Draft:Colon lymphoma

Colon lymphomas are a rare gastrointestinal track tumor and are often referred to as colorectal cancer (CRC). They have also been identified has colorectal cancers (CRC)Lymphomas are a group of blood cancers that develop from lymphocytes (a type of white blood cell). The name often refers to just the cancerous versions rather than all such tumors.

There are many subtypes of lymphomas. The two main categories of lymphomas are Hodgkin's lymphomas (HL) and the non-Hodgkin lymphomas (NHL). The World Health Organization (WHO) includes two other categories as types of lymphoma: multiple myeloma and immunoproliferative diseases. About 90% of lymphomas are non-Hodgkin lymphomas. Lymphomas and leukemias are a part of the broader group of tumors of the hematopoietic and lymphoid tissues. Colon lymphomas are most commonly classified as a non-Hodgkin lymphoma.

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, 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 85%, while that for non-Hodgkin lymphomas is 69%. 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 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.
 * B symptoms (systemic symptoms) – can be associated with both Hodgkin lymphoma and non-Hodgkin lymphoma. They consist of:
 * Fever
 * Night sweats
 * Weight loss
 * Abdominal pain and cramps
 * Rectal bleeding
 * Malabsorption
 * Severe constipation or bowel obstruction
 * Other symptoms:
 * irritability
 * anxiety
 * depression
 * fatigue
 * insomnia

Causes
Lymphoma develops due to overly activated lymphocytes (white blood cells). The over activated cells are caused by DNA mutations. These mutations cause the cells to constantly growing and multiplying by bypassing programmed cell death called, apoptosis. Unfortunately, there is not one main cause that leads to someone developing colon lymphoma but there are many risk factors involved. Patients with the following risk factors should take extra precautions and speak with a doctor about a colonoscopy or stool test for early detection.

Risk factors:


 * Age, Sex, and Race
 * most commonly found in men
 * someone over 50
 * African Americans
 * Jewish decent
 * Genetics
 * someone with a family history of colon cancer and cancers in general
 * inherited: hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis. Both only account for 5% of colon cancers.
 * Immune System Problems
 * someone who has a personal history of polyps and inflammatory intestinal disease like ulcerative colitis, IBS, and Crohn's
 * HIV patients decreases their ability to fight off cancer because of the CD4 levels being low
 * Previous Cancers
 * seen in someones family history or the patient themself
 * Other Risks
 * over use of tobacco and alcohol, obesity, and being physically inactive

Mechanism & Pathophysiology
Colorectal lymphomas develop from chromosomal instability, micro-satellite instability, and CpG island methylator phenotype. The chromosomal instability is most often seen due to mutations in the cells controlling tumor suppression within the cell cycle. Both micro-satellite and phenotype instability are seen due to impaired DNA repair mechanisms.

Micro-satellite instability (MSI) is a key biomarker in patients with T-cell colon lymphomas. Micro-satellite instability is when DNA sequences become damaged and unstable due to inactivation of genes. These instabilities will cause the DNA sequences to become mismatched thus deleted or inserted incorrectly. There are repair mechanisms in place to correct these mutations. MSIs have been seen more commonly in patients with a hereditary cancer known as Lynch Syndrome. Lynch syndrome have mutations in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2.

Chromosomal instability is the most common and seen in 85% of colorectal cancers. Chromosomal instability is mostly seen as aneuploidy or polyploidy. Oncogenesis has been researched as a mechanism for colorectal lymphomas but the exact mechanism that causes this genomic instability has not been completely understood.

CpG island methylator phenotype (CIMP) is caused by hypermethylation, genetic control that is imperative for gene inactivation in cancer cells. The mechanism for CIMPs is unknown but researchers believe it to be heterogeneous. Some studies have shown that DNA methyltransferases are being over-expressed in some CIMPs but there has not been enough cases to represent this information accurately. One idea that researchers are looking into is the aging process and how it affects tumor suppressor genes. Currently, CIMPs are being used as a screening mechanism for colorectal cancers.

Diagnosis


Lymphoma is definitively diagnosed by a lymph node biopsy, meaning a partial or total excision of a lymph node examined under the microscope. This examination reveals histopathological features that may indicate lymphoma. After lymphoma is diagnosed, a variety of tests may be carried out to look for specific features characteristic of different types of lymphoma. These include:
 * Immunophenotyping
 * Flow cytometry
 * Fluorescence in situ hybridization testing
 * Blooding and imaging testing

There are several colorectal screening test that can be performed to come to a better diagnosis. For example: stool test to look for bloody stool, colonoscopy to look for polyps within the large intestine, and fecal DNA testing to look at genetic mutations within the stool.

Classification


Lymphomas in the strict sense are any neoplasms of the lymphatic tissues (lympho- + -oma). 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).

Hodgkin lymphoma
Hodgkin lymphoma accounts for about 15% of lymphomas. It differs from other forms of lymphoma 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
Non-Hodgkin lymphomas, 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 prognosis vary by type. The incidence of non-Hodgkin lymphoma increases with age. It is further divided into several subtypes. Non-Hodgkin lymphomas mostly originate from B cells, T cells , and NK cells.

Epstein-Barr virus-associated lymphoproliferative diseases
Epstein-Barr virus-associated lymphoproliferative diseases are a group of benign, pre-malignant, and malignant diseases of lymphoid cells, i.e. B cells, T cells, NK cells, and histiocytic-dendritic cells in which one or more of these cell types is infected with the Epstein-Barr virus (EBV). 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 (2016) 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 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, is based upon the foundations laid within the "revised European-American lymphoma classification" (REAL). This system groups lymphomas by cell type (i.e. the normal cell type that most resembles the tumor) 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 of, albeit markedly abnormal, lymphocytes of mature B cell lineage.

Of the many forms of lymphoma, some are categorized as indolent (e.g. small lymphocytic lymphoma), compatible with a long life even without treatment, whereas other forms are aggressive (e.g. Burkitt's lymphoma), 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 (usually a hematopathologist).

WHO divides GI lymphomas into several categories: large cell, extranodal marginal zone (MALT), Burkitt, peripheral T cell, mantle cell, and follicular cell. Large B-cell lymphoma is the most common within those who get diagnosed with colon lymphoma.

Lymphoma subtypes (WHO 2008)
 * B-cell chronic lymphocytic leukemia/small cell lymphoma
 * 3 to 4% of lymphomas in adults
 * Small resting lymphocytes mixed with variable numbers of large activated cells, lymph nodes diffusely effaced
 * CD5, surface immunoglobulin
 * 5-year survival rate 50%.
 * Occurs in older adults, usually involves lymph nodes, bone marrow and spleen, most patients have peripheral blood involvement, indolent


 * B-cell prolymphocytic leukemia
 * Lymphoplasmacytic lymphoma (such as Waldenström macroglobulinemia)
 * Splenic marginal zone lymphoma
 * Hairy cell leukemia
 * Plasma cell neoplasms:
 * Plasma cell myeloma (also known as multiple myeloma)
 * Plasmacytoma
 * Monoclonal immunoglobulin deposition diseases
 * Heavy chain diseases
 * Extranodal marginal zone B cell lymphoma, also called MALT lymphoma
 * About 5% of lymphomas in adults
 * Variable cell size and differentiation, 40% show plasma cell differentiation, homing of B cells to epithelium creates lymphoepithelial lesions.
 * CD5, CD10, surface Ig
 * Frequently occurs outside lymph nodes, very indolent, may be cured by local excision


 * Nodal marginal zone B cell lymphoma
 * Follicular lymphoma
 * About 40% of lymphomas in adults
 * Small "cleaved" cells (centrocytes) mixed with large activated cells (centroblasts), usually nodular ("follicular") growth pattern
 * CD10, surface Ig
 * 72–77%
 * Occurs in older adults, usually involves lymph nodes, bone marrow and spleen, associated with t(14;18) translocation overexpressing Bcl-2, indolent


 * Primary cutaneous follicle center lymphoma
 * Mantle cell lymphoma
 * 3 to 4% of lymphomas in adults
 * Lymphocytes of small to intermediate size growing in diffuse pattern
 * CD5
 * 50% to 70%
 * Occurs mainly in adult males, usually involves lymph nodes, bone marrow, spleen and GI tract, associated with t(11;14) translocation overexpressing cyclin D1, moderately aggressive


 * Diffuse large B cell lymphoma, not otherwise specified
 * About 40 to 50% of lymphomas in adults
 * Variable, most resemble B cells of large germinal centers, diffuse growth pattern
 * Variable expression of CD10 and surface Ig
 * 5-year survival 60%
 * Occurs in all ages, but most commonly in older adults, may occur outside lymph nodes, aggressive


 * Diffuse large B-cell lymphoma associated with chronic inflammation
 * Epstein–Barr virus-positive DLBCL of the elderly
 * Lymphomatoid granulomatosis
 * Primary mediastinal (thymic) 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
 * < 1% of lymphomas in the United States
 * Round lymphoid cells of intermediate size with several nucleoli, starry-sky appearance by diffuse spread with interspersed apoptosis
 * CD10, surface Ig
 * 5-year survival 50%
 * Endemic in Africa, sporadic elsewhere, more common in immunocompromised and children, often visceral involvement, highly aggressive


 * 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 / Sezary syndrome
 * Most common cutaneous lymphoid malignancy
 * Usually small lymphoid cells with convoluted nuclei that often infiltrate the epidermis, creating Pautrier microabscesseses
 * CD4
 * 5-year survival 75%
 * Localized or more generalized skin symptoms, generally indolent, in a more aggressive variant, Sézary's disease, skin erythema and peripheral blood involvement


 * Primary cutaneous CD30-positive T cell lymphoproliferative disorders
 * Primary cutaneous anaplastic large cell lymphoma
 * Lymphomatoid papulosis
 * Peripheral T-cell lymphoma not otherwise specified
 * Most common T cell lymphoma
 * Variable, usually a mix small to large lymphoid cells with irregular nuclear contours
 * CD3
 * Probably consists of several rare tumor types, often disseminated and generally aggressive


 * Angioimmunoblastic T cell lymphoma
 * Anaplastic large cell lymphoma


 * B-lymphoblastic leukemia/lymphoma not otherwise specified
 * B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities
 * T-lymphoblastic leukemia/lymphoma
 * 15% of childhood acute lymphoblastic leukemia and 90% of lymphoblastic lymphoma.
 * Lymphoblasts with irregular nuclear contours, condensed chromatin, small nucleoli and scant cytoplasm without granules
 * TdT, CD2, CD7
 * It often presents as a mediastinal mass because of involvement of the thymus. It is highly associated with NOTCH1 mutations, and is most common in adolescent males.


 * Classical Hodgkin lymphomas:
 * Nodular sclerosis form of Hodgkin lymphoma
 * Most common type of Hodgkin lymphoma
 * Reed-Sternberg cell variants and inflammation, usually broad sclerotic bands that consist of collagen
 * CD15, CD30
 * Most common in young adults, often arises in the mediastinum or cervical lymph nodes


 * Mixed cellularity Hodgkin lymphoma
 * Second-most common form of Hodgkin lymphoma
 * Many classic Reed-Sternberg cells and inflammation
 * CD15, CD30
 * Most common in men, more likely to be diagnosed at advanced stages than the nodular sclerosis form Epstein-Barr virus involved in 70% of cases


 * Lymphocyte-rich
 * Lymphocyte depleted or not depleted
 * Nodular lymphocyte-predominant Hodgkin lymphoma


 * Associated with a primary immune disorder
 * Associated with the human immunodeficiency virus (HIV)
 * 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 (1982), and REAL (1994).

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 (low, intermediate, high, and miscellaneous) 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 it made no distinction between T-cell lymphomas and B-cell lymphomas. It was widely accepted at the time of its publication, but is now obsolete. It is still used by some cancer agencies for compilation of lymphoma statistics and historical rate comparisons.

In 1994, the Revised European-American Lymphoma (REAL) classification applied immunophenotypic and genetic features in identifying distinct clinicopathologic entities among all the lymphomas except Hodgkin lymphoma. For coding purposes, the ICD-O (codes 9590–9999) and ICD-10 (codes C81-C96) are available.

Staging
After a diagnosis and before treatment, a cancer is staged. This refers to determining if the cancer has spread, and if so, whether locally or to distant sites. Staging is reported as a grade between I (confined) and IV (spread). Staging is carried out because the stage of a cancer impacts its prognosis and treatment.

The Ann Arbor staging system is routinely used for staging of both HL and NHL. In this staging system, I represents a localised disease contained within a lymph node group, II represents the presence of lymphoma in two or more lymph nodes groups, III represents spread of the lymphoma to lymph nodes groups on both sides of the diaphragm, and IV indicates spread to tissue outside the lymphatic system. Different suffixes imply involvement of different organs, for example S for the spleen and H for the liver. Extra-lymphatic involvement is expressed with the letter E. In addition, the presence of B symptoms or their absence is expressed with B and A, respectively. B symptoms are defined as the presence of one of three symptoms: Unintentional weightloss of 10% body weight in the last 6 months, night sweats, and persistent fever of 38 °C or more.

CT scan or PET scan imaging modalities are used to stage a cancer. PET scan is advised for FDG avid lymphomas, for example Hodgkins Lymphoma as a staging tool that can even replace bone marrow biopsy. For other lymphomas CT scan is recommended for staging.

Age and poor performance status are established poor prognostic factors, as well.

Differential diagnosis
Certain lymphomas (extranodal NK/T-cell lymphoma, nasal type and type II enteropathy-associated T-cell lymphoma) can be mimicked by two benign diseases which involve the excessive proliferation of non-malignant NK cells in the GI tract, natural killer cell enteropathy, a disease wherein NK cell infiltrative lesions occur in the intestine, colon, stomach, or esophagus, and lymphomatoid gastropathy, a disease wherein these cells' infiltrative lesions are limited to the stomach. These diseases do not progress to cancer, may regress spontaneously and do not respond to, and do not require, chemotherapy or other lymphoma treatments.

Treatment
Prognoses and treatments are different for HL and between all the different forms of NHL, and also depend on the grade of tumour, referring to how quickly a cancer replicates. Paradoxically, high-grade lymphomas are more readily treated and have better prognoses: Burkitt lymphoma, for example, is a high-grade tumor known to double within days, and is highly responsive to treatment. Lymphomas may be curable if detected in early stages with modern treatment. In some advanced stages surgery may be necessary to partially remove the colon.

Low-grade
Many low-grade lymphomas remain indolent for many years. Treatment of the nonsymptomatic patient is often avoided. In these forms of lymphoma, such as follicular lymphoma, watchful waiting is often the initial course of action. This is carried out because the harms and risks of treatment outweigh the benefits. If a low-grade lymphoma is becoming symptomatic, radiotherapy or chemotherapy are the treatments of choice; although they do not cure the lymphoma, they can alleviate the symptoms, particularly painful lymphadenopathy. Patients with these types of lymphoma can live near-normal lifespans, but the disease is incurable. Some centers advocate the use of single agent rituximab in the treatment of follicular lymphoma rather than the wait and watch approach. Watchful waiting is not a good strategy for all patients, as it leads to significant distress and anxiety in some patients. It has been equated with watch and worry.

High-grade
Treatment of some other, more aggressive, forms of lymphoma can result in a cure in the majority of cases, but the prognosis for patients with a poor response to therapy is worse. Treatment for these types of lymphoma typically consists of aggressive chemotherapy, including the CHOP or R-CHOP regimen. A number of people are cured with first-line chemotherapy. Most relapses occur within the first two years, and the relapse risk drops significantly thereafter. For people who relapse, high-dose chemotherapy followed by autologous stem cell transplantation is a proven approach.

Hodgkin lymphoma
Hodgkin lymphoma typically is treated with radiotherapy alone, as long as it is localized.

Advanced Hodgkin disease requires systemic chemotherapy, sometimes combined with radiotherapy. Chemotherapy used includes the ABVD regimen, which is commonly used in the United States. Other regimens used in the management of Hodgkin lymphoma include BEACOPP and Stanford V. Considerable controversy exists regarding the use of ABVD or BEACOPP. Briefly, both regimens are effective, but BEACOPP is associated with more toxicity. Encouragingly, a significant number of people who relapse after ABVD can still be salvaged by stem cell transplant.

Palliative care
Palliative care, a specialized medical care focused on the symptoms, pain, and stress of a serious illness, is recommended by multiple national cancer treatment guidelines as an accompaniment to curative treatments for people suffering from lymphoma. It is used to address both the direct symptoms of lymphoma and many unwanted side effects that arise from treatments. The most common side effects one might experience are nausea, vomiting, diarrhea or constipation, and fatigue. Palliative care can be especially helpful for children who develop lymphoma, helping both children and their families deal with the physical and emotional symptoms of the disease. For these reasons, palliative care is especially important for patients requiring bone marrow transplants.

Immunotherapy
Immunotherapy has been used in patients with advanced stages of colon lymphomas. Immunotherapy will use the patients own immune system to fight off the cancer. This type of treatment is composed of white blood cells, organs, and tissues that are all associated with the lymph system. There are different types of immunotherapies in use: immune checkpoint inhibitors, T-cell transfer, monoclonal antibodies, vaccines, and modulators.


 * Immune Checkpoint Inhibitors: block checkpoints throughout the cell cycle, for example: PD-1.
 * T-cell Transfer: immune cells from the tumor will be taken to the lab, colonized, and put back into the body to help the patients T cells fight off the cancer
 * Monoclonal Antibodies: antibodies that are modified in the lab to target the specific cancer cell found within the patient
 * Vaccine: simply boost the immune system to responding to the cancer cells within the patient but these vaccines do not prevent the cancer
 * Modulators: specifically targets the part of the immune system and increases the bodies response to cancer

Epidemiology


Lymphoma is the most common form of hematological malignancy, or "blood cancer", in the developed world. Colon lymphomas because of their rarity only account for 15%-20% of all gastrointestinal tract. Taken together, lymphomas represent 5.3% of all cancers (excluding simple basal cell and squamous cell skin cancers) in the United States and 55.6% of all blood cancers.

According to the U.S. National Institutes of Health, lymphomas account for about 5%, and Hodgkin lymphoma in particular accounts for less than 1% of all cases of cancer in the United States. Colorectal cancers will account for roughly 150,000 diagnosis between both men and women every year. In 2013, roughly 1,177,556 people in the United States were living with colorectal lymphomas.

According to the Formosan Journal of Surgery, most lymphomas of the colon are non-Hodgkin's large B-cell lymphomas but only account for 0.2-0.6% for colon cancers as a whole. Colorectal cancer is the number three killer in the United States according to a study done in 2016. Patients with a weakened immune system such as from HIV infection or from certain drugs or medication also have a higher incidence of lymphoma.

History
Thomas Hodgkin published the first description of lymphoma in 1832, specifically of the form named after him. Since then, many other forms of lymphoma have been described. A man named I.M.P. Dawson discovered what is now known as primary colon lymphoma in 1961. His criteria that must be met were:


 * 1) no enlargement of lymph nodes upon examination
 * 2) no enlargement of mediastinal lymph nodes on a chest radiograph
 * 3) normal hematologic levels upon bone marrow biopsy
 * 4) no liver or spleen enlargement

The reason he set this as the criteria to be met is because most colon and gastrointestinal lymphomas lack the common signs and symptoms of the systemic disease.

Research
The two types of lymphoma research are clinical or translational research and basic research. Clinical/translational research focuses on studying the disease in a defined and generally immediately patient-applicable way, such as testing a new drug in patients. Studies may focus on effective means of treatment, better ways of treating the disease, improving the quality of life for patients, or appropriate care in remission or after cures. Hundreds of clinical trials are being planned or conducted at any given time.

Basic science research studies the disease process at a distance, such as seeing whether a suspected carcinogen can cause healthy cells to turn into lymphoma cells in the laboratory or how the DNA changes inside lymphoma cells as the disease progresses. The results from basic research studies are generally less immediately useful to patients with the disease, but can improve scientists' understanding of lymphoma and form the foundation for future, more effective treatments.

One study recently looked at checkpoint inhibitors, PD-1, as a target for future cancer treatments. PD-1 inhibitors are most often seen in micro-satellite lymphomas, a metastatic colorectal cancer. Research has shown that 35% of colorectal cancers can be link to genetics but more research still needs to be conducted. The National Cancer Institute is currently researching targeted therapies for metastatic colorectal cancers that have specifically been linked to genetic mutations like Lynch Syndrome.