Figure 19.1 Summary of chapter: four key tumours.
Reported prognostic factors for worse outcome are male sex and no surgical treatment. The male sex was associated with a three times higher mortality, while the absence of surgical intervention was associated with a 15-fold increase in risk of mortality [3].
19.2 SOLID PSEUDOPAPILLARY NEOPLASM (BOX 19.1)
SPN is the most common pancreatic tumour in children [4,10–12], with a reported male-to-female ratio of 1:10 in the general population [13] and of 1:1.75 in the paediatric age group [14]. Lee et al. [15] showed that in children, the tumour was located more frequently in the head of the pancreas (67%), rather than in the body or tail of the pancreas, where it is mostly found in adults (81%) [14].
SPN is a low-grade malignant tumour, usually indolent, but with metastatic potential [5]. The cure rate was reported to be above 90% with complete surgical resection, even in the presence of metastasis [3].
19.2.1 Clinical features
The patients commonly present with abdominal pain or mass [11,14], with or without the association of other symptoms like nausea, vomiting and weight loss [16]; anorexia; or weight gain [14]. Some tumours are incidental findings [14] during clinical examination for other reasons, or present with right upper abdominal swelling not associated with other signs or symptoms [17]. Jaundice is unusual, even if the tumour is located in the head of the pancreas [17]. Physical examination may show a palpable firm mass in the epigastrium.
Laboratory tests are usually normal [17], with the exception of serum concentrations of amylase and lipase, which have previously been reported to be elevated [12]. Tumour markers are usually negative, including α-fetoprotein (α-FP), carbohydrate antigen* 19–9 (CA 19–9), adrenocorticotropic hormone (ACTH), carcinoembryonic antigen, homovanillic and vanillylmandelic acid, β-human chorionic gonadotropin (β-HCG), chromogranin A, gastrin, glucagon, somatostatin, uric acid, vasoactive intestinal peptide, CA 72–4 and enolase [14,18], with rare reports of elevated lactate dehydrogenase, CA 125 [14] and CA 19–9 [12]. In a study which included adults and the paediatric population, one case of abnormal β-HCG was seen [13].
On ultrasound (US), the tumours appear well demarcated, approximately spherical in shape, solid or solid–cystic, with variable vascular flow on colour Doppler images [16]. On computed tomography (CT) scan, the lesions have heterogeneous enhancement, depending on the amount of intratumoural haemorrhage and on the cystic–solid component ratio. Foci of calcification are sometimes noted [16–20].
The best imaging technique for children is magnetic resonance imaging (MRI), due to its higher sensitivity for pancreatic masses [10] and better visualisation of tumour components, as areas of intratumoural haemorrhage, which show high signal intensity on T1-weighted imaging (T1-WI) and heterogeneous signal intensity on T1-weighted imaging (T2-WI), and peripheral fibrous pseudocapsule, which appears as a hypointense rim on both T1-WI and T2-WI [16], or as variable signal intensity on T2- WI and of low signal intensity on T1-WI, which is often enhanced after gadolinium application [17]. Both the intramural haemorrhage and the fibrous capsule are important for the diagnosis of SPN, due to their scarce presence in other pancreatic neoplasms [17].
Figure 19.2 Solid pseudopapillary tumour (Frantz tumour). Pancreatic biopsy from a 15-year-old girl with a pancreatic cystic–solid mass. At microscopy, the tumour is composed of a relatively monomorphic and loose cell population which tend to be more cohesive around fibrovascular stalks (a). Immunohistochemistry shows that these cells stain for β-catenin (b) and CD10 (not shown). Magnification, 100×.
This tumour has been known by many names over the past 40 years. In 1959, V. K. Frantz described the key clinical and histological features [48]. Later in 1970, A.
B. Hamoudi et al. described its ultrastructural characteristics [49]. Both authors have lent their names to this unusual neoplastic entity. Otherwise, its name has been descriptive, with solid and papillary tumour; papillary cystic tumour; solid–cystic tumour; and solid, cystic, and papillary epithelial neoplasm being used in the literature.
Finally, in 1996 the WHO proposed the name solid pseudopapillary tumour.
19.2.3 Pathology
Lee et al. compared tumour characteristics in children and adults and found that the mean tumour size in children was greater than the one found in the adult population (8.0 vs. 6.0 cm) [15].
On gross examination, the tumours are solid–cystic or entirely solid, encapsulated or showing a peritumoural enhancement of the fibrous tissue (pseudocapsule), with areas of characteristic haemorrhage and necrosis on the cut section [6,14].
On microscopical examination, SPNs are composed of relatively uniform small cells, polygonal or cuboidal in shape, with clear or eosinophilic cytoplasm, sometimes with intracytoplasmic vacuoles [16,21]. Fibrovascular stalks are surrounded by one or more layers of discohesive tumour cells without central-orientated nuclei, forming a pseudo-papillary pattern. Some of the neoplastic cells contain hya-line globules [21]. Mitotic figures are usually rare, but a moderate or high mitotic rate and nuclear polymorphism are occasionally present [10]. Cystic change, intratumoural haemorrhage, cholesterol clefts, foamy macrophages and myxoid stroma are also noted [21]. Perineural and vascular invasion and peripancreatic tumoural deposits are sometimes seen [10].
On immunohistochemistry, the cytoplasm of the tumour cells stains positive for CD10 in 80% of cases [22]. The cells show a paranuclear dot-like staining with CD99 [21] and a positive stain for progesterone, but negative for oestrogen. Synaptophysin is positive in 70% of the cases, in a rather patchy than diffuse pattern; neuron-specific enolase is diffusely positive; and chromogranin A is negative. AE1/AE3 shows positive in up to 75% of the cases, but with a lower intensity than in the normal pancreatic epithelium [22]. E-cadherin immunostain shows nuclear positivity or absence of membrane staining depending on the antibody (antibody that recognises the intracytoplasmic domain of E-cadherin vs. antibody against the extracellular domain of E-cadherin) [22].
The activation of the Wnt* pathway is expressed immunohistochemically through 100% of cases, showing nuclear and cytoplasmic immunoreactivity for β-catenin [13], but only 85%–90% of SPNs have exon 3 mutations. Mutations in other exons could explain the positivity for the remaining 10%–15% of cases [22].
It has been reported that fine-needle percutaneous aspiration, which has a decreased risk of peritoneal carcinomatoses, can be suggestive for the diagnosis of SPN [23] and, together with the clinical presentation and the characteristic imaging features [2], can help in the differential diagnosis.
19.2.4 Treatment and prognosis
Surgical resection remains the only curative option for patients with SPN, consisting of either a Whipple-like procedure or distal pancreatectomy ± splenectomy.
More conservative procedures (e.g. pylorus-preserving pancreaticoduodenectomy) [10], duodenum-preserving pancreatic head resection [19] and less invasive approaches, including laparoscopic enucleation, have been attempted [10]. Although it appears that positive resection margins might not affect the outcome of all patients [10], in the series of Speer et al., the only recurrence was seen in a patient with a resection specimen which had positive surgical resection margins, thus making complete resection with negative margins an imperative in the treatment of children with pancreatic SPN [14]. Transarterial embolisation and radiofrequency ablation have been used efficiently and safely to reduce the size of very large tumours [24].
Postoperative complications include pancreatitis, leakage from the distal common bile duct repair site, pseudocyst formation and delayed gastric emptying [12].
The overall survival of patients with SPN is significantly better than that of patients with other histologic types of tumours, reported as high as 100% on 5-year follow-up [11]. Tumour recurrence and metastatic disease have been reported years after curative surgical attempt [5]; therefore, long-term follow-up is important in the management of these children [13].
PB has been reported as one of the most common pancreatic tumours in the paediatric age group [11], although there are reported series which completely lack them [10]. Children with PB present at a younger age, in general during the first decade of life, when compared with patients with other histological types of pancreatic tumours which are usually diagnosed after the age of 10 [3,11]. The tumours appear to arise in different anatomical parts of the pancreas with similar frequency [25], and ectopic PB has also been reported [26].
Figure 19.3 Coronal section (a) of solid and cystic tumour of body of pancreas in 5-year-old child. There is obvious calcification of the wall. The tumour was metastatic to the liver (b) and regional nodes, with invasion of the portal vein. Histology showed PB.
19.3.1 Clinical features
Clinical presentation is usually with abdominal pain accompanied by vomiting, jaundice and weight loss. A palpable mass in the epigastric area is usually found on examination [25]. Incidental detection after a casual physical exam has also been reported in patients with otherwise no signs or symptoms of disease [27].
Laboratory tests show elevated serum levels of α-FP, certainly higher than the age-related reference, in most of the cases, making it a valuable diagnostic and therapeutic marker [27
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