Introduction

Pancreatic solid pseudopapillary neoplasm (SPN) is a rare tumor of low malignant potential that predominantly affects young women and is characterized pathologically by a pseudopapillary structure. Surgical resection is the only curative treatment for SPN, and there are few effective treatment options for patients with metastasis. However, the natural history of SPN, their molecular biological characteristics, and the factors that determine its malignant potential have not been clarified. Recently, organoid culture technology has enabled more specific and precise analyses using only cultured tumor cells. In this study, we aimed to clarify the molecular biological mechanisms that define the origin of SPN, what genetic factors define the malignant transformation of SPN by combining advanced high throughput technology and organoid technology, and examined its correlation with clinical findings.

Aims & Methods

Age, gender, tumor diameter, and presence or absence of malignant pathological findings were extracted from six SPN cases resected from December 2019 to April 2021 at our hospital. In addition, organoids were derived from tumor and normal pancreatic tissues. Gene expression of the organoids and surgical samples were analyzed by RNA-seq.

Results

The median age of the patients was 41 years (IQR: 38-49 years) with a male-to-female ratio of 1:7. The median tumor diameter was 34 mm (IQR: 18-101 mm). Three patients had nerve plexus or vascular invasion, and one of them had liver metastasis. SPN with malignant findings showed significantly increased nucleus diameter (mean 5.8 μm vs. 8.1 μm, p<0.001). The results suggest molecular biological differences associated with malignant transformation. RNA-Seq was performed using normal and tumor surgical tissues, as well as normal and tumor organoids generated from the surgical samples. Comparison of tumor and normal tissue from surgical specimens showed marked changes in gene expression related to cellular localization, and this feature was even more pronounced in tumors with higher grades of malignancy. A similar trend was observed using organoids.

Conclusion

We examined clinical features and performed RNA-seq using surgical tissues and organoids to elucidate the gene expression patterns that characterize SPN. We found that SPN showed a significant enlargement of cell nuclei in high-grade cases, and that there were clear differences in gene expression related to cellular localization and extracellular matrix. Based on the findings of this study, we hope to elucidate the molecular biological mechanisms leading to the development of novel therapies for SPN.

Introduction

Recent developments in diagnostic imaging have increased the detection rate of lymphoma, for which a clear, histopathological diagnosis is critical for the subsequent choice of therapeutic regimen. Over the past decade, endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/B) has become widely-used means of tissue collection. However the open lymph node biopsy has conventionally been used to diagnose lymphoma histologically, and the evidence backing the use of EUS-FNA/B for this purpose is still limited.

Aims & Methods

The present study aimed to compare the performance of EUS-FNA/B and the open biopsy for diagnosing lymphoma by retrospectively analyzing 1113 patients with 1224 lesions who underwent either of the two methods at the study center between 2012 and 2024. The patients’ background, pathological diagnosis, procedural factors, and complications were evaluated. The performance of the open biopsy was compared with that of EUS-FNAB in diagnosing lymphoma in accordance with the 5^th edition of the World Health Organization classification of hematolymphoid tumours ¹⁾ (WHO classification).

Results

An open biopsy was performed for 943 lesions, 621 of which were malignant lymphomas, with the face, head, neck, axilla or groin, limb, and other areas being the site of 46, 556, 96, 225, 4, and 16 lesions, respectively. EUS-FNAB was performed for 281 lesions, 82 of which were malignant lymphomas, with the intra-abdominal area, mediastinum, and rectum being the site of 270, 10, and 1 lesion, respectively. The needle gauge used for FNA was 19G, 22G, and 25G in 1, 143, and 36 lesions, respectively, while and the needle gauge for FNB was 20G, 22G, and 25G in 3, 74, and 3 lesions, respectively. The mean number of punctures was 2.3 (range 1-9). EUS-FNAB involved significantly fewer, procedural complications than the open biopsy (14/943 vs 0/281; p=0.04). According to the WHO classification, the diagnostic performance (95% confidence interval) of the open biopsy has sensitivity 93.4 % (91.1-95.2), specificity 100.0 % (98.3-100.0), positive predictive value 100.0 % (99.0-100.0), and negative predictive value 88.7 % (85.0-91.8). The diagnostic performance (95% confidence interval) of EUS-FNAB according to the same classification has sensitivity 79.3 % (68.9-87.4), specificity 100.0 % (97.2-100.0), positive predictive value 100 % (91.8-100.0), and negative predictive value 92.1 % (87.7-95.3 %). Between the groups, there was no significant difference in the proportion of lesions for which immunostaining was able to be performed (615/621 vs 80/82; p = 0.24). The positive diagnosis rate was significantly higher for the open biopsy (580/621 vs 27/40; p < 0.001) but did not differ significantly for the EUS-FNB (580/621 vs 38/42; p = 0.52). Univariate and multivariate analyses found that needle type (FNB needle) was a procedural factor in EUS (needle type, gauge, number of punctures, stroke length) contributing to the diagnosis of lymphoma (odds ratio: 3.83; p = 0.037).

Conclusion

EUS was less complicated than the open biopsy as means of collecting tissue for histologically diagnosing lymphoma, and EUS-FNB had a positive diagnosis rate comparable to that of the open biopsy.

References

1. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022 Jul;36(7):1703-1719.