Re-evaluation of 33 'unclassified' eosinophilic renal cell carcinomas in young patients.
AIMS
We sought to determine if some unclassified renal cell carcinomas (RCCs) in children and young adults that are characterised by predominantly eosinophilic cytoplasm are related to the recently described succinate dehydrogenase (SDH)-deficient RCC, fumarate hydratase (FH)-deficient RCC or eosinophilic solid and cystic (ESC) RCC.


METHODS AND RESULTS
We reviewed 33 unclassified RCCs with predominantly eosinophilic cytoplasm in patients aged 35 years or younger. Immunohistochemistry (IHC) for SDHB, FH and CK20 (a marker of ESC) was performed in all cases. IHC for 2-succinocysteine (2SC) was performed on RCC with loss of FH labelling. Four RCC (12%) (median age 18 years) demonstrated loss of FH labelling as well as aberrant 2SC labelling, and were thus classified as FH-deficient RCCs. Importantly, none of these cases demonstrated the characteristic macronucleoli typical of FH-deficient RCC. Eight RCC (24%) (median age 20.5 years) demonstrated loss of SDHB and were reclassified as SDH-deficient RCCs. Importantly, only four of eight SDH-deficient RCC demonstrated the characteristic cytoplasmic vacuoles and inclusions of typical SDH-deficient RCC. Ten RCC (30%) (median age 27 years) were reclassified as ESC RCCs. Four of 10 ESC RCC were multifocal (one bilateral), four of 10 ESC RCC occurred in males and one patient presented with liver and lung metastases, all not described previously in ESC. Eleven RCC (33%) remained unclassified.


CONCLUSIONS
Pathologists should have a low threshold for performing FH, SDHB and CK20 IHC when confronted with unclassified eosinophilic RCC or 'oncocytoma' in young patients.
['Li|Yunjie|Y|', 'Reuter|Victor E|VE|', 'Matoso|Andres|A|http://orcid.org/0000-0003-0990-1115', 'Netto|George J|GJ|', 'Epstein|Jonathan I|JI|http://orcid.org/0000-0003-1839-6472', 'Argani|Pedram|P|http://orcid.org/0000-0001-8797-9474']
D000293:Adolescent D000328:Adult D002292:Carcinoma, Renal Cell D042963:Electron Transport Complex II D004804:Eosinophils D005260:Female D005649:Fumarate Hydratase D006801:Humans D007680:Kidney Neoplasms D008297:Male D008661:Metabolism, Inborn Errors D028361:Mitochondrial Diseases D009123:Muscle Hypotonia D009386:Neoplastic Syndromes, Hereditary D011596:Psychomotor Disorders D055815:Young Adult
renal cell carcinoma fumarate hydratase eosinophilic solid and cystic RCC paediatric succinate dehydratase