Questions on bone involvement

I wrote these posts in direct response to an email I received from a person in the MastAttack Facebook group (feel free to join) who follows the blog. This person had the following questions:

1) Are osteosclerotic lesions the same as/affiliated with the terms sclerotic, blastic and osteoblast?

Lisa’s response: Sclerotic is associated with the term osteosclerotic. Osteosclerotic means “bone hardening”. Sclerotic can also be used to describe other pathologies, like dermatosclerotic.

Blastic is associated with the term osteoblast, but it can also mean several other cell types. One example of the word “blast” is to mean an immature blood cell. In this context, high levels of blasts can mean severe infection or blood cancers. Osteoblast is the cell type that makes new bone. So osteosclerosis is thought to occur because osteoblasts work faster at laying down new bone than osteoclasts work at eating up old bone.

2) Are osteolytic lesions the same as/affiliated with the terms lytic and osteoclast?

Lisa’s response: Lytic is associated with the term osteolytic. Lytic is the adjective form of lysis, which means to rupture. Osteolysis is caused by two distinct processes occurring together: the first is that rapid growth of abnormal cells (like neoplastic mast cells) inhibits the action of osteoblasts, which normally lay down new bone; and the second is that osteoclast activity is increased, so bone is being absorbed very quickly.

3) If above correlations are correct, A&C below seem contradictory to me, as do B&D.??? Perhaps I’m confused when I isolate it out of context (it was conversation where you were clarifying for someone that osteoporosis wasn’t criteria for SM). (Lisa’s note: Statements A, B, C and D are below these questions for reference.)

Lisa’s response: In multiple studies, patients with ISM, SSM, ASM and SM-AHNMD have been identified as having osteosclerosis. In the largest study (Barete 2010), they found osteosclerosis was more closely associated with aggressive forms of SM (SM-AHNMD and ASM). However, they are still only talking about four people in the aggressive group as opposed to two people in the other (ISM/SSM) group. So in that study, more people with aggressive disease had osteosclerosis than those who had less aggressive disease. In another study, there was no correlation found between osteosclerosis and disease severity.

In particular, what we do not know is whether or not osteosclerosis makes progression more likely by itself. The most robust study found that osteosclerosis in conjunction with swelling of the liver and spleen, presence of multilineage KIT mutation and high increase of baseline serum tryptase warranted careful monitoring for progression. So I’m not convinced that osteosclerosis as a standalone marker is immediately concerning regarding progression, but taken along with these other factors, it may be an indication for cytoreductive therapy.

4) Ultimately, I’m trying to get straight in my mind which is the “worse” lesion (or maybe it’s apples/oranges?) as it pertains to potential progression to an advanced SM category.

Lisa’s response: As pertains to mast cell pathology, large osteolytic lesions are considered the “worst” in that they immediately put you in the ASM category. Again, the only other way this happens is if you have multiple bone breaks as a result of severe osteoporosis (in which osteoporosis is not the qualifier, but the breaks).

So I would consider osteosclerosis as being less severe than osteolytic lesions for the specific purpose of staging SM. However, osteosclerosis is associated with some additional clinical considerations, like blood count abnormalities and higher tryptase, so that should be monitored carefully. Ultimately, this is an issue of research focusing – we need enough time to identify ISM, SSM, ASM and SM-AHNMD patients with osteosclerosis, osteoporosis and osteolysis and determine whether or not osteosclerosis by itself is a determinant of disease progression.

 

Statements:

Note: Both A and B are comments I made as part of a larger FB thread regarding what constitutes “bone involvement” as a diagnostic criterion in staging of SM.

A) Lisa Klimas Osteosclerotic lesions are not immediately a red flag in SM, and about half of SM patients have bone involvement. I wrote a couple of in depth posts about bone manifestations of SM that you may find helpful. I can’t cut and paste in comments on FB for some reason, but google “mastattack bone manifestations of sm” and it comes right up. It’s a two part series.

Lisa’s Response: This was part of a conversation about what constitutes “bone involvement” as a diagnostic marker in staging of SM. It is possible to have ISM or SSM and have osteosclerotic lesions. It does not immediately move you into ASM territory. My phrasing here was poor in that I used bone involvement very broadly (meaning anything involving your bones rather than just the types that affect staging), so that is my fault in that it was confusing.

B) Lisa Klimas Skeletal involvement as applies to mast cell disease means osteolytic lesions, which is a marker for ASM ONLY when you meet the criteria for SM already.

Lisa’s Response: This was part of that same conversation, in which we were discussing bone lesions. One of the markers that qualifies a person as having ASM as opposed to ISM is “bone involvement,” which is defined as large osteolytic lesions or successive fractures due to severe osteoporosis. Here, I was discussing lesions, which is why I omitted the successive fractures. As explained in the earlier part of this post, the osteoporosis does not qualify as “bone involvement” as criteria for ASM – it is the successive fractures.

C) Osteosclerosis is more closely associated with aggressive forms of SM.

Lisa’s Response: This was in reference to the Barete 2010 paper.

D) (I know these are older articles): “The severity of bone lesions on x-ray correlate with urinary histamine levels. Lytic lesions, which are the predominant finding, have been associated with moderate increases in bone marrow mast cells. Significantly more mast cell infiltration has been correlated with sclerotic ”

Reference: Jianguo Tao, Keith Flaherty and Adam Bagg. Unusual Hematologic Malignancies. Case 1. Hematologic Malignancy Presenting With Diarrhea and Bony Lesions: Systemic Mastocytosis. Journal of Clinical Oncology, Vol 20, No 17 (September 1), 2002: pp 3737-3744

Lisa’s Response: The paper quoted is from 2002 and the reference for this above statement is from 1992. It involved a patient group of nine people. Criteria for SM/ASM/etc were different then. I am waiting on a hard copy of the 1992 paper referenced and will do a follow up post when I have been able to review the primary source. This is the reference for the 1992 paper:

Reference: de Gennes C, Kuntz D, de Vernejoul MC. Bone mastocytosis. A report of nine cases with a bone histomorphometric study. Clin Orthop Relat Res. 1992 Jun; (279):281-91.