ANAPLASTIC LARGE CELL LYMPHOMA
Anaplastic large cell lymphomas (ALCL) may be confused with carcinomas and are
associated with the Ki-1 (CD30) antigen. These lymphomas are usually of T-cell
origin, often present with extranodal disease, and are found especially in the skin.
The translocation of chromosomes 2 and 5 creates a unique fusion protein with a nucleophosmin-ALK. Patients whose lymphomas express ALK (immunohistochemistry) are usually younger and may have systemic symptoms, extranodal disease, and advanced stage disease; however, they have a more favorable survival rate than that of ALK-negative patients. Patients with these types of lymphomas are generally treated the same as patients with
diffuse large cell lymphomas and have as good a prognosis as comparably staged
patients. Anaplastic large cell lymphoma in children is usually
characterized by systemic and cutaneous disease and has high response rates and
good OS with doxorubicin-based combination chemotherapy.
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.[120,121,122,123,124,125] 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. In addition to
doxorubicin-based combination chemotherapy, the increased risk of CNS
involvement and of local recurrence has led to recommendations for radiation
therapy locally, often prior to the start of chemotherapy, and for intrathecal
prophylaxis and/or prophylactic cranial radiation therapy.[121,125,127,128,129,130] The highly
aggressive course, with poor response and short survival with standard
therapies, especially for patients with advanced stage disease, has led some investigators to recommend bone marrow or peripheral
stem cell transplantation consolidation.[122,123,124] 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.[132,133] 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.[134,135,136] Patients present with profound lymphadenopathy, fever, night
sweats, weight loss, skin rash, a positive Coomb’s test, and polyclonal
hypergammaglobulinemia. 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 peripheral stem cell support has been described in anecdotal reports. Occasional spontaneous
remissions and protracted responses to steroids only have been reported. B-cell EBV genomes are detected in most affected patients.