Clinicopathological Correlates of Hormone Expression-Based Subtypes of Non-Functioning Duodenal/Ampullary Neuroendocrine Tumors: A Multicenter Study of 151 Cases
Bibliographic record
Abstract
Duodenal neuroendocrine tumors (Duo-NETs) may arise in the ampullary and non-ampullary duodenum. Non-functioning Duo-NETs (NF-Duo-NETs), which account for most cases, may express various hormones. Previous studies have suggested that hormone production might be associated with biological aggressiveness. Current treatment protocols are based on functionality, tumor size, and location, but small NF-Duo-NETs may also have metastatic potential. We aimed to investigate whether tumor cell subtyping, based on hormone expression, could provide further insights into NF-Duo-NET biological behavior. We analyzed the clinico-pathological correlates of hormone expression in a multicenter series of 151 NF-Duo-NETs, subdividing tumors into five subtypes: gastrin-producing G-cell NETs (Gas-NETs), somatostatin-producing D-cell NETs (Som-NETs), serotonin-producing enterochromaffin-cell NETs (Ser-NETs), plurihormonal NETs, and gastrin-, somatostatin-, and serotonin-negative NETs (GSSN-NETs). Som-NETs were the most frequent (31%), followed by plurihormonal NETs (26%), Gas-NETs (24%), GSSN-NETs (13%), and Ser-NETs (4%). Som-NETs and GSSN-NETs were more commonly located in the ampullary region and showed significantly larger size, more frequent lymphatic and/or vascular invasion, and higher pT, pN, and American Joint Committee on Cancer (AJCC-9th edition) stages compared to Gas-NETs, which were often (77%) diagnosed at AJCC stage I. Ampullary Som-NETs showed a more invasive and metastatic potential compared to non-ampullary Som-NETs, while, among plurihormonal NETs, the predominantly expressed hormone influenced tumor biological features, with gastrin-predominant NETs showing less invasive potential. At logistic regression, both tumor cell subtype and tumor size were independently associated with aggressiveness (pT3, pN1, or pM1 stage at diagnosis). Hormonal expression profiling may be clinically relevant in NF-Duo-NETs, independently of tumor size.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".