Aids Diagnosis of an Occult Malignancy Hehua Huang MD Maria Miranda Taylor MD Rachel Rangwala MD Holli M Mason MD Department of Pathology and Laboratory Medicine HarborUCLA Medical Center ID: 1036801
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1. Therapeutic Response to Apheresis Aids Diagnosis of an Occult MalignancyHehua Huang, MD; Maria Miranda Taylor, MDRachel Rangwala, MD; Holli M. Mason, MDDepartment of Pathology and Laboratory MedicineHarbor-UCLA Medical Center1000 W. Carson St. Torrance, CA 90502
2. Objectives1. Identify a syndrome that can have several etiologies, including paraneoplastic processes.2. Outline paraneoplastic neurologic disorders (PND).3. Predict common applications of therapeutic apheresis.
3. Our Patient56-year-old woman, no significant past medical history No significant family historyPresents with neurological symptomsJaw clenchingFacial droopDiplopia
4. Initial Work-upLumbar puncture: Non-contributoryMRI (brain): Non-contributoryRuled out stroke, drugs, EtOHDDx: RhombencephalitisAka “brainstem encephalitis”Caused by infections, autoimmune diseases, or paraneoplastic syndromesPresents with headaches, vomiting, fever and variable neurologic sx, e.g., AMS, cranial nerve paresisPt is treated with steroids and discharged home
5. Rhombencephalitis(Brainstem Encephalitis)
6. Rhombencephalitis(Brainstem Encephalitis)BLight micrograph from a section of the brainstem from a patient with colon cancer and paraneoplastic brainstem encephalitis associated with anti-Ma2 antibodies.
7. Paraneoplastic SyndromeGroup of rare disorders triggered by an abnormal immune system response to a neoplasmAntibodies or T-cells mistakenly attack normal cells in the Assoc w/lung, ovarian, lymphatic, or breast neoplasms. Neurologic symptoms generally develop over a period of days to weeks and usually occur prior to the tumor is discovered. Symptoms may include difficulty in walking or swallowing, loss of muscle tone, loss of fine motor coordination, slurred speech, memory loss, vision problems, sleep disturbances, dementia, seizures, sensory loss in the limbs, and vertigo or dizziness.
8. Paraneoplastic Neurologic SyndromesParaneoplastic syndromes (PNSs) result from systemic reactions to neoplasms, often mediated by immunologic or hormonal mechanisms.
9. Pathophysiological mechanisms for paraneoplastic neurological disorders (PND)
10. Classis Paraneoplastic Neurologic Syndromes
11. Well Characterized Onconeuronal Antibodies and Related Tumors
12. Management of PNSLimited studies evaluating treatment efficacy for PNSTwo major principles: treatment of underlying cancer and immunotherapy initiation.Acute immunotherapies should be utilized as soon as a PNS diagnosis is suspectedDevine M etc. Paraneoplastic neurological syndromes: clinical presentations and management. Ther Adv Neurol Disord. 2021 Feb 1;14:1756286420985323
13. Symptoms Worsen…Patient returned a month later with worsening symptomsProgressive dysphagiaNystagmusInvoluntary tongue biting from extreme jaw clenchingLeft facial twitchingPt became poorly responsiveUnable to protect her airway intubated
14. Additional WorkupRepeat MRI (brain): NegativeRepeat LP: NegativeCultures for Bacterial, viral, fungal infection: NegativeHeavy metal toxin screens: NegativeComplete paraneoplastic antibody workup performed: NegativeNeuronal Nuclear antibodyPurkinje cell Cytoplasmic antibodyAnti-Hu, Anti-Ri, Anti-Yo, Anti-NMDA receptor antibodyAnti-GAD (glutamic acid decarboxylase)
15. Patient statusWorsening of extreme jaw clenching causing loss of portions of her tongue, anterior 2/3 was lostAll teeth extractedGiven infectious etiologies ruled out: Therapeutic plasma Exchange (TPE) for possible immune-mediated rhombencephalitis is started
16. Apheresis
17. American Society for Apheresis: Indications for TPE
18. Response to TPEAfter 5 TPE: bruxism improves but diplopia and nystagmus persistsPartial response to initial TPE prompts more thorough investigation for occult malignancy despite negative PNAb panel.Additional 5 TPE: continued improvement but symptoms persistedUltrasound of Left breast revealed a small lump; biopsy showed metastatic IDC with mucinous features excisedOutpatient chemotherapy significantly improved neurologic symptoms
19. Therapeutic plasma exchange may be utilized to evaluate and treat rare paraneoplastic syndromes even after paraneoplastic Ab results are negative.Response to TPE may indicate an immune-mediated process and the need to pursue occult malignancies.TPE response may be variable but this case shows the short-course benefits.Conclusion:
20. Thank youReferences:H Shafi, H Mason, DJ Chaffin, E Klapper. Plasma Exchange in a Rare Neoplastic Disorder. Transfusion. 2013 Sept;53:s2, SP151.https://ilovemydentist.com.mx/blog/bruxism-yes-you-might-be-involuntarily-clenching-your-teeth-at-night/https://www.youtube.com/watch?v=qH8nkLC-qrghttps://sclerodermainfo.org/insurance-coverage-for-therapeutic-plasma-exchange-in-the-u-s/https://www.youtube.com/watch?v=qH8nkLC-qrg PERM variant (Progressive encephalomyelitis with rigidity and myoclonus)Padmanabhan, A, Connelly-Smith, L, Aqui, N, et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher. 2019; 34: 171– 354. https://doi.org/10.1002/jca.21705https://radiopaedia.org/articles/rhombencephalitis?lang=ushttps://www.hopkinsvasculitis.org/types-vasculitis/behcets-disease/9) A.A. Madhavan, C.M. Carr, P.P. Morris, E.P. Flanagan, A.L. Kotsenas, C.H. Hunt, L.J. Eckel, E.P. Lindell and F.E. Diehn American Journal of Neuroradiology October 2020, DOI: https://doi.org/10.3174/ajnr.A6815 Alavi, Samin. “Paraneoplastic Neurologic Syndromes in Children: A Review Article.” Iranian Journal of Child Neurology 7 (2013): 6 - 14. January 2021 Therapeutic Advances in Neurological Disorders 14:175628642098532 DOI:10.1177/1756286420985323 Devine MF, Kothapalli N, Elkhooly M, Dubey D. Paraneoplastic neurological syndromes: clinical presentations and management. Ther Adv Neurol Disord. 2021 Feb 1;14:1756286420985323. doi: 10.1177/1756286420985323. PMID: 33796141; PMCID: PMC7970694.