Reactive angioendotheliomatosis or intravascular histiocytosis? An immunohistochemical and ultrastructural study in two cases of intravascular histiocytic cell proliferation

Abstract

Two elderly women with complex medical histories presented with erythematous patches, in one case involving the face and forearms, and in the other both elbows. Punch biopsies from both patients revealed intravascular proliferations of medium-sized and large cells with luminal occlusion typical of angioendotheliomatosis. Immunostaining did not show either lymphocytic or endothelial cell antigens but was consistent with a histiocytic differentiation of the intravascular cells in both cases, and was further substantiated by ultrastructural examination in one case. One patient received a course of cyclophosphamide therapy over 15 days. Skin lesions faded but did not disappear. The patient died 10 months later from cardiac and renal failure, which was most probably unrelated to the skin lesions. In the other case, lesions diminished but did not entirely resolve with treatment with low doses of oral prednisone. Angioendotheliomatosis can be divided into a malignant variant, which is an angiotropic lymphoma mostly of B-cell phenotype, and a benign, reactive variant, which is characterized by a proliferation of cells expressing endothelial cell markers. Only one case of angioendotheliomatosis with cells of histiocytic differentiation has been published previously under the name of intravascular histiocytosis. Our cases are very similar to the latter. The question arises as to whether intravascular histiocytic cell proliferation is a neoplastic proliferation of histiocytes or an early stage of classic reactive angioendotheliomatosis representing the residual cells associated with organization of microthrombi, which will be later followed by endothelial cell proliferation.

Intravascular histiocytosis associated with rheumatoid arthritis

“…This rare disorder was firstly described by O'Grady et al in 1994 [9]. However, these reported cases have used different terms, involving intravascular histiocytosis, cutaneous histiocytic lymphangitis and intravascular or intralymphatic histiocytosis [2,3,8,10]. Also similar skin lesions were named angioendotheliomatosis with rheumatoid arthritis [4].…”

“…Also similar skin lesions were named angioendotheliomatosis with rheumatoid arthritis [4]. Furthermore, Rieger et al suggested that intravascular histiocytosis might be the early stage of reactive angioendotheliomatosis [10]. Rare cases of intravascular histiocytosis presenting with a clinical and histologic picture similar to that of reactive angioendotheliomatosis but showing intravascular cells with a histiocytic immunophenotype have been described [3,11].…”

“…Histopathologically, chronic erythematous lesions showed features of histiocytic aggregation in dilated dermal vessels [3,8,10].…”

Cheilitis granulomatosa und Melkersson-Rosenthal-Syndrom

“…Rieger et al [7] spekulieren, dass verschiedene entzünd-liche Stimuli, z. B. Kryoproteine, zu einer thrombotischen Okklusion kleiner Gefäße führen, was wiederum eine Adhä-sion mononukleärer Zellen bewirkt und durch Expression "histiozytärer" Marker (CD68+, CD163+ Mac387+, CD1A−, S100−) zu reaktiven Veränderungen an der Basallamina mit Formation endothe- Es wird diskutiert, dass die intralymphatische Histiozytose eine Stenose oder Okklusion der lymphatischen Abflusswege mit konsekutivem Stauungsödem induzieren kann, klinisch der teigig-derben Schwellung entsprechend.…”

“…Ätiologisch werden die intralymphatischen histiozytären Aggregate entweder als Resultat einer "zellulären Drainage" des entzündlichen Prozesses der Synovia über die Lymphbahnen interpretiert [3] oder im Rahmen der vaskulären Histiozytose als frühe Form einer reaktiven Angioendotheliomatose [7].…”