Plasmacytoma is a

plasma cell dyscrasia Plasma cell dyscrasias (also termed plasma cell disorders and plasma cell proliferative diseases) are a spectrum of progressively more severe monoclonal gammopathies in which a clone or multiple clones of pre-malignant or malignant plasma cells ( ...

in which a plasma cell

tumour A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

grows within

soft tissue Soft tissue is all the tissue in the body that is not hardened by the processes of ossification or calcification such as bones and teeth. Soft tissue connects, surrounds or supports internal organs and bones, and includes muscle, tendons, ...

or within the

axial skeleton The axial skeleton is the part of the skeleton that consists of the bones of the head and trunk of a vertebrate. In the human skeleton, it consists of 80 bones and is composed of six parts; the skull (22 bones), also the ossicles of the middle ...

. The International Myeloma Working Group lists three types: solitary plasmacytoma of bone (SPB); extramedullary plasmacytoma (EP), and multiple plasmacytomas that are either primary or recurrent. The most common of these is SPB, accounting for 3–5% of all plasma cell malignancies. SPBs occur as lytic lesions within the axial skeleton and extramedullary plasmacytomas most often occur in the

upper respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to t ...

(85%), but can occur in any soft tissue. Approximately half of all cases produce

paraproteinemia Monoclonal gammopathy, also known as paraproteinemia, is the presence of excessive amounts of myeloma protein or monoclonal gamma globulin in the blood. It is usually due to an underlying immunoproliferative disorder or hematologic neoplasms, esp ...

. SPBs and extramedullary plasmacytomas are mostly treated with radiotherapy, but surgery is used in some cases of extramedullary plasmacytoma. The skeletal forms frequently progress to multiple myeloma over the course of 2–4 years. Due to their cellular similarity, plasmacytomas have to be differentiated from multiple myeloma. For SPB and extramedullary plasmacytoma the distinction is the presence of only one lesion (either in bone or soft tissue), normal bone marrow (<5% plasma cells), normal skeletal survey, absent or low paraprotein and no end organ damage.

Signs and symptoms

For SPB the most common presenting symptom is that of pain in the affected bone.

Back pain Back pain is pain felt in the back. It may be classified as neck pain (cervical), middle back pain (thoracic), lower back pain (lumbar) or coccydynia (tailbone or sacral pain) based on the segment affected. The lumbar area is the most common ...

and other consequences of the bone lesion may occur such as

spinal cord compression Spinal cord compression is a form of myelopathy in which the spinal cord is compressed. Causes can be bone fragments from a vertebral fracture, a tumor, abscess, ruptured intervertebral disc or other lesion. When acute it can cause a medica ...

pathological fracture A pathologic fracture is a bone fracture caused by weakness of the bone structure that leads to decrease mechanical resistance to normal mechanical loads. This process is most commonly due to osteoporosis, but may also be due to other pathologie ...

. Around 85% of extramedullary plasmacytoma presents within the

mucosa, causing possible symptoms such as

epistaxis A nosebleed, also known as epistaxis, is bleeding from the nose. Blood can flow down into the stomach, and cause nausea and vomiting. In more severe cases, blood may come out of both nostrils. Rarely, bleeding may be so significant that low bl ...

rhinorrhoea Rhinorrhea, rhinorrhoea, or informally runny nose is the free discharge of a thin mucus fluid from the nose; it is a common condition. It is a common symptom of allergies (hay fever) or certain viral infections, such as the common cold or COVID-1 ...

and nasal obstruction. In some tissues it may be found as a palpable mass.

Diagnosis

Serum protein electrophoresis normal and paraprotein

The diagnosis of plasmacytoma uses a diverse range of interdisciplinary techniques including

serum protein electrophoresis Serum protein electrophoresis (SPEP or SPE) is a laboratory test that examines specific proteins in the blood called globulins. The most common indications for a serum protein electrophoresis test are to diagnose or monitor multiple myeloma, a ...

bone marrow biopsy Bone marrow examination refers to the pathologic analysis of samples of bone marrow obtained by bone marrow biopsy (often called trephine biopsy) and bone marrow aspiration. Bone marrow examination is used in the diagnosis of a number of conditio ...

, urine analysis for

Bence Jones protein Bence Jones protein is a monoclonal globulin protein or immunoglobulin light chain found in the urine, with a molecular weight of 22–24 kDa. Detection of Bence Jones protein may be suggestive of multiple myeloma or Waldenström's macroglobuli ...

and

complete blood count A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and pl ...

, plain film radiography,

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...

and

PET-CT Positron emission tomography–computed tomography (better known as PET-CT or PET/CT) is a nuclear medicine technique which combines, in a single gantry, a positron emission tomography (PET) scanner and an x-ray computed tomography (CT) scan ...

. Serum protein electrophoresis separates the proteins in the liquid part of the blood (serum), allowing the analysis of antibodies. Normal blood serum contains a range of antibodies and are said to be polyclonal, whereas serum from a person with plasmacytoma may show a

monoclonal Monoclonality refers to the state of a line of cells that have been derived from a single clonal origin. Thus "monoclonal cells" can be said to form a single clone. The term ''monoclonal'' comes from the Ancient Greek ''monos'', meaning "alone" o ...

spike. This is due to an outgrowth of a single type of plasma cell that forms the plasmacytoma and produces a single type of antibody. The plasma cells are said to be monoclonal and the excessively produced antibody is known as monoclonal protein or

paraprotein A myeloma protein is an abnormal antibody (immunoglobulin) or (more often) a fragment thereof, such as an immunoglobulin light chain, that is produced in excess by an abnormal monoclonal proliferation of plasma cells, typically in multiple myelo ...

Paraprotein A myeloma protein is an abnormal antibody (immunoglobulin) or (more often) a fragment thereof, such as an immunoglobulin light chain, that is produced in excess by an abnormal monoclonal proliferation of plasma cells, typically in multiple myelo ...

s are present in 60% of SPB and less than 25% of extramedullary plasmacytoma. Bone marrow biopsies are performed to ensure the disease is localised; and in SPB or extramedullary plasmacytoma there will not be an increase of monoclonal plasma cells. Tissue biopsies of SPB and extramedullary plasmacytoma are used to assess the

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...

of the plasma cells. Histological analyses can be performed on these biopsies to see what

cluster of differentiation The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophen ...

(CD) markers are present and to assess monoclonality of the cells. CD markers can aid in the distinction of extramedullary plasmacytoma from lymphomas. Skeletal surveys are used to ensure there are no other

primary tumors A primary tumor is a tumor growing at the anatomical site where tumor progression began and proceeded to yield a cancerous mass. Most cancers develop at their primary site but then go on to metastasize or spread to other parts of the body. These fur ...

within the

. MRI can be used to assess tumor status and may be advantageous in detecting primary tumors that are not detected by plain film radiography.

may also be beneficial in detecting extramedullary tumours in individuals diagnosed with SPB. CT imaging may be better than plain film radiography for assessing bone damage. An important distinction to be made is that a true plasmacytoma is present and not a systemic plasma cell disorder, such as multiple myeloma. The difference between plasmacytoma and multiple myeloma is that plasmacytoma lacks increased blood calcium, decreased kidney function, too few red blood cells in the bloodstream, and multiple bone lesions (collectively termed CRAB).

Classification

Plasmacytoma is a

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

of plasma cells. The cells are identical to those seen in multiple myeloma, but they form discrete masses of cells in the skeleton (solitary plasmacytoma of bone; SPB) or in soft tissues (extramedullary plasmacytoma; EP). They do not present with

systemic disease A systemic disease is one that affects a number of organs and tissues, or affects the body as a whole. Examples * Mastocytosis, including mast cell activation syndrome and eosinophilic esophagitis * Chronic fatigue syndrome * Systemic vas ...

, which would classify them as another systemic plasma cell disorder. The International Myeloma Working Group (IMWG) has published criteria for the diagnosis of plasmacytomas. They recognise three distinct entities: SPB, extramedullary plasmacytoma and multiple solitary plasmacytomas (+/- recurrent). The proposed criteria for SPB is the presence of a single bone lesion, normal bone marrow (less than 5% plasma cells), small or no paraprotein, no related organ involvement/damage and a normal skeletal survey (other than the single bone lesion). The criteria for extramedullary plasmacytoma are the same but the tumor is located in soft tissue. No bone lesions should be present. Criteria for multiple solitary plasmacytomas (+/- recurrent) are the same except either multiple solitary bone or soft tissue lesions must be present. They may occur as multiple primary tumors or as a recurrence from a previous plasmacytoma.

Association with the Epstein–Barr virus

Rarely, the

Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is b ...

(EBV) is associated with multiple myeloma and plasmacytomas, particularly in individuals who have an immunodeficiency due to e.g.

HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...

organ transplantation Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transpor ...

, or a chronic inflammatory condition such as

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...

. EBV-positive multiple myeloma and plasmacytoma are classified together by the World Health Organization (2016) as Epstein–Barr virus-associated lymphoproliferative diseases and termed Epstein–Barr virus-associated plasma cell myeloma. EBV-positivity is more common in plasmacytoma than multiple myeloma. The tissues involved in EBV+ plasmacytoma typically show foci of EBV+ cells with the appearance of rapidly proliferating

immature Mature is the adjectival form of maturity, as immature is the adjectival form of immaturity, which have several meanings. Mature or immature may also refer to: * Mature, a character from ''The King of Fighters'' series *"Mature 17+", a rating in ...

or poorly differentiated plasma cells. These cells express products of EBV genes such as EBER1 and EBER2. EBV-positive plasmacytoma(s) is more likely to progress to multiple myeloma than EBV-negative plasmacytoma(s) suggesting that the virus may play a role in the progression of plasmacytoma to multiple myeloma.

Treatment

Radiotherapy is the main choice of treatment for both SPB and extramedullary plasmacytoma, and local control rates of >80% can be achieved. This form of treatment can be used with curative intent because plasmacytoma is a radiosensitive tumor. Surgery is an option for extramedullary plasmacytoma, but for cosmetic reasons it is generally used when the lesion is not present within the head and neck region. Another option is the possible combination of radiotherapy with anti- multiple myeloma treatment. In a study that included 68 patients, a group of 8 patients who were treated with radio- and chemotherapy (with or without surgery) were less likey to have a relapse of plasmacytoma, progress to multiple myeloma, or die compared with patients who were treated with radiotherapy and/or surgery alone rogression free survival (PFS), overall median: not reached vs. 48.0 months; respectively Concerning that study, a large prospective trial is needed to evaluate the impact of adding systemic anti-myeloma treatment to local radiotherapy.

Prognosis

Most cases of SPB progress to multiple myeloma within 2–4 years of diagnosis, but the overall median survival for SPB is 7–12 years. 30–50% of extramedullary plasmacytoma cases progress to multiple myeloma with a median time of 1.5–2.5 years. 15–45% of SPB and 50–65% of extramedullary plasmacytoma are disease free after 10 years.

Epidemiology

Plasmacytomas are a rare form of cancer. SPB is the most common form of the disease and accounts for 3-5% of all plasma cell malignancies. The median age at diagnosis for all plasmacytomas is 55. Both SPB and extramedullary plasmacytoma are more prevalent in males; with a 2:1 male to female ratio for SPB and a 3:1 ratio for extramedullary plasmacytoma.

Terminology

There can be some ambiguity when using the word. "Plasmacytoma" is sometimes equated with "

" or "solitary myeloma". It is often used as part of the phrase "solitary plasmacytoma". or as part of the phrase "extramedullary plasmacytoma". In this context, "extramedullary" means outside of the bone marrow.

References

External links

Overview
at

National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...

{{Lymphoid malignancy Hematologic malignant neoplasms Lymphoid-related cutaneous conditions Epstein–Barr virus–associated diseases