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CARCINOID TUMORS OF THE APPENDIX VERMIFORM IN CHILDREN - TEN YEAR ANALYSIS OF 1503 APPENDECTOMIESZlatan Zvizdić, Aleksandra Đuran, Kenan Karavdić, Azur Jakić, Emir Milišić

ABSTRACTBackground. Appendiceal carcinoid tumors (ACTs) occur very rarely, although they are the most common potentially malignant lesions of the appendix. There is no staging system for ACTs and therefore there is no precise surgical treatment of carcinoid tumors with different localization and different histological types. The purpose of this study was to analyze the frequency of carcinoid tumors of the appendix in children as well as to determine the cor-relation between the size and localisation of tumors in the appendix with the outcome of their treatment. Materials and methods. The study included 1503 children aged 14 years or less who un-derwent appendectomy and were evaluated to identify the existence of appendiceal carci-noid tumors in pathological specimens. Results. The incidence of appendiceal carcinoid tumors was 0.27 %. All patients had local-ized disease at the tip of the appendix. Primary tumor size was between 0.2 cm and 1.6 cm (mean of 0.85 cm). We found that the depth of tumor invasion was beyond the muscularis propria in all cases. Anatomo-pathological examination in all cases showed well-differen-tiated endocrine tumors. No patient has had evidence of recurrent or metastatic disease, up to seven years after surgery, (mean follow-up duration: 2.6 years).Conclusion. Carcinoid tumors are rare, but are the most common malignant lesions of the appendix. The most common clinical presentation of ACTs is acute appendicitis. Surgery for carcinoids of the appendix is usually curative while the need for additional surgical resec-tion is determined by the size and histological features of the tumor.

KEY WORDS: Appendiceal carcinoid tumor, children, pathology, surgery, prognosis.

INTRODUCTIONLanghans first described a gut carcinoid tumor in 18671 but Lubarsch first wrote a detailed writ-ten record of such a lesion in 18882. The term carcinoid (karzinoide tumoren) was intro-duced by Oberndorfer in 19073. In 1928, Masson identified the subepithelial “Kultschitzky” cells as the origin of appendiceal carcinoid tumors and demonstrated that these cells exhibit both en-docrine and neural characteristics4. Carcinoid tumors are the most common neuroendocrine

Zlatan Zvizdić1

Aleksandra Đuran2

Kenan Karavdić1

Azur Jakić1

Emir Milišić1

1Clinic for Pediatric Surgery,2Department of Clinical Pathology and Cytology,

Clinical Center University of Sarajevo

Bolnička 25, 71000 SarajevoBosnia and Herzegovina

E-mail: zlatan.zvizdic@gmail.com

PROFESSIONAL PAPER

(2011) 1:100-103

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tumors but at the same time the represent only 0.49% of all malignancies5. Carcinoid tumors have traditionally been classified as foregut, mid-gut and hindgut carci-noid tumors6. Due to the different biological and clini-cal features of carcinoid tumors within these groups, the recent classification of these tumors are taken into ac-count not only the site of origin but also the histological characteristics of the tumors7. The estimated prevalence is 1.5 clinical cases per 100,000 population, however, autopsy data shows the prevalence to be roughly 650 cases per 100,000 population8. The most common tu-mour localisation is the GI tract (74%), and within the GI tract most tumours occur in the small bowel (29%), appendix (20%) and rectum (13%)9. Most of these tu-mors occur in adults and are extremely rare in children. Appendiceal carcinoid tumors (ACTs) occur very rarely, although it is the most common potentially malignant lesion of the appendix10. In children, ACTs are the most common11,12. More than 70% of those tumors occur at the tip of the appendix and their discovery is usually an incidental finding in appendectomy speciment13. There is no staging system for ACTs and therefore there is no precise surgical treatment of carcinoid tumors with dif-ferent localizations and different histological types14. The prognosis for patients with completely resected lo-calized disease is excellent15. The aim of our study is to report the experiences of the Clinic for Pediatric Surgery, Sarajevo in the manage-ment of appendiceal carcinoid tumors in children and to determine the correlation between the size and local-isation of the tumors in the appendix with the outcome of their treatment.

PATIENTS AND METHODSMedical records of all patients aged 14 years or less who underwent appendectomy at the Clinic for Pediatric Surgery, University Clinical Center, Sarajevo, Bosnia and Herzegovina between January 1, 2001 and Decem-ber 31, 2010, were evaluated to identify the existence of appendiceal carcinoid tumors in pathological speci-mens. The collected data included: gender, the patients’ age, indication for surgery, tumor localization in the ap-pendix, the diameter of the lesion, the depth of tumor invasion, histological type of the tumor, and follow-up.

The pathological diagnosis was confirmed in each case using established histological criteria16.

RESULTS1503 children underwent appendectomy during the study period and 4 of them or 0.27% were found to have histological evidence of carcinoid tumors of the appendix. Among children with confirmed carcinoid tumor there were 2 girls and 2 boys with a mean age of 10 years (range: 7-14 years). Open appendectomy was performed in 1501 and laparoscopic appendectomy in 2 cases. All patients in our study with histologically proven carcinoid tumor had symptoms of acute appen-dicitis preoperatively. All patients had localized disease at the tip of the appendix. The tumor size was 1 cm or less in three cases of appendix specimens. In the fourth case, the tumor size was 1.6 cm. Thus, primary tumor size was between 0.2 cm to 1.6 cm- mean of 0.85 cm. In no case was residual or metastatic disease identified. We analyzed the depth of tumor invasion in all our patients with carcinoid tumor of the appendix and found that the depth of tumor invasion was beyond the muscularis propria in all cases. Anatomo-pathological examination in all cases showed small, uniformly stained clear cells with moderate amounts of finely granular cytoplasm arranged in solid, trabecular, insular, and organoid pat-terns with tiny islands of tumor cells surrounded by thin layers of stroma. The histologic features of our ap-pendiceal carcinoids are shown in Figure 1,2,3,4 and 5.

DISCUSSIONCarcinoid tumors represent the largest number of neu-roendocrine tumors and represent a significant diag-nostic and therapeutic challenge for clinicians. Carci-noid tumors are in general quite rare but the incidence is probably higher because many people who have carcinoid tumors are often asymptomatic. The most common site of carcinoid tumor occurrence is in the appendix in children15. Although most appendiceal car-cinoides are clinically silent and behave benignly, they do have the potential to metastasize17. In the present study, only 4 ACTs were found in the 1503 pathologic appendiceal speciment in the last ten years. The incidence was 0.27% what is compatible with other studies12,14. These findings suggest that ACTs are

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rare tumors. In the our study, the age of the patients ranged from 7 to 14 years with a mean of 10 years. Male to female ratio was 2:2. These finding are compatible with other studies12,15. All patients in our study in whom histologically proven carcinoid tumor had symptoms of acute appendicitis preoperatively as observed in other studies12. Data in the literature about the depth of in-vasion of ACTs are compatibile with our result12. Our study suggests that no medical therapy is indicated in patients with resected appendiceal carcinoide tumors. Our results are consistent with those from multiple

studies in which none of patients with ACTs less than 2.0 cm experienced lymph node or distant metastases over a follow-up period18,19.

Carcinoid tumors are rare, but the most common malig-nant lesions of the appendix. The most common clinical presentation of ACTs has acute appendicitis. Surgery for the carcinoids of the appendix is usually curative while the need for additional surgical resection is determined by the size and histological features of the tumor.

Figure 1. Photomicrograph of „typical“ appendiceal carci-noid tumor (ACTs) (hematoxylin and eosin; 40 x) character-ized by nested growth pattern and uniform appearance of nuclei. No necrosis or mitotic figures are present.

Figure 2. Photomicrograph of ACTs stained by hema-toxylin and eosin; (20x).

Figure 3. Photomicrograph of ACTs stained by CEA (20x). Tumor cells show that stained negative for carcinoembryonic antigen (CEA).

Figure 4. Photomicrograph of ACTs sample immunostained for chromogranin A (20x). Tumor cells show that stained positive for chromogranin A.

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Figure 5. Photomicrograph of ACTs sample immunostained by serotonin (10x). Tumor cells show that stained positive for serotonin.