Multiple myeloma

myelomabone-marrow cancerbone marrow cancerKahler's diseasemyeloma proteinsMyelomatosisPlasma cell myelomabone cancerbone marrow diseasecancer
Multiple myeloma (MM), also known as plasma cell myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies.wikipedia
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Plasma cell dyscrasias

plasma cell dyscrasiaMGUSIgM monoclonal gammopathy of undetermined significance
Multiple myeloma may develop from monoclonal gammopathy of undetermined significance that progresses to smoldering multiple myeloma.
At the other end of this spectrum, detection of the myeloid protein is due to a hematological malignancy, i.e. multiple myeloma, Waldenström's macroglobulinemia, or other B cell-associated neoplasm, that has developed, often in a stepwise manner, from their MGUS precursors.

Bone marrow examination

bone marrow biopsybone marrow aspirationbone marrow aspirate
Multiple myeloma is diagnosed based on blood or urine tests finding abnormal antibodies, bone marrow biopsy finding cancerous plasma cells, and medical imaging finding bone lesions.
Bone marrow examination is used in the diagnosis of a number of conditions, including leukemia, multiple myeloma, lymphoma, anemia, and pancytopenia.

Plasmacytoma

Extramedullary plasmacytomaPlasmocytomaPlasmacytoma, extramedullary
When one tumor is present, it is called a plasmacytoma; more than one is called multiple myeloma.
The skeletal forms frequently progress to multiple myeloma over the course of 2–4 years.

Bone pain

BoneOstealgia
As it progresses, bone pain, bleeding, frequent infections, and anemia may occur.

Targeted therapy

targeted therapiestargeted cancer therapyMolecular Targeted Therapy
Remissions may be brought about with steroids, chemotherapy, targeted therapy, and stem cell transplant.
There are targeted therapies for lung cancer, colorectal cancer, head and neck cancer, breast cancer, multiple myeloma, lymphoma, prostate cancer, melanoma and other cancers.

Kyphosis

hunchbackhunchbackedhump
Involvement of the vertebrae may lead to spinal cord compression or kyphosis.
It can result from degenerative disc disease; developmental abnormalities, most commonly Scheuermann's disease; osteoporosis with compression fractures of the vertebra; multiple myeloma; or trauma.

Serum free light-chain measurement

free light chainsInvolved/Uninvolved light chain ratioserum free light chain assays
Myeloma cells produce monoclonal proteins of varying types, most commonly immunoglobulins (antibodies) and free light chains, resulting in abnormally high levels of these proteins in the blood.
These tests are used as an aid in the diagnosis and monitoring of multiple myeloma and related disorders.

Amyloidosis

amyloid degenerationamyloidosesfamilial amyloidosis
Complications may include amyloidosis.

Myeloma protein

paraproteinparaproteinsabnormal antibodies
The abnormal plasma cells produce abnormal antibodies, which can cause kidney problems and overly thick blood.
A myeloma protein is an abnormal immunoglobulin fragment, such as an immunoglobulin light chain, that is produced in excess by an abnormal monoclonal proliferation of plasma cells, typically in multiple myeloma.

Hypercalcaemia

hypercalcemiahigh blood calciumhigh blood calcium levels
Another common finding is high blood calcium levels.

RANKL

TNFSF11RANKL inhibitorRANK ligand
Myeloma bone disease is due to the overexpression of receptor activator for nuclear factor κ B ligand (RANKL) by bone marrow stroma.
RANKL derived from other cell types contributes to bone loss in conditions involving inflammation such as rheumatoid arthritis, and in lytic lesions caused by cancer, such as in multiple myeloma.

Immunodeficiency

immunocompromisedimmune deficiencyimmunodeficient
Rarely, Epstein-Barr virus (EBV) is associated with multiple myeloma, particularly in individuals who have an immunodeficiency due to e.g. HIV/AIDS, organ transplantation, or a chronic inflammatory condition such as rheumatoid arthritis.
This includes many types of cancer, particularly those of the bone marrow and blood cells (leukemia, lymphoma, multiple myeloma), and certain chronic infections.

Monoclonal gammopathy of undetermined significance

MGUSmonoclonal gammopathies, benignbenign monoclonal gammopathy
MGUS resembles multiple myeloma and similar diseases, but the levels of antibodies are lower, the number of plasma cells (white blood cells that secrete antibodies) in the bone marrow is lower, and it rarely has symptoms or major problems.

Hyperviscosity syndrome

hyperviscosityblood hyperviscosityoverly thick blood
The abnormal plasma cells produce abnormal antibodies, which can cause kidney problems and overly thick blood.
Hyperviscosity occurs from pathologic changes of either cellular or protein fractions of the blood such as is found in polycythemias, multiple myeloma (particularly IgA and IgG3), leukemia, monoclonal gammopathies such as Waldenström macroglobulinemia, sickle cell anemia, and sepsis.

Plasma cell leukemia

In a small percentage of multiple myeloma cases, further genetic and epigenetic changes lead to the development of a plasma cell clone that moves from the bone marrow into the circulatory system, invades distant tissues, and thereby causes the most malignant of all plasma cell dyscrasias, plasma cell leukemia.
PCL may present as primary plasma cell leukemia, i.e. in patients without prior history of a plasma cell dyscrasia or as secondary plasma cell dyscrasia, i.e. in patients previously diagnosed with a history of its predecessor dyscrasia, multiple myeloma.

Serum protein electrophoresis

serum proteinsblood protein electrophoresiselectrophoresis
Being asymptomatic, monoclonal gammapathy of undetermined significance and smoldering multiple myeloma are typically diagnosed fortuitously by detecting a myeloma protein on serum protein electrophoresis tests done for other purposes.
The most common indications for a serum protein electrophoresis test are to diagnose or monitor multiple myeloma, a monoclonal gammopathy of uncertain significance (MGUS), or further investigate a discrepancy between a low albumin and a relatively high total protein.

Bone marrow

marrowred bone marrowbone marrow stroma
Myeloma bone disease is due to the overexpression of receptor activator for nuclear factor κ B ligand (RANKL) by bone marrow stroma. The plasma cells can also form a mass in the bone marrow or soft tissue.
The normal bone marrow architecture can be damaged or displaced by aplastic anemia, malignancies such as multiple myeloma, or infections such as tuberculosis, leading to a decrease in the production of blood cells and blood platelets.

Nephrocalcinosis

Increased bone resorption leads to hypercalcemia and causes nephrocalcinosis, thereby contributing to the kidney failure.

Precancerous condition

premalignantprecancerouspre-malignant
The initial change, often involving one chromosome 14 translocation, establishes a clone of bone marrow plasma cells that causes the asymptomatic disorder MGUS, which is a premalignant disorder characterized by increased numbers of plasma cells in the bone marrow or the circulation of a myeloma protein immunoglobulin.
Some of the most common precancerous conditions include certain colon polyps, which can progress into colon cancer, monoclonal gammopathy of undetermined significance, which can progress into multiple myeloma or myelodysplastic syndrome.

Hypogammaglobulinemia

agammaglobulinemiahypogammaglobulinaemiaHereditary hypogammaglobulinemia
A selected group of people with documented hypogammaglobulinemia may benefit from replacement immunoglobulin therapy to reduce the risk of infection.
These include blood cancers such as chronic lymphocytic leukemia (CLL), lymphoma, or myeloma, HIV, nephrotic syndrome, poor nutrition, protein-losing enteropathy, getting an organ transplant, or radiation therapy.

Spinal cord compression

cord compressioncompressioncompression of the spinal cord
Involvement of the vertebrae may lead to spinal cord compression or kyphosis.
Tumors that commonly cause cord compression are lung cancer (non-small cell type), breast cancer, prostate cancer, renal cell carcinoma, thyroid cancer, lymphoma and multiple myeloma.

Smouldering myeloma

Smoldering multiple myelomaindolent or smolderingsmoldering myeloma
Further and more rapid evolution causes the overtly malignant stage of multiple myeloma and can subsequently lead to the extremely malignant stage of secondary plasma cell leukemia.

Immunoglobulin M

IgMIgM antibodiesimmunoglobulin mu-chains
In theory, multiple myeloma can produce all classes of immunoglobulin, but IgG paraproteins are most common, followed by IgA and IgM.
First, the high molecular weight protein produced by some multiple myeloma patients was recognized to be a tumor-produced γ-macroglobulin, and we now know that because the tumor is a clone the IgM it produces is homogeneous.

FAM46C

These include ATM, BRAF, CCND1, DIS3, FAM46C, KRAS, NRAS and TP53.
Deletion and/ or mutation of FAM46C has been associated with impaired overall survival in Myeloma patients.

Proximal renal tubular acidosis

Primary tubular proximal acidosistype II kidney tubular acidosis
Light chains produce myriad effects that can manifest as the Fanconi syndrome (type II kidney tubular acidosis).