Table 2. Gross, Morphologic, IHC and Molecular Findings for TC-PD RCCs.
| Final Label | Age | Sex | Classification∼ | Gross# | Siteˆ | TC-Proportion& | Nucleoli% | Necrosis$ | Sarcomatoid$ | ISUP Grade$ | FH IHC© | 2SC IHC© | FH Mutation |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TC-D 1 | 18 | M | FH-D | 1, 3 | - | 1 | 2 | 0 | 0 | 4 | lost | - | - |
| TC-D 2 | 20 | M | FH-D | 2 | C,M | 1 | 2 | 1 | 0 | 3 | lost | pos (3+) | - |
| TC-D 3 | 25 | M | FH-D | 1 | C,M | 3 | 1 | 0 | 0 | 3 | lost | pos (3+) | homozygous Y251fs |
| TC-D 4 | 40 | M | FH-D | 1,3 | C | 3 | 2 | 0 | 0 | 3 | lost | pos (3+) | homozygous K80fs |
| TC-D 5 | 42 | M | FH-D | 2 | C,M | 3 | 2 | 0 | 0 | 3 | lost | pos (3+) | - |
| TC-D 6 | 42 | F | FH-D | 2 | C,M | 2 | 2 | 0 | 0 | 3 | lost | pos (3+) | homozygous R101X |
| TC-D 7 | 42 | F | FH-D | 2 | C,M | 1 | 2 | 0 | 0 | 3 | lost | pos (3+) | focal deletion |
| TC-D 8 | 44 | M | FH-D | 1 | C,M | 3 | 2 | 0 | 0 | 4 | lost | pos (3+) | - |
| TC-D 9 | 45 | F | FH-D | 2 | C,M | 1 | 2 | 0 | 0 | 3 | lost | pos (3+) | - |
| TC-D 10 | 46 | M | FH-D | 2,3 | C,M | 1 | 1 | 0 | 0 | 3 | lost | pos (3+) | - |
| TC-D 11 | 46 | M | FH-D | 2 | C,M | 1 | 2 | 1 | 0 | 3 | lost | pos (3+) | - |
| TC-D 12 | 52 | M | FH-D | - | M | 1 | 2 | 2 | 1 | 4 | lost | pos (3+) | - |
| TC-D 13 | 53 | M | FH-D | 1,3 | M | 2 | 1 | 0 | 0 | 3 | lost | pos (3+) | - |
| TC-D 14 | 59 | M | FH-D | 2 | C,M | 2 | 2 | 1 | 0 | 3 | lost | pos (3+) | - |
| TC-D 15 | 61 | M | FH-D | 1, 3 | C,M | 2 | 2 | 0 | 0 | 3 | lost | - | - |
| TC-D 16 | 67 | M | FH-D | 2 | C,M | 1 | 2 | 0 | 0 | 3 | lost | pos (3+) | K230R |
| TC-D 17 | 34 | F | FH-D* | 2 | M | 2 | 2 | 0 | 0 | 4 | weak | pos (3+) | V279F |
| TC-D 18 | 40 | F | FH-D* | 1 | C | 3 | 1 | 0 | 0 | 3 | weak | pos (3+) | R233H |
| TC-D 19 | 71 | M | FH-D* | - | M | 2 | 1 | 0 | 0 | 3 | weak | pos (3+) | heterozygous N188T, H318Y |
| TC-D 20 | 16 | F | FH-S | 1 | M | 3 | 1 | 0 | 0 | 3 | weak | pos (3+) | Hypermutated |
| TC-D 21 | 35 | M | FH-S | 2 | C,M | 3 | 2 | 0 | 0 | 3 | weak | pos (3+) | - |
| TC-D 22 | 50 | M | FH-S | 2 | C | 2 | 2 | 0 | 0 | 3 | weak | pos (3+) | - |
| TC-D 23 | 53 | M | FH-S | 2 | C,M | 3 | 2 | 0 | 0 | 4 | weak | pos (3+) | - |
| TC-D 24 | 53 | F | FH-S | 1 | C | 2 | 2 | 0 | 0 | 3 | weak | pos (3+) | - |
| TC-D 25 | 70 | M | FH-R | 1 | C | 2 | 1 | 2 | 0 | 3 | retained | neg (1+) | - |
| TC-D 26 | 71 | M | FH-R | 1 | C,M | 3 | 2 | 0 | 0 | 3 | retained | neg (1+) | - |
| TC-D 27 | 74 | M | FH-R | - | - | 2 | 1 | 1 | 0 | 3 | retained | neg (1+) | None |
| TC-D 28 | 80 | F | FH-R | 1 | C | 3 | 1 | 1 | 1 | 3 | retained | neg (1+) | None |
| TC-D 29 | 86 | M | FH-R | 1,3 | C | 3 | 1 | 1 | 0 | 3 | retained | neg (1+) | - |
Abbreviations: ‘-’, no data; TC-PD, tubulocystic carcinoma with poorly differentiated foci; FH, fumarate hydratase; RCC, renal cell carcinoma; IHC, immunohistochemistry; HLRCC, hereditary leiomyomatosis renal cell carcinoma syndrome; met., metastatic;
Classification – Final integrating IHC and molecular findings; FH-D, FH-deficient RCC; FH-S, FH-suspicious RCC; FH-R, FH-retained RCC,
indicates IHC suspicious case reclassified as FH-D based on NGS findings
Gross: gross appearance described as 1, circumscribed; 2, infiltrative/ill-defined; 3, cystic/multicystic
Site: anatomic localization on the kidney; M, predominantly medullary; C, predominantly cortical, C,M, involving both cortex and medulla
TC-Proportion: extent of tubulocystic pattern; 1, focal <10%; 2, non-focal 10-50%; 3, predominant >50%.
Nucleoli: degree of HLRCC-like prominent, viral inclusion-like nucleoli with perinuclear halo; 1, focal; 2 diffuse.
Necrosis (0, absent; 1, present <50%, 2, present >50%), sarcomatoid transformation (0, absent; 1, present), and ISUP grade (3, grade 3; 4, grade 4) per 2012 ISUP Vancouver Classification recommended criteria.
Immunohistochemistry for FH evaluated as retained if expressed equivalent to internal control endothelium, weak, decreased, or lost if negative. IHC for 2SC was deemed positive if strong, diffuse (3+) and nucleocytoplasmic, 2+ if weaker, or negative (0-1+) as reported previously (Chen et al. Am J Surg Pathol 2014).