Merlin-deficient renal cell carcinoma often exhibits high-grade cytology, admixed architectural patterns, sclerotic and mucinous stroma, inflammatory infiltrates and calcifications
Yang Liu and Luting Zhou contributed equally to this work.
Abstract
Aims
Recent studies have enhanced our understanding of NF2-mutated renal neoplasms, particularly the emerging entity of biphasic hyalinizing psammomatous renal cell carcinoma (BHP RCC) characterised by biphasic features and NF2 alterations. Subsequent studies have established that NF2-mutated renal carcinomas frequently exhibit high-grade features. This study aimed to confirm the diagnostic utility of merlin (encoded by NF2) immunohistochemistry and expand our understanding of NF2-mutated renal neoplasms.
Methods and results
This study included 14 NF2-mutated renal neoplasms. All cases underwent comprehensive histopathological, immunohistochemical, and molecular analyses. Definitive diagnosis was achieved in only three cases. The remaining 11 neoplasms, termed ‘merlin-deficient RCC’ in this study, mostly defied conventional categorization and shared morphological features including high-grade eosinophilic cytology (11/11), stromal sclerosis (11/11), mixed growth patterns (10/11), significant inflammatory infiltrates (9/11), foamy histiocyte aggregates (4/11), calcifications (3/11), and mucinous stroma (2/11). Four patients exhibited at least focal sarcomatoid morphology. The predominant architectural patterns comprised tubular structures, followed by nested, papillary, solid, cord-like, and cystic configurations. Merlin loss was observed in all evaluable cases. Extended analysis revealed merlin deficiency in 33% (1/3) of high-grade mucinous tubular and spindle cell carcinomas (MTSCC) and 25% (2/8) of collecting duct carcinomas (CDC) with unknown molecular profiles.
Conclusion
Our results suggest that merlin-deficient RCC represents a distinct molecularly defined, high-grade entity encompassing the recently recognized BHP RCC along with subsets of papillary RCC, sarcomatoid RCC, MTSCC, CDC, and unclassified high-grade RCC.
Graphical Abstract
NF2/merlin-deficient RCC may be a potential high-grade entity with a relatively consistent morphology which was scattered in BHP RCC, papillary RCC, sarcomatoid RCC, mucinous tubular and spindle cell carcinoma, collecting duct carcinoma, and unclassified RCC.
Conflict of interest
None.
Open Research
Data availability statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
