Discussion:
We report two pediatric cases of JMML with diagnostic
challenges.5 The first patient had a KRAS mutation
which is a diagnostic criterion for JMML, but was also found on genomic
testing to have a translocation of NUP98::NSD1 , which makes this
case qualify as an AML according to the recent 5th WHO
and International Consensus Classification (ICC)
classifications.4,10 Notably, a few JMML patients have
been reported with structural rearrangements that are typically
associated with AML (e.g. inversion 3 andNUP98::NSD1 ).6 NUP98::NSD1 translocations can be missed on routine karyotyping and are
independently associated with very poor prognosis.11These patients, including our first patient, require aggressive
treatment and in fact may respond well to JMML therapy.
The ICC classification includes a distinct entity of Noonan
syndrome–associated myeloproliferative disorder (NS-MPD), to
characterize patients with Noonan syndrome and germline mutations inPTPN11 , KRAS , NRAS or RIT1 experiencing a
transient myeloproliferative disorder in the first year of
life.12 These patients may be appropriately managed
with close observation or mild chemotherapy.5,13 A
recent study of a cohort of patients with NS-MPD further shows variable
clinical outcomes.14 The disease onset within
1-year-old age and high VAF of PTPN11 mutation in our second
patient raised a differential diagnosis of NS-MPD. However, this
mutation was confirmed to be somatic in nature; and the blasts show
aberrant immunophenotype.15 Hence, the findings fit
JMML, and the patient received chemotherapy followed by BMT.
Interestingly, Glu76 Lys of PTPN11 has been the most affected residue in
JMML.16
In summary, our JMML cases demonstrate some common diagnostic pitfalls.
It is important to recognize these unusual features of JMML and further
risk stratify JMML, especially because rare JMML may
self-resolve,14,17 and a significant percentage of
JMML relapse after BMT.18