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Liu Y, Peng J, Zhao Y, Wang W. Emerging pathological diagnostic strategies for solid pseudopapillary neoplasm of the pancreas: insights from omics and innovative techniques. J Pathol Clin Res 2025; 11:e70029. [PMID: 40312910 PMCID: PMC12046068 DOI: 10.1002/2056-4538.70029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 02/21/2025] [Accepted: 03/31/2025] [Indexed: 05/03/2025]
Abstract
Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare, low-grade malignant tumor, representing 0.9-2.7% of all exocrine pancreatic tumors. SPN patients generally have a favorable prognosis with a 5-year survival rate exceeding 95% following complete surgical resection. Accurate diagnosis is crucial to avoid unnecessary treatments. Currently, SPN diagnosis relies on imaging techniques such as CT and MRI, along with immunohistochemical analysis of biopsy and resection samples. The main challenge in diagnosis is the potential inability to accurately identify recurrent or metastatic SPN, as well as 'malignant' SPN, due to the lack of specific biomarkers. Advances in high-throughput omics technologies, including genomics, transcriptomics, proteomics and metabolomics, have opened new avenues for identifying novel biomarkers for SPN. Additional, liquid biopsy techniques have enabled more comprehensive analysis of biosamples such as pancreatic cyst fluid, offering promising prospects for preoperative diagnosis. This review highlights recent research on SPN diagnosis, focusing on immunohistochemical markers, tissue sampling methods and the potential of omics approaches. It also discusses the challenges and opportunities in improving diagnostic accuracy, particularly for high-grade and metastatic SPNs.
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Affiliation(s)
- Yuanhao Liu
- Department of PathologyPeking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeBeijingPR China
| | - Junya Peng
- Institute of Clinical MedicinePeking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeBeijingPR China
- State Key Laboratory of Complex, Severe, and Rare DiseasesPeking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeBeijingPR China
| | - Yupei Zhao
- State Key Laboratory of Complex, Severe, and Rare DiseasesPeking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeBeijingPR China
- Department of General SurgeryPeking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeBeijingPR China
- Department of Basic Medical SciencesSchool of Medicine, Tsinghua UniversityBeijingPR China
- Peking University‐Tsinghua Center for Life SciencesBeijingPR China
| | - Wenze Wang
- Department of PathologyPeking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeBeijingPR China
- Molecular Pathology Research Center, Department of PathologyPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingPR China
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Xu YC, Fu DL, Yang F. Unraveling the enigma: A comprehensive review of solid pseudopapillary tumor of the pancreas. World J Gastrointest Oncol 2024; 16:614-629. [PMID: 38577449 PMCID: PMC10989376 DOI: 10.4251/wjgo.v16.i3.614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 12/28/2023] [Accepted: 01/16/2024] [Indexed: 03/12/2024] Open
Abstract
Solid pseudopapillary tumor of the pancreas (SPTP) is a rare neoplasm predominantly observed in young females. Pathologically, CTNNB1 mutations, β-catenin nuclear accumulation, and subsequent Wnt-signaling pathway activation are the leading molecular features. Accurate preoperative diagnosis often relies on imaging techniques and endoscopic biopsies. Surgical resection remains the mainstay treatment. Risk models, such as the Fudan Prognostic Index, show promise as predictive tools for assessing the prognosis of SPTP. Establishing three types of metachronous liver metastasis can be beneficial in tailoring individualized treatment and follow-up strategies. Despite advancements, challenges persist in understanding its etiology, establishing standardized treatments for unresectable or metastatic diseases, and developing a widely recognized grading system. This comprehensive review aims to elucidate the enigma by consolidating current knowledge on the epidemiology, clinical presentation, pathology, molecular characteristics, diagnostic methods, treatment options, and prognostic factors.
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Affiliation(s)
- Ye-Cheng Xu
- Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - De-Liang Fu
- Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Feng Yang
- Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Fudan University, Shanghai 200040, China
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Maimaijiang A, Wang H, Li W, Wang Y. Diagnosis and treatment of solid pseudopapillary neoplasm of the pancreas in children: A report of 18 cases. Front Pediatr 2022; 10:899965. [PMID: 36061381 PMCID: PMC9429827 DOI: 10.3389/fped.2022.899965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Accepted: 07/14/2022] [Indexed: 11/13/2022] Open
Abstract
Purpose To explore the incidence, imaging and treatment of solid pseudopapillary tumor of pancreas in children, and Summarize the experience of treatment. Methods The clinical data of 18 children with a solid pseudopapillary tumor of the pancreas treated in our hospital from January 2012 to June 2021 were analyzed retrospectively. The age range was 8-16 years old, the average age was 11.67 years old, and the median age was 11.5 years old, namely, three boys with an average age of 10 years old and 15 girls with an average age of 12 years old. In total, two cases were admitted to the hospital because of trauma, seven cases were found in physical examination, and nine cases were admitted with the abdominal pain as the main complaint. Enhanced CT examination was performed before operation, nuclear magnetic resonance examination and abdominal ultrasound examination were performed in some children, and plain CT scan was performed after operation. Results Solid pseudopapillary tumor of the pancreas can occur in all parts of the pancreas, especially in the body and tail of the pancreas. Among the 18 cases, SPN occurred in the head of pancreas in 5 cases (27.78%), the neck of pancreas in 2 cases (11.11%), and the body and tail of pancreas in 11 cases (61.11%). All the 18 children were treated by operation. among them, 4 cases underwent choledochal pancreatico duodenectomy (1 case), 4 cases underwent pancreaticoduodenectomy combined with splenectomy (3 cases), 6 cases underwent spleen-preserving pancreatectomy / tail pancreatectomy (1 case), 3 cases underwent enucleation of pancreatic tumor due to exogenous growth, 1 case underwent laparoscopic partial pancreatectomy and pancreaticoenterostomy. Laparotomy was performed in 12 cases and endoscopic surgery in 6 cases. Postoperative pathology confirmed solid pseudopapillary tumor of the pancreas. None of the patients received radiotherapy and chemotherapy after operation and were followed up for 6 months to 2 years. There was no recurrence, metastasis or pancreatic dysfunction. Conclusion Solid pseudopapillary tumor of pancreas in children is a rare, low-grade malignant solid tumor with no specific clinical manifestations and laboratory examinations. Preoperative diagnosis mainly depends on enhanced CT. Surgical resection of tumor is a reliable treatment, and the specific operation is mainly based on the experience of the chief surgeon, the location of the tumor and the invasion of surrounding tissue. At present, there is no evidence of the effectiveness of other treatment options, and surgical resection of the tumor has a good prognosis.
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Molecular Alterations in Solid Pseudopapillary Neoplasm of the Pancreas: The Achilles Heel in Conquering Pancreatic Tumorigenesis. Pancreas 2021; 50:1343-1347. [PMID: 35041331 DOI: 10.1097/mpa.0000000000001928] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Solid pseudopapillary neoplasms of the pancreas are overwhelmingly benign tumors predominately observed in women in the third decade of life. However, their malignant potential, based on local recurrences and metastases, has brought into question the available evidence on their biological behavior. Solid pseudopapillary neoplasms have distanced themselves from other pancreatic tumors with varying morphological appearance, immune profile, and histogenesis. In review of the literature, PubMed was queried using search strings, including "solid pseudopapillary neoplasm" and "molecular," and "immunohistochemistry." Alternative searches were also conducted given the variability in tumor name, including "solid pseudopapillary tumor" and "Frantz tumor." This article provides an in-depth review into the molecular pathways that contribute to the pathogenesis of solid pseudopapillary neoplasms. It also discusses the implications of existing molecular pathways toward tumor aggressiveness and recurrence potential.
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La Rosa S, Bongiovanni M. Pancreatic Solid Pseudopapillary Neoplasm: Key Pathologic and Genetic Features. Arch Pathol Lab Med 2021; 144:829-837. [PMID: 31958381 DOI: 10.5858/arpa.2019-0473-ra] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/05/2019] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Solid pseudopapillary neoplasm of the pancreas is a low-grade malignant tumor generally associated with a good prognosis. Solid pseudopapillary neoplasms show peculiar morphologic features, but sometimes the differential diagnosis with other pancreatic neoplasms (ie, pancreatic neuroendocrine tumors) can be a challenging task, especially in cytologic or biopsy specimens. In these cases immunohistochemistry is a useful tool, but the diagnostic utility of several proposed immunohistochemical markers is questionable. In recent years, despite several attempts to characterize the pathogenetic, molecular, and prognostic features of solid pseudopapillary neoplasms, they still remain unclear. OBJECTIVE.— To give the reader a comprehensive update on this entity. DATA SOURCES.— The PubMed database (US National Library of Medicine) was searched using the following string: pseudopapillary tumor [AND/OR] neoplasm [AND/OR] pancreas. All articles written in English were included. In addition, because a heterogeneous terminology has been used in the past to define solid pseudopapillary neoplasms, the reference lists of each paper selected in the PubMed database were also reviewed. CONCLUSIONS.— This review gives a comprehensive update on the pathologic, clinical, and molecular features of solid pseudopapillary neoplasms, particularly addressing issues and challenges related to diagnosis. In addition, we have tried to correlate the molecular alterations with the morphologic and clinical features.
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Affiliation(s)
- Stefano La Rosa
- From the Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland (Dr La Rosa); Synlab Swiss SA, Pathology, Lausanne, Switzerland (Dr Bongiovanni)
| | - Massimo Bongiovanni
- From the Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland (Dr La Rosa); Synlab Swiss SA, Pathology, Lausanne, Switzerland (Dr Bongiovanni)
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A Review of Clinicopathological Characteristics and Treatment of Solid Pseudopapillary Tumor of the Pancreas with 2450 Cases in Chinese Population. BIOMED RESEARCH INTERNATIONAL 2020; 2020:2829647. [PMID: 32685461 PMCID: PMC7352122 DOI: 10.1155/2020/2829647] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 06/20/2020] [Indexed: 02/07/2023]
Abstract
Background Solid pseudopapillary tumor of the pancreas (SPTP) has been reported as a rare disease with low malignant potential. The aim of this study was to summarize experiences of the diagnosis and treatment for the patients reported in the Chinese population. Method 2450 SPTP cases reported in English and Chinese literature before Jan 2020 were for our review and analysis retrospectively. Result There are 389 male cases and 2061 female cases, and the ratio of male/female was 1 : 5.3. The average age was 29.3 years. The main clinical symptoms were upper abdominal pain and bloating discomfort in 51.6% of the cases and epigastric mass. 38.6% of the tumor was located at the head of the pancreas and 55.4% at the body and tail of the pancreas. The most frequent operative styles were tumor enucleation (38.4%). Pathology showed that the average diameter of the tumor was 8.2 cm and 12.3% of SPTP was malignant. 98.3% of cases had favorable survival. Conclusions SPTP is a rare indolent tumor occurring mainly in young women, and the main clinical performances are abdominal mass and abdominal pain; most tumors are distributed at the head and the tail of the pancreas; the prognosis after complete resection is excellent.
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Molecular Diagnosis of Cystic Neoplasms of the Pancreas: a Review. J Gastrointest Surg 2020; 24:1201-1214. [PMID: 32128679 DOI: 10.1007/s11605-020-04537-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Accepted: 01/29/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND The prevalence of incidental pancreatic cystic neoplasms (PCNs) has increased dramatically with advancements in cross-sectional imaging. Diagnostic imaging is limited in differentiating between benign and malignant PCNs. The aim of this review is to provide an overview of biomarkers that can be used to distinguish PCNs. METHODS A review of the literature on molecular diagnosis of cystic neoplasms of the pancreas was performed. RESULTS Pancreatic cysts can be categorized into inflammatory and non-inflammatory lesions. Inflammatory cysts include pancreatic pseudocysts. Noninflammatory lesions include both mucinous and non-mucinous lesions. Mucinous lesions include intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm. Non-mucinous lesions include serous cystadenoma and solid-pseudopapillary tumor of the pancreas. Imaging, cyst aspiration, and histologic findings, as well as carcinoembryonic antigen and amylase are commonly used to distinguish between cyst types. However, molecular techniques to detect differences in genetic mutations, protein expression, glycoproteomics, and metabolomic profiling are important developments in distinguishing between cyst types. DISCUSSION Nomograms incorporating common clinical, laboratory, and imaging findings have been developed in a better effort to predict malignant IPMN. The incorporation of top molecular biomarker candidates to nomograms may improve the predictive ability of current models to more accurately diagnose malignant PCNs.
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Zalatnai A, Kis-Orha V. Solid-pseudopapillary Neoplasms of the Pancreas is still an Enigma: a Clinicopathological Review. Pathol Oncol Res 2019; 26:641-649. [PMID: 31209654 PMCID: PMC7242268 DOI: 10.1007/s12253-019-00671-8] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 05/20/2019] [Indexed: 02/07/2023]
Abstract
The solid-pseudopapillary neoplasm of the pancreas is a rare but enigmatic entity occurring mainly in young women. Since the first description by V. Frantz in 1959 the terminology of this tumor has continuously changed but it has remained simply descriptive, because the exact histogenesis is still obscure. Although in majority of cases the survival is excellent, nevertheless, the expected prognosis is not exactly predictable. In this review the authors aim to summarize its clinico-pathological features, the expected biological behavior, the molecular alterations, the immune phenotype and discuss the putative histogenesis. From diagnostic point of view, the salient histological characteristic findings are analyzed that would help to differentiate it from other, look-alike pancreatic tumors, and suggestions are made about the desirable content of the histological report.
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Affiliation(s)
- Attila Zalatnai
- First Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, H-1085 Üllői út, Budapest, 26, Hungary.
| | - Viktória Kis-Orha
- First Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, H-1085 Üllői út, Budapest, 26, Hungary
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Kim EK, Jang M, Park M, Kim H. LEF1, TFE3, and AR are putative diagnostic markers of solid pseudopapillary neoplasms. Oncotarget 2017; 8:93404-93413. [PMID: 29212159 PMCID: PMC5706805 DOI: 10.18632/oncotarget.21854] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Accepted: 09/23/2017] [Indexed: 12/11/2022] Open
Abstract
The diagnosis of solid pseudopapillary neoplasms (SPNs) is challenging because some SPNs share many similar morphological and immunohistochemical features with other pancreatic neoplasms. In this study, we investigated potential diagnostic markers of SPN. Based on the SPN-specific upregulated genes from a previous DNA microarray and proteome study, we selected six immunohistochemical markers [beta-catenin, androgen receptor (AR), lymphoid enhancer-binding factor 1 (LEF1), transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3), fused in sarcoma (FUS), and WNT inhibitory factor 1 (WIF-1)]. We also evaluated the Ki-67 proliferative index to investigate its associations with prognosis. To validate these markers, we studied 91 SPNs as well as 51 pancreatic ductal carcinomas (PDC) and 48 neuroendocrine tumors (NET) as controls. We found frequent and diffuse nuclear expressions of β-catenin (98.9%), AR (81.3%), LEF1 (93.4%), TFE3 (74.7%), FUS (84.6%), and cytoplasmic expression of WIF-1 (96.7%) in SPNs. In contrast, PDCs and NETs showed no expression. (P < 0.001). When beta-catenin, LEF1, and TFE3 staining were combined, the sensitivity and specificity were 100% and 91.9%, respectively. Four (4.4%) SPNs showed distant metastasis and these tumors were associated with a relatively high Ki-67 proliferative index (≥ 5%; P = 0.013). We identified LEF1, TFE3, and AR as putative diagnostic markers of SPN, auxiliary to β-catenin. Incorporated into an immunohistochemical panel, these markers could be beneficial to distinguish SPN from PDC and NET. In addition, we suggest that the Ki-67 proliferative index can be a predictive marker of metastasis in SPNs.
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Affiliation(s)
- Eun Kyung Kim
- Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Mi Jang
- Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Minhee Park
- Departments of Pathology and Brain, Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hoguen Kim
- Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.,Departments of Pathology and Brain, Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.,Healthcare Review and Assessment Committee, Health Insurance Review & Assessment Service, Seoul, Republic of Korea
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Sui X, Hu Y, Zhang C, Pan H, Li D. Prostate cancer metastasis to the distal phalanx of the left hallux: The first confirmed case and literature review. Oncol Lett 2016; 12:1074-1078. [PMID: 27446396 DOI: 10.3892/ol.2016.4701] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Accepted: 05/26/2016] [Indexed: 12/19/2022] Open
Abstract
Prostate cancer is one of the most common carcinomas in Asia, as well as all over the world. The vast majority of prostate cancer patients present with bone metastases, which mainly involve the axial bones, with pain as the most common symptom. The present study reports the first case of prostate cancer metastasis to the hallux in a 73-year-old man who presented with pain and a swollen phalanx of the left hallux. This symptom developed gradually over a period of several months and could not be improved with the common treatments. Due to a pathological fracture, amputation of the left phalanx was performed. Notably, the immunohistochemical examinations of the surgical sample demonstrated the presence of a metastatic lesion from prostate cancer. The present study describes an unusual presentation involving phalangeal metastasis in a prostate cancer patient, and a systematic review of reported cases of rare metastatic events in prostate cancer is also discussed.
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Affiliation(s)
- Xinbing Sui
- Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China
| | - Yan Hu
- Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China
| | - Cheng Zhang
- Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China
| | - Hongming Pan
- Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China
| | - Da Li
- Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China
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Alpha-methylacyl-CoA racemase is expressed in a majority of pancreatic neoplasms of neuroendocrine, acinar, and solid pseudopapillary differentiation. Pathology 2015; 47:466-8. [PMID: 26126032 DOI: 10.1097/pat.0000000000000278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Abstract
Solid-pseudopapillary neoplasm of the pancreas (SPN) is an uncommon low-grade malignant neoplasm occurring mostly in young women. In addition to its distinctive pathological appearance of pseudopapillae with poorly cohesive neoplastic cells, rare variants exist raising the differential diagnosis especially with neuroendocrine neoplasms. The overall prognosis for patients with SPNs is excellent after surgical resection. Nevertheless, 10% of cases may have malignant behavior characterized by tumor recurrence and/or metastasis. Despite numerous studies, the histogenesis of this neoplasm remains unclear. Distinctive molecular alterations such as the presence of CTNNB1 mutations are observed in nearly all cases, while mutations classically observed in ductal adenocarcinoma, such as KRAS, TP53, and SMAD4, are not observed in SPNs, reinforcing its distinct nature compared to all other pancreatic neoplasms. Recent transcriptional studies have shown that activation of the Wnt/beta-catenin pathway in these tumors is associated with the upregulation of genes belonging to Notch, Hedgehog, and androgen receptor signaling pathways.
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Affiliation(s)
- Benoît Terris
- Service de Pathologie, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Hôpitaux universitaires Paris-Centre, Site Cochin, Paris, France.
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