Discussion response

Multiple myeloma (MM) “is a clonal plasma cell cancer characterized by the slow proliferation of tumor cell masses in the bone marrow associated with lytic bone lesions” (McCance & Huether, 2019). It is the second most common type of blood cancer after lymphoma (Kasandijian, 2016; Rajkumar & Kumar, 2016 as cited in Richardson et al., 2021) and for unknown reasons, the reported incidence has doubled in the last 20 years (McCance & Huether, 2019). Rare variants include solitary myeloma (plasmacytoma) and smoldering myeloma. Solitary plasmacytoma is a single malignant mass in the bone or soft tissue accounting for approximately 1% of plasma cell malignancies (Goldman & Schafer, 2012 as cited in McCance & Huether, 2019) and smoldering myeloma presents without symptoms but elevated M protein, which is a plasma abnormal antibody (McCance & Huether, 2019). Solitary plasmacytoma is the only curable type of plasma cell malignancy (Sacharian & Friend, 2020).

            In myelomas, immunoglobulin (Ig), most commonly of the IgG class is produced and secreted by the malignant plasma cells and is “seen as a monoclonal component (M-protein) on serum electrophoresis” (Richardson et al., 2021). MM remains a biologically complex, incurable disease and at this point treatment options and focus include “symptomatic support therapy, high-dose chemotherapy, bone marrow hematopoietic stem cell transplantation, and cellular immunotherapy” (Hosoya & Sidana, 2021; Jiang et al., 2020 as cited in Pan et al., 2021). According to American Cancer Society (2020 as cited in Sacharian & Friend, 2020), the overall five-year survival rate of MM is 52% and most are diagnosed in the later stages of the disease process. The amount of M preing in the blood may be used as a mesure of the ectent of the disease or as a measure of response to therapy” (McCance & Huether, 2019).

            MM progression includes metastasis of tumor cells, immune escape, resistance of apoptosis, and proliferation of malignant cells that are not dependent on the bone marrow microenvironment (Vozella et al., 2021; Jia et al., 2021; Chen et al., 2021 as cited in Pan et al., 2021). Patients may have signs and symptoms such as bone pain due to the bone tissue destruction (80% affected experience bone lesion), fatigue, weakness, bruising or bleeding easily, weight loss, anorexia, and trouble breathing associated with pain or they could be completely asymptomatic with occurrence of only incidental lab findings (Sacharian & Friend, 2020) such as proteinuria (in 90% of those with MM), anemia (72%), hypercalcemia (in 13%) (McCance & Huether,, 2019), leukopenia, or thrombocytopenia (Sacharian & Friend, 2020). Amyloidosis, the process of antibody proteins increasing in number and sticking together in peripheral nerves and organs, stiffening and thickening them, causes those affected to experience “extreme exhaustion, purple spots on the skin, enlarged tongue, diarrhea, edema, and tingling and numbness in the legs and feet” (Woo & Robinson, 2019). Acute or chronic renal failure secondary to hypercalcemia occurs in 19% of the cases and 20% experience hyperviscosity syndrome due to the high concentration of paraprotein in the blood, causing interference of blood circulation to various sites such as brain, kidneys, or extremities (McCance & Huether, 2019). 

            The most common bones affected in descending order of frequency are “vertebrae, ribs, skull, pelvis, femur, clavicle, and scapula” (McCance & Huether, 2019) so it could be very likely for someone to present with a chief complaint of back or other musculoskeletal pain. “It is common for those with myeloma to be treated for a slipped vertebral disc or arthritis” (McCance & Huether, 2019). As a result of weakened vertebrae, spinal cord compression is prevalent in about 10% of individuals (McCance & Huether, 2019). Erythrocyte sedimentation rate (ESR) is elevated in MM, infectious spinal disease, and ankylosing spondylitis which could help rule out a differential diagnosis such as osteoarthritis or mechanical cause of pain (Seller & Symons, 2018) and skeletal imaging should be obtained for lytic bone lesions (Sacharian & Friend, 2020).  Seller & Symons (2018) explain if one endorses “low back pain” that an MRI or CT (if MRI is contraindicated or not available)

            should be used not to make a diagnosis but to confirm one made by history and physical examination…after seven weeks of conservative management…unless

            evidence of a motor, sensory, reflex, sphincter, or autonomic deficit is present or if major trauma, infection, or neoplasia is suspected.

            The vague symptoms of myeloma can be recalled using the acronym CRAB: C- hyperCalcemia, R- Renal involvement, A- Anemia, and B- Bone lesions, however, identification of one only after onset of CRAB symptoms essentially means end-organ damage is already taking place (Zetlmeisl, 2020). International Myeloma Working Group and National Comprehensive Cancer Network updated their 2009 guidelines to include free light chain serum testing in initial myeloma diagnostic workup and by 2014, CRAB symptoms were no longer needed to diagnose myeloma; if there was greater than ten percent clonal plasma cells detected in one’s bone marrow and at least one myeloma defining event (Zetlmeisl, 2020). Free light assays “are very sensitive and specific tests that measure free antibody light chains in serum” and when used in combination with serum protein electrophoresis (SPE) and immunofixation electrophoresis, myeloma diagnosis is increased to 100% compared to SPE alone (Katzmann, 2009 as cited in Zetlmeisl, 2020).  

            National Cancer Institute (2020 as cited in Sacharian & Friend, 2020) explains that detecting the level of plasma cells in a bone marrow biopsy will help determine the extent of the disease. Pan et al. (2021) found secreted protein acidic and rich in cysteine (SPARC) to be highly expressed in MM and those with lower SPARC levels to have a significantly higher three-year survival rate compared to those with higher serum levels of expression. Their study concluded “interference of overexpression of SPARC vector can affect the biological behaviors of MM cells, such as proliferation, migration, invasion, and apoptosis” (Pan et al., 2021). 

            Wang et al.’s study (2021) showed those with MM had higher expression levels of COX6C gene and genes encoding ribosomal proteins, but lower levels of NOD2 expression compared to controls and that those MM patients with increased NOD2 and decreased COX6X expression levels had a higher survival ratio compared to those MM patients that had decreased NOD2 and increased COX6X expression levels. Therefore, “the NOD2 and COX6C genes might be used as prognostic biomarkers in MM” (Wang et al., 2021). 

            References

McCance, K. L. & Huether, S. E. (2019). Pathophysiology the biologic basis for disease in adults and children (8^th ed.). Elsevier. 

Richardson, P. G., Harrison, S. J., Bringhen, S., Schjesvold, F., Yong, K., Campana, F., Le-Guennec, S., Macé, S., & Dimopoulos, M. A. (2021). Isatuximab for relapsed/refractory multiple myeloma: review of key subgroup analyses from the Phase III ICARIA-MM study. Future Oncology, 17(34), 4797–4812. https://doi.org/10.2217/fon-2021-0568

Pan, Qiqun, Tangfei Li, Zhangqin Luo, and Pengji Pan. 2021. “Expression of Cysteine-Rich Secreted Acidic Protein in Multiple Myeloma and Its Effect on the Biological Behavior of Cancer Cells.” Evidence-Based Complementary & Alternative Medicine (ECAM), October, 1–8. doi:10.1155/2021/6101060.

Sacharian, K., & Friend, P. (2020). Multiple Myeloma Prevention, Screening, Treatment, and Survivorship Recommendations. Oncology Nursing Society Voice, 35(6), 36–37.

Seller, R. H. & Symons, A. B. (2018). Differential diagnosis of common complaints (7^th ed.). Elsevier.

Wang, F., Liu, R., Yang, J., & Chen, B. (2021). New insights into genetic characteristics between multiple myeloma and COVID‐19: An integrative bioinformatics analysis of gene expression omnibus microarray and the cancer genome atlas data. International Journal of Laboratory Hematology, 43(6), 1325–1333. https://doi.org/10.1111/ijlh.13717

Zetlmeisl, M. (2020). Advances in oncology technology and free light chain testing. Medical Laboratory Observer, 52(3), 24–26.