The current World Health Organization (WHO) criteria for
systemic mastocytosis (SM) were adopted in 2001. The criteria are as follows:
Major criterion:
1.
Multifocal, dense aggregates of mast cells (15
or more) in sections of bone marrow and confirmed by tryptase
immunohistochemistry or other special stains.
Translation: several groups of at least 15 mast cells clustered together
are found in bone marrow, and are confirmed to be mast cells by using special
stains and looking under the microscope.
Minor criteria:
1.
In bone marrow biopsy section, more than 25% of
mast cells in infiltrate have atypical morphology, or of all mast cells in
aspirate smear, more than 25% are immature or atypical. Translation: in the solid portion of the bone
marrow obtained by biopsy, 25% or more of the mast cells clustered together don’t
look like normal mast cells; or in the liquid portion obtained during the bone
marrow biopsy (known as the aspirate), 25% or more of mast cells look
underdeveloped and or don’t look like normal mast cells.
2.
Mast cells co-express CD117 with CD2 and/or
CD25. Translation: mast cells have
specific receptors on their cell surfaces.
3.
Detection of KIT point mutation at codon 816 in
bone marrow, blood, or other extracutaneous organs. Translation: Mast cells found in tissue (that
is NOT skin) are CKIT+.
4.
Serum tryptase is persistently > 20
ng/mL. (Note: not applicable for cases
of SM-AHNMD.)
SM is diagnosed if one major and one minor, or three minor
criteria are met. Under the WHO
guidelines, seven distinct subclassifications of SM are recognized: cutaneous
mastocytosis; indolent systemic mastocytosis; systemic mastocytosis with
associated clonal hematologic non mast cell lineage disease; aggressive
systemic mastocytosis; mast cell leukemia; mast cell sarcoma; and
extracutaneous mastocytoma.
A paper published in 2008 evaluated the utility of the
current diagnostic criteria. Of 59
patients with clinically suspected SM, 90% of them met the WHO criteria. The remaining 6 patients, all had negative
bone marrow biopsies; but 5 had mast cells that looked unusual (atypical
morphology), 5 had the specific cell receptors noted in the diagnostic
criteria, 2 had the CKIT mutation (CKIT+), and 2 had elevated tryptase. Based on these findings, the group determined
that the WHO criteria are neither completely sensitive not specific for SM, and
were found to cause false-negatives.
This means that people who actually had SM were told they did not.
Other groups have also noted that the WHO criteria are not
always effective. In particular, we now
know that it can take several bone marrow biopsies in order to find the region where
mast cells are clustering; thus, it is possible for patients to be diagnosed as
negative until they have had several bone marrow biopsies.
In addition to some doctors feeling the criteria are
lacking, others feel that some subclassifications of SM should be reclassified
to better represent their pathology and prognosis.
In 2010, Dr. Pardanini, a hematologist at the Mayo clinic, proposed
revised guidelines for SM. He recommended the following:
1.
Placement of mast cell leukemia in the same
category as AML (acute myeloid leukemia) and other related cancers. MCL progresses more like AML than SM, and
also usually occurs spontaneously, rather than as a progression from SM. Pardanini feels that the fact that some MCL
cells are CKIT+ is not enough to classify it as SM, particularly as it is also
positive for other genes that indicate similarity to blood cancers.
2.
Elimination of the SM-AHNMD category. SM-CMML (chronic myelomonocytic leukemia) and
SM-myelodysplastic syndrome (SM-MDS) should be categorized as MDS/MPN (myelodysplastic/myeloproliferative
neoplasm) due to their similar prognosis and pathology. However, he felt that there should be a new
SM-MPN category as some SM patients also have a coexisting myeloproliferative
neoplasm.
3.
Smoldering SM (SSM) should be classified as
distinct from indolent SM (ISM) due to its much worse prognosis and more
aggressive disease.
4.
Bone marrow mastocytosis (BMM) had little
clinical relevance and should be eliminated.
One of the frustrating aspects of this disease is that due to its rarity, there is often dissent among experts on various topics, including diagnosis, classification of subvariants, and treatment.
Sources:
http://bloodjournal.hematologylibrary.org/content/115/13/2720.full#T1
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