Metastatic well differentiated neuroendocrine carcinoma in liver
Short Summary

78-year-old male was diagnosed with Metastatic well differentiated neuroendocrine carcinoma in liver. There is an undefined finding in the cecum that might be the primary tumor, and hepatic metastases that can be surgically respected. The imaging tests support the assumption that the primary tumor is in the small intestine.

Patient's Questions
The dilemma :
The gastroenterologist suggests, that since there is no way for biopsy at this region, there is a place for a surgical intervention. That is, resection of the ascending colon, resection of the primary in the small intestines and resection of the metastases in the liver.
The surgeon is not in a hurry to resect an unclear finding in the cecum, but rather wait a month or two for the primary tumor to grow and then do an explorative laparotomy.
The patient would like another opinion or look on this controversy.
Also, he asks regarding a double balloon enteroscopy. Can the test locate the primary tumor? can the test explain the finding in the cecum ?

And if the primary tumor is not located, should the metastases in liver be resected ?

Medical Background

Expert's Opinion

Patient's History
Sex: M,Age: 78
Diagnosis: Metastatic well differentiated neuroendocrine carcinoma in liver (non functioning)
Case history:
Medical background: Diabetes Mellitus, type II, with peripheral sensorial neuropathy treated with oral hypoglycemics.
Out of normal health, an abdominal US was done and a metastatic tumor was found in the liver, left lobe.
On liver FNB : Metastatic well differentiated neuroendocrine carcinoma, grade 2.
Immunostains:  Synaptophysin, chromogranin, CK7, and CK20: all positive.
Ki67 stain is positive in 15% of the tumor cells.
TTF1,PSA,CEA,NSE and hepatocyte are all negative.
Adjacent liver: normal hepatic tissue.
A workup was done in order to find the primary tumor.
  1. The patient is in a good general state. No relevant pathological findings on physical examination.
  2. Gastroscopy , colonoscopy and video capsule of the small intestines did not discover a primary tumor.
An Enterographic  CT of pelvis and abdomen was done with an IV contrast material after drinking LAEVOLAC.
On CT:
 A hypodense lesion in segment 3 of the liver with a diameter of 3.3 cm with peripheral contrast media enhancement. Apart of this liver is in normal size and density.
There are changes in the walls of the Cecum and ascending colon in the shape of widened and curly blood vessels with fast venal drainage. These changes are characteristic of angiodysplasia.
There is a thickening of iliocecal valve, especially the lower valve, with hyper enhancement , perhaps as part of the angiodysplasia, but other processes at this level cannot be ruled out. Immediately above this level there is a structure resembling a bagel in a general diameter of 3.3 cm and a radius of a bagel of 11mm. The meaning of this structure is not clear, but it is getting enhancement in the arterial stage and a density of 63HU at the later stage . later the density falls to 40HU. Apart from that intestine loops of the small and large intestines are at normal size without thickening of the walls and without enhancements of the mucosa.
The described findings were not present on previous CT’s.
The tumor does not release any peptide that can be identified and that could help in follow-up.
Blood serotonin , urine 5 HIAA , Chromogranin A, CEA, Gastrin, CA 19.9 – are all normal.
Below is the summary of tests looking for the primary tumor of neuroendocrine tumor or a metastatic carcinoid:
February 2008 – an incidental finding of a 3cm lesion in the left lobe of liver.
February 2008- Abdominal CT – hepatic lesion is found
February 2008 – FNB of liver – described above
February 2008- Colonoscopy and Gastroscopy – Normal
March 2008 – General CT, Chest – Normal
March 2008 – Video-capsule of small intestine – Normal
March 2008 – Bone scan - Normal
March 2008 – Somatostatin Scan – no new finding
March 2008 – Gastrin test – Normal
March 2008 – Abdominal CT in addition to condensed cuts to pancreas – Normal
April 2008 – PET-FDG – no new findings
April 2008 – EUS – Endoscopy of upper gastric system- 2 metastases in left lobe of liver (and not one as was seen before)
April 2008 – CT Enterography – above iliocecal valve a bagel like structure, unclear significance.
Urine 5-HIAA – Normal
Chromogranin , Serotonon – Normal
Expert's Answer
I assume that this gentleman is in good general health, although having diabetes mellitus type 2. He is therefore able to undergo surgery. Proliferation capacity of the tumor is somewhat higher than we expect for a classical midgut carcinoid, usually less than 2 % Ki-67 positive cells. Therefore, this might be a more aggressive form of carcinoid, with the primary located in the cecal area or in the ascending colon. The angio-dysplastic changes and the bagel formed lesion might be metastases in the mesenteric lymph nodes. Based on the actual clinical situation I strongly recommend surgery and not a wait-and-see approach. By surgery one can localize the primary tumor in the abdomen with resection of the primary tumor, lymph node metastases and also the two liver metastases seen on endoscopic ultrasonography. I do not think that balloon-enteroscropy will change the current situation and I can not see any advantage of waiting with the surgery if the patient is fit for surgery at this moment. Sometimes fibrosis around the primary and mesenteric metastases might cause acute ileus and thereby the patient will be in a worse condition. After the surgery it is important to follow this patient very carefully and also to think about adjuvant medical treatment, depending on the situation at surgery. Due to high proliferation capacity and the liver metastases, temozolomide in combination with capecitabine might be an option.