CRA39 PRIMARY PULMONARY HYALINIZING CLEAR CELL CARCINOMA IN A PATIENT WITH PRIOR NASOPHARYNGEAL CARCINOMA: A MOLECULAR DIAGNOSTIC CHALLENGE

Nor Safiqah Sharil^1,2, Boon Hau Ng¹, Rose Azzlinda Osman¹, Hsueh Jing Low³, Nik Nuratiqah Nik Abeed¹, Andrea Yu-Lin Ban¹

1.      Respiratory Unit, Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Hospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia.
2.      Internal Medical Unit, Faculty of Medicine and Health Science, Universiti Sains Islam Malaysia, Nilai, Negeri Sembilan.
3.      Department of Anesthesiology and Critical Care, Faculty of Medicine, Universiti Kebangsaan Malaysia, Hospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia.

Introduction
Hyalinizing clear cell carcinoma (HCCC) is a rare low-grade malignancy of salivary gland origin, with pulmonary involvement being exceptionally rare. Fewer than 10 cases of primary bronchial HCCC have been reported to date. In patients with a prior malignancy, such lesions are often presumed to be metastatic. We report a diagnostically challenging case of pulmonary HCCC in a patient with a history of nasopharyngeal carcinoma (NPC), confirmed via EWSR1 gene rearrangement.

Case report
A 74-year-old Chinese man, a non-smoker, was under oncology surveillance for recurrent NPC, previously treated with chemoradiotherapy in 2022 and gemcitabine-carboplatin in 2024. PET-CT in March 2025 showed an FDG-avid right hilar mass (SUVmax 5.1), raising concern for metastasis. Bronchoscopy revealed complete obstruction of the right middle lobe (RML) bronchus. The biopsy revealed a low-grade epithelial neoplasm with clear cell morphology in a hyalinized stroma. Immunohistochemistry was inconclusive for lung adenocarcinoma or NPC metastasis. Fluorescence in situ hybridization (FISH) confirmed the presence of EWSR1 gene rearrangement, diagnostic of HCCC. Retrospective review of previous NPC histology showed no clear cell features and was negative for EWSR1 fusion. The lesion was concluded to be a second primary—pulmonary HCCC—with possible bony metastasis based on sclerotic spinal lesions.

Conclusion
This case illustrates the diagnostic challenge in distinguishing between rare pulmonary primaries and metastases or post-radiation changes, particularly in oncology survivors. The use of FISH to confirm EWSR1 rearrangement was pivotal in establishing the diagnosis of HCCC. Pulmonary HCCC may present as an endobronchial mass with FDG avidity, mimicking more common malignancies. Awareness of this rare entity and early incorporation of molecular diagnostics are essential to avoid misdiagnosis and guide appropriate management in complex oncological cases.