Fenestrating Adenocarcinoma
Bibliographic record
Abstract
Most salivary gland tumors are found to have genetic fusions driving their oncogenesis, with an explosion of such findings in recent years. They typically represent previously identified and well-characterized tumors and the fusions are generally not necessary for diagnosis but rather serve as diagnostic arbitrators in challenging cases. That said, occasional unexpected molecular findings are broadening our understanding of these common tumors and have led to the emergence of new entities, some of which were "hiding in plain sight" and are quite common, like secretory carcinoma. In contrast, others are sufficiently rare that molecular testing was required to identify them in small cohorts, combining cases from multiple institutions, such as microcribriform adenocarcinoma. Recently, we identified a rare case of tongue adenocarcinoma with EWSR1::BEND2 fusion with an unusual morphology, and 2 additional cases were subsequently briefly reported in the literature. In this study, we collected and analyzed a total of 7 cases that show variable but consistent morphology, including a fenestrating glandular appearance, occasional squamous or basaloid growth, and focal mucinous cells. The tumors showed a predilection for the pharynx with 4 cases in the base of the tongue, one case in the tonsil/oropharyngeal wall, one case in the nasopharynx, and only one nonpharyngeal case in the trachea. No oral cavity or major salivary gland tumors were found with this set of findings to date. The tumors showed some aggressive tendencies, with 2/4 with follow-up information having adverse outcomes, including lymph node metastases in 2 cases and 1 of these cases also having brain metastases, recurrence, and death from disease. All cases tested showed EWSR1::BEND2 fusion by NGS, as well as CK7/BEND2 positivity, and S100 negativity by immunohistochemistry. The tumors showed variable p63 staining depending on whether squamous or basaloid features were present. A tissue microarray (TMA) stained with an antibody directed against the BEND2 protein showed no significant staining in any other salivary tumor type. The constellation of findings in this cohort is highly suggestive of a specific entity, and we propose the appellation "Fenestrating Adenocarcinoma (FAC)" of the salivary gland.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".