Diffuse large B-cell lymphoma encompasses a biologically and clinically diverse set of diseases, many of which cannot be separated from one another by well-defined and widely accepted criteria. The World Health Organization (WHO) classification system defines more than a dozen subtypes, each of which can be differentiated based on the location of the tumor, the presence of other cells within the tumor (such as T cells), and whether the patient has certain other illnesses related to DLBCL. One of these well-defined groupings of particular note is "primary mediastinal (thymic) large B cell lymphoma", which arises within the thymus or mediastinal lymph nodes.

In some cases, a tumor may share many features with both DLBCL and Burkitt's lymphoma. In these situations, the tumor is classified as simply “B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma”. A similar situation can arise between DLBCL and Hodgkin's lymphoma; the tumor is then classified as “B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Hodgkin’s lymphoma”.

When a case of DLBCL does not conform to any of these subtypes, and is also not considered unclassifiable, then it is classified as “diffuse large B-cell lymphoma, not otherwise specified” (DLBCL, NOS). The majority of DLBCL cases fall into this category. Much research has been devoted to separating this still-heterogeneous group; such distinctions are usually made along lines of cellular morphology, gene expression, and immunohistochemical properties.

General signs and symptoms include depression, fever, weight loss, loss of appetite, loss of hair or fur and vomiting. Lymphoma is the most common cancerous cause of hypercalcemia (high blood calcium levels) in dogs. It can lead to the above signs and symptoms plus increased water drinking, increased urination, and cardiac arrhythmias. Hypercalcemia in these cases is caused by secretion of parathyroid hormone-related protein.

Multicentric lymphoma presents as painless enlargement of the peripheral lymph nodes. This is seen in areas such as under the jaw, the armpits, the groin, and behind the knees. Enlargement of the liver and spleen causes the abdomen to distend. Mediastinal lymphoma can cause fluid to collect around the lungs, leading to coughing and difficulty breathing. Hypercalcemia is most commonly associated with this type.

Gastrointestinal lymphoma causes vomiting, diarrhea, and melena (digested blood in the stool). Low serum albumin levels and hypercalcemia can also occur.

Lymphoma of the skin is an uncommon occurrence. The epitheliotropic form typically appears as itchy inflammation of the skin progressing to nodules and plaques.

The non-epitheliotropic form can have a wide variety of appearances, from a single lump to large areas of bruised, ulcerated, hairless skin. The epitheliotropic form must be differentiated from similar appearing conditions such as pemphigus vulgaris, bullous pemphigoid, and lupus erythematosus.

Signs for lymphoma in other sites depend on the location. Central nervous system involvement can cause seizures or paralysis. Eye involvement, seen in 20 to 25 percent of cases, can lead to glaucoma, uveitis, bleeding within the eye, retinal detachment, and blindness. Lymphoma in the bone marrow causes anemia, low platelet count, and low white blood cell count.

The cancer is classified into low and high grade types. Classification is also based on location. The four location types are multicentric, mediastinal, gastrointestinal, and extranodal (involving the kidney, central nervous system, skin, heart, or eye). Multicentric lymphoma, the most common type (by greater than 80 percent), is found in the lymph nodes, with or without involvement in the liver, spleen, or bone marrow. Mediastinal lymphoma occurs in the lymph nodes in the thorax and possibly the thymus. Gastrointestinal lymphoma occurs as either a solitary tumor or diffuse invasion of the stomach or intestines, with or without involvement in the surrounding lymph nodes, liver or spleen. Classification is further based on involvement of B-lymphocytes or T-lymphocytes. Approximately 70 percent are B-cell lymphoma. Cutaneous lymphoma can be classified as epitheliotropic (closely conforming to the epidermis) or non-epitheliotropic. The epitheliotropic form is typically of T-cell origin and is also called mycosis fungoides. The non-epitheliotropic form is typically of B-cell origin.

Diffuse large B-cell lymphoma (DLBCL or DLBL) is a cancer of B cells, a type of white blood cell responsible for producing antibodies. It is the most common type of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,000 people per year in the USA and the UK. This cancer occurs primarily in older individuals, with a median age of diagnosis at approximately 70 years of age, though it can also occur in children and young adults in rare cases. DLBCL is an aggressive tumor which can arise in virtually any part of the body, and the first sign of this illness is typically the observation of a rapidly growing mass, sometimes associated with B symptoms—fever, weight loss, and night sweats.

The causes of diffuse large B-cell lymphoma are not well understood. Usually DLBCL arises from normal B cells, but it can also represent a malignant transformation of other types of lymphoma or leukemia. An underlying immunodeficiency is a significant risk factor. Infection with Epstein–Barr virus has also been found to contribute to the development of some subgroups of DLBCL.

Diagnosis of DLBCL is made by removing a portion of the tumor through a biopsy, and then examining this tissue using a microscope. Usually a hematopathologist makes this diagnosis. Several subtypes of DLBCL have been identified, each having a different clinical presentation and prognosis. However, the usual treatment for each of these is chemotherapy, often in combination with an antibody targeted at the tumor cells. Through these treatments, more than half of patients with DLBCL can be cured, and the overall five-year survival rate for older adults is around 58%.

Follicular lymphoma is a type of blood cancer. It is the most common of the indolent (slow-growing) non-Hodgkin's lymphomas, and the second-most-common form of non-Hodgkin's lymphomas overall. It is defined as a lymphoma of follicle center B-cells (centrocytes and centroblasts), which has at least a partially follicular pattern. It is positive for the B-cell markers CD10, CD19, CD22, and usually CD20, but almost always negative for CD5.

There are several synonymous and obsolete terms for this disease, such as CB/CC lymphoma (Centroblastic and Centrocytic lymphoma), nodular lymphoma and Brill-Symmers Disease.

Lymphoma may present with certain nonspecific symptoms; if the symptoms are persistent, an evaluation to determine their cause, including possible lymphoma, should be undertaken.

- Lymphadenopathy or swelling of lymph nodes, is the primary presentation in lymphoma.

- B symptoms (systemic symptoms) – can be associated with both Hodgkin lymphoma and non-Hodgkin lymphoma. They consist of:

- Fever

- Night sweats

- Weight loss

- Other symptoms:

- Loss of appetite or anorexia

- Fatigue

- Respiratory distress or dyspnea

- Itching

At diagnosis, patients typically are in their 60s and present to their physician with advanced disease. About half have either fever, night sweats, or unexplained weight loss (over 10% of body weight). Enlarged lymph nodes (for example, a "bump" on the neck, armpits or groin) or splenomegaly are usually present. Bone marrow, liver and GI tract involvement occurs relatively early in the course of the disease.

Patients usually present with constitutional symptoms (malaise, weight loss, fatigue), and hepatosplenomegaly is commonly found on physical exam. Lymphadenopathy is also found to a lesser extent. Due to the aggressive nature of the disease, patients may initially present at a more advanced stage, with coagulopathies, hemophagocytic syndrome, and multi-organ failure.

Patients with Hodgkin's lymphoma may present with the following symptoms:

- Lymph nodes: the most common symptom of Hodgkin's is the painless enlargement of one or more lymph nodes, or lymphadenopathy. The nodes may also feel rubbery and swollen when examined. The nodes of the neck and shoulders (cervical and supraclavicular) are most frequently involved (80–90% of the time, on average). The lymph nodes of the chest are often affected, and these may be noticed on a chest radiograph.

- Itchy skin

- Night sweats

- Unexplained weight loss

- Splenomegaly: enlargement of the spleen occurs in about 30% of people with Hodgkin's lymphoma. The enlargement, however, is seldom massive, and the size of the spleen may fluctuate during the course of treatment.

- Hepatomegaly: enlargement of the liver, due to liver involvement, is present in about 5% of cases.

- Hepatosplenomegaly: the enlargement of both the liver and spleen caused by the same disease.

- Pain following alcohol consumption: classically, involved nodes are painful after alcohol consumption, though this phenomenon is very uncommon, occurring in only two to three percent of people with Hodgkin's lymphoma, thus having a low sensitivity. On the other hand, its positive predictive value is high enough for it to be regarded as a pathognomonic sign of Hodgkin lymphoma. The pain typically has an onset within minutes after ingesting alcohol, and is usually felt as coming from the vicinity where there is an involved lymph node. The pain has been described as either sharp and stabbing or dull and aching.

- Back pain: nonspecific back pain (pain that cannot be localised or its cause determined by examination or scanning techniques) has been reported in some cases of Hodgkin's lymphoma. The lower back is most often affected.

- Red-coloured patches on the skin, easy bleeding and petechiae due to low platelet count (as a result of bone marrow infiltration, increased trapping in the spleen etc.—i.e. decreased production, increased removal)

- Systemic symptoms: about one-third of patients with Hodgkin's disease may also present with systemic symptoms, including low-grade fever; night sweats; unexplained weight loss of at least 10% of the patient's total body mass in six months or less, itchy skin (pruritus) due to increased levels of eosinophils in the bloodstream; or fatigue (lassitude). Systemic symptoms such as fever, night sweats, and weight loss are known as B symptoms; thus, presence of fever, weight loss, and night sweats indicate that the patient's stage is, for example, 2B instead of 2A.

- Cyclical fever: patients may also present with a cyclical high-grade fever known as the Pel-Ebstein fever, or more simply "P-E fever". However, there is debate as to whether the P-E fever truly exists.

- Nephrotic syndrome can occur in individuals with Hodgkin's lymphoma and is most commonly caused by minimal change disease.

A primary CNS lymphoma usually presents with seizure, headache, cranial nerve findings, altered mental status, or other focal neurological deficits typical of a mass effect. Systemic symptoms may include fever, night sweats, or weight loss.Other symptoms include

- diplopia

- dysphagia

- vertigo

- monocular vision loss

- progressive dementia or stupor in patients with a nonfocal neurologic exam and minimal abnormalities on MRI (more common in AIDS patients)

- facial hypoesthesia

The symptoms of AIDS-related lymphoma can include: weight loss, fever, and night sweats.

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.

Diagnosis usually occurs at an early stage of disease progression.

Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma (NHL), comprising about 6% of NHL cases. There are only about 15,000 patients presently in the U.S.

MCL is a subtype of B-cell lymphoma, due to CD5 positive antigen-naive pregerminal center B-cell within the mantle zone that surrounds normal germinal center follicles. MCL cells generally over-express cyclin D1 due to a t(11:14) chromosomal translocation in the DNA. Specifically, the translocation is at t(11;14)(q13;q32).

Ann Arbor staging is used to classify tumors and symptoms. Stage IV disease is very rare.

Follicular dendritic cells are localized in germinal centers of lymphoid follicles and have an integral role in regulation of the germinal center reaction and present antigens to B cells. Most cases of FDCS develop in the lymph nodes, but about 30% develop in extranodal sites. In 1998 the largest study on the disease was a retrospective review with fifty-one patients. Of these fifty-one patients, no conclusive pattern was found in regard to age, sex, race or presentation. The median patient age was 41 (range 14–76), and while most cases presented with cervical and axillary lymphadenopathy, 17 presented in extranodal sites including the liver, spleen, bowel and pancrease. With such a range of patient histories no definitive cause has been linked to FDCS. There has, however, been some evidence that previous exposure to the Epstein Barr Virus (EBV) or diagnosis of Castleman's disease can increase the risk of developing FDCS—medical literature in 2000 reported approximately 12% of all cases of FDC tumors are associated with EBV, with variance in different organs, but the role of EBV remains unclear in FDC tumor pathogenesis; and EBV does not appear to play a role in the transformation process of Castleman's disease to FDC sarcoma because all cases the report found associated with Castleman's disease were EBV negative.

Symptoms of FDCS vary, and are largely dependent on the part of the body the tumor develops. The most common symptom is painless swelling in lymph nodes. This symptom alone, however, is nonconclusive as it is associated with many other diseases including the common cold. Other symptoms include cough, sore throat, difficulty swallowing, weight loss and tiredness. In cases that present in extranodal sites outside of the head and neck region, organ specific symptoms are observed.

Intravascular large B-cell lymphoma (ILBCL), also referred to as angiotropic large-cell lymphoma, angiotropic large-cell lymphoma, intralymphatic lymphomatosis, intravascular lymphomatosis, and, less specifically, intravascular lymphoma and malignant angioendotheliomatosis is a rare form of lymphoma.

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%.

The majority of thyroid lymphomas are non–Hodgkin's B-cell lymphomas; the rest exhibit properties of T-cell lymphomas .

- Diffuse large B-cell lymphoma with marginal zone

- Diffuse large B-cell lymphoma without marginal zone

- Marginal zone В-cell lymphoma of mucosa-associated lymphoid tissue (MALT)

- Follicular lymphoma

According to the WHO criteria, the disease is morphologically graded into:

- grade 1 (<5 centroblasts per high-power field (hpf))

- grade 2 (6–15 centroblasts/hpf)

- grade 3 (>15 centroblasts/hpf).

Grade 3 is further subdivided into:

- grade 3A (centrocytes still present)

- grade 3B (the follicles consist almost entirely of centroblasts)

The WHO 2008 update classifies grades 1 and 2 now as low grade follicular lymphoma, grade 3A as high grade follicular lymphoma, and grade 3B as Diffuse Large B Cell Lymphoma (DLBCL).

Lymphomas in the strict sense are any neoplasms of the lymphatic tissues ("" + "") . The main classes are malignant neoplasms (that is, cancers) of the lymphocytes, a type of white blood cell that belongs to both the lymph and the blood and pervades both. Thus, lymphomas and leukemias are both tumors of the hematopoietic and lymphoid tissues, and as lymphoproliferative disorders, lymphomas and lymphoid leukemias are closely related, to the point that some of them are unitary disease entities that can be called by either name (for example, adult T-cell leukemia/lymphoma).

Several classification systems have existed for lymphoma, which use histological and other findings to divide lymphoma into different categories. The classification of a lymphoma can affect treatment and prognosis. Classification systems generally classify lymphoma according to:

- Whether or not it is a Hodgkin lymphoma

- Whether the cell that is replicating is a T cell or B cell

- The site from which the cell arises

Lymphoma can also spread to the central nervous system, often around the brain in the meninges, known as lymphomatous meningitis (LM).

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.

As other thyroid lesions, thyroid lymphoma affects predominantly females over 70 years of age with a history of Hashimoto's thyroiditis. Thus, Hashimoto's thyroiditis is considering as risk factor for thyroid lymphoma development.

The thyroid lymphoma manifests as rapidly enlarging neck mass causing respiratory difficulty. On physical examination, patients usually exhibit a firm thyroid and lymphadenopathy.

A primary central nervous system lymphoma (PCNSL), also known as microglioma and primary brain lymphoma, is a primary intracranial tumor appearing mostly in patients with severe immunodeficiency (typically patients with AIDS). PCNSLs represent around 20% of all cases of lymphomas in HIV infections (other types are Burkitt's lymphomas and immunoblastic lymphomas). Primary CNS lymphoma is highly associated with Epstein-Barr virus (EBV) infection (> 90%) in immunodeficient patients (such as those with AIDS and those immunosuppressed), and does not have a predilection for any particular age group. Mean CD4+ count at time of diagnosis is ~50/uL. In immunocompromised patients, prognosis is usually poor. In immunocompetent patients (that is, patients who do not have AIDS or some other immunodeficiency), there is rarely an association with EBV infection or other DNA viruses. In the immunocompetent population, PCNSLs typically appear in older patients in their 50's and 60's. Importantly, the incidence of PCNSL in the immunocompetent population has been reported to have increased more than 10-fold from 2.5 cases to 30 cases per 10 million population. The cause for the increase in incidence of this disease in the immunocompetent population is unknown.

Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), is a subtype of peripheral T-cell lymphoma. Peripheral T-cell lymphoma (PTCL) is defined as a diverse group of aggressive lymphomas that develop from mature-stage white blood cells called T-cells and natural killer cells (NK cells) (see figure for an overview of PTCL subtypes). PTCL is a type of non-Hodgkin's lymphoma (NHL). NHL affects two particular types of white blood cells: B-cells and T-cells. PTCL specifically affects T-cells, and results when T-cells develop and grow abnormally.

PTCL-NOS, the most common subtype of PTCL, is aggressive and predominantly nodal. There are two morphologic variants: the T-zone lymphoma variant and the lymphoepithelioid cell variant.

- T-zone lymphoma is so named for its involvement in a specific area of the lymph node that consists of a dense accumulation of T-cells.

- Lympho-epithelioid lymphoma, also called Lennert's lymphoma, is rare and generally affects older individuals.