Pancreatic serous cystadenoma (SCA) is a rare exocrine neoplasm of the pancreas with benign behavior. Histologically, it consists predominantly of small cysts lined by uniform cuboidal epithelia that are rich in glycogen and secrete serous fluid [1,2]. Radiological studies, including computed tomography (CT) and endoscopic ultrasonography (EUS), can accurately assist in the diagnosis of SCA [2,3]. Nonetheless, histological evaluation of cytology or surgical specimens continues to be the gold standard for definitive diagnosis [2,[4], [5], [6]].

In clinical practice, pancreatic well-differentiated neuroendocrine tumors (WDNETs) remains in the differential diagnosis for pancreatic SCA. Morphologically, tumor cells from both entities share characteristics such as abundant cytoplasm, distinct cytoplasmic borders, and rich vascularity [1,7]. Additionally, cytology specimens are typically small and paucicellular, providing limited tissue for comprehensive evaluations. Given the significant management and prognostic implications of differentiating pancreatic SCA, a benign neoplasm, from pancreatic WDNET, a neoplasm with metastatic potential, pathologists frequently use adjunct immunohistochemical staining for neuroendocrine markers to achieve an accurate diagnosis. Commonly used neuroendocrine markers for this purpose include chromogranin and synaptophysin [[7], [8], [9]]. Although one study has shown chromogranin to be largely negative in pancreatic SCA, controversy remains regarding whether pancreatic SCA expresses synaptophysin [10,11].

Insulinoma-associated 1 (INSM1), a transcription factor recently identified as playing a role in various neuroepithelial developmental pathways [[12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]], was initially isolated from human insulinoma and glucagonoma samples, which is reflected in its name. Subsequent research has demonstrated that INSM1 is both sensitive and specific for neuroendocrine tumors arising from diverse anatomical locations, such as the lung, head and neck, pancreas, adrenal gland, uterine cervix, prostate, and skin [[23], [24], [25], [26], [27], [28], [29], [30], [31]]. However, the expression profile of INSM1 has not yet been characterized in any extensive case series of pancreatic SCA.

Given the paucity of data evaluating INSM1 expression in pancreatic SCA, we sought to thoroughly characterize the INSM1 expression profile in pancreatic SCA and determine its significance with respect to clinical parameters and histological features. To our knowledge, this is the first study to examine the INSM1 expression profile in both surgical resection and cytology specimens of pancreatic SCA.