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would have been gained if the values of MVD and OPN expression were taken at different time points,
regarding therapy response, so this remains a goal for our next investigation.

It is obvious that nothing can be concluded on the bases of two cases, but this review of our two patients
encourages us, and we hope other research groups to continue analyzing cases of extramedullary MM
(especially in large clinical trials) and investigating various factors of the microenvironment in this
particular type of MM, including angiogenesis and OPN. If angiogenesis were proven as an important
pathogenetic factor in EMD, it would provide a wide range of possibilities for the treatment of the most
aggressive forms of MM, such as EMD. The same could be true for OPN, whose biological function in MM
and EMD should also be clarified in future research with the possibility of pharmacological inhibition of its
biological effect.

DECLARATIONS
Authors’ contributions
Designed the paper and wrote the manuscript: Valković T, Stanić Damić M, Valković F
Designed the paper, wrote the manuscript and reviewed and approved the manuscript: Jonjić N

Availability of data and materials
Authors declare that data and supplementary figures supporting their findings can be found in Clinical
Hospital Center Rijeka.

Financial support and sponsorship
This work was supported by the Research Support of the University of Rijeka: grant No. 918.10.0104.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Written informed consent was obtained from the patients.

Consent for publication
Written informed consent was obtained from the patients for publication of this case reports and any
companying images.

Copyright
© The Author(s) 2022.

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