Angiolymphoid hyperplasia with eosinophilia is a benign vascular lesion most commonly found in the head and neck regions, especially within the periauricular area. Orbital involvement is uncommon, with only 10 cases reported by 1991. In 1995, Jayamanne et al. described a case of conjunctival angiolymphoid hyperplasia with eosinophilia/Kimura disease in which they used those two terms interchangeably, tending to favor the latter diagnosis.6 Two case reports of angiolymphoid hyperplasia with eosinophilia by Esmaili et al.7 and Huang et al.8 followed in 2008 describing a nonpainful, erythematous, and well-circumscribed soft-tissue mass of the conjunctiva.
Angiolymphoid hyperplasia with eosinophilia has a slight female predominance with a median age of onset of 32 years and low incidence among black patients. Interestingly, orbital involvement tends to occur significantly later in life, with the average onset at age 56.5 years and males being affected more frequently.9 The age range for conjunctival disease, including our case, is between 11 and 50 years (mean = 24 years) with males and females being equally affected.7,8
Rosai et al. suggested benign neoplasm or reactive hyperplasia of endothelial cells as the primary mechanism of angiolymphoid hyperplasia with eosinophilia lesion formation.10 Others proposed that susceptible individuals could develop hyperplasia of vascular tissue in response to trauma or infection or due to hormonal imbalance related to hypersensitivity reaction or pregnancy.1,8,11 Fernandez et al. postulated that renin might be accountable for formation and growth of angiolymphoid hyperplasia with eosinophilia.11 They demonstrated the presence of renincontaining cells surrounding vascular structures; however, none of them were endothelial, mast, or lymphoid cells.
Clinically, cutaneous lesions of angiolymphoid hyperplasia with eosinophilia have been described as single dome-shaped, light pink to red-brown papules or nodules. Although uncommon, multiple lesions can occur in the head and neck region.1 Archer et al. observed that all reported orbital lesions were solitary in nature.9 Among three previously reported conjunctival angiolymphoid hyperplasia with eosinophilia nodules, the first case was a single erythematous elevation, the second case involved two separate lesions with one of them being ulcerated, and the third case was a single white ulcerated lesion (Table 2).6–8 In orbital disease, patients complain of proptosis, eyelid edema, palpable mass, abnormal motility, pain, and discomfort,9 whereas conjunctival lesions appear to be asymptomatic.
Table 2: Cases of Conjunctival Angiolymphoid Hyperplasia With Eosinophilia (Epithelioid Hemangioma)
Infrequently, the following associated findings may be observed with angiolymphoid hyperplasia with eosinophilia: regional adenopathy (19% Olsen and Helwig), peripheral blood eosinophilia, and elevated immunoglobulin-E levels.1,5,12
Histopathologically, the angiolymphoid hyperplasia with eosinophilia lesions show proliferating blood vessels lined by atypical endothelial cells and an inflammatory infiltrate dominated by eosinophils and lymphocytes localized to the different levels of the dermis and subcutaneous tissue.1,5,12 Endothelial cells are plump with abundant eosinophilic cytoplasm and have scalloped borders, simulating epithelial cells lining blood vessels and protruding into the lumina (hence the name “epithelioid hemangioma”).13 Endothelial aggregates of small capillary-sized vessels around a larger artery are characteristic of angiolymphoid hyperplasia with eosinophilia.1,5,8 Arteriovenous shunts are commonly found, especially in the deeper tissue. Lymphoid follicles are rare. Various immunohistochemical studies can be used to facilitate the diagnosis of angiolymphoid hyperplasia with eosinophilia. The cells comprising such lesions show positive reaction for endothelial markers such as factor VIII, Ulex europaeus agglutinin-1 (UEA-1), and CD 31.1,5,14,15
Preoperative diagnosis of angiolymphoid hyperplasia with eosinophilia is uncommon, and the differential diagnoses include Kimura disease, lymphoproliferative disorder, epithelioid hemangioendothelioma, angiosarcoma, and insect bites, to name a few. The contention as to whether angiolymphoid hyperplasia with eosinophilia and Kimura disease represent the same disease dates back to 1969. Although recognizing the histologic differences between the two entities, Wells and Whimster2 suggested that observed variations denote temporal progression of the same disease with angiolymphoid hyperplasia with eosinophilia being an earlier stage and Kimura disease representing the later stage. Indeed, there is a significant clinical and histological overlap between them. They both occur as nodules in head and neck regions and both contain similar histologic findings including vascular proliferation, inflammatory infiltrate, and lymphoid follicles with germinal centers. However, Kimura disease occurs more commonly in adolescent Asian males with higher incidence of adenopathy, eosinophilia, and elevated Ig-E, whereas angiolymphoid hyperplasia with eosinophilia tends to affect women of middle age and various ethnicities. Histologically, fibrosis, vascular proliferation in inflamed stroma, and lymphoid follicles with germinal centers are more characteristic of Kimura disease.5 In addition, Kimura disease can be associated with nephropathy.12 To date, any definite association between the two remains uncertain.
Treatment strategies for angiolymphoid hyperplasia with eosinophilia include observation, cryotherapy, laser ablation, excision, steroids, radiation, and chemotherapy either alone or in different combinations. The post-excisional recurrence rate is 33% and has been associated with intravascular endothelial proliferation, arteriovenous shunts, absence of cellular pleomorphism, and abnormal mitotic figures; however, surgical excision remains the preferred therapy.1,12
The rarity of ocular involvement and consistent nosological confusion makes it difficult to establish the exact number of reported cases of conjunctival angiolymphoid hyperplasia with eosinophilia. In the literature search conducted for this article, we were able to find two cases of conjunctival angiolymphoid hyperplasia with eosinophilia and one case was designated as conjunctival angiolymphoid hyperplasia with eosinophilia/Kimura disease. We report the fourth case of this disease. Most of the information regarding epidemiology, histopathologic features, clinical presentation, treatment, and prognosis for angiolymphoid hyperplasia with eosinophilia lesions has to be extrapolated from previous reports of subcutaneous and orbital involvement. The diagnosis of such lesions would most likely require biopsy because most of the reported lesions are diagnosed by histopathologic examination. Ophthalmologists’ recognition and further reporting of conjunctival angiolymphoid hyperplasia with eosinophilia would help future understanding of this uncommon and obscure disease.