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findings, the histopathological diagnosis of ILPMD was made by a dermatopathologist (A.R.S.). A review of the literature for this diagnosis recommended a systemic workup to include complete blood count with differential, complete metabolic panel and serum protein electrophoresis, Lyme serology, and serum RPR. All these studies were normal. Abdominal ultrasound was also recommended to evaluate for the presence of organomegaly. This was performed and was normal except for a 5-cm mass in the liver that was thought to be a benign hemangioma. Follow-up CT scan of abdomen was also consistent with a benign hemangioma of the liver, and a follow-up ultrasound 6 months later confirmed the mass was stable in size. At the 19-month follow up, the patient was doing well, and there was no sign of recurrence at the site of excision of the lesion.
DISCUSSION ILPMD is a benign idiopathic lesion characterized clinically by either papules or plaques with or without surface erosion. The histopathologic hallmark of ILPMD consists of dense plasma cell infiltrates within the dermis or submucosa. The plasma cells are frequently admixed with lymphocytes and occasionally with neutrophils and eosinophils. Accompanying the dermal infiltrates are variable epidermal or epithelial changes. The latter structures are usually atrophic, and vacuolar interface change may be present. Zoon described a peculiar basal keratinocyte alteration known as “lozenge-shape” where the horizontal axis of these cells exceeds the vertical axis in length, resulting in a diamond shape. Other microscopic findings include dermal or submucosal fibrosis and small vessel proliferation.1 Following Zoon’s report of lesions on the glans penis, similar cases have been described on the vulva, buccal mucosa, palate, nasal aperture, gingiva, lips, tongue, epiglottis, larynx, and other mucosal surfaces.2 ILPMD has been described under various names including plasmacytosis mucosae, plasmacytosis orificialis, and plasma cell mucositis. In the upper aerodigestive tract, ILPMD presents as intensely erythematous mucosa with surface changes described variously as papillomatous, cobblestone, nodular, or velvety. Histologically, the differential diagnosis includes lichen planus, plasmacytoma, syphilis, and Lyme disease.1 Lichen planus is characterized by basal vacuolar keratinocyte alteration, Civatte bodies (dyskeratotic keratinocytes), and a moderate to dense inflammatory infiltrate with a predominance of lymphocytes rather than plasma cells.1 Plasmacytomas are circumscribed dense dermal infiltrates with atypical plasma cells. Immunostains demonstrate monotypism of light chain immunoglobulins.1 In secondary syphilis, the epidermis may be normal, psoriasiform, necrotic, or ulcerated. Dermal infiltrates of plasma cells, lymphocytes, and histiocytes may be perivascular, lichenoid, nodular, or diffuse. Endothelial swelling and vascular proliferation can also be found. Spirochetes may be demonstrated with special stains, and serological tests are usually positive.3 Erythema chronicum migrans, the typical rash of Lyme disease is characterized histopathologically by perivascular infiltrates of lymphocytes, plasma cells, and mast cells around the upper dermal vessels.4 Treatment of ILPMD has been reported as only variably successful. Treatment modalities that have been tried include corticosteroids (topical, intralesional, and systemic), antibiotics, destruction of the tissue (liquid nitrogen, CO2 laser, and electrocoagulation), excision, and radiation therapy. No treatment is consistently effective.2 No studies report a progression of ILPMD to malignancy of any type.2 Haqqie et al.5 have previously reported ILPMD involving the tarsal conjunctiva that was possibly a mucosal manifestation of ocular Lyme disease based on immunochemical results, positive serology, and response to antibiotics. However, chronic
Case Reports
irritation could not be ruled out. To this knowledge, the authors report the first case of ILPMD of the skin of the eyelid. They recommend including this rare lesion in the differential diagnosis of symptomatic eyelid lesions and highlight the appropriate systemic workup in the event of this diagnosis.
REFERENCES 1. Brix WK, Nassau SR, Patterson JW, et al. Idiopathic lymphoplasmacellular mucositis-dermatitis. J Cutan Pathol 2010;37:426–31. 2. Bharti R, Smith DR. Mucous membrane plasmacytosis: a case report and review of the literature. Dermatol Online J 2003;9:15. 3. Bolognia JL. Dermatology, 2nd ed. St. Louis, MO: Mosby Elsevier, 2008. 4. Duray PH. The surgical pathology of human Lyme disease. An enlarging picture. Am J Surg Pathol 1987;11 Suppl 1:47–60. 5. Haqqie N, Wroblewski D, Meyer DR, et al. Idiopathic lymphoplasmacellular mucositis-dermatitis (plasmacytosis mucosae) of the tarsal conjunctiva. J Cutan Pathol 2011;38:597–9.
A Case Series of Patients Diagnosed With Orofacial Granulomatosis Presenting Primarily With Dense Infiltrates and Severe Periorbital Edema Esfandiar J. Sabet-Peyman, M.D., and Julie A. Woodward, M.D. Abstract: Orofacial granulomatosis is a relapsing nonnecrotizing granulomatous syndrome that classically presents with lip and perioral swelling. Over the years, several patients have been referred to the Duke Eye Center Oculoplastics Department for severe, progressive, recurrent eyelid swelling interfering with both their functional vision and their appearance. In this IRB approved retrospective case series, we describe the clinical course of 5 such patients, including their presenting symptoms, diagnosis, and response to treatment. We hope that oculoplastics specialists will consider this entity in the differential diagnosis of periorbital edema and consider initiating localized antiinflammatory treatment once the diagnosis has been made.
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rofacial granulomatosis is a nonnecrotizing inflammatory disease process in the same family as Melkersson-Rosenthal syndrome (MRS) and granulomatous cheilitis.1–3 Although the phenotypic presentation can widely vary, the most common presenting symptom is orofacial edema.1–5 Perioral edema alone characterizes granulomatous cheilitis3, and the triad of orofacial edema, tongue fissuring, and facial nerve paralysis is known as MRS.1–4,6 The etiology of the disease is unknown; however, delayed hypersensitivity appears to play a role.3,5,7 Associations have been made with diseases such as sarcoidosis, Crohn disease, systemic lupus erythematosis, periodontal disease, viral infections, migraine headaches,1–3 and inciting agents such as dental amalgam,3,5 cinnamon,5,7 and infection1–3 have been suggested. There is no gold standard treatment at this time, although systemic steroids appear to be the most commonly Department of Oculoplastics, Duke Eye Center, Durham, North Carolina, U.S.A. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Julie A. Woodward, M.D., Department of Oculoplastics, Duke Eye Center, 2351 Erwin Road, Durham, NC 27710. E-mail: [email protected] DOI: 10.1097/01.iop.0000440702.85663.e5
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FIG. 1. A, Patient 1 demonstrating significant improvement in upper and lower eyelid edema and palpebral fissures after 4 years of serial treatment with local eyelid injections of combined kenalog 40 mg/cc and 2% lidocaine with epinephrine mixed 1:1 in addition to systemic methotrexate 20 mg once weekly. B, Patient 2 showing marked improvement of lower eyelid festoons after 6 months of local injections of combined kenalog 40 mg/cc, 5-fluorouracil 50 mg/cc, and lidocaine 2% with epinephrine mixed 1:1:1 alternating with kenalog 40 mg/cc and lidocaine 2% with epinephrine mixed 1:1. There was also mild improvement in upper eyelid edema following bilateral upper eyelid blepharoplasty and serial localized injections. C, Patient 3 showing markedly improved eyelid edema and induration after 3 eyelid debulking operations, systemic therapy with infliximab, several oral prednisone tapers, and serial local eyelid injections of combined kenalog 40 mg/cc, 5-FU 50 mg/cc, and 2% lidocaine with epinephrine mixed 1:1:1 over the past 4 years. D, Patient 4 demonstrating significant improvement in the palpebral fissure following bilateral levator aponeurosis advancement and subsequent serial eyelid injections of kenalog 40 mg/cc and 2% lidocaine with epinephrine mixed 1:1 administered over 7 months. E, Patient 5 showing significant improvement in the right lower eyelid edema after repeat injections of kenalog 40 mg/cc, 5-FU 50 mg/cc, and 2% lidocaine with epinephrine mixed 1:1:1 alternating with kenalog 40 mg/cc and lidocaine 2% with epinephrine mixed 1:1 over the past 5 years.
used and effective treatment of this disorder.1–4,6 Case series of patients presenting with MRS and granulomatous cheilitis have been published in the neurology2 and oral pathology literature;1,5,7 however, this is the first case series, to our knowledge, of patients with orofacial granulomatosis presenting predominantly with ocular findings photographed before and after localized treatment. In this report, we summarize the presenting features, diagnostic measures, treatments, and treatment
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responses of 5 patients referred to the Duke Eye Center department of oculoplastics presenting with severe periorbital edema.
METHODS Institutional Review Board approval was obtained from Duke Hospital, and guidelines of the Health Insurance Portability and Accountability Act were observed. Patients with periorbital edema and biopsy-proven orofacial granulomatosis were included in this retrospective
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FIG. 2. Courtesy of Alan D. Proia, M.D, Ph.D, Department of Pathology, Duke Hospital, 2301 Erwin Road, Durham, NC 27710. A, This hematoxylin-eosin stained photomicrograph taken from a pathologic study specimen from patient 1 demonstrates granulomatous inflammation (epithelioid cells and multinucleated giant cells) adjacent to lymphatics. The magnification bar is 25 μm in length. B, This hematoxylin-eosin stained photomicrograph taken from a pathologic study specimen from patient 2 shows granulomatous inflammation adjacent to a lymphatic channel. The magnification bar is 25 μm in length. C, This D2-40 antibody (binds lymphatic endothelial cells) stained photomicrograph taken from a pathologic study specimen from patient 3 shows granulomatous inflammation within a lymphatic channel. The magnification bar is 25 μm in length. D, This hematoxylin-eosin stained photomicrograph taken from a pathologic study specimen from patient 4 shows granulomatous inflammation within a lymphatic channel. The magnification bar is 25 μm in length. E, This hematoxylin-eosin stained photomicrograph taken from a pathologic study specimen from patient 5 shows granulomatous inflammation adjacent to a blood vessel and a lymphatic channel. The magnification bar is 25 μm in length. chart review. All the clinic notes of all 5 of the patients that qualified for the study were reviewed for presenting symptoms, surgical procedures, systemic and local treatments, and the response to such treatments during patient follow up. The database of patient photographs was also reviewed to find pictures of the patients before and after treatment. Exclusion criteria included patients lost to follow up and patients without biopsy-proven orofacial granulomatosis as determined by the Duke pathology service.
RESULTS Patient 1 is a 17-year-old Indian student who first noted bilateral lower eyelid edema starting 4 months after being hit in the face with a basketball. Basic laboratory work, including complete blood count and complete metabolic panel, and CT imaging of the orbits were unremarkable. His medical history was noncontributory. His edema improved with a systemic prednisone taper starting at 40 mg daily; however, it rebounded as he tapered off. After 3 additional unsuccessful attempts to treat the edema with oral prednisone, the patient was referred to the Duke Eye Center department of oculoplastics for management. The examination was significant for bilateral upper and lower eyelid edema and induration (Fig. 1A) and partial left-sided facial nerve palsy. There was no tongue fissuring. The patient was started on a higher dose prednisone taper of 60 mg daily, and a diagnostic biopsy of the skin of the right lower eyelid and left upper eyelid was then scheduled. The surgical pathologic study from both sites showed focal nonnecrotizing granulomatous inflammation characterized by a small, ill-defined aggregate of epithelioid cells adjacent to lymphatic channels within the dermis (Fig. 2A). The pathologist made the diagnosis of orofacial granulomatosis. He was subsequently referred to rheumatology and started on methotrexate 15 mg per os daily with a slow prednisone taper. This combination treatment stabilized the edema for several months, but eventually, he developed rebound eyelid edema in addition to right-sided lip and left-sided chin induration which brought him back to clinic (Fig. 3A). At that time, a 1:1:1 combination of kenalog 40 mg/cc, 5-fluorouracil (5-FU) 50 mg/cc, and lidocaine 2% with epinephrine was mixed, and 0.3 cc was injected in each of his lower eyelids, and 0.4 cc was injected in his right lip and left chin. Repeat local injections of
kenalog 40 mg/cc and lidocaine 2% with epinephrine mixed 1:1 in addition to systemic treatment with methotrexate 20 mg weekly has enabled him to stop oral steroids and has greatly improved his eyelid (Fig. 1A) and perioral edema and induration (Fig. 3B). Patient 2 is a 57-year-old Caucasian male truck driver presenting with the chief complaint of vision loss due to severe eyelid swelling. His symptoms first began 3 years prior to seeing us and had progressed to the point of impairing his ability to drive and earn a livelihood. His medical history was significant for diabetes mellitus type II, hypertension, and cholesterol, all controlled with medications. The margin reflex distance 1 (MRD 1) was 0.5 mm in OU, palpebral fissures (PFs) measured 6 mm OU, and levator function (LF) was 13 mm OU. He presented with 4+ upper and lower eyelid edema and induration with mild tongue fissuring and no facial palsy. He underwent bilateral upper eyelid blepharoplasty with lacrimal gland biopsy. Both skin and lacrimal gland were sent to the pathologic study laboratory. The skin biopsy confirmed the diagnosis of orofacial granulomatosis (Fig. 2B); however, the lacrimal gland tissue was unremarkable. Following surgery, the patient noted a “world of difference” (Fig. 1B); however, the edema persisted, and treatment was initiated with local injections of 0.3 cc of a 1:1:1 combination of kenalog 40 mg/ cc, 5-FU 50 mg/cc, and lidocaine 2% with epinephrine alternating with kenalog 40 mg/cc and lidocaine 2% with epinephrine mixed 1:1. These injections stabilize his eyelid edema and induration for approximately 3 months before it rebounds. He returns regularly for repeat injections. Patient 3 is a 51-year-old African-American male presenting with severe upper and lower eyelid edema and induration causing complete closure of his OD and near complete closure of his OS (Fig. 1C). He first developed symptoms 3 years prior to being referred by his outside ophthalmologist. Medical history was significant for eczema, arthritis, cardiomegaly, and hypertension, all controlled with medications. His PFs measured 0 mm on the right side and 1 mm on the left. He did not have tongue fissuring or a facial palsy. Given the severe mechanical ptosis caused by the periorbital induration, he was scheduled for an anterior orbitotomy for biopsy and debulking of the mass lesion in addition to a right-sided levator aponeurosis advancement. The pathologic study showed nonnecrotizing granulomatous inflammation
FIG. 3. Patient 1 with right-sided lip and left-sided chin induration responsive to serial local injections of kenalog 40 mg/cc and 2% lidocaine with epinephrine mixed 1:1. Photograph A was taken prior to treatment. Photograph B was taken 1 year after receiving local injections every 3 months.
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within lymphatics, consistent with orofacial granulomatosis (Fig. 2C). He was subsequently referred to dermatology, and systemic treatment with oral prednisone 60 mg daily and infliximab 5 mg/kg was initiated. His eyelid edema and induration mildly improved. Two additional periorbital debulking operations were performed, first on the upper eyelids, then on the lower eyelids. The patient’s PF significantly improved despite significant amounts of lingering edema. Five months after surgery, local injections of 0.3 cc consisting of kenalog 40 mg/cc, 5-FU 50 mg/cc, and lidocaine 2% with epinephrine mixed 1:1:1 was administered to each of his 4 eyelids. Despite his sensitivity to the local injections, the patient returns approximately every 3 months for more treatment to prevent recurrence of the edema and induration. Patient 4 is a 67-year-old Caucasian male presenting with progressive bilateral upper and lower eyelid edema and induration starting several years prior to referral to the Duke Eye Center. He had been evaluated previously by several physicians without a working diagnosis. He presented with a chief complaint of progressive obscuration of his vision from his edematous eyelids. His MRD 1 measured 0.5 mm on the right side and 1 mm on the left side, PFs measured 5 mm on the right side and 6 mm on the left side, and LF was 18 mm OU. He had 2+ upper and lower eyelid edema and induration on examination (Fig. 1D), and Goldmann visual fields showed improvement from 12° to 50° on the right side and 30° to 60° on the left side with upper eyelid taping. The examination was also significant for right perioral lip edema and ptosis of the right corner of his mouth. No tongue fissuring was noted. He underwent a bilateral anterior orbitotomy with biopsy of the lacrimal glands and bilateral levator aponeurosis advancement. An eyelid skin sample was also sent to pathologic study. The pathologic study showed normal lacrimal gland tissue, but the skin findings were consistent with orofacial granulomatosis (Fig. 2D). Following surgery, low-dose oral prednisone 20 mg was initiated. One month after surgery, the patient received local injections of 0.3 cc of kenalog 40 mg/cc and 2% lidocaine with epinephrine mixed 1:1 to each of his 4 eyelids. The oral prednisone was stopped. The patient was very happy at his next visit 1 month later and desired more injections which he received. This patient follows up approximately every 3 months for the same local injections and is no longer using systemic therapy. Patient 5 is a 33-year-old Caucasian male who presented with right-sided periorbital and facial swelling that first started 5 years prior to presentation. He had been seen by an outside ophthalmologist who had performed right upper eyelid biopsies of the edematous skin which was diagnosed as orofacial granulomatosis. The pathologic study slides were later independently reviewed by the Duke pathology service who agreed that it was consistent with orofacial granulomatosis. After trying tacrolimus ointment without effect, he was started on a high dose, slow prednisone taper which helped the edema but caused a weight gain of 40 pounds. Subsequent to the taper, the patient was treated with cellcept, clofazimine, dapsone, thalidomide, methotrexate, etanercept, and infliximab by his rheumatologist, all with little effect. Of all these treatments, oral prednisone seemed to be most effective. The patient was referred to Duke Department of Oculoplastics for further management. The examination was significant for nontender right upper and lower eyelid edema and a fissured tongue but no facial nerve palsy (Fig. 1E). At the initial visit, given the preexisting diagnosis of orofacial granulomatosis, the patient was treated with local injections of kenalog 40 mg/ml, 5-FU 50 mg/ml, and 2% lidocaine with epinephrine mixed 1:1:1. A total of 0.5 cc was injected in the right upper and lower eyelid. One month later, he underwent a right anterior orbitotomy for exploration and biopsy and a right levator aponeurosis advancement. The pathologic study report showed perivascular chronic inflammation and rare perivascular granulomas consistent with orofacial granulomatosis (Fig. 2E). Depots of triamcinolone (from the previous injection) were found and may have caused the dissolution of granulomas according to the report. Serial local injections have controlled his eyelid
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edema and induration, enabling him to wean off all systemic medications and drop back down to his baseline weight.
DISCUSSION Orofacial granulomatosis represents a spectrum of nonnecrotizing granulomatous inflammation most commonly affecting the soft tissues of the oral and maxillofacial regions.1–3,6 This series documents the treatment course and response of 5 patients presenting predominantly with periorbital edema and induration diagnosed with orofacial granulomatosis. Three of the 5 patients had some form of ancillary perioral involvement. Patient 1 had recurrent right-sided lip and left-sided chin induration which also responded to the local injections. Patient 4 was noted to have right perioral edema and ptosis of the right corner of his mouth. And patient 5 had a fissured tongue originally described in the triad of Melkersson-Rosenthal syndrome. There were no oral findings besides those noted for these 3 patients. As described in the literature, orofacial granulomatosis is not restricted to the the perioral region. Indeed, there need not be perioral findings at all.1,2,6 All 5 of our patients were referred by outside physicians to the Department of Oculoplastics at the Duke Eye Center with severe nontender upper and lower eyelid edema and induration causing functional vision loss due to mechanical ptosis. Most patients were undiagnosed and had tried systemic therapies with variable results. One of our patients had a mild response to methotrexate therapy and another to infliximab; however, of the systemic therapies, oral prednisone seemed to be the most effective as suggested by the literature.1–4,6 Biopsies taken from the dermis and orbicularis over the edematous upper and/or lower eyelid clinched the diagnosis in each case, demonstrating nonnectrotizing granulomatous inflammation most commonly found adjacent to lymphatic and vascular channels as shown in the photomicrographs (Fig. 2). Lacrimal gland biopsies, however, taken at the same time in a couple of the patients were unremarkable. Depending on the amount of edema and induration, patients may or may not have had combined debulking and/ or levator aponeurosis advancement. Patients that had surgical debulking with levator aponeurosis advancement had functional improvements in their PFs; however, the edema and induration recurred in every case without some form of anti-inflammatory therapy, either systemic or local. Given the adverse effects of prolonged systemic therapy with prednisone, methotrexate, and/or infliximab, we attempted to treat the disfiguring recurrent edema with 0.3 cc local injections consisting of kenalog 40 mg/cc, 2% lidocaine with epinephrine, with or without 5-FU 50 mg/cc mixed 1:1:1 in each edematous eyelid. In each case, patients were happy with the effects of these injections and routinely returned approximately every 3 months for additional injections. This strategy enabled the reduction and/or discontinuation of systemic steroids and steroid-sparing agents in most cases. Ophthalmologists, and particularly oculoplastics specialists, should include orofacial granulomatosis in the differential of nontender, severe, recurrent eyelid edema and consider the diagnostic and treatment approaches highlighted in this report in treating their patients.
REFERENCES 1. Mignogna MD, Fedele S, Lo Russo L, et al. The multiform and variable patterns of onset of orofacial granulomatosis. J Oral Pathol Med 2003;32:200–5. 2. Elias MK, Mateen FJ, Weiler CR. The Melkersson-Rosenthal syndrome: a retrospective study of biopsied cases. J Neurol 2013;260:138–43.
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3. Rana AQ, Siddiqui I, Zangeneh M, et al. Predicting treatment-seeking for visual hallucinations among Parkinson’s disease patients. Psychiatry Clin Neurosci 2013;67:509–16. 4. Akarsu C, Atasoy P, Erdoğan S, et al. Bilateral upper eyelid edema in Melkersson-Rosenthal syndrome. Ophthal Plast Reconstr Surg 2005;21:243–5. 5. Mignogna MD, Pollio A, Leuci S, et al. Clinical behaviour and long-term therapeutic response in orofacial granulomatosis patients treated with intralesional triamcinolone acetonide injections alone or in combination with topical pimecrolimus 1%. J Oral Pathol Med 2013;42:73–81. 6. Rawlings NG, Valenzuela AA, Allen LH, et al. Isolated eyelid edema in Melkersson-Rosenthal syndrome: a case series. Eye (Lond) 2012;26:163–6. 7. Campbell H, Escudier MP, Brostoff J, et al. Dietary intervention for oral allergy syndrome as a treatment in orofacial granulomatosis: a new approach? J Oral Pathol Med 2013;42:517–22.
Unusual Presentation of Xanthogranuloma on the Eyelid of an Adult Elizabeth Chiang, M.D., Ph.D., Gary Lissner, M.D., and Paul J. Bryar, M.D. Abstract: A 46-year-old man presented with an unusual papillary eyelid lesion in which histopathological study revealed a cutaneous xanthogranuloma. The clinical appearance was distinctively different from juvenile xanthogranuloma. There was no evidence of an infiltrative and orbital process consistent with adult orbital xanthogranulomatous disease. The histopathologic examination of the lesion revealed well-differentiated histiocytes with foamy cytoplasm. Immunohistochemistry stains were positive for CD163 and Factor XIIIa and negative for CD34, CD1A, CD117, and S100. The final histopathologic diagnosis was cutaneous xanthogranuloma.
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he authors report an unusual presentation of a cutaneous xanthogranuloma. The case report demonstrates the variability and possible appearances of cutaneous xanthogranuloma and the means to make the correct diagnosis. Informed consent was obtained, and the review adhered to the tenets of the Declaration of Helsinki.
Case Reports
On external examination, a mass lesion with a 4 × 4 mm base and 6 mm long was seen on the right upper eyelid margin. The mass appeared to displace eyelashes rather than cause loss of eyelashes (Fig. 1). Extraocular movements were full with no restriction. There was no proptosis as measured with exophthalmometry. The remainder of the patient’s slit lamp examination was unremarkable. The clinical impression was a papillary lesion. The mass was excised and sent for pathologic study. Histopathologic examination revealed w ell-differentiated histiocytes with foamy cytoplasm. (Fig. 2, A and B) Immunohistochemistry stains were positive for CD163 and Factor XIIIa and negative for CD34, CD1A, CD117, and S100. (Fig. 2, C and D) The final pathologic diagnosis was cutaneous xanthogranuloma.
DISCUSSION Xanthogranulomatous diseases have a variety of presentations but are linked by common histopathology. 1 Xanthogranuloma can be classified into 2 groups: juvenile xanthogranulomas (JXGs) that present as distinct lesions and orbital xanthogranulomas that are infiltrative in nature. 2 JXG characteristically develops as a well-demarcated mass that may present as a single or multiple raised nodules. Cutaneous nodules are found most commonly on the head, neck, or upper trunk and less commonly on the extremities. The nodules are yellow-brown to reddish in color, measuring a few millimeters to a few centimeters in diameter.3,4 There are reported cases of JXG in a variety of organs including the lung, skeletal muscle, bone, central nervous system, liver, spleen, and testes.4 Ocular involvement of JXG includes lesions found on the limbus, cornea, conjunctiva, iris, ciliary body, and optic nerve.5–8 There is a bimodal distribution of JXG with most occurring prior to the age of 1 year and a second grouping between 20 and 30 years of age.9 Up to 15% of cutaneous “juvenile” xanthogranuloma lesions can occur in adults, and JXG skin lesions have been reported in individuals in their seventh decade of life.4,10 Various terms have been used to describe these cutaneous JXG lesions in adults including “juvenile xanthogranuloma in an adult” or “adult xanthogranuloma.” The orbital xanthogranulomatous diseases are a heterogeneous group of disorders with 4 different clinical syndromes: adult-onset xanthogranuloma, adult-onset asthma and periocular xanthogranuloma, necrobiotic xanthogranuloma, and ErdheimChester disease. The 4 different clinical syndromes of xanthogranuloma in the orbit present as an infiltrating lesion, often bilaterally,
CASE REPORT A 46-year-old Caucasian man presented with a 1-year history of an enlarging solitary lesion on his right upper eyelid. The patient reported rare irritation in the area of the lesion but denied any discharge or bleeding. He had no visual complaints. He had no previous eyelid bumps, skin diseases, or skin cancers. The patient had an anxiety disorder for which he was taking psychiatric medication and was otherwise healthy. Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A. Accepted for publication August 3, 2013. Supported from an unrestricted grant from Research to Prevent Blindness, New York, NY. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Gary Lissner, M.D., Department of Ophthalmology, Northwestern University, 645 North Michigan Ave., Suite 440, Chicago, IL 60611. E-mail: [email protected] DOI: 10.1097/01.iop.0000440703.67932.37
FIG. 1. Patient presented with a papillary mass on the right upper eyelid margin.
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findings, the histopathological diagnosis of ILPMD was made by a dermatopathologist (A.R.S.). A review of the literature for this diagnosis recommended a systemic workup to include complete blood count with differential, complete metabolic panel and serum protein electrophoresis, Lyme serology, and serum RPR. All these studies were normal. Abdominal ultrasound was also recommended to evaluate for the presence of organomegaly. This was performed and was normal except for a 5-cm mass in the liver that was thought to be a benign hemangioma. Follow-up CT scan of abdomen was also consistent with a benign hemangioma of the liver, and a follow-up ultrasound 6 months later confirmed the mass was stable in size. At the 19-month follow up, the patient was doing well, and there was no sign of recurrence at the site of excision of the lesion.
DISCUSSION ILPMD is a benign idiopathic lesion characterized clinically by either papules or plaques with or without surface erosion. The histopathologic hallmark of ILPMD consists of dense plasma cell infiltrates within the dermis or submucosa. The plasma cells are frequently admixed with lymphocytes and occasionally with neutrophils and eosinophils. Accompanying the dermal infiltrates are variable epidermal or epithelial changes. The latter structures are usually atrophic, and vacuolar interface change may be present. Zoon described a peculiar basal keratinocyte alteration known as “lozenge-shape” where the horizontal axis of these cells exceeds the vertical axis in length, resulting in a diamond shape. Other microscopic findings include dermal or submucosal fibrosis and small vessel proliferation.1 Following Zoon’s report of lesions on the glans penis, similar cases have been described on the vulva, buccal mucosa, palate, nasal aperture, gingiva, lips, tongue, epiglottis, larynx, and other mucosal surfaces.2 ILPMD has been described under various names including plasmacytosis mucosae, plasmacytosis orificialis, and plasma cell mucositis. In the upper aerodigestive tract, ILPMD presents as intensely erythematous mucosa with surface changes described variously as papillomatous, cobblestone, nodular, or velvety. Histologically, the differential diagnosis includes lichen planus, plasmacytoma, syphilis, and Lyme disease.1 Lichen planus is characterized by basal vacuolar keratinocyte alteration, Civatte bodies (dyskeratotic keratinocytes), and a moderate to dense inflammatory infiltrate with a predominance of lymphocytes rather than plasma cells.1 Plasmacytomas are circumscribed dense dermal infiltrates with atypical plasma cells. Immunostains demonstrate monotypism of light chain immunoglobulins.1 In secondary syphilis, the epidermis may be normal, psoriasiform, necrotic, or ulcerated. Dermal infiltrates of plasma cells, lymphocytes, and histiocytes may be perivascular, lichenoid, nodular, or diffuse. Endothelial swelling and vascular proliferation can also be found. Spirochetes may be demonstrated with special stains, and serological tests are usually positive.3 Erythema chronicum migrans, the typical rash of Lyme disease is characterized histopathologically by perivascular infiltrates of lymphocytes, plasma cells, and mast cells around the upper dermal vessels.4 Treatment of ILPMD has been reported as only variably successful. Treatment modalities that have been tried include corticosteroids (topical, intralesional, and systemic), antibiotics, destruction of the tissue (liquid nitrogen, CO2 laser, and electrocoagulation), excision, and radiation therapy. No treatment is consistently effective.2 No studies report a progression of ILPMD to malignancy of any type.2 Haqqie et al.5 have previously reported ILPMD involving the tarsal conjunctiva that was possibly a mucosal manifestation of ocular Lyme disease based on immunochemical results, positive serology, and response to antibiotics. However, chronic
Case Reports
irritation could not be ruled out. To this knowledge, the authors report the first case of ILPMD of the skin of the eyelid. They recommend including this rare lesion in the differential diagnosis of symptomatic eyelid lesions and highlight the appropriate systemic workup in the event of this diagnosis.
REFERENCES 1. Brix WK, Nassau SR, Patterson JW, et al. Idiopathic lymphoplasmacellular mucositis-dermatitis. J Cutan Pathol 2010;37:426–31. 2. Bharti R, Smith DR. Mucous membrane plasmacytosis: a case report and review of the literature. Dermatol Online J 2003;9:15. 3. Bolognia JL. Dermatology, 2nd ed. St. Louis, MO: Mosby Elsevier, 2008. 4. Duray PH. The surgical pathology of human Lyme disease. An enlarging picture. Am J Surg Pathol 1987;11 Suppl 1:47–60. 5. Haqqie N, Wroblewski D, Meyer DR, et al. Idiopathic lymphoplasmacellular mucositis-dermatitis (plasmacytosis mucosae) of the tarsal conjunctiva. J Cutan Pathol 2011;38:597–9.
A Case Series of Patients Diagnosed With Orofacial Granulomatosis Presenting Primarily With Dense Infiltrates and Severe Periorbital Edema Esfandiar J. Sabet-Peyman, M.D., and Julie A. Woodward, M.D. Abstract: Orofacial granulomatosis is a relapsing nonnecrotizing granulomatous syndrome that classically presents with lip and perioral swelling. Over the years, several patients have been referred to the Duke Eye Center Oculoplastics Department for severe, progressive, recurrent eyelid swelling interfering with both their functional vision and their appearance. In this IRB approved retrospective case series, we describe the clinical course of 5 such patients, including their presenting symptoms, diagnosis, and response to treatment. We hope that oculoplastics specialists will consider this entity in the differential diagnosis of periorbital edema and consider initiating localized antiinflammatory treatment once the diagnosis has been made.
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rofacial granulomatosis is a nonnecrotizing inflammatory disease process in the same family as Melkersson-Rosenthal syndrome (MRS) and granulomatous cheilitis.1–3 Although the phenotypic presentation can widely vary, the most common presenting symptom is orofacial edema.1–5 Perioral edema alone characterizes granulomatous cheilitis3, and the triad of orofacial edema, tongue fissuring, and facial nerve paralysis is known as MRS.1–4,6 The etiology of the disease is unknown; however, delayed hypersensitivity appears to play a role.3,5,7 Associations have been made with diseases such as sarcoidosis, Crohn disease, systemic lupus erythematosis, periodontal disease, viral infections, migraine headaches,1–3 and inciting agents such as dental amalgam,3,5 cinnamon,5,7 and infection1–3 have been suggested. There is no gold standard treatment at this time, although systemic steroids appear to be the most commonly Department of Oculoplastics, Duke Eye Center, Durham, North Carolina, U.S.A. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Julie A. Woodward, M.D., Department of Oculoplastics, Duke Eye Center, 2351 Erwin Road, Durham, NC 27710. E-mail: [email protected] DOI: 10.1097/01.iop.0000440702.85663.e5
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FIG. 1. A, Patient 1 demonstrating significant improvement in upper and lower eyelid edema and palpebral fissures after 4 years of serial treatment with local eyelid injections of combined kenalog 40 mg/cc and 2% lidocaine with epinephrine mixed 1:1 in addition to systemic methotrexate 20 mg once weekly. B, Patient 2 showing marked improvement of lower eyelid festoons after 6 months of local injections of combined kenalog 40 mg/cc, 5-fluorouracil 50 mg/cc, and lidocaine 2% with epinephrine mixed 1:1:1 alternating with kenalog 40 mg/cc and lidocaine 2% with epinephrine mixed 1:1. There was also mild improvement in upper eyelid edema following bilateral upper eyelid blepharoplasty and serial localized injections. C, Patient 3 showing markedly improved eyelid edema and induration after 3 eyelid debulking operations, systemic therapy with infliximab, several oral prednisone tapers, and serial local eyelid injections of combined kenalog 40 mg/cc, 5-FU 50 mg/cc, and 2% lidocaine with epinephrine mixed 1:1:1 over the past 4 years. D, Patient 4 demonstrating significant improvement in the palpebral fissure following bilateral levator aponeurosis advancement and subsequent serial eyelid injections of kenalog 40 mg/cc and 2% lidocaine with epinephrine mixed 1:1 administered over 7 months. E, Patient 5 showing significant improvement in the right lower eyelid edema after repeat injections of kenalog 40 mg/cc, 5-FU 50 mg/cc, and 2% lidocaine with epinephrine mixed 1:1:1 alternating with kenalog 40 mg/cc and lidocaine 2% with epinephrine mixed 1:1 over the past 5 years.
used and effective treatment of this disorder.1–4,6 Case series of patients presenting with MRS and granulomatous cheilitis have been published in the neurology2 and oral pathology literature;1,5,7 however, this is the first case series, to our knowledge, of patients with orofacial granulomatosis presenting predominantly with ocular findings photographed before and after localized treatment. In this report, we summarize the presenting features, diagnostic measures, treatments, and treatment
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responses of 5 patients referred to the Duke Eye Center department of oculoplastics presenting with severe periorbital edema.
METHODS Institutional Review Board approval was obtained from Duke Hospital, and guidelines of the Health Insurance Portability and Accountability Act were observed. Patients with periorbital edema and biopsy-proven orofacial granulomatosis were included in this retrospective
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FIG. 2. Courtesy of Alan D. Proia, M.D, Ph.D, Department of Pathology, Duke Hospital, 2301 Erwin Road, Durham, NC 27710. A, This hematoxylin-eosin stained photomicrograph taken from a pathologic study specimen from patient 1 demonstrates granulomatous inflammation (epithelioid cells and multinucleated giant cells) adjacent to lymphatics. The magnification bar is 25 μm in length. B, This hematoxylin-eosin stained photomicrograph taken from a pathologic study specimen from patient 2 shows granulomatous inflammation adjacent to a lymphatic channel. The magnification bar is 25 μm in length. C, This D2-40 antibody (binds lymphatic endothelial cells) stained photomicrograph taken from a pathologic study specimen from patient 3 shows granulomatous inflammation within a lymphatic channel. The magnification bar is 25 μm in length. D, This hematoxylin-eosin stained photomicrograph taken from a pathologic study specimen from patient 4 shows granulomatous inflammation within a lymphatic channel. The magnification bar is 25 μm in length. E, This hematoxylin-eosin stained photomicrograph taken from a pathologic study specimen from patient 5 shows granulomatous inflammation adjacent to a blood vessel and a lymphatic channel. The magnification bar is 25 μm in length. chart review. All the clinic notes of all 5 of the patients that qualified for the study were reviewed for presenting symptoms, surgical procedures, systemic and local treatments, and the response to such treatments during patient follow up. The database of patient photographs was also reviewed to find pictures of the patients before and after treatment. Exclusion criteria included patients lost to follow up and patients without biopsy-proven orofacial granulomatosis as determined by the Duke pathology service.
RESULTS Patient 1 is a 17-year-old Indian student who first noted bilateral lower eyelid edema starting 4 months after being hit in the face with a basketball. Basic laboratory work, including complete blood count and complete metabolic panel, and CT imaging of the orbits were unremarkable. His medical history was noncontributory. His edema improved with a systemic prednisone taper starting at 40 mg daily; however, it rebounded as he tapered off. After 3 additional unsuccessful attempts to treat the edema with oral prednisone, the patient was referred to the Duke Eye Center department of oculoplastics for management. The examination was significant for bilateral upper and lower eyelid edema and induration (Fig. 1A) and partial left-sided facial nerve palsy. There was no tongue fissuring. The patient was started on a higher dose prednisone taper of 60 mg daily, and a diagnostic biopsy of the skin of the right lower eyelid and left upper eyelid was then scheduled. The surgical pathologic study from both sites showed focal nonnecrotizing granulomatous inflammation characterized by a small, ill-defined aggregate of epithelioid cells adjacent to lymphatic channels within the dermis (Fig. 2A). The pathologist made the diagnosis of orofacial granulomatosis. He was subsequently referred to rheumatology and started on methotrexate 15 mg per os daily with a slow prednisone taper. This combination treatment stabilized the edema for several months, but eventually, he developed rebound eyelid edema in addition to right-sided lip and left-sided chin induration which brought him back to clinic (Fig. 3A). At that time, a 1:1:1 combination of kenalog 40 mg/cc, 5-fluorouracil (5-FU) 50 mg/cc, and lidocaine 2% with epinephrine was mixed, and 0.3 cc was injected in each of his lower eyelids, and 0.4 cc was injected in his right lip and left chin. Repeat local injections of
kenalog 40 mg/cc and lidocaine 2% with epinephrine mixed 1:1 in addition to systemic treatment with methotrexate 20 mg weekly has enabled him to stop oral steroids and has greatly improved his eyelid (Fig. 1A) and perioral edema and induration (Fig. 3B). Patient 2 is a 57-year-old Caucasian male truck driver presenting with the chief complaint of vision loss due to severe eyelid swelling. His symptoms first began 3 years prior to seeing us and had progressed to the point of impairing his ability to drive and earn a livelihood. His medical history was significant for diabetes mellitus type II, hypertension, and cholesterol, all controlled with medications. The margin reflex distance 1 (MRD 1) was 0.5 mm in OU, palpebral fissures (PFs) measured 6 mm OU, and levator function (LF) was 13 mm OU. He presented with 4+ upper and lower eyelid edema and induration with mild tongue fissuring and no facial palsy. He underwent bilateral upper eyelid blepharoplasty with lacrimal gland biopsy. Both skin and lacrimal gland were sent to the pathologic study laboratory. The skin biopsy confirmed the diagnosis of orofacial granulomatosis (Fig. 2B); however, the lacrimal gland tissue was unremarkable. Following surgery, the patient noted a “world of difference” (Fig. 1B); however, the edema persisted, and treatment was initiated with local injections of 0.3 cc of a 1:1:1 combination of kenalog 40 mg/ cc, 5-FU 50 mg/cc, and lidocaine 2% with epinephrine alternating with kenalog 40 mg/cc and lidocaine 2% with epinephrine mixed 1:1. These injections stabilize his eyelid edema and induration for approximately 3 months before it rebounds. He returns regularly for repeat injections. Patient 3 is a 51-year-old African-American male presenting with severe upper and lower eyelid edema and induration causing complete closure of his OD and near complete closure of his OS (Fig. 1C). He first developed symptoms 3 years prior to being referred by his outside ophthalmologist. Medical history was significant for eczema, arthritis, cardiomegaly, and hypertension, all controlled with medications. His PFs measured 0 mm on the right side and 1 mm on the left. He did not have tongue fissuring or a facial palsy. Given the severe mechanical ptosis caused by the periorbital induration, he was scheduled for an anterior orbitotomy for biopsy and debulking of the mass lesion in addition to a right-sided levator aponeurosis advancement. The pathologic study showed nonnecrotizing granulomatous inflammation
FIG. 3. Patient 1 with right-sided lip and left-sided chin induration responsive to serial local injections of kenalog 40 mg/cc and 2% lidocaine with epinephrine mixed 1:1. Photograph A was taken prior to treatment. Photograph B was taken 1 year after receiving local injections every 3 months.
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within lymphatics, consistent with orofacial granulomatosis (Fig. 2C). He was subsequently referred to dermatology, and systemic treatment with oral prednisone 60 mg daily and infliximab 5 mg/kg was initiated. His eyelid edema and induration mildly improved. Two additional periorbital debulking operations were performed, first on the upper eyelids, then on the lower eyelids. The patient’s PF significantly improved despite significant amounts of lingering edema. Five months after surgery, local injections of 0.3 cc consisting of kenalog 40 mg/cc, 5-FU 50 mg/cc, and lidocaine 2% with epinephrine mixed 1:1:1 was administered to each of his 4 eyelids. Despite his sensitivity to the local injections, the patient returns approximately every 3 months for more treatment to prevent recurrence of the edema and induration. Patient 4 is a 67-year-old Caucasian male presenting with progressive bilateral upper and lower eyelid edema and induration starting several years prior to referral to the Duke Eye Center. He had been evaluated previously by several physicians without a working diagnosis. He presented with a chief complaint of progressive obscuration of his vision from his edematous eyelids. His MRD 1 measured 0.5 mm on the right side and 1 mm on the left side, PFs measured 5 mm on the right side and 6 mm on the left side, and LF was 18 mm OU. He had 2+ upper and lower eyelid edema and induration on examination (Fig. 1D), and Goldmann visual fields showed improvement from 12° to 50° on the right side and 30° to 60° on the left side with upper eyelid taping. The examination was also significant for right perioral lip edema and ptosis of the right corner of his mouth. No tongue fissuring was noted. He underwent a bilateral anterior orbitotomy with biopsy of the lacrimal glands and bilateral levator aponeurosis advancement. An eyelid skin sample was also sent to pathologic study. The pathologic study showed normal lacrimal gland tissue, but the skin findings were consistent with orofacial granulomatosis (Fig. 2D). Following surgery, low-dose oral prednisone 20 mg was initiated. One month after surgery, the patient received local injections of 0.3 cc of kenalog 40 mg/cc and 2% lidocaine with epinephrine mixed 1:1 to each of his 4 eyelids. The oral prednisone was stopped. The patient was very happy at his next visit 1 month later and desired more injections which he received. This patient follows up approximately every 3 months for the same local injections and is no longer using systemic therapy. Patient 5 is a 33-year-old Caucasian male who presented with right-sided periorbital and facial swelling that first started 5 years prior to presentation. He had been seen by an outside ophthalmologist who had performed right upper eyelid biopsies of the edematous skin which was diagnosed as orofacial granulomatosis. The pathologic study slides were later independently reviewed by the Duke pathology service who agreed that it was consistent with orofacial granulomatosis. After trying tacrolimus ointment without effect, he was started on a high dose, slow prednisone taper which helped the edema but caused a weight gain of 40 pounds. Subsequent to the taper, the patient was treated with cellcept, clofazimine, dapsone, thalidomide, methotrexate, etanercept, and infliximab by his rheumatologist, all with little effect. Of all these treatments, oral prednisone seemed to be most effective. The patient was referred to Duke Department of Oculoplastics for further management. The examination was significant for nontender right upper and lower eyelid edema and a fissured tongue but no facial nerve palsy (Fig. 1E). At the initial visit, given the preexisting diagnosis of orofacial granulomatosis, the patient was treated with local injections of kenalog 40 mg/ml, 5-FU 50 mg/ml, and 2% lidocaine with epinephrine mixed 1:1:1. A total of 0.5 cc was injected in the right upper and lower eyelid. One month later, he underwent a right anterior orbitotomy for exploration and biopsy and a right levator aponeurosis advancement. The pathologic study report showed perivascular chronic inflammation and rare perivascular granulomas consistent with orofacial granulomatosis (Fig. 2E). Depots of triamcinolone (from the previous injection) were found and may have caused the dissolution of granulomas according to the report. Serial local injections have controlled his eyelid
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edema and induration, enabling him to wean off all systemic medications and drop back down to his baseline weight.
DISCUSSION Orofacial granulomatosis represents a spectrum of nonnecrotizing granulomatous inflammation most commonly affecting the soft tissues of the oral and maxillofacial regions.1–3,6 This series documents the treatment course and response of 5 patients presenting predominantly with periorbital edema and induration diagnosed with orofacial granulomatosis. Three of the 5 patients had some form of ancillary perioral involvement. Patient 1 had recurrent right-sided lip and left-sided chin induration which also responded to the local injections. Patient 4 was noted to have right perioral edema and ptosis of the right corner of his mouth. And patient 5 had a fissured tongue originally described in the triad of Melkersson-Rosenthal syndrome. There were no oral findings besides those noted for these 3 patients. As described in the literature, orofacial granulomatosis is not restricted to the the perioral region. Indeed, there need not be perioral findings at all.1,2,6 All 5 of our patients were referred by outside physicians to the Department of Oculoplastics at the Duke Eye Center with severe nontender upper and lower eyelid edema and induration causing functional vision loss due to mechanical ptosis. Most patients were undiagnosed and had tried systemic therapies with variable results. One of our patients had a mild response to methotrexate therapy and another to infliximab; however, of the systemic therapies, oral prednisone seemed to be the most effective as suggested by the literature.1–4,6 Biopsies taken from the dermis and orbicularis over the edematous upper and/or lower eyelid clinched the diagnosis in each case, demonstrating nonnectrotizing granulomatous inflammation most commonly found adjacent to lymphatic and vascular channels as shown in the photomicrographs (Fig. 2). Lacrimal gland biopsies, however, taken at the same time in a couple of the patients were unremarkable. Depending on the amount of edema and induration, patients may or may not have had combined debulking and/ or levator aponeurosis advancement. Patients that had surgical debulking with levator aponeurosis advancement had functional improvements in their PFs; however, the edema and induration recurred in every case without some form of anti-inflammatory therapy, either systemic or local. Given the adverse effects of prolonged systemic therapy with prednisone, methotrexate, and/or infliximab, we attempted to treat the disfiguring recurrent edema with 0.3 cc local injections consisting of kenalog 40 mg/cc, 2% lidocaine with epinephrine, with or without 5-FU 50 mg/cc mixed 1:1:1 in each edematous eyelid. In each case, patients were happy with the effects of these injections and routinely returned approximately every 3 months for additional injections. This strategy enabled the reduction and/or discontinuation of systemic steroids and steroid-sparing agents in most cases. Ophthalmologists, and particularly oculoplastics specialists, should include orofacial granulomatosis in the differential of nontender, severe, recurrent eyelid edema and consider the diagnostic and treatment approaches highlighted in this report in treating their patients.
REFERENCES 1. Mignogna MD, Fedele S, Lo Russo L, et al. The multiform and variable patterns of onset of orofacial granulomatosis. J Oral Pathol Med 2003;32:200–5. 2. Elias MK, Mateen FJ, Weiler CR. The Melkersson-Rosenthal syndrome: a retrospective study of biopsied cases. J Neurol 2013;260:138–43.
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3. Rana AQ, Siddiqui I, Zangeneh M, et al. Predicting treatment-seeking for visual hallucinations among Parkinson’s disease patients. Psychiatry Clin Neurosci 2013;67:509–16. 4. Akarsu C, Atasoy P, Erdoğan S, et al. Bilateral upper eyelid edema in Melkersson-Rosenthal syndrome. Ophthal Plast Reconstr Surg 2005;21:243–5. 5. Mignogna MD, Pollio A, Leuci S, et al. Clinical behaviour and long-term therapeutic response in orofacial granulomatosis patients treated with intralesional triamcinolone acetonide injections alone or in combination with topical pimecrolimus 1%. J Oral Pathol Med 2013;42:73–81. 6. Rawlings NG, Valenzuela AA, Allen LH, et al. Isolated eyelid edema in Melkersson-Rosenthal syndrome: a case series. Eye (Lond) 2012;26:163–6. 7. Campbell H, Escudier MP, Brostoff J, et al. Dietary intervention for oral allergy syndrome as a treatment in orofacial granulomatosis: a new approach? J Oral Pathol Med 2013;42:517–22.
Unusual Presentation of Xanthogranuloma on the Eyelid of an Adult Elizabeth Chiang, M.D., Ph.D., Gary Lissner, M.D., and Paul J. Bryar, M.D. Abstract: A 46-year-old man presented with an unusual papillary eyelid lesion in which histopathological study revealed a cutaneous xanthogranuloma. The clinical appearance was distinctively different from juvenile xanthogranuloma. There was no evidence of an infiltrative and orbital process consistent with adult orbital xanthogranulomatous disease. The histopathologic examination of the lesion revealed well-differentiated histiocytes with foamy cytoplasm. Immunohistochemistry stains were positive for CD163 and Factor XIIIa and negative for CD34, CD1A, CD117, and S100. The final histopathologic diagnosis was cutaneous xanthogranuloma.
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he authors report an unusual presentation of a cutaneous xanthogranuloma. The case report demonstrates the variability and possible appearances of cutaneous xanthogranuloma and the means to make the correct diagnosis. Informed consent was obtained, and the review adhered to the tenets of the Declaration of Helsinki.
Case Reports
On external examination, a mass lesion with a 4 × 4 mm base and 6 mm long was seen on the right upper eyelid margin. The mass appeared to displace eyelashes rather than cause loss of eyelashes (Fig. 1). Extraocular movements were full with no restriction. There was no proptosis as measured with exophthalmometry. The remainder of the patient’s slit lamp examination was unremarkable. The clinical impression was a papillary lesion. The mass was excised and sent for pathologic study. Histopathologic examination revealed w ell-differentiated histiocytes with foamy cytoplasm. (Fig. 2, A and B) Immunohistochemistry stains were positive for CD163 and Factor XIIIa and negative for CD34, CD1A, CD117, and S100. (Fig. 2, C and D) The final pathologic diagnosis was cutaneous xanthogranuloma.
DISCUSSION Xanthogranulomatous diseases have a variety of presentations but are linked by common histopathology. 1 Xanthogranuloma can be classified into 2 groups: juvenile xanthogranulomas (JXGs) that present as distinct lesions and orbital xanthogranulomas that are infiltrative in nature. 2 JXG characteristically develops as a well-demarcated mass that may present as a single or multiple raised nodules. Cutaneous nodules are found most commonly on the head, neck, or upper trunk and less commonly on the extremities. The nodules are yellow-brown to reddish in color, measuring a few millimeters to a few centimeters in diameter.3,4 There are reported cases of JXG in a variety of organs including the lung, skeletal muscle, bone, central nervous system, liver, spleen, and testes.4 Ocular involvement of JXG includes lesions found on the limbus, cornea, conjunctiva, iris, ciliary body, and optic nerve.5–8 There is a bimodal distribution of JXG with most occurring prior to the age of 1 year and a second grouping between 20 and 30 years of age.9 Up to 15% of cutaneous “juvenile” xanthogranuloma lesions can occur in adults, and JXG skin lesions have been reported in individuals in their seventh decade of life.4,10 Various terms have been used to describe these cutaneous JXG lesions in adults including “juvenile xanthogranuloma in an adult” or “adult xanthogranuloma.” The orbital xanthogranulomatous diseases are a heterogeneous group of disorders with 4 different clinical syndromes: adult-onset xanthogranuloma, adult-onset asthma and periocular xanthogranuloma, necrobiotic xanthogranuloma, and ErdheimChester disease. The 4 different clinical syndromes of xanthogranuloma in the orbit present as an infiltrating lesion, often bilaterally,
CASE REPORT A 46-year-old Caucasian man presented with a 1-year history of an enlarging solitary lesion on his right upper eyelid. The patient reported rare irritation in the area of the lesion but denied any discharge or bleeding. He had no visual complaints. He had no previous eyelid bumps, skin diseases, or skin cancers. The patient had an anxiety disorder for which he was taking psychiatric medication and was otherwise healthy. Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A. Accepted for publication August 3, 2013. Supported from an unrestricted grant from Research to Prevent Blindness, New York, NY. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Gary Lissner, M.D., Department of Ophthalmology, Northwestern University, 645 North Michigan Ave., Suite 440, Chicago, IL 60611. E-mail: [email protected] DOI: 10.1097/01.iop.0000440703.67932.37
FIG. 1. Patient presented with a papillary mass on the right upper eyelid margin.
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