Management of Multiple Myeloma - Episode 3

Case 1: Molecular Testing in Myeloma

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARDAjai Chari, MD:To summarize, we have a 74-year-old gentleman with some mild renal insufficiency and symptomatic myeloma. Pei, from a pathology perspective, what do you think is the appropriate diagnostic workup for this type of patient?

Pei Lin, MD:For patients with a diagnosis of myeloma, we usually like to start with peripheral blood, to assess whether there are increased circulating plasma cells. We also perform a bone marrow aspiration and biopsy to assess the extent of disease involvement. Sometimes the aspirate can estimate the tumor load. Through the biopsy, we usually perform CD138 to see the extent of tumor infiltration. We also assess…

Ajai Chari, MD:If you have clear evidence of monoclonality, why do you need a marrow?

Pei Lin, MD:The marrow assessment is very important. We also assess the vessels. We evaluate for amyloid deposition. We also assess for lytic lesions. It’s an overall evaluation of the bone pathology as well as the neoplastic cells. Additionally, the morphology of the plasma cells, particularly the plasmablastic variant, is known to be an adverse prognostic factor. So, these are also reported.

Ajai Chari, MD:Are there any additional considerations for an older patient?

Pei Lin, MD:For older patients, concurrent cytopenias or any other factors would raise concurrent MDS [myelodysplastic syndrome]. For instance, we routinely perform an iron stain. Some patients who come in have anemia. They may have other concurrent disease that may be related or unrelated to myeloma. For instance, this patient has anemia, but this patient could have anemia due to some other cause as well. So, this is very important. It comes down to an assessment of the cytogenetics and FISH [fluorescence in situ hybridization]. This particular patient has a t(14;16) translocation, which is, as you mentioned, an adverse prognostic factor. We also perform conventional cytogenetics and a FISH panel to make sure that there is no other concurrent adverse prognostic factor, such as t(4;14) or deletion 17p. These adverse prognostic factors could add to a poor prognosis.

Ajai Chari, MD:Maybe we can just close the pathology component with the relative laboratory work?

Pei Lin, MD:Yes. We also perform flow cytometry. This gives us a baseline as to what the phenotype is. The myeloma cells usually have aberrant expression of CD56. Sometimes they have loss of CD45. This will be very important for future follow up studies, for monitoring of minimal residual disease.

Ajai Chari, MD:Perhaps you could, since you brought up the flow, mention light chain restriction? What is the difference between myeloma and lymphoma, in terms of cytoplasmic versus surface?

Pei Lin, MD:The plasma cells usually have the cytoplasm with the light chain restriction, whereas the B cells usually just have surface light chain restrictions. Plasma cells, as we know, are terminally differentiated. They lose the surface light chain expression. The light chain assessment is sometimes difficult because some myelomas can be non-secretory. So, it will be very important to assess the overall patterns. The aberrant surface expression could be an indication of aberrant malignancy rather than these cytoplasmic restriction patterns itself.

Ajai Chari, MD:Great. Thank you so much for that important pathology perspective.

Transcript edited for clarity.