Thread by @ManniMD1

The correct answer to this question was smoldering myeloma.

Time for an educational 🧵for trainees/health care folks of all specialties about how we diagnose myeloma!

What are CRAB criteria? How is anemia defined? (Key to this Q)

Whats the deal with "SLiM" criteria?

#mmsm

https://twitter.com/ManniMD1/status/1645905833749012480

What are CRAB features?

Hypercalcemia
Anemia
Lytic Bone Lesions
Renal Failure

Anemia is defined as a Hb value of 2 g/dL or 20g/L below lowest limit of normal for the lab, or less than 10g/DL (100g/L)

Is there something magical however about a Hb of 10.1 versus 9.9?

This is where we recognize that there is some arbitrariness/clinical decision making involved.

In general, very mild anemia such as this case would not qualify as a CRAB criteria, and this would be referred to as smoldering myeloma.

Also, sometimes anemia can be from causes other than myeloma. Especially if the plasma cell burden is low (10-20%), must evaluate for other causes of anemia and alternate explanations. Sometimes you can have smoldering myeloma with iron deficiency anemia, or MGUS with anemia!

55 yr old gentleman with HTN, DM, CKD and a long standing creatinine of ~2-3 mg/DL develops neuropathy.

Workup shows M spike 1.2 g/DL.

K/L ratio is abnormal at 12. Bone marrow biopsy shows 15% plasma cells. PET/CT/MRI neg. Kidney biopsy with diabetic changes.

Diagnosis?

The correct answer here is smoldering myeloma.

Why?

More than 10% plasma cells (less than 10% would be MGUS territory)

And no CRAB/SLiM features that you can attribute to the myeloma.

The elevated creatinine is attributed to diabetes.

This is important to recognize!

Since we are talking creatinine, what is the creatinine value as defined in CRAB?

Renal insufficiency is defined as creatinine clearance <40 mL per minute or serum creatinine >177mol/L (>2mg/dL).

What about hypercalcemia?

While hypercalcemia is rarely isolated manifestation of myeloma, the high calcium level must be >0.25 mmol/L (>1mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11mg/dL).

Now lets talk about the SLiM features

Often a source of confusion!

57 yr old gentleman on routine labs found to have elevated protein.

CBC Normal, CMP normal other than total protein= 9.3 g/DL.
M spike=2.1 g/DL.
K/L ratio= 12
Bone marrow biopsy= 15% monoclonal plasma cells
Skeletal survey= Negative

Diagnosis?

The correct answer to this question is that further advanced imaging is needed.

A skeletal survey can miss up to 40% of lytic lesions that would otherwise be picked up via advanced imaging such as MRI, low dose whole body CT or PET/CT!

You now proceed with a whole body diffusion weighted MRI (myeloma MRI).

You find no lytic lesions, but you do find two focal bone marrow lesions, one measuring 1.2 cm, and another measuring 0.8 cm.

Diagnosis?

A common source of confusion are focal bone marrow lesions on MRI versus "lytic lesion".

Focal lesions are early, abnormal areas in bone marrow seen on MRI that signal the development of a full-on lytic lesion within the next few years.

Different than an "actual lytic lesion"!

In 2014, the definition of myeloma changed to include these as myeloma defining event:

-more than 1 focal bone marrow lesion of at least 5 mm on MRI
-involved/uninvolved light chain ratio of grt than 20
-bone marrow plasma cell % of grt than 60

These are called SLiM criteria!

So above patient has MM, because of presence of focal bone marrow lesions, even in absence of other CRAB features.

The three aforementioned findings were added because the risk of MM was felt to be 70-80% in the next two years for such patients based on limited data at that time

Now the reality is that as more data has accumulated, the actual risk of progression of these patients has found to be much lower.

More in the ballpark of 30% in next two years, as opposed to 80%!

pubmed.ncbi.nlm.nih.gov/36969337/

Hence today, there is some controversy with treating those with SLiM criteria alone (no CRAB features) too!

This thread is getting long and should come to an end, so we must summarize key findings!

⭐️The degree of anemia matters. Not all mild anemia in setting of plasma cell clonality is myeloma!
⭐️Degree of renal dysfunction matters too. Not all renal dysfunction is related
⭐️ A focal bone marrow lesion on MRI is different than a "lytic" lesion. Both can diagnose MM though

Thanks for reading. Cannot capture all nuances but hopefully helpful for trainees and other specialties!

@AaronGoodman33 @nihardesai7 @HemOncFellows @rajshekharucms @Eddie_Cliff @HadidiSamer @TheFellowOnCall

END.

Involved/uninvolved light chain ratio of greater than 100*

Not 20.

Sorry for the error!