Lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes. The name typically refers to just the cancerous versions rather than all such tumors. Signs and symptoms may include enlarged lymph nodes, fever, drenching sweats, unintended weight loss, itching, and constantly feeling tired. The enlarged lymph nodes are usually painless. The sweats are most common at night.
Many subtypes of lymphomas are known. The two main categories of lymphomas are the non-Hodgkin lymphoma and Hodgkin lymphoma . Lymphomas, leukemias and myelomas are a part of the broader group of tumors of the hematopoietic and lymphoid tissues.
Risk factors for Hodgkin lymphoma include infection with Epstein–Barr virus and a history of the disease in the family. Risk factors for common types of non-Hodgkin lymphomas include autoimmune diseases, HIV/AIDS, infection with human T-lymphotropic virus, immunosuppressant medications, and some pesticides. Eating large amounts of red meat and tobacco smoking may also increase the risk. Diagnosis, if enlarged lymph nodes are present, is usually by lymph node biopsy. Blood, urine, and bone marrow testing may also be useful in the diagnosis. Medical imaging may then be done to determine if and where the cancer has spread. Lymphoma most often spreads to the lungs, liver, and brain.
Treatment may involve one or more of the following: chemotherapy, radiation therapy, proton therapy, targeted therapy, and surgery. In some non-Hodgkin lymphomas, an increased amount of protein produced by the lymphoma cells causes the blood to become so thick that plasmapheresis is performed to remove the protein. Watchful waiting may be appropriate for certain types. The outcome depends on the subtype, with some being curable and treatment prolonging survival in most. The five-year survival rate in the United States for all Hodgkin lymphoma subtypes is 89%, while that for non-Hodgkin lymphomas is 74%. Worldwide, lymphomas developed in 566,000 people in 2012 and caused 305,000 deaths. They make up 3–4% of all cancers, making them as a group the seventh-most-common form. In children, they are the third-most-common cancer. They occur more often in the developed world than in the developing world.
Signs and symptoms
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. It is generally painless.
- B symptoms – can be associated with both Hodgkin lymphoma and non-Hodgkin lymphoma. They consist of:
- * Fever
- * Night sweats
- * Weight loss
- Other symptoms:
- * Anemia, bleeding, increased susceptibility to infections
- * Loss of appetite or anorexia
- * Fatigue
- * Respiratory distress or dyspnea
- * Itching
Diagnosis
- Immunophenotyping
- Flow cytometry
- Fluorescence in situ hybridization testing
Classification
Lymphoma can also spread to the central nervous system, often around the brain in the meninges, known as lymphomatous meningitis.
Hodgkin lymphoma
Hodgkin lymphoma accounts for about 15% of lymphomas. It differs from other forms of lymphomas in its prognosis and several pathological characteristics. A division into Hodgkin and non-Hodgkin lymphomas is used in several of the older classification systems. A Hodgkin lymphoma is marked by the presence of a type of cell called the Reed–Sternberg cell.Non-Hodgkin lymphomas
s, which are defined as being all lymphomas except Hodgkin lymphoma, are more common than Hodgkin lymphoma. A wide variety of lymphomas are in this class, and the causes, the types of cells involved, and the prognoses vary by type. The number of cases per year of non-Hodgkin lymphoma increases with age. It is further divided into several subtypes.Epstein–Barr virus-associated lymphoproliferative diseases
are a group of benign, premalignant, and malignant diseases of lymphoid cells in which one or more of these cell types is infected with the Epstein–Barr virus. The virus may be responsible for the development and/or progression of these diseases. In addition to EBV-positive Hodgkin lymphomas, the World Health Organization includes the following lymphomas, when associated with EBV infection, in this group of diseases: Burkitt lymphoma; large B cell lymphoma, not otherwise specified; diffuse large B cell lymphoma associated with chronic inflammation; fibrin-associated diffuse large B cell lymphoma; primary effusion lymphoma; plasmablastic lymphoma; extranodal NK/T cell lymphoma, nasal type; peripheral T cell lymphoma, not otherwise specified; angioimmunoblastic T-cell lymphoma; follicular T cell lymphoma; and systemic T cell lymphoma of childhood.WHO classification
The WHO classification, published in 2001 and updated in 2008, 2017, and 2022, is based upon the foundations laid within the "revised European–American lymphoma classification". This system groups lymphomas by cell type and defining phenotypic, molecular, or cytogenetic characteristics. The five groups are shown in the table. Hodgkin lymphoma is considered separately within the WHO and preceding classifications, although it is recognized as being a tumor, albeit markedly abnormal, of lymphocytes of mature B cell lineage.Of the many forms of lymphoma, some are categorized as indolent, compatible with a long life even without treatment, whereas other forms are aggressive, causing rapid deterioration and death. However, most of the aggressive lymphomas respond well to treatment and are curable. The prognosis, therefore, depends on the correct diagnosis and classification of the disease, which is established after examination of a biopsy by a pathologist.
Lymphoma subtypes
- B-cell chronic lymphocytic leukemia/small cell lymphoma
- B-cell prolymphocytic leukemia
- Lymphoplasmacytic lymphoma
- Splenic marginal zone lymphoma
- Hairy cell leukemia
- Plasma cell neoplasms:
- * Plasma cell myeloma
- * Plasmacytoma
- * Monoclonal immunoglobulin deposition diseases
- * Heavy chain diseases
- Extranodal marginal zone B cell lymphoma, also called MALT lymphoma
- Nodal marginal zone B cell lymphoma
- Follicular lymphoma
- Primary cutaneous follicle center lymphoma
- Mantle cell lymphoma
- Diffuse large B-cell lymphoma, not otherwise specified
- Diffuse large B-cell lymphoma associated with chronic inflammation
- Epstein–Barr virus positive diffuse large B-cell lymphoma, not otherwise specified
- Lymphomatoid granulomatosis
- Primary mediastinal large B-cell lymphoma
- Intravascular large B-cell lymphoma
- ALK+ large B-cell lymphoma
- Plasmablastic lymphoma
- Primary effusion lymphoma
- Large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease
- Burkitt lymphoma/leukemia
- T-cell prolymphocytic leukemia
- T-cell large granular lymphocyte leukemia
- Aggressive NK cell leukemia
- Adult T-cell leukemia/lymphoma
- Extranodal NK/T-cell lymphoma, nasal type
- Enteropathy-associated T-cell lymphoma
- Hepatosplenic T-cell lymphoma
- Blastic NK cell lymphoma
- Mycosis fungoides/Sézary syndrome
- Primary cutaneous CD30-positive T-cell lymphoproliferative disorders
- * Primary cutaneous anaplastic large cell lymphoma
- * Lymphomatoid papulosis
- Peripheral T-cell lymphoma not otherwise specified
- Angioimmunoblastic T-cell lymphoma
- Anaplastic large cell lymphoma: ALK-positive and ALK-negative types
- Breast plant-associated anaplastic large cell lymphoma
- B-lymphoblastic leukemia/lymphoma not otherwise specified
- B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities
- T-lymphoblastic leukemia/lymphoma
- Classical Hodgkin lymphomas:
- * Nodular sclerosis form of Hodgkin lymphoma
- * Mixed cellularity Hodgkin lymphoma
- * Lymphocyte-rich
- * Lymphocyte depleted or not depleted
- Nodular lymphocyte-predominant Hodgkin lymphoma
- Associated with a primary immune disorder
- Associated with the human immunodeficiency virus
- Post-transplant
- Associated with methotrexate therapy
- Primary central nervous system lymphoma occurs most often in immunocompromised patients, in particular those with AIDS, but it can occur in the immunocompetent, as well. It has a poor prognosis, particularly in those with AIDS. Treatment can consist of corticosteroids, radiotherapy, and chemotherapy, often with methotrexate.
Previous classifications
Several previous classifications have been used, including Rappaport 1956, Lennert/Kiel 1974, BNLI, Working formulation, and REAL.The Working Formulation of 1982 was a classification of non-Hodgkin lymphoma. It excluded the Hodgkin lymphomas and divided the remaining lymphomas into four grades related to prognosis, with some further subdivisions based on the size and shape of affected cells. This purely histological classification included no information about cell surface markers or genetics and made no distinction between T-cell lymphomas and B-cell lymphomas. It was widely accepted at the time of its publication but by 2004 was obsolete.
In 1994, the Revised European-American Lymphoma classification applied immunophenotypic and genetic features in identifying distinct clinicopathologic entities among all the lymphomas except Hodgkin lymphoma. For coding purposes, the ICD-O and ICD-10 are available.