Therapeutic Challenges in Occult Malignancy Presenting as Stroke

1. Therapeutic Challenges in Occult Malignancy Presenting as Stroke Dr. Suhaniya Samarasinghe1, Dr. Cara Owens1, Dr. Richard Morgan1 & Dr. A. Merwick2 Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9TR; 2.Neurology Dept, Beaumont Hospital, Dublin 9, Ireland

2. Introduction • Thrombosis as a complication of cancer was first proposed by Trousseau in 1865 • 15% of cancer patients have evidence of CVA (autopsy)1 • Mechanisms of stroke in cancer include conventional causes – hypercoagulability2 and non-bacterial thrombotic endocarditis2,3 • Usually present as multiple lesions involving multiple arterial territories • We describe three cases of stroke as first presentation of occult malignancy • Treatment of stroke in cancer patients can be a challenge

3. Case 1 • PC - Right UL weakness • Discharged from hospital following investigation for abdominal pain day before • Developed arm weakness as inpatient: no action taken • Unable to use handrail at home; dropped porcelain clock • Admitted later that evening • PMH – hypercholestrolemia, hyperthyroidism, paranoid delusional disorder, depression

4. Investigations • Bloods - K+ 3.2, LFT NAD, Ca2+ 2.18, PO4 0.72, Mg 0.77, Alb 28, CRP 141, FBC: NAD, Clotting NAD, TSH 5.75; T4 13.8 • 48 hr tape – NSR • ECHO – LVEF 70 – 75%, no cardiac source for emboli • CTH – Likely old infarct in right basal ganglia • MRI brain – multiple acute infarcts involving cerebral and cerebellar hemispheres - very suggestive of multiple emboli from a central embolic source

5. MRI Head (initial)

6. Elizabeth Mcmenemy MRI

7. Treatment • New RSW – repeat CTH showed lacunar infarct despite full dose anticoagulation • USS KUB – normal kidneys, complex pelvic mass; free fluid in pelvis • Tumour markers – CEA 30, CA 12-5 1545, CA15-5 150, CA19-9 1708

8. CT Chest/Abd/Pelvis • Thorax: R pleural effusion, pericardial effusion, atelectasis; right PE’s • Abdo/pelvis: large complex mass; pelvic varices; ovaries not seen separately; thickened caecum & ascend colon; R kidney?infarction

9. MRI Pelvis

10. CT Chest/Abd Non occlusive filling defects in Rt middle lobe lateral segmental branch and right lower lobe artery

11. Repeat MRI Head Multiple signal foci on both T2 and FLAIR weighted sequences are demonstrated in both cerebellar hemispheres. Acute infarction. Appearances consistent with multi territorial acute embolic infarcts which have progressed

12. Case 2 • PC – LSW, slurred speech • PMH – NAD • Initial CT head – no acute infarct, mature lacunar infarct • Ongoing LSW, dysphasia

13. Investigations • MRI head – large acute right ACA and MCA territory infarcts with associated mass effect. Multiterritorial acute and subacute infarct ?central embolic cause • Bloods – eGFR > 90, bilirubin 31, ALT 45, AP 382, GGT 604, Prot 50, Alb 23, CRP 72.6, Hb 103, WBC 16.3, Plt 100 • Liver function tests worsening

14. MRI Head

15. CT Chest/Abd/Pelvis • Bilateral pulmonary emboli, gastric outlet obstruction, multiple liver metastases, intrahepatic bile duct dilatation • Consolidation RLL – cannot exclude bronchoalveolar cell carcinoma • Likely renal and splenic infarcts; nodule in thyroid • CEA 8, CA12-5 4526, CA15-3 69, CA19-9 insufficient sample • Reviewed by gastroenterology ?further invasive tests +/- biopsy – not a candidate given poor prognosis

16. CT Chest/Abd/Pelvis

18. Case 3 • PC – 85 y/o lady presenting with RSW • PMH – atrial fibrillation on direct oral anticoagulant • Initial CTH – large left MCA infarct • Patient not a candidate for thrombolysis

19. CT Head

20. Investigations • Admission bloods – Na 134, K 4.9, Ur 16.7, Cr 118, eGFR 38, bilirubin 9, ALT 49, AP 529, Prot 61, Alb 18, Glob 43, CRP 373.8, Hb 116, WBC 22.2, Plt 386, MCV 79.2, PT 10.9, APTT 24.2 • Tumour markers - CEA 43, CA12-5 4142, CA15-3 92, CA19-9 44520 • CT Chest/Abd/Pelvis – evidence of likely T4 N0 M1 cancer of pancreas with lung and liver metastases • Patient too unwell for tissue diagnosis

21. CT Chest/Abd/Pelvis

22. Stroke and Cancer • 15 % cancer patients have CVA (autopsy) 2 • CVA as first sign is rarely reported 2 • Mechanisms: • conventional causes • Hypercoagulable state (DIC).3 (D-dimer independent predictor for stroke involving non-conventional mechanisms)4 • NBTE 2,3 • NBTE: underestimated – no TOE; MUCIN-SECRETING ADENOCARCINOMAS 2 • Consider systemic cancer work up: unclear origin; early vascular recurrence 2, infarct whilst on anticoagulation • Consider concealed cancer in patients with multiple infarcts on DWI MRI5

23. Malignancy screening in cryptogenic stroke • Detailed history – including environmental exposure • Physical examination – consider breast or testicular exam • Serological work-up – e.g. D-dimer • Imaging – if suspicion of malignancy Always consider cancer in patient with cryptogenic stroke or early vascular recurrence

24. References • Hart, R.G., Diener, H.C., Coutts, S.B., Easton, J.D., Granger, C.B., Martin, M.D., O’Donnell, M.J., Sacco, R.L. and Collolly, S.J.. Embolic strokes of undetermined source: the case for a new clinical construct (2014) The Lancet neurology 13 (4) 429-438. • Taccone, F.S., Jeangette, S.M. and Blecic, S.A. (2008) First ever stroke as initial presentation of systemic cancer. J Stroke Cerebrovasc Dis. 17 (4): 169-174 • Cestari, D.M., Weine, D.D., Panageas, K.S., Segal, A.Z., DeAngelis, L.M. (2004) Stroke in patients with cancer: incidence and etiology. Neurology62: 2025-2030 • Kim, S., Man-Hong, J., Young Kim, h., Lee, J., Chung, P.W., Park, K.Y., Kim, G.M., Lee, K.H., Chung, C.S. and Bang, O.Y. (2010) Ischaemic stroke in cancer patients with and without conventional mechanisms. Stroke41: 798-801 • Kwon, H.M., Kang, B.S. and Yoon, B.W. (2007) Stroke as the first manifestation of concealed cancer. J Neurol Sci 258: 80-83 Poster: 3rd ESOC 2017, Prague 16-18 May Oral presentation: 7th International Conference Geriatrics & Gerontology Conference 2017, 4-5 Sept