Rare case : Adenocarcinoma with Brain Metastasis
Case Report :
A 60 year old man presented with confusion for 2 weeks. He had trouble with word finding and had perseverating speech. He had progressive weakness in his lower extremities to the extent of not being able to ambulate. There was also loss of bowel control. He had shortness of breath with any activity. There is a 12 pack year history of smoking but there is no history of using any other form of drug. He was being treated for stage IVa adenocarcinoma (acinar type) of the lung (EGFR wild and ALK translocation negative) which was diagnosed about a year ago. He received six cycles of therapy with Carboplatin, Altima and Pembrolizumab as part of a clinical trial and also received Docetaxel and Ramcirumab therapy after. There was a prior history of prostate cancer (Gleason 7) 10 years ago without recurrence which was treated with prostatectomy and external beam radiation. Prostate specific antigen was <0.1 ng/mL.
On exam he was seen to be awake and oriented to self and the city but not time. He was able to identify objects and repeat phrases, though at times he would perseverate. He was slow to respond and could calculate normally. His right hip flexion and knee extension was 4/5 in strength. His reflexes were reduced (1+) in the right triceps, patella and bilateral ankles.
MRI imaging of his brain, cervical and thoracic spine revealed numerous hyperintensities which were suspicious for metastatic lesions in brain. They were present in both supratentorial and infratentorial brain parenchyma with the largest lesion located at the right frontal lobe measuring at 9 x 7 mm in size. The picture was peculiar for miliary appearance in the brain. He was also started on Levetiracetam 500 mg twice a day dose for seizure prevention. He was tried on whole brain radiation therapy and continued with chemotherapy (Docetaxel and Ramucirumab).
Several cases associated with metastasis to the brain include those with miliary appearance. Previously described as carcinomatosis encephalitis, it is now frequently reported with advanced imaging techniques. A retrospective analysis of cases with brain metastasis has depicted an association of miliary pattern with exon 19 deletion (1). At least 17 cases were reported in literature which had miliary brain metastasis in conjunction with adenocarcinoma of lung (2). Though earlier cases did not include information about the genetic mutation with the pathology, more recent studies and meta-analysis report Exon 19 deletion (EGFR mutation) was associated with greater probability of multiple cerebral metastasis (2). Further these patients did not have any history of smoking. Dziadziuszko et al (3) demonstrated a ROS1 gene mutation in a lung cancer patient with miliary metastasis and history of smoking. This case is unique because of the absence of mutation to the EGFR or ALK gene and a positive history of smoking. Unfortunately, our patient failed both chemotherapy as well as whole brain radiation therapy and had to be transferred to hospice center for end of life care.