Arian Lasocki1,2 and Grant McArthur2,3
1Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia, 2The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia, 3Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
Synopsis
In small intracranial melanoma metastases, MRI evidence of
melanin was more common in BRAFV600-mutant patients than
BRAF-wildtype, supporting that melanin content is greater in not just the
primary, but also in the distant metastases. Haemorrhage and central necrosis were
more common in larger metastases. Central necrosis was also more common in BRAF-mutant
patients who had not previously received anti-BRAF therapy, suggesting that metastases
in BRAF-mutant patients have a tendency to central necrosis, though this is
modified by anti-BRAF therapy, thus resulting in more solid metastases.
Introduction
Intracranial melanoma metastases (IMM) may exhibit intrinsic
T1 hyperintensity (T1H)1,
but there are also other causes of T1H2, the most important in the
context of melanoma being haemorrhage. For the detection of blood products in
clinical practice, older gradient echo-based sequences have now been largely
superseded by techniques such as Susceptibility Weighted Imaging (SWI), due to
their greater sensitivity3.
BRAF mutation status is a key factor in the clinical course
of patients with metastatic melanoma. BRAFV600 mutations have been
associated with more pigmentation in primary melanomas4-6,
but data on the melanin content of metastases is limited7.
The only previous study correlating T1 signal on MRI with BRAF status has been
by Bordia et al, and this failed to find any significant differences8.
With the likelihood of haemorrhage increasing with lesion size9,
we aimed to examine the differences in signal characteristic between BRAFV600-mutant
(BRAFmut) and BRAF-wildtype (BRAFwt) IMM, with a focus on
small (<10 mm) lesions.Methods
MRI brain studies of patients who attended the Skin and
Melanoma Medical Oncology outpatient clinic between July 2015 and June 2017
were reviewed as part of a previous study10.
Patients were included if their first diagnosis of IMM was detected on brain
MRI examinations performed in our radiology department, prior to any local
therapy. All examinations included were performed on a 3-Tesla MRI using a
standardised protocol including 1mm volumetric pre- and post-contrast
T1-weighted imaging (T1WI), axial T2-weighted imaging, axial FLAIR
(fluid-attenuated inversion recovery) and SWI. Individual IMM were assessed on the MRI on which they were
first visible, stratified by size: either ≥10 mm in long axis (larger IMM) or
2-9 mm (small IMM). Up to 10 metastases in each group were assessed per
patient. For each lesion, the following features were assessed: long and short
axis diameters; presence of T1H and, if present, whether it could be
confidently attributed to melanin as opposed to haemorrhage; evidence of
haemorrhage based on SWI; and presence of central necrosis. Assessment was
performed blinded to BRAF status. Differences between groupings were assessed
using Pearson’s chi-squared test.Results
73 patients met the inclusion criteria – 44 BRAFmut
and 29 BRAFwt. 267 IMM were assessed, 172 (64%) BRAFmut
and 95 BRAFwt, with a median of 2 IMM per
patient (interquartile range 1-4). Most IMM (67%) were 2-9 mm in size.
Haemorrhage was significantly more common in larger IMM (44 of 87, or 51%)
compared to small IMM (36 of 180, or 20%; p<0.0001), but not significantly
different between the BRAFmut and BRAFwt cohorts. Central
necrosis was more common in larger IMM (38 or 87, or 44%) than small IMM (12 of
180, or 7%; p<0.0001), and more common in BRAFmut IMM (40 of 172,
or 23%) than BRAFwt (10 of 95, or 11%; p=0.011). In the BRAFmut
cohort, this rate of central necrosis was significantly higher (p=0.0001) in
patients without prior or current anti-BRAF therapy (33%), compared to patients
who had received previous anti-BRAF treatment (7%). In small IMM, MRI evidence
of melanin was significantly more common in BRAFmut patients (50 of
119, or 42%) compared to BRAFwt (16 or 61, 26%; p=0.038). There was
no significant difference for larger IMM, however. The presence of T1H
throughout all assessable IMM (with at least 2 IMM) was higher in the BRAFmut
cohort (7 of 24 assessable patients, or 29%) than in BRAFwt patients
(1 of 14, 7%), though this difference did not reach statistical significance
(p=0.085) due to the small numbers. Discussion
The higher incidence of T1H in small BRAFmut IMM
supports that melanin content is greater in not just the primary, but also in
the distant metastases, though the difference was modest. Interestingly, T1
signal frequently varies between lesions even within a given patient. While T1
hyperintensity was less common in BRAFwt patients, the incidence was
nevertheless reasonably high, suggesting that pre-contrast volumetric T1WI is a
valuable part of the MRI brain protocol for all melanoma patients regardless of
BRAF status – especially as, when utilising a gradient echo-based volumetric
technique, small IMM readily identifiable on pre-contrast T1WI can be obscured
by vascular enhancement after contrast administration. It is to be expected that both haemorrhage and central
necrosis are more common in larger IMM. The finding that central necrosis is
also systematically more common in BRAFmut IMM is interesting and
unexpected, however. Perhaps counter-intuitively, this was predominantly the
case in patients who had not previously received anti-BRAF therapy, suggesting
that BRAFmut IMM have a tendency to central necrosis, though this is
modified by anti-BRAF therapy, thus resulting in more solid IMM.Conclusion
T1H
attributable to melanin is more common in BRAFmut IMM than BRAFwt,
but this difference is modest. This highlights the value of assessing
pre-contrast T1WI in all melanoma patients regardless of BRAF status. It is
common for IMM to have a variable appearance within a given patient. Haemorrhage
is a common finding in both BRAFmut and BRAFwt IMM,
especially when larger. Central necrosis is also associated with increased
lesion size, and more common in BRAFmut patients who have not
previously received anti-BRAF therapy, suggesting that anti-BRAF therapy may
alter the patterns of IMM development and/or growth. Acknowledgements
NilReferences
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