Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jul 6;10(7):629.
doi: 10.3390/biology10070629.

Clinical and Biological Characteristics of Medullary and Extramedullary Plasma Cell Dyscrasias

Snjezana Janjetovic  1   2 , Philipp Lohneis  3   4 , Axel Nogai  5 , Derya Balci  5   6 , Leo Rasche  7 , Doris Jähne  8 , Carsten Bokemeyer  1 , Georgia Schilling  1   9 , Igor Wolfgang Blau  5   10 , Martin Schmidt-Hieber  2   5   11
Affiliations

Clinical and Biological Characteristics of Medullary and Extramedullary Plasma Cell Dyscrasias

Snjezana Janjetovic et al. Biology (Basel). .

Abstract

Background: Extramedullary plasma cell (PC) disorders may occur as extramedullary disease in multiple myeloma (MM-EMD) or as primary extramedullary plasmocytoma (pEMP)/solitary osseous plasmocytoma (SOP). In this study, we aimed to obtain insights into the molecular mechanisms of extramedullary spread of clonal PC. Methods: Clinical and biological characteristics of 87 patients with MM-EMD (n = 49), pEMP/SOP (n = 20) and classical MM (n = 18) were analyzed by using immunohistochemistry (CXCR4, CD31, CD44 and CD81 staining) and cytoplasmic immunoglobulin staining combined with fluorescence in situ hybridization (cIg-FISH). Results: High expression of CD44, a cell-surface glycoprotein involved in cell-cell interactions, was significantly enriched in MM-EMD (90%) vs. pEMP/SOP (27%) or classical MM (33%) (p < 0.001). In addition, 1q21 amplification by clonal PC occurred at a similar frequency of MM-EMD (33%), pEMP/SOP (57%) and classical MM (44%). Conversely, del(17p13), t(4;14) and t(14;16) were completely absent in pEMP/SOP. Besides this, 1q21 amplification was identified in 64% of not paraskeletal samples from MM-EMD or pEMP compared to 9% of SOP or paraskeletal MM-EMD/pEMP and 44% of classical MM samples, respectively (p = 0.02). Conclusion: Expression of molecules involved in homing and cytogenetic aberrations differ between MM with or without EMD and pEMP/SOP.

Keywords: cytogenetics; extramedullary; immunohistochemistry; multiple myeloma; plasma cell disorder.

PubMed Disclaimer

Conflict of interest statement

S.J.: financial support of educational meetings by Celgene GmbH, Sobi GmbH, Bristol-Myers Squibb GmbH, AOP Orphan GmbH and Amgen GmbH. P.L.: none. A.N.: none. D.B.: none. L.R.: speaker honoraria from BMS/Celgene, Sanofi, GSK, Oncopeptides and Janssen. D.J.: none. C.B.: personal fees from Sanofi Aventis, Merck KgA, Bristol-Myers Squibb, Merck Sharp & Dohme, Lilly Imclone, Bayer Healthcare, GSO Contract Research, AOK Rheinland-Hamburg and Novartis. G.S.: none. I.W.B.: none. M.S.-H.: advisory role or expert testimony (no personal fees): Celgene GmbH, Kite/Pharma Gilead and Sanofi. Other financial relationships: financial support of educational meetings at the Carl-Thiem-Klinikum Cottbus gGmbH by Janssen-Cilag GmbH, Takeda Pharma Vertrieb GmbH & Co. KG, Novartis Pharma Oncology, Pfizer Pharma GmbH, Roche Pharma AG, Vifor Pharma.

Figures

Figure 1
Figure 1
Distribution of locations of MM-EMD (n = 49) vs. pEMP/SOP (n = 20). Shown are percentages of patients. MM-EMD multiple myeloma with extramedullary disease; pEMP/SOP primary extramedullary plasmocytoma/solitary osseous plasmocytoma; CNS central nervous system.
Figure 2
Figure 2
Expression of CXCR4, CD31, CD44 and CD81 by cPC. (A) Classical (medullary/osseous) MM vs. MM-EMD vs. pEMP/SOP. CD81 expression was not identified in any of 42 studied samples (not shown). (B) Classical MM vs. SOP or MM-EMD/pEMP paraskeletal vs. MM-EMD/pEMP not paraskeletal. Shown are percentages of samples with a moderate or strong expression intensity (vs. negativity or low expression) from tested samples. (C) Representative immunohistochemistry study on tissue microarrays (TMA) showing strong CD31 expression of cPC (left, buccal MM-EMD) and lack of CD81 expression (right, MM-EMD with skin infiltration).
Figure 2
Figure 2
Expression of CXCR4, CD31, CD44 and CD81 by cPC. (A) Classical (medullary/osseous) MM vs. MM-EMD vs. pEMP/SOP. CD81 expression was not identified in any of 42 studied samples (not shown). (B) Classical MM vs. SOP or MM-EMD/pEMP paraskeletal vs. MM-EMD/pEMP not paraskeletal. Shown are percentages of samples with a moderate or strong expression intensity (vs. negativity or low expression) from tested samples. (C) Representative immunohistochemistry study on tissue microarrays (TMA) showing strong CD31 expression of cPC (left, buccal MM-EMD) and lack of CD81 expression (right, MM-EMD with skin infiltration).
Figure 3
Figure 3
Cytogenetic aberrations of cPC. (A) Classical (medullary/osseous) MM vs. MM-EMD vs. pEMP/SOP. (B) Classical MM vs. SOP or MM-EMD/pEMP paraskeletal vs. MM-EMD/pEMP not paraskeletal. Shown are percentages of patients with a distinct cytogenetic aberration (from evaluated patients). (C) Representative cIg-FISH study showing C-MYC amplification in a patient with MM-EMD (skin infiltration). Amplified signals for C-MYC (red arrows) and two signals for p7t1 (centromere 7, green arrows) are demonstrated. Blue color stains intracytoplasmic light chains.
Figure 3
Figure 3
Cytogenetic aberrations of cPC. (A) Classical (medullary/osseous) MM vs. MM-EMD vs. pEMP/SOP. (B) Classical MM vs. SOP or MM-EMD/pEMP paraskeletal vs. MM-EMD/pEMP not paraskeletal. Shown are percentages of patients with a distinct cytogenetic aberration (from evaluated patients). (C) Representative cIg-FISH study showing C-MYC amplification in a patient with MM-EMD (skin infiltration). Amplified signals for C-MYC (red arrows) and two signals for p7t1 (centromere 7, green arrows) are demonstrated. Blue color stains intracytoplasmic light chains.
Figure 4
Figure 4
Overall survival of patients with MM with (– –) or without EMD (--) at diagnosis vs. pEMP/SOP (──). Shown are Kaplan–Meier estimates.
See this image and copyright information in PMC

References

    1. Bladé J., Fernández de Larrea C., Rosiñol L., Cibeira M.T., Jiménez R., Powles R. Soft-tissue plasmacytomas in multiple myeloma: Incidence, mechanisms of extramedullary spread, and treatment approach. J. Clin. Oncol. 2011;29:3805–3812. doi: 10.1200/JCO.2011.34.9290. - DOI - PubMed
    1. Caers J., Paiva B., Zamagni E., Leleu X., Bladé J., Kristinsson S.Y., Touzeau C., Abildgaard N., Terpos E., Heusschen R., et al. Diagnosis, treatment, and response assessment in solitary plasmacytoma: Updated recommendations from a European Expert Panel. J. Hematol. Oncol. 2018;11:10. doi: 10.1186/s13045-017-0549-1. - DOI - PMC - PubMed
    1. Varettoni M., Corso A., Pica G., Mangiacavalli S., Pascutto C., Lazzarino M. Incidence, presenting features and outcome of extramedullary disease in multiple myeloma: A longitudinal study on 1003 consecutive patients. Ann. Oncol. 2010;21:325–330. doi: 10.1093/annonc/mdp329. - DOI - PubMed
    1. Usmani S.Z., Heuck C., Mitchell A., Szymonifka J., Nair B., Hoering A., Alsayed Y., Waheed S., Haider S., Restrepo A., et al. Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents. Haematologica. 2012;97:1761–1767. doi: 10.3324/haematol.2012.065698. - DOI - PMC - PubMed
    1. Pour L., Sevcikova S., Greslikova H., Kupska R., Majkova P., Zahradova L., Sandecka V., Adam Z., Krejci M., Kuglik P., et al. Soft-tissue extramedullary multiple myeloma prognosis is significantly worse in comparison to bone-related extramedullary relapse. Haematologica. 2014;99:360–364. doi: 10.3324/haematol.2013.094409. - DOI - PMC - PubMed