Extranodal NK-/T-cell lymphoma
Extranodal NK-/T-cell lymphoma (nasal type) is an aggressive lymphoma marked by extensive necrosis and angioinvasion, most often presenting in extranodal sites, in particular the nasal or paranasal sinus region.[135,136,137,138] Other extranodal sites include the palate, trachea, skin, and gastrointestinal tract. Hemophagocytic syndrome may occur; historically, these tumors were considered part of lethal midline granuloma. In most cases, Epstein-Barr virus (EBV) genomes are detectable in the tumor cells and immunophenotyping shows CD56 positivity. Cases with blood and marrow involvement are considered NK-cell leukemia. The increased risk of CNS involvement and of local recurrence has led to recommendations for radiation therapy locally, concurrently, or prior to the start of chemotherapy, and for intrathecal prophylaxis and/or prophylactic cranial radiation therapy.[140,141,142,143,144,145] The highly aggressive course, with poor response and short survival with standard therapies, especially for patients with advanced stage disease or extranasal presentation, has led some investigators to recommend bone marrow or peripheral stem cell transplantation consolidation.[136,137,138,146,147] NK-/T-cell lymphoma that presents only in the skin has a more favorable prognosis, especially in patients with coexpression of CD30 with CD56.
Lymphomatoid granulomatosis is an EBV-positive large B-cell lymphoma with a predominant T-cell background.[149,150] The histology shows association with angioinvasion and vasculitis, usually manifesting as pulmonary lesions or paranasal sinus involvement. Patients are managed like others with diffuse large cell lymphoma and require doxorubicin-based combination chemotherapy.
Angioimmunoblastic T-cell lymphoma
Angioimmunoblastic T-cell lymphoma was formerly called angioimmunoblastic lymphadenopathy with dysproteinemia. Characterized by clonal T-cell receptor gene rearrangement, this entity is managed like diffuse large cell lymphoma.[151,152,153] Patients present with profound lymphadenopathy, fever, night sweats, weight loss, skin rash, a positive Coomb test, and polyclonal hypergammaglobulinemia. (For information on night sweats, weight loss, and skin rash, refer to the PDQ summaries on Fever, Sweats, and Hot Flashes, Nutrition in Cancer Care, and Pruritus, respectively.) Opportunistic infections are frequent because of an underlying immune deficiency. Doxorubicin-based combination chemotherapy is recommended as it is for other aggressive lymphomas. Myeloablative chemotherapy and radiation therapy with autologous or allogeneic peripheral stem cell support has been described in anecdotal reports.[146,154,155] Occasional spontaneous remissions and protracted responses to steroids only have been reported. B-cell EBV genomes are detected in most affected patients.
Peripheral T-cell lymphoma
Patients with peripheral T-cell lymphoma have diffuse large cell or diffuse mixed lymphoma that expresses a cell surface phenotype of a postthymic (or peripheral) T-cell expressing CD4 or CD8 but not both together. Peripheral T-cell lymphoma encompasses a group of heterogeneous nodal T-cell lymphomas that will require future delineation. This includes the so-called Lennert lymphoma, a T-cell lymphoma admixed with a preponderance of lymphoepithelioid cells. Most investigators report worse response and survival rates for patients with peripheral T-cell lymphomas than for patients with comparably staged B-cell aggressive lymphomas.[158,159,160] Therapy involves doxorubicin-based combination chemotherapy, which is also used for B-cell diffuse large cell lymphoma. Most patients present with multiple adverse prognostic factors (i.e., older age, stage IV, multiple extranodal sites, and elevated LDH), and these patients have a low (<20%) failure-free survival and OS at 5 years. High-dose chemotherapy with hematopoietic stem cell support has been applied to patients with advanced-stage peripheral T-cell lymphoma. Evidence for this approach is anecdotal.[146,154,161] Anecdotal responses have also been seen with alemtuzumab, an anti-CD52 monoclonal antibody, or denileukin diftitox, a toxin-antibody ligand, after relapse from previous chemotherapy.[162,163] An unusual type of peripheral T-cell lymphoma occurring mostly in young men, hepatosplenic T-cell lymphoma, appears to be localized to the hepatic and splenic sinusoids, with cell surface expression of the T-cell receptor gamma/delta.[164,165,166,167,168] Another variant, subcutaneous panniculitis-like T-cell lymphoma, is localized to subcutaneous tissue associated with hemophagocytic syndrome.[169,170,171,172] These patients have cells that express alpha/beta phenotype. Those with gamma-delta phenotype have a more aggressive clinical course and are classified as cutaneous gamma-delta T-cell lymphoma.[173,174,175] These patients may manifest involvement of the epidermis, dermis, subcutaneous region, or mucosa. These entities have extremely poor prognoses with an extremely aggressive clinical course and are treated with the same paradigm as for the highest-risk groups with diffuse large B-cell lymphoma.