What is Plasma Cell Cancer?

Plasma cell neoplasms (PCN) are a group of disorders in which mature B cells, a type of white blood cell, abnormally multiply and produce a specific type of protein, referred to as paraprotein or M-protein. These cloned cells are usually seen in several conditions under the umbrella term of plasma cell neoplasms. According to the World Health Organisation (WHO) classification from 2017, this group includes different conditions like non-IgM monoclonal gammopathy of undetermined significance (MGUS), plasmacytoma, monoclonal immunoglobulin deposition diseases, plasma cell myeloma (PCM), and plasma cell neoplasms with associated paraneoplastic syndrome. Each one of these has unique characteristics but all fall under the category of Plasma cell neoplasms.

What Causes Plasma Cell Cancer?

The exact cause of plasma cell neoplasms, which are abnormal growths of cells in the immune system, isn’t currently known. There are a few factors that are thought to potentially contribute to the development of these conditions. For example, long-term or chronic exposure to infections, chronic diseases, radiation, or certain harmful substances is believed to possibly play a role.

Some studies have found that specific jobs, such as beauty specialists, farmers, and those who frequently misuse laxatives, can lead to a higher risk of plasma cell neoplasms due to their exposure to specific substances. Some people seem to have a genetic predisposition to these conditions, as families with a history of disorders involving the overgrowth of lymph cells have a higher occurrence of a certain type of plasma cell neoplasm, known as non-immunoglobulin(Ig)-M monoclonal gammopathy of undetermined significance.

Risk Factors and Frequency for Plasma Cell Cancer

PCM, also known as plasma cell myeloma, is a type of disease that is both symptom-producing and well-researched. It’s a common kind of tumor, making up about 1% of all malignant, or dangerous, tumors. Of all cancers originating from blood cells (hematopoietic neoplasms), it accounts for 10-15%. Furthermore, it’s the cause of up to 20% of all deaths from blood-related cancers. PCM usually affects older adults, typically those 50 or older. The average age of diagnosis is 66 years old. Men and African Americans are particularly at a higher risk.

PCM also has a preceding disease called non-Ig-M monoclonal gammopathy of undetermined significance. This condition leads up to PCM and is found in about 4% of all plasma cell tumors.

PCM is symptomatic and well-studied.
It makes up about 1% of malignant tumors and 10-15% of cancer originating from blood cells.
It accounts for up to 20% of all deaths from blood-related cancers.
PCM predominantly affects older adults of 50 years or older, with the average diagnosis age being 66.
This disease has a higher prevalence in men and African Americans.
The condition known as non-Ig-M monoclonal gammopathy of undetermined significance can precede PCM and is found in 4% of all plasma cell tumors.

Signs and Symptoms of Plasma Cell Cancer

Plasma cell neoplasms is a term referring to various diseases involving an overgrowth of certain white blood cells. The way these diseases show up can differ greatly. One key part of diagnosing these diseases is a thorough patient history, physical exam, and lab tests to check if the patient has plasma cell myeloma (PCM), a type of cancer, or a precancerous stage of PCM, such as MGUS or smoldering PCM.

People with MGUS often don’t have any symptoms. This condition has around a 1% risk of developing into a plasma cell disease like PCM, solitary plasmacytoma, or amyloidosis (a condition where abnormal proteins build up in your organs).

PCM is the main type of plasma cell neoplasm. Symptoms can vary a lot. Some people have no symptoms, while others may experience serious ones. PCM can trigger effects like fatigue, pale skin, bleeding, infections, and CRAB symptoms, which stand for hypercalcemia (high calcium levels in the blood), renal insufficiency (kidney problems), anemia (low red blood cell count), and bone lesions (abnormal areas in the bone). Further complications can occur if the cancer cells spread to other organs, leading to an enlarged liver, spleen, or lymph nodes. Other possible signs of advanced PCM include general fatigue, weakness, weight loss, and having a fever.

PCM comes in three varieties:

“Smoldering” plasma cell myeloma: shows classic signs of PCM in the blood and bone marrow, but the patient doesn’t have any symptoms.
Non-secretory myeloma: this type doesn’t produce a certain protein associated with PCM (known as M-protein), although high levels of light chains (a part of the immune system) can be detected in the blood.
Plasma cell leukemia (PCL): this is a serious form of PCM where there’s a large amount of clonal plasma cells (a certain type of white blood cell) present in the body and symptoms of CRAB are more commonly found.

Plasmacytoma is another type of plasma cell neoplasm. This condition is usually categorized into solitary bone plasmacytoma (SBP), where plasma cells gather and cause damage in a single bone, and extramedullary (extraosseous) plasmacytoma (EMP), where the plasma cell growth happens in tissues other than bone. Symptoms of plasmacytoma generally relate to the location of the tumour.

Monoclonal immunoglobulin deposition diseases are conditions where abnormal immune proteins collect in body tissues, causing them to malfunction. Two such diseases include primary amyloidosis and light and heavy chain deposition diseases. Symptoms from these diseases can vary widely based on which organs are affected.

Some plasma cell neoplasms can cause other conditions. For example, in POEMS syndrome, fibrous and bone changes can occur along with symptoms including nerve problems, enlarged organs, endocrine (hormone) issues, abnormal immune protein (monoclonal gammopathy), and skin changes. TEMPI syndrome is another condition connected with plasma cell neoplasms, although it’s not yet fully defined as a separate disease.

Testing for Plasma Cell Cancer

When doctors suspect that a patient has plasma cell neoplasms, a type of cancer that starts in plasma cells, they may run several tests to identify it. The initial set of tests includes a complete blood count (a test that measures the amount of various types of cells in the blood), a blood smear (which gives a visual picture of the blood cells), and tests for the levels of calcium and creatinine in the blood (which can provide clues about the health of the kidneys). The doctors also test for specific proteins in the blood and urine that increase when plasma cells become cancerous.

If results from these tests suggest plasma cell neoplasms, the doctors may then ask for more tests. These can include a biopsy, where a tiny piece of bone marrow (the spongy part inside your bones) is removed and studied under a microscope, urine tests, and blood tests for other proteins and substances.

One particular blood smear finding, called a plasma cell, is very telling. These are large, round cells that produce antibodies, which help the body fight infections. In people with plasma cell neoplasms, there are usually more plasma cells than normal. Sometimes, these plasma cells look either too mature or too immature, both of which are warning signs.

Doctors also use special tests to identify plasma cell proteins. These tests, involving staining processes called immunohistochemical staining and flow cytometry, can help doctors make a definite diagnosis.

One particular protein, known as M protein, is often found in the blood or urine of people with plasma cell neoplasms. Its presence, especially at high levels, can help doctors distinguish plasma cell neoplasms from other similar conditions.

Many people with plasma cell neoplasms also have something called ‘lytic bone lesions’ on their skeleton. These are areas where the cancer has damaged the bone, making it weaker. To look for these, doctors use imaging techniques like X-ray, PET-CT (a special type of scan that combines two methods to produce a 3D image), or MRI (a type of scan that uses strong magnetic fields to create detailed images of the inside of the body.)

Treatment Options for Plasma Cell Cancer

The treatment for plasma cell neoplasms, a type of cancer that starts in your plasma cells, depends on the specific type of disease. Non-IgM MGUS, a condition where there are more plasma cells in your bone marrow than normal but not enough to cause symptoms, is generally managed simply by keeping a close eye on it since it does not often progress to a more serious condition. SBP and EMP, other types of plasma cell neoplasms, are often treated with localized radiotherapy, a cancer treatment that uses high doses of radiation to kill cancer cells.

There’s no standard treatment for plasmacytomas, which are tumors of plasma cells, but they are highly sensitive to radiotherapy. So, local radiation therapy, which focuses radiation in a specific area, is often effective. For PCM, a plasma cell cancer also known as multiple myeloma, treatment depends on how severe the disease is. Every patient should be checked to see if they’re suitable for autologous hematopoietic cell transplantation (HCT), a procedure that infuses healthy blood-forming stem cells into the patient’s body. Studies have shown that intense chemotherapy followed by HCT can increase survival rates compared to just using chemotherapy alone.

For patients categorized as high or intermediate risk, a combination of induction chemotherapy, followed by HCT and maintenance therapy, is often recommended. Some patients can’t undergo high-dose chemotherapy and autologous HCT, in which case chemotherapy alone will be the only treatment option. Some examples of these chemotherapy medications include bortezomib, lenalidomide, dexamethasone (VRd); bortezomib, cyclophosphamide, dexamethasone (VCd); and bortezomib, melphalan, prednisone (VMP). Chemotherapy should be continued until the patient has reached a stable phase, where the M-protein (a protein that can indicate the presence of certain types of cancer) is steady and the disease is not progressing.

The best way to check how well the treatment is working is to measure the level of M-protein in the patient’s blood and urine. It is important to remember, though, that every patient’s situation and treatment plan will be unique to them, and require a team of health professionals to provide the best care.

Amyloidosis
Immunoglobin-related amyloidosis
Light chain-associated renal disorders
Light chain deposition disease
Monoclonal gammopathies of uncertain origin
Multiple myeloma
Plasmacytoma

What to expect with Plasma Cell Cancer

The outlook for plasma cell neoplasms – a type of cancer in plasma cells – varies based on the specific type of disease. The prognosis can depend on different factors, including the stage of disease, genetic characteristics, age, overall health status, response to treatment, and the nature of the disease itself.

The Durie and Salmon staging system predicts how severe the disease is and its prognosis using certain clinical parameters. This system generally categorizes the disease as low, intermediate, and high. The International Staging System, another tool to predict the survival of individuals with this condition, uses indicators such as serum beta-2 microglobulin and albumin levels.

Genetic characteristics are also used to categorize the prognosis into standard, intermediate, and high-risk. Preservation of certain chromosomes or deletion of others plays a role in determining the risk group.

Non-Ig M MGUS is not typically considered a neoplastic process, meaning that it’s not usually manifested as a tumor. The risk of this turning into plasma cell neoplasms, solitary plasmacytoma, or amyloidosis, a disease where harmful proteins accumulate in your organs, is about 1%. Factors affecting progression include the size and type of M proteins. Specific levels of immunoglobulins, a type of protein, can indicate a low or high risk of progression.

Solitary bone plasmacytoma (SBP) has a likelihood of turning into plasma cell neoplasms in upto 60% of the patients. A solid plasmacytoma (EMP) has a more gradual development, with recurrences in about 25% of patients.

Monoclonal immunoglobulin deposition disorders tend to have a poor prognosis, with heart and liver failure and infection being the main causes of death. Patients with primary amyloidosis have an average survival of around 2 years. If patients have both amyloidosis and plasma cell neoplasms, their survival expectancy is even shorter.

On a positive note, survival rates for these conditions have improved. People with POEMS syndrome, a rare disorder that affects multiple body systems, have a better overall outlook compared to other plasma cell neoplasm, with a median survival rate of about 14.7 years.