<unk>  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<unk> . After<unk>  is diagnosed, a variety of tests may be carried out to look for specific features characteristic of different types of<unk> . These include: * Immunophenotyping * Flow cytometry * Fluorescence in situ hybridization testing Classification Lymph node with mantle cell<unk>  (low-power view, H&E) According to the World Health Organization (WHO),<unk>  classification should reflect in which lymphocyte population the neoplasm arises. Thus, neoplasms that arise from precursor lymphoid cells are distinguished from those that arise from mature lymphoid cells. Most mature lymphoid neoplasms comprise the non-Hodgkin<unk> s. Historically, mature histiocytic and dendritic cell (HDC) neoplasms have been considered mature lymphoid neoplasms, since these often involve lymphoid tissue.<unk>  can also spread to the central nervous system, often around the brain in the meninges, known as<unk> tous meningitis (LM). Hodgkin<unk>  Hodgkin<unk>  accounts for about 15% of<unk> s. It differs from other forms of<unk> s in its prognosis and several pathological characteristics. A division into Hodgkin and non-Hodgkin<unk> s is used in several of the older classification systems. A Hodgkin<unk>  is marked by the presence of a type of cell called the Reed–Sternberg cell. Non-Hodgkin<unk> s Non-Hodgkin<unk> s, which are defined as being all<unk> s except Hodgkin<unk> , are more common than Hodgkin<unk> . A wide variety of<unk> s 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<unk>  increases with age. It is further divided into several subtypes. Epstein–Barr virus-associated lymphoproliferative diseases Epstein–Barr virus-associated lymphoproliferative diseases are a group of benign, premalignant, and malignant diseases of lymphoid cells, i.e. B cells, T cells, NK cells, and histiocytic-dendritic cells in which<unk>  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<unk> s, the World Health Organization (2016) includes the following<unk> s, when associated with EBV infection, in this group of diseases: Burkitt<unk> ; large B cell<unk> , not otherwise specified; diffuse large B cell<unk>  associated with chronic inflammation; fibrin-associated diffuse large B cell<unk> ; primary effusion<unk> ; plasmablastic<unk> ; extranodal NK/T cell<unk> , nasal type; peripheral T cell<unk> , not otherwise specified; angioimmunoblastic T cell<unk> ; follicular T cell<unk> ; and systemic T cell<unk>  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<unk>  classification" (REAL). This system groups<unk> s 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<unk>  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<unk> , some are categorized as indolent (e.g. small lymphocytic<unk> , compatible with a long life even without treatment, whereas other forms are aggressive (e.g. Burkitt's<unk> , causing rapid deterioration and death. However, most of the aggressive<unk> s 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).<unk>  subtypes (WHO 2008) DNA-microarray analysis of Burkitt's<unk>  and diffuse large B-cell<unk>  (DLBCL) showing differences in gene expression patterns. Colors indicate levels of expression; green indicates genes that are underexpressed in<unk>  cells (as compared to normal cells), whereas red indicates genes that are overexpressed in<unk>  cells. * B-cell chronic lymphocytic leukemia/small cell<unk>  :: 3 to 4% of<unk> s 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<unk>  (such as Waldenström macroglobulinemia) * Splenic marginal zone<unk>  * 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<unk> , also called MALT<unk>  :: About 5% of<unk> s 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<unk>  * Follicular<unk>  :: About 40% of<unk> s in adults :: Small "cleaved" cleft cells (centrocytes) mixed with large activated cells (centroblasts), usually nodular ("follicular") growth pattern :: CD10, surface Ig :: About 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<unk>  * Mantle cell<unk>  :: About 3 to 4% of<unk> s in adults :: Lymphocytes of small to intermediate size growing in diffuse pattern :: CD5 :: About 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<unk> , not otherwise specified :: About 40 to 50% of<unk> s in adults :: Variable, most resemble B cells of large germinal centers, diffuse growth pattern :: Variable expression of CD10 and surface Ig :: Five-year survival rate 60% :: Occurs in all ages, but most commonly in older adults, may occur outside lymph nodes, aggressive * Diffuse large B-cell<unk>  associated with chronic inflammation * Epstein–Barr virus-positive DLBCL of the elderly *<unk> toid granulomatosis * Primary mediastinal (thymic) large B-cell<unk>  * Intravascular large B-cell<unk>  * ALK+ large B-cell<unk>  * Plasmablastic<unk>  * Primary effusion<unk>  * Large B-cell<unk>  arising in HHV8-associated multicentric Castleman's disease * Burkitt<unk> /leukemia :: 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<unk>  *<unk> toid papulosis * Peripheral T-cell<unk>  not otherwise specified :: Most common T cell<unk>  :: 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<unk>  * Anaplastic large cell<unk> : ALK-positive and ALK-negative types * Breast plant-associated anaplastic large cell<unk>  * 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<unk> . :: 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<unk> s: * Nodular sclerosis form of Hodgkin<unk>  :: Most common type of Hodgkin<unk>  :: 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<unk>  :: Second-most common form of Hodgkin<unk>  :: 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<unk>  * Associated with a primary immune disorder * Associated with the human immunodeficiency virus (HIV) * Post-transplant * Associated with methotrexate therapy * Primary central nervous system<unk>  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<unk> . It excluded the Hodgkin<unk> s and divided the remaining<unk> s 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<unk> s and B-cell<unk> s. It was widely accepted at the time of its publication but is now obsolete. In 1994,
Lymphoma
Cat-scratch disease
Thymoma
Paracoccidioidomycosis
Thyroid nodule
Meningioma
Myoma
Branchial cleft cyst