RAIN Clinicopathologic Conference 2019 nasopharyngeal squamous cell - PowerPoint PPT Presentation

Case 59-year-old man with a past medical history of remote RAIN Clinicopathologic Conference 2019 nasopharyngeal squamous cell carcinoma, hypothyroidism, gallbladder polyps, and latent tuberculosis status-post 9-month course of isoniazid presented with progressive headache, Sara C. LaHue, MD nausea with emesis, and gait instability. UCSF Department of Neurology Nicole Rosendale, MD UCSF Department of Neurology Melike Pekmezci, MD UCSF Department of Pathology 2 History of Present Illness History of Present Illness  Well until 3 weeks prior to presentation:  A few days later presented to Primary Care: Developed nausea, vomiting, subjective fevers, and headache. Headache persisted. - -  Presented to outside hospital-affiliated Urgent Care Clinic. New intermittent bilateral leg weakness and right foot numbness, - resulting in gait instability. Continued to have emesis during appointment. - New hiccups. - Hospital transfer discussed but patient declined. -  Underwent MRI brain and lumbar spine  Upcoming cholecystectomy for polyps already scheduled. Results prompted admission to local hospital and then UCSF - transfer. 3 4 1

Past Medical History Medications  Nasopharyngeal squamous cell carcinoma  Levothyroxine 50mcg daily. Diagnosed 1990s, status-post radiation and chemotherapy -  Hypothyroidism  Keppra 500mg twice a day and prednisone 50mg daily (started prior to transfer)  Latent tuberculosis Diagnosed 2016, completed 9-month course of isoniazid -  Gallbladder polyps  Chronic gastritis with Helicobacter pylori infection  Iron deficiency anemia 5 6 Social History Family History  Lives with wife in Milpitas, California; they have three  Mother: liver cancer children.  Maternal uncle: liver cancer  Originally from Hong Kong but lived in the United States for  Several family members had nasopharyngeal carcinoma. decades.  No family history of neurological disease.  Retired computer engineer; works part-time as a consultant.  No alcohol, tobacco or illicit drug use.  Travel history: San Diego and Seattle (past year). Hong Kong (two years prior), Mexico (fishing trip, two years prior). 7 8 2

Physical Exam Labs Vital Signs T 97.5°F, HR 58, BP 125/78 mmHg, RR 18  General Cachectic appearance, otherwise unremarkable.   Normal BMP, CBC, LFTs Mental status Alert, fully oriented, but slowed responses.   Cerebrospinal fluid: Yellow-appearing fluid Cranial nerves Bilateral temporal disc blurring. Bilateral lateral gaze  restriction. Pupils 4mm briskly reactive. Right-sided upper motor neuron Tube 4: - facial weakness.  WBC 2 (monocyte predominant) Motor Decreased bulk throughout. No pronator drift. Full strength.   RBC 199 Sensory. Diminished to vibration in feet bilaterally.   Protein 1836 Reflexes 3+ right patella otherwise 2+ throughout.   Glucose 75 (normal serum) Coordination Intact finger-nose-finger and heel-knee-shin.  Gait Wide based and imbalanced.  9 10 CT Brain without Contrast MRI Brain – DWI 11 12 3

MRI Brain – T2 FLAIR MRI Brain – T2 FLAIR 13 14 MRI Brain with Gad T2 FLAIR 15 16 4

T2 FLAIR Gad Enhanced T2 FLAIR Gad Enhanced 17 18 Initial thoughts? Nicole Rosendale, MD T2 FLAIR Gad Enhanced 19 20 5

Approach Key Points - History  Key points  59 year old man with: History hypothyroidism - - Exam remote nasopharyngeal carcinoma (1990s) s/p radiation and - - chemotherapy Evaluation & Treatment - latent TB s/p 9-months of isoniazid -  Broad differential diagnosis  Subacute, progressive headache, persistent nausea/emesis  Further workup  More acute, intermittent bilateral leg weakness and right foot  Diagnosis numbness 22 Key Points - Exam Key Points – Evaluation & Treatment Labs:  Basic labs are normal. - Cachectic No CSF pleocytosis but markedly elevated protein and yellow in color  - Encephalopathic  Papilledema & bilateral abducens palsy  Right upper motor neuron facial weakness but normal power in  body Increased tone in legs  Large fiber sensory neuropathy in feet  Brisk R patellar reflex  Wide based gait  23 24 6

Key Points – Evaluation and Treatment Framework for creating a differential  V = vascular  A = alcohol  Imaging:  I = infectious  B = behavioral Multifocal intraparenchymal and intraventricular cystic lesions on -  T = toxic (toxic-metabolic) MRI  C = congenital  A = autoimmune  Partial ring enhancement of parenchymal lesions and intraventricular  D = degenerative lesions & leptomeningeal enhancement coating spinal cord  M = metabolic (malignancy)  E = endocrine Possible abnormality in lung apex -  I = iatrogenic  K = karyotype  N = neoplastic (neurodegenerative)  Transferred on Keppra and prednisone  S = structural (social, systemic) 25 26 Initial differential diagnosis Nasopharyngeal carcinoma  Pros:  Neoplastic  Infectious Nasopharyngeal Neurocysticercosis - Personal history - - carcinoma Tuberculosis - Of cases reported, lung - Lymphoma - involvement also present Fungi - CNS metastases - - Plausible mechanism Glioblastoma -  Cons:  Autoimmune Subependymoma or other - Sarcoidosis - Met to CNS is rare - intraventricular tumor IgG4-related disease - - Remote history 27 28 7

Lymphoma CNS metastases  Pros:  Pros: Age (typically 40-70s) Cachectic - - Presenting with encephalopathy, Lung mass - - focal deficits  Cons:  Cons: Intraventricular metastases are rare - Usually homogenously enhancing - Typically ring enhancing, located at - Steroid responsive the grey-white junction - 29 30 Other neoplasms Neurocysticercosis Glioblastoma  Most common primary brain tumor in adults -  Pros: Typically parenchymal with IV invasion - Traveled to an endemic area (Central & - Intraventricular tumors South America, Asia, Africa)  Ependymoma – pediatric tumor Racemose NCC is often basilar - - predominant Central neurocytoma – typically younger (20- - 40 y/o)  Cons: Meningioma – homogenously enhance - Seizures common - Subependymoma – correct age - No calcifications on head CT - Wouldn’t explain spinal involvement - Typically ring enhancing - 31 32 8

Tuberculosis Fungi Coccidiomycosis  Typically leads to meningitis without parenchymal  Pros: - lesions Non-specific headache, malaise, - Many have concomitant spinal abnormalities - focal deficits Aspergillosis  Basilar predominant - Typically disseminated -  Cons: Cryptococcus  Bland CSF - Usually in immunocompromised individuals - Typically ring enhancement - Typically meningitis without discrete lesions - (cryptococcoma) Underwent appropriate treatment - for latent TB Leads to CSF pleocytosis  33 34 Sarcoidosis IgG4-Related Disease  Pros:  Pros: Encephalopathy, focal deficits (cranial Can have intraventricular involvement - - neuropathy), headache CSF pleocytosis is variable - Bland CSF - Lung lesion (although apical, not hilar) -  Cons:  Cons: Typically presents over months to years - Steroid responsive - Steroid responsive - Lesions are typically smaller - 35 36 9

Summary of Differential Diagnosis Further diagnostic considerations • CNS metastases • Lymphoma  CT chest: characterize lung mass Neoplasm • GBM  PET: evaluate for potential biopsy target  Ophthalmologic exam: helpful for lymphoma, sarcoid • Neurocysticercosis Infectious  Labs: ACE, NCC testing, beta-d-glucan, galactomannan  Biopsy • Sarcoid Autoimmune 38 37 Hospital Course Hospital Course  Initial concern for neurocysticercosis  Initial differential included: Started on Prednisone 50 mg daily Infection: neurocysticercosis, less likely atypical bacteria, fungal - - or mycobacterial Keppra 500 mg twice a day for seizure prophylaxis - Malignancy, especially metastatic -  Neurosurgery was consulted: no role for EVD or surgery.  Seen by Ophthalmology: no orbital or ocular cysts or infection  Due to concern for deterioration with anti-parasitic medication  Cycticercosis Ab serum: negative initiation, he was transferred to UCSF for further care. Could be negative in setting of early severe infection - 39 40 10