Appendiceal Neuroendocrine Neoplasms (ANENs)

1
Appendiceal Neuroendocrine Neoplasms (ANENs)

• Krystallenia Alexandraki
• Endocrinologist

Endocrine Department, Pathophysiology Clinic,
Laikon Hospital, National and Kapodistrian
University of Athens
2
NEN of the Appendix (ANEN)- Epidemiology

• Incidence
• 0.15 (SEER)/ 106/ yr
• 0.4-0.6/106/ yr
• Incidence of appendectomies -
• 3-9/1000 procedures

ENETS Consensus, 2012
3
Patient 1, A. K.

• 27 year-old woman, previously in good health
• 2/2004 - abdominal pain
• Appendicectomy Small tumor noted at base of
  appendix

4
Patient 1, A.K. - histopathology

• 1.1 cm WDNEN.
• penetrates the serosa
• Do not extend into the mesoappendiceal fat
• Not evidence of angioinvasion
• Ki-67 lt 1.
• Tumour close to the surgical margins

5
Patient 2, F. S.

• 25 year-old woman, previously in good health.
• 7/05- abdominal pain
• Appendicectomy Small tumor noted at tip of
  appendix

6
Patient 2, F.S. - histopathology

• 1.2 cm WDNEN.
• the tumor penetrates through all layers of the
  appendix and and invades the mesoappendiceal fat.
  
• Ki-67 1
• Surgical margins - free of tumor.
• immunohistochemistry
• CgA ()ve, NSE ()ve, s??apt?f?s??? ()ve, CD56
  ()ve

7
Patient 3, K. T.

• 19 year-old woman, previously in good health.
• 7/06- chronic abdominal pain
• Appendicectomy Small tumor noted at the base of
  appendix and close to the surgical margins

8
Patient 3, K.T. - histopathology

• 0.8 cm WDNEN.
• the tumor penetrates through all layers of the
  appendix and the muscular wall.
• Low Ki-67 (few cells)
• Surgical margins - free of tumor.
• immunohistochemistry
• CgA ()ve, NSE ()ve, Synaptophysin ()ve, CD56
  ()ve

9
Patients A. K. - F. S. K.T.What next?

• Nothing?
• Right hemicolectomy?

10
Histopathology characteristics
K. T.
Appendix)
base
Tip
base
0.8
Yes
no
no
no
close
few cells
Alexandraki, J Endocrinol Invest 2011
11
Probability of metastasis in appendiceal NET is
related to tumor size
Histopathology Characteristics in Presented
Patients Tumor Size
lt10
5-25
lt1 cm
gt 2 cm
1-2 cm
Less clear-mets in 10 or none
Cured by simple appendicectomy exception base/
MAIgt3mm /incomplete resection
12
Histopathology Characteristics in Presented
Patients Penetration to Serosa

• Serosa involvement is demonstrated to be present
  in up to 70 of all malignant NETs, but is judged
  to be unrelated to outcome in the published
  literature, Stinner and Rothmund, 2005.
• Invasion of the serosa is not correlated with
  lymph node metastasis and has no impact on
  survival, ENETS Consensus, 2008.

13
Histopathology Characteristics in Presented
Patients Localisation
Tip Mid-appendix Base
prevalence 60-75 5-20 lt10

• Lesions at the base of the appendix are more
  likely to produce local recurrence than those at
  the tip if treated only by simple
  appendicectomy, Sutton, 2003.
• Incomplete resection after appendicectomy? mets
  NEN at the base more aggressive therapy in NEN
  1-2cm in size, ENETS Consensus, 2012.

14
Histopathology Characteristics in Presented
Patients Mesoappendiceal invasion (MAI)

• in up to 20 of adults and 40 of children
  Rossi, 2003
• The depth of invasion beyond 3 mm reflects the
  aggressiveness ENETS Consensus, 2012.

15
Histopathology Characteristics in Presented
Patients Additional criteriaKi-67 index

• The role of proliferation markers such as Ki-67
  and mitotic activity is not precisely defined for
  appendiceal NETs.it might justified to use these
  items even for NETs of the appendix regarding the
  basic biological principles of proliferating
  tissue, although this reflects a very low level
  of evidence, Stinner and Rothmund, 2005
• Additional criteria such as ki-67 of 3 or
  angioinvasion aid decision making, ENETS
  Consensus, 2012

16
Histopathology after RHC
A.K. S.F. K.T.
Period to RHC (months) 1 2 9

• F. S. 1/10 LN-metastatic NEN
• K.T. 1/14 LN-metastatic NEN

• A. K. 0/36 LNs persistent disease in proximity
  of the primary

17
Follow-up

• A. K.-34 yrs old
• Post-operative complication ileus re-operated
• abdominal CT and MRI 10 years later free of
  disease- 1 full-term pregnancy

• F. S.32 yrs old
• No post-operative complications
• Abdominal ultrasound
• and abdominal CT every 5 yrs- 9 yrs free of
  disease- nulliparous

• K. T. 25 yrs old
• Post-operative complication ileus re-operated
• Abdominal MRI every 2-3 yrs- 8 yrs free of -

18
BIOCHEMICAL PROFIL
?.?. F.S. K.T.
CgA (ng/ml, 19,4-98,1) 31,5 39.3 40
5-???? (-) (-) (-)
OCTREOSCAN (-) (-) (-)
CT ABDOMEN Pericaecal adhesions and mesenteric lymph nodes
U/S ABDOMEN No pathology
MRI ABDOMEN No pathology
19
5-HTP PET SCAN A.K. (-)ve
Indium-111-pentetreotide scintigraphy- A.K. False
()ve result
20
Three patients summary Aims

• Three patients with Appendiceal NENs had
• Grey Zone tumors with respect to size
• Mesoappendiceal invasion (MAI) and base
  localisation
• Regional lymph node metastasis and residual
  disease
• Patients with MAI and 1-2cm in max diameter might
  have a higher risk of local metastasis than
  previously considered.
• ANEN lt1cm, simple appendicectomy is curative and
  sufficient only exception NEN at the base of the
  appendix and incompletely resected or MAI 3 mm

21
Acknowledgments
Thank you