Solid pseudopapillary tumor of pancreas (SPT) is a unique tumor entity, a rare group of potentially low malignant pancreatic tumors, accounting for only 0.17%-2.7% of pancreatic tumors. SPT has clear pathomorphological features and diverse immunohistochemical characteristics. Surgical resection is the most direct and effective treatment, and the postoperative prognosis is good. The relatively few reports in China may be related to the lack of understanding of SPT, which is reviewed as follows. SPT is a relatively rare pancreatic tumor, which was first reported by Frantz in 1959, and has been given various diagnostic names by domestic and foreign scholars according to its characteristic pathological patterns of solid, cystic and pseudopapillary structures, such as solid cystic tumor of the pancreas, papillary cystic tumor of the pancreas, cystic tumor of the pancreas, cystic tumor of the pancreas, cystic tumor of the pancreas, and cystic tumor of the pancreas. In 1996, the WHO unified them as “solid pseudopapillary neoplasm” (solid pseudopapillary neoplasm). “It is defined as an epithelial tumor with solid nest-like and pseudopapillary structures formed by morphologically uniform cells, often with hemorrhage and cystic changes, and reclassified as a lesion of unknown origin, whose histology and biological behavior remained unclear until recently. For the determination of its benign and malignant nature, the WHO classified SPT as a tumor of junctional malignant potential. Unlike the 1996 WHO definition, SPT has been classified as a special tumor of the pancreas since 2000, which is separate from the category of cystic tumors of the pancreas. The histological origin of SPT is still controversial, but there are four categories: ductal cell origin, alveolar cell origin, endocrine cell origin and pluripotent stem cell origin. Most scholars believe that SPT originated from pancreatic tissue, but with the in-depth study of SPT immunohistochemistry, it was found that the tumor had multi-directional expression, i.e. pancreatic endocrine, exocrine and focal epithelial expression, suggesting that SPT most likely originated from pancreatic embryonic pluripotent stem cells. They suggested that peripheral nerve sheath tumors and melanomas with melanin deposits are differentiated from the neural crest, and therefore speculated that SPT may originate from the neural crest. Other theories suggest that SPT originates from the genital crest, on the grounds that SPT occurs mainly in adolescent and fertile females and its occurrence may be related to sex hormones. During the reproductive period, elevated levels of progesterone stimulate tumor growth, and the rise and fall of hormone levels during the menstrual cycle could reasonably explain the large foci of hemorrhagic necrosis in SPT. In 11 patients with SPT reported by Fei Miao et al, immunohistochemical assays showed positive expression of neuron specific enolase (NSE) and chromogranin (CgA) compared to α1-antitrypsin (α1-AT) and α1- Kosmah et al. showed that SPT has a complex immunophenotype, which is not consistent with any cellular phenotype of the pancreas, and therefore the pancreatic origin of SPT is considered unlikely. Morales, in a report of a pregnant woman with SPT, found that her tumor had a faster growth rate, which may be related to the higher progesterone level in her body after pregnancy. The different hypotheses on tissue origin suggest that SPT is more likely to originate from stem cells. Although the distinct pathomorphological features and immunohistochemical characteristics of diverse expressions make the diagnosis of SPT not difficult, the tissue origin and pathogenesis of this tumor are still unclear, the morphology appears benign, but still metastasis can occur, and the available morphological and biological behavioral data cannot predict its malignant behavior yet, and further studies are still needed. 3. Pathological features 3.1 Gross, SPT can occur in any part of the pancreas, but is mostly seen in the head and tail of the pancreas. The gross specimens showed round or oval tumors, 8-20 cm in diameter, with exophytic and swelling growth, intact envelope and clear boundaries with surrounding tissues, a few with incomplete envelope and signs of infiltration into surrounding tissues, so benign SPT is considered a tumor with malignant potential. The gross specimen is lobulated, light brown, and cystic in nature. 3.2 Microscopic examination, histopathological manifestations of SPT are different from other pancreatic tumors, as smaller tumors are solid, while larger tumors often have specific pseudopapillary structures. The pathological diagnosis mainly relies on the typical light microscopic presentation. The most important features of light microscopy are solid and papillary structures, as well as cystic structures due to tumor metaplasia and hemorrhage. The tumor cells are uniform in size and arranged in solid patches with varying degrees of sclerosis. Areas of degenerative necrosis form pseudopapillae and vesicles due to cell dissociation. The eosinophilic tumor cells are arranged around fibrovascular tips to form pseudopapillary structures. Currently, most scholars believe that the pseudopapillary area is caused by the gradual degeneration of the solid tumor area. In the early stage of degeneration, the mutual adhesion between cells decreases, and some of the cells away from the vessels begin to fall off, and finally only one or several layers of cells around the vessels remain, forming a pseudopapillary structure. The process from solid zone to pseudopapillary zone is actually progressive degeneration. The cystic zone is essentially formed by tumor degeneration and shedding, which may be accompanied by intra-tumor hemorrhage, necrosis, cystic degeneration, foam cell aggregation and cholesterol granuloma formation. 3.3 Immunohistochemistry, vimentin, α1-AT and α1-ACT mostly show diffuse positivity, NSE, Syn, S-100 and CgA may show (+)/(-), CA199 and CEA are generally expressed negatively, ER, PR and CK (+)/(-), where α1-antitrypsin (α1-AT) and vimentin ( vimentin) staining positively is more supportive of the diagnosis of this disease. 3.4 The tumor cells in the fine needle aspiration and smear were characteristic branching and papillary cell clusters with a clear vascular axis, covered with one or more layers of consistent cells with round or ovoid nuclei. The chromatin is granular or dotted, often with nuclear grooves and small nucleoli. The cytoplasm is eosinophilic and granular, with poorly defined borders. There are also some scattered cells, often with naked nuclei and fragmented cytoplasm. The smear background is still clean, sometimes with foamy cells, gravelly bodies and hemorrhages, and occasionally with large eosinophilic droplets. While the above-mentioned types of pathological features mainly demonstrate the benign growth of SPT, the pathological features in the two cases of invasive SPT reported by Laura et al. were more specific, and the patients died 6 and 16 months after diagnosis, respectively, with the following pathological manifestations: (i) a diffuse growth pattern with extensive foci of tumor necrosis; (ii) nuclear schizophrenia was common; and (iii) the presence of undifferentiated components, such as sarcomatoid carcinoma components. The presence of these features in SPT should be brought to the attention of the physician, as they may be indicative of a poor prognosis to some extent, and although SPT has an intact envelope, a small amount of infiltration of the surrounding pancreatic tissue can be seen. Interestingly, tumor tissue may be seen to cross over with normal pancreatic tissue without interstitial reaction. It appears as pancreatic follicles and islets embedded in the parenchyma of the tumor rim, while the tumor nests are also insularly embedded in the normal pancreatic tissue. True hemangioma plugs are rare, but they can also directly infiltrate the nerves and deeper surrounding tissues. These are the indicators of malignancy of the tumor, and once they appear, the diagnosis of solid pseudopapillary carcinoma of the pancreas can be made. SPT is a potentially low-grade malignant tumor with slow growth and no specific clinical manifestations. Most patients are asymptomatic, resulting in a large tumor size at the time of detection. Some patients only present with vague pain and distension in the upper or lateral abdomen, which may worsen at night. When the tumor increases in size, it can show symptoms of compression, such as intestinal obstruction due to compression of duodenum by tumor in the head of the pancreas, and distention and discomfort in the upper abdomen due to compression of stomach. A large mass can be palpated in the upper abdomen during physical examination. Because of the soft texture of SPT tumor, it rarely causes obstruction of bile duct or pancreatic duct, and jaundice rarely occurs even if the tumor is located in the head of pancreas. A small number of patients present with ruptured tumor and bleeding, and some of them may have weight loss.Sakagami et al. reported a case of a 21-year-old female patient who presented with acute abdominal pain and was admitted with a diagnosis of acute pancreatitis. Liver metastases and peritoneal metastases can be found in about 15% of patients, mostly at the time of initial diagnosis, and rarely several years after resection of the mass. Even when metastases are present, patients do not experience significant discomfort and usually survive with the tumor for many years. 5. Diagnosis SPT has no specific clinical manifestations and is poorly understood, so early diagnosis is difficult and many misdiagnoses occur even in patients with obvious symptoms. In a retrospective analysis of patients with SPT, Lee et al. described the ultrasound findings as: a solid or cystic-solid mass with an intact envelope, and in some cases, septa and calcifications within the tumor. The tumor has an intact envelope, about 2-4 mm thick, with smooth inner wall and obvious enhancement after enhancement, with clear demarcation from the pancreas and smooth margins. In tumors with predominantly cystic structure or similar ratio of cystic and solid structures, the solid parts are distributed as attached nodules, floating clouds or cystic and solid parts; (3) even if the tumor is large in size, the pancreatic duct and bile duct obstruction and dilatation or vascular invasion are rarely seen on CT, and the tumor surrounding tissues are mostly pushed and displaced. The T1-weighted image shows high intensity signal, while the T2-weighted image shows low or heterogeneous signal. Endoscopic ultrasound shows an irregular, thick-walled, cystic mass with a hyperechoic ring of calcification, and SPT is similar to some diseases in terms of imaging features, making preoperative qualitative diagnosis difficult. In recent years, preoperative imaging-guided fine-needle aspiration cytology can further improve the diagnostic yield. In a retrospective survey of 150 patients with SPT, the use of preoperative fine-needle aspiration cytology increased the diagnostic rate to 70%, and Pettinato summarized the data of 50 cases and suggested that the preoperative and intraoperative fine-needle aspiration cytopathology of SPT is significantly different from other pancreatic tumors and is a reliable basis for the diagnosis of this rare pancreatic tumor. The differential diagnosis of this tumor needs to be distinguished from pancreatic tumors with cystic manifestations, such as pancreatic plasmacytoma and pancreatic mucinous cystadenoma, non-functional islet cell tumor and pancreaticoblastoma. Non-functional islet cell tumors occur in middle-aged and older people and do not tend to develop in women, as they do not cause endocrine symptoms, These manifestations are easily confused with SPT and sometimes need to be confirmed by surgical pathology and immunohistochemical staining. SPT in children needs to be differentiated from pancreaticoblastoma, which usually develops around the age of 7 years without gender differences, and has a cystic component on pathological examination due to central necrosis. When the patient is a pregnant woman, if she has persistent vomiting, after excluding thyroid disease, gastroesophageal reflux disease and cholestatic disease, SPT should be considered as the tumor cells of SPT are responsive to progesterone, which may lead to rapid growth of tumor cells during pregnancy. SPT is a benign tumor with malignant potential, junctional tumor or low-grade malignant tumor, which grows slowly and is not sensitive to radiotherapy and chemotherapy. The size of the tumor should not be used as a marker for resection, even for patients with limited liver metastases or local recurrence, surgical resection can have a good effect. The tumor was located in the head of the pancreas, approximately 12 cm × 14 cm, and had 12 liver metastases; the primary and metastatic foci were removed in two separate surgical procedures, and the patient recovered well after surgery. It was reported in the literature that the longest survival of SPT patients with liver metastases was 11 years after aggressive surgical treatment. The common surgical procedures for SPT include tumor enucleation, pancreatic segmental resection, pancreatic tail resection and pancreaticoduodenectomy, etc., which are chosen according to the intraoperative exploration and operator’s experience. As long as the tumor is completely removed, the prognosis is good. Local resection is suitable for tumors with intact envelope, located on the surface of the pancreas, or growing outward to form an exophytic tumor, without invading the adjacent large blood vessels or organs, with clear boundaries with the surrounding tissues and easy to peel off, and no malignant cells are found by intraoperative freezing. The tumor should be dissected along the tumor envelope and the tip or root of the tumor adjacent to the pancreas should be carefully dissected for complete excision to avoid residual tumor and damage to pancreatic tissue. Pancreatic segmental resection is suitable for patients whose tumors are mostly located in the pancreatic parenchyma and adjacent to the pancreatic ducts and blood vessels, which can easily damage the pancreas and its pancreatic ducts and cause postoperative complications during dissection. The focus of surgery is to separate the tumor to reveal the pancreatic tissue, and then perform segmental resection of the pancreas including the tumor without dissecting along the tumor envelope. In cases where the mass is located in the head and/or neck of the pancreas and wraps around the pancreatic duct, especially with aggressive features, pancreaticoduodenectomy can be performed. For those located in the tail of the pancreas, pancreatic caudal resection in combination with spleen is feasible. In cases with existing liver metastases and large vessel invasion, aggressive surgical resection can still achieve good results. In view of the biological characteristics and good prognosis of this tumor, surgery should neither be easily abandoned because of the large size of the tumor or invasion of surrounding structures, nor should the scope of surgery be blindly expanded. Lymph node metastasis is very rare in SPT, only 5 cases of lymph node metastasis among 500 cases of SPT have been reported in the literature, and SPT is not sensitive to chemotherapy and radiotherapy, so there are not many related reports in the literature and further data are lacking. 8. Prognosis The prognosis of SPT is relatively optimistic, and most patients can be cured after active surgical treatment. Patients with distant metastases can also receive good results with surgery as long as their systemic condition allows. The longest reported survival after surgery for SPT cases has been 21 years and continues to be followed up. The factors affecting prognosis are unclear, and Martin et al. showed that local infiltration, vascular or peritoneal metastases were not prognostic factors for overall survival. These observations were made in a retrospective analysis and need to be clarified by further studies.