Lymphomatoid Granulomatosis: A Rare Lymphoproliferative Disorder on the Differential Diagnosis for Brain and Spinal Cord Lesions
Dhvani Raghupathy1, Keirsyn Criss2, Sneha Lingam2, Deepal Shah-Zamora3, Emily Pharr4, Rakhee Vaidya5, Kathryn Mercer2, Danielle Maracaja2, Roy Strowd6
1Wake Forest School of Medicine, 2Wake Forest Baptist Health, 3Atrium Health Wake Forest Baptist, 4Wake Forest University School of Med., 5Atrium Health Wake Forest, 6Wake Forest School Of Medicine
Objective:
To convey the importance of considering lymphomatoid granulomatosis as a differential diagnosis in patients presenting with steroid-responsive pulmonary and neurologic lesions.  
Background:
Lymphomatoid granulomatosis is a rare EBV-driven angioinvasive and angiodestructive B-cell lymphoproliferative disorder. Lungs are most commonly affected, followed by the central nervous system (CNS), skin, kidneys, and liver. Within the CNS, spinal cord involvement is rare.
Design/Methods:
N/A
Results:

A 58-year-old woman with an incidental subpleural nodule found in 2020 during evaluation of exertional angina developed persistent respiratory symptoms after COVID-19 infection. PET CT demonstrated active lesions in the lungs and frontoparietal lobes. After initial diagnosis of squamous cell carcinoma (SCC) on endobronchial fine needle aspirates, a brain biopsy found perivascular and intraparenchymal inflammatory changes without evidence of malignancy. SCC was not confirmed in subsequent biopsies. Rheumatologic evaluation of diffuse arthralgias was unremarkable. Serial MRI brain revealed resolution of previously enhancing lesions after steroid treatment and new regions of parenchymal and leptomeningeal enhancement.  

Three months later, she developed left leg weakness and paresthesias. MRI revealed new contrast-enhancing cerebellar and occipital lesions, as well as a longitudinal partially ring-enhancing lesion in the thoracic spinal cord. Imaging also demonstrated  lesions in the lungs and lumbar paraspinal musculature. Spinal fluid studies showed 39 nucleated cells (lymphocyte predominant), 129 mg/dl protein, and normal glucose. Repeat lung biopsy with wedge resection confirmed grade III lymphomatoid granulomatosis. High-dose steroids provided near-resolution of symptoms. She is receiving systemically directed chemotherapy in a clinical trial with dramatic reduction in lung and CNS lesion burden. 

Conclusions:
Lymphomatoid granulomatosis is a rare disease involving the lungs and brain most commonly, with rare involvement of the spinal cord. Prompt treatment is critical because this disease can progress to diffuse large B-cell lymphoma. This case demonstrates the importance of pursuing biopsy in the setting of steroid-responsive lesions in the brain, spinal cord, and lungs.
10.1212/WNL.0000000000205803