SPN account for only 1–2 % of all pancreatic tumors, but they are the most common pediatric pancreatic neoplasms, representing over 50 % of the total [29–34]. SPNs are found almost exclusively in young women. In one large review of SPNs, more than 90 % of patients were female, and 85 % were under 30 years of age [35]. Patients with SPN typically present with nonspecific abdominal complaints and a palpable abdominal mass [36]. Other signs and symptoms can include gastrointestinal obstruction, jaundice, or pancreatitis.

SPNs are partially cystic and partially solid masses arising from the pancreas. The tumors are usually large at diagnosis and compress adjacent structures [37].

Ultrasound: On ultrasound, a SPN appears as a large heterogeneous mass, usually well demarcated with an echogenic rim. SPNs can have variable internal characteristics. Most commonly, they have a complex internal architecture with echogenic solid components and hypoechoic cystic components (Fig. 9.7a) [37].

CT: On CT, SPNs have a hypodense rim. The solid component of the tumor is isodense to the remainder of the pancreas, while the cystic component has a density slightly greater than water [37]. Fluid-debris levels are present in up to 20 % of tumors, and calcifications can be seen in one-third of cases [37]. After the administration of contrast, SPNs enhance mildly in their solid portions. The fluid and debris do not enhance (Figs. 9.7b and 9.8a).

MRI: MR imaging shows a pancreatic mass with a hypointense capsule on T1-W and T2-W images. There is often internal high signal on T1-W images due to intratumoral hemorrhage [37]. Compared with the pancreas, the solid portions of the mass are hypointense to isointense on T1-W images and slightly hyperintense on T2-W images [37]. The enhancement pattern of SPNs on MRI resembles that seen on CT, with early peripheral, heterogeneous enhancement that gradually diffuses with time (Fig. 9.8b) [37].

Gross and microscopic features: Grossly, SPNs form large, circumscribed tumors with degenerative and hemorrhagic change [37]. The tumors measure of 6–10 cm and occur throughout the pancreas, though some studies report a predilection for the head or tail [37]. Histologically, the tumor contains merging solid, pseudopapillary, and cystic regions (Fig. 9.9) [37]. Solid sheets of uniform, epithelial cells may resemble endocrine tumors. Characteristic perivascular pseudopapillae frequently contain pools of mucinous material. Hemorrhage and/or necrosis are common features.

Immunohistochemistry and other special stains: Immunohistochemistry reveals a complex array of reactive antibodies including CD56, CD10, nuclear beta-catenin, alpha-1 antitrypsin, progesterone receptors, and synaptophysin [38, 39]. Ultrastructural studies also document acinar, ductal, and endocrine features [40].

Molecular diagnostic features and cytogenetics: Mutations of the beta-catenin gene CNNB1, nuclear accumulation of beta-catenin protein, and alterations in the Wnt-signaling pathway are commonly found in SPN [38, 41–43]. The accumulation of protein products of chromosome 11q genes, such as cyclin D1, CD56, and FLI-1, is also characteristic [44]. Allelic loss on chromosome 5q22.1 was frequently found by Min Kim et al. [42]. Between chromosomes 13 and 17 resulting in a loss of 13q14 → qter and 17p11 → pter was described in one SPN.

SPNs are usually slow-growing tumors with a benign clinical course [37]. Because of the potential for aggressive behavior, they should be completely resected if possible. Nearly 85 % are confined to the pancreas, and 95 % of these are cured with resection [37]. Metastases develop in 7–16 %, usually in older women and most commonly occur in the liver [37].

Pancreatoblastoma, the most common pancreatic tumor in young children, typically occurs in children between 1 and 8 years of age (mean age 5 years), but it also has been reported in adolescents [45]. Overall, it accounts for 0.2 % of pancreatic tumors [37] and is more common in children of Asian descent and males (M:F = 1.14:1 to 2.7:1) [37, 45]. Pancreatoblastoma has been associated with Beckwith–Wiedemann syndrome and familial adenomatous polyposis (FAP).

Patients present with a large abdominal mass, abdominal distension, and upper abdominal pain. On laboratory examination, serum α-fetoprotein (AFP) is elevated in up to 33–70 % of patients [37, 45]. Other elevated serum tests can include α-1-antitrypsin and lactate dehydrogenase. Tumor hormones can cause endocrine syndromes such as Cushing syndrome and the syndrome of inappropriate antidiuretic hormone [45].

Pancreatoblastoma most commonly occurs in the head of the pancreas, although it can occur at any site [45]. The liver is the most common site of metastasis, followed by the lungs and regional lymph nodes [45]. Metastases are present in 35 % of patients at diagnosis [45].

On imaging, the mass is often very large with a mean diameter of 7–18 cm [45]. Because of the large size, it can be difficult to determine the organ or origin.

Ultrasound: At ultrasound, pancreatoblastoma appears as a heterogeneous, well-circumscribed mass with cystic and solid components [37]. The cystic structures are hypoechoic with internal septa. When solid components are present, they appear hypoechoic to the normal pancreas.

CT: On CT, pancreatoblastoma appears as a well to partially circumscribed mass arising from the pancreas [37]. The tumor has a heterogeneous appearance with hypodense cystic areas and enhancing septa. Small punctate or curvilinear calcifications may be present (Fig. 9.10) [37].

MRI: On MRI, pancreatoblastoma is hypointense to isointense on T1-W images and hyperintense on T2-W images. Due to internal necrosis, the mass has a heterogeneous appearance.

Gross and microscopic features: Grossly, pancreatoblastomas are partially encapsulated, large (mean diameter = 10.6 cm ), solitary masses [46]. Microscopic examination shows a cellular tumor with a variety of patterns, including prominent acinar differentiation and lesser degrees of endocrine and ductal differentiation (Fig. 9.11). Often, bands of spindled stromal cells separate solid and lobular sheets of epithelial cells. Endocrine differentiation has been observed in only a few instances. Squamoid corpuscles, a characteristic feature, may range from clusters of nondescript cells to clear squamous cells with keratinization.

Immunohistochemistry and other special stains: Immunohistochemical stains highlight acinar differentiation with trypsin and chymotrypsin expression. Squamous corpuscles show a characteristic epithelial immunoprofile: keratins 8, 18, 19, and EMA are positive, whereas cytokeratin in negative or heterogeneously positive [47]. Immunohistochemical staining may demonstrate focal endocrine differentiation via chromogranin, synaptophysin, and neuron-specific enolase expression.

Molecular diagnostic features and cytogenetics: Genetic alterations are not well defined in pancreatoblastoma. Allelic loss of 11p has been reported [48].

Surgical resection remains the mainstay of therapy for pancreatoblastoma. Primary resection may not be possible in patients with large tumors involving major blood vessels or adjacent organs. In these patients and those with metastases, neoadjuvant chemotherapy is often the first line of treatment [45]. Pancreatoblastomas have a high recurrence rate. After resection, patients are monitored with serial imaging and serum AFP levels.

Pancreatic NETs are rare tumors in children and typically occur in middle aged adults. They may be asymptomatic or present with a hormone secretion syndrome. The latter tumors are said to be functioning or hyperfunctioning [37], whereas all other tumors are either nonfunctioning or clinically silent. Insulinomas are the most common subtype followed by gastrinomas [37].

The clinical presentation of pancreatic NET depends on tumor function. Insulinomas can present with symptoms of hypoglycemia that resolve with glucose [37]. In young children, hypoglycemia can cause behavioral problems, seizures, or coma [37]. Gastrinomas cause Zollinger-Ellison syndrome or diarrhea. Nonfunctioning pancreatic neuroendocrine tumors present later, often with symptoms due to mass effect.

Pancreatic neuroendocrine tumors vary in their location in the pancreas depending on the type of tumor. Insulinomas occur more commonly in the body and tail of the pancreas, whereas gastrinomas and nonfunctioning tumors are more common in the head (Fig. 9.12) [37].

Ultrasound: Insulinomas are typically small round or ovoid tumors that appear hypoechoic with a hyperechoic rim. Larger pancreatic NETs are usually heterogeneous with foci of cystic change, hemorrhage, and necrosis. There can be small echogenic areas of calcification on ultrasound [37].

CT: On CT, insulinomas are small tumors that avidly enhance during the arterial phase. The larger tumors are heterogeneous with enhancing solid portions and non-enhancing cystic areas [37]. Larger tumors are more likely to be associated with liver metastases.

MRI: Insulinomas are hyperintense on T1-W and T2-W images (Fig. 9.13). They avidly enhance on the arterial phase of imaging.

Nuclear medicine: Somatostatin receptor imaging can be useful to localize a tumor; however, only 60–75 % of pancreatic NET express somatostatin receptors.

Gross and microscopic features: Grossly, pancreatic neuroendocrine tumors are round or ovoid tumors. Small tumors are solid and homogeneous, while larger tumors have an incomplete fibrous pseudocapsule and contain cysts, necrosis, or hemorrhage [37].

Histologically, pancreatic NETs contain sheets or nests of monomorphic cells arranged in one of three patterns: the trabecular pattern with or without a gyriform arrangement, the acinar or glandular pattern, or the medullary or solid pattern (Fig. 9.13a) [37]. The intervening stroma is variable and can contain numerous blood vessels. Insulinomas characteristically contain amyloid that shows green birefringence when stained with Congo red [37].

Immunohistochemistry and other special stains: Pancreatic NETs generally show strong reactivity with antibodies to synaptophysin and chromogranin A. Detection of one or more peptide hormones in tumor tissue is common, even in nonfunctioning tumors. Expression of cytokeratin 19 has been associated with poor outcome in several studies [49, 50] but not in others [51].

Molecular diagnostic features and cytogenetics: Familial inherited syndromes, such as the multiple endocrine neoplasia (MEN) 1, von Hippel-Lindau, NF1, or tuberous sclerosis, may be associated with pancreatic NETs. In sporadic pancreatic NET tumors, losses of chromosome 1 and 11q and gain on 9q have been identified [52].

Surgical excision can cure both non-metastatic pancreatic NET and its associated clinical syndrome [37]. For tumors with metastatic disease at presentation, the optimal therapeutic approach and outcome are not clear. In one study of 19 pediatric patients with pancreatic NET, there was a 50 % 5-year survival rate [28].

Hepatoblastoma, the most common primary hepatic malignancy in childhood, accounts for between 65 and 80 % of all pediatric liver tumors [59–61]. It primarily occurs in young children and peaks during infancy (median age at diagnosis of 18 months) [59]. Hepatoblastoma is rare in older children; 90–95 % of new cases occur before 4 years of age [59, 62].

During the past 20 years, the incidence of hepatoblastoma has increased approximately 4 % per year, faster than for any other childhood cancer [63]. Currently, its overall incidence is 10.5 cases per million in children <1 year of age and 5.4 cases per million in children 1–4 years of age [63].

There are many known risk factors for hepatoblastoma including male gender, very low birth weight (<1,500 g), and genetic syndromes such as FAP, Beckwith–Wiedemann syndrome, hemihypertrophy, and trisomy 18 [63].

Patients with hepatoblastoma usually present with a palpable abdominal mass. Non-specific symptoms such as anorexia and weight loss may occur [60, 64]. Serum AFP is elevated in 90 % of patients, although a small subset of tumors with a worse prognosis does not express it [62, 64].

Imaging is used for diagnosis and staging of hepatoblastoma. The combination of the clinical and imaging findings in a child between 6 months and 3 years of age is essentially diagnostic of hepatoblastoma [65]. Hepatoblastoma can present with a solitary mass, a dominant mass with satellite lesions, or as multifocal disease [65].

Radiography: Abdominal radiography shows hepatomegaly and displacement of loops of bowel. Occasionally calcifications can be identified in the right upper quadrant [64].

Ultrasound: Ultrasound is often used as the first imaging test in a patient with hepatoblastoma. It can confirm the presence of a mass, localize the mass to the liver, and evaluate its vascular supply [65]. The tumor is usually hyperechoic compared to the background liver and shows a heterogeneous echotexture (Figs. 9.14a and 9.15a) [65]. Calcifications appear as hyperechoic foci with posterior acoustic shadowing (Fig. 9.15a). Necrosis and internal hemorrhage appear as anechoic intratumoral foci [65]. Color Doppler interrogation assists in evaluating the patency of the hepatic veins, inferior vena cava, and portal veins.

CT: Generally, hepatoblastoma appears as a well-defined, hypodense mass of the liver (Fig. 9.14b, c; Figs. 9.15b and Fig. 9.16a, b) [64]. Calcifications are present in approximately 50 % of tumors [64]. The calcifications are usually small and fine in epithelial tumors and coarse in mixed mesenchymal-epithelial tumors [65].

After the administration of contrast, the tumor enhances to a lesser degree than the background liver [64, 65]. During the arterial phase of enhancement, there may be septa or a peripheral rim of enhancement [64, 65].

Metastases are present in 20 % of patients at diagnosis and almost always occur in the lungs. Because of this, a chest CT should be performed at diagnosis [65].

MRI: The MRI appearance of hepatoblastoma varies with histologic subtype. Epithelial tumors have a homogeneous appearance and are hypointense on T1-W images (Fig. 9.15c) and hyperintense on T2-W imaging (Figs. 9.15d and 9.16c) [65]. Mixed epithelial-mesenchymal tumors are heterogeneous due to hemorrhage, necrosis, fibrosis, calcification, cartilage, and septa [65]. The variable composition of these tumors imparts a heterogeneous appearance on T1 and T2-W images. Septa appear hypointense on both T1 and T2-W images.

Post-contrast images are performed in the hepatic arterial and portal venous phases. The tumor enhances to a lesser degree than the background liver. Post-contrast imaging also defines the vascular anatomy and determines the presence of vascular invasion. Tumor thrombosis appears as an enhancing mass enlarging the involved vessel (Fig. 9.16d). This differs from bland thrombosis, which neither enhances nor enlarges vessels.

With hepatocyte-specific contrast agents, hepatoblastomas [57, 58] can have a variable appearance during the hepatocyte phase of imaging (Fig. 9.14d). Most tumors are hypointense during the hepatocyte phase, but a small number variably retain contrast [58]. It is not yet known if contrast retention occurs more commonly in certain histologic subtypes.

Gross and microscopic features: Grossly, hepatoblastoma usually appears as a well-defined liver mass. About 60 % occur in the right lobe [66]. The tumor may have a variegated appearance due to its mixed histologic composition and areas of hemorrhage, necrosis, or calcification [64].

Histologically, hepatoblastoma is classified into two broad types with multiple distinct patterns (Table 9.1) (Figs. 9.17, 9.18, 9.19, and 9.20) [64]. The epithelial type of hepatoblastoma occurs most commonly and comprises multiple subtypes including fetal, embryonal, small cell undifferentiated, and rhabdoid (Fig. 9.17) [60]. Nearly one-third of hepatoblastomas are well differentiated epithelial tumors with pure fetal histology (Fig. 9.18) [64]. These tumors are composed of small cuboidal cells arranged in thin trabeculae and containing varying amounts of glycogen and lipid. Like fetal liver, these characteristics impart an alternating light–dark pattern at low-power microscopy. More poorly differentiated epithelial tumors contain both fetal and embryonal components (Fig. 9.17). Embryonal tumors contain small, round, blue cells with less cytoplasm than fetal cells, often arranged in epithelial rosettes. The most poorly differentiated epithelial hepatoblastoma, the small cell undifferentiated tumor (Fig. 9.19), totally lacks recognizable hepatocytic differentiation and fails to express INI1 [64]. At times, these lesions exhibit a rhabdoid phenotype, with cytoplasmic inclusions and positivity for epithelial and mesenchymal markers (see Chap. xx, Renal for further discussion).