PAX6 emerges as the most reliable transcription factor for duodenal neuroendocrine tumors, expressed in 85% of cases, while most tumors show mixed hormone patterns rather than single profiles, according to a retrospective analysis that offers practical guidance for diagnostic workups.
The single-center study of 53 patients suggests pathologists should consider broader hormone panels when evaluating duodenal NETs, as 57% expressed multiple hormones simultaneously. Gastrin predominated in 66% of cases, appearing with diffuse staining in 43% and focal staining in 23%.
Key diagnostic takeaways include PAX6 as a more reliable marker than CDX2, which appeared in only 65% of tumors. ARX was expressed in 33% of cases, while PAX4 was absent in all tumors studied.
Serotonin-positive tumors may warrant enhanced surveillance, as serotonin expression showed a trend toward predicting recurrence and metastasis. Among the 26% of tumors expressing serotonin, none were associated with carcinoid syndrome, but the finding suggests potential prognostic significance.
Tumor stage—particularly lymph node metastasis—was a stronger predictor of adverse outcomes than Ki67 index. PAX6 expression was associated with smaller tumor size and lower grade, while somatostatin expression was more frequent in younger patients.
For tumor boards, the research indicates that traditional single-hormone classification systems may oversimplify duodenal NET biology and current diagnostic approaches. Pancreatic polypeptide appeared in 38% of tumors, somatostatin in 25%, and peptide YY in 19%, suggesting comprehensive hormone panels provide more complete tumor characterization.
The researchers examined consecutively diagnosed cases from 2012 to 2022. Patient ages ranged from 33 to 81 years (mean 65), with 30 men and 23 women. Specimens consisted of 18 biopsies, 19 endoscopic mucosal resections, and 16 surgical resections. Among 22 patients with available lymph node data, 68% had nodal metastases.
Study limitations include the single-center design and modest sample size of 53 patients, which may limit broader generalizability. However, the findings provide immediate practical value for immunohistochemical workups and may influence how pathologists approach duodenal NET classification.
Tumor morphology was assessed with hematoxylin–eosin staining, and immunohistochemistry was performed for transcription factors PAX6, CDX2, ARX, and PAX4, as well as for multiple gastrointestinal hormones. Hormone and transcription factor expression was recorded as positive or negative, with positive results further categorized as diffuse or focal, strong or weak. Ki67 labeling index and tumor stage were recorded for all cases, and statistical analyses included non-parametric tests and χ² or Fisher exact testing.
The authors reported no competing interests.
Source: Endocrine Pathology
