W. RICHARDGREEN MD
Copyright 2004 American Medical Association. All Rights Reserved.Applicable FARS/DFARS Restrictions Apply to Government Use.2004
Kimura disease (KD) is an inflammatory condition that classically manifestsas painless subcutaneous nodules of the head and neck in young Asian males.1,2 Histologically, it is characterizedas lymphoid follicles with germinal centers, distinguished by an eosinophilicinfiltrate and varying degrees of fibrosis.2 Thismakes the diagnosis of KD challenging as these histological features may overlapthat of idiopathic orbital inflammation3 orangiolymphoid hyperplasia with eosinophilia (ALHE).1,2 Wediscuss a unique case of KD with bilateral orbital involvement in an AfricanAmerican male. Based on our English-language MEDLINE literature search, toour knowledge, this seems to be the first clearly documented case of KD withsimultaneous bilateral lacrimal gland involvement. This case is particularlyintriguing as it occurred in a non-Asian patient.
A 24-year-old urban African American man was seen with bilateral uppereyelid swelling, discomfort, and intermittent vertical diplopia of 1 year'sduration. His medical history was noncontributory. Ophthalmic examinationrevealed bilateral upper eyelid edema and a palpable mass in the anterosuperiortemporal aspect of both orbits (Figure 1).No lymphadenopathy of the head and neck was appreciated. A computed tomographicscan showed bilateral lacrimal gland enlargement without adjacent bony erosion(Figure 2). Workup disclosed normalfindings on a chest radiograph and for serum urea nitrogen, serum creatinine,and angiotensin-converting enzyme levels, and negative findings for antinuclearbody, antineutrophil cytoplasmic antibody, rapid plasma reagin, and purifiedprotein derivative (tuberculin). However, a complete blood cell count revealeda high eosinophil distribution of 24% (reference range, 0%-6%). An excisionalbiopsy via anterior orbitotomy (Figure 3)demonstrated lacrimal gland atrophy, fibrosis, lymphoid hyperplasia, and prominenteosinophilic infiltrate (Figure 4).There was no evidence of vasculitis or prominent vascular endothelial cellproliferation. The results of flow cytometric analyses were normal and specialstains for parasites were negative. The patient was given the provisionaldiagnosis of idiopathic orbital inflammation and was treated with prednisone,60 mg/d. His eyelid edema and discomfort were improved at the 1-month follow-up,but the treatment with prednisone was discontinued because of the patient'sconstitutional complaints. A follow-up computed tomographic scan showed aslight decrease in the size of the lacrimal glands.
A 24-year-old African-Americanman had bilateral upper eyelid swelling and palpable masses in the anteriorsuperolateral orbit.
Computed tomographic scan showedbilateral lacrimal gland enlargement without bony involvement.
Intraoperative view showing massivelacrimal gland enlargement. The biopsy was performed by left-sided anteriororbitotomy.
A, Biopsy specimen of lacrimalgland shows multiple lymphoid follicles with germinal centers (hematoxylin-eosin,original magnification ×40). B, Biopsy specimen at higher magnificationshows fibrosis with prominent eosinophilic infiltrate. Note that capillariesare lined by normal-appearing flat endothelial cells (hematoxylin-eosin, originalmagnification ×200).
Nine months after the initial manifestation, the patient had a tender,right submandibular mass measuring 3 cm in width. On physical examination,an additional 1-cm-wide mass was palpated in the left side of the neck, suggestinglymphadenopathy. An incisional biopsy specimen showed lymphoid proliferationwith germinal centers, periductal fibrosis, and eosinophilic infiltrate, similarto that of his lacrimal gland with the addition of eosinophilic abscesses.A complete blood cell count continued to show an elevated eosinophilic distributionof 23%. A serum IgE level showed hypergammaglobulinemia of 973 IU/mL (referencerange, <91 IU/mL). The combination of a neck mass with classic KD histopathologicalfeatures almost identical to that of his lacrimal gland, persistent peripheraleosinophilia, and elevated IgE levels without any signs of allergic or othersystemic process established the diagnosis of KD. The patient was treatedwith cyclosporine, 100 mg twice daily, for 1 month and prednisone, 10 mg/d,for 6 months and demonstrated moderate improvement of swelling and pain atthe last follow-up visit.
Kimura disease is an inflammatory process whose characteristics mayoverlap those of ALHE, also known as "epithelioid hemangioma." Despite confusionin the earlier literature, they are considered 2 distinct clinicopathologicaldiagnoses with different epidemiological, clinical, and histopathologicalcharacteristics.1,2
Kimura disease almost exclusively affects young Asian males,1,4,5 ranging inage from 2 through 59 years.1,5 Incontrast, ALHE predominates in the West, particularly affecting white womenin early to middle adult life.1,6 Kimuradisease typically manifests as firm subcutaneous nodules that commonly involvethe periauricular, parotid, or submandibular regions.1 Regionallymphadenopathy and salivary gland involvement is common.1,2,5 Angiolymphoidhyperplasia with eosinophilia develops as smaller red papules or plaques,also of the head and neck1,2 usuallywithout lymphadenpathy or salivary gland involvement.1,4 Systemically,many patients with KD have elevated IgE levels, with reports demonstratingup to a 98% incidence of eosinophilia in KD vs 24% in ALHE.1,4 Kimuradisease has been reported to be associated with asthma, tuberculosis, nephroticsyndrome, and Loeffler syndrome.1,7 Angiolymphoidhyperplasia with eosinophilia may have a benign neoplastic origin or representa secondary reaction to inflammation or other insult such as AIDS, trauma,infection, pregnancy, or hormonal imbalance.1,6,8
Authors have reviewed recent cases of KD and ALHE and better definedtheir histological characteristics.2,5 Kimuradisease is identified by follicular lymphoid hyperplasia with germinal centersembedded in a fibrocollagenous stroma.1,2 Capillaryproliferation is not characteristic of KD, but if present, the blood vesselsare thin walled and lined by flat endothelial cells.5 Eosinophilicinfiltrate is typical and eosinophilic abscesses are common.5 Thedefining feature of ALHE is an abnormal proliferation of vascular endothelialcells that are plump, atypical, cobblestonelike or histiocytoid.2,6,8 Aninflammatory infiltrate is also characteristic of ALHE but usually containsfewer eosinophils than that of KD.2
According to the 2002 review by Yeung and Ma,7 43cases of KD involving the orbit, lacrimal gland, eyelid, conjunctiva, or chorioretina,have been identified, predominantly in Asian patients. Patients with orbitalKD may have exophthalmos, eyelid swelling, a palpable mass, ocular dysmotility,ptosis, tearing, pruritis, pain, or headache.1,4,5,7 Thesuperior orbit has been found to be the most common location of disease.5,9 However, only 8 reported orbitalcases had bilateral involvement, with none of these clearly documenting bilaterallacrimal gland involvment. Our patient's initial manifestation involving bilaterallacrimal gland enlargement and inflammatory signs led us to initially pursuea workup for conditions such as syphilis, sarcoidosis, tuberculosis, and Wegenergranulomatosis. Other possible considerations in the differential includedHodgkin or non-Hodgkin lymphoma, pyogenic granuloma, eosinophilic granuloma,parasitic infection, benign papillary endothelial hyperplasia, Kaposi sarcoma,angiosarcoma, retrobulbar optic nerve meningioma or glioma, recurrent choroidalmelanoma, and metastases, which were excluded by clinical and histologicalevaluation.1,7 The rarityof KD in this setting, especially in a non-Asian patient led us to considera diagnosis of exclusion, orbital pseudotumor (ie, idiopathic orbital inflammation),which can manifest in a similar manner. Idiopathic orbital inflammation ishistopathologically diverse and an eosinophilic infiltrate can also be seen.3 However, the subsequent occurrence of a lesionwith similar histopathological features in our patient's neck, a more typicallocation for KD, in combination with persistent peripheral eosinophilia andelevated IgE levels, helped establish the diagnosis of KD. Angiolymphoid hyperplasiawith eosinophilia was ruled out because vascular proliferation of endothelialcells was not a predominant feature of the specimen.
In summary, we report a unique case of KD demonstrating bilateral lacrimalgland involvement in a non-Asian patient. Since this disease may involve theorbit and possibly have systemic involvement, it is important that physiciansbe aware of this unusual manifestation.
The authors have no relevant financial interest in this article.
Corresponding author: Dale R. Meyer, MD, Department of Ophthalmology,Lions Eye Institute, 35 Hackett Blvd, Albany, NY 12208.
Yoganathan P, Meyer DR, Farber MG. Bilateral Lacrimal Gland Involvement With Kimura Disease in an AfricanAmerican Male. Arch Ophthalmol. 2004;122(6):917-919. doi:10.1001/archopht.122.6.917