TABLE 3.

Diffuse Large B-Cell Lymphoma Variants and Related Disorders Requiring Special Treatment Approaches

	Special treatment approaches
Morphological variants
Plasmablastic	Usually CD20-negative, so rituximab is not useful
DLBCL arising from lymphomatoid granulomatosis	Sometimes relapses as low-grade lymphomatoid granulomatosis and can be treated with interferon or rituximab
Specific sites of involvement
Testes	Frequent CNS metastasis and recurrence in the opposite testicle necessitate CNS prophylaxis and scrotal irradiation
CNS	Does not benefit from CHOP-R and requires high-dose intravenous methotrexate-based regimen
Skin	Must distinguish between cutaneous DLBCL, leg type, which requires systemic treatment such as CHOP-R, and other tumors (termed cutaneous follicule center cell lymphoma) that need only local treatment
Highly proliferative variants
Lymphoma with features intermediate between DLBCL and Burkitt lymphoma	Have a high failure rate with CHOP-R and are best treated with Burkitt regimens (eg, EPOCH-R, CODOX-M/IVAC)
Double-hit lymphoma (MYC and BCL-2)
MYC-positive
Other subtype
Mediastinal gray zone lymphoma	The best treatment is uncertain. The most common treatment is CHOP-R followed by radiotherapy

CNS = central nervous system; DLBCL = diffuse large B-cell lymphoma.