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Immunohistochemical Investigations of Orbital Infantile Hemangiomas and Adult Encapsulated Cavernous Venous Lesions (Malformation Versus Hemangioma)

Osaki, Tammy H. M.D.*†; Jakobiec, Frederick A. M.D., D.SC.*‡; Mendoza, Pia R. M.D.*‡; Lee, Yongjae M.D.§; Fay, Aaron M.D.*‖

Ophthalmic Plastic and Reconstructive Surgery: May/June 2013 - Volume 29 - Issue 3 - p 183–195
doi: 10.1097/IOP.0b013e31828b0f1f
Original Investigation
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Purpose: Immunohistochemical studies have begun to advance knowledge regarding the pathogenesis of vascular anomalies in many anatomical regions. However, the immunohistochemical features of most orbital tumors have been overlooked. Therefore, a comparative immunohistochemical study of a series of the 2 most common orbital vascular lesions— infantile hemangioma (IH) and encapsulated cavernous venous lesion (ECVL), the latter also termed cavernous hemangioma or venous malformation—was undertaken.

Methods: Twenty surgically excised orbital tumors diagnosed clinically and histopathologically as IHs (10 cases) or “cavernous hemangioma” (10 cases) were evaluated pathologically and immunohistochemically using hematoxylin and eosin, Alcian blue, Masson trichrome, GLUT-1, CD31, CD34, D2-40, smooth muscle actin (SMA), desmin, and Ki-67 probes.

Results: All cases reacted strongly with the traditional blood vessel endothelial markers CD31 and CD34 and were negative for D2-40, a selective marker for lymphatic endothelium. All IH were positive for GLUT-1, and all ECVL were negative for GLUT-1. In IH, SMA (but not desmin) stained a monolayer of pericytes and in ECVL multilaminar smooth muscle vascular mural cells and intravascular (interstitial) stromal cells. Nuclear Ki-67 immunostaining was strongly positive in IH (average of 16.3%) and close to zero in ECVL.

Conclusions: Immunophenotypic results for ECVL and IH demonstrated no overlapping staining patterns. Infantile hemangioma had the classical architecture of capillaries. Because of the constant presence of mural smooth muscle, it was concluded that ECVL is an accurate and descriptive term. However, desmin negativity in ECVL indicates myofibroblastic differentiation rather than full-fledged smooth muscle differentiation. Infantile hemangioma may display ectatic channels as the lesion ages but does not acquire multilaminar smooth muscle walls. Its pericytes lack cytoplasmic filaments and desmin reactivity but are SMA-positive because of the presence of poorly polymerized actin in the cytosol. In IH, Ki-67 positivity was observed in the endothelial cells of the solid and more ectatic regions. In contrast, the virtual absence of Ki-67 positivity in ECVL lends further support for the interpretation that it is more closely related to a malformation than a benign neoplasm.

Immunohistochemical staining definitively separated infantile hemangiomas from encapsulated cavernous venous lesions (so-called cavernous hemangiomas) based on their distinctive cytoarchitectures and excluded the participation of lymphatic endothelia in all cases of both kinds of lesions.

*Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, U.S.A.;Department of Ophthalmology, Federal University of Sao Paulo—UNIFESP, Sao Paulo, SP, Brazil; ‡David G. Cogan Laboratory of Ophthalmic Pathology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, U.S.A.; §Department of Ophthalmology, School of Medicine, Ulsan University, Ulsan, Korea; and ‖Department of Ophthalmic Plastic and Reconstructive Surgery, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, U.S.A.

Accepted for publication January 31, 2013.

Tammy H. Osaki received the Gillingham award from the Pan American Ophthalmological Foundation and Retina Research Foundation.

The authors have no financial or conflicts of interest to disclose.

Address correspondence and reprint requests to Frederick A. Jakobiec, M.D., D.SC., David G. Cogan Laboratory of Ophthalmic Pathology, Massachusetts Eye and Ear Infirmary, Suite 328, 243 Charles Street, Boston, MA 02114. E-mail: Fred_Jakobiec@meei.harvard.edu

© 2013 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.