Soft-Tissue Plasmacytomas in Multiple Myeloma: Incidence, Mechanisms of Extramedullary Spread, and Treatment Approach

Abstract

We provide an overview on soft-tissue extramedullary plasmacytomas (EMPs) in multiple myeloma (MM). We reviewed the incidence of EMPs in MM, myeloma bone marrow homing, possible mechanisms of extramedullary spread, and prognosis and response to therapy. The incidence of EMPs is 7% to 18% at MM diagnosis and up to 20% at relapse. The current notion that EMPs are more frequent after treatment with novel agents remains to be proven, especially considering that different patterns of disease recurrence can emerge as patients live longer in the era of novel drugs. Bone marrow genetic abnormalities are not associated with extramedullary spread per se, which also suggests that microenvironmental interactions are key. Possible mechanisms of extramedullary spread include decreased adhesion molecule expression and downregulation of chemokine receptors. EMPs usually show plasmablastic morphology with negative CD56 expression. High-dose therapy with autologous stem-cell transplantation (ASCT) can overcome the negative prognostic impact of extramedullary disease in younger selected patients. EMPs do not typically respond to thalidomide alone, but in contrast, responses to bortezomib have been reported. The incidence of EMPs in patients with MM is high and is associated with poor outcome in patients treated conventionally. A potential first-line treatment option seems to be a bortezomib-containing regimen followed by ASCT, whenever possible. Experimental studies on the mechanisms of myeloma cell adhesion, myeloma growth at extramedullary sites, and drug sensitivity are priorities for this area of continuing therapeutic challenge.

Inflammatory environment created by fibroblast aggregates induces growth arrest and phenotypic shift of human myeloma cells

“…However, in some patients with MM, the PCs proliferation escapes the BM microenvironment influences and it results in extramedullary disease (EMD), which can constitute the most prominent clinical feature of the disease [5]. It is supposed, that EMD represents an entity in which the clonal PCs have lost their dependence on the BM milieu for growth due to altered expression of their homing and adhesion molecules [6]. Thus, in cases of extramedullary MM, the tumor cells do not only home to the BM niches but colonize the other organs, including subcutaneous sites, liver, kidney, gut, lungs, and rarely central nervous system [7].…”

Lesiones cutáneas en mieloma múltiple: Descripción de un caso y revisión de la literatura

“…La fisiopatología no está del todo clara, pero podría deberse a una disminución de expresión de moléculas de adhesión, como VLA-4 y CD44, sumado a una pérdida de CD56, lo que facilitaría la diseminación hematógena, al disminuir la adherencia de las células plasmáticas a la médula ósea 15,16 . En cuanto a la histopatología, los plasmocitomas cutáneos se dividen en dos grupos: los con patrón nodular y con patrón intersticial.…”

Clinical impact of immunophenotypic remission after allogeneic hematopoietic cell transplantation in multiple myeloma

“…The incidence of extramedullary disease (EMD) in first relapse post allografting was monitored, and EMD was defined as previously described. 21 First pulls of BM samples had to contain at least 13 000 cells/uL for flow cytometry MRD studies. Plasma cell quantification was obtained by 4-6-color staining with the following monoclonal antibodies: CD38, CD138, CD56, CD19, CD45, cyKappa, cyLambda.…”

“…Alive patients were censored as of 1 October 2013. OS and EFS curves were estimated by the Kaplan-Meier method and compared using the log-rank 21 in the clinical course before allografting, occurrence of acute and chronic GVHD (any vs none) and disease response (CR/IR, CR/no IR, no CR/IR, no CR/no IR). Six-and 12-month landmark analyses were performed to estimate survival by disease response.…”