Metastatic well differentiated neuroendocrine carcinoma in liver_2
Short Summary

78-year-old male was diagnosed with metastatic well differentiated neuroendocrine carcinoma with unknown primary. He recently underwent explorative laparotomy that revealed solitary metastasis in the liver, and a hard lesion in the mid-ileum suspicious for the primary carcinoid. A frozen section showed foreign body type giant cell granuloma. Left lateral segmentectomy of the liver showed a white hard lesion. The expert recommends a regular follow-up that should consist of abdominal ultrasonography combined with CT or MRI.

Patient's Questions
1)    How to continue the follow-up as no primary or secondary were found and no endocrine markers?
 
2)    Is adjuvant medical treatment needed? According to which protocol ?
 
3)    How to measure response to treatment ? side effects ?
 
4)    What is the success rate of your recommended adjuvant treatment ?
Medical Background

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 CThepatic 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 Enterographyabove iliocecal valve a bagel like structure, unclear significance.
Urine 5-HIAA – Normal
Chromogranin , Serotonon – Normal
~~~~~~~~~~~                                                                                              
Updated medical information regarding the patient , after the surgery that was preformed recently.
Male, age: 78
Diagnosis
: Metastatic well differentiated neuroendocrine carcinoma with unknown primary.
On July 2008 – explorative laparotomy was preformed including intra-abdominal U.S., with careful examination of different parts of the abdomen : Stomach-Duodenum, small bowel, colon, rectum, pancreas (head and body) all with no pathology. Liver – normal structure except a solitary metastasis in the known area. In the mid-ileum a hard lesion – 3 mm in size with retraction of the tissue around - was found suspicious for the primary carcinoid. An 8 cm segment of the ileum was resected. However a frozen section pathologic examination showed “ foreign body type giant cell granuloma” . This lesion and the “bagel form lesion near the cecum could be secondary to shred wounds. A small lymph node was free of tumor.
Left lateral segmentectomy of the liver , measuring 13x10x4 cm was preformed. It showed a white hard lesion the size of 4x3.5x2cm. Free margin of resection was 1.7 cm.
Post operative course was normal, without temperature.
The patient was discharged from the hospital on July 2008. Hemoglobin went down from 14gr to 9.5gr, but no blood – transfusion was necessary.
The patient is in quite good health except D.M. type 2 controlled oral hypoglycemic.

Expert's Opinion

It is certainly an unusual case of neuroendocrine carcinoma, where no primary tumor could be located. It is described in single cases that you might have primary neuroendocrine tumors in the liver, but I could not find out if the lesion removed from the liver actually showed viable tumor. Fine needle aspiration however demonstrated previously a neuroendocrine carcinoma grade 2. I do not think this patient should have any adjuvant medical treatment at the moment, but should only be followed regularly. Abdominal ultrasonography seems to be the most sensitive method to pick up this tumor and therefore I would recommend during the first two years. Ultrasonography every three months, combined with CT or MRI every six month. After about one year I would recommend a new somatostatin receptor scintigraphy.

""