Supplementary Material for: Unveiling Occult Nasopharyngeal (Undifferentiated) Carcinoma: A Case Series Highlighting the Worth of Fine-Needle Aspiration Cytology as a Frontline Diagnostic Tool for Hidden Lethal Malignancies

Introduction: Nasopharyngeal carcinoma (NPC) represents a significant burden in Asia, especially in Southern China, with cervical lymph nodes being one of the most common sites of metastasis. At times, peripheral lymphadenopathy may be the only manifestation of an occult primary tumor. Case Presentation: We report three cases: the first with classical cervical lymphadenopathy, while two with rare unusual presentations-right preauricular and right periorbital lesions. The cytological evaluation in all revealed metastatic undifferentiated NPC, which led to the identification of an occult nasopharyngeal primary. Conclusion: This series highlights the indispensable role of FNAC with a dual-stain approach and intricate diagnostic challenges in deciphering occult undifferentiated NPC. To the best of our knowledge, this is the first series to formally document a significant observation-stain-dependent cytologic shift in undifferentiated NPC: tumor cells appeared as dispersed with hyperchromatic homogeneously dark-stained naked nuclei mimicking lymphoma on Giemsa, but as loosely-cohesive clusters or syncytial sheets with vesicular nuclei on Papanicolaou. Giemsa alone risks mimicking lymphoma and Papanicolaou alone risks mimicking metastatic carcinoma. Such perplexing cytomorphological variations with two stains risk erroneous diagnoses, yet offer a unique clue to undifferentiated NPC. Thus, extensive cytologic sampling with dual-stain strategy enables early recognition of an aggressive, elusive and often misdiagnosed malignancy, significantly improving survival in cases that would otherwise be fatal.