Rare abdominal cancers

Stomach cancer

Tumours of the stomach might be benign (hamartoma, teratoma) or malignant (lymphoma, rhabdomyosarcoma, GIST). Primary adenocarcinoma of the stomach is rare in children, and has been reported more often in individuals with the Peutz-Jeghers syndrome. The prognosis is very poor.

Gastrointestinal stromal tumour (GIST)

Gastrointestinal stromal tumours (GIST) are very rare in children and adolescents: only about 0.5 to 2.7 percent of all GIST cases are diagnosed in patients under the age of 20. The so-called paediatric GIST is defined as a GIST diagnosed in a patient aged less than 18. Paediatric GIST typically occurs in adolescent girls, and is located in the stomach, usually in multiple foci, an epiteloid subtype. In contrast to GIST in adults, the paediatric GIST is wild-type, i.e. there is no mutation in genes KIT/PDGFR/SDHA-D/BRAF. The development of paediatric GIST is linked to four predisposition syndromes (neurofibromatosis type 1, Carney complex, Carney-Stratakis syndrome, and familial GIST). Chronic microcytic anaemia, resulting from a chronic bleeding into the gastrointestinal tract, is the dominant clinical symptom of paediatric GIST. Only a minority of paediatric GISTs are metastatic at the time of diagnosis; and unlike adult GISTs, metastases are often present in lymph nodes. The clinical behaviour is indolent but aggressive. Radical surgery is the choice of treatment for patients with localised GIST. Biopsy is not recommended due to the risk of bleeding and dissemination. There are no treatment guidelines for advanced cases of paediatric GIST; biological therapy is indicated (sunitinib as the first-line treatment), but its results have not been evaluated yet.

Neuroendocrine neoplasias (NEN)

The most common representative of neuroendocrine neoplasias (NEN) is a well-differentiated neuroendocrine tumour (also known as carcinoid in older nomenclature). Information on NEN in children and adolescents under the age of 20 is rather limited; the disease is more prevalent in adolescent girls. Appendix is the most common location of NEN in children. In most cases, it is found accidentally during appendectomy; carcinoid syndrome (skin flushing, watery diarrhoea, tachycardia) is usually not present. Therapy is determined by the presence of risk factors (tumour size and location in the appendix, depth of invasion into the bowel wall, and other histological parameters). According to the latest WHO classification from 2010, all neuroendocrine neoplasias of appendix are classified as malignant tumours. Appendectomy is curative in the majority of patients, and subsequent cancer treatment is not necessary. Hemicolectomy is indicated when high-risk signs are present. Prognosis of the disease is excellent: more than 95% of patients are alive 5 years after diagnosis.

Neuroendocrine carcinomas (mostly small-cell carcinomas) are highly malignant tumours with a poor prognosis; they can develop anywhere in the body, but the area of large bowel is the most common location. Radical resection (if possible) is the choice of treatment, followed by chemotherapy. Prognosis is rather poor: the median survival time does not exceed 5 months.

Pancreatic cancer

Two types of tumours are represented in children and adolescents: solid pseudopapillary neoplasm of the pancreas, and pancreatoblastoma. Neuroendocrine tumours of the pancreas are exceptionally rare in children; clinical symptoms and treatment procedures do not differ significantly from those in adults.

Solid pseudopapillary neoplasm of the pancreas (SPN)

Solid pseudopapillary neoplasm of the pancreas (SPN) arises from exocrine pancreas cells, and accounts for less than 1% of all pancreatic cancers. It typically occurs in adolescent girls, located in the area of head of pancreas and/or tail of pancreas. Clinical symptoms are typically unspecific (vague abdominal pain, dyspepsia), or are not present at all. The tumour is often found accidentally, sometimes it is a palpable mass. From the biological point of view, the tumour has a benign behaviour but a malignant potential. In a vast majority of cases, diagnosis is established during the surgery, which is also the choice of treatment. The prognosis is usually very good: more than 90% of patients are alive 5 years after diagnosis. Chemotherapy might be indicated for patients with metastatic disease, which is also curable. Radiotherapy is not indicated.

Pancreatoblastoma

Pancreatoblastoma accounts for 0.5% of pancreatic non-endocrine tumours; the median age at the time of diagnosis is 5 years, with a predominance in girls. The tumour grows slowly, and therefore a well-demarcated palpable tumour mass is the most common symptom, whereas pain, weight loss and dyspepsia are less common. Radical resection is the choice of treatment, chemotherapy is only indicated for a metastatic disease. Unfavourable prognostic factors involve the age above 16, the impossibility of radical resection, and the presence of metastases.

Colorectal cancer (CRC)

Colorectal cancer (CRC) is very rare in children and adolescents: less than 1% of all CRC cases are diagnosed in children under the age of 15, and about 1.5% of all CRC cases are diagnosed in adolescents. CRC is more prevalent in boys, mostly located in the ascending colon. Hereditary predisposition plays a very important role in the development of CRC: polyposis syndromes (familial adenomatous polyposis - FAP, Gardner’s syndrome, Peutz-Jeghers syndrome, Cowden syndrome) and non-polyposis syndromes (Lynch syndrome), inflammatory bowel diseases (ulcerative colitis, Crohn’s disease), as well as the radiation exposure. Approximately 15 to 20 percent of patients have familial CRC without clearly defined genetic characteristics. Most cases of CRC are mucinous, poorly differentiated. The symptoms are unspecific (abdominal pain, weight loss, bleeding and anaemia). Diagnosis and treatment follow the guidelines for adult patients. Mortality rates correlate with the age: about 65% of adolescent patient are alive 5 years after diagnosis. Patients with a confirmed hereditary burden need to be followed up in a cancer outpatient department, and colonoscopy should be performed at regular intervals. Prophylactic colectomy is indicated in these individuals at the age of around 20 years. As for patients with familial adenomatous polyposis (FAP), the development of new polyps in large bowels can be limited by the administration of non-steroidal anti-inflammatory drugs (celecoxib).

Renal cell carcinoma (RCC)

Less than 2% of all renal cell carcinomas (RCC) in the population are diagnosed in patients under the age of 21. The average age of adolescent patients at the time of diagnosis is 17 years. Adenocarcinoma of the kidney is classified into four histological types (clear-cell, papillary, chromophobe, and collecting duct carcinoma). Xp11.2 translocation renal cell carcinoma is a subtype of RCC characterised by translocations involving a breakpoint at the TFE3 gene (Xp11.2). It is sometimes referred to as the paediatric RCC. Xp11.2 translocation is present in approximately 30–45% of paediatric RCC. It is an aggressive tumour with an unknown aetiology; familial occurrence and a link to a mutation in the von Hippe-Lindau gene has been described. The tumour manifests itself clinically as a palpable mass; haematuria or abdominal pain are less common symptoms. RCC is a chemoresistant tumour, radical resection is the choice of treatment.

Peritoneal mesothelioma

Peritoneal mesothelioma is an extremely rare cancer with a very poor prognosis and a median survival time around 1 year. Only about 2–5% of all mesotheliomas occur in children and adolescents under the age of 20. Aetiology is unknown. Symptoms are mostly unspecific (abdominal pain, ascites, loss of appetite, weight loss). Paraneoplastic manifestations (venous thrombosis, thrombocytosis, hyperglycaemia) might be present in some patients. Mesothelioma remains limited to the parietal and/or visceral peritoneum, distant metastases are unusual. Surgical resection is the choice of treatment; if possible, this should be followed by locoregional (hyperthermic intraperitoneal chemotherapy) or systemic chemotherapy. These treatment procedures have significantly improved the median survival time: more than 50% of patients are nowadays alive 5 years after diagnosis.

Pheochromocytoma, paraganglioma

Pheochromocytoma is a rare tumour arising from the chromaffin cells of adrenal medulla, whereas paraganglioma is an identical tumour arising from extra-adrenal tissues. About 30% of these tumours have a hereditary origin (mutation in the SDH gene) or are associated with genetic syndromes (MEN 2 and von Hippel-Lindau syndrome, neurofibromatosis type 1). They manifest themselves clinically by the production of catecholamines (paroxysmal hypertension, headache, palpitations, tremor). Parasympatic paraganliomas do not produce hormones. The clinical course might vary from an indolent behaviour to a highly malignant course. Surgical resection is the choice of treatment, chemotherapy has a very limited effect. Radiation therapy (MIBG therapy) and biological therapy (somatostatin analogues, multikinase inhibitors and antiangiogenic therapy) might play a role in the treatment. The prognosis is rather poor in malignant advanced pheochromocytomas.

Adrenocortical carcinoma (ACC)

Adrenocortical carcinoma (ACC) can develop at any age, and is more prevalent in girls. Its aetiology is usually unknown, hereditary predisposition syndromes (Beckwith-Wiedemann syndrome, MEN1 and Li-Fraumeni syndrome, Carney complex) and hemihypertrophy might play a role. Clinical symptoms are usually related to the hormonal activity of the tumour (Cushing’s syndrome, virilisation, hyperglycaemia, hypokalaemia, hypertension), but the tumour can also be hormonally inactive (only palpable mass). It forms early metastases, and therefore it is usually diagnosed as a locally advanced or metastastic disease. The prognosis depends on the tumour size and weight, absence of metastases, and the patient’s age (prognosis is better in children under the age of 3). Radical resection provides a good chance of long-term survival: 75% of patients with localised tumour are alive 5 years after diagnosis. The prognosis is fatal at advanced stages of the disease with metastases: the median survival time usually does not exceed one year.