463 Unique pediatric notochord tumor case. A final diagnosis that was fulfilled with immunohistochemical and clinical pitfalls

Introduction/Objective Chordomas are tumors derived from notochord remnants that predominantly affect the skull and spine.1 The Prior edition of the World Health Organization - Blue book characterized conventional, chondroid, and dedifferentiated chordomas based on histological and immunostaining characteristics. Multiple cases of chordoma have been described with similar histology and presentation differing from the main subtypes. This subtype now classified by the WHO, called poorly differentiated chordoma (PDC), highlights many pitfalls, as they share similar morphology with rhabdoid tumors, epithelioid sarcoma, and conventional chordomas.2 PDC is rare, with under 60 cases reported in medical literature in 2019. PDC presents pediatrically and has worse outcomes compared to other subtypes. Chordomas present in the skull, spine, and sacrum/coccyx.2 Some chordomas arise from extra-axial regions, although these chordomas are exceedingly rare with only 28 cases reported in literature in 2018.3 Histologically PDC can vary, typically having sheets of epithelioid cells with nuclear pleomorphism and eosinophilic cytoplasm. Chondromyxoid stroma and physaliphorous cells are not normally present.2, 4 Necrosis and mitotic figures can be present and elevated.4 Immunohistochemically all reported cases of PDC are positive for brachyury, characteristic of notochord tumors and chordomas, cytokeratin, and EMA.2, 4-7 PDC rarely expresses the S100 protein found in conventional chordomas.2, 4, 6, 8 Methods/Case Report A 7-year-old boy presented with a several-month history of coccygeal pain accompanied by constipation, and urinary retention and incontinence. MRI imaging identified a sacral-region 2.7 x 4.9 cm lobulated mass that extended through multiple bilateral sacral foramina with associated expansion of the sacral canal and foramina. There was no evidence of direct involvement of the sacrum. These findings were initially suggestive of epithelioid malignant peripheral nerve sheath tumors (MPNST). The biopsy showed epithelioid cells with pleomorphic nuclei and eosinophilic cytoplasm, in a background of widespread necrosis and focal chondromyxoid stroma. Furthermore, rare possible physaliphorous-like cells and patchy rhabdoid cytological features were noted. Immunohistochemical stains showed diffuse cytokeratin expression and INI-1 loss. Extra-renal rhabdoid tumor, epithelioid sarcoma, and epithelioid MPNST were included in the differential. However, S-100 was negative, arguing against epithelioid MPNST. At this point, the possible physaliphorous-like cells were initially disregarded, as radiologically the tumor had no relationship with the axial skeleton and chordomas were lower in the differentials. However, brachyury surprisingly was diffusely positive on the neoplastic cells regardless of cytological features. Expert’s opinion was consulted favoring Extra-axial poorly differentiated chordoma with INI/SMARB-1 loss, which is believed to be unique. Results NA Conclusion Poorly differentiated chordoma is a newly defined subtype of chordoma that poses many pitfalls in the differential diagnosis of pediatric tumors. Although now recognized by the WHO, the few reported cases of PDC leave much to be learned about the presentation and development of this rare tumor. Our patient presented symptoms consistent with a variety of pediatric tumors, and biopsy and immunohistochemical analysis further complicated diagnosis. Upon analysis from an outside expert, the diagnosis was achieved through brachyury staining and SMARB1/INI loss on immunohistochemical staining. Brachyury is diagnostic for notochord tumors like chordomas, and SMARB1/INI loss is characteristic of PDC. Brachyury staining could therefore be used in further differential diagnosis of pediatric tumors with rhabdoid morphology, regardless of the location. The PDC in this patient is unique: an extra-axial tumor in the pre-sacral region with histological and immunohistochemical features that resemble Epithelioid sarcoma, Rhabdoid tumor, and epithelioid MPNST. Furthermore, PDC has been noted to lack physaliphorous cells in many cases, which were focally found on biopsy of the sacral mass of our patient. Our patient represents a novel and informative case of a rare tumor that will help further characterize PDC and extra-axial chordoma.