Puppy with a mast cell tumour on pinna

Re: Puppy with a mast cell tumour on pinna

Gerry Polton — Mon, 03 Mar 2014 08:36:16 GMT

Great photos, thank you. That makes it a lot easier to advise. I would be comfortable with excisional biopsy in this case now that you know the diagnosis. I hear the hiss of collective sharp intakes of breath. This is a small mast cell tumour in a location with plenty of 'spare' tissue for a good clean margin. I believe that if you were to trace a 2cm margin around this mass you could excise the tumour completely with a full thickness of pinna without compromising the blood supply to the tissue distal to the hole you have created. It would have a superior cosmetic finish to the simple pinnectomy but it would be more complicated to perform. The simpler technique is to undertake pinnectomy. While there is valid debate about how to remove it, there is no doubt that this a tumour that should be removed.

To answer other outstanding questions: in my opinion additional (immuno)histochemical evaluations are an excellent way of generating ill-justified financial returns in most cases. The most significant determinant of prognosis in canine cutaneous mast cell tumours remains histological grade (according to Patnaik, not to Kiupel). There are cases where the clinician struggles to make a judgement about the risk of local recurrence or metastasis. Those cases are the intermediate grade tumours which might be reported to have been incompletely excised or the ones with a mitotic index of two or more (let's say up to four). Those cases are not the high-grade tumours or the ones with high mitotic indices (five or greater). We know they are bad; there is no value in doing another test which tells you that for a second time. So, for those in-betweener cases, we need another test that is going to tip us one way or another. Ki-67 +/- AgNOR are very good for that purpose and that purpose alone. They are not a substitute for good intepretation of histological grade characteristics.

Different labs try to follow the same techniques for staining for these things. However, there are intrinsic differences between the outputs generated (you would not believe how different results can be even with apparently the same technique employed). Therefore, it is appropriate for different labs to use their preferred technique and score system, so long as it is at least internally validated. So, it is perfectly appropriate for Bridge Pathology to have a cut-off of 1.8% and GD to use 93/1000. It would otherwise be a bit like Usain Bolt getting a new coach who advised training by running against me over 100 metres and then thinking, if he beat me, that he done rather well. In reality, we would expect him to apply a standard that better suited normal for him.

Anyway, that's enough from me.

Gerry

Re: Puppy with a mast cell tumour on pinna

John Flynn — Sun, 02 Mar 2014 20:46:09 GMT

Interesting, Chris.

I should probably look into the whole Ki67 thing again as I could be missing a trick and have written off something useful just because I got too confused (and then bored) trying to figure out how to use a result a few years back.

[quote user="Christopher Saul"]The thing is, Ki67 is independent of histological grade[/quote]

It is, but if we take the Scase 06 study you mention, more Patnaik grade1 tumours (4/15 = 27%) had a "high" Ki67 than grade 2 tumours (14/70 = 20%). While this trend is to Ki67 independence to histological grade (at least between grades 1 & 2 patnaik in this study), in of itself that fact is not inspiring as to its independent prognostic utility as none of the grade 1 tumour dog's died due to a MCT.

[quote user="Christopher Saul"]In my own anecdotal experience I have seen MCTs with a low MI and a high Ki67. To rely on histo alone one would dismiss these tumours as benign but the high Ki67 means you treat them as malignancies.[/quote]

1) What are you classing as a "high" Ki67 index as different labs (and published studies) define this rather differently (not dissimilar from their inherent variation in subjective grade perhaps under either Patnaik or Kiupel scale?)

2) This experience does not validate the approach necessarily; you have treated them as malignancies, but that experience does not mean much beyond what is inferred from published studies on which you have based this treatment algorithm (even with the memorable case that behaved atypically by all standards but Ki67)..

3) If this is on incisional biopsies, then the validity of the Scase 06 study is further called into question as it is not clear how the technique and therefore "cut-off" interpretation applies to incisional biopsies?

[quote user="Christopher Saul"]Just my 2 pence[/quote]

Useful insights as always - thanks for sharing

Re: Puppy with a mast cell tumour on pinna

Stephen Courtney — Sun, 02 Mar 2014 15:18:49 GMT

I would recommend a biopsy before pinnectomy - While MCTs are rare at this age, they are not impossible and yet, it looks like a histiocytoma, and mast cells can be present in inflamed tissue, without necessarily being malignant.....

I've never forgotten a 6 month old GSD with a funny boney mass that had two path professors arguing about the diagnosis - osteosarc or inflammation - and after the owner elected to do nothing, the dog went on to live a normal lifespan.

I have also had mast cells diagnosed by FNA that morphed into something else when the surgical biopsy was submitted

Re: Puppy with a mast cell tumour on pinna

Christopher Saul — Sun, 02 Mar 2014 13:11:14 GMT

[quote user="John Flynn"]So how do folk actually interpret these Ki67's and do you actually think that they alter your case approach, and if so are you sure that the alteration is justified based on the validity of the testing?[/quote]

The thing is, Ki67 is independent of histological grade (unlike AgNOR)

In my own anecdotal experience I have seen MCTs with a low MI and a high Ki67. To rely on histo alone one would dismiss these tumours as benign but the high Ki67 means you treat them as malignancies. One in particular sticks out in the memory with an MI of 0 and ranked as low grade by both Patnaik and Kiupel grading systems. It did prove to be malignant in its behaviour - there was evidence of spread to the local lymph node.

There is literary evidence out there to support the theory that Ki67 is prognostic - Scase et al from 2006 (off the top of my head but can't remember the others as I'm out and about on my phone here) - divided a group of MCTs classified as intermediate into low and high grades based on Ki67 and found a very significant correlation with outcome

That said, I'm by no means saying that Ki67 is the holy grail or a golden bullet. As with all diagnostic tests, it merely represents a piece of the jigsaw and no more. I wouldn't, for instance, treat a mass with a high MI as a low grade tumour simply because it has a low Ki67 (but then again, I wouldn't bother running a Ki67 on a tumour with a high MI, I'd treat it as potentially malignant anyway). It is an adjunctive test, something to add onto more conventional tests, and can NEVER replace them.

So if Ia tumour has already demonstrated gross metastatic potential or a high MI and/or high histological grade, then Ki67 adds nothing because you would treat it as potentially malignant anyway (i.e. a low Ki67 would not change your mind). BUT if the inverse is true and if there are no other indicators of malignant behaviour, then adding Ki67 adds an extra layer of comfort before treating it as benign.

I think that out of the proliferation markers available - Ki67, AgNOR and PCNA, if funds are limited and you can only run one - then chose Ki67 because it is independent of his otological grade, unlike the others...

Just my 2 pence

Chris

Re: Puppy with a mast cell tumour on pinna

Bob Russell — Fri, 28 Feb 2014 15:18:31 GMT

I think I would be happier with more confirmation of the diagnosis before lopping off the pinna. Not a big job to do a biopsy. Would probably do an impression smear as well.

Both easy and should get results rapidly. Confirmation should get the owners firmly on-side!

If it is indeed a mast cell tumour off the pinna would come! Make it clear to the owner just how lucky they are that this is an area where surgical margins are easy.

Of course warn them mast cell tumours can behave in unpredictable ways!

Re: Puppy with a mast cell tumour on pinna

Linda Filshie — Fri, 28 Feb 2014 15:01:31 GMT

That certainly looks like darier's (sp?) sign on the post-FNA pic.

Re: Puppy with a mast cell tumour on pinna

Rob Davis — Fri, 28 Feb 2014 14:14:09 GMT

[quote user="shanley barber"]Hi Gerry, Thank you very much for the offer; once the cytology report is back, I will take and post some pics. Thanks again, Shanley

[/quote]

Hi all, Shanley's not in today so she's asked me to post these pictures on her behalf:

The pathologist's report is as follows:

DESCRIPTION

Pinna. Cellularity is moderate and preservation/staining poor. Proportionally the

smears contain moderate to large numbers of red blood cells and moderate numbers of

cells with moderate amount of cytoplasm with abundant small granules and round to

oval nuclei with unremarkable chromatin. Occasional keratin shards from fingerprints

origin are present.

DIAGNOSIS

Pinna. Mast cell tumour.

COMMENT

Despite the young age of this Labrador, the fine-needle aspiration of the nodule on

the lateral aspect of the pinna, yields abundant mast cells. This harvest is

consistent with a mast cell tumour. Given the unusual age presentation, requesting

mast cell prognostic tests at the time of histopathology of the mass, may help to

identify mutations (exon 11 and ) which is made predisposed this animal to develop

further masses.

Re: Puppy with a mast cell tumour on pinna

John Flynn — Fri, 28 Feb 2014 10:45:07 GMT

I would second either an incisional biopsy (do no harm, get more info) or whip off the pinna (it's straightforward and dog won't be any worse off, "pinnal-sparing" would be purely cosmetic from the owner's perspective and surgery from a cosmetic perspective is a grey-zone at best for me; in the event that was nasty malignancy, you've removed the primary as best you can which is usually part of any treatment plan).

[quote user="Tim Charlesworth"]Ki67 index[/quote]

I know this is only part of prognostic info to be interpreted with respect to others such as mitotic index and perhaps further cell proliferation analyses (PCNA, AgNOR), a c-kit PCR, and KIT immunohistochemistry etc, but I remain a little concerned that its use is poorly validated and not really helpful in the average mast cell excision decision making process.

I used to send these to Bridge Pathology in Bristol a few years back, and believed it to be a useful cut-and-dry grading tool at the time, and interpreted it with a strict cut-off of 1.8% as per Maglennon et al. (2008).

Then I realised that other labs, such as GD Animal Health Service in Netherlands, base their interpretations on the work of Abadie et al. (1999) with a 9.3% cut-off between "good" and "bad".

Indeed, as I contacted various labs to determine how they interpreted Ki67 indices on MCTs, it became clear that there was little by means of consensus, with many prominent labs basing their interpretation on unpublished internal protocols. For example, at Michigan State University cut-offs have been internally statistically determined by ROC and evaluation is based on number of positive cells within a certain number of reticles (as opposed to field of vision since that varies from scope to scope). Based on this method their cut-off is 23 and their methodology is not compatible with the aforementioned published studies.

So, with so many unknowns and apparent lack of general consensus and validity for Ki67 testing and how to interpret it, I just gave up and went back to standard H/P.

So how do folk actually interpret these Ki67's and do you actually think that they alter your case approach, and if so are you sure that the alteration is justified based on the validity of the testing? If the interpretation is based often on correlation with other indices such as mitotic index (rather than independent clinical outcome data), then is it possible that this is another example of Emperor's New Clothes? Has there been anything new published since I last looked that I should take a look at?

I still find that MCT's are a very rare cause of euthanasing a dog, while they are a very common presentation in the consulting room. This does make me wonder if I am not possibly sometimes guilty of over-complicating their management?

Just some thoughts to prompt discussion

Re: Puppy with a mast cell tumour on pinna

Tim Charlesworth — Fri, 28 Feb 2014 09:13:34 GMT

[quote user="Anthony Todd"]

A dinosaureal question? Seeing as i looked like a S/C smartie....

Cryosurgery? and repeat as necessary [no red stars just a polite put-down with an explanation will do.

[/quote]

Hi Anthony, I think that cryo is probably an underused treatment for small, superficial but benign masses eg on the ear tips. If you Cryo this mass then you won't be able to do normal histopath on the mass, however, and you can get a lot of prognostic information this way eg tumour grade, Ki67 index etc which you can use to guide further monitoring/treatment. Normal margins of excision would be 2 cm lateral and so there would be a significant risk of recurrence if you just cryo'd the mass itself (and there would be no histological examination of margins) and so I would always excise these even if you left the wound open to granulate. The other concern would be potential degranulation/histamine release from the tumour during the cryotherapy itself.

Re: Puppy with a mast cell tumour on pinna

Tim Charlesworth — Fri, 28 Feb 2014 09:00:40 GMT

Hi Shanley, not going to add anything to this other than reinforcing that these are surgical cases. We do see MCT's in young dogs but it is relatively unusual. It may be worth taking an incisional biopsy from this one to confirm the diagnosis, determine the grade of the MCT (if confirmed) and therefore determine what margins you need (if it's low grade you may not need the "normal 2cm"). By incisional biopsy I mean just take a very small wedge from the mass itself and don't be tempted to "whip it off" and do an excisional biopsy as this will make any further attempts at resection (and possible preservation of the pinna) more difficult. It would be worth pretreating the dog with antihistamines as a precaution before biopsying the mass. The other thing to consider is staging the mass to see if its spread: We usually take FNA's/excision of local LN's + ultrasound + FNA of liver/spleen. Most owners are much happier to put their dog through pinnectomy if everyone is as certain as they can be that this is going to be curative.

On a related note - it is possible to reconstruct a pinna by using a type of distant direct flap ie taking some scruff skin and pursuading it to heal to the pinna remnant. Not commonly done but the technique is out there..

Re: Puppy with a mast cell tumour on pinna

Michael Woodhouse — Fri, 28 Feb 2014 01:46:45 GMT

[quote user="Anthony Todd"]Cryosurgery? and repeat as necessary [no red stars just a polite put-down with an explanation will do.[/quote]

No disrespect to the OP, but specialist pathologists sometimes sit a little on the fence when calling round cells tumours. Given the age of the dog and lack of a pathologists opinion other (benign) tumours would be on my DDx list. In those cases some of those respond well to cryosurgery.

Re: Puppy with a mast cell tumour on pinna

Anthony Todd — Thu, 27 Feb 2014 18:28:09 GMT

A dinosaureal question? Seeing as it looked like a S/C smartie....

Cryosurgery? and repeat as necessary [no red stars just a polite put-down with an explanation will do.

Re: Puppy with a mast cell tumour on pinna

shanley barber — Thu, 27 Feb 2014 15:22:53 GMT

Hi Gerry, Thank you very much for the offer; once the cytology report is back, I will take and post some pics. Thanks again, Shanley

Re: Puppy with a mast cell tumour on pinna

Gerry Polton — Thu, 27 Feb 2014 08:23:54 GMT

Hi Shanley

The answer below which states that surgery is your only option is the only correct answer. Medical therapy is not going to achieve a full life free from complications of either the tumour or the treatment. Median time to progression for mast cell tumours in dogs receiving masitinib with no prior intelligent selection of treatment candidates is only 118 days! The only question that remains is how much surgery. The beauty of operating on the pinna is that you can usually easily obtain decent surgical margins without compromising cosmetic appearance enormously. In some specific pinna locations you can obtain good margins without removing the whole pinna. Make sure you know the vasculature of the pinna before making your cuts if you do a partial pinnectomy. If you can post a photo I would be happy to comment further.

Yours

Gerry

Re: Puppy with a mast cell tumour on pinna

Michael Woodhouse — Thu, 27 Feb 2014 01:50:30 GMT

Could the degranulating mast cells be an artefact from the FNA?

Re: Puppy with a mast cell tumour on pinna

Braden Collins — Wed, 26 Feb 2014 23:00:16 GMT

Surgery is your only curative treatment option assuming not high grade so excise with sufficient margins is your only option IMHO. Better to be disfigured than dead I reckon. I'd wait for lab confirmation of course.

Re: Puppy with a mast cell tumour on pinna

Julian Earl — Wed, 26 Feb 2014 21:51:16 GMT

If confirmed as a MCT, the Masivet. I've had tremendous success with aggressive, widespread MCTs and would probably go down that route. It requires a lot of monitoing but hugely effective IME.