A 14-year-old adolescent boy presented with swelling of his neck. Computed tomography scans showed a 4.5-cm conglomeration along the right posterior jugular chain with associated lymphadenopathy bilaterally. Biopsy showed a partially effaced lymph node architecture with nodules surrounded by sclerotic bands (panel A: hematoxylin and eosin [H&E] stain, original magnification ×5); scattered large to giant tumor cells surrounded by small lymphocytes, eosinophils, histiocytes, and neutrophils (panel B: H&E stain, original magnification ×400); tumor cells resembling Reed-Sternberg cells with an “owl’s eye” appearance (panel C: H&E stain, original magnification ×1000); and small clusters of tumor cells, lacunar cells, and mummified cells. The neoplastic cells expressed CD30 (panel D: subset, original magnification ×400), CD15 (panel E: rare, original magnification ×400), fascin, and MUM1 (panel F: subset, original magnification ×400), without CD20, PAX5 (panel G: original magnification ×400), CD79a, CD45, or other lymphoid markers. Tumor cells were strongly positive for Epstein-Barr virus small RNA by in situ hybridization (panel H: ×400; EBER, Epstein-Barr virus encoded RNA). Initially, PAX5-negative nodular sclerosis classic Hodgkin lymphoma was considered. Because of an unexpected positron emission tomography-avid signal in the right nasopharyngeal area, additional stains were performed. Tumor cells, in singles, cords, or aggregates expressed cytokeratins AE1/AE3 (panel I: ×400), CK19 (panel J: ×400), Cam5.2 (panel K: ×400), and p53 but not CK7/20, and revealed a diagnosis of nonkeratinizing squamous cell carcinoma, undifferentiated subtype (formerly nasopharyngeal carcinoma).

This case highlights the striking resemblance between rare metastatic carcinoma and classic Hodgkin lymphoma both clinically and pathologically, posing a potential diagnostic pitfall.