Protocol for Insulinoma GA

RE: Protocol for Insulinoma GA

Anthony Dennison — Tue, 21 Jun 2016 09:16:20 GMT

Sorry Tim, I think rather than the final diagnosis it was the progression of the case that was more interesting. The dog presented with signs that would indicate an insulinoma, though insulin wasn't above the reference range it was inappropriately high. Original histopath reports (and I got them double checked) were insistent that it was a carcinoma of the exocrine pancreas.

This didn't fit the clinical picture as blood glucose normalised after surgery so we investigated further and the diagnosis has since changed to carcinoma of endocrine pancreas. The suggestion of writing the case up was by Iain.

RE: Protocol for Insulinoma GA

Tim Charlesworth — Mon, 20 Jun 2016 17:53:34 GMT

I may be missing something here (perfectly possible) but canine Insulinoma is usually malignant (most carcinoma) and by definition is endocrine and so I'm not sure what the novel aspect of this one is? Sorry - not meant to sound critical but I don't see why this would be written up/published?

Tim

RE: Protocol for Insulinoma GA

Anthony Dennison — Mon, 20 Jun 2016 17:04:26 GMT

Just an update on this case - I spoke to Iain Grant at NorthWest Surgeons who couldn't believe that it was a carcinoma as normally buyt the time they are detected there are gross metastases throughout the abdomen.

Immunohistochemistry was done and results are as below:

IMMUNOHISTOCHEMICAL RESULTS
The neoplastic cells show a moderate to strong and diffuse
cytoplasmic positive immunolabeling for endocrine markers
chromogranin A and synaptophysin. In addition, approximately
the 10% of neoplastic cells show a strong cytoplasmic positive
immunolabeling for cytokeratin (epithelial marker).

INTERPRETATION
On the basis of the results of the immunohistochemical
analysis, this is a carcinoma of neuroendocrine origin. These
changes, along with the clinical presentation of the disease
(e.g. low glucose and increased insulinemia) support the
definitive diagnosis of insulin secreting tumour (insulinoma).
Considering the degree of tissue infiltration, this is
considered an islet cell carcinoma. This tumour can
metastasize to regional lymph nodes (e.g. duodenal,
mesenteric, hepatic and splenic) and distant sites (liver,
mesentery).

So, it was a carcinoma, but of endocrine rather than exocrine pancreas. In the past week the dog has started becoming hypoglycaemic again so we suspect either a regrowth of the tumour or metastases. Plan is to start low dose prednisolone to help with the hypoglycaemia, and speak to the owner about starting on doxorubicin.

As far as Iain is aware, this is the first case he has ever heard of with this presentation and type of tumour, so I may write it up at some point.

RE: Protocol for Insulinoma GA

Anthony Dennison — Thu, 19 May 2016 11:21:26 GMT

Gerry Polton is there a specific protocol you would recommend? Is it worth pursuing chemo given that there is no sign of spread?

RE: Protocol for Insulinoma GA

Anthony Dennison — Thu, 19 May 2016 09:50:54 GMT

Histopath report is back (see below). Good news is on the CT and ultrasound scans we did prior to the ex-lap there was no sign of spread. So, chemotherapy time I think!

DIAGNOSIS
Pancreatic carcinoma, acinar or ductal cell in origin.

PROGNOSIS
Guarded to poor.

CLINICAL HISTORY
History of constantly low glucose (below 5) and
seizure. High insulin is also reported (ref n 1003169075).
There is a nodule in the pancreas and multiple nodules on the
small intestine. Neoplasia with spread suspected.

HISTOLOGY
Right limb of pancreas with nodule. Blocks A to C) one section
each (in C section of the nodule). In the sections of blocks A
and B, the exocrine and endocrine pancreas are unremarkable. In
the section of block C, there is a well demarcated,
unencapsulated neoplastic proliferation of polygonal cells
arranged in cords and irregular tubules and supported by
abundant desmoplastic stroma. The cells have scant amounts of
eosinophilic cytoplasm, round to oval nuclei with finely
stippled chromatin and one nucleolus occasionally prominent.

Anisocytosis and anisokaryosis are moderate. Mitoses are
atypical, 0-2 per high power filed (40x).

Serosal (jejunum) nodule. Block D) I have asked to examine
another section in order to better characterize the lesion.
This does not look like a metastases of the carcinoma.

COMMENT
In the pancreas of Lexia there is a carcinoma of the exocrine
pancreas. This might arise from the acinar cells or, more
likely in my opinion, from the pancreatic ducts. Pancreatic
carcinoma is an aggressive and metastasizing disease. You can
discuss this case with an oncologist. Check of the lymph nodes
and distant sites to exclude metastases is recommended.

RE: Protocol for Insulinoma GA

Emily Rainbow — Sun, 15 May 2016 19:32:39 GMT

Interesting case Dennison!

RE: Protocol for Insulinoma GA

Anthony Dennison — Fri, 13 May 2016 16:22:28 GMT

Update on this case:

CT showed no mets, however for some reason the cranial abdomen was missed off so couldn't exactly say whether there was a mass or not. Plan was to repeat CT FOC, with our machine we can perform an angiogram by giving the contrast at the start of the scan.

However she collapsed on Wednesday night and had hypoglycaemic seizures. 24 hours on a glucose drip later, during which time we had an ultrasonographer come in to scan her (nothing found), we ex-lapped her this morning.

Small, approx 1.5cm diameter nodule in the middle of the pancreas. Where it was we had to removed the right limb. During surgery I noticed some white nodules/plaques on the serosal surface of the intestines - just the odd one approx 1-2mm diameter dotted around, so I scraped one off to go for histo too.

Now to await results!

RE: Protocol for Insulinoma GA

Anthony Dennison — Tue, 03 May 2016 16:44:06 GMT

Update:

Insulin came back as 25.4, within the reference range (5-40) but according to one of the Idexx internal medics, still high relative to the blood glucose reading.

Dog is booked in for a CT scan on Thursday. I'll let you know the results!

RE: Protocol for Insulinoma GA

Andrew Kent — Sun, 01 May 2016 09:56:23 GMT

the sensitivity of ex-lap for the primary lesion is high, but for metastatic disease is low.

The point of imaging these cases is not to confirm diagnosis (I agree that in many cases we can be fairly certain from bloods etc) it's to assess for location of mass (and therefore possibility of resection) and mets.

and CT can answer that question in a much quicker and less invasive way than anything else.

Andy

RE: Protocol for Insulinoma GA

grumpyoldman — Fri, 29 Apr 2016 19:11:51 GMT

[quote user="Andrew Kent"]The sensitivity of ultrasound for insulinoma varies with different studies but is likely to only be 35-50% so you could try it but wouldnt be too optimistic.[/quote]

Won't that depend on the machine and the operator?.

What is the sensitivity of an Ex lap ?

If the insulin is high and the glucose persistently low , and there are no other " big liver masses " given the age of animal etc what else could it be ?

RE: Protocol for Insulinoma GA

Andrew Kent — Thu, 28 Apr 2016 20:01:41 GMT

[quote user="Anthony Dennison"]

[quote user="Andrew Kent"]CT is so quick that you will probably be fine, I would typically image on a different occasion to surgery in order to plan better for the procedure. Remember for insulinoma that the CT should be an arterial phase to have a good chance of picking up a mass which requires use of a timed pressure injection.[/quote]

Unfortunately we have one of the new BCF CT scanners, which is cone-beam rather than helical or spiral and therefore we can only get venous phase. Would an experienced ultrasonographer be able to pick something up, or am I better referring somewhere that can do arterial phase CT?

[/quote]

I suppose that depends whether multiple imaging modalities would be possible. The sensitivity of ultrasound for insulinoma varies with different studies but is likely to only be 35-50% so you could try it but wouldnt be too optimistic.

Equally standard CT can pick up 60-70% of cases but dual phase CT detects nearly all cases if performed correctly.

Andy

RE: Protocol for Insulinoma GA

Anthony Dennison — Thu, 28 Apr 2016 09:04:24 GMT

RE: Protocol for Insulinoma GA

Thomas Johnson — Wed, 27 Apr 2016 16:58:35 GMT

[quote user="Andrew Kent"]

Hi Anthony,

The key with insulinoma GA is monitoring and responding to what you find. I don't routinely give IV glucose (as that triggers more insulin release) but use it as needed depending on frequent BG measurement. Obviously starve for as little period as possible and get eating as soon as possible afterwards.

[/quote]

This article in the Veterinary Times suggests using medetomidine as part of the protocol as it is an insulin antagonist:

http://www.vettimes.co.uk/article/anaesthesia-for-patients-with-endocrine-diseases/

RE: Protocol for Insulinoma GA

Andrew Kent — Wed, 27 Apr 2016 11:59:03 GMT

Hi Anthony,

CT is so quick that you will probably be fine, I would typically image on a different occasion to surgery in order to plan better for the procedure. Remember for insulinoma that the CT should be an arterial phase to have a good chance of picking up a mass which requires use of a timed pressure injection.

Andy

RE: Protocol for Insulinoma GA

grumpyoldman — Wed, 27 Apr 2016 00:01:39 GMT

I have seen and operated on 5 of these over about 30 years , the last one carried on meds free for 5 years ,if your sure just go for the ex lap and feel for the nodule. My last one presented as a collapsing hindlimb weakness but also had those odd muscle fasiculations and tremors that are so odd. The histo report was grim ,but the expected mets never happened. CT + contrast probably a good idea though pre op.