The primary pancreatic tumors of childhood can be classified into the following four categories:
Solid pseudopapillary tumor of the pancreas, also known as Frantz tumor, is the most common pediatric pancreatic tumor, accounting for up to 70% of cases in most institutional series.[1,2] This tumor has low malignant potential and most commonly affects females of reproductive age (median age, 21 years), with a predilection for Black people and East Asian people.[2,3,4] There is no known genetic or hormonal factor to explain the strong female predilection, although it has been noted that all tumors express progesterone receptors.
Histologically, the tumors are characterized by a combination of solid, pseudopapillary, and cystic changes. The fragility of the vascular supply leads to secondary degenerative changes and cystic areas of hemorrhage and necrosis. The cells surrounding the hyalinized fibrovascular stalks form the pseudopapillae. A highly specific paranuclear dot-like immunoreactivity pattern for CD99 has been described.
Solid pseudopapillary tumor of the pancreas is a very friable tumor, and tumor rupture and hemoperitoneum have been reported.[2,3,4] Tumors can occur throughout the pancreas and are often exophytic. On imaging, the mass shows typical cystic and solid components, with intratumoral hemorrhage and a fibrous capsule. A retrospective review of the National Cancer Database identified 21 pediatric patients (younger than 18 years) and 348 adult patients with solid pseudopapillary neoplasm of the pancreas. When compared with their adult counterparts, children with solid pseudopapillary neoplasms had similar disease severity at presentation, received similar treatments, and experienced equivalent postoperative outcomes.
The outcome of solid pseudopapillary tumors of the pancreas is excellent, with 10-year survival rates exceeding 95%.
Treatment of Solid Pseudopapillary Tumor of the Pancreas
Treatment options for solid pseudopapillary tumor of the pancreas include the following:
Treatment of solid pseudopapillary tumor of the pancreas is surgical; however, preoperative and operative spillage is not unusual. Whipple procedures (pancreaticoduodenectomy) are often necessary, but non-Whipple pancreatic-sparing resections may be possible utilizing a pancreatico-jejunostomy procedure. Surgery is usually curative, although local recurrences occur in 5% to 15% of the cases. A retrospective review of the Italian Pediatric Rare Tumor Registry identified 43 pediatric patients diagnosed with solid pseudopapillary tumor of the pancreas between 2000 and 2018.[Level of evidence: 3iiA] The median age at diagnosis was 13.2 years (range, 7–18 years). Only one patient presented with metastatic disease. At follow-up (median, 8.4 years; range, 0–17 years), one recurrence occurred in a patient who had intraoperative rupture, and all patients were alive.
Metastatic disease, usually in the liver, may occur in up to 15% of the cases.[2,3,4,5,6] Single-agent gemcitabine has been reported to be effective in cases of unresectable or metastatic disease.
Incidence and Risk Factors
Pancreatoblastoma accounts for 10% to 20% of all pancreatic tumors during childhood. It is the most common pancreatic tumor of young children and typically presents in the first decade of life, with a median age at diagnosis of 5 years.[1,2]
Patients with Beckwith-Wiedemann syndrome have an increased risk of developing pancreatoblastoma; this syndrome is identified in up to 60% of cases of pancreatoblastoma developing during early infancy and in 5% of children developing pancreatoblastoma later in life. Pancreatoblastoma has also been associated with familial adenomatous polyposis syndromes.
Histology and Molecular Features
This tumor is thought to arise from the persistence of the fetal analog of pancreatic acinar cells. Pathology shows an epithelial neoplasm with an arrangement of acinar, trabecular, or solid formations separated by dense stromal bands.CTNNB1 and IGF2 gene mutations have been described in some cases, suggesting that pancreatoblastoma might result from alterations in the normal pancreas differentiation.[5,6]
Although approximately one-half of the cases originate in the head of the pancreas, jaundice is uncommon. Close to 80% of the tumors secrete alpha-fetoprotein, which can be used to measure response to therapy and monitor for recurrence. In some cases, the tumor may secrete adrenocorticotropic hormone (ACTH) or antidiuretic hormone, and patients may present with Cushing syndrome and the syndrome of inappropriate antidiuretic hormone secretion. Metastases are present in 30% to 40% of the patients, usually involving liver, lungs, and lymph nodes.
Using a multimodality approach, close to 80% of patients can be cured.
Treatment of Pancreatoblastoma
Treatment options for pancreatoblastoma include the following:
Surgery is the mainstay in the treatment of pancreatoblastoma, and a complete surgical resection is required for cure. Because of the common origin in the head of the pancreas, a Whipple procedure is usually required.[7,8]
For large, unresectable, or metastatic tumors, preoperative chemotherapy is indicated; pancreatoblastoma commonly responds to chemotherapy, and a cisplatin-based regimen is usually recommended. The PLADO regimen, which includes cisplatin and doxorubicin, is the most commonly used regimen, and treatment is modeled after the management of hepatoblastoma, with two to three cycles of preoperative therapy, followed by resection and adjuvant chemotherapy.[2,4,9,10]
Although radiation therapy has been used in unresectable or relapsed cases, its role in the treatment of microscopic disease after surgery has not been defined.
Incidence and Risk Factors
Islet cell tumors represent approximately 15% of pediatric pancreatic tumors in most series.[1,2,3] These tumors usually present in middle age and may be associated with multiple endocrine neoplasia type 1 (MEN1) syndrome; less than 5% of islet cell tumors occur in children. (Refer to the PDQ summary on Childhood Multiple Endocrine Neoplasia [MEN] Syndromes Treatment for more information.)
The most common type of functioning islet cell tumor is insulinoma, followed by gastrinoma.
Nonfunctioning tumors are extremely rare in pediatrics, except when associated with MEN1 syndrome. Islet cell tumors are typically solitary; when multiple tumors are present, the diagnosis of MEN1 syndrome should be considered.
On imaging, these tumors are usually small and well defined. Somatostatin receptor scintigraphy is useful for the location of islet cell tumors; however, only 60% to 70% express somatostatin receptor.
Treatment of Islet Cell Tumors
Treatment options for islet cell tumors include the following:
Treatment of islet cell tumors includes medical therapy for control of the syndrome and complete surgical resection. For patients with malignant tumors and unresectable or metastatic disease, chemotherapy and mTOR inhibitors are recommended.
The management of these tumors in children follows the consensus guidelines established for adult patients.[3,6] (Refer to the PDQ summary on adult Pancreatic Neuroendocrine Tumors [Islet Cell Tumors] Treatment for more information.)
Incidence and Risk Factors
Pancreatic carcinomas (acinar cell carcinoma and ductal adenocarcinoma) are extremely rare in children. These malignancies represent less than 5% of pediatric pancreatic tumors and include the following:[1,2]
Refer to the following PDQ summaries for more information:
Presenting symptoms are nonspecific and are related to local tumor growth. However, 4% to 15% of adult patients with acinar cell carcinoma may present with a lipase hypersecretion syndrome, manifesting as peripheral polyarthropathy and painful subcutaneous nodules.
Treatment of Pancreatic Carcinoma
(Refer to the PDQ summary on Pancreatic Cancer Treatment [Adult] for information about the treatment of pancreatic carcinoma.)
Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.
Cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975. Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered for children and adolescents with cancer. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:
(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)
Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics. At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapy for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%. Childhood and adolescent cancer survivors require close monitoring because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years. The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 persons. Therefore, all pediatric cancers are considered rare.
The designation of a rare tumor is not uniform among pediatric and adult groups. Adult rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people, and they are estimated to account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[5,6] Also, the designation of a pediatric rare tumor is not uniform among international groups, as follows:
Most cancers within subgroup XI are either melanomas or thyroid cancer, with the remaining subgroup XI cancer types accounting for only 1.3% of cancers in children aged 0 to 14 years and 5.3% of cancers in adolescents aged 15 to 19 years.
These rare cancers are extremely challenging to study because of the low incidence of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers.
Information about these tumors may also be found in sources relevant to adults with cancer such as the PDQ summaries on Pancreatic Cancer Treatment (Adult) and adult Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
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Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of pediatric pancreatic cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Childhood Pancreatic Cancer Treatment are:
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Levels of Evidence
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The preferred citation for this PDQ summary is:
PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Pancreatic Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/pancreatic/hp/child-pancreatic-treatment-pdq. Accessed <MM/DD/YYYY>.
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Last Revised: 2021-06-23
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