A through E, Clinical photographs and radiologic findings in patients with orbital ALHE. The photographs show an anterior orbital mass that involves the left side with mild swelling and ptosis in patient 1 (A), patient 2 (B), patient 4 (D), and patient 5 (E). C, The computed tomogram in patient 3 shows an extraconal mass in the right orbit. E, In patient 5, there is marked involvement of the upper and lower eyelids.
A through E, Histologic examination with hematoxylin-eosin stain reveals inflammation marked by a large number of eosinophils admixed with lymphocytes and plasma cells in all patients. Vascular proliferation of the capillaries, arterioles, and venules are best seen in patient 3 (C) and patient 4 (D). The endothelial cells lining the vessels are histiocyte-like and contain intracytoplasmic vacuoles, which are depicted with arrowheads in patient 5 (E) but were present in all patients.
Customize your JAMA Network experience by selecting one or more topics from the list below.
Azari AA, Kanavi MR, Lucarelli M, et al. Angiolymphoid Hyperplasia With Eosinophilia of the Orbit and Ocular Adnexa: Report of 5 Cases. JAMA Ophthalmol. 2014;132(5):633–636. doi:10.1001/jamaophthalmol.2013.8243
To report the clinical and histopathologic findings of ocular adnexal angiolymphoid hyperplasia with eosinophilia, an unusual but often misdiagnosed benign disorder.
The ophthalmologic findings of angiolymphoid hyperplasia with eosinophilia with ocular adnexal involvement are variable and include eyelid swelling, ptosis, proptosis, and loss of vision. Imaging studies typically reveal a well-circumscribed mass in the orbit. The condition may resemble other diseases that involve the orbit and ocular adnexal tissue, such as lymphoma, hemangioma, sarcoidosis, and dermoid cyst. Histopathologic analysis reveals marked vascular proliferation with an accompanying inflammation composed of numerous eosinophils, lymphocytes, and plasma cells.
Conclusions and Relevance
Angiolymphoid hyperplasia with eosinophilia is a rare disease that can affect the ocular adnexal tissue. The clinical presentation is often nonspecific; therefore, histopathologic studies are essential for diagnosis and subsequent management of this benign condition.
Angiolymphoid hyperplasia with eosinophilia (ALHE), also known as epithelioid hemangioma, is a rare, benign disorder characterized by marked vascular proliferation and inflammation. The usual sites of involvement are the subcutaneous tissues of the head and neck. Involvement of the ocular adnexa, including the orbits, has also been reported in the literature.1,2 Similar to many tumors that involve the ocular adnexa or orbit, the presenting signs, symptoms, and radiologic findings in ALHE are nonspecific; therefore, histologic evaluation is essential in making the diagnosis. We report the clinical (Figure 1) and histopathologic (Figure 2) findings in 5 patients with ocular adnexal ALHE who presented to us in a 20-year period. Thirty-six cases of ALHE in 21 reports with orbital and ocular adnexal involvement have been reported previously in the literature. To our knowledge, the current report is the largest case series reported in the literature.
Five patients (3 men and 2 women) had ALHE diagnosed at a range of 11 to 86 years. The clinical and histopathologic characteristics of the patients are summarized in the Table. In all 5 patients, ALHE presented unilaterally with eyelid swelling. Four patients had orbital involvement, with the imaging studies revealing an intraorbital mass (patients 1, 3, and 4) or enlargement of the lacrimal gland (patient 2). All the patients with orbital involvement presented with ptosis and eyelid swelling. Furthermore, all the patients with orbital involvement were initially clinically misdiagnosed by the referring ophthalmologist; in 2 patients lymphoma was suspected, and in 2 patients the initial clinical impression was sarcoidosis. The 2 patients who were suspected of having sarcoidosis were younger and had mildly elevated serum angiotensin-converting enzyme (ACE) levels. Only 1 patient was suspected of having ALHE before histopathologic evaluation (patient 5); this patient had a history of multiple scalp lesions consistent with ALHE. All of the patients with orbital involvement underwent incisional biopsy, and 1 patient was given oral steroids as well (patient 1). The patient with eyelid involvement underwent total excisional biopsy. The histopathologic findings in all patients include proliferation of the small capillaries (thin-walled vessels that connected the arterioles and venules), arterioles (small blood vessels that have a muscular wall and extend from an artery), and venules (small blood vessels that have thinner muscular wall and are more collapsible). The endothelial cells lining the vessels are histiocyte-like and demonstrate intracytoplasmic vacuolization. Furthermore, all patients had lymphoplasmacytic inflammation with the presence of numerous eosinophils. True lymph follicles with well-differentiated germinal centers were either absent (patients 1 and 4) or present in small numbers (patients 2, 3, and 5). The patients were followed up for 3 months to 6 years after the initial biopsy. In 4 of 5 patients, no recurrence was noted during any of the follow-up visits.
Angiolymphoid hyperplasia with eosinophilia is a benign condition seen more commonly in non-Asian races usually with a female preponderance.2 The clinical presentation is variable, and the definitive diagnosis requires histopathologic examination. The histologic findings typically demonstrate a well-circumscribed lesion composed of vascular proliferation and inflammation. The vascular component is characterized by proliferation of capillaries, arterioles, and venules; the inflammation is usually lymphoplasmacytic, with numerous eosinophils present.2 Angiolymphoid hyperplasia with eosinophilia is distinguishable from Kimura disease (KD), a closely related condition that shares many of the clinical and histologic features of ALHE.2 In ALHE, proliferating arterioles, venules, and capillaries are often seen; furthermore, the vascular endothelium in ALHE frequently demonstrates atypia3 and intracytoplasmic vacuoles.2 This finding is in contrast to the vascular proliferation in KD, where mostly a proliferation of the capillaries is seen and the endothelial cells do not demonstrate atypia. Other histologic features of ALHE that help to distinguish it from KD are relative paucity of follicles and fibrosis.2 Both ALHE and KD can also be distinguished based on their clinical features. Angiolymphoid hyperplasia with eosinophilia is more commonly seen in middle-aged whites, whereas KD is more commonly seen in young Asians. The duration of the disease is generally shorter (1-4 years) for ALHE compared with KD (up to 25 years). Furthermore, patients with KD often have adenopathy, nephropathy, and systemic eosinophilia.2
The exact pathogenesis of ALHE remains unknown; however, it has been proposed that ALHE may represent a benign proliferation of the endothelial cells in response to trauma or inflammation.3 Treatment consists primarily of surgical excision or debulking.1 Other forms of treatment include irradiation, oral and intralesional steroids, and cytotoxic agents.2 Because most lesions regress spontaneously, it is reasonable to observe the lesion waiting for spontaneous regression after an incisional biopsy. This may be the preferred approach in areas where extensive resections may be disfiguring. Recurrence may occur after incomplete excision.3
The described patients share the histologic features unique to ALHE, including proliferation of arterioles and venules, nuclear atypia of the vascular endothelium, and paucity of follicles. The clinical picture was variable. Ptosis was the most common sign and was seen in 4 patients. Two of the patients were adolescents, in contrast to the typical presentation in middle-aged patients. Preoperatively, patients were believed to have lymphoma, hemangioma, or lacrimal gland involvement from sarcoidosis. Two of the younger patients in our series had mildly elevated serum ACE levels; 1 patient had further pulmonary workup, the results of which were normal. On biopsy, no histologic evidence of granulomatous inflammation suggestive of sarcoidosis was seen in any of the patients, and all the findings were consistent with ALHE. In general, elevated serum ACE levels may be present in younger patients even in the absence of granulomatous disease.4 Patient 5 was presented as an ophthalmic image in the literature but not discussed in detail.5
In conclusion, ALHE is a rare orbital and ocular adnexal disease that presents with a variety of nonspecific symptoms, such as blurred vision, proptosis, diplopia, and lid swelling. A definitive diagnosis of ALHE can only be made by histopathologic analysis; therefore, microscopic evaluation of the biopsied specimens is essential for definitive diagnosis and proper management.
Submitted for Publication: June 7, 2013; final revision received October 28, 2013; accepted November 16, 2013.
Corresponding Author: Amir A. Azari, MD, Department of Ophthalmology and Visual Sciences, University of Wisconsin, 600 Highland Ave, Room F4/349, Madison, WI 53792 (firstname.lastname@example.org).
Published Online: March 27, 2014. doi:10.1001/jamaophthalmol.2013.8243.
Author Contributions: Drs Azari and Kanavi had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Azari, Lee.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Azari, Albert.
Critical revision of the manuscript for important intellectual content: Azari, Kanavi, Lucarelli, Lee, Lundin, Potter.
Statistical analysis: Lundin.
Obtained funding: Albert.
Administrative, technical, or material support: Azari, Kanavi, Lucarelli, Lee, Albert.
Study supervision: Azari, Kanavi, Potter, Albert.
Conflict of Interest Disclosures: None reported.
Funding/Support: This work was supported by Core Grant for Vision Research P30-EY016665 from the National Institutes of Health and an unrestricted department award from the Research to Prevent Blindness.
Role of the Sponsors: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.