which neoplastic lymphocytes that express the alk tyrosine kinase receptor protein infiltrate lymph nodes as well as extranodal sites, e.g. the mediastinum, bones, bone marrow, nasopharynx, tongue, stomach, liver, spleen, and skin. about 60% of these individuals present with advanced disease. alk+ lbcl has an overall 5 year survival rate of ~34%. plasmablastic lymphoma main article: plasmablastic lymphoma plasmablastic lymphoma (pbl) is a dlbcl in which neoplastic immunoblastic or plasmablastic cells embedded in a background of other cell types infiltrate the oral/nasal cavity or much less often the gastrointestinal tract. some 70% of individuals with pbl are infected with ebv and/or (particularly those with oral/nasal cavity disease) human immunodeficiency virus (hiv). pbl is an aggressive disease with a median survival time of ~15 months. intravascular large b-cell lymphoma main article: intravascular large b-cell lymphoma intravascular large b-cell lymphoma (ivlbcl) is a dlbcl in which medium- to large-sized neoplastic b-cells infiltrate small- to medium-sized blood vessels and sinusoids in the liver, spleen, and/or bone marrow. ivlbcl may be associated with the hemophagic syndrome (i.e. excessive cytokine secretion and systemic inflammation). patients with the latter syndrome have very short survival times. the poor prognosis of this disease has been significantly improved by rituximab or similar immunochemotherapy drugs but significant proportions of these responding cases relapse, often with central nervous system involvement. large b-cell lymphoma with irf4 rearrangement large b-cell lymphoma with irf4 rearrangement (lbcl with irf4 rearrangement) is a dlbcl in which tissue infiltrates containing intermediate- or large-sized neoplastic b-cells strongly express a chromosomal translocation involving the irf4 gene on the short arm of chromosome 6. these cells form follicular, follicular and diffuse, or entirely diffuse infiltrates in waldeyer's tonsillar ring or other regions of the head and neck. the disease, which represents ~0.05% of all dlbcl, occurs primarily in children and young adults and typically has a good prognoses. cases with a follicular pattern of tissue infiltrates often have indolent disease and an excellent prognosis following excision and may not need chemotherapy. cases with a purely diffuse tissue infiltrate pattern, in contrast, often do require chemotherapy. primary mediastinal large b-cell lymphoma main article: primary mediastinal large b-cell lymphoma primary mediastinal large b-cell lymphoma (pmbl), also termed primary mediastinal (thymic) large b-cell lymphoma, is a dlbcl in which neoplastic b-cells infiltrates are commonly located in sclerotic/fibrous tissues of the thymus and mediastinal lymph nodes. the disease represents 6–10% of all dlbcl cases, presents with early stage disease in ~80% of cases, and has an overall survival rate at 5 years of 75–85%. primary cutaneous diffuse large b-cell lymphoma, leg type main article: primary cutaneous diffuse large b-cell lymphoma, leg type primary cutaneous diffuse large b-cell lymphoma, leg type (pcdlbcl-lt) is a dlbcl in which diffuse patterns of immunoblastic and/or centroblastic b-cells infiltrate the dermis and/or subcutaneous tissue principally, but not exclusively, of the legs. this disease's 5-year overall survival rate is 50–60%. primary diffuse large b-cell lymphoma of the central nervous system main article: primary central nervous system lymphoma primary diffuse large b-cell lymphoma of the central nervous system (dlbcl-cns, also termed primary central nervous system lymphoma ) is a dlbcl in which diffuse patterns of neoplastic b-cells with centroblastic, immunoblastic, or poorly differentiated features infiltrate the brain, spinal cord, leptomeninges, or eye. the disease usually presents as a single lesion with a predilection for the supratentorial region of the brain but may involve the eye in 15–25% of cases, the cerebrospinal fluid in 7–42% of cases, and the spinal cord in ~1% of cases. the disease has a 5-year overall survival rate of ~30%. diffuse large b-cell lymphoma associated with chronic inflammation main articles: diffuse large b-cell lymphoma associated with chronic inflammation and fibrin-associated diffuse large b-cell lymphoma diffuse large b-cell lymphoma associated with chronic inflammation (dlbcl-ci) is an epstein–barr virus-associated lymphoproliferative disease arising in persons with a long and persistent history of chronic inflammation. the disease's lesions consist of large, mature-appearing b-cells infiltrating the lung's pleura and nearby tissues. most cases have occurred in patients who were given a pneumothorax (i.e. therapeutic introduction of air into the chest cavity in order to collapse and thereby "rest" the lung) to treat pulmonary tuberculosis that had progressed to a pyothorax (i.e. pus in the pleural cavity). fibrin-associated large b-cell lymphoma (fa-dlbcl), often considered a sub-type of dlbcl-ci, is an infiltration of large neoplastic b-cells and fibrin affix to a prosthesis (e.g., cardiac valve, orthopaedic device) or accumulate within a hydrocele, pseudocyst, cardiac myxoma, or chronic subdural hematoma. the b-cells in these lesions are often but not always infected with the epstein–barr virus. dlbcl-ci occurring in cases of pleural empyema (sometimes termed pyothorax-associated lymphoma, i.e. pal) is an aggressive lymphoma with a five-year overall survival rate of 20–35%; fa-dlbcl, when involving the heart (e.g. occurring on myxommas or prosthetic valves) or vasculature structures (e.g. on thrombus-laden vascular grafts), may involve life-threatening cardiovascular complications, particularly strokes. outside of these complications, however, dlbcl-ci usually has a highly favorable outcome. lymphomatoid granulomatosis main article: lymphomatoid granulomatosis lymphomatoid granulomatosis (lyg) is a dlbcl in which large, atypical b-cells with immunoblastic or hodgkin disease-like features that are infected by the epstein-barr virus center around and destroy the microvasculature. lymphomatoid granulomatosis almost always involves the lung but may concurrently involve the brain, peripheral nervous system, skin, kidneys, liver, gastrointestinal tract, and/or upper respiratory tract; lyg has an increased incidence in persons with wiskott–aldrich syndrome or hiv or who are immunosuppression due to chemotherapy or organ transplantation. the disease's prognosis is highly variable: patients with low grade disease often require no therapy except watchful waiting while patients with high grade disease usually require chemotherapy. primary effusion lymphoma main article: primary effusion lymphoma primary effusion lymphoma (pel) is a dlbcl in which neoplastic b cells that resemble immunoblasts, plasmablasts, or reed–sternberg cells infiltrate the pleural, pericardial, or peritoneal membranes that surround the lungs, heart, and abdominal organs, respectively. this infiltration leads to the seeping of fluid into the cavities which are encased by these membranes, i.e. it leads to pleural effusions, pericardial effusions, and abdominal ascites. some cases of pel also involve the gastrointestinal tract and lymph nodes. the disease occurs primarily in people who are immunosuppressed or test positive for hiv and are also latently infected with kaposi's sarcoma-associated herpesvirus; pel is an aggressive disease with an overall 1 year survival rate of ~30%. epstein–barr virus-positive diffuse large b-cell lymphoma, not otherwise specified main article: epstein–barr virus-associated lymphoproliferative diseases § epstein–barr virus-positive diffuse large b cell lymphoma, not otherwise specified epstein–barr virus-positive diffuse large b cell lymphoma, not otherwise specified (ebv+ dlbcl, nos) is a b-cell lymphoma in which neoplastic b-cells that are infected with the epstein-barr virus cause a disease that does not fit into other subtypes of dlbcl. in ebv+ dlbcl, small neoplastic b-cells, other lymphocyte typess, plasma cells, histiocytes and epithelioid cells interspersed with reed–sternberg-like cells infiltrate, almost exclusively, lymph nodes. elderly patients with the disease have median survival times of ~2 years while young patients have long-term treatment-related remissions in >80% of cases. hhv8-positive diffuse large b-cell lymphoma, nos main articles: hhv8-positive diffuse large b-cell lymphoma and hhv-8-associated mcd hhv8-positive diffuse large b-cell lymphoma, nos (hhv8+ dlbcl, nos; also termed hhv8-positive diffuse large b-cell lymphoma ) is a dlbcl in which kaposi's sarcoma-associated herpesvirus-infected, medium- to large-size neoplastic b-cells that resemble lymphocytes or immunoblasts infiltrate lymph nodes (~80% of cases) and, when disseminated (20% of cases), the liver and spleen. this infiltration usually disrupts the normal architecture of the involved tissues. hhv8+ dlbcl develops in hiv-infected individuals in ~50% of cases, in individuals with multicentric castleman disease, plasma cell variant in uncommon cases, and in individuals with kaposi sarcoma in rare cases. hhv8+ dlbcl commonly takes an aggressive course and has a poor prognosis. related disorders helicobactor pylori associated diffuse large b-cell lymphoma main article: helicobacter pylori § diffuse large b-cell lymphoma rare cases of dlbcl are associated with the presence of the bacterium, helicobacter pylori, in the neoplastic b-cells. while the histology of helicobactor pylori-associated diffuse large b-cell lymphoma (h. pylori+ dlbcl) is typical of dlbcl, the disease is sometimes a progression of mantle cell lymphoma, is often restricted to the stomach, is less aggressive that most dlbcl cases, and may respond to a drug regimen consisting of antibiotics and proton pump inhibitors directed at killing the bacterium. perhaps because of these features of the disease, h. pylori+ dlbcl has not been classified as a dlbcl by the world health organization, 2016. recent studies suggest that localized, early-stage h. pylori+ dlbcl, when limited to the stomach, is successfully treated with h. pylori eradication protocols consisting of two or more antibiotics plus a proton pump inhibitor. however, these studies also agree that patients treated with one of these h. pylori eradication regimes need to be carefully followed: those unresponsive to, or worsening on, these regimens should be switched to a chemotherapy regimen (e.g. r-chop) and/or, for complicated bulky disease, surgery and/or local radiotherapy. epstein–barr virus-positive mucocutaneous ulcer main articles: mouth ulcer and epstein–barr virus-associated lymphoproliferative diseases § epstein–barr virus-positive mucocutaneous ulcer epstein-barr virus-positive mucocutaneous ulcer (ebvmcu) was first described as a lymphoproliferative disorder in which epstein–barr virus-infected b-cells proliferate and cause ulcerations in the mucous membranes and skin of immunosuppressed individuals. its lesions consist of epstein–barr virus-positive, variable-sized, atypical b-cells that by conventional histopathologic criteria indicate the lesions are a form of dlbcl. since these lesions regress spontaneously without anti-cancer treatment, ebvmcu is now considered a pseudo-malignant disorder. elderly individuals that evidence the disease but have no other cause for immunosuppression may exhibit a relapsing and remitting course with their ulcers worsening but then regressing spontaneously. persistent and/or severely symptomatic cases have had excellent responses to rituximab. individuals developing these ulcers as a consequence of immunosuppressive therapy generally have a remission after the dosage of the drugs used in their immunosuppressive treatments are reduced. most of these patients do not relapse.