Re-classification of Historic Cases of Sinonasal Undifferentiated Carcinoma using Contemporary Diagnostic Understanding
Dr Blake Lindsay, ENT Registrar, Royal Prince Alfred Hospital, Sydney, Australia
Authors List
Lindsay, B., Rhinology and Skull Base Research Group, St Vincent’s Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
Nguyen, MA., Royal Prince Alfred Hospital, Sydney, Australia
Sacks, PL., Rhinology and Skull Base Research Group, St Vincent’s Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
Brown, J., St Vincents Hospital, Sydney, Australia
Earls, P., St Vincents Hospital, Sydney, Australia
Gupta, R., Royal Prince Alfred Hospital, Sydney, Australia
Harvey, R., Rhinology and Skull Base Research Group, St Vincent’s Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
Campbell, R., Rhinology and Skull Base Research Group, St Vincent’s Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
Introduction: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive malignancy of the nasal and paranasal sinus epithelium, characterized by rapid progression and poor prognosis. Diagnosing SNUC is often a diagnosis of exclusion when histopathological features do not meet criteria for other sinonasal carcinomas. Advances in understanding newly described neoplasms (e.g. NUT midline carcinoma) and subsets of SNUC (e.g. SMARCA4 and SMARCB1-deficient sinonasal carcinoma) suggest that cases historically labelled as SNUC may represent distinct entities under current pathology criteria.
Aim: This study re-evaluates historical tissue samples from patients diagnosed with SNUC in New South Wales, Australia, over 24 years. Using contemporary diagnostic criteria and techniques, we aim to classify these cases into newly recognized subsets or alternative diagnoses and correlate these with patient outcomes.
Methods: Archived tumour specimens with a diagnosis of SNUC were subjected to histopathological re-review, immunohistochemical (IHC) analysis with contemporarily available stains (NUT, SMARCA4, INI-1). Molecular profiling via next-generation sequencing (NGS) was completed in viable samples which were not re-classified by IHC. Findings were correlated with clinical presentations, treatment courses, and outcomes.
Results: Twenty-three patients were identified from our records (age 53.6±15.5yrs, 47.8% female), and twenty with viable tissue for re-evaluation with immunohistochemistry. Immunohistochemical analysis revealed two cases of SMARCB1/INI-1 deficient carcinoma, and 0 cases of SMARCA4 and NUT midline carcinoma. NGS was completed in 8 viable samples, and did not lead to a change in diagnosis in any sample. However, all had genetic mutations potentially targetable by immunotherapy. Median survival of patients re-classified with SMARCB1/INI-1 deficient carcinoma was 29.0 months (95% CI: 19.8 – 38.3), compared to 66.5 months (95% CI: 15.7 – not reached) for the remaining group.
Conclusion: This study highlights the value of ensuring modern immunohistochemical classification and possible identification of actionable mutations from NGS for SNUC patients.
Lindsay, B., Rhinology and Skull Base Research Group, St Vincent’s Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
Nguyen, MA., Royal Prince Alfred Hospital, Sydney, Australia
Sacks, PL., Rhinology and Skull Base Research Group, St Vincent’s Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
Brown, J., St Vincents Hospital, Sydney, Australia
Earls, P., St Vincents Hospital, Sydney, Australia
Gupta, R., Royal Prince Alfred Hospital, Sydney, Australia
Harvey, R., Rhinology and Skull Base Research Group, St Vincent’s Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
Campbell, R., Rhinology and Skull Base Research Group, St Vincent’s Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
Introduction: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive malignancy of the nasal and paranasal sinus epithelium, characterized by rapid progression and poor prognosis. Diagnosing SNUC is often a diagnosis of exclusion when histopathological features do not meet criteria for other sinonasal carcinomas. Advances in understanding newly described neoplasms (e.g. NUT midline carcinoma) and subsets of SNUC (e.g. SMARCA4 and SMARCB1-deficient sinonasal carcinoma) suggest that cases historically labelled as SNUC may represent distinct entities under current pathology criteria.
Aim: This study re-evaluates historical tissue samples from patients diagnosed with SNUC in New South Wales, Australia, over 24 years. Using contemporary diagnostic criteria and techniques, we aim to classify these cases into newly recognized subsets or alternative diagnoses and correlate these with patient outcomes.
Methods: Archived tumour specimens with a diagnosis of SNUC were subjected to histopathological re-review, immunohistochemical (IHC) analysis with contemporarily available stains (NUT, SMARCA4, INI-1). Molecular profiling via next-generation sequencing (NGS) was completed in viable samples which were not re-classified by IHC. Findings were correlated with clinical presentations, treatment courses, and outcomes.
Results: Twenty-three patients were identified from our records (age 53.6±15.5yrs, 47.8% female), and twenty with viable tissue for re-evaluation with immunohistochemistry. Immunohistochemical analysis revealed two cases of SMARCB1/INI-1 deficient carcinoma, and 0 cases of SMARCA4 and NUT midline carcinoma. NGS was completed in 8 viable samples, and did not lead to a change in diagnosis in any sample. However, all had genetic mutations potentially targetable by immunotherapy. Median survival of patients re-classified with SMARCB1/INI-1 deficient carcinoma was 29.0 months (95% CI: 19.8 – 38.3), compared to 66.5 months (95% CI: 15.7 – not reached) for the remaining group.
Conclusion: This study highlights the value of ensuring modern immunohistochemical classification and possible identification of actionable mutations from NGS for SNUC patients.
