Horner syndrome & Diffuse large B-cell lymphoma

Thanks Aya for presenting an excellent case! Also many thanks to Vinay Prasad for attending and shedding wisdom on the history and diagnosis of lymphoma. This was a case of a patient presenting with recurrent syncope, found on exam to have Horner syndrome and diagnosed with pancoast tumor on biopsy found to be consistent with "double-hit" diffuse large B cell lymphoma. The patient was found to not be in tumor lysis and was started on R-EPOCH to treat lymphoma.

horner

(Img: UtD)

Main points:

  • 1) The sympathetic trunk spans the area of the hypothalamus down to approximately the T2 spinal cord level and normally innervates muscles of the eyelid (superior tarsal muscle), pupil (pupillary dilator muscle) and sweat glands. Horner syndrome consists of the triad of “ptosis, miosis and anhidrosis” and is caused by damage along any portion of the sympathetic trunk.

  • 2) When Horner syndrome is present on exam, consider cross sectional imaging of the neck AND chest given the location of the sympathetic trunk.

  • 3) Diffuse large B-cell lymphoma can be an aggressive disease and oncologic emergencies to consider evaluating for include tumor lysis syndrome (hydrate and trend TLS labs) as well as evaluating for airway compromise (ENT consult) and cord compression (neurosurgery consult) if suspected.


Want to learn more?

Framework for Horner syndrome

One approach to Horner syndrome can be to think about ipsilateral CNS vs pre/postganglionic lesions. As pictured above, the first order neurons start in the hypothalamus and terminate at C8-T2, the preganglionic neurons terminate at the superior cervical ganglion and postganglionic neurons terminate at the site of innervation.

  • Central Nervous System

    • Any lesions of the hypothalamus, brainstem and spinal cord (eg demyelination from multiple sclerosis, vascular abnormalities, tumors, vertebral stroke eg. Wallenberg / lateral medullary syndrome)
  • Peripheral Nervous System (preganglionic and postganglionic)

    • Neck/ cervical roots – cervical rib, aortic aneurysm, surgery/ trauma
    • Apical lung disease – Pancoast tumor (which can also associated with shoulder/arm symptoms and voice changes from compression of brachial plexus, SVC, and recurrent laryngeal nerve and usually is 2/2 lung cancer but can be any malignancy that occurs at the lung apex and includes infections such as TB and pneumonia)
    • Internal carotid artery – eg dissection (which can present with headache, blurry vision, pulsatile tinnitus in a patient who has had trauma to the neck/ or risk factors such as collagen vascular disease)
    • Middle ear disease
    • Cavernous sinus disease
    • Skull base lesions
    • Thyroid cancer
    • Headache syndrome such as cluster headaches

Diffuse large B-cell lymphoma

Workup of diffuse large B-cell lymphoma includes biopsy (FNA although excisional or core usually needs to be performed to get more tissue) to be sent for IHC and flow cytometry, serum LDH (IPI prognostic score), tumor lysis labs (patients at risk), PET-CT (staging) as well as HIV, hepatitis B, TTE, and fertility/ sperm banking prior to starting therapy with combination cytotoxic chemotherapy and rituximab.

Since we see this diagnosis fairly often as it is the most common lymphoma in the Western world, here is an an excellent review article on diffuse large B-cell lymphoma from Annals of Oncology that goes through diagnosis, staging (including review of double-hit vs double-expressor), and current treatment options for patients with this disease. The standard of care in most cases is R-CHOP.

rchop

(Img: http://www.nejm.org/doi/pdf/10.1056/NEJMct1114348 )

Here are some additional papers that Aya identified regarding how aggressive to be in treatment of double-hit lymphoma given its poor prognosis:

  • 2014 Blood paper: non-randomized retrospective study of patients with double-hit lymphoma showed daEPOCH-R had the highest response rate, but insignificant overall survival benefit
  • 2014 British Journal of Haematology paper: retrospective study of patients with double-hit lymphoma showing better 2-year event-free survival (EFS) in the R-EPOCH group
  • 2016 ASH presentation: randomized phase III of patients with advanced DLBCL found no difference in EFS in patients treated with R-EPOCH in comparison to R-CHOP, although the n for double-hit lymphoma is likely too small to draw conclusions