# Metastatic HPV-Related Multiphenotypic Sinonasal Carcinoma: A Case Report and Review of the Literature

## TL;DR

This paper reports the first case of a rare HPV-related cancer spreading to the liver, challenging its known indolent behavior.

## Contribution

The first documented case of metastatic liver involvement in HPV-related multiphenotypic sinonasal carcinoma.

## Key findings

- HMSC can exhibit aggressive systemic progression, including early liver metastasis.
- HPV35, a rare subtype, was identified in this case of HMSC.
- Early detection of distant metastases is critical for managing HMSC.

## Abstract

Human papillomavirus (HPV)–related multiphenotypic sinonasal carcinoma (HMSC) is a rare neoplasm characterized by a paradoxical clinical course. Despite its high-grade histologic features, HMSC exhibits an unexpectedly indolent clinical behavior, marked by frequent local recurrences but limited metastatic potential. We report the first case of HMSC metastasis to the liver with the earliest known distant progression.

A 53-year-old male who presented with unilateral epistaxis was found to have T4aN0M0 HPV35-positive HMSC of the left maxillary sinus, with erosion into the orbital floor. He underwent induction chemotherapy, endoscopic resection with negative margins, and adjuvant chemoradiation. He did well until surveillance PET-CT at 10 months revealed asymptomatic hepatic metastases confirmed by biopsy. He was treated with transarterial chemoembolization and pembrolizumab before developing locoregional recurrence involving the orbital apex and cavernous sinus 5 months later.

Several case reports demonstrate HMSC's potential for aggressive behavior, including intracranial extension and rapid recurrence. However, distant metastases (DM) are rare, with only three documented cases of pulmonary metastases and one digital metastasis, occurring years after initial treatment. We present the first reported case of HMSC with metastasis to the liver, marking the earliest known distant recurrence. This case challenges the current paradigm by highlighting HMSC's potential for aggressive systemic progression. Molecularly, this tumor harbored high-risk HPV35, a rarely reported subtype. Despite HMSC's typically indolent course, this case underscores the importance of vigilant surveillance to detect early DM and guide therapeutic management.