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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
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).
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 symptoms of AIDS-related lymphoma can include: weight loss, fever, and night sweats.
Individuals with this type of cancer experience almost no symptoms at all.
- Painless Lymphadenopathy
- Fatigue
- Weight loss
- Fevers
- Night sweat
Currently, Burkitt lymphoma can be divided into three main clinical variants: the endemic, the sporadic, and the immunodeficiency-associated variants.
- The endemic variant (also called "African variant") most commonly occurs in children living in malaria endemic regions of the world (e.g., equatorial Africa, Brazil, and Papua New Guinea). Epstein-Barr virus (EBV) infection is found in nearly all patients. Chronic malaria is believed to reduce resistance to EBV, allowing it to take hold. The disease characteristically involves the jaw or other facial bone, distal ileum, cecum, ovaries, kidney, or breast.
- The sporadic type of Burkitt lymphoma (also known as "non-African") is the most common variant found in places where malaria is not holoendemic. The tumor cells have a similar appearance to the cancer cells of classical endemic Burkitt lymphoma. Sporadic lymphomas are rarely associated with the Epstein–Barr virus. Non-Hodgkin lymphoma, which includes Burkitt's, accounts for 30–50% of childhood lymphoma. The jaw is less commonly involved, compared to the endemic variant. The ileocecal region is the common site of involvement.
- Immunodeficiency-associated Burkitt lymphoma is usually associated with HIV infection or occurs in the setting of post-transplant patients who are taking immunosuppressive drugs. Burkitt lymphoma can be one of the diseases associated with the initial manifestation of AIDS.
By morphology (i.e., microscopic appearance) or immunophenotype, it is almost impossible to differentiate these three clinical variants. Immunodeficiency-associated Burkitt lymphoma may demonstrate more plasmacytic appearance or more pleomorphism, but these features are not specific.
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).
Burkitt lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, a surgeon who first described the disease in 1958 while working in equatorial Africa.
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.
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
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.
Cats that develop lymphoma are much more likely to develop more severe symptoms than dogs. Whereas dogs often appear healthy initially except for swollen lymph nodes, cats will often be physically ill. The symptoms correspond closely to the location of the lymphoma. The most common sites for alimentary (gastrointestinal) lymphoma are, in decreasing frequency, the small intestine, the stomach, the junction of the ileum, cecum, and colon. Cats with the alimentary form of lymphoma often present with weight loss, rough hair coat, loss of appetite, vomiting and diarrhea, although vomiting and diarrhea are commonly absent as symptoms. The tumor can also cause life-threatening blockage of the intestine. Cats with the mediastinal form often have respiratory distress and fluid in the thoracic cavity. If lymphoma develops in the kidney, the cat may have increased water consumption and increased urination. Lymphoma of the kidney presents as bilateral kidney enlargement and failure. If the lymphoma is located in the nose, the cat may have discharge from the nose and facial swelling. Lymphoma of the heart causes congestive heart failure, pericardial effusion, and cardiac arrhythmias. Ocular lymphoma in cats often presents as anterior uveitis (inflammation of the inside of the eye). Cats who are also infected with FeLV often present with pale mucous membranes due to anemia. Anemia is a common problem in all cats with lymphoma, but hypercalcemia is rare.
Diagnosis is similar to dogs, except cats should be tested for FeLV and FIV. It is important to differentiate the alimentary form of lymphoma from inflammatory bowel disease because the signs are so similar in cats. A biopsy is necessary to do this. One approach to differentiate inflammatory bowel disease from is to test the infiltrating lymphocytes for their monoclonal origin in lymphomas.
"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).
MALT lymphoma (MALToma) is a form of lymphoma involving the mucosa-associated lymphoid tissue (MALT), frequently of the stomach, but virtually any mucosal site can be afflicted. It is a cancer originating from B cells in the marginal zone of the MALT, and is also called extranodal marginal zone B cell lymphoma.
Cutaneous lymphoma, also known as lymphoma cutis, is when lymphoma involves the skin. It is characterized by a proliferation of lymphoid tissue.
There are two main classes of lymphomas that affect the skin:
- Cutaneous T-cell lymphoma
- Cutaneous B-cell lymphoma
Initial symptoms can be nonspecific, particularly in children. Over 50% of children with leukemia had one or more of five features: a liver one can feel (64%), a spleen one can feel (61%), pale complexion (54%), fever (53%), and bruising (52%). Additionally, recurrent infections, feeling tired, arm or leg pain, and enlarged lymph nodes can be prominent features. The B symptoms, such as fever, night sweats, and weight loss, are often present as well.
Central nervous system (CNS) symptoms such cranial neuropathies due to meningeal infiltration are identified in less than 10% of adults and less than 5% of children, particularly mature B-cell ALL (Burkitt leukemia) at presentation.
The signs and symptoms of ALL are variable and include:
- Generalized weakness and feeling tired
- Anemia
- Dizziness
- Headache, vomiting, lethargy, nuchal rigidity, or cranial nerve palsies (CNS involvement)
- Frequent or unexplained fever and infection
- Weight loss and/or loss of appetite
- Excessive and unexplained bruising
- Bone pain, joint pain (caused by the spread of "blast" cells to the surface of the bone or into the joint from the marrow cavity)
- Breathlessness
- Enlarged lymph nodes, liver and/or spleen
- Pitting edema (swelling) in the lower limbs and/or abdomen
- Petechiae, which are tiny red spots or lines in the skin due to low platelet levels
- Testicular enlargement
- Mediastinal mass
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.
Historically, they have been most commonly divided by the stage of maturation at which the clonal (neoplastic) lymphoid population stopped maturing:
- Acute lymphoblastic leukemia
- Chronic lymphocytic leukemia
However, the influential WHO Classification (published in 2001) emphasized a greater emphasis on cell lineage. To this end, lymphoid leukemias can also be divided by the type of cells affected:
- B-cell leukemia
- T-cell leukemia
- NK-cell leukemia
The most common type of lymphoid leukemia is B-cell chronic lymphocytic leukemia.
A B-cell leukemia is any of several types of lymphoid leukemia which affect B cells.
Types include (with ICD-O code):
- 9823/3 - B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma
- 9826/3 - Acute lymphoblastic leukemia, mature B-cell type
- 9833/3 - B-cell prolymphocytic leukemia
- 9835/3-9836/3 - Precursor B lymphoblastic leukemia
- 9940/3 - Hairy cell leukemia
The most common symptoms in children are easy bruising, pale skin, fever, and an enlarged spleen or liver.
Damage to the bone marrow, by way of displacing the normal bone marrow cells with higher numbers of immature white blood cells, results in a lack of blood platelets, which are important in the blood clotting process. This means people with leukemia may easily become bruised, bleed excessively, or develop pinprick bleeds (petechiae).
White blood cells, which are involved in fighting pathogens, may be suppressed or dysfunctional. This could cause the patient's immune system to be unable to fight off a simple infection or to start attacking other body cells. Because leukemia prevents the immune system from working normally, some patients experience frequent infection, ranging from infected tonsils, sores in the mouth, or diarrhea to life-threatening pneumonia or opportunistic infections.
Finally, the red blood cell deficiency leads to anemia, which may cause dyspnea and .
Some patients experience other symptoms, such as feeling sick, having fevers, chills, night sweats, feeling fatigued and other flu-like symptoms. Some patients experience nausea or a feeling of fullness due to an enlarged liver and spleen; this can result in unintentional weight loss. Blasts affected by the disease may come together and become swollen in the liver or in the lymph nodes causing pain and leading to nausea.
If the leukemic cells invade the central nervous system, then neurological symptoms (notably headaches) can occur. Uncommon neurological symptoms like migraines, seizures, or coma can occur as a result of brain stem pressure. All symptoms associated with leukemia can be attributed to other diseases. Consequently, leukemia is always diagnosed through medical tests.
The word "leukemia", which means 'white blood', is derived from the characteristic high white blood cell count that presents in most afflicted patients before treatment. The high number of white blood cells are apparent when a blood sample is viewed under a microscope, with the extra white blood cells frequently being immature or dysfunctional. The excessive number of cells can also interfere with the level of other cells, causing further harmful imbalance in the blood count.
Some leukemia patients do not have high white blood cell counts visible during a regular blood count. This less-common condition is called "aleukemia". The bone marrow still contains cancerous white blood cells which disrupt the normal production of blood cells, but they remain in the marrow instead of entering the bloodstream, where they would be visible in a blood test. For an aleukemic patient, the white blood cell counts in the bloodstream can be normal or low. Aleukemia can occur in any of the four major types of leukemia, and is particularly common in hairy cell leukemia.
"T-cell leukemia" describes several different types of lymphoid leukemias which affect T cells.
The most common T-cell leukemia is precursor T-cell lymphoblastic leukemia. It causes 15% of acute leukemias in childhood, and also 40% of lymphomas in childhood. It is most common in adolescent males. Its morphology is identical to that of "precursor B-cell lymphoblastic leukemia". Cell markers include TdT, CD2, CD7. It often presents as a mediastinal mass because of involvement of the thymus. It is highly associated with NOTCH1 mutations.
Other types include:
- Large granular lymphocytic leukemia
- Adult T-cell leukemia/lymphoma
- T-cell prolymphocytic leukemia
In practice, it can be hard to distinguish T-cell leukemia from T-cell lymphoma, and they are often grouped together.
Clinically and pathologically, leukemia is subdivided into a variety of large groups. The first division is between its "acute" and "chronic" forms:
- Acute leukemia is characterized by a rapid increase in the number of immature blood cells. The crowding that results from such cells makes the bone marrow unable to produce healthy blood cells. Immediate treatment is required in acute leukemia because of the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. Acute forms of leukemia are the most common forms of leukemia in children.
- Chronic leukemia is characterized by the excessive buildup of relatively mature, but still abnormal, white blood cells. Typically taking months or years to progress, the cells are produced at a much higher rate than normal, resulting in many abnormal white blood cells. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy. Chronic leukemia mostly occurs in older people, but can occur in any age group.
Additionally, the diseases are subdivided according to which kind of blood cell is affected. This divides leukemias into lymphoblastic or "lymphocytic leukemias" and myeloid or "myelogenous leukemias":
- In lymphoblastic or lymphocytic leukemias, the cancerous change takes place in a type of marrow cell that normally goes on to form lymphocytes, which are infection-fighting immune system cells. Most lymphocytic leukemias involve a specific subtype of lymphocyte, the B cell.
- In myeloid or myelogenous leukemias, the cancerous change takes place in a type of marrow cell that normally goes on to form red blood cells, some other types of white cells, and platelets.
Combining these two classifications provides a total of four main categories. Within each of these main categories, there are typically several subcategories. Finally, some rarer types are usually considered to be outside of this classification scheme.
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.
T-cell leukemia describes several different types of lymphoid leukemia which affect T cells.
Types include:
- Large granular lymphocytic leukemia
- Adult T-cell leukemia/lymphoma
- T-cell prolymphocytic leukemia
In practice, it can be hard to distinguish T-cell leukemia from T-cell lymphoma, and they are often grouped together.
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.