Acinar Cystic Transformation of the Pancreas

Abstract

Acinar cystic transformation (ACT) of the pancreas, previously called acinar cell cystadenoma, is a poorly understood and rare entity among pancreatic cystic lesions. This study aims to clarify its real nature. This research cohort included 25 patients with pancreatic ACT, representing the largest series in the literature. We describe their clinicopathological features and molecular profile using next-generation sequencing. ACT arose more often in women (F/M≃2:1), in the body-tail region, with a mean size of ~4 cm. At the latest follow-up, all patients were alive and disease free. Histologically, a typical acinar epithelium lined all cysts, intermingled with ductal-like epithelium in 11/25 (44%) cases. All the cases lacked any evidence of malignancy. Three ACT showed peculiar features: 1 showed an extensive and diffuse microcystic pattern, and the other 2 harbored foci of low-grade pancreatic intraepithelial neoplasia (PanIN) in the ductal-like epithelium. Next-generation sequencing revealed the presence of 2 pathogenic/likely pathogenic mutations in 2 different cases, 1 with ductal-like epithelium and 1 with PanIN, and affecting KRAS (c.34G>C, p.G12R) and SMO (c.1685G>A, p.R562Q) genes, respectively. The other case with PanIN was not available for sequencing. Overall, our findings support that ACT is a benign entity, potentially arising from heterogeneous conditions/background, including: (1) acinar microcysts, (2) malformations, (3) obstructive/inflammatory setting, (4) genetic predisposition, (5) possible neoplastic origin. Although all indications are that ACT is benign, the potential occurrence of driver mutations suggests discussing a potential role of long-term surveillance for these patients.

Acinar Cystic Transformation of the Pancreas With Main Pancreatic Duct Dilation and Distal Pancreatic Atrophy

“…19,20 While initially hypothesized to be the benign precursor of acinar cystadenocarcinoma, ACT is now considered to have no malignant potential. 4,5,11,13 Exceptions may include cases with mural nodules, driver mutations, or pancreatic intraepithelial neoplasia. 9,10,13 These may benefit from long-term surveillance with eventual surgical intervention and intermittent postresection imaging surveillance because of the theoretical concern for malignant transformation.…”

“…12 Reasons to consider surgery include local expansion, development of symptoms, and desire to exclude PCLs associated with malignancy. 6,9,[12][13][14] Most surgical cases require extensive pancreatic resections. Common features of this case are that the original cyst was incidentally discovered and was initially believed to be a pseudocyst or MCN, leading to surgical intervention.…”

“…Microscopically, cysts are lined by cuboidal or columnar acinar epithelium that stain periodic acid–Schiff-positive and often have intracellular apical eosinophilic zymogen granules. 5–8,11–15 Interspersed ductal-like epithelium is noted in just under half of the cases. 5 Cellular atypia or mitoses, necrosis, infiltrative growth, or other evidence of malignancy is absent.…”

“…5 Cellular atypia or mitoses, necrosis, infiltrative growth, or other evidence of malignancy is absent. 5,11–14 Immunohistochemistry is diffusely positive for β-catenin, trypsin, chymotrypsin, and cytokeratin 7 and patchy for cytokeratin 19. 6,9,12,14 ACT is also p53-negative and lack proliferative activity (Ki67 index of < 1%).…”

Pancreatic Acinar Cystic Transformation

“…Hence, there can be a sporadic type of ACT and a familial type resulting from a hereditary predisposition. Luchini et al 8 recently published a series of 25 patients with histologically confirmed ACT in which histopathological and molecular findings argue for a heterogeneous entity with possible different etiopathogenesis.…”