What are myeloma bone lesions (lytic and focal)?

Myeloma cells live in the bone marrow, which is at the center of the bones. One of the primary complications that we see from multiple myeloma is that the myeloma cells can actually stimulate other cells in the bones to eat away at the bones. This causes holes in the bones, weakening them, which predisposes to fractures, causes bone pain, and releases calcium out of the bones into the blood. This can raise the blood calcium level and make people feel worse.

When we see evidence that the myeloma cells have caused the bone to be eaten away, those holes in the bones appear as dark spots on X-rays, which we call lytic bone lesions. "Lytic" comes from the Greek word for eating away or breaking down. These lytic bone lesions are very important to identify because we know for sure that in patients with lytic bone lesions, giving bone-strengthening medications like zoledronate, pamidronate, or denosumab can decrease the appearance of new lytic bone lesions, improve bone pain, decrease the risk of fractures, and perhaps also help patients with myeloma to live longer.

In addition to seeing lytic bone lesions, we sometimes talk about focal bone lesions. This refers to the detection of collections of plasma cells within the bone marrow, whether or not they're actually injuring the bones. This usually involves imaging techniques other than the regular X-rays that we use to find lytic lesions. We would typically find lytic lesions on plain X-rays or CT scans, whereas focal bone lesions are usually found on MRI scans or PET scans, which have the ability to actually see into the bone marrow and find collections of abnormal cells, which are presumed to be plasma cells.

While lytic bone lesions might require therapies in and of themselves to reduce pain or the risk of fractures, focal bone lesions are generally more useful as a prognostic marker. Patients with smoldering myeloma who have a lot of focal bone lesions might be at a particularly high risk of progression to active myeloma and might therefore benefit from earlier institution of chemotherapy. The appearance of focal bone lesions on a PET scan after successful treatment of myeloma might indicate that although the patient is in a good response, it wouldn't qualify as a complete or stringent complete response.

What is the difference between an osteolytic lesion and a focal lesion?

A focal lesion, as we call it in the literature and in research, is an accumulation of plasma cells, a small myeloma tumor in the bone marrow that has not destroyed the surrounding bone yet. An osteolytic lesion, on the other hand, is when this tumor causes an osteolytic hole in the bone. So, a focal lesion has no hole in the bone, while an osteolytic lesion causes a hole in the bone. A focal lesion can eventually lead to an osteolytic lesion, but it hasn't done so yet. When it's only a focal lesion, without low-dose CT scans, it won't show the hole in the bone.

Do lytic lesions ever go away?

In general, while focal bone lesions can go away with therapy because we're killing the plasma cells, lytic bone lesions, which involve destruction of the bone, often don't change in appearance over the course of myeloma therapy. We do think that as we treat patients with myeloma and give them bone-strengthening treatments, their bones do get stronger and the risk of fractures decreases. But often, the appearance of the bones on X-ray stays the same. Occasionally, some patients will be able to see that some of those holes seem to fill in, but for most people, the bone still looks the same even when they're in complete response and feel much better. The risk of fractures is much lower, but the bone appearance remains unchanged.

Can lytic and focal lesions happen in the same location?

Sometimes, focal bone lesions happen at the same location as lytic bone lesions, so that a collection of plasma cells will directly stimulate destruction of the bone in that spot. But often, they're at different places completely. This is most easily seen on PET-CT scans, where one can see focal bone lesions on the PET part of the scan and lytic bone lesions on the CT scan. Often, these will be in the same place, but sometimes you’ll see some lytic lesions that don’t have any uptake of the radioactive sugar used in the PET scan, while at the same time, you might see areas with increased uptake of the radioactive sugar without any evidence of bone destruction at that spot.