AIDS-related lymphoma | |
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Specialty | Hematology and oncology |
AIDS-related lymphoma describes lymphomas occurring in patients with acquired immunodeficiency syndrome (AIDS). [1] [2]
A lymphoma is a type of cancer arising from lymphoid cells. In AIDS, the incidence 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). [3]
The histologic classification of the lymphoma, as well as the locations and severity of the disease, all influence the clinical presentation of HIV-related lymphomas. [4] HIV-related lymphomas are more likely to present with advanced stage disease, constitutional symptoms (also known as "B" symptoms; fever, weight loss, and night sweats), extranodal involvement, or disease involving unusual locations (such as the body cavity or soft tissue) than lymphomas in the HIV-negative population. [5] [6]
HIV-related lymphomas can present with a variety of clinical symptoms, including organomegaly, lymphadenopathy, and/or constitutional symptoms. Unknown fever, cytopenias, tumor lysis syndrome (including lactic acidosis, hyperkalemia, hyperuricemia, hypocalcemia, hyperphosphatemia, and elevated lactate dehydrogenase), and other isolated laboratory abnormalities (such as hypercalcemia) are observed in certain patients. [7]
HIV-positive individuals' lymphomas vary widely and can be classified into several histologic subtypes. [8] The two primary lymphoma types that develop in HIV-positive individuals are non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). [9]
Diffuse large B-cell lymphoma is a highly aggressive type of B-cell lymphoma. It is distinguished by the widespread proliferation of large neoplastic B lymphocytes with nuclei that are equal to or larger than normal histiocytic nuclei. [10] The illness manifests with B symptoms at an advanced stage of the illness. It mostly affects patients who are severely immunosuppressed and can occur at nodal or extranodal sites, with the gastrointestinal tract being the most common site. [11] [12] It makes up between 45 and 50 percent of all lymphomas seen in this group, making it the most prevalent AIDS-associated lymphoma subtype. [13] [14] All ages are affected by DLBCL, which typically manifests as a rapidly growing lymph node mass in the neck or abdomen. [15] Up to 40% of patients have extranodal extramedullary disease, and about 30% of patients exhibit B symptoms. [16]
The second most prevalent NHL subtype that affects HIV-positive individuals with a comparatively high CD4 cell count is Burkitt's lymphoma. Patients typically have elevated lactate dehydrogenase levels and poor performance status. [15] The central nervous system is involved in 8 to 28% of cases, with extranodal involvement occurring more frequently. [11] It usually manifests at a younger age and with CD4 cell counts greater than 200 cells/μL. [17] It develops quickly and is a kind of tumor that starts from B cells. In addition, it is fatal if untreated. [18] Burkitt's lymphoma is linked to a high incidence of oral cavity involvement and makes up 10-15% of AIDS-defining lymphomas. [15] Three clinical subtypes of Burkitt's lymphoma have been identified: endemic, sporadic, and immunodeficiency-related. [19] Thirty to forty percent of AIDS-related NHL cases are Burkitt's lymphoma subtype, which is most prevalent in HIV/AIDS patients. [18]
Primary central nervous system lymphoma (PCNSL) is a subtype of NHL that impacts the eyes, brain, spine, and cerebrospinal fluid in the central nervous system. [20] It appears in patients who have severe immune suppression; since the advent of highly active antiretroviral therapy, its incidence has declined in these patients. The majority of PCNSL linked to HIV is Epstein-Barr virus positive. [15] Furthermore, unlike HIV-negative PCNSL, patients typically present with multiple brain lesions and/or changes in mental status or focal neurologic symptoms. [14] [21] Changes in mental state, intracranial pressure symptoms (headache, nausea, vomiting, papilledema), and local compression symptoms (epilepsy, memory loss, unstable gait, visual impairment, slurred speech) are the most common symptoms of PCNSL. [22]
Primary effusion lymphoma is a distinct subtype of aggressive B-cell NHL. It is brought on by HHV8, commonly referred to as KSHV, or Kaposi sarcoma-associated herpesvirus. [23] [24] It is uncommon, making up 0.3% of NHL in the general population and 4% of NHL linked to HIV. Between 60 and 90 percent of cases of primary effusion lymphoma have EBV co-infection, although its pathogenesis is unknown. [15] There are malignant lymphomatous effusions in the pericardium, peritoneal cavity, and pleural space. [25]
Plasmablastic lymphoma (PBL) originates from terminally differentiated, activated B-cells at the post-germinal center that are changing from immunoblasts to plasma cells. [15] About 2% of all AIDS-associated lymphomas are PBL-associated lymphomas. [26] HIV infection is closely associated with this uncommon form of lymphoma, which primarily affects the oral cavity. [27] With a widespread proliferation of massive neoplastic cells that resemble B-cell immunoblasts but have the immunophenotype of plasma cells, it is incredibly aggressive. [28]
Hodgkin lymphoma (HL) is one of the most common cancers that do not indicate AIDS, and since highly active antiretroviral therapy was introduced, its incidence has increased. It is a germinal center-derived cell that produces Hodgkin Reed–Sternberg (HRS) cells. [15] It is more common in immunocompromised individuals, especially those with HIV. [29] Compared to mild immune compromise, the incidence of HL is lower in states of extreme immunodeficiency. It's possible that there was insufficient immunological contact between non-neoplastic inflammatory cells and HRS cells. [30]
HIV-positive patients have a higher incidence of malignancies for a variety of reasons. These consist of inflammation, cytokine dysregulation, and persistent antigenic stimulation. [15] Moreover, oncogenic viruses are more likely to infect HIV/AIDS patients. [31] Thus, a variety of factors, such as a compromised immune system, genetic changes, viral infection, and persistent B cell activation, contribute to the pathogenesis of HIV/AIDS-associated lymphoma. [15]
Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredness. Other symptoms may include bone pain, chest pain, or itchiness. Some forms are slow-growing while others are fast-growing.
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 tumours. 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.
Burkitt lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa. It is a highly aggressive form of cancer which often, but not always, manifests after a person develops acquired immunodeficiency from infection with Epstein-Barr Virus or Human Immunodeficiency Virus (HIV).
Tumors of the hematopoietic and lymphoid tissues or tumours of the haematopoietic and lymphoid tissues are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues 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 aplasia, myeloproliferation and lymphoproliferation 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 hematological malignancies. Hematological malignancies are malignant neoplasms ("cancer"), and they are generally treated by specialists in hematology and/or oncology. In some centers "hematology/oncology" is a single subspecialty of internal medicine while in others they are considered separate divisions. Not all hematological disorders are malignant ("cancerous"); these other blood conditions may also be managed by a hematologist.
Adult T-cell leukemia/lymphoma is a rare cancer of the immune system's T-cells caused by human T cell leukemia/lymphotropic virus type 1 (HTLV-1). All ATL cells contain integrated HTLV-1 provirus further supporting that causal role of the virus in the cause of the neoplasm. A small amount of HTLV-1 individuals progress to develop ATL with a long latency period between infection and ATL development. ATL is categorized into 4 subtypes: acute, smoldering, lymphoma-type, chronic. Acute and Lymphoma-type are known to particularity be aggressive with poorer prognosis.
Primary effusion lymphoma (PEL) is classified as a diffuse large B cell lymphoma. It is a rare malignancy of plasmablastic cells that occurs in individuals that are infected with the Kaposi's sarcoma-associated herpesvirus. Plasmablasts are immature plasma cells, i.e. lymphocytes of the B-cell type that have differentiated into plasmablasts but because of their malignant nature do not differentiate into mature plasma cells but rather proliferate excessively and thereby cause life-threatening disease. In PEL, the proliferating plasmablastoid cells commonly accumulate within body cavities to produce effusions, primarily in the pleural, pericardial, or peritoneal cavities, without forming a contiguous tumor mass. In rare cases of these cavitary forms of PEL, the effusions develop in joints, the epidural space surrounding the brain and spinal cord, and underneath the capsule which forms around breast implants. Less frequently, individuals present with extracavitary primary effusion lymphomas, i.e., solid tumor masses not accompanied by effusions. The extracavitary tumors may develop in lymph nodes, bone, bone marrow, the gastrointestinal tract, skin, spleen, liver, lungs, central nervous system, testes, paranasal sinuses, muscle, and, rarely, inside the vasculature and sinuses of lymph nodes. As their disease progresses, however, individuals with the classical effusion-form of PEL may develop extracavitary tumors and individuals with extracavitary PEL may develop cavitary effusions.
Primary central nervous system lymphoma (PCNSL), also termed primary diffuse large B-cell lymphoma of the central nervous system (DLBCL-CNS), is a primary intracranial tumor appearing mostly in patients with severe immunodeficiency. It is a subtype and one of the most aggressive of the diffuse large B-cell lymphomas.
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.
Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,000 people per year in the US and UK. This cancer occurs primarily in older individuals, with a median age of diagnosis at ~70 years, although it can occur in young adults and, in rare cases, children. DLBCL can arise in virtually any part of the body and, depending on various factors, is often a very aggressive malignancy. The first sign of this illness is typically the observation of a rapidly growing mass or tissue infiltration that is sometimes associated with systemic B symptoms, e.g. fever, weight loss, and night sweats.
Intraocular lymphoma is a rare malignant form of eye cancer. Intraocular lymphoma may affect the eye secondarily from a metastasis from a non-ocular tumor or may arise within the eye primarily. PIOL is a subset of primary central nervous system lymphoma (PCNSL). PCNSL are most commonly a diffuse large B-cell immunohistologic subtype of non-Hodgkin's lymphoma according to the World Health Organization (WHO) classification of lymphomas. The most common symptoms of PIOL include blurred or decreased vision due to tumor cells in the vitreous. Most cases of PIOL eventuate to central nervous system involvement (PCNSL) while only 20% of PCNSL lead to intraocular (PIOL) involvement. PIOL and PCNSL remain enigmas because both structures are immunologically privileged sites and so do not normally have immune cells trafficking through these structures. What is more, while the vast majority of PCNSL in patients with acquired immune deficiency syndrome (AIDS) is related to the Epstein-Barr virus (EBV), the development of PCNSL and PIOL in immunocompetent patients is unknown and shows no general relation to infectious DNAs.
Aggressive lymphoma, also known as high-grade lymphoma, is a group of fast growing non-Hodgkin lymphoma.
Panobinostat, sold under the brand name Farydak, is a medication used for the treatment of multiple myeloma. It is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor.
Hodgkin lymphoma (HL) is a type of lymphoma in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells are present in the patient's lymph nodes. The condition was named after the English physician Thomas Hodgkin, who first described it in 1832. Symptoms may include fever, night sweats, and weight loss. Often, nonpainful enlarged lymph nodes occur in the neck, under the arm, or in the groin. Persons affected may feel tired or be itchy.
The stages of HIV infection are acute infection, latency, and AIDS. Acute infection lasts for several weeks and may include symptoms such as fever, swollen lymph nodes, inflammation of the throat, rash, muscle pain, malaise, and mouth and esophageal sores. The latency stage involves few or no symptoms and can last anywhere from two weeks to twenty years or more, depending on the individual. AIDS, the final stage of HIV infection, is defined by low CD4+ T cell counts, various opportunistic infections, cancers, and other conditions.
Plasmablastic lymphoma (PBL) is a type of large B-cell lymphoma recognized by the World Health Organization (WHO) in 2017 as belonging to a subgroup of lymphomas termed lymphoid neoplasms with plasmablastic differentiation. The other lymphoid neoplasms within this subgroup are: plasmablastic plasma cell lymphoma ; primary effusion lymphoma that is Kaposi's sarcoma-associated herpesvirus positive or Kaposi's sarcoma-associated Herpesvirus negative; anaplastic lymphoma kinase-positive large B-cell lymphoma; and human herpesvirus 8-positive diffuse large B-cell lymphoma, not otherwise specified. All of these lymphomas are malignancies of plasmablasts, i.e. B-cells that have differentiated into plasmablasts but because of their malignant nature: fail to differentiate further into mature plasma cells; proliferate excessively; and accumulate in and injure various tissues and organs.
Large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease is a type of large B-cell lymphoma, recognized in the WHO 2008 classification. It is sometimes called the plasmablastic form of multicentric Castleman disease. It has sometimes been confused with plasmablastic lymphoma in the literature, although that is a dissimilar specific entity. It has variable CD20 expression and unmutated immunoglobulin variable region genes.
Human herpesvirus 8 associated multicentric Castleman disease is a subtype of Castleman disease, a group of rare lymphoproliferative disorders characterized by lymph node enlargement, characteristic features on microscopic analysis of enlarged lymph node tissue, and a range of symptoms and clinical findings.
Epstein–Barr virus–associated lymphoproliferative diseases are a group of disorders in which one or more types of lymphoid cells, i.e. B cells, T cells, NK cells, and histiocytic-dendritic cells, are infected with the Epstein–Barr virus (EBV). This causes the infected cells to divide excessively, and is associated with the development of various non-cancerous, pre-cancerous, and cancerous lymphoproliferative disorders (LPDs). These LPDs include the well-known disorder occurring during the initial infection with the EBV, infectious mononucleosis, and the large number of subsequent disorders that may occur thereafter. The virus is usually involved in the development and/or progression of these LPDs although in some cases it may be an "innocent" bystander, i.e. present in, but not contributing to, the disease.
Indolent lymphoma, also known as low-grade lymphoma, is a group of slow-growing non-Hodgkin lymphomas (NHLs). Because they spread slowly, they tend to have fewer signs and symptoms when first diagnosed and may not require immediate treatment. Symptoms can include swollen but painless lymph nodes, unexplained fever, and unintended weight loss.
Mature T-cell lymphoma, also called peripheral T-cell lymphoma, is a group of rare, aggressive lymphomas that develop from mature white blood cells and originate from lymphoid tissues outside of the bone marrow. Mature T-cell lymphoma is under the category of non-Hodgkin lymphoma. Mature T-cell lymphomas account for 10% to 15% of all lymphomas and is more common in Asia than in Europe and America. Its common subtypes include angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma and peripheral T-cell lymphoma not otherwise specified. While different subtypes have variable symptoms, common symptoms include enlarged painless lymph nodes, fever, weight loss, rash and night sweats.