Sporadic Oncocytic Tumors with Features Intermediate between Oncocytoma and Chromophobe Renal Cell Carcinoma: Comprehensive Clinico-Pathological and Genomic Profiling
Bibliographic record
Abstract
ABSTRACT Background Morphology, clinical behavior, and genomic profiles of renal oncocytoma (RO) and its malignant counterpart chromophobe renal cell carcinoma (ChRCC) are distinctly different. However, there is a substantial group of sporadic oncocytic tumors with peculiar hybrid phenotypes as well as a perplexing degree of morphologic and immunohistochemical overlap between classic RO and ChRCC with eosinophilic cytoplasm. The aim of this study is to provide detailed characterization of these hybrid tumors. Design Thirty eight sporadic oncocytic neoplasms with ambiguous morphology from two institutions were reviewed by 4 pathologists. CKIT positivity was used as a selection criterion. We correlated CK7 and S100A1 immunostaining and detailed morphologic features with cytogenetic profiles. DNA from the FFPE tissues was extracted and analyzed using Cytogenomic Microarray Analysis (CMA) to evaluate copy number alterations and ploidy. Results CMA categorized cases into 3 groups: RO (N=21), RO variant (N=7) and ChRCC (N=10). Cytogenetic RO had either no CNA (48%) or loss of chromosome 1p, X or Y (52%). RO-variant had additional chromosomal losses [-9q, –14 (n=2), –13] and chromosomal gains [+1q (n=2), +4, +7 (n=2), +13, +19, +20, and +22]. ChRCC were either hypodiploid with numerous monosomies (40%) or hypotetraploid with multiple relative losses (60%). RO, RO-variant and ChRCC groups differed significantly in tumor architecture (p<0.01), stroma (p=0.013), presence of nuclear wrinkling, perinuclear halos and well-defined cell borders in >5% cells (p<0.01), focal cell clearing (p=0.048) and CK7 expression (p<0.02). Pathologic prediction of cytogenetic subtype using only two categories (benign RO or malignant ChRCC) would overcall or undercall up to 40% of tumors that were ChRCC based on cytogenetics. This finding provides the rationale for an intermediate diagnostic category of so-called hybrid tumors (HOCT). HOCT was a heterogeneous group enriched for cytogenetic RO-variant. Other HOCTs have a profile of either RO or ChRCC. Conclusions Genomic profile allows classification of oncocytic tumors with ambiguous morphology into RO, RO-variant and ChRCC. Several architectural and cytologic features combined with CK7 expression are significantly associated with cytogenetic RO, RO-variant or ChRCC tumors. Doubled hypodiploidy by whole genome endoduplication is a common phenomenon in eosinophilic ChRCC. Parts of this study were presented in an abstract form at the 104 th annual meeting of the United Stated and Canadian Academy of Pathology, Boston, March 21–27, 2015
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".