has become the standard approach in many specialized sarcoma centers because it facilitates tumor downsizing, eradicates occult micrometastatic disease, and provides valuable prognostic information through assessment of histological response [12]. However, surgery remains the cornerstone of local control in resectable lesions. In the head and neck region, complete resection may be technically demanding because of the intimate relationship between the tumor and major vessels, cranial nerves, and the upper aerodigestive tract. In the present case, controlled aspiration of the cystic content substantially reduced tumor volume and allowed meticulous dissection while preserving all major cervical neurovascular structures, thereby facilitating complete excision without intraoperative complications.

Several prognostic factors have been consistently associated with survival in patients with Ewing sarcoma, including metastatic disease at diagnosis, tumor size, axial location, histological response to chemotherapy, surgical margin status, and local recurrence [12–15]. Patients with localized disease treated using contemporary multimodal protocols currently achieve 5-year overall survival rates approaching 70–80%, whereas the presence of metastatic disease at diagnosis remains associated with a markedly poorer prognosis [13–15].

Finally, our case expands the clinicoradiological spectrum of cervical extraskeletal Ewing sarcoma. To our knowledge, reports describing a giant predominantly multiloculated cystic cervical EES containing abundant serous fluid and closely mimicking a congenital branchial cleft cyst remain exceptionally scarce. This unusual presentation underscores the importance of maintaining a high index of suspicion when evaluating rapidly enlarging cystic neck masses in young adults. Early histopathological diagnosis, multidisciplinary management, and prompte initiation of oncological treatment remain essential for improving clinical outcomes.