How would you treat a patient with two concurrent plasmacytomas whose bone marrow showed no evidence of multiple myeloma and has no other MM defining features?

This is by definition Multiple Myeloma and I would treat it as such with systemic induction chemotherapy followed by transplant. These patients do better than the standard MM oftentimes. IMWG Criteria for the Diagnosis of MM | Inl Myeloma Fn

While I would want to have a little bit more information before giving any final recommendations (are these extramedullary? What are the specific locations? If sinonasal that would make me think of underlying HIV), in general, I would assume that this represents systemic disease and that if one were (theoretically) to sample enough areas of bone marrow throughout the body, one would find clonal plasma cells. And sometimes whole body diffusion weighted MRI can highlight likely areas of bone marrow involvement. It is also noted that more sensitive methods such as mass spectrometry are proving useful for identifying monoclonal proteins in cases otherwise thought to be nonsecretory based on traditional methods (Giles et al., PMID 34871382).

I wo...

The short answer, in my mind, is an n=1 approach but almost always in favor of systemic therapy as if this were normal multiple myeloma. Different terms have been proposed for this rare presentation, either "multiple solitary plasmacytomas" or "macrofocal myeloma" (I prefer the latter).

My guess is that, depending on how deeply one looked on a random bone marrow biopsy, clonal plasma cells would be found. For example, a more sensitive flow assay (or NGF) - or NGS based on IgH sequencing of a plasmacytoma and subsequent evaluation of the bone marrow - would likely yield some marrow involvement < 1%. To be clear, I wouldn't recommend actually doing this since it wouldn't change my management, but I do think the cells are there.

In general, I ...