Journal of Pediatric Ophthalmology and Strabismus

Short Subjects 

Conjunctival Angiolymphoid Hyperplasia With Eosinophilia in a Child

Liliya Shevchenko, DO; Thomas Aaberg, Jr., MD; Hans E. Grossniklaus, MD

Abstract

Angiolymphoid hyperplasia with eosinophilia is a rare benign vascular proliferation with lymphocytic and eosinophilic infiltrate. Angiolymphoid hyperplasia with eosinophilia presents as single or multiple dome-shaped papules or plaques involving the dermis and subcutaneous tissues of the head and neck region. Conjunctival angiolymphoid hyperplasia with eosinophilia is rare, with only two previous case reports.

From Michigan State University and Metro Health Hospital (LS), Grand Rapids, Michigan; Retina Specialists of Michigan (TA), Grand Rapids, Michigan; and Emory Eye Center (HEG), Atlanta, Georgia.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Liliya Shevchenko, DO, 2757 Leonard St., Suite 200, Grand Rapids, MI 49525. E-mail: liliyashevchenko@hotmail.com

Received: May 25, 2011
Accepted: September 06, 2012
Posted Online: December 04, 2012

Abstract

Angiolymphoid hyperplasia with eosinophilia is a rare benign vascular proliferation with lymphocytic and eosinophilic infiltrate. Angiolymphoid hyperplasia with eosinophilia presents as single or multiple dome-shaped papules or plaques involving the dermis and subcutaneous tissues of the head and neck region. Conjunctival angiolymphoid hyperplasia with eosinophilia is rare, with only two previous case reports.

From Michigan State University and Metro Health Hospital (LS), Grand Rapids, Michigan; Retina Specialists of Michigan (TA), Grand Rapids, Michigan; and Emory Eye Center (HEG), Atlanta, Georgia.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Liliya Shevchenko, DO, 2757 Leonard St., Suite 200, Grand Rapids, MI 49525. E-mail: liliyashevchenko@hotmail.com

Received: May 25, 2011
Accepted: September 06, 2012
Posted Online: December 04, 2012

Introduction

Many believe angiolymphoid hyperplasia with eosinophilia to be a reactive rather than a neoplastic entity. It represents a vaguely defined spectrum of vascular lesions of the skin including epithelioid hemangioma,1,2 inflammatory angiomatous nodule,3 and Kimura disease (benign inflammatory condition that presents as painless subcutaneous masses in the head and neck region, predominantly in Asian males).4,5 Orbital involvement is rare, and conjunctival involvement is exceptionally uncommon. There have been two previous case reports of conjunctival angiolymphoid hyperplasia with eosinophilia, and one case of conjunctival angiolymphoid hyperplasia with eosinophilia/Kimura disease.6–8 Due to nomenclatural confusion between the abovementioned entities in western literature, the true number of angiolymphoid hyperplasia with eosinophilia cases may be underreported.

Case Report

A 12-year-old boy presented with a 7-month history of a red eye, not associated with pain, palpable tenderness, photophobia, or decreased vision. The redness persisted despite use of topical prednisolone and loteprednol etabonate. He had no other known medical problems. The visual acuities were 20/20 and 20/25 in the right and left eyes, respectively. The intraocular pressures were at 19 and 18 mm Hg in the right and left eyes, respectively. Slit-lamp examination of the right eye was normal. Slit-lamp examination of the left eye showed a nodular area of scleral injection and edema that extended over approximately three clock hours of the globe between 12:00 and 3:00 o’clock circumferentially and 7.0 mm from the limbus (Figure 1). The remainder of the examination was normal.

Clinical appearance shows a nodular, firm, pink mass, outlined by arrows.

Figure 1. Clinical appearance shows a nodular, firm, pink mass, outlined by arrows.

With laboratory results pending, the initial diagnosis of scleritis was made and the patient was given 400 mg of ibuprofen three times daily and topical prednisolone acetate four times daily. One week later, the lesion remained unchanged. Imaging and blood work results were noncontributory (Table 1). The possibility of benign lymphocytic infiltrate was considered. Excisional biopsy of the episcleral nodule was performed. Examination showed a cellular proliferation with associated vascular channels and numerous plump endothelial cells in the substantia propria. Immunostain for CD31 was positive in several areas of the lesion. Scattered lymphocytes and eosinophils were also present (Figures 23). Based on these findings, the diagnosis of angiolymphoid hyperplasia with eosinophilia (epithelioid hemangioma) was made.

Results of Diagnostic Tests

Table 1: Results of Diagnostic Tests

Numerous plump endothelial cells (arrows) with centrally placed nuclei line small vascular lumens containing erythrocytes (hematoxylin–eosin, original magnification ×25).

Figure 2. Numerous plump endothelial cells (arrows) with centrally placed nuclei line small vascular lumens containing erythrocytes (hematoxylin–eosin, original magnification ×25).

An immunostain for CD 31 highlights endothelial cells in the lesion (peroxidase anti-peroxidase, original magnification ×100).

Figure 3. An immunostain for CD 31 highlights endothelial cells in the lesion (peroxidase anti-peroxidase, original magnification ×100).

Discussion

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.

Cases of Conjunctival Angiolymphoid Hyperplasia With Eosinophilia (Epithelioid Hemangioma)

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.

References

  1. Olsen TG, Helwig E. Angiolymphoid hyperplasia with eosinophilia: a clinicopathologic study of 116 patients. J Am Acad Dermatol. 1985;12:781–796. doi:10.1016/S0190-9622(85)70098-9 [CrossRef]
  2. Wells GC, Whimster IW. Subcutaneous angiolymphoid hyperplasia with eosinophilia. Br J Dermatol. 1969;81:1–15. doi:10.1111/j.1365-2133.1969.tb15914.x [CrossRef]
  3. Wilson-Jones E, Bleehen SS. Inflammatory angiomatous nodules with abnormal blood vessels occurring about the ears and scalp. Br J Dermatol. 1969;81:804–816. doi:10.1111/j.1365-2133.1969.tb15948.x [CrossRef]
  4. Kimura T, Yoshimura S, Ishikawa W. Unusual granulation combined with hyperplastic change of lymphatic tissue. Trans Soc Pathol Jpn. 1948;37:179–180.
  5. Urabe A, Tsuneyoshi M, Enjoji M. Epithelioid hemangioma versus Kimura’s disease: a comparative clinicopathologic study. Am J Surg Pathol. 1987;11:758–766. doi:10.1097/00000478-198710000-00003 [CrossRef]
  6. Jayamanne DG, Webber SK, Ridley RE, Cottrell DG, McCarthy JH. Angiolymphoid hyperplasia with eosinophilia (Kimura disease) of the conjunctiva. Br J Ophthalmol. 1995;79:1053–1054. doi:10.1136/bjo.79.11.1053 [CrossRef]
  7. Esmaili DD, Chang EL, O’Hearn TM, Smith RE, Rao NA. Simultaneous presentation of Kimura disease and angiolymphoid hyperplasia with eosinophilia. Ophthal Plast Reconstr Surg. 2008;24:310–311. doi:10.1097/IOP.0b013e31817e9bba [CrossRef]
  8. Huang M, Lloyd WC, O’Hara M. Angiolymphoid hyperplasia with eosinophilia: an unusual presentation in a child. J AAPOS. 2008;12:302–304. doi:10.1016/j.jaapos.2007.12.010 [CrossRef]
  9. Archer KF, Hurwitz JJ, Heathcote G. Orbital angiolymphoid hyperplasia with eosinophilia: presentation as chalazion. Ophthal Plast Reconstr Surg. 1991;7:208–221. doi:10.1097/00002341-199109000-00010 [CrossRef]
  10. Rosai J, Gold J, Landy R. The histiocytoid hemangiomas: a unifying concept embracing several previously described entities of skin, soft tissue, large vessels, bone, and heart. Hum Pathol. 1979;10:707–730. doi:10.1016/S0046-8177(79)80114-8 [CrossRef]
  11. Fernandez LA, Olsen TG, Barwick KW, Sanders M, Kaliszewski C, Inagami T. Renin in angiolymphoid hyperplasia with eosinophilia: its possible effect on vascular proliferation. Arch Pathol Lab Med. 1986;110:1131–1135.
  12. Buggage RR, Spraul CW, Wojno TH, Grossniklaus HE. Kimura disease of the orbit and ocular adnexa. Surv Ophthalmol. 1999;44:79–91. doi:10.1016/S0039-6257(99)00064-8 [CrossRef]
  13. Gabbedy R, Nash S. Neoplasms and other tumors. In: Yanoff M, Sassani JW, eds. Ocular Pathology. Philadelphia: Elsevier; 2009:573.
  14. Cham E, Smoller BR, Lorber D, Victor TA, Cibull TL. Epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia) arising on the extremities. J Cutan Pathol. 2010;37:1045–1052. doi:10.1111/j.1600-0560.2009.01400.x [CrossRef]
  15. Pettinato G, Insabato L, De Chiara A, Ruocco V, Bucci L. Fine-needle aspiration cytology of angiolymphoid hyperplasia with eosinophilia: a case report with electron microscopy and immunohistochemistry. Diagn Cytopath. 1989;5:88–94. doi:10.1002/dc.2840050117 [CrossRef]

Results of Diagnostic Tests

Test Ordered Result/Value Reference Ranges
Complete blood cell count with manual differential Normal without eosinophilia
C-reactive protein < 0.2 mg/L 0.0–9.9 mg/L
Erythrocyte sedimentation rate 4 mm/hr 0–15 mm/hr
Angiotensin converting enzyme 61 U/La 20–60 U/L
Classic antineutrophil cytoplasmic antibody Negative Negative
Protoplasmic-staining antineutrophil cytoplasmic antibody Negative Negative
Rheumatoid factor Within normal limits
Chest radiograph Within normal limitsb

Cases of Conjunctival Angiolymphoid Hyperplasia With Eosinophilia (Epithelioid Hemangioma)

Report Jayamanne et al.6, 1995 Esmaili et al.7, 2008 Huang et al.8, 2008 Current Case
Age (y) 24 50 11 12
Location Right: inferior temporal bulbar conjunctiva Left: inferior lateral bulbar conjunctiva Right: inferior nasal limbus Left: superior lateral
Duration Unknown 3 months 2 years 7 months
Pain Absent Absent Absent Absent
Lymphoid follicles Present Absent Faint Absent
Initial impression Infectious, foreign body Conjunctival cyst Phlyctenule, pyogenic granuloma Nodular sclertitis

10.3928/01913913-20121127-04

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