PMC8392782_01
MRI brain with and without contrast shows progressive MBM. (a) Initial imaging revealed an asymptomatic solitary non-hemorrhagic lesion in the left temporal lobe measuring 0.5 cm in diameter. (b) Two months later, imaging showed an increase in the size of the lesion measuring 1.6 cm x 1.4 cm, with surrounding vasogenic edema on T2 fluid attenuated inversion recovery (FLAIR) sequences; but, no new metastatic lesions, acute hemorrhage or hypophysitis were identified. (c) Four months later, MRI revealed a large intracranial hemorrhage in the site of the known left temporal lobe lesion, measuring 4.7 cm x 3.4 cm with a 4 mm midline shift, with minimal enhancement suggesting the intracranial hemorrhage was related to treatment changes.
10.1177_2050313X211042215-fig1.jpg
PMC8392782_01_10.1177_2050313X211042215-fig1.jpg
fig1-2050313X211042215
A 28-year-old woman with widespread metastatic melanoma BRAF V600E mutant, involving the lungs, right breast, liver, and bone, was found to have a new asymptomatic metastatic lesion in her brain in the left temporal lobe, measuring approximately 0.5 cm, on magnetic resonance imaging (MRI; Figure 1). Regarding work up, the MRI of the brain demonstrated increase in the size of the lesion measuring 1.5 cm in diameter (three-fold increase in diameter compared with baseline) with some vasogenic edema that was not significant to cause her symptoms, and no other acute findings (Figure 1). Two weeks after discharge from the hospital, she had a symptomatic intracranial hemorrhage in the site of her known MBM in the left temporal lobe (Figure 1).
Treatment timeline.. The patient received C1 and C2 of combined ipilimumab (Ipi) 3 mg/kg IV and nivolumab (Nivo) 1 mg/kg IV (denoted with red stars).She developed a progressive motor weakness 9 days (D) status post (SP) C2 (red arrow) and was started on daily methylprednisolone 1 mg/kg twice a day (BID), with an additional high dose methylprednisolone IV (IVMP) 1 g/day for 3 days (blue four-arm stars). She had no clinical improvement and was subsequently treated with other immune suppressive therapies including IV immune globulin (IVIG) 0.4 g/kg/day for 5 days (for three cycles) and infliximab 5 mg/kg once (represented with blue diamonds and blue triangle, respectively), as well as the acetylcholinesterase inhibitor pyridostigmine to rule out an over-imposed myasthenia-like syndrome (represented with blue dot). Electromyogram/nerve conduction studies (EMG/NCS) performed on three different occasions, consistently revealed a pure motor axonal neuropathy (denoted with green stars). Re-staging studies demonstrated systemic disease progression, and the patient was started on treatment with dabrafenib and trametinib (denoted with red dots). She had an intracranial hemorrhage of her left temporal lobe lesion with a rapid neurological decline, and underwent an emergency craniotomy for tumor resection and hematoma evacuation, with subsequent radiation therapy (RT) to her lower thoracic spine 2000 cGy in five fractions for disease progression and fractionated stereotactic radiotherapy (FSRT) 2500 cGy in five fractions to the left temporal lobe cavity (depicted with red dots).
10.1177_2050313X211042215-fig2.jpg
PMC8392782_01_10.1177_2050313X211042215-fig2.jpg
fig2-2050313X211042215
She was immediately started on daily high dose IV methylprednisolone (IVMP) 1 mg/kg twice a day (BID; at 3D SP onset of symptoms; Figure 2). She was started on IV immune globulin (IVIG; 0.4 g/kg daily for 5 days, at 5D SP onset of symptoms; Figure 2). However, on Day 5 her weakness continued to progress despite IVMP and IVIG, and was treated with infliximab 5 mg/kg IV once, pyridostigmine 120 mg every 8 h (at 7D SP onset of symptoms), and a boost of high dose IVMP 1 g/day for 3 days (at 8D SP onset of symptoms; Figure 2). SP C2 & 12D SP onset of symptoms (see Supplementary Table 1). She received a repeat cycle of IVIG at 15D and 77D given delayed signs of inflammation on repeat cerebrospinal fluid (CSF) analysis (Figure 2). Given progression of her metastatic disease, she subsequently received radiation therapy (RT) to her lower thoracic spine (2000 cGy in five fractions) and fractioned stereotactic radiation therapy (FSRT, 2500 cGy in five fractions) to the left temporal cavity, followed by whole brain radiation therapy (8/10 treatments) with adjuvant temozolomide several months later (Figure 2).
EMG/NCS and RNS. EMG/NCS were performed at three different time points, that is, at 5D, 14D, and 44D SP onset of symptoms. (a-c) Decreased in the compound of muscle action potentials (CMAP) in the right median and peroneal nerves at three different time points with preserved sensory NCS (not shown). (d) F-wave latency of the median nerve was normal (other nerves tested not shown). See Supplementary Table 2. (e) RNS of the median nerve failed to show a decrement response (other nerves tested not shown).
10.1177_2050313X211042215-fig3.jpg
PMC8392782_01_10.1177_2050313X211042215-fig3.jpg
fig3-2050313X211042215
Table 2). These studies also showed normal sensory nerve action potentials (SNAPs) and repetitive nerve stimulation (RNS; Figure 3(e)).
Pathology findings of the left quadriceps biopsy. H&E stains of (a) Cuffing and transmural vascular involvement. (b) Perivascular lymphocytic cuffing. (c) Isolated myonecrosis with no evidence of thrombosis or fibrinoid necrosis. (d) Trichrome stain showing mildly atrophic fibers with no evidence of fiber type groups atrophy suggestive of disuse. Immunohistochemistry stains for (e) CD3 maker for T cells (f) CD4 marker for T helper cells, (g) CD8 marker for cytotoxic T cells, and (h) CD20 marker for B cells.. Original magnification 200x for all images.
10.1177_2050313X211042215-fig4.jpg
PMC8392782_01_10.1177_2050313X211042215-fig4.jpg
fig4-2050313X211042215
The pathology showed an inflammatory process suggestive of small vessel vasculitis, with scattered interstitial small vessels showing transmural inflammation and endothelial destruction with no evidence of thrombosis or fibrinoid necrosis (Figure 4).