Diagnostic insights into solid pseudopapillary neoplasms of the pancreas: a decade of experience with pediatric representation.

Abstract

Background: Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare, low-grade malignancies that predominantly affect young females. Their diagnosis is often facilitated by a characteristic histomorphological pattern and immunohistochemical profile. However, diagnostic challenges persist, especially in pediatric and atypical presentations. Recent attention has focused on the diagnostic value of CD99 and LEF1 in distinguishing SPNs from other pancreatic neoplasms.

Objective: To evaluate the diagnostic accuracy and utility of CD99 and LEF1 as immunohistochemical markers for SPNs.

Methods: A retrospective analysis of 60 SPN cases diagnosed between 2015 and 2024 was performed. Histopathological features were systematically reviewed, and immunohistochemical staining for CD99, LEF1, β-catenin, Cyclin D1, PR, Ki-67 was evaluated. Immunohistochemical marker interpretation was standardized using internally validated thresholds informed by existing literature: CD99 was considered positive with ≥ 10% cytoplasmic staining exhibiting paranuclear accentuation; β-catenin positivity was defined by ≥ 5% nuclear localization; Cyclin D1 by ≥ 10% moderate-to-strong nuclear staining; and progesterone receptor (PR) expression by ≥ 1% nuclear positivity, consistent with hormone receptor evaluation guidelines. Marker expression was statistically analyzed for their associations.

Results: SPNs exhibited a strong female predilection (F:M ratio ≈ 7:1), with a mean age of 32.5 years. Pediatric cases (n = 4) displayed higher mean expression of CD99 (73.8%) and LEF1 (86.5%) compared to adults. CD99 showed cytoplasmic positivity with paranuclear accentuation in 96.7% of cases, while LEF1 demonstrated nuclear staining in 91.7%. β-catenin nuclear localization was observed in 95% of tumors, reflecting Wnt/β-catenin pathway activation. Cyclin D1 and PR were expressed in 90% and 88.3% of cases, respectively. Co-expression of β-catenin, CD99, LEF1, Cyclin D1, and PR was observed in 73.3% of tumors. CD99 and LEF1 inversely correlated with tumor size and proliferative activity (Ki-67), whereas Cyclin D1 and Ki-67 positively correlated with tumor size and lymphovascular invasion (LVI). Pediatric tumors generally exhibited favorable profiles, with limited evidence of LVI.

Conclusion: SPNs present with distinctive immunohistochemical signatures that are critical for accurate diagnosis, particularly in morphologically ambiguous or pediatric cases. CD99 and LEF1 are highly sensitive markers that, in combination with β-catenin and Cyclin D1, enhance diagnostic precision. These findings emphasize the central role of Wnt/β-catenin signaling in SPN pathogenesis and underscore the importance of integrating clinicopathological and molecular data for comprehensive tumor assessment.