Abstract
PURPOSE: This study aims to characterize the rare morphological variant of nasopharyngeal carcinoma known as reticular and myxoid nasopharyngeal carcinoma (RMNK-NPC), which poses diagnostic challenges due to its resemblance to salivary gland tumors. We seek to detail its histopathological and immunohistochemical features, clarify differential diagnoses, and evaluate clinical outcomes. METHODS: Cases of RMNK-NPC were retrospectively identified from pathology consultation archives and multidisciplinary conference records in Taiwan. Histopathological features, including results of previously performed immunohistochemical stains and Epstein-Barr virus-encoded RNA (EBER) in situ hybridization, were reviewed by three pathologists. Relevant clinical information and imaging findings were collected when available. A literature search was conducted to identify previously reported cases with similar histological features. RESULTS: The cohort included eight patients (7 males, 1 female; median age 65.5 years). Clinical presentations included advanced-stage tumors with lymph node metastases in seven patients and distant metastasis in two patients. All tumors exhibited myxoid stroma with reticular, trabecular, and cord-like arrangements of epithelioid to spindle cells, with transition to non-keratinizing squamous cell carcinoma (NKSCC) in three cases. Immunohistochemistry showed consistent positivity for pan-cytokeratin and squamous markers, while other myoepithelial markers were mostly negative, except SOX10. EBER ISH showed strong nuclear positivity in most cases, confirming EBV association. Limited follow-up data for four patients who received chemoradiotherapy showed stable disease at 3-4 months in two. The other two patients died at 42 and 108 months, respectively, from unrelated causes, with no recurrence observed. CONCLUSION: RMNK-NPC represents an EBV-associated NPC with unique histomorphology that overlaps with salivary gland tumors. Accurate diagnosis relies on comprehensive immunohistochemical panels and EBER ISH. Awareness of this entity is crucial to avoid misdiagnosis and guide appropriate treatment.