In children, Appendicular Neuroendocrine Tumors (carcinoid tumors of the appendix) ANETs are rare and an incidence of about one case per thousand of evaluated patients has been proposed but variations of this rate have also been reported in the literature [1] [2] . Neuroendocrine Tumors are known to occur throughout the gastrointestinal tract, but most common sites are appendix, small bowel and rectum [3] [4] . The clinical presentation of ANETs may be similar to that of acute appendicitis, but in majority these tumors are either identified on histological examination of resected appendix or incidentally found during abdominal surgery performed for another pathology [5] . Untreated ANETs may cause recurrent episodes of abdominal pain due to incomplete or complete obstruction of the appendiceal lumen. ANETs are usually benign neoplasm and the uncommon occurrence of metastasis to liver and retroperitoneum has been reported [6] .

We report our experience with ANETs in children from a tertiary care hospital, which covers pediatric surgical service for a country with 2 million populations. During 6-year period, there were 700 appendectomies performed in children (≤14 years) and we collected only 3 cases of ANETs diagnosed incidentally from histological examination of resected appendix specimens. We have reviewed the clinical presentation, diagnosis and management of these cases.

Neuroendocrine tumors are considered to be of neuroectodermal origin and classified as part of the other amine precursor uptake and decarboxylation neoplasms [3] [4] . The reported incidence of ANETs in children (≤14 years) range from 0.08% to 0.7% in surgical specimen [5] [7] and prevalence in our study was 0.03 in 700 surgical resected specimen of pediatric appendectomies carried out at our institute in last 6 years.

Presentation of ANETs in children is variable. Most common presentation is like acute appendicitis, whereas in others ANET may be an incidental finding during surgery. Some children may present with recurrent abdominal pain due to partial obstruction of the appendiceal lumen or rarely children with ANETs have presented with clinical signs of peritonitis [8] . Symptoms of carcinoid syndrome such as flushing and diarrhea due to increased urine excretion of 5-HIAA have also been reported with liver or retroperitoneal metastases [7] . However, in majority of children aneuroendocrine tumor is usually an incidental finding during histological examination of the resected appendix [1] [2] [7] as happened in all cases in this case series. In all our patients ANETs were discovered during routine histological examination of resected appendix followed by specific Immuno-histo- chemical staining (Figure 1 and Figure 2) and none of these children presented with any carcinoid syndrome symptoms. Post-operative imaging with CT abdomen and 5-HIAA excretions were also unremarkable suggesting that ANETs are usually non-aggressive in paediatric age group.

Most of the ANETs are localized at the tip of the appendix but have also been reported in the mid portion (20%) and at the base of the appendix (5%) [9] . In our study, the tumors were located at the tip (1 case) and in

the mid appendix (2 cases) with a diameter of 1 cm or less (Table 1).

The management of ANETs depends much on the size, site and depth of the primary tumor. It is generally agreed that appendectomy is sufficient in children with incidental small (<2 cm) ANET localized at tip or in mid appendix and no further surgical intervention is indicated if follow up CT scan of abdomen and 24-h urine 5-HIAA are normal [2] [10] . This practice was followed up in our case series since the diagnosis was made from the appendectomy specimens and additional post-operative evaluation with CT abdomen and urinary excretion of 5-HIAA in all cases were not indicative of any further intervention.

The management of large (>2 cm) ANETs located at base of appendix and extending into the mesoappendix has been a controversial subject. A more extensive surgical procedure such as right hemicolectomy, ileocecal resection and caecotomy has been recommended in adults [2] . However, in paediatric age group with large ANETs a more limited surgical approach has been advocated [8] . Till to date, there is only one documented case of metastatic ANET [6] ; this child had a large (5 cm) ANET and had right hemicolectomy, which contained one lymph node with a metastatic deposit. At 3-year follow-up this patient remained clinically and radiologically disease-free.

There is no consensus regarding the guidelines of clinical follow-up and utility of imaging and neuroendocrine markers in pediatric patients with ANETs since there are not many series published in pediatric literature. In some series, the children were followed up clinically and with ultrasound imaging [11] where as others have advocated using a combination of annual urinary serotonin metabolites and abdominal ultrasonography as

M = Male; RLQ = Right Lower Quadrant; WBC = White blood cells; CRP = C-reactive protein; CT Abd = Computerized Tomography of abdomen; 5-HIAA = 5-hydroxyindoleacetic acid.

first-line screening tools [8] [9] [12] . Since our case series is too small to draw a recommendation, we still agree with Kulkarni et al. that children with small (<2 cm) ANETs and with no associated risk factors should have a regular annual clinical follow up to monitor the outcome and prognosis.

In summary, ANETs in pediatric age group usually present like acute appendicitis and are discovered incidentally during histological examination of the resected appendix. ANETs in children are less aggressive and the prognosis is excellent after appendectomy. We advocate obligatory review of histopathology of resected specimen to document prevalence of these tumors in children.

We gratefully acknowledge the Medical Research Centre, Hamad Medical Corporation for their support in publishing this article.

The authors declare that there are no conflicts of interest.