Angiolymphoid hyperplasia with eosinophilia (ALHE) is an unusual but distinctive vascular tumour typically presenting in women during their early to mid-adult life. Although most lesions are located in the subcutis or dermis of the head and neck (Enzinger & Weiss 1995), ALHE is reportedly uncommon in the periocular region (Buggage et al. 1999). Because of the presumed neoplastic origin ALHE has alternatively been termed epitheloid haemangioma and histiocytic haemangioma. Conversely, Kimura’s disease (KD) most probably represents an allergic or autoimmune response preferentially occurring in the head and neck region of young Asian males. Because ALHE and KD share many clinical and histopathological features these lesions have repeatedly been confused and the designations used interchangeably. Overwhelming data now indicate that significant differences exist and in general pathology these entities are separated (Urabe et al. 1987; Chan et al. 1989), but in ophthalmology the original, unifying concept has largely remained unchanged. Even authoritative ophthalmic textbooks currently report ALHE and KD as being one single entity (Rubin & Jakobiec 1994; Jakobiec et al. 1996). Only very recently were two cases of periocular KD reported with the purpose to separate this entity from ALHE (Buggage et al. 1999). Herein we present a case of periocular ALHE with features clearly distinguishable from KD in further support of the concept that KD and ALHE are two separate entities.
ABSTRACT. Purpose: To emphasize the differences between angiolymphoid hyperplasia with eosinophilia (ALHE) and Kimura’s disease (KD), two entities often confused in the ophthalmic literature.
Methods: Case report of a subcutaneous mass in the periocular region of a 45-year old woman and a MEDLINE review of the ophthalmic and non-ophthalmic literature on ALHE and KD.
Results: The clinical and histopathological findings of the present case were consistent with ALHE, but not with KD. A survey of the current ophthalmic literature indicates that these two designations are still often used synonymously, despite that non-ophthalmic papers now separate ALHE from KD.
Conclusion: The clinical and histopathological features of ALHE are most often distinctly different from KD and these entities should be clearly separated in the ophthalmic literature.
A 45-year old Caucasian woman presented with a history of a slowly growing mass over the previous 6–8 months. Examination revealed a palpable mass located immediately superior to the medial part of the left eyebrow. Surgery was performed and a well-circumscribed subcutaneous mass was found. Following complete excision, the specimen was fixed in 4% formaldehyde and submitted for histopathological examination. There have been no signs of recurrence after a follow-up period of 18 months.
The mass measured 11×10×7 mm in size and was cut in two halves. The cut surface disclosed a central, softer core surrounded by a rim of denser tissue. Both halves were paraffin embedded and routinely processed for light microscopy. Briefly, sections were cut at 4 μm and stained with haematoxylin and eosin, the van Gieson stain for collagen, the periodic acid-Schiff stain and Alcian blue. In addition, sections were immunostained for the CD45 (clone OPD4; product code M0742) and CD20 (clone B-Ly1; product code M0774) markers (Dako, Carpinteria, CA, USA) using the standard avidin-biotin complex method to detect T and B cells, respectively.
Examination by light microscopy disclosed a central vessel with a partly eroded wall. The central vessel was surrounded by slightly oedematous myxoid tissue that stained positive for Alcian blue. This softer core was encompassed by denser, more cellular tissue, which in part was lined by a thin pseudocapsule of compressed fibrous tissue (Fig. 1). At higher magnification, the cellular component consisted of small vessels featuring plump endothelial cells surrounded by inflammatory cells including a large proportion of eosinophils, but also some lymphocytes and plasma cells (Figs. 2, 3). A few lymphoid follicles were present in the periphery of the lesion immediately beneath the thin pseudocapsule (Fig. 1). While lymphocytes in the germinal centre were largely positive for CD20 (B cells), lymphocytes in the periphery were positive for CD45 (T cells). The overall features were consistent with those previously reported in cases of ALHE, but distinctly different from KD.
A survey using the search words ALHE or KD or histiocytoid haemangioma or epitheloid haemangioma was performed. The survey included accessing the MEDLINE website http://www.ncbi.nlm.nih.gov/PubMed/medline. html (National Library of Medicine, Washington, DC, USA) on the Internet combined with a CD-ROM search of a database containing the ophthalmic literature of Embase for the past 10 years (Silverplatter, Norwood, MA, USA). Retrieved papers included 7 periocular lesions designated exclusively as ALHE. These papers are listed below.
Kimura’s disease and ALHE share some similarities, but many clinical and histopathological features remain distinctly different (Chan et al. 1989). The essential characteristics have been summarised (Table 1). The plump endothelial cell characteristic of ALHE probably remains the key to separation of these entities and the alternative designations epitheloid haemangioma and histiocytic haemangioma reflect the presumed endothelial cell origin and neoplastic pathogenesis of ALHE. Interestingly, some data now indicate that 60% of ALHE lesions include the presence of an intimately associated medium-sized artery or vein. Often these vessels feature vascular damage such as fibrointimal proliferation, disruption or duplication of the elastic lamina and disruption of the vessel wall (Fetsch & Weiss 1991). This has generated speculations of vessel damage causing endothelial cell hyperplasia leading to ALHE. The findings of the present case are consistent with this hypothesis.
The history of KD being confused with ALHE has been nicely outlined by Buggage et al. (1999). Briefly, the misconception of ALHE and KD being two ends of the spectrum of the same disease dates back to the report by Wells and Whimster (1969). Pioneering work by Rosai et al. (1982) later postulated that ALHE and KD are two separate entities and this concept was gradually accepted by most branches of surgical pathology.
However, it would appear that ophthalmic pathology lagged behind and recently Milite and McCormick (1996) noted that among the 17 cases at that time reported as periocular KD and/or ALHE, only three authors clearly differentiated ALHE from KD. Buggage et al. (1999) very recently reviewed 33 cases diagnosed as eosinophilic granuloma, KD, ALHE or KD/ALHE involving the orbit or ocular adnexa. A revised diagnosis of KD was offered for 19 cases and ALHE for three. The remaining 19 cases were considered indeterminate based on the published histopathological information. Even when including the case by Milite & McCormick, data suggest that ALHE is rarer than KD in the periocular region with only 7 cases being designated as periocular ALHE and possibly only three remaining after review (Archer et al. 1991; Bostad & Pettersen 1982; Cook & Stafford 1988; Dhermy et al. 1979; Eisenberg & Lowlicht 1985; Milite & McCormick 1996; Sheren et al. 1989). The findings of the present case favour ALHE as an entity separate from KD in keeping with views currently held by most soft tissue tumour pathologists. The histopathological features are also consistent with ALHE being caused by vascular trauma leading to endothelial cell hyperplasia.
Stefan Seregard, MD, PhD
Ophthalmic Pathology and Oncology Service
St. Erik’s Eye Hospital
SE-112 82 Stockholm
Received on November 22nd, 1999.
Accepted on August 25th, 2000.