HEPATIC EPITHELIOID HEMANGIOENDOTHELIOMA - BIOLOGICAL QUESTIONS BASEDON PATTERN OF RECURRENCE IN AN ALLOGRAFT AND TUMOR IMMUNOPHENOTYPE

Epithelioid hemangioendothelioma (EHE) is best considered a vascular n eoplasm of intermediate malignancy. Although usually progressive, the clinical course is highly unpredictable. The present communication des cribes a case of extensive recurrent hepatic EHE, limited to the liver allograft and initially manifest as an insidious seeding of individua l tumor cells in areas of perivenular inflammation associated with rej ection. A detailed immunophenotypic characterization of this and a sma ll series of EHE was carried out in an effort to highlight subtle dise ase recurrence and to gain possible insights into tumor biology associ ated with this intriguing disease, In a series of five cases of hepati c EHE, CD34 (QB-END/10) was found to be more sensitive than Factor VII I (F-VIII) for recognition of the disease, similar to previous reports . The former diffusely and distinctly stained both epithelioid and den dritic tumor cells, whereas staining for the latter was focal, indisti nct, and showed a high background. Although the tumor cells were negat ive for some markers of dendritic or macrophage maturation, such as CD 1a, S100 protein, Mac 387, CD68, and LN3, there was marked infiltratio n of hepatic EHE by factor XIIIa + (F-XIIIa), Mac 387+, CD68+, and LN3 + macrophages and dendrocytes, most of which were interpreted as react ive. The ''reactive'' macrophage and dendrocyte populations were prese nt throughout the fibrotic stroma and intermingled with the epithelioi d clusters of EKE. Interestingly, a small subset of tumor cells coexpr essed CD34 or F-VIII and F-XIIIa, the last of which is normally restri cted to cells of the monocyte/macrophage lineage and cytokine activate d microvascular endothelium in vitro. The known association of F-XIIIa + dendrocytes with granulation tissue, repair and fibrogenesis, and th e modulation of F-XIIIa and F-VIII expression by inflammatory cytokine s led us to speculate that EHE lesions may derive from primitive ''ret iculoenothelial'' cells that can differentiate along endothelial and d endritic pathways. The EHE lesions may represent a neoplastic analogue of wound healing. Thus, the variability in F-VIII staining, the stron g expression of CD34, the infiltration of EHE lesions with F-XIIIa+ de ndrocytes, and the coexpression of CD34 and F-XIIIa on a subset of tum or cells may have an important biological basis.