Adrenocorticotropic hormone (ACTH)-secreting pancreatic neuroendocrine tumors (PanNETs), although rare, are responsible for about 15% of ectopic Cushing syndrome (CS). They represent a challenging entity because their preoperatory diagnosis is frequently difficult, and clear-cut morphologic criteria useful to differentiate them from other types of PanNETs have not been defined. Ectopic ACTH secretion associated with CS can also be rarely due to pancreatic acinar cell carcinoma (ACC) and pancreatoblastoma, rare tumor types with morphologic features sometimes overlapping those of PanNETs and, for this reason, representing a diagnostic challenge for pathologists. We herein describe the clinicopathologic and immunohistochemical features of 10 PanNETs and 1 ACC secreting ACTH and associated with CS together with an extensive review of the literature to give the reader a comprehensive overview on ACTH-producing pancreatic neoplasms. ACTH-secreting PanNETs are aggressive neoplasms with an immunohistochemical profile that partially overlaps that of pituitary corticotroph adenomas. They are generally large and well-differentiated neoplasms without distinctive histologic features but with signs of aggressiveness including vascular and perineural invasion. They are more frequent in female individuals with a mean age of 42 years. At 5 and 10 years after diagnosis, 35% and 16.2% of patients, respectively, were alive. ACTH-secreting ACCs and pancreatoblastomas are very aggressive pediatric tumors with a poor prognosis. Using an appropriate immunohistochemical panel including ACTH, β-endorphin, trypsin, and BCL10 it is possible to recognize ACTH-secreting PanNETs and to distinguish them from the very aggressive ACTH-secreting ACCs.
尽管分泌促肾上腺皮质激素（ACTH）的胰腺神经内分泌肿瘤（PanNETs）较为罕见，但约占异位库欣综合征（CS）的15%。由于这些病例的术前诊断常常比较困难且缺乏与其他类型PanNETs明确鉴别的形态学诊断标准，因而是一类具有挑战性的病例。在少数情况下，伴库欣综合征的胰腺分泌ACTH肿瘤也可能是胰腺腺泡细胞癌（ACC）和胰母细胞瘤，而这些肿瘤类型在形态学特点上与PanNETs又有相似，因而对于病理学家来说这类肿瘤的诊断也具有挑战性。我们在此描述了10例 PanNETs和1例 分泌ACTH且与CS相关的ACC的临床病理及免疫组化特点并回顾相关文献，对分泌ACTH的胰腺肿瘤做一全面概述。分泌ACTH的PanNETs是一类侵袭性肿瘤，其免疫组化表达部分与垂体促肾上腺皮质激素细胞腺瘤重叠。这些肿瘤一般体积较大、分化较好，肿瘤并无独特组织学特征但具有侵袭性，可侵犯血管和神经。女性多见，平均年龄为42岁。诊断后5年和10年生存率分别为35%和16.2%。分泌ACTH的ACCS和胰母细胞瘤是高侵袭性的儿童肿瘤且预后很差。适当的使用免疫组化染色套餐包括ACTH、β-内啡肽、胰蛋白酶和BCL10可以识别分泌ACTH的PanNETs并将其与高侵袭性的分泌ACTH的ACC相鉴别。