Tiane Chen

Background: Well-differentiated pancreatic neuroendocrine tumors (PanNETs) develop in ~80% of patients with multiple endocrine neoplasia type 1 (MEN1) and remain the leading cause of MEN1-related mortality. Whether MEN1-associated PanNETs display distinct clinicopathologic or prognostic characteristics compared with non-MEN1 PanNETs remains incompletely defined. Methods: We retrospectively reviewed clinical, pathological, and outcome data from 817 patients who underwent surgical resection for well-differentiated PanNETs, including 39 MEN1-associated and 778 non-MEN1 PanNETs, with a total of 7752 person-years of follow-up. Tumor characteristics, stage, and survival outcomes were compared between two groups. Results: MEN1-associated PanNETs represented 4.8% of the cohort and included both functional and non-functional tumors. Patients with MEN1 more frequently had functional tumors, with insulinomas and gastrinomas predominating. Patients with MEN1 were significantly younger at surgery. Tumor size and grade distribution were similar between the two groups, although tumors >2 cm were more prevalent in patients with MEN1. MEN1-associated tumors demonstrated significantly lower rates of lymphovascular and perineural invasion, but similar rates of lymph node metastasis and stage III disease when only lymph node metastases attributable to a pancreatic primary were included. Long-term overall survival, disease-specific survival, and cumulative incidence of relapses did not differ significantly between MEN1 and non-MEN1 patients. Conclusions: In this retrospective cohort of surgically resected, well-differentiated PanNETs, MEN1-associated tumors exhibited similar histologic grade and tumor size distributions to non-MEN1 PanNETs. MEN1 status was associated with a higher prevalence of functional tumors and lymph node metastases, but lower rates of vascular and perineural invasion. Despite these features, no statistically significant differences in long-term overall survival, disease-specific survival, or cumulative incidence of relapse were observed between surgically resected patients with and without MEN1, though the study was underpowered to detect modest differences.

Background/Objectives: The training of diagnostic pancreatic pathologists is largely limited by the diversity of available pathology images, especially those of rare diseases or conditions. Methods: Using a cohort of seven pancreatic neoplasms, we developed an iterative, pathologist-in-the-loop workflow integrating scalable tile pruning, generative-model optimization, and postprocessing truncation. Two pathologists evaluated synthetic-image quality and subtype representation on a 0–3 scale; the independent pathologist was blinded to image source and truncation condition and also rated curated real training tiles. Results: Untruncated images had lower class-balanced FID than per-class-truncated images (6.64 versus 29.08) and higher recall and coverage, whereas truncation increased precision. The independent pathologist rated per-class-truncated images higher than matched non-truncated images (mean difference 0.80, bootstrap 95% CI 0.57–1.03). Quadratic-weighted Cohen’s κ was 0.599 (95% CI 0.489–0.691); after grouping ratings as 0–1 versus 2–3, raw agreement was 80.7% (95% CI 75.0–86.4%). Conclusions: Per-class truncation improved independently rated image quality and subtype representation. Successful synthetic histology generation requires careful data curation, domain-specific oversight, and independent validation; clinical utility requires separate task-based evaluation.

Background: Well-differentiated pancreatic neuroendocrine tumors (PanNETs) develop in ~80% of patients with multiple endocrine neoplasia type 1 (MEN1) and remain the leading cause of MEN1-related mortality. Whether MEN1-associated PanNETs display distinct clinicopathologic or prognostic characteristics compared with sporadic PanNETs remains incompletely defined. Methods: We retrospectively reviewed clinical, pathological, and outcome data from 817 patients who underwent surgical resection for well-differentiated PanNETs, including 39 MEN1-associated and 778 non-MEN1 tumors, with a total of 7,752 person-years of follow-up. Tumor characteristics, stage, and survival outcomes were compared between two groups. Results: MEN1-associated PanNETs represented 4.8% of the cohort and included both functional and non-functional tumors. Patients with MEN1 more frequently had functional tumors, with insulinomas and gastrinomas pre-dominating. Patients with MEN1 were significantly younger at surgery. Tumor size and grade distribution were similar between two groups, although tumors >2 cm were more prevalent in patients with MEN1. MEN1-associated tumors demonstrated significantly lower rates of lymphovascular and perineural invasion, but similar rates of lymph node metastasis and stage III disease when only lymph node metastases attributa-ble to a pancreatic primary were included. Long-term overall survival, disease-specific survival, and cumula-tive incidence of relapses did not differ significantly between MEN1 and non-MEN1 patients. Conclusions: Surgically resected MEN1-associated PanNETs show comparable histologic grade and tumor size to sporadic PanNETs. MEN1 is associated with more functional tumors and lymph node metastases, but less vascu-lar/perineural invasion. Despite these features, long-term overall survival, disease-specific survival and cu-mulative incidence of relapse are comparable between surgically resected patients with and without MEN1.

Acinar cell carcinomas (ACCs) of the pancreas typically demonstrate distinct morphologic features including minimal fibrous stroma, acinar architecture, single prominent nucleoli and eosinophilic cytoplasmic granules. We report seven cases of metastatic carcinomas to the liver with acinar cell differentiation (two carcinomas with pure acinar cell differentiation, four carcinomas with mixed acinar neuroendocrine differentiation, one mixed acinar ductal carcinoma) that lacked many of these features, and, as a result, were misclassified. The cases were prospectively identified in our routine confirming consultation service. Clinical data and histology were retrospectively reviewed. The seven patients ranged in age from 48-72 years with a male predominance (5 males, 2 females). Five patients had a known pancreatic mass, and all patients had multiple liver lesions on initial imaging, prompting liver biopsies. Three of seven tumors in the liver were initially diagnosed at the submitting institution as high-grade neuroendocrine tumors (NETs) as they all expressed synaptophysin and/or chromogranin, had a high Ki67 proliferation index, and lacked cytoplasmic granules. The remaining four tumors in the liver were initially diagnosed as adenocarcinoma as they lacked prominent nucleoli, had prominent fibrotic stroma (3 cases), lacked eosinophilic cytoplasmic granules (3 cases), and/or had significant nuclear pleomorphism (1 case). In all cases, reevaluation at the time of consultation with an extended immunohistochemical panel revealed the expression of pancreatic exocrine enzymes (trypsin, chymotrypsin, and/or BCL10), confirming acinar differentiation. All six patients with follow-up died within 1 to 24 months of initial diagnosis. In conclusion, metastatic ACC should be considered in differential diagnosis of the more common liver metastasis of pancreatic origin, NET and PDAC. ACC metastatic to the liver may lack hallmark morphologic features such as prominent nucleoli and eosinophilic cytoplasmic granules and may express neuroendocrine markers (mimicking NET) or exhibit prominent fibrotic stroma and pleomorphism (mimicking PDAC). Immunolabeling for acinar cell markers is warranted for cases of purported PDAC/NET with atypical features, such as purported NET with high Ki67 index and/or only patchy neuroendocrine marker labeling, or purported PDAC with luminal proteinaceous secretions rather than mucin and/or minimal pleomorphism.