(A) Diffuse large B-cell lymphoma (DLBCL or DLBL)[?]Diffuse Large B-Cell LymphomaoDiffuse large B-cell lymphoma (DLBCL) is the most common form of NHL.oEach year in the United States there are about 25,000 new cases.oThere is a slight male predominance. The median patient age is about 60 years, but DLBCL also occurs in young adults and children. Germinal centre or post germinal center B celloDiverse chromosomal re-arrangements, most often BC26 (30%), BCL2 (10%), or C-MYC (5%).oAll ages, most common in Adults, 30% extranodal, aggressiveoTHC positive for CD10, CD20, CD10 & BCL6oPathogenesis:-Genetic, gene expression profiling, and immunohistochemical studies indicate that DLBCL is molecularly heterogeneous.-One frequent pathogenic event is dysregulation of BCL6, a DNA-binding zinc-finger transcriptional repressor that is required for the formation of normal germinal centers.-About 30% of DLBCLs contain various translocations that have in common a breakpoint in BCL6 at chromosome 3q27.-Acquired mutations in BCL6 promoter sequences that abrogate BCL6 autoregulation (an important negative-regulatory mechanism) are seen even more frequently.oImmunophenotype:-These mature B-cell tumors express CD19 and CD20 and show variable expression of germinal center B-cell markers such as CD10 and BCL6. Most have surface Ig.oSpecial Subtypes: Immunodeficiency-associated large B-cell lymphoma, Primary effusion lymphomaoClinical Features:-DLBCL typically presents as a rapidly enlarging mass at a nodal or extranodal site.-It can arise virtually anywhere in the body.-Waldeyer ring, the oropharyngeal lymphoid tissue that includes the tonsils and adenoids, is involved commonly.-Primary or secondary involvement of the liver and spleen may take the form of large destructive masses.-Extranodal sites include the gastrointestinal tract, skin, bone, brain, and other tissues.-Bone marrow involvement is relatively uncommon and usually occurs late in the course.-Rarely, a leukemic picture emerges.Other Options[?]Hairy cell Leukemia:-This rare but distinctive B-cell neoplasm constitutes about 2% of all leukemias.-Hairy cell leukemias are associated in more than 90% of cases with activating point mutations in the serine/threonine kinase BRAF, which is positioned immediately downstream of RAS in the MAPK signaling cdscade[?]Burkitt's lymphoma:-Within the category of Burkitt Lymphoma fall (1) African (endemic) Burkitt lymphoma, (2) sporadic (non-endemic) Burkitt lymphoma, and (3) a subset of aggressive lymphomas occurring in individuals infected with HIV.-Burkitt lymphomas occurring in each of these settings are histologically identical but differ in some clinical, genotypic, and virologic characteristics.-All forms of Burkitt lymphoma are highly associated with translocations of the MYC gene on chromosome 8 that lead to increased MYC protein levels.-Essentially all endemic Burkitt lymphomas are latently infected with EBV, which is also present in about 25% of HIV-associated tumors and 15% to 20% of sporadic cases.-Characteristic "starry sky" pattern.-When the bone marrow is involved, aspirates reveal tumor cells with slightly clumped nuclear chromatin, two to five distinct nucleoli, and royal blue cytoplasm containing clear cytoplasmic vacuoles.[?]Mantle Cell lymphoma:-Mantle cell lymphoma is an uncommon lymphoid neoplasm that makes up about 2.5% of NHL in the United States and 7% to 9% of NHL in Europe.-It usually presents in the fifth to sixth decades of life and shows a male predominance.-As the name implies, the tumor cells closely resemble the normal mantle zone B cells that surround germinal centers.-Virtually all mantle cell lymphomas have an (11;14) translocation involving the IgH locus on chromosome 14 and the cyclin D1 locus on chromosome 11 that leads to over expression of cyclin D1.-Most common presentation is painless lymphadenopathy.-Symptoms related to involvement of the spleen (present in -50% of cases) and gut are also common.