Tesadüfen Tespit Edilen Appendisal Nöroendokrin Tümörlerde (aNET) İnvaziv Histolojik Özelliklerin Klinikopatolojik Korelasyonu
Year 2024,
Volume: 8 Issue: 3, 291 - 298, 30.12.2024
Ceren Sayar
,
Haldun Umudum
,
Recep Bedir
,
Zafer Turan
Abstract
Amaç: Apendiks Nöroendokrin Tümörleri (aNET'ler) nadir görülen ve çoğunlukla akut apandisit nedeniyle ameliyat edilen hastalarda tesadüfen
saptanan tümörlerdir. Bunlar yavaş ilerleyen ve çoğunlukla iyi huylu tümörlerdir ancak metastaz riski taşırlar. Bu çalışma, ANET vakalarının
evre ve derecelendirme parametreleri dışındaki agresif davranışlarla ilişkili invazif histolojik özelliklerini tanımlamayı amaçlamaktadır.
Gereç ve Yöntemler: Bu retrospektif çalışma hasta demografik özelliklerini, cerrahi sınır durumunu ve tümörlerin patolojik özelliklerini
içermektedir. Adenokarsinom özellikleri, goblet hücresi özellikleri ve karma özellikler gösteren ANET'ler çalışmamıza dahil edilmedi.
Bulgular: Tümörlü olguların yaş ortalaması 41'dir (11-61). Ortalama tümör çapı 6,8 mm olarak bulundu. Tümörlerin çoğu distal apendiks
yerleşimlidir (55.5%). Tümörlerin tamamı invaziv özellik göstermektedir. Dört vakada submukozaya (pT₁), dört vakada muskularis propriaya
(pT₁), sekiz vakada subserozaya (pT₃) ve dört vakada mezoapendikse (pT₃) invazyon görüldü. Sadece 2.derece özellikleri ve MAI'si olan bir
olgu için takip bilgisi mevcuttu, ek cerrahi tedaviye gerek duyulmadı ve 3 yıllık takipte metastaz olmaksızın hayatta kaldı.
Sonuç: Birinci derece ve evre-1 tümörler olsa bile metastaz riski taşıyan invaziv özellikler gösterebilir. LVI ve PNI ANET evrelemesinde
yer almasa da hastalığın seyrini etkileyen önemli faktörlerdir. Literatürde invaziv histolojik özellikler sergileyen hastalarda tamamlayıcı sağ
hemikolektomi yapılmasının tavsiye edilebilirliği konusunda fikir birliği yoktur. Bu bireyler için düzenli takip aralıklarının sürdürülmesinin
akıllıca olacağına inanıyoruz.
Ethical Statement
Ethics committee approval was given by Recep Tayyip Erdogan University Faculty of Medicine, Non-Interventional Clinical Research Ethics Committee (document number E-40465587-050.01.04-384, decision number 2022/76).
Thanks
I would like to thank Dr.Ayberk DURSUN and Dr.Ceren GÜMEDAĞ for their contributions.
References
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neuroendocrine neoplasia: analysis of 50 patients. Cir Cir.
2022;90(92):75-80.
- 2. Bayhan Z, Yildiz YA, Akdeniz Y, Gonullu E, Altintoprak F, Mantoglu
B, vd. Appendix Neuroendocrine Tumor: Retrospective
Analysis of 4026 Appendectomy Patients in a Single Center.
Emerg Med Int. 2020;2020:4030527.
- 3. Connor SJ, Hanna GB, Frizelle FA. Appendiceal tumors: retrospective
clinicopathologic analysis of appendiceal tumors from
7,970 appendectomies. Dis Colon Rectum. 1998;41(1):75-80.
- 4. Demiral G, Çolakoğlu MK, Kalcan S, Özdemir A, Demir A,
Pergel A. Incidental appendix neuroendocrine tumor and current
treatment approach in patients with acute appendicitis.
Acta Oncol Turc. 2018;51(1):17-20.
- 5. Eğin S, Kamalı G, Kamalı S, Gökçek B, Yeşiltaş M, Hot S, vd.
Neuroendocrine tumor of the appendix: Twelve years of results
from a single institution. Ulus Travma Ve Acil Cerrahi Derg
Turk J Trauma Emerg Surg TJTES. 2019;25(2):118-22.
- 6. Cañizares Quisiguiña SI, Guamán Maldonado LV, Hidalgo Jaramillo
IM, Borja Herrera TP, Carrión Guzmán C de LÁ. Incidental
neuroendocrine tumor of a complete subserosal appendix:
an unusual presentation of a rare anatomical variation. A case
report and review of literature. BMC Surg. 2021;21(1):421.
- 7. Landry JP, Voros BA, Ramirez RA, Boudreaux JP, Woltering
EA, Thiagarajan R. Management of Appendiceal Neuroendocrine
Tumors: Metastatic Potential of Small Tumors. Ann Surg
Oncol. 2021;28(2):751-7.
- 8. Pape UF, Niederle B, Costa F, Gross D, Kelestimur F, Kianmanesh
R, vd. ENETS Consensus Guidelines for Neuroendocrine
Neoplasms of the Appendix (Excluding Goblet Cell Carcinomas).
Neuroendocrinology. 2016;103(2):144-52.
- 9. Kleiman DA, Finnerty B, Beninato T, Zarnegar R, Nandakumar
G, Fahey TJ, vd. Features Associated With Metastases Among
Well-Differentiated Neuroendocrine (Carcinoid) Tumors of the
Appendix: The Significance of Small Vessel Invasion in Addition
to Size. Dis Colon Rectum. 2015;58(12):1137-43.
- 10. Sommer C, Gumy Pause F, Diezi M, Rougemont AL, Wildhaber
BE. A National Long-Term Study of Neuroendocrine Tumors
of the Appendix in Children: Are We Too Aggressive? Eur J
Pediatr Surg Off J Austrian Assoc Pediatr Surg Al Z Kinderchir.
Ekim 2019;29(5):449-57.
- 11. Wu H, Chintagumpala M, Hicks J, Nuchtern JG, Okcu MF, Venkatramani
R. Neuroendocrine Tumor of the Appendix in Children.
J Pediatr Hematol Oncol. 2017;39(2):97-102.
- 12. Alkhayyat M, Saleh MA, Coronado W, Abureesh M, Zmaili M,
Qapaja T, vd. Epidemiology of neuroendocrine tumors of the
appendix in the USA: a population-based national study (2014-
2019). Ann Gastroenterol. 2021;34(5):713-20.
- 13. Mullen JT, Savarese DMF. Carcinoid tumors of the appendix: a
population-based study. J Surg Oncol. 2011;104(1):41-4.
- 14. Moertel CG, Weiland LH, Nagorney DM, Dockerty MB. Carcinoid
tumor of the appendix: treatment and prognosis. N Engl J
Med. 1987;317(27):1699-701.
- 15. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE,
Brookland RK, vd. The Eighth Edition AJCC Cancer Staging
Manual: Continuing to build a bridge from a population-based
to a more “personalized” approach to cancer staging. CA Cancer
J Clin. 2017;67(2):93-9.
- 16. Kudaş İ, Erdem O, Topçu A, Şişik A. Carcinoid tumor of appendix:
Review of consecutive 5131 appendectomy. J Surg Med.
2018;2(2):134-6.
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Statistics for Public Health, Version. www.OpenEpi.
com, updated 2013/04/06, accessed 2024/08/26.
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A flexible statistical power analysis program for the social, behavioral,
and biomedical sciences. Behavior Research Methods,
2007;39(2), 175-191.
- 19. Cohen, J. (1988). Statistical Power Analysis for the Behavioral
Sciences (2nd ed.). Routledge. https://doi.
org/10.4324/9780203771587.
- 20. Grozinsky-Glasberg S, Alexandraki KI, Barak D, Doviner V, Reissman
P, Kaltsas GA, vd. Current size criteria for the management
of neuroendocrine tumors of the appendix: are they valid?
Clinical experience and review of the literature. Neuroendocrinology.
2013;98(1):31-7.
- 21. Volante M, Daniele L, Asioli S, Cassoni P, Comino A, Coverlizza
S, vd. Tumor staging but not grading is associated with
adverse clinical outcome in neuroendocrine tumors of the appendix:
a retrospective clinical pathologic analysis of 138 cases.
Am J Surg Pathol. 2013;37(4):606-12.
- 22. In’t Hof KH, van der Wal HC, Kazemier G, Lange JF. Carcinoid
tumour of the appendix: an analysis of 1,485 consecutive
emergency appendectomies. J Gastrointest Surg Off J Soc
Surg Aliment Tract. 2008;12(8):1436-8.
- 23. Yilmaz M, Akbulut S, Kutluturk K, Sahin N, Arabaci E, Ara C,
vd. Unusual histopathological findings in appendectomy specimens
from patients with suspected acute appendicitis. World J
Gastroenterol. 2013;19(25):4015-22.
- 24. Roggo A, Wood WC, Ottinger LW. Carcinoid tumors of the appendix.
Ann Surg. 1993;217(4):385-90.
- 25. Pawa N, Clift AK, Osmani H, Drymousis P, Cichocki A, Flora R,
Goldin R, Patsouras D, Baird A, Malczewska A, Kinross J, Faiz
O, Antoniou A, Wasan H, Kaltsas GA, Darzi A, Cwikla JB, Frilling
A. Surgical Management of Patients with Neuroendocrine
Neoplasms of the Appendix: Appendectomy or More. Neuroendocrinology.
2018;106(3):242-251.
- 26. Boudreaux JP, Klimstra DS, Hassan MM, Woltering EA,
Jensen RT, Goldsmith SJ, vd. The NANETS consensus guideline
for the diagnosis and management of neuroendocrine tumors:
well-differentiated neuroendocrine tumors of the Jejunum,
Ileum, Appendix, and Cecum. Pancreas. 2010;39(6):753-66.
- 27. Elkbuli A, Sanchez C, McKenney M, Boneva D. Incidental neuro-
endocrine tumor of the appendix: Case report and literature
review. Ann Med Surg 2012. 2019;43:44-7.
- 28. Maggard MA, O’Connell JB, Ko CY. Updated population-based
review of carcinoid tumors. Ann Surg. 2004;240(1):117-22.
- 29. Volante M, Grillo F, Massa F, Maletta F, Mastracci L, Campora
M, vd. Neuroendocrine neoplasms of the appendix, colon and
rectum. Pathologica. 2021;113(1):19-27.
- 30. Assarzadegan N, Montgomery E. What is New in the 2019
World Health Organization (WHO) Classification of Tumors of
the Digestive System: Review of Selected Updates on Neuroendocrine
Neoplasms, Appendiceal Tumors, and Molecular
Testing. Arch Pathol Lab Med. 2021;145(6):664-77.
- 31. Alexandraki KI, Kaltsas GA, Grozinsky-Glasberg S, Chatzellis
E, Grossman AB. Appendiceal neuroendocrine neoplasms:
diagnosis and management. Endocr Relat Cancer.
2016;23(1):R27-41.
Clinicopathological Correlation of Invasive Histological Features in Incidentally Detected Appendiceal Neuroendocrine Tumors (aNETs)
Year 2024,
Volume: 8 Issue: 3, 291 - 298, 30.12.2024
Ceren Sayar
,
Haldun Umudum
,
Recep Bedir
,
Zafer Turan
Abstract
Aim: Appendiceal Neuroendocrine Tumors (aNETs) are rare and mostly detected incidentally patients operated on acute appendicitis. These
are indolent tumors and mostly benign, however they carry risk of metastasis. This study aims to identify invasive histological features of
aNET cases, that are correlated with aggressive behavior other than stage and grading parameters.
Material and Methods: This retrospective study includes patient demographics, surgical margin status and pathological features of tumors.
ANETs showing adenocarcinoma features, goblet cell features, and mixed features were not included in our study.
Results: The mean age of cases with tumors is 41years (11-61 years). The mean tumor diameter was found to be 6.8 mm. Most of tumors
were located in the distal appendix (55.5%). All of the tumors show invasive features. Four cases showed invasion to submucosa (pT₁),
four cases to muscularis propria (pT₁), eight cases to subserosa (pT₃), and four cases to mesoappendix (pT₃). Follow-up information was
available for only one case with Grade-2 features and MAI, no additional surgical treatment was required, and he has survived at 3-year
follow-up with no metastasis.
Conclusion: Even if it is grade 1stage 1 tumors, may exhibit invasive features with a risk of metastasis. Although LVI and PNI are not
included in ANET staging, they are important factors affecting the course of the disease. The literature lacks consensus on the advisability
of performing completion right hemicolectomy in patients exhibiting invasive histological features. We believe it prudent to maintain regular
follow-up intervals for these individuals
References
- 1. Terzioğlu SG, Kılıç MÖ, Öksüz P, Gürer A. Appendiceal
neuroendocrine neoplasia: analysis of 50 patients. Cir Cir.
2022;90(92):75-80.
- 2. Bayhan Z, Yildiz YA, Akdeniz Y, Gonullu E, Altintoprak F, Mantoglu
B, vd. Appendix Neuroendocrine Tumor: Retrospective
Analysis of 4026 Appendectomy Patients in a Single Center.
Emerg Med Int. 2020;2020:4030527.
- 3. Connor SJ, Hanna GB, Frizelle FA. Appendiceal tumors: retrospective
clinicopathologic analysis of appendiceal tumors from
7,970 appendectomies. Dis Colon Rectum. 1998;41(1):75-80.
- 4. Demiral G, Çolakoğlu MK, Kalcan S, Özdemir A, Demir A,
Pergel A. Incidental appendix neuroendocrine tumor and current
treatment approach in patients with acute appendicitis.
Acta Oncol Turc. 2018;51(1):17-20.
- 5. Eğin S, Kamalı G, Kamalı S, Gökçek B, Yeşiltaş M, Hot S, vd.
Neuroendocrine tumor of the appendix: Twelve years of results
from a single institution. Ulus Travma Ve Acil Cerrahi Derg
Turk J Trauma Emerg Surg TJTES. 2019;25(2):118-22.
- 6. Cañizares Quisiguiña SI, Guamán Maldonado LV, Hidalgo Jaramillo
IM, Borja Herrera TP, Carrión Guzmán C de LÁ. Incidental
neuroendocrine tumor of a complete subserosal appendix:
an unusual presentation of a rare anatomical variation. A case
report and review of literature. BMC Surg. 2021;21(1):421.
- 7. Landry JP, Voros BA, Ramirez RA, Boudreaux JP, Woltering
EA, Thiagarajan R. Management of Appendiceal Neuroendocrine
Tumors: Metastatic Potential of Small Tumors. Ann Surg
Oncol. 2021;28(2):751-7.
- 8. Pape UF, Niederle B, Costa F, Gross D, Kelestimur F, Kianmanesh
R, vd. ENETS Consensus Guidelines for Neuroendocrine
Neoplasms of the Appendix (Excluding Goblet Cell Carcinomas).
Neuroendocrinology. 2016;103(2):144-52.
- 9. Kleiman DA, Finnerty B, Beninato T, Zarnegar R, Nandakumar
G, Fahey TJ, vd. Features Associated With Metastases Among
Well-Differentiated Neuroendocrine (Carcinoid) Tumors of the
Appendix: The Significance of Small Vessel Invasion in Addition
to Size. Dis Colon Rectum. 2015;58(12):1137-43.
- 10. Sommer C, Gumy Pause F, Diezi M, Rougemont AL, Wildhaber
BE. A National Long-Term Study of Neuroendocrine Tumors
of the Appendix in Children: Are We Too Aggressive? Eur J
Pediatr Surg Off J Austrian Assoc Pediatr Surg Al Z Kinderchir.
Ekim 2019;29(5):449-57.
- 11. Wu H, Chintagumpala M, Hicks J, Nuchtern JG, Okcu MF, Venkatramani
R. Neuroendocrine Tumor of the Appendix in Children.
J Pediatr Hematol Oncol. 2017;39(2):97-102.
- 12. Alkhayyat M, Saleh MA, Coronado W, Abureesh M, Zmaili M,
Qapaja T, vd. Epidemiology of neuroendocrine tumors of the
appendix in the USA: a population-based national study (2014-
2019). Ann Gastroenterol. 2021;34(5):713-20.
- 13. Mullen JT, Savarese DMF. Carcinoid tumors of the appendix: a
population-based study. J Surg Oncol. 2011;104(1):41-4.
- 14. Moertel CG, Weiland LH, Nagorney DM, Dockerty MB. Carcinoid
tumor of the appendix: treatment and prognosis. N Engl J
Med. 1987;317(27):1699-701.
- 15. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE,
Brookland RK, vd. The Eighth Edition AJCC Cancer Staging
Manual: Continuing to build a bridge from a population-based
to a more “personalized” approach to cancer staging. CA Cancer
J Clin. 2017;67(2):93-9.
- 16. Kudaş İ, Erdem O, Topçu A, Şişik A. Carcinoid tumor of appendix:
Review of consecutive 5131 appendectomy. J Surg Med.
2018;2(2):134-6.
- 17. Dean AG, Sullivan KM, Soe MM. OpenEpi: Open Source Epidemiologic
Statistics for Public Health, Version. www.OpenEpi.
com, updated 2013/04/06, accessed 2024/08/26.
- 18. Faul, F., Erdfelder, E., Lang, A.-G., & Buchner, A. G*Power 3:
A flexible statistical power analysis program for the social, behavioral,
and biomedical sciences. Behavior Research Methods,
2007;39(2), 175-191.
- 19. Cohen, J. (1988). Statistical Power Analysis for the Behavioral
Sciences (2nd ed.). Routledge. https://doi.
org/10.4324/9780203771587.
- 20. Grozinsky-Glasberg S, Alexandraki KI, Barak D, Doviner V, Reissman
P, Kaltsas GA, vd. Current size criteria for the management
of neuroendocrine tumors of the appendix: are they valid?
Clinical experience and review of the literature. Neuroendocrinology.
2013;98(1):31-7.
- 21. Volante M, Daniele L, Asioli S, Cassoni P, Comino A, Coverlizza
S, vd. Tumor staging but not grading is associated with
adverse clinical outcome in neuroendocrine tumors of the appendix:
a retrospective clinical pathologic analysis of 138 cases.
Am J Surg Pathol. 2013;37(4):606-12.
- 22. In’t Hof KH, van der Wal HC, Kazemier G, Lange JF. Carcinoid
tumour of the appendix: an analysis of 1,485 consecutive
emergency appendectomies. J Gastrointest Surg Off J Soc
Surg Aliment Tract. 2008;12(8):1436-8.
- 23. Yilmaz M, Akbulut S, Kutluturk K, Sahin N, Arabaci E, Ara C,
vd. Unusual histopathological findings in appendectomy specimens
from patients with suspected acute appendicitis. World J
Gastroenterol. 2013;19(25):4015-22.
- 24. Roggo A, Wood WC, Ottinger LW. Carcinoid tumors of the appendix.
Ann Surg. 1993;217(4):385-90.
- 25. Pawa N, Clift AK, Osmani H, Drymousis P, Cichocki A, Flora R,
Goldin R, Patsouras D, Baird A, Malczewska A, Kinross J, Faiz
O, Antoniou A, Wasan H, Kaltsas GA, Darzi A, Cwikla JB, Frilling
A. Surgical Management of Patients with Neuroendocrine
Neoplasms of the Appendix: Appendectomy or More. Neuroendocrinology.
2018;106(3):242-251.
- 26. Boudreaux JP, Klimstra DS, Hassan MM, Woltering EA,
Jensen RT, Goldsmith SJ, vd. The NANETS consensus guideline
for the diagnosis and management of neuroendocrine tumors:
well-differentiated neuroendocrine tumors of the Jejunum,
Ileum, Appendix, and Cecum. Pancreas. 2010;39(6):753-66.
- 27. Elkbuli A, Sanchez C, McKenney M, Boneva D. Incidental neuro-
endocrine tumor of the appendix: Case report and literature
review. Ann Med Surg 2012. 2019;43:44-7.
- 28. Maggard MA, O’Connell JB, Ko CY. Updated population-based
review of carcinoid tumors. Ann Surg. 2004;240(1):117-22.
- 29. Volante M, Grillo F, Massa F, Maletta F, Mastracci L, Campora
M, vd. Neuroendocrine neoplasms of the appendix, colon and
rectum. Pathologica. 2021;113(1):19-27.
- 30. Assarzadegan N, Montgomery E. What is New in the 2019
World Health Organization (WHO) Classification of Tumors of
the Digestive System: Review of Selected Updates on Neuroendocrine
Neoplasms, Appendiceal Tumors, and Molecular
Testing. Arch Pathol Lab Med. 2021;145(6):664-77.
- 31. Alexandraki KI, Kaltsas GA, Grozinsky-Glasberg S, Chatzellis
E, Grossman AB. Appendiceal neuroendocrine neoplasms:
diagnosis and management. Endocr Relat Cancer.
2016;23(1):R27-41.