05b Paraneoplastic syndrome

Question 1

Hypercalcemia caused by ectopic production of PTHrP

Answer 1

Etiology: overproduction of parathyroid hormone-related protein, excess production of 1,25-dihydroxyvitamin D -> enhanced GI Ca absorption
Clinical manifestations: >14 mg/dL Ca (hypercalcemia)
Diagnosis: hypercalcemia, hypophosphatemia, metabolic alkalosis, elevated PTHrP
Treatment: forced diuresis (furosemide/loop diuretics), biphosphonates (PZE), oral phosphorus, dialysis, calcitonin, glucocorticoids

Question 2

Ectopic vasopressin

Answer 2

Etiology: SIADH, reset osmostat controlling thirst
CM: hyponatremia in lab, asymptomatic, no IV fluids/medication
Diagnosis: low blood salt, high urine salt
Treatment: gradual and slow, fluid restriction, salt tablets, demeclocycline, vaptans

Question 3

Cushing syndrome

Answer 3

Etiology: ectopic ACTH production, increased/unregulated POMC gene
CM: less weight gain + centripetal fat redistribution*, metabolic problems, increased skin pigmentation
Diagnosis: free cortisol urine (>2-4x), high plasma ACTH, do not respond to glucocorticoid suppression
treatment: mental, DM, hypokalemia, fatigue, VT, adrenalectomy, block steroids

Question 4

Tumor-induced hypoglycemia

Answer 4

Etiology: excess IGF-2 (produce precursors, bind to IGF-1r)
Diagnosis: low serum glu, suppressed insulin levels
Treatment: eliminate medications, frequent meals, inc blood glucose

Question 5

HCG production

Answer 5

Etiology: ectopic or eutopic
CM: men inc estrogen, women asymptomatic
Treatment: treat malignancy

Question 6

Oncogenic osteomalacia

Answer 6

Etiology: hypophosphatemia oncogenic osteomalacia, TIO, production of phospatoin/FGF23 (inhibit renal absorption + vitD),
CM: reduced serum phosphorus, renal phosphate wasting, bone pain/waste, muscle weakness, low vitD
Treatment: resect tumor, vitD supplement, octreotide treatment

Question 7

Consumptive hypothyroidism

Answer 7

Etiology: overexpression of type 3 deiodinase = degrades T4/T3
CM: low T4/T3, high TSH, elevated rT3
Treatment: treat hemangioma, L-thyroxine replacement, steroid and propranolol to inhibit GF pathways

Question 8

Erythrocytosis

Answer 8

Etiology: Renal CA, hepatoma, cerebellar hemangioblastomas
Protein: EPO
CM: elevated hematocrit, elevated red cell mass, EPO level, asymptomatic
Treatment: resect tumor, rad/chemo, phleb

Question 9

Granulocytosis

Answer 9

Etiology: inc WBC, GI cancers
Protein: G-CSF, CM-CSF, IL2
CM: asymptomatic
Treatment: treat underlying disease

Question 10

Thrombocytosis

Answer 10

Etiology: increase platelet
Protein: IL6, thrombopoietin
Asymptomatic

Question 11

Eosinophilia

Answer 11

Etiology: lymphoma/leukemia
Protein: IL5
CM: asymptomatic, short breath, wheezing

Question 12

Thrombophlebitis and DVT

Answer 12

Trousseau’s syndrome
Pathogenesis: immobilization, tumor obstruction, post op DVT (bed ridden), chronic IV catheters, chemotherapeutic agents, APAS
CM: edema, pain, varicosities, pulmonary embolism
Diagnosis: impedance plethysmography/bilateral compression UTS, venography, D-dimer (pulmo embolism), pulmo (ABG, ECG, etc)
Treatment: unfractionated heparin/LMWH, warfarin, IVC filter, oral anticoagulant, prophylaxis for surgery

Question 13

CNS Paraneoplastic neurologic disorders

Answer 13

antibody associated immune response -> react with neurons and tumor
CD4 and CD8 infiltrates
Classic syndromes (with cancer association) vs non-classic syndromes (no cancer association)

Question 14

Approach to patients with PND of CNS and dorsal root ganglia

Answer 14

Diagnosis = clinical + radiologic + CSF finding
presence of anti-neuronal antibodies (neuronal/neuromuscular junction antibodies)
MRI and CSF studies for ruling out
CSF profile: mild/moderate pleocytosis
Electrophysiologic test
Biopsy

Question 15

Approach to patients with PND of nerve and muscle

Answer 15

Clinical + electrophysiologic test + pathologic grounds

Involved: peripheral nerve + NMJ + muscle

Question 16

Encephalomyelitis and focal encephalitis

Answer 16

Encephalomyelitis: multi-focal inflammation, dorsal root ganglia + autonomic dysfunction, SLCL
Clinicopathologic syndromes: cortical encephalitis, limbic encephalitis, brain stem encephalitis, cerebellar gait and limb ataxia, myelitis, autonomic dysfunction
Treatment: immunotherapy (IV Ig, plasma exchange, cyclophosphamide/tacrolimus)

Question 17

Encephalitides with antibodies to cell-surface/synaptic proteins

Answer 17

1 Can occur with and without tumor association
2 Some predominate in young individuals
3 Pts respond to treatment and immunotherapy

Tumors associated with intracellular antigens: SCLS
Tumors associated with cell surface/synaptic antigens: SCLS, thymoma, Hodgkin lymphoma

Question 18

Paraneoplastic cerebellar degeneration

Answer 18

Preceded by prodrome (dizziness, oscillopsia, blurry/double vision nausea, vomiting)
PE: downbeating nystagmus, opsoclonus
MRI: cerebellar atrophy
Tumors: SCLC, breast/ovarian cancer, Hodgkin’s lymphoma

Antibodies:
Anti-Yo (PCA1): breast/gyne
MGluR1: highly responsive
Tr/VGCC: less responsive

Question 19

Paraneoplastic opsoclonus-myoclonus

Answer 19

Opsoclonus: involuntary, chaotic saccades in all directions
Opso-myoclonus: lung/breast cancer, pedia neuroblastoma, ovarian teratoma
Treatment: treat tumor, immunotherapy

Question 20

Paraneoplastic stiff-person syndrome

Answer 20

Muscle rigidity, improves with sleep
Lower trunk and legs

Main targets of autoantibodies: GAD, amphiphysin, glycine receptor
Treatment: glucocorticoids, GABA-ergic transmission, IVIG, plasma exchange, Rituximab

Question 21

Paraneoplastic sensory neuropathy/dorsal root gangliopathy

Answer 21

Sensory deficits: symmetric/asymmetric, painful dysesthesia, radicular pain, dec/absent reflexes
Electrophysiologic studies: dec/absent sensory nerve potentials, normal motor conduction velocities
SCLC and Hu antibodies

Question 22

Paraneoplastic peripheral neuropathies

Answer 22

Guillain-Barre syndrome and brachial plexitis: lymphoma
Monoclonal gammopathies
Vasculitis of the nerve and muscle: SCLC and lymphoma
Peripheral nerve hyperexcitability/ neuromyotoma/ Isaac’s syndrome
Acute necrotizing myopathy: elevated muscle enzymes, muscle biopsy with extensive necrosis

Question 23

Paraneoplastic visual syndrome

Answer 23

1 Cancer-associated retinopathy: photosensitive, loss of vision and color, central/ring scotoma
2 Melanoma-associated retinopathy: night blindness, photopsia, ERG
3 Paraneoplastic optic neuritis/uveitis: encephalomyelitis, CRMP5 antibodies

Treatment: glucocor, plasma ex, IV Ig, rituximab, alemtuzumab

Question 24

Conditions strongly suggesting malignancy

Answer 24

1 Acanthosis nigricans: adenocarcinoma of the stomach
2 Triple palms: hyperkeratosis
3 Acrokeratosis paraneoplastica (Bazex syndrome): psoriasis; SSCa of upper aerodigestive tract
4 Florid cutaneous papillomatosis: warty, gastric adenocarcinoma
5 Paraneoplastic pemphigus: painful blisters
6 Carcinoid syndrome: paroxysmal flushing, bronchoconstriction, GI hypermotility, CD
7 Erythema gyratum
8 Necrolytic migratory erythema: unusual dermatosis, recent-onset diabetes, weight loss, wax and wane
9 Cutaneous T-cell lymphoma: mycosis fungoides
10 Alopecia
11 Acneiform eruptions: from EGFR inhibitors