IntroductionThe widespread use of high-resolution, cross-sectional imaging has led to a dramatic increase in the incidental detection of pancreatic cystic lesions (PCLs), confronting clinicians with a high-stakes diagnostic challenge [1]. The central task is to accurately risk-stratify these lesions, distinguishing benign, non-neoplastic entities from pancreatic cystic neoplasms (PCNs) that harbor malignant potential [2]. This distinction is critical, as misclassification can lead either to unnecessary, high-morbidity pancreatectomy for benign cysts or, conversely, a missed opportunity to resect a pre-malignant or early-stage malignant tumor [3].Among the most frequent and consequential diagnostic dilemmas is the differentiation between a pancreatic pseudocyst (PPC)—a non-neoplastic, encapsulated fluid collection arising from pancreatitis—and a mucinous cystic neoplasm (MCN). PPCs are the most common PCL, accounting for approximately 75% of cases, and are defined by a fibrous wall devoid of an epithelial lining [5]. In contrast, MCNs are true neoplasms characterized by mucin-producing epithelial cells and an underlying ovarian-like stroma, carrying a significant risk of malignant transformation that prompts recommendations for surgical resection [6]. Despite these distinct pathologies, their radiological features can overlap substantially; large or complex PPCs containing debris can mimic the septations, wall thickening, and internal complexity characteristic of an MCN, creating significant diagnostic ambiguity from imaging alone [5].When initial imaging is inconclusive, a multimodal diagnostic algorithm is essential [3]. Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) allows for high-resolution morphologic assessment and cyst fluid acquisition [7]. Subsequent analysis of the cyst fluid for tumor markers, such as carcinoembryonic antigen (CEA), and cytology provides critical data to resolve the differential [8]. While high levels of CEA are strongly suggestive of a mucinous lesion, elevated amylase points towards a pseudocyst, and cytology can confirm malignancy, each test has known limitations [8].However, extreme clinical presentations, such as a cyst of massive size, can heavily bias initial interpretation towards neoplasia, creating a significant diagnostic pitfall that may lead to premature closure. In this report, we present the case of a patient with a 1.85-liter pancreatic cyst whose immense size and complex features on imaging were highly suggestive of an MCN. We detail the systematic application of a multimodal diagnostic approach that successfully averted a misdiagnosis, underscoring the principle that even in the face of atypical features, a stepwise, evidence-based evaluation is paramount to ensure correct diagnosis and guide appropriate management.
