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.

Most people are diagnosed without symptoms as the result of a routine blood test that shows a high white blood cell count. Less commonly, CLL may present with enlarged lymph nodes without a high white blood cell count or no evidence of the disease in the blood. This is referred to as small lymphocytic lymphoma. In some individuals, the disease comes to light only after the cancerous cells overwhelm the bone marrow resulting in anemia producing tiredness or weakness.

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)

Chronic lymphoid leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on there is typically no symptoms. Latter non-painful lymph nodes swelling, feeling tired, fever, or weight loss for no clear reason may occur. Enlargement of the spleen and anemia may also occur. It typically worsens gradually.

Risk factors include having a family history of the disease. Agent Orange and certain insecticides might also be a risk. CLL results in the build up of B cell lymphocytes in the bone marrow, lymph nodes, and blood. These cells do not function well and crowd out healthy blood cells. It is divided into two main types those with a mutated IGHV gene and those without. Diagnosis is typically based on blood tests finding high numbers of mature lymphocytes and smudge cells.

Management of early disease is generally with watchful waiting. Infections should more readily be treated with antibiotics. In those with significant symptoms chemotherapy or immunotherapy may be used. The medications fludarabine, cyclophosphamide, and rituximab are typically the initial treatment in those who are otherwise healthy.

CLL affected about 904,000 people globally in 2015 and resulted in 60,700 deaths. The disease most common occurs in people over the age of 50. Males are affected more often than females. It is much less common in people from Asia. Five-year survival following diagnosis is approximately 83% in the United States. It represents less than 1% of deaths from cancer.

The signs and symptoms of non-Hodgkin's lymphoma vary depending upon its location within the body. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and feeling tired. Other symptoms may include bone pain, chest pain, or itchiness. Some forms are slow growing while others are fast growing. Enlarged lymph nodes may cause lumps to be felt under the skin when they are close to the surface of the body. Lymphomas in the skin may also result in lumps, which are commonly itchy, red or purple. Lymphomas in the brain can cause weakness, seizures, problems with thinking and personality changes.

There are numerous kinds of lymphomas involving B cells. The most commonly used classification system is the WHO classification, a convergence of more than one, older classification systems.

The B-cell lymphomas are types of lymphoma affecting B cells. Lymphomas are "blood cancers" in the lymph nodes. They develop more frequently in older adults and in immunocompromised individuals.

B-cell lymphomas include both Hodgkin's lymphomas and most non-Hodgkin lymphomas. They are typically divided into low and high grade, typically corresponding to indolent (slow-growing) lymphomas and aggressive lymphomas, respectively. As a generalisation, indolent lymphomas respond to treatment and are kept under control (in remission) with long-term survival of many years, but are not cured. Aggressive lymphomas usually require intensive treatments, with some having a good prospect for a permanent cure.

Prognosis and treatment depends on the specific type of lymphoma as well as the stage and grade. Treatment includes radiation and chemotherapy. Early-stage indolent B-cell lymphomas can often be treated with radiation alone, with long-term non-recurrence. Early-stage aggressive disease is treated with chemotherapy and often radiation, with a 70-90% cure rate. Late-stage indolent lymphomas are sometimes left untreated and monitored until they progress. Late-stage aggressive disease is treated with chemotherapy, with cure rates of over 70%.

Splenic lymphoma with villous lymphocytes is a rare type of lymphoma that involves mature B cells. Older names include "lymphoma simulating hairy cell leukemia" and "lymphoplasmacytic lymphoma with circulating villous lymphocytes". Whether this condition is identical to splenic marginal zone lymphoma, or only highly similar, is a matter of debate.

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.

The many different forms of lymphoma probably have different causes. These possible causes and associations with at least some forms of NHL include the following:

- Infectious agents:

- Epstein-Barr virus: associated with Burkitt's lymphoma, Hodgkin's lymphoma, follicular dendritic cell sarcoma, extranodal NK-T-cell lymphoma

- Human T-cell leukemia virus: associated with adult T-cell lymphoma

- Helicobacter pylori: associated with gastric lymphoma

- HHV-8: associated with primary effusion lymphoma, multicentric Castleman disease

- Hepatitis C virus: associated with splenic marginal zone lymphoma, lymphoplasmacytic lymphoma and diffuse large B-cell lymphoma

- HIV infection

- Some chemicals, like polychlorinated biphenyls (PCBs), diphenylhydantoin, dioxin, and phenoxy herbicides.

- Medical treatments, like radiation therapy and chemotherapy

- Genetic diseases, like Klinefelter's syndrome, Chédiak-Higashi syndrome, ataxia telangiectasia syndrome

- Autoimmune diseases, like Sjögren’s syndrome, celiac disease, rheumatoid arthritis, and systemic lupus erythematosus.

Primary cutaneous immunocytoma is a skin condition that represents a low grade B-cell lymphoma related to marginal zone B-cell lymphoma but with a predominance of cells having plasmacytic features.

Bing–Neel syndrome (BNS) is an extremely rare neurologic complication of Waldenström macroglobulinemia (WM), which is a chronic lymphoproliferative disorder.

There's no clear definition of BNS but what is known so far is that unlike WM, It involves the central nervous system (CNS), infiltrated by differentiated malignant B cells and by having hyperglobulinemia. This infiltration increases blood viscosity, which impairs blood circulation through small blood vessels of the brain and the eye. Some scientists proposed that a person diagnosed with BNS is typically classified into Group A and Group B depending on whether or not plasma cells are present within the brain parenchyma, leptomeninges, dura, and/or the cerebral spinal fluid (CSF). Symptoms are diverse and nonspecific, and they can vary depending on which aspect of the CNS is being affected. Symptoms can include a range of severity of nausea and seizures. Since the symptoms vary, there are multiple treatment options to treat the symptoms for this non-curable disease. Although there is no specific set of diagnosis for BNS, different combinations of diagnostic tools are used to narrow down and conclude the presence of BNS.

Symptoms of BNS gradually progress over the span of a week or even a month, and there is typically a delay in diagnosis after the initial symptoms arise. Although BNS arises due to complications from WM, some individuals may experience symptoms of BNS without having a past history of WM.

Given that BNS is so rare, the symptoms are diverse and nonspecific. Symptoms range in severity from nausea to seizures and are characterized by how they interfere with the function of the CNS. Where certain symptoms are present depends on which branch of the CNS is being affected by plasma B-cells. People diagnosed with BNS experience some sensory symptoms as well. Some sensory symptoms include a pin and needles sensation experienced in the lower limbs, the hands, and in the arms, along with pain and extreme numbness.

Proliferating angioendotheliomatosis has historically been divided into two groups, (1) a reactive, involuting type and (2) a malignant, rapidly fatal type.

The reactive involuting type is uncommon and occurs in patients with various diseases including subacute bacterial endocarditis and end-stage atherosclerotic disease. Patients present with various skin lesions and rashes - mostly commonly on the thighs. Treatment aimed at the underlying condition hastens the resolution of the lesions.

The malignant type is an intravascular lymphoma, usually of the diffuse B-cell type. It progresses rapidly through involvement of multiple body systems and mortality occurs in less than a year from the initial diagnosis. The average age of patients newly diagnosed is 55 years. Currently the causative mechanism is unknown. In a few cases treatment with palliative chemotherapy has been effective.

Proliferating angioendotheliomatosis may be divided into the following types:

IgG4-related disease (IgG4-RD), formerly known as IgG4-related systemic disease, is a chronic inflammatory condition characterized by tissue infiltration with lymphocytes and IgG4-secreting plasma cells, various degrees of fibrosis (scarring) and a usually prompt response to oral steroids. In approximately 51–70% of people with this disease, "serum" IgG4 concentrations are elevated during an acute phase.

It is a relapsing–remitting disease associated with a tendency to mass forming, tissue-destructive lesions in multiple sites, with a characteristic histopathological appearance in whichever site is involved. Inflammation and the deposition of connective tissue in affected anatomical sites can lead to organ dysfunction, or even organ failure, if not treated.

Early detection is important to avoid organ damage and potentially serious complications. Treatment is recommended in all symptomatic cases of IgG4-RD and also in asymptomatic IgG4-RD involving certain anatomical sites.

IgG4-related disease has been described as an indolent condition. Although possibly based on opinion rather than on objective assessments, symptoms, if any, are commonly described as mild in the medical literature. This can be in spite of considerable underlying organ destruction. People are often described as being generally well at the time of diagnosis, although some may give a history of weight loss.

Pain is generally not a feature of the inflammation. However it may occur as a secondary effect, for example due to either obstruction or compression.

Often diagnosis is made due to the presence of painless swellings or mass lesions, or due to complications of masses, e.g. jaundice due to involvement of the pancreas, biliary tree or liver. Symptoms are commonly attributed to other conditions and other diagnoses may have been made years before diagnosis, e.g. urinary symptoms in men attributed to common prostate conditions. Lesions may also be detected incidentally on radiological images, but can be easily misdiagnosed as malignancies.

Reported cases do include some significant symptoms or findings however:

Autoimmune polyendocrine syndrome type 1 symptoms and signs include the following:

- Hypoparathyroidism

- Hypogonadism

- Vitiligo

- Alopecia

- Malabsorption

- Anemia

- Cataract

- Adrenal hyperplasia

Niemann–Pick type C has a wide clinical spectrum. Affected individuals may have enlargement of the spleen (splenomegaly) and liver (hepatomegaly), or enlarged spleen or liver combined (hepatosplenomegaly), but this finding may be absent in later onset cases. Prolonged jaundice or elevated bilirubin can present at birth. In some cases, however, enlargement of the spleen or liver does not occur for months or years – or not at all. Enlargement of the spleen or liver frequently becomes less apparent with time, in contrast to the progression of other lysosomal storage diseases such as Niemann–Pick disease, Types A and B or Gaucher disease. Organ enlargement does not usually cause major complications.

Progressive neurological disease is the hallmark of Niemann–Pick type C disease, and is responsible for disability and premature death in all cases beyond early childhood. Classically, children with NPC may initially present with delays in reaching normal developmental milestones skills before manifesting cognitive decline (dementia).

Neurological signs and symptoms include cerebellar ataxia (unsteady walking with uncoordinated limb movements), dysarthria (slurred speech), dysphagia (difficulty in swallowing), tremor, epilepsy (both partial and generalized), vertical supranuclear palsy (upgaze palsy, downgaze palsy, saccadic palsy or paralysis), sleep inversion, gelastic cataplexy (sudden loss of muscle tone or drop attacks), dystonia (abnormal movements or postures caused by contraction of agonist and antagonist muscles across joints), most commonly begins with in turning of one foot when walking (action dystonia) and may spread to become generalized, spasticity (velocity dependent increase in muscle tone), hypotonia, ptosis (drooping of the upper eyelid), microcephaly (abnormally small head), psychosis, progressive dementia, progressive hearing loss, bipolar disorder, major and psychotic depression that can include hallucinations, delusions, mutism, or stupor.

In the terminal stages of Niemann–Pick type C disease, the patient is bedridden, with complete ophthalmoplegia, loss of volitional movement and severe dementia.

Symptoms are related to the organs in which sphingomyelin accumulates. Enlargement of the liver and spleen (hepatosplenomegaly) may cause reduced appetite, abdominal distension, and pain. Enlargement of the spleen (splenomegaly) may also cause low levels of platelets in the blood (thrombocytopenia).

Accumulation of sphingomyelin in the central nervous system (including the cerebellum) results in unsteady gait (ataxia), slurring of speech (dysarthria), and difficulty in swallowing (dysphagia). Basal ganglia dysfunction causes abnormal posturing of the limbs, trunk, and face (dystonia). Upper brainstem disease results in impaired voluntary rapid eye movements (supranuclear gaze palsy). More widespread disease involving the cerebral cortex and subcortical structures causes gradual loss of intellectual abilities, causing dementia and seizures.

Bones also may be affected: symptoms may include enlarged bone marrow cavities, thinned cortical bone, or a distortion of the hip bone called coxa vara. Sleep-related disorders, such as sleep inversion, sleepiness during the day and wakefulness at night, may occur. Gelastic cataplexy, the sudden loss of muscle tone when the affected patient laughs, is also seen.

Niemann–Pick disease, SMPD1-associated refers to two different types of Niemann–Pick disease which are associated with the SMPD1 gene.

There are approximately 1,200 cases of NPA and NPB worldwide with the majority of cases being Type B or an intermediate form.

Descriptions of type E and type F have been published, but they are not well characterized, and are currently classified under type B.

Autoimmune polyendocrine syndrome type 1 (APS-1), also known as autoimmune polyendocrinopathy-candidiasis–ectodermal dystrophy/dysplasia (APECED), autoimmune polyglandular syndrome type 1, Whitaker syndrome, or candidiasis-hypoparathyroidism–Addison's disease syndrome, is a subtype of autoimmune polyendocrine syndrome (autoimmune polyglandular syndrome) in which multiple endocrine glands dysfunction as a result of autoimmunity. It is a genetic disorder inherited in autosomal recessive fashion due to a defect in the "AIRE" gene (autoimmune regulator), which is located on chromosome 21 and normally confers immune tolerance.

Autoimmune pancreatitis (AIP) is an increasingly recognized type of chronic pancreatitis that can be difficult to distinguish from pancreatic carcinoma but which responds to treatment with corticosteroids, particularly prednisone. There are two categories of AIP: Type 1 and Type 2, each with distinct clinical profiles.

Type 1 AIP is now regarded as a manifestation of IgG4-related disease, and those affected have tended to be older and to have a high relapse rate. Type 1 is associated with pancreatitis, Sjogren syndrome, Primary sclerosing cholangitis and Inflammatory bowel disease. Patients with Type 2 AIP do not experience relapse, tend to be younger and not associated with systemic disease. AIP occurring in association with an autoimmune disorder has been referred to as "secondary" or "syndromic" AIP. AIP does not affect long-term survival.

In type II hypersensitivity (also tissue-specific, or cytotoxic hypersensitivity) the antibodies produced by the immune response bind to antigens on the patient's own cell surfaces. The antigens recognized in this way may either be intrinsic ("self" antigen, innately part of the patient's cells) or extrinsic (adsorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen). These cells are recognized by macrophages or dendritic cells, which act as antigen-presenting cells. This causes a B cell response, wherein antibodies are produced against the foreign antigen.

An example of type II hypersensitivity is the ABO blood incompatibility where the red blood cells have different antigens, causing them to be recognized as different; B cell proliferation will take place and antibodies to the foreign blood type are produced. IgG and IgM antibodies bind to these antigens to form complexes that activate the classical pathway of complement activation to eliminate cells presenting foreign antigens. That is, mediators of acute inflammation are generated at the site and membrane attack complexes cause cell lysis and death. The reaction takes hours to a day.

Type II reactions can affect healthy cells. Examples include red blood cells in autoimmune hemolytic anemia and acetylcholine receptors in myasthenia gravis.

Another example of type II hypersensitivity reaction is Goodpasture's syndrome where the basement membrane (containing collagen type IV) in the lung and kidney is attacked by one's own antibodies.

Another form of type II hypersensitivity is called antibody-dependent cell-mediated cytotoxicity (ADCC). Here, cells exhibiting the foreign antigen are tagged with antibodies (IgG or IgM). These tagged cells are then recognised by natural killer cells (NK) and macrophages (recognised via IgG bound (via the Fc region) to the effector cell surface receptor, CD16 (FcγRIII)), which in turn kill these tagged cells.