ML-11 DETECTION OF MYD88 MUTATIONS FROM CELL FREE DNA AIDS IN THE DIAGNOSIS OF CENTRAL NERVOUS SYSTEM LYMPHOMAS

Abstract BACKGROUND Diagnosis of primary central nervous system lymphomas (PCNSL) can be challenging. We have shown that the detection of MYD88 mutation in cell free DNA (cfDNA) taken from cerebrospinal fluid (CSF) is reliable (JCO Precision Oncology, 2019; Leukemia and Lymphoma, 2019). We report four cases in which detection of MYD88 mutation aided in the diagnosis. CASE 1 A 67-year-old man with a history of systemic B-cell lymphoma, experienced right hemiparesis. MRI showed a slightly enhancing lesion located in the midbrain. MYD88 L265P mutation was found by digital droplet PCR analysis of cfDNA extracted from CSF. The patient underwent a needle biopsy, and was diagnosed as diffuse large B-cell lymphoma. CASE 2 A 32-year-old man was diagnosed as having a demyelinating lesion after experiencing severe headaches. A small enhancing lesion was found in the right frontal lobe, and the patient was treated with steroids. The lesions repeatedly disappeared and reappeared and finally, stopped responding to steroids. MYD88 mutation was detected. A biopsy was performed, and the diagnosis was PCNSL. CASE 3 A 49-year-old man underwent a biopsy for a right frontal lesion after experiencing memory loss; the pathology showed broad T-cell infiltration but only some perivascular B-cells with slight atypia. The patient was tapered off steroids, and the lesion spread rapidly. An open biopsy was performed, but the pathology was not typical for B-cell lymphoma. The patient’s symptoms rapidly worsened, and whole brain irradiation was performed. At recurrence, MYD88 mutation was detected. CASE 4 An 82-year-old man presented with blurred vision. Vitreous humor biopsy was inconclusive for ocular lymphoma. A head MRI showed an intracranial lesion which spontaneously regressed. MYD88 was detected, and the patient is being closely observed. CONCLUSION Detection of MYD88 mutation from cfDNA extracted from CSF can aid in the diagnosis of CNS lymphoma, especially in atypical cases.

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Primary Central Nervous System Lymphoma Mimicking Longitudinally Extensive Transverse Myelitis

The Neurohospitalist ◽

10.1177/1941874420967560 ◽

2020 ◽

pp. 194187442096756

Author(s):

Prashant Anegondi Natteru ◽

Shashank Shekhar ◽

Lakshmi Ramachandran Nair ◽

Hartmut Uschmann

Keyword(s):

Central Nervous System ◽

Nervous System ◽

B Cell ◽

Cell Lymphoma ◽

Central Nervous System Lymphoma ◽

B Cell Lymphoma ◽

Oligoclonal Bands ◽

Relative Reduction ◽

Thalamic Lesion ◽

The Right

Primary central nervous system lymphoma (PCNSL) is an uncommon variant of extra-nodal non-Hodgkin’s lymphoma. Three regions can be involved in PCNSL: the brain, the spine, or the vitreus and retina. Spinal PCNSL is rare. It can mimic neoplasm, infection, and inflammation. Diagnostic confirmation is by tissue biopsy, and even then, tissue corroboration may be altered by an inflammatory overlay. We report a 59-year-old woman who we saw after she had 4 weeks of ascending tetraparesis plus bowel and bladder incontinence. Upon presentation, the patient was ventilator-dependent and locked-in. She reported normal sensation through eye-blinking. Magnetic resonance imaging (MRI) brain revealed signal intensity in the bilateral corona radiata and restricted diffusion in the right thalamus, whereas, MRI cervical, and thoracic spine showed T2 prolongation in the anterior medulla and upper cervical cord, with enhancement to C2-C3, and long segment hyperintensity from T1-T9 levels, respectively, suggestive of neuromyelitis optica spectrum disorder. Cerebrospinal fluid cytomorphology and flow cytometry were inconclusive for lymphoma/leukemia, but oligoclonal bands were present. Serum aquaporin-4 (AQP-4) antibodies were negative. MR spectroscopy demonstrated NAA reduction, mild lipid lactate peak, and relative reduction of choline on the side of the lesion, favoring demyelination. She received 5-days of intravenous methylprednisolone, followed by 7 sessions of plasma exchange without clinical improvement. Stereotactic biopsy of the right thalamic lesion revealed diffuse large B-cell lymphoma. PCNSL can mimic a demyelinating process early on, as steroid treatment could disrupt B-cell lymphoma cells, thus masking the correct diagnosis.

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