HPV-Associated Sarcomatoid (Spindle Cell) Carcinoma of the Base of the Tongue with HRAS and TERT Promoter Mutations

Abstract

Background: Sarcomatoid carcinoma is an aggressive and uncommon variant of squamous cell carcinoma that is rarely encountered in the oropharynx. Distinguishing this entity from true sarcomas or reactive stromal proliferations can be challenging, particularly in cases where the conventional squamous component is minimal or not readily apparent. Molecular characterization of head and neck sarcomatoid carcinomas remains sparse.

Methods: A 62-year-old male with no significant past medical history presented with an exophytic mass involving the right base of tongue and floor of mouth. The lesion exhibited a reddish base with a whitish-black surface and areas of ulceration. The patient had a longstanding smoking history. Imaging revealed a metabolically active lesion in the right tongue base. He underwent right partial glossectomy, right marginal mandibulectomy, and right selective neck dissection, followed by adjuvant radiotherapy.

Results: Histopathologic evaluation demonstrated a malignant neoplasm predominantly composed of spindle and pleomorphic cells with eosinophilic cytoplasm and elongated to rounded nuclei showing vesicular chromatin and prominent nucleoli. There was brisk mitotic activity (>20 mitoses per 10 high-power fields) and focal necrosis. A transition from high-grade squamous dysplasia to invasive carcinoma was identified, with the tumor predominantly exhibiting spindle cell morphology and a minor conventional squamous component. Metastatic involvement was identified in 3 of 30 lymph nodes (right levels 2A and 2B). Immunohistochemically, the spindle cells were positive for cytokeratin, CD10, and p16, and demonstrated high-risk HPV E6/E7 mRNA expression by in situ hybridization; they were negative for p40 and p63. Molecular profiling identified pathogenic variants in HRAS (p.G12S), EZH2 (p.P262fs), and the TERT promoter (c.-146C>T). At 6-month follow-up, the patient remains disease-free with no evidence of recurrence or metastasis.

Conclusions: We report a rare case of HPV-associated sarcomatoid carcinoma of the base of the tongue. The predominance of spindle cell morphology combined with an atypical immunophenotype-lack of squamous markers and strong p16 expression-poses a significant diagnostic challenge, particularly in small biopsies. Comprehensive diagnostic evaluation, including HPV-specific testing such as in situ hybridization, is critical for accurate diagnosis.

Keywords: HPV; NGS; Oropharynx; Sarcomatoid carcinoma.