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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.
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.
The symptoms of AIDS-related lymphoma can include: weight loss, fever, and night sweats.
Most individuals with non-gastric MALT have no symptoms
- Symptoms depend on where the cancer originates:
- Mass in the salivary gland
- Redness and sensitivity of the eye
- Mass in the thyroid
- Problems swallowing
- Cough
- Shortness of breath
- Fever
- Weight loss
- Red-brown discoloration of the skin
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%.
Individuals with this type of cancer experience almost no symptoms at all.
- Painless Lymphadenopathy
- Fatigue
- Weight loss
- Fevers
- Night sweat
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 spleen and liver are always involved, with bone marrow involvement frequently present. Nodal involvement is exceedingly rare.
The typical clinical finding in a patient with hepatosplenic T-cell lymphoma is hepatosplenomegaly.
The clinical presentation varies according to the type of ALCL. Two of the ALCL subtypes are systemic lymphomas, in that they usually present with enlarged lymph nodes in multiple regions of the body, or with tumors outside the lymph nodes (extranodal) such as bone, intestine, muscle, liver, or spleen. These 2 subtypes usually associate with weight loss, fevers and night sweats, and can be lethal if left untreated without chemotherapy. The third type of ALCL is so-called cutaneous ALCL, and is a tumor that presents in the skin as ulcers that may persist, or occasionally may involute spontaneously, and commonly recur. This type of ALCL usually manifests in different regions of the body and may extend to regional lymph nodes, i.e., an axillary lymph node if the ALCL presents in the arm.
A rare subtype of ALCL has been identified in a few women who have silicone breast implants (protheses) as a result of breast reconstruction after a diagnosis of breast cancer. The tumor initially manifests with swelling of the breast due to fluid accumulation around the implant. The disease may progress to invade the tissue surrounding the capsule, and if left untreated may progress to the axillary lymph nodes.
It typically presents at a late stage and is often associated with systemic symptoms ("B symptoms").
Symptoms of Richter’s transformation in a CLL patient include fever (without infection), an elevated serum levels of lactate dehydrogenase, and rapidly enlarging lymph nodes. While about 8% of all CLL patients will have elevated levels of serum lactate dehydrogenase (LDH), more than 50% of CLL patients with Richter's transformation will have elevated LDH levels.
Richter's can appear suddenly, even in patients who were in remission.
AIDS-related lymphoma describes lymphomas occurring in patients with acquired immunodeficiency syndrome (AIDS).
A lymphoma is a type of cancer arising from lymphoid cells. In AIDS, the incidences of non-Hodgkin's lymphoma, primary cerebral lymphoma and Hodgkin's disease are all increased. There are three different varieties of AIDS-related lymphoma: Diffuse large B-cell lymphoma, B-cell immunoblastic lymphoma, and Burkitt's lymphoma (small non-cleaved cell lymphoma).
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.
Hodgkin's lymphoma (HL) is a type of lymphoma, which is generally believed to result from white blood cells of the lymphocyte kind. Symptoms may include fever, night sweats, and weight loss. Often there will be non-painful enlarged lymph nodes in the neck, under the arm, or in the groin. Those affected may feel tired or be itchy.
About half of cases of Hodgkin's lymphoma are due to Epstein–Barr virus (EBV). Other risk factors include a family history of the condition and having HIV/AIDS. There are two major types of Hodgkin lymphoma: classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Diagnosis is by finding Hodgkin's cells such as multinucleated Reed–Sternberg cells (RS cells) in lymph nodes.
Hodgkin lymphoma may be treated with chemotherapy, radiation therapy, and stem cell transplant. The choice of treatment often depends on how advanced the cancer has become and whether or not it has favorable features. In early disease, a cure is often possible. The percentage of people who survive five years in the United States is 86%. For those under the age of 20, rates of survival are 97%. Radiation and some chemotherapy drugs, however, increase the risk of other cancers, heart disease, or lung disease over the subsequent decades.
In 2015 about 574,000 people had Hodgkin's lymphoma, and 23,900 died. In the United States, 0.2% of people are affected at some point in their life. The most common age of diagnosis is between 20 and 40 years old. It was named after the English physician Thomas Hodgkin, who first described the condition in 1832.
Richter's syndrome (RS), also known as Richter's transformation, is a transformation which occurs in about 5-10% of B cell chronic lymphocytic leukemia (CLL) and hairy cell leukemia into a fast-growing diffuse large B cell lymphoma, a variety of non-Hodgkin lymphoma which is refractory to treatment and carries a bad prognosis. There is also a less common variant in which the CLL changes into a Hodgkin's lymphoma. Rarely, transformations to a form of myeloid leukemia have been observed. These extraordinarily rare transformations carry a very poor prognosis.
Richter's transformation affects about 5% of CLL patients at some point during their lives.
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.
Extranodal NK/T-cell lymphoma, nasal type which was known as angiocentric lymphoma in the REAL classification, and also as nasal-type NK lymphoma, NK/T-cell lymphoma, and polymorphic/malignant midline reticulosis is a cutaneous condition which in Korea is reported to be the most common form of cutaneous lymphoma after mycosis fungoides.
Extranodal NK-T-cell lymphoma is a type of lymphoma.
It is called "extranodal" to emphasize that the location is typically not in the lymph node, and is sometimes further qualified as "nasal type". The nasal cavity, nasopharynx and upper aerodigestive tract are often involved, although extranasal presentations do occur (skin, gastrointestinal tract, eye, testis, lung, soft tissue). There is a strong association with Epstein–Barr virus.
The NCCN guidelines recommend either high-dose radiotherapy alone for stage I without high risk features, or concurrent chemoradiotherapy for stage I and II with either of two regimens. Asparaginase containing regimens have been used in advanced stage disease.
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.
Anaplastic large-cell lymphoma (ALCL) is a type of non-Hodgkin lymphoma involving aberrant T cells or null lymphocytes. It is described in detail in the "Classification of Tumours of the Haematopoietic and Lymphoid Tissues" edited by experts of the World Health Organisation (WHO). The term anaplastic large cell lymphoma (ALCL) encompasses at least 4 different clinical entities, all sharing the same name, and histologically have also in common the presence of large pleomorphic cells that express CD30 and T-cell markers. Two types of ALCL present as systemic disease and are considered as aggressive lymphomas, while two types present as localized disease and may progress locally.
Its name derives from anaplasia and large-cell lymphoma.
"MALT lymphoma" is an often multifocal disease in the organ of origin and is frequently macroscopically indistinguishable from other disease processes in the GI tract. Endoscopy is key to diagnosing "MALT lymphoma", with multiple biopsies of the visible lesions required, as well as samples of macroscopically normal tissue, termed gastric mapping. Histologically, there is expansion of the marginal zone compartment with development of sheets of neoplastic small lymphoid cells. The morphology of the neoplastic cells is variable with small mature lymphocytes, cells resembling centrocytes (centrocyte like cells), or marginal zone/monocytoid B cells. Plasmacytoid or plasmacytic differentiation is frequent. Lymphoid follicles are ubiquitous to "MALT lymphoma" but may be indistinct as they are often overrun or colonized by the neoplastic cells. Large transformed B cells are present scattered among the small cell population. If these large cells are present in clusters or sheets, a diagnosis of associated large B-cell lymphoma should be considered. A characteristic feature of MALT lymphoma is the presence of neoplastic cells within epithelial structures with associated destruction of the glandular architecture to form lymphoepithelial lesions.
"MALT lymphoma" may be difficult to distinguish from reactive infiltrates, and in some cases, multiple endoscopies are required before a confident diagnosis is reached. The Wotherspoon score, which grades the presence of histological features associated with "MALT lymphoma", is useful in expressing confidence in diagnosis at presentation.
Immunohistochemistry can be used to help distinguish "MALT lymphoma" from other small B-cell NHLs. B-cell-associated antigens such as CD19, CD20, CD22, and CD79a are usually expressed. In contrast to small lymphocytic lymphoma and MCL, staining for CD5 is usually negative, and these lymphomas can be further distinguished with CD23 (positive in small lymphocytic lymphoma) and CyclinD1 (positive in MCL).
This disease is typically found and diagnosed in peripheral blood, and while it can involve any organ, it is usually found in the spleen, liver, and bone marrow.
Very rarely, chloroma can occur without a known pre-existing or concomitant diagnosis of acute leukemia, acute promyleocytic leukemia or MDS/MPS; this is known as primary chloroma. Diagnosis is particularly challenging in this situation (see below). In almost all reported cases of primary chloroma, acute leukemia has developed shortly afterward (median time to development of acute leukemia 7 months, range 1–25 months). Therefore, primary chloroma could be considered an initial manifestation of acute leukemia, rather than a localized process, and could be treated as such. Where disease development or markers indicate progresses to acute promyleocytic leukemia (AML3) treatment should be tailored to this form of disease.
A myeloid sarcoma (chloroma, granulocytic sarcoma, extramedullary myeloid tumor), is a solid tumor composed of immature white blood cells called myeloblasts. A chloroma is an extramedullary manifestation of acute myeloid leukemia; in other words, it is a solid collection of leukemic cells occurring outside of the bone marrow.
ATL is usually a highly aggressive non-Hodgkin's lymphoma with no characteristic histologic appearance except for a diffuse pattern and a mature T-cell phenotype. Circulating lymphocytes with an irregular nuclear contour (leukemic cells) are frequently seen. Several lines of evidence suggest that HTLV-1 causes ATL. This evidence includes the frequent isolation of HTLV-1 from patients with this disease and the detection of HTLV-1 proviral genome in ATL leukemic cells. ATL is frequently accompanied by visceral involvement, hypercalcemia, skin lesions, and lytic bone lesions. Bone invasion and osteolysis, features of bone metastases, commonly occur in the setting of advanced solid tumors, such as breast, prostate, and lung cancers, but are less common in hematologic malignancies. However, patients with HTLV-1–induced ATL and multiple myeloma are predisposed to the development of tumor-induced osteolysis and hypercalcemia. One of the striking features of ATL and multiple myeloma induced bone disease is that the bone lesions are predominantly osteolytic with little associated osteoblastic activity. In patients with ATL, elevated serum levels of IL-1, TGFβ, PTHrP, macrophage inflammatory protein (MIP-1α), and receptor activator of nuclear factor-κB ligand (RANKL) have been associated with hypercalcemia. Immunodeficient mice that received implants with leukemic cells from patients with ATL or with HTLV-1–infected lymphocytes developed hypercalcemia and elevated serum levels of PTHrP. Most patients die within one year of diagnosis.
Infection with HTLV-1, like infection with other retroviruses, probably occurs for life and can be inferred when antibody against HTLV-1 is detected in the serum.