The extracellular matrix in “Sclerosing” follicular center cell lymphomas: An immunohistochemical and ultrastructural study

Abstract

"Sclerosis" is frequently seen in follicular center cell (FCC) lymphomas. The mechanism of its deposition, as well as its composition and significance, are unknown. Several clinical studies have suggested that the course of these lymphomas is more indolent than that of lymphomas of the same histologic type without sclerosis. Nine immunologically characterized cleaved FCC lymphomas with sclerosis and 14 reactive lymph nodes with follicular hyperplasia were investigated by special staining methods, electron microscopy, and immunohistochemical studies with antibodies to types I, III, IV, and V collagen, laminin, and fibronectin. The sclerotic tissue in FCC lymphomas stained uniformly with periodic acid-Schiff (PAS) and Masson's stain, with the patterns ranging from delicate filamentous strands to dense doubly refractile bands. Ultrastructurally, the bands of connective tissue were continuous with the adventitia of vessels and composed of varying amounts of banded collagen (types I and III) admixed with filamentous and flocculent material. In all cases the neoplastic lymphocytes were separated from the extra-cellular matrix by fibroblasts and myofibroblasts with long cell processes. Immunohistochemical studies demonstrated intense staining of sclerotic bands with antibodies to fibronectin and type I collagen and, usually, weaker marking with antibodies to types III and V collagen. No significant staining of sclerotic bands was found with antibodies to type IV collagen or with laminin. Weak pericellular staining for type V collagen was present in eight of nine lymphomas and half of the control lymph nodes. These studies suggest that the increased amounts of extracellular matrix in cleaved FCC lymphomas are produced primarily by fibroblasts and myofibroblasts and represent predominantly fibronectin and types I, III, and V collagen. The composition of the sclerotic areas of FCC lymphomas is similar immunohistochemically to that of the capsule and trabeculae of reactive lymph nodes, which are also intimately associated with fibroblasts and myofibroblasts.