The clinical presentation of primary PCL (pPCL) indicates a far more aggressive disease than that of a typical multiple myeloma case with its clinical features being a combination of those found in multiple myeloma and acute leukemia. Like multiple myeloma patients, pPCL patients exhibit pathologically high levels of monoclonal plasma cells in their bone marrow plus a malignant plasma cell-secreted circulating monoclonal myeloma protein, either IgG, IgA, a light chain, or none in 28-56%, 4-7%, 23-44%, or 0-12% of cases, respectively. Similar to B cell leukemias, but unlike multiple myeloma, pPCL patients exhibit relative high frequencies of splenomegaly, lymphadenopathy, hepatomegaly, kidney failure, bone marrow failure (i.e. thrombocytopenia, anemia, and/or, rarely, leukopenia), central nervous system defects, and peripheral neuropathies due to the invasion of these tissues by plasma cells and/or the deposition of their circulating monoclonal immunoglobulin in them. Compared to multiple myeloma patients, pPCL patients also: exhibit 1) high rates of developing an hypercalcemic crisis, i.e. an potentially life-threatening episode of high ionic calcium (Ca) levels in the blood due to excess bone re-absorption and/or renal failure; b) higher levels of serum lactate dehydrogenase and Beta-2 microglobulin; and c) lower rates of bone but higher rates of soft tissue plasma cell tumors termed plasmacytomas.

Plasma cell leukemia (PCL) is a plasma cell dyscrasia, i.e. a disease involving the malignant degeneration of a subtype of white blood cells called plasma cells. It is the terminal stage and most aggressive form of these dyscrasias, constituting 2% to 4% of all cases of plasma cell malignancies. 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. The two forms of PCL appear to be at least partially distinct from each other. In all cases, however, PCL is an extremely serious, life-threatening, and therapeutically challenging disease.

Signs and symptoms of WM include weakness, fatigue, weight loss, and chronic oozing of blood from the nose and gums. Peripheral neuropathy occurs in 10% of patients. Enlargement of the lymph nodes, spleen, and/or liver are present in 30–40% of cases. Other possible signs and symptoms include blurring or loss of vision, headache, and (rarely) stroke or coma.

Waldenström's macroglobulinemia (WM), also known as lymphoplasmacytic lymphoma, is a type of cancer affecting two types of B cells, lymphoplasmacytoid cells and plasma cells. Both cell types are white blood cells. WM is characterized by having high levels of a circulating antibody, immunoglobulin M (IgM), which is made and secreted by the cells involved in the disease. WM is an "indolent lymphoma" (i.e., one that tends to grow and spread slowly) and a type of lymphoproliferative disease which shares clinical characteristics with the indolent non-Hodgkin lymphomas. WM is commonly classified as a form of plasma cell dyscrasia. Similar to other plasma cell dyscrasias that, for example, lead to multiple myeloma, WM is commonly preceded by two clinically asymptomatic but progressively more pre-malignant phases, IgM monoclonal gammopathy of undetermined significance (i.e. IgM MGUS) and smoldering Waldenström's macroglobulinemia. The WM spectrum of dysplasias differs from other spectrums of plasma cell dyscrasias in that it involves not only aberrant plasma cells but also aberrant lymphoplasmacytoid cells and that it involves IgM while other plasma dyscrasias involve other antibody isoforms.

WM is a rare disease, with only about 1,500 cases per year in the United States. While the disease is incurable, it is treatable. Because of its indolent nature, many patients are able to lead active lives, and when treatment is required, may experience years of symptom-free remission.

Due to the systemic nature of this disease, neoplastic cells can be found in lymph nodes, liver, spleen, skin, and bone marrow.

Acute mast cell leukemia is a rapidly progressive disorder with leukemic mast cells in blood and in large numbers in marrow. The common signs and symptoms include fever, headache, flushing of face and trunk. The typical cutaneous mast cell infiltrates of urticaria pigmentosa are usually not present before, during, or after diagnosis in patients who have mast cell leukemia. Symptoms include abdominal pain, bone pain, and peptic ulcer which are more prevalent than in other subtypes of acute myeloid leukemia. These former symptoms are due to release of a substance called histamine from neoplastic mast cells. Enlargement of the liver and spleen, or hepatosplenomegaly is characteristic. The mast cells release also many anticoagulants like heparin which can lead to serious bleeding. Liver and splenic dysfunction also contributes to hemorrhage. Involvement of the bone can lead to osteoporosis. Abdominal ultrasound or computerized tomography (CT) scanning is used to look for hepatosplenomegaly and lymphadenopathy. Plain radiography and bone densitometry can be used to assess bone involvement and the presence of osteoporosis. Endoscopy and biopsy can be useful if gut involvement is suspected.

Patients with this disease usually present at an advanced stage and show systemic involvement. The clinical findings typically include a pruritic skin rash and possibly edema, ascites, pleural effusions, and arthritis.

Mast cell leukemia is an extremely aggressive subtype of acute myeloid leukemia that usually occurs "de novo" but can, rarely, evolve from transformation of chronic myeloid leukemia into the more aggressive acute myeloid leukemia. In a small proportion of cases, acute mast cell leukemia may evolve from a more progressive form of systemic mastocytosis. The diagnosis of acute mast cell leukemia by the WHO criteria includes the requirement for a prevalence of 20% neoplastic mast cells in marrow and 10% in blood. If the mast cells represent less than 10% of blood cells, the tumor is called "aleukemic" mast cell leukemia.

Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs. They develop from bone marrow hematopoietic stem cells and constitute < 0.4% of peripheral blood mononuclear cells (PBMC).

In humans they exhibit plasma cell morphology and express CD4, HLA-DR, CD123, blood-derived dendritic cell antigen-2 (BDCA-2), Toll-like receptor (TLR) 7 and TLR9 within endosomal compartments, but do not express high levels of CD11c or CD14, which distinguishes them from conventional dendritic cells or monocytes, respectively. Mouse pDC express CD11c, B220, BST-2/Tetherin (mPDCA) and Siglec-H and are negative for CD11b.

As components of the innate immune system, these cells express intracellular Toll-like receptors 7 and 9 which detect ssRNA and unmethylated CpG DNA sequences, respectively. Upon stimulation and subsequent activation, these cells produce large amounts (up to 1,000 times more than other cell type) of type I interferon (mainly IFN-α (alpha) and IFN-β (beta)), which are critical pleiotropic anti-viral compounds mediating a wide range of effects.

The number of circulating pDCs are found to be decreased during chronic HIV infection as well as HCV infection.

Plasma cells, also called plasma B cells, plasmocytes, plasmacytes, or effector B cells, are white blood cells that secrete large volumes of antibodies. They are transported by the blood plasma and the lymphatic system. Plasma cells originate in the bone marrow; B cells differentiate into plasma cells that produce antibody molecules closely modelled after the receptors of the precursor B cell. Once released into the blood and lymph, these antibody molecules bind to the target antigen (foreign substance) and initiate its neutralization or destruction.

Plasmablastic lymphoma is a type of large B-cell lymphoma, recognized in the WHO 2008 classification. It is CD20 negative, and has an immunophenotype that resembles plasma cells. In formal use, lymphomas with plasmablastic immunophenotype such as primary effusion lymphoma, ALK+ large B-cell lymphoma, large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease and extracavitary HHV–8-positive lymphoma are not part of this category, although sometimes the literature has confused this point.

Macroglobulinemia is the presence of increased levels of macroglobulins in the circulating blood.

It is a plasma cell dyscrasia, resembling leukemia, with cells of lymphocytic, plasmacytic, or intermediate morphology, which secrete a monoclonal immunoglobulin M component. There is diffuse infiltration by the malignant cells of the bone marrow and also, in many cases, of the spleen, liver, or lymph nodes. The circulating macroglobulin can produce symptoms of hyperviscosity syndrome: weakness, fatigue, bleeding disorders, and visual disturbances. Peak incidence of macroglobulinemia is in the sixth and seventh decades of life. (Dorland, 28th ed)

The median age of diagnosis is approximately fourth and fifth decades. The disease often arises in the oral cavity, particularly in HIV disease, but other sites include nasal cavity, gastrointestinal tract, skin, bone soft tissue, and lung. There is usually immunodeficiency, such as HIV, organ transplants, autoimmune diseases

Like Burkitt's lymphoma, the morphology has a "starry sky". However, the immunophenotype resembles plasma cells: CD45-, CD20-, CD79a+/-, PAX5-, CD38+, CD38+ and MUM1+. Ki67 is over 90%. EBV is positive in 75%; HHV-8 is negative.

Causes of paraproteinemia include the following:

- Leukemias and lymphomas of various types, but usually B-cell Non-Hodgkin lymphomas with a plasma cell component.

- Myeloma

- Plasmacytoma

- Lymphoplasmacytic lymphoma

- Idiopathic (no discernible cause): some of these will be revealed as leukemias or lymphomas over the years.

- Monoclonal gammopathy of undetermined significance

- Primary AL amyloidosis (light chains only)

People with monoclonal gammopathy generally do not experience signs or symptoms. Some people may experience a rash or nerve problems, such as numbness or tingling. Severe renal disease has also been found in a subset of those with monoclonal gammopathy. MGUS is usually detected by chance when the patient has a blood test for another condition or as part of standard screening.

Gene expression profiling has revealed that diffuse large B-cell lymphoma (DLBCL) is composed of at least 3 different sub-groups, each having distinct oncogenic mechanisms that respond to therapies in different ways. Germinal Center B-Cell like (GCB) DLBCLs appear to arise from normal germinal center B cells, while Activated B-cell like (ABC) DLBCLs are thought to arise from postgerminal center B cells that are arrested during plasmacytic differentiation. The differences in gene expression between GCB DLBCL and ABC DLBCL are as vast as the differences between distinct types of leukemia, but these conditions have historically been grouped together and treated as the same disease.

Because many organs can be affected by myeloma, the symptoms and signs vary greatly. A mnemonic sometimes used to remember some of the common symptoms of multiple myeloma is CRAB: C = calcium (elevated), R = renal failure, A = anemia, B = bone lesions. Myeloma has many other possible symptoms, including opportunistic infections (e.g., pneumonia) and weight loss. CRAB symptoms and proliferation of monoclonal plasma cells in the bone marrow are part of the diagnostic criteria of multiple myeloma.

Monoclonal gammopathy of undetermined significance (MGUS, "unknown" or "uncertain" may be substituted for "undetermined"), formerly benign monoclonal gammopathy, is a condition in which an abnormal immunoglobin protein (known as a paraprotein) is found in the blood during standard laboratory blood tests. MGUS resembles multiple myeloma and similar diseases, but the levels of antibody are lower, the number of plasma cells (white blood cells that secrete antibodies) in the bone marrow is lower, and it has no symptoms or major problems. However, multiple myeloma develops at the rate of about 1.5% a year, so doctors recommend monitoring it yearly.

The progression from MGUS to multiple myeloma usually involves several steps. In rare cases, it may also be related with a slowly progressive symmetric distal sensorimotor neuropathy.

The most common clinical finding is hepatosplenomegaly. Pruritus, gout, and mucocutaneous bleeding are occasionally seen.

Tumors of the hematopoietic and lymphoid tissues or haematopoietic and lymphoid malignancies are tumors that affect the blood, bone marrow, lymph, and lymphatic system. As those elements are all intimately connected through both the circulatory system and the immune system, a disease affecting one will often affect the others as well, making myeloproliferation and lymphoproliferation (and thus the leukemias and the lymphomas) closely related and often overlapping problems.

While uncommon in solid tumors, chromosomal translocations are a common cause of these diseases. This commonly leads to a different approach in diagnosis and treatment of haematological malignancies.

Haematological malignancies are malignant neoplasms ("cancer"), and they are generally treated by specialists in hematology and/or oncology. In some centers "Haematology/oncology" is a single subspecialty of internal medicine while in others they are considered separate divisions (there are also surgical and radiation oncologists). Not all haematological disorders are malignant ("cancerous"); these other blood conditions may also be managed by a hematologist.

Hematological malignancies may derive from either of the two major blood cell lineages: myeloid and lymphoid cell lines. The myeloid cell line normally produces granulocytes, erythrocytes, thrombocytes, macrophages and mast cells; the lymphoid cell line produces B, T, NK and plasma cells. Lymphomas, lymphocytic leukemias, and myeloma are from the lymphoid line, while acute and chronic myelogenous leukemia, myelodysplastic syndromes and myeloproliferative diseases are myeloid in origin.

A subgroup of them are more severe and are known as haematological malignancies (American spelling hematological malignancies) or blood cancer. They may also be referred to as liquid tumors.

B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system by secreting antibodies. Additionally, B cells present antigen (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines.

In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ. (The "B" from B cells comes from the name of this organ, where it was first discovered by Chang and Glick, and not from bone marrow as commonly believed).

B cells, unlike the other two classes of lymphocytes, T cells and natural killer cells, express B cell receptors (BCRs) on their cell membrane. BCRs allow the B cell to bind a specific antigen, against which it will initiate an antibody response.

Multiple myeloma, also known as plasma cell myeloma, is a cancer of plasma cells, a type of white blood cell normally responsible for producing antibodies. Often, no symptoms are noticed initially. When advanced, bone pain, bleeding, frequent infections, and anemia may occur. Complications may include amyloidosis.

The cause is unknown. Risk factors include drinking alcohol, obesity, radiation exposure, family history, and certain chemicals. The underlying mechanism involves abnormal plasma cells producing abnormal antibodies which can cause kidney problems and overly thick blood. The plasma cells can also form a mass in the bone marrow or soft tissue. When only one mass is present, it is known as a plasmacytoma while more than one is known as multiple myeloma. 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. Another common finding is high blood calcium levels.

Multiple myeloma is considered treatable, but generally incurable. Remissions may be brought about with steroids, chemotherapy, thalidomide or lenalidomide, and stem cell transplant. Bisphosphonates and radiation therapy are sometimes used to reduce pain from bone lesions.

Globally, multiple myeloma affected 488,000 people and resulted in 101,100 deaths in 2015. In the United States, it develops in 6.5 per 100,000 people per year and 0.7% of people are affected at some point in their lives. It usually occurs around the age of 61 and is more common in men than women. Without treatment, typical survival is seven months. With current treatments, survival is usually 4–5 years. This gives a five-year survival rate around 49%. The word myeloma is from the Greek "myelo-" meaning "marrow" and "-oma" meaning "tumor".

Plasmacytoma is a plasma cell dyscrasia in which a plasma cell tumour grows within soft tissue or within the axial skeleton.

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

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

Paraproteinemia, also known as monoclonal gammopathy, is the presence of excessive amounts of paraprotein or single monoclonal gammaglobulin in the blood. It is usually due to an underlying immunoproliferative disorder or hematologic neoplasms, especially multiple myeloma. It is sometimes considered equivalent to plasma cell dyscrasia.