What is your differential diagnosis?

Systemic malignancy: lymphoproliferative disorder, multiple myeloma or solid organ malignancy

What are conditions are associated with a monoclonal gammopathy?

MGUS, autoimmune disease, plasma cell disorders (e.g. myeloma, smouldering myeloma, amyloidosis), lymphoproliferative disorders, viral infections

Good to read: BMJ Best Practice: Evaluation of Monoclonal Gammopathies

What is the diagnosis?

Diffuse large B cell lymphoma, germinal centre sub-type.

This is based on the Hans algorithm and expression of CD10 by the tumour.

What further investigations would you request that would alter your management of this patient?

FISH for c-myc, bcl-2 and bcl-6 translocations. Double hit lymphomas are much more difficult to treat and retrospective studies suggest they benefit from intensification of chemotherapy.

How would you treat this patient?

This patient has DLBCL and requires chemotherapy. She also requires CNS prophylaxis given her neurological symptoms. The additional use of intravenous methotrexate at a dose of 3.5g/m2 is based on a retrospective series from Boston.

Patients were classified as high risk if they had disease in >2 extranodal sites with an elevated LDH, or disease involvement at anatomically high-risk sites such as the testes, bone marrow or epidural involvement. At a median follow-up of 33 months, there were only 2 CNS recurrences (3%) in the high-risk population.