Hi Gang! I know this thread is a bit old but let me see if I can do a bit of clarification here.

The original question - "How are aggressive masto or mcas defined?"


First of all, the name "masto" does not mean mastocytosis, but is the name we patients give to ALL mast cell disorders independent of the form.  Having clarified this we move on to another misunderstanding - that of what aggressive means.

The word "aggressive" is a medical term applied to diseases which are aggressive in nature in that they attack the body and kill it quickly, in an aggressive nature like cancer.   When mastocytosis presents itself as an aggressive disease it is very easy to see because it wrecks total havoc in the blood markers (CBCs and clotting testing as well as other exams).  Aggressive SM is a proliferative disease where the MCs aggregate and proliferate invading tissues.  It isn´t that they are replicating like a cancer, but that they end up crowding out the healthy cells and since they are cloning themselves so quickly they soon crowd out all the other normal cells and thus they proliferate within the pancreas, spleen, lymphnodes, bone marrow, liver, because this is where the MC is fabricated or where it is filtered and this is why it "invades" these tissues.   It´s not really invading per se, its just that this are the places where the cells are made or filtered and the production is so intense that the tissues can´t get rid of them enough, like stock in a manufacturig company which cant pass on it´s product fast enough.  This causes those organs to stop functioning properly because there´s not enough room to function correctly.  

So, an aggressive SM has CBCs and other blood tests which are WAY out of normal, they also have an elevated tryptase and there is also organ malfunction and increased size due to the over production of aggregated MCs.   The MCs are produced non-aggregated but quickly aggregated due to a substance which binds them together when they are malignant.  The normal MCs which are also produced don´t aggregate and they remain normal.  The both are being produced at the same time, only those which have the specific defect upon Kit are those which aggregate.


Aggressive SM is EASILY FOUND!  If your doctors are not doing somersaults and hopping out of their chairs when they see your CBCs then RELAX you don´t have aggressive SM!!    

Another thing they don´t tell us is that in "adult onset" masto, be it SM or MCAS, when it finally shows itself it will do so either in a mild fashion or in an aggressive fashion.  I´m NOT talking about the symptoms!

A major rule of masto -  THE SYMPTOMS HAVE NOTHING TO DO WITH THE AGGRESSIVITY OF THE DISEASE!  They are two totally separate things!  Many doctors don´t know this and so they don´t tell us to help us calm down when they raise the suspicion.  Severe symptoms don´t mean aggressive disease.  They are totally separate and we don´t use the word aggressive with symptoms because this creates confusion amongst us patients regarding the danger we are potentially in.

Now, as to MCAS, this is a totally BENIGN disease, even though this patient can often be sicker than the SM patient.  The authorities are now beginning to see that many of the MCAS pts can be horribly sicker than the SM patient and they don´t know why.  But recent research has revealed that there is MORE THAN ONE DEFECT upon Kit and that depending upon the defect or defectS which the patient has inherited, this may be what determines how the patient presents their disease.   They know that the c-kit mutation D816V is what is behind the proliferative form which causes SM, however, since there are now more defects, they are beginning to suspect that the patients who have MMAS and MCAS may have these instead.  Until the appropriate tests for the different defects has been made available, we can test for only the one defect.  Until they begin testing for the others they will not see any patterns being raised.


Now, on to increased MCs.  

The rule is, where there is inflammation, you have MCs present.  They are usually normal MCs which are called to the spot by themselves and other inflammatory cells.  This is their normal function.   In a mast cell disorder, even though it is not known as an inflammatory disease, it will naturally create increased inflammation due to all of the extra inflammatory mediators being chronically released.  So the picture of a masto patient is one of chronic inflammation everywhere.  Most of those MCs are NORMAL.  So, in reducing the inflammation, those MCs should diminish as well.  

Mastocytocytic Enterocolitis is a finding of MC aggregates within the intestines.  These patients don´t have a diagnosis of mastocytosis because they don´t have enough focals of MC aggregates and their tryptase is not increased enough.  Having increased numbers of MCs don´t hack it if they are loose because that´s what is usually seen in inflammed intestines.   If the eosinophils are increased then this can be an eosinophilic disease but not necessarily mast cell driven and this is the issue.  Remember, where there is inflammation there are MCs - but are they defective, that is the question!   So, for now, they will only nominate it ME when they find MC aggregates.   But it is very typical to find this inflammatory response within the intestines in MCAS as well as SM, yes!

When looking all inflammation and the MCs there is a need to see how increased the numbers of MCs are.  In most cases you will see numbers like 35x/field.  This is increased but nothing surprising and is often seen in various disorders.  But it´s when you get up into the 100s that they begin to bug out the eyes of the doctors for this is definitely way off.   This is what is called a MC hyperplasia and it is often seen in SM.  This is why they count the MCs to see exactly how many their are and try to figure out what they are doing.   If you have numbers of MCs which run up into the 100s but they are loose and NOT aggregated then this is an MC hyperplasia and not mastocytosis.  SM does this and MMAS may do this as well, however MCAS does NOT!  MCAS does not cause any pathological damage according to the authorities.

In looking for pathological damage, the immunohistochemical testing also looks at the lymphocytes.  They want to know if these are normal or reactive and this is because in SM the lymphocytes will also aggregate.  This is totally not normal and so when they see the lymphocytes aggregated they need to know if they are malignant because if they are then you have lymphoma, another cancer of the blood.  But when the aggregated lymphocytes are normal, then this is mastocytosis doing this for the very same substance which aggregates the malignant MCs will also aggregate the normal lymphocytes.  

Now, as to MMAS.   This is a diagnosis which has one foot in between the two diagnoses, but before I can clarify it, I must go on to MCAS and explain what it is.  

MCAS is really a dumping ground diagnosis.  It is for those who don´t fullfill the WHO criteria for SM (they show pathological damage in the sign of raised tryptase, or MC aggregates or their MCs are morphed but they don´t quite fulfill all the criteria in some form or another - so they get slapped with MCAS since the Drs don´t quick know what to do with them otherwise).   Then there is non-clonal MCAS, which is a bit of a misnomer since all mast cell disorders are clonal in having a defect on Kit, but science is ahead of the criteria so this still must catch up to science.  

NC-MCAS is a form of masto which has NO PATHOLOGICAL DAMAGE according to Dr. Escribano.  These patients really defy diagnosis in that many of them respond properly to treatment however, they don´t have "elevated" trytpase and often won´t show elevated histamines or prostaglandins either.  They may show one or two but not all three.   And yet, their tryptase can be within normal levels.   Recent research is showing that there are some patients with SM who have low trytpase levels, below 13ng!  So the researchers are beginning to scratch their heads once again at this disease which refuses to be boxed in!

So, back to MMAS.   MMAS is a diagnosis which is poorly understood still.  In this diagnosis you have pathological damage which lines up with SM, but the tryptase is not necessarily elevated and as to the c-kit mutation D816V, because nobody has yet tested this patient for the other defects on kit, it´s really hard to pin it down to just this one for there may be other defects behind this diagnosis.   They have thought that this patient could be a "pre-SM" patient moving on into SM as the disease progresses, but after Dr. Escribano did a profile of the patients this patient seemed to be different in that they don´t have urticaria nor do they have angioedema and it seems more frequent in men.  They also go through a lot more syncope than other patients.  


Well, sorry this is late, but I hope it helps to clarify some of the doubts.


Lisa

Thanks Peter, you´re a real mate!!!!