The role of the perifollicular sinus in determining the complex immunoarchitecture of angioimmunoblastic T-cell lymphoma

The growth of angioimmunoblastic T-cell lymphoma (AIL) in lymph node often produces complex patterns of neoplastic T cells and nonneoplastic B cells that complicate diagnosis. To understand better how these different patterns of B-cell expansion arise, we compared the microanatomic localization of B cells and T cells within the follicular, paracortical, and sinusoidal compartments in 30 patients with AIL (including 10 with multiple sequential samples) with that seen in 33 cases of other types of T-cell lymphoma. With early or partial nodal involvement in AIL, germinal center B-cell expansions were relatively undisturbed and often associated with a variably distended D2-40+ CD31+ perifollicular sinus that surrounded most of the follicular compartment. Identifiable tumor T cells resided mostly in the paracortex. In later stages of AIL with more complete nodal effacement, bcl-6+ follicular B-cell proliferations shifted to distorted FDC networks arrayed along patent trabecular sinuses and were more intermixed with tumor T cells. In both AIL and other T-cell lymphomas, the density and locations of follicular B cells as well as bcl-6-negative monocytoid B cells were largely related to the patency of adjacent sinuses, except in Epstein-Barr virus (EBV)+ and histiocyte-rich B-cell proliferations, which arose in paracortical locations. The prominence of the perifollicular sinus in early stages of AIL resembled that seen in reactive lymphadenitis during conditions of lymphatic engorgement and implicates cytokines within lymph fluid in maintaining both the normal and altered germinal center reactions. Patterns of sinus drainage largely explain the useful changes in B-cell distribution that occur in nodal T-cell lymphomas and represent an important tool in classification and diagnosis of these tumors.