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Complex limbal choristomas in linear nevus sebaceous syndrome
Complex Limbal Choristomas in Linear Nevus Sebaceous Syndrome Jacque L. Duncan, MD,1 Mahin Golabi, MD,2 Douglas R. Fredrick, MD,1 Creig S. Hoyt, MD,1 David G. Hwang, MD,1 Steven G. Kramer, MD,1 Edward L. Howes, Jr., MD,3 Emmett T. Cunningham, Jr., MD, PhD1,4 Objective: This study aimed to describe the clinical and histopathologic findings in four patients with complex limbal choristomas associated with linear nevus sebaceous syndrome (LNSS), a rare disorder including nevus sebaceous, seizures, and mental retardation, and often accompanied by ocular anomalies. Design: Small observational case series. Methods: A retrospective review of the clinical and histopathologic records of four patients. Results: Each of four patients had complex limbal choristomas in the setting of clinical and histopathologic LNSS. The limbal choristomas were multiple in three patients and bilateral in two patients. Most choristomas involved the superotemporal limbus (6 of 10), although nasal (3 of 10) and inferior (1 of 10) limbal tumors also were present. Three patients had significant corneal astigmatism or involvement of the central cornea requiring surgical removal of their choristomas, one accompanied by a lamellar keratoplasty and another accompanied by two consecutive penetrating keratoplasties. Each graft eventually vascularized, reducing vision. One patient’s vision was limited by amblyopia and another by occipital cortical dysgenesis with visual impairment. Histopathologic examination of the excised choristomas showed foci of lacrimal gland (3 of 4 patients), adipose tissue (3 of 4), neural tissue (1 of 4), cartilage (1 of 4), lymphoid follicles (1 of 4), skin adnexal tissue (1 of 4), and smooth muscle (1 of 4). Other associated ocular findings included an eyelid mass (1 of 4), colobomas of the eyelid (3 of 4), colobomas of the choroid and retina (2 of 4), nonparalytic strabismus (2 of 4), scleral ectasia (1 of 4), partial oculomotor palsy with ptosis and anisocoria (1 of 4), microphthalmia (1 of 4), hypertelorism (1 of 4), and cortical visual impairment (1 of 4). Conclusions: Complex limbal choristomas, although rare, can occur in the setting of LNSS and can be associated with multiple ocular and systemic abnormalities. Visual prognosis appears poor in most cases despite aggressive management. Ophthalmology 1998;105:1459 –1465 Linear nevus sebaceous syndrome (LNSS), or nevus sebaceous of Jadassohn, is a rare disorder defined initially by Feuerstein and Mims1 to include nevus sebaceous, seizures, and mental retardation. Ocular involvement now is recognized to occur in up to 50% of patients with LNSS.2 The ocular anomaly reported most often in LNSS is limbal choristoma,3–26 defined as an abnormal congenital mass at the limbus that contains tissues not characteristic of that location.12 Several different histopathologic types of limbal choristomas have been described, Originally received: August 25, 1997. Revision accepted: January 18, 1998. Manuscript no. 97488 1 Department of Ophthalmology, University of California, San Francisco, School of Medicine, San Francisco, California. 2 Department of Pediatrics, University of California, San Francisco, School of Medicine, San Francisco, California. 3 Department of Pathology, University of California, San Francisco, School of Medicine, San Francisco, California. 4 The Francis I. Proctor Foundation, San Francisco, California. This work was supported by an unrestricted grant from Research to Prevent Blindness. Reprint requests to Emmett T. Cunningham, Jr., MD, PhD, The Francis I. Proctor Foundation, UCSF School of Medicine, San Francisco, CA 941430944.
including dermoids, lipodermoids, and single-tissue and complex choristomas.27 Complex choristomas are most rare and are characterized by the presence of two or more ectopic tissues.27 We describe here the clinical presentation, management, and histopathology of four patients with complex limbal choristomas in the setting of LNSS.
Case Reports Case 1. LM was the female product of a 35-week gestation. There was no family history of consanguinity or birth defects. Delivery was by Cesarean section because of placenta previa with maternal hemorrhage. Shortly after birth, the patient was noted to have a limbal mass on the right eye (Fig 1A), and a linear nevus on her posterior scalp (Fig 1B), consistent with the diagnosis of LNSS. Other abnormalities noted shortly after birth included frontal bossing, hypoplastic ears, and hypertelorism. Postnatal development was normal with no evidence of seizures. At 2 years of age, the patient was referred to the cornea service of the University of California, San Francisco (UCSF), for evaluation and treatment of the right limbal tumor. Examination at that time showed a right superotemporal limbal mass encroaching on central cornea. Vision was central, steady, and maintained bilaterally, but mild with-the-rule astigmatism was present in the right
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Figure 1. A, limbal mass, right eye, encroaching on central cornea. B, salmon-colored linear nevus, posterior scalp. C, low-power view of excised limbal mass (A). To the right is a disorganized dermis-like connective tissue (open arrow), and to the left are adipose tissue and lacrimal gland (arrowheads). These findings resemble those present in Figure 2C and D (stain, hematoxylin– eosin; magnification, ⫻40). D, histopathology of scalp lesion (B). The epidermis is thickened because of hyperplasia and slight hyperkeratosis (arrowheads). The dermal appendage structures such as hair shafts are somewhat hypoplastic (arrows) (stain, hematoxylin– eosin; magnification, ⫻40). E, rightsided ptosis and mydriasis, with the larger right pupil most noticeable in light. Ocular motility was normal. F, magnetic resonance imaging axial scan of the brain showing scattered subcortical foci in the peritrigonal white matter bilaterally (arrows), which were hypointense on T1, hyperintense on T2, and nonenhancing, consistent with white matter dysgenesis or scar.
A
B
C
D
E eye. The limbal mass was excised, and a free-hand peripheral lamellar keratoplasty was performed. Histopathologic examination of the excised tumor showed a nonkeratinizing stratified squamous epithelium covering densely packed and disorganized collagenous connective tissue. Adipose tissue, dilated capillaries, and ectopic lacrimal gland also were present (Fig 1C). The scalp lesion was excised at the same time as the limbal tumor and showed keratinizing stratified squamous epithelium with mild hyperkeratosis, papillomatosis, and acanthosis covering a disorganized collagenous connective tissue, which contained primitive mesenchymal cells, immature hair structures, and sebaceous glands (Fig 1D). Nine months after surgery, the patient developed right-sided ptosis and mydriasis, with the larger right pupil most noticeable in light (Fig 1E). Ocular motility was normal. A partial right thirdnerve paresis was diagnosed. A magnetic resonance imaging scan of the brain showed no abnormalities in the region of the oculomotor nucleus, fasciculus, or nerve but did show scattered abnormal foci in the peritrigonal white matter bilaterally (Fig 1F). These subcortical foci were hypointense on T1, hyperintense on T2, and nonenhancing, consistent with white matter dysgenesis or scar. With time, the ptosis and anisocoria resolved, but the patient developed both superficial and deep corneal vascularization of the
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F lamellar graft, associated with mild-to-moderate graft haze. Visual acuity in the right eye decreased to 20/100, and esotropia developed despite aggressive patching and refractive management of the residual irregular astigmatism. Case 2. AE was the female product of a normal full-term pregnancy. There was no family history of consanguinity or birth defects. Delivery was vaginal and uncomplicated. Shortly after birth, the patient was noted to have limbal tumors on the right eye, a right upper eyelid defect (Fig 2A), and a linear nevus and patchy alopecia on her scalp (Fig 2B), consistent with the diagnosis of LNSS. Postnatal development was normal with no evidence of seizures. The patient was referred to the pediatric ophthalmology service at UCSF at 9 months of age for evaluation and treatment of her right limbal tumors. Examination at that time showed a large superotemporal limbal mass involving the central cornea and a second, smaller superonasal limbal mass on the right. The limbal masses were excised and a penetrating keratoplasty was performed. Examination of the right eye at the time of surgery showed optic disc tilting and temporal peripapillary chorioretinal atrophy consistent with myopia. Histopathologically, the right limbal masses all were similar and showed nonkeratinizing stratified squamous epithelium covering a loose connective tissue that contained lacrimal gland, adipose tissue, lymphoid follicles, and smooth muscle tissue (Figs 2C, 2D). The
Duncan et al 䡠 Complex Limbal Choristomas in LNSS
Figure 2. A, limbal tumors, right eye, with right upper eyelid coloboma. B, linear nevus and patchy alopecia, anterior scalp (arrows). C, low-power view of excised limbal lesion (A). Nodular aggregates of lymphocytes are apparent just beneath the epithelium (arrow). As in the first case, lacrimal gland and adipose tissue are prominent (arrowheads). In addition, bands of smooth muscle can be identified at the base of the lesion (open arrow) (stain, hematoxylin– eosin; magnification, ⫻40). D, higher power view of (C). Glandular tissue (arrowhead), fat (open arrow), and bundles of smooth muscle (arrows) (stain, hematoxylin– eosin; magnification, ⫻200). E, an immunoperoxidase stain for smooth muscle actin. The interlacing bands are strongly positive. An S-100 stain for peripheral nerve was negative (stain, hematoxylin– eosin; magnification, ⫻200).
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Figure 3. A, linear nevus, scalp (arrowheads). B, superotemporal and inferotemporal limbal masses and a nasal limbal mass associated with scleral ectasia, right eye. C, a coloboma of the left upper eyelid with trichiasis and flesh-colored mass at the lid margin also was present. The limbal tumors are poorly visualized but evident inferonasally. D, histopathologic findings in excised limbal tumor (A). Epithelium is artifactitiously folded on itself (top of photograph). Fibroadipose tissue surrounds a large plaque of hyaline cartilage (lower portion of photograph) (stain, hematoxylin– eosin; magnification, ⫻50).
presence of smooth muscle was confirmed immunohistochemically using smooth muscle actin antiserum (Fig 2E). An S-100 immunoperoxidase stain, used to identify neural tissue, was negative. One month after removal of the limbal masses, the patient developed graft vascularization. Repeat penetrating keratoplasty was performed, but the graft revascularized 18 months after the second surgery. Vision was light perception at last follow-up, and the patient was using a scleral prosthesis. The right upper eyelid coloboma noted at birth was repaired with a right posterior auricular skin graft at 3 months of age. Subsequent keloid formation necessitated two additional eyelid reconstructive procedures at 2 and 8 years of age. Results from punch biopsy of the linear nevus on the anterior scalp showed few hair follicles and no sebaceous gland abnormalities. The linear nevus has been monitored closely but has shown no evidence of malignant transformation. Case 3. HS was the male product of a full-term pregnancy complicated by prolonged rupture of membranes and group B streptococcal pneumonia. There was no family history of consanguinity or birth defects. Shortly after birth, the patient was noted to have bilateral limbal tumors, a linear nevus on his scalp (Fig 3A), developmental delay, and seizures, all consistent with the diagnosis of LNSS. The patient was referred to the pediatric ophthalmology service at UCSF for evaluation of bilateral limbal masses at the age of 27 months. Examination of the right eye showed superotemporal and inferotemporal limbal masses and a nasal limbal mass associated with scleral ectasia (Fig 3B). Examination of the left eye showed nasal and superotemporal limbal tumors (Fig 3C). Vision was central, steady, and maintained bilaterally, but with-the-rule astigmatism was present in the right eye. Other ocular findings included a coloboma of the left upper eyelid with trichiasis, a flesh-colored mass at the lid margin, and a left inferonasal chorioretinal coloboma with peripapillary atrophy. By 5 years of age, the patient began to develop amblyopia and esotropia in the right eye. The superotemporal and inferotemporal right limbal masses were removed, and the right lateral rectus muscle was resected. Scleral ectasia prohibited removal of the
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nasal limbal mass or recession of the medial rectus muscle. The patient subsequently underwent resection of the left limbal masses and repair of the left upper eyelid coloboma with resection of the left upper eyelid tumor. Right esotropia persisted, and the patient developed amblyopia despite aggressive postoperative patching. The patient was lost to follow-up at 5 years of age. Histopathologically, the right limbal mass showed a nonkeratinizing stratified squamous epithelium over a loose connective tissue containing lacrimal gland, cartilage, and adipose tissue (Fig 3D). The left upper eyelid mass showed keratinizing stratified squamous epithelium with hair follicles covering striated muscle, adipose tissue, sweat glands, and lacrimal gland tissue (not shown). The patient had been noted at birth to have a linear nevus present on the scalp (Fig 3A), confirmed histologically (not shown). The linear nevus was monitored closely until age 5 years and showed no evidence of malignant transformation. Case 4. NR was the male product of a pregnancy complicated by parvovirus infection with documented maternal seroconversion at 15 weeks’ gestation, a right pleural effusion drained in utero, onset of preterm labor at 28 weeks, and an emergency Cesarean section delivery performed for breech presentation at 30 weeks. There was no family history of consanguinity or birth defects. The patient required prolonged hospitalization with respiratory support because of severe respiratory distress syndrome and bronchopulmonary dysplasia. Shortly after birth, the patient was noted to have a right eyelid defect with a prolapsing mass, a left limbal mass, extensive skin abnormalities, and a seizure disorder, consistent with the diagnosis of LNSS. The patient was referred to the pediatric ophthalmology service on the third day of life. Examination showed a coloboma of the right upper eyelid extending from the midline to the medial canthus, a pedunculated superotemporal limbal mass, and microphthalmia with a corneal diameter of 8 mm. Dilated fundus examination of the right eye showed a large inferonasal chorioretinal coloboma involving the posterior pole and a tilted optic disc. Examination of the left eye showed a superotemporal limbal mass. The left anterior segment and fundus were otherwise normal. The right superotemporal mass was removed and a tarsorrhaphy per-
Duncan et al 䡠 Complex Limbal Choristomas in LNSS
Figure 4. Histopathologic changes of the excised superotemporal limbal tumor (right eye). The appearance is that of skin with an overlying epidermis, primitive hair follicles, and dermis-like connective tissue. A large nerve bundle is seen to the right (arrowheads) (stain, hematoxylin– eosin; magnification, ⫻40).
formed on the third day of life. Histopathologically, the pedunculated mass was covered with keratinizing stratified squamous epithelium and included skin adnexal structures and neural tissue (Fig 4). Release of the tarsorrhaphy and examination of the right eye at 13 months of age showed an unreactive right pupil and immobilization of the globe by dense conjunctival scarring. The patient was noted to fix and follow well with the left eye, which showed a visual acuity of approximately 20/300 using Teller acuity cards. Neurologic imaging showed occipital cortical dysgenesis with right ventricular dilation. Definitive repair of the right upper eyelid defect was performed at 18 months of age. Skin findings included patchy alopecia; a linear, raised, fleshcolored lesion on the midline of the forehead and the chin; and raised white streaky lesions from the right ear down the right neck as well as on the inner right arm and inner right thigh. Skin biopsy results of a lesion showed papillated epidermal hyperplasia with inflamed vascular proliferation, consistent with linear nevus sebaceous (not shown). Additional systemic findings included supraventricular tachycardia, coarctation of the aorta with hypertension, pulmonary lymphangiectasis, right hemihypertrophy, right inguinal hernia, cryptorchidism, micropenis, and bilateral renal cystic dysplasia.
Discussion We have presented the clinical characteristics of four patients with LNSS and complex limbal choristomas. The limbal tumors most often were superotemporal, although inferior and nasal masses also were present. The choristomas were bilateral in two patients. Three patients required surgical removal of their choristomas, either because of astigmatism or involvement of the central cornea. The fourth patient’s tumor was removed at the time of a lid coloboma repair. Removal of one choristoma was accompanied by a lamellar keratoplasty and a second by two consecutive penetrating keratoplasties. Each graft eventually vascularized, reducing vision. One patient’s vision was limited by amblyopia and another by occipital cortical dysgenesis with visual impairment. Although not part of the original description by Feuerstein and Mims,1 associated ocular anomalies occur in up to 50% of patients with LNSS,2 most commonly limbal
tumors.3–26 Several histopathologic types of limbal tumors have been described, including dermoids, lipodermoids, and single-tissue and complex choristomas.27 Complex choristomas are rare and are characterized by the presence of two or more ectopic tissues.27 All four of the choristomas in our cases were histopathologically complex, showing foci of lacrimal gland (3 of 4), adipose tissue (3 of 4), neural tissue (1 of 4), cartilage (1 of 4), lymphoid follicles (1 of 4), skin adnexal tissue (1 of 4), and smooth muscle (1 of 4). Ectopic tissues reported previously in complex choristomas included lacrimal or serous gland,5–10,12–16,18 –20,25,28 neural tissue,5,7,13,14,16,21,22,28 cartilage,5,7,8,10 –15,18,19,21 smooth muscle,7 fat,7,8,11–15,17,20,24,25,28 hair follicles,9,21 sebaceous glands,9,12,21 bone,13,14,21,22 sweat glands,12,21 lymphoid follicles,12 and bone marrow.21,22 The surgical treatment of patients with limbal choristomas has not been well addressed.29 In general, superficial lamellar keratectomy with lamellar keratoplasty is preferred to penetrating keratoplasty, since lamellar graft vascularization tends to produce only mild haze and irregular astigmatism, whereas vascularization after penetrating keratoplasty more often results in complete graft opacification, frequently from endothelial decompensation and corneal edema.15,30 –34 Mansour and associates15 reported a patient with LNSS and bilateral total conjunctival choristomas who underwent lamellar keratectomy complicated by corneal perforation requiring penetrating keratoplasty. The corneal graft vascularized after 4 months. In this series, the first patient (case 1) underwent lamellar keratoplasty with poor resultant vision due to irregular astigmatism and amblyopia, whereas the second patient (case 2) underwent two consecutive penetrating keratoplasties with graft failure after each procedure. Associated ocular findings present in our cases included an eyelid mass (1 of 4), colobomas of the eyelid (3 of 4), colobomas of the choroid and retina (2 of 4), nonparalytic strabismus (2 of 4), partial oculomotor palsy with ptosis and anisocoria (1 of 4), microphthalmia (1 of 4), hypertelorism (1 of 4), and cortical visual impairment (1 of 4). Previously reported ocular findings associated with LNSS in addition to the complex limbal choristomas discussed above have included microphthalmia,14,23,35–37 macrophthalmia,38 eyelid coloboma,6,10,19,23,24,37,39 – 42 eyelid angiolipoma,38 ptosis,16,21,28,35,43– 46 corneal vascularization,9,13,14,21,24, 36,37,41,42,47,48 iris coloboma,9,47,49,50 cataract,46,50 Coats’ disease,51 chorioretinal coloboma,2,9,13,17,18,21,47 staphyloma,5,13,48,52 choroidal osteoma,19 optic disc coloboma,17– 19,42,49,53,54 optic nerve glioma,55 nystagmus,9,18,23,35, 47,51,56 –58 strabismus,13,16,19,23,24,28,41,46,49,51,54,59 – 64 pseudopapilledema,64 and cortical visual impairment.56,58 Unilateral third cranial nerve palsy has been reported twice before in the literature,16,28 sparing the pupil in one case.28 To our knowledge, transient partial third-nerve palsy as occurred in our case 1 has not been reported. The skin abnormalities were the first findings to be described in LNSS and have been characterized most extensively. In 1895, Jadassohn65 described “Talgdru¸sen– naevi” or sebaceous-gland nevi consisting entirely of large but histologically normal sebaceous lobules. Robinson66 introduced the term “naevus sebaceous of Jadassohn” in 1932 and presented the first histologic evidence of the
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Ophthalmology Volume 105, Number 8, August 1998 association of the nevus with malignancy in a patient with basal cell epithelioma. Mehregan and Pinkus67 presented a comprehensive analysis of the histologic characteristics of nevus sebaceous in patients of different ages and divided the natural history of nevus sebaceous into three phases. They described nevus sebaceous as a skin lesion found primarily on the face or scalp, characterized histopathologically by papillomatous hyperplasia of the epidermis, large sebaceous glands of normal structure, small malformed hair roots, and hyperplastic, cystic apocrine glands.67 In young patients, the sebaceous gland abnormalities can be minimal to absent and can show nonspecific histopathologic changes on biopsy. Such nonspecific changes were observed in punch biopsy specimens taken from two patients in the current series, both of whom were very young. In the second and most characteristic phase, large sebaceous glands and hyperplastic apocrine glands predominate, whereas in the third phase, the skin lesions may undergo malignant transformation.27 For this reason, linear sebaceous nevi should be excised or monitored closely for evidence of growth or change. Neurologic disorders were part of the original description of LNSS by Feuerstein and Mims,1 which included nevus sebaceous, seizures, and mental retardation. A number of other neurologic abnormalities have been reported, most related to abnormal central nervous system development.26 Commonly reported disorders include hemiparesis,2,20,23,40,41,43,45,54,68 –70 quadriparesis,47,71 hypotonia,14,18,42,43,49,50,53,54,56,58,72–74 reflex abnormalities,2,23,43,45,47,58,63,72 gait disorders,23,41 diencephalic syndrome,47,75 and microcephaly.49,70 Frequently reported neurologic imaging results include cortical atrophy,7,13,19,22,41 dilated ventricles,13,23,41,42,47,53,63 and hemimegalencephaly.54,55,58,74 Two of our four cases presented with neurologic involvement, including developmental delay and seizures. Over the past 35 years, numerous systemic abnormalities have been described in association with LNSS, none of which is either common or specific.9,11,39,40,44,47,50,52,54,56,70,76,77 The patient in case 4 in our study presented with a number of systemic findings, including pulmonary lymphangiectasis, supraventricular tachycardia, coarctation of the aorta, renal cystic dysplasia, right inguinal hernia, cryptorchidism, micropenis, and right hemihypertrophy. The patient in case 1 had frontal bossing and hypoplastic ears. Ocular findings have been reported frequently in patients with LNSS and often alert the physician to the diagnosis. Although limbal tumors are the most common ocular manifestation of LNSS,3–26 complex limbal choristomas are rare. Visual prognosis in patients with LNSS and complex limbal choristomas appears guarded, despite aggressive treatment.
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¨ ber eine seltene angeborene Mißbildung der 4. Kranz HW. U Haut mit doppelseitigem symmetrischem Lipodermoid der Conjunctiva bulbi. Arch Ophthalmol 1927;118:167–74. 5. Sherman AR. Teratoid tumor of conjunctiva and other developmental anomalies with naevus verrucosus of scalp. Report of a Case. Arch Ophthalmol 1943;29:441–5. 6. Go¨rdu¸ren S. Aberrant lacrimal gland associated with other congenital abnormalities. Br J Ophthalmol 1962;46:277– 80. 7. Lall K. Teratoma of conjunctiva. Acta Ophthal (Kobenhavn) 1962;40:555– 8. 8. Moynahan EJ, Wolff OH. A new neuro-cutaneous syndrome (skin, eye and brain) consisting of linear naevus, bilateral lipo-dermoid of the conjunctivae, cranial thickening, cerebral cortical atrophy and mental retardation [case report]. Br J Dermatol 1967;79:651–2. 9. Monahan RH, Hill CW, Venters HD. Multiple choristomas, convulsions and mental retardation as a new neurocutaneous syndrome. Am J Ophthalmol 1967;64(3 Suppl):529 –32. 10. Lantis S, Leyden J, Thew M, Heaton C. Nevus sebaceus of Jadassohn. Part of a new neurocutaneous syndrome? Arch Dermatol 1968;98:117–23. 11. Haberland C, Perou M. Encephalocraniocutaneous lipomatosis. A new example of ectomesodermal dysgenesis. Arch Neurol 1970;22:144 –55. 12. Benjamin SN, Allen HF. Classification for limbal dermoid choristomas and branchial arch anomalies. Presentation of an unusual case. Arch Ophthalmol 1972;87:305–14. 13. Wilkes SR, Campbell RJ, Waller RR. Ocular malformation in association with ipsilateral facial nevus of Jadassohn. Am J Ophthalmol 1981;92:344 –52. 14. Shochot Y, Romano A, Barishak YR, et al. Eye findings in the linear sebaceous nevus syndrome: a possible clue to the pathogenesis. J Craniofac Genet Dev Biol 1982;2:289 –94. 15. Mansour AM, Laibson PD, Reinecke RD, et al. Bilateral total corneal and conjunctival choristomas associated with epidermal nevus. Arch Ophthalmol 1986;104:245– 8. 16. Baker RS, Ross PA, Baumann RJ. Neurologic complications of the epidermal nevus syndrome. Arch Neurol 1987;44: 227–32. 17. Diven DG, Solomon AR, McNeely MC, Font RL. Nevus sebaceus associated with major ophthalmologic abnormalities. Arch Dermatol 1987;123:383– 6. 18. Katz B, Wiley CA, Lee VW. Optic nerve hypoplasia and the syndrome of nevus sebaceous of Jadassohn. A new association. Ophthalmology 1987;94:1570 – 6. 19. Lambert HM, Sipperley JO, Shore JW, et al. Linear nevus sebaceous syndrome. Ophthalmology 1987;94:278 – 82. 20. Roth AM, Keltner JL. Linear nevus sebaceous syndrome. J Clin Neuroophthalmol 1993;13:44 –9. 21. Pe’er J, Ilsar M. Epibulbar complex choristoma associated with nevus sebaceus. Arch Ophthalmol 1995;113:1301– 4. 22. Pin˜ol Aguade´ J, Mascaro´ JM, Botella R. Sı´ndrome del nevus epide´rmico. Medicina Cuta´nea 1970;5:99 –104. 23. Zaremba J, Wislawski J, Bidzinski J, et al. Jadassohn’s naevus phakomatosis: I. A report of two cases. Journal of Mental Deficiency Research 1978;22:91–102. 24. Sehgal VN, Ramesh V, Ghorpade A. Naevus sebaceous associated with ocular dermolipoma. J Dermatol 1984;11:97– 8. 25. Brodsky MC, Kincannon JM, Nelson–Adesokan P, Brown HH. Oculocerebral dysgenesis in the linear nevus sebaceous syndrome. Ophthalmology 1997;104:497–503. 26. Zaremba J. Jadassohn’s naevus phakomatosis: 2. A study based on a review of thirty-seven cases. Journal of Mental Deficiency Research 1978;22:103–23. 27. Elsas FJ, Green WR. Epibulbar tumors in childhood. Am J Ophthalmol 1975;79:1001–7.
Duncan et al 䡠 Complex Limbal Choristomas in LNSS 28. Haslam RHA, Wirtschafter JD. Unilateral external oculomotor nerve palsy and nevus sebaceous of Jadassohn. Arch Ophthalmol 1972;87:293–300. 29. Shields JA, Shields CL, DePotter P. Surgical management of conjunctival tumors the 1994 Lynn B. McMahan Lecture. Arch Ophthalmol 1997;115:808 –15. 30. Hwang DG, Hwang PH. Pediatric penetrating keratoplasty. Sem Ophthalmol 1991;6:212– 8. 31. Mansour AM, Barber JC, Reinecke RD, Wang FM. Ocular choristomas. Surv Ophthalmol 1989;33:339 –58. 32. Sugar HS. The oculoauriculovertebral dysplasia syndrome of Goldenhar. Am J Ophthalmol 1966;62:678 – 82. 33. Mohan M, Mukherjee G, Panda A. Clinical evaluation and surgical intervention of limbal dermoid. Indian J Ophthalmol 1981;29:69 –73. 34. Zaidman GW, Johnson B, Brown SI. Corneal transplantation in an infant with corneal dermoid. Am J Ophthalmol 1982;93:78–83. 35. Blazquez JLM, Viota JFL, Luengo OA, et al. Nevus sebaceo de Jadassohn con espasmos infantiles asociados. Anales Espanoles de Pediatria 1988;28:266 – 8. 36. Geißler H. Systematisierter Naevus sebaceus in Kombination mit epileptiformen Krampfanfa¨llen. Dermatologische Wochenschrift 1966;152:1291–3. 37. Alfonso I, Howard C, Lopez PF, et al. Linear nevus sebaceous syndrome. A review. J Clin Neuroophthalmol 1987;7:170 –7. 38. Gooskens RH, Veiga–Pires JA, van Nieuwenhuizen O, Kaiser MC. CT of sebaceous nevus syndrome (Jadassohn disease). AJNR Am J Neuroradiol 1983;4:203–5. 39. Nuno K, Mihara M, Shimao S. Linear sebaceous nevus syndrome. Dermatologica 1990;181:221–3. 40. Kousseff BG. Hypothesis: Jadassohn nevus phakomatosis: a paracrinopathy with variable phenotype. Am J Med Genet 1992;43:651– 61. 41. Jancar J. Naevus syringocystadenomatosus papilliferus with skull and brain lesions, hemiparesis, epilepsy and mental retardation. Br J Dermatol 1970;82:402–5. ¨ zsan H, Turanli AY, et al. A new neurocutaneous 42. Ku¸c¸u¸ko¨du¸k S, O syndrome: nevus sebaceus syndrome. Cutis 1993;51:437–41. 43. Solomon LM, Fretzin DF, Dewald RL. The epidermal nevus syndrome. Arch Dermatol 1968;97:273– 85. 44. Tobias N. Nevus unius lateris, with unilateral hemiatrophy of left side of body [case report]. Archives of Dermatology and Syphilology 1927;15:83– 4. 45. Campbell WW, Buda FB, Sorensen G. Linear nevus sebaceous syndrome: neurological aspects documented by brain scans correlated with developmental history and radiographic studies. Mil Med 1978;143:175– 8. 46. Leyh F, Loewel R. Ein Fall von Schimmelpenning-FeuersteinMims-Syndrom mit allma¨hlicher Kataraktentwicklung. Z Haut Kr 1973;48:695– 8. 47. Marden PM, Venters HD Jr. A new neurocutaneous syndrome. Am J Dis Child 1966;112:79 – 81. 48. Chaurasia BD, Goswami HK. Congenitally malformed female infant with hairy pinnae. Clin Genet 1971;2:111– 4. 49. Besser FS. Linear sebaceous naevi with convulsions and mental retardation (Feuerstein–Mims’ syndrome), vitamin-D-resistant rickets. Proc R Soc Med 1976;69:518 –20. 50. Choi BH, Kudo M. Abnormal neuronal migration and gliomatosis cerebri in epidermal nevus syndrome. Acta Neuropathol (Berl) 1981;53:319 –25. 51. Burch JV, Leveille AS, Morse PH. Ichthyosis hystrix (epidermal nevus syndrome) and Coats’ disease. Am J Ophthalmol 1980;89:25–30. 52. Tripp JH, Joseph MC, Reay HA. A new neurocutaneous syndrome (skin, eye, brain and heart syndrome). Proc R Soc Med 1971;64:23– 4.
53. Moskowitz R, Honig PJ. Nevus sebaceus in association with an intracranial mass. J Am Acad Dermatol 1982;6:1078 – 80. 54. Clancy RR, Kurtz MB, Baker D, et al. Neurologic manifestations of the organoid nevus syndrome. Arch Neurol 1985;42: 236 – 40. 55. Sato K, Kubota T, Kitai R. Linear sebaceous nevus syndrome (sebaceous nevus of Jadassohn) associated with abnormal neuronal migration and optic glioma: case report. Neurosurgery 1994;35:318 –20. 56. Lansky LL, Funderburk S, Cuppage FE, et al. Linear sebaceous nevus syndrome. A hamartoma variant. Am J Dis Child 1972;123:587–90. 57. Carter BS, Hurst DL. Magnetic resonance imaging of the brain in the linear sebaceous nevus syndrome. J Child Neurol 1990; 5:68 –9. 58. Hager BC, Dyme IZ, Guertin SR, et al. Linear nevus sebaceous syndrome: megalencephaly and heterotopic gray matter. Pediatr Neurol 1991;7:45–9. 59. Cavenagh EC, Hart BL, Rose D. Association of linear sebaceous nevus syndrome and unilateral megalencephaly. AJNR Am J Neuroradiol 1993;14:405– 8. 60. Bianchine JW. The nevus sebaceous of Jadassohn. A neurocutaneous syndrome and a potentially premalignant lesion. Am J Dis Child 1970;120:223– 8. 61. Leonidas JC, Wolpert SM, Feingold M, McCauley RG. Radiographic features of the linear nevus sebaceous syndrome. AJR Am J Roentgenol 1979;132:277–9. 62. Marks JG, Tomasovic JJ. Linear nevus sebaceus syndrome. J Am Acad Dermatol 1980;2:31–2. 63. Kurokawa T, Sasaki K, Hanai T, et al. Linear nevus sebaceus syndrome. Report of a case with Lennox–Gastaut syndrome following infantile spasms. Arch Neurol 1981;38:375–7. 64. Campbell SH, Patterson A. Pseudopapilloedema in the linear naevus syndrome. Br J Ophthalmol 1992;76:372– 4. 65. Jadassohn J. II. Bemerkungen zur Histologie der systematisirten Naevi und u¸ber “Talgdru¸sen–naevi.” Arch Dermatol Syph 1895;33:355–94. 66. Robinson SS. Naevus sebaceus (Jadassohn): report of four cases. Arch Dermat Syph 1932;26:663–70. 67. Mehregan AH, Pinkus H. Life history of organoid nevi: special reference to nevus sebaceus of Jadassohn. Arch Dermatol 1965;91:574 – 88. 68. Andriola M. Nevus unius lateralis and brain tumor. Am J Dis Child 1976;130:1259 – 61. 69. Solomon LM, Esterly NB. Epidermal and other congenital organoid nevi. Curr Probl Pediatr 1975;6:1–56. 70. Grebe TA, Rimsza ME, Richter SF, et al. Further delineation of the epidermal nevus syndrome: two cases with new findings and literature review. Am J Med Genet 1993;47:24 –30. 71. Sugarman GI, Reed WB. Two unusual neurocutaneous disorders with facial cutaneous signs. Arch Neurol 1969;21:242–7. 72. Lovejoy FH Jr, Boyle WE Jr. Linear nevus sebaceous syndrome: report of two cases and a review of the literature. Pediatrics 1973;52:382–7. 73. Chalhub EG, Volpe JJ, Gado MH. Linear nevus sebaceous syndrome associated with porencephaly and nonfunctioning major cerebral venous sinuses. Neurology 1975;25:857– 60. 74. Patrizi A, Pizzino D, Tullini A, et al. Sindrome del nevo lineare sebaceo con emimegalencefalia. Su di un caso [Eng Abstr] G Ital Dermatol Venereol 1989;124:55– 8. 75. Meyerson LB. Nevus unius lateralis, brain tumor, and diencephalic syndrome. Arch Dermatol 1967;95:501– 4. 76. Mollica F, Pavone L, Nuciforo G. Linear sebaceous nevus syndrome in a newborn. Am J Dis Child 1974;128:868 –71. 77. O’Neill EM. Linear sebaceous naevus syndrome with oncogenic rickets and diffuse pulmonary angiomatosis. J R Soc Med 1993;86:177– 8.
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including dermoids, lipodermoids, and single-tissue and complex choristomas.27 Complex choristomas are most rare and are characterized by the presence of two or more ectopic tissues.27 We describe here the clinical presentation, management, and histopathology of four patients with complex limbal choristomas in the setting of LNSS.
Case Reports Case 1. LM was the female product of a 35-week gestation. There was no family history of consanguinity or birth defects. Delivery was by Cesarean section because of placenta previa with maternal hemorrhage. Shortly after birth, the patient was noted to have a limbal mass on the right eye (Fig 1A), and a linear nevus on her posterior scalp (Fig 1B), consistent with the diagnosis of LNSS. Other abnormalities noted shortly after birth included frontal bossing, hypoplastic ears, and hypertelorism. Postnatal development was normal with no evidence of seizures. At 2 years of age, the patient was referred to the cornea service of the University of California, San Francisco (UCSF), for evaluation and treatment of the right limbal tumor. Examination at that time showed a right superotemporal limbal mass encroaching on central cornea. Vision was central, steady, and maintained bilaterally, but mild with-the-rule astigmatism was present in the right
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Figure 1. A, limbal mass, right eye, encroaching on central cornea. B, salmon-colored linear nevus, posterior scalp. C, low-power view of excised limbal mass (A). To the right is a disorganized dermis-like connective tissue (open arrow), and to the left are adipose tissue and lacrimal gland (arrowheads). These findings resemble those present in Figure 2C and D (stain, hematoxylin– eosin; magnification, ⫻40). D, histopathology of scalp lesion (B). The epidermis is thickened because of hyperplasia and slight hyperkeratosis (arrowheads). The dermal appendage structures such as hair shafts are somewhat hypoplastic (arrows) (stain, hematoxylin– eosin; magnification, ⫻40). E, rightsided ptosis and mydriasis, with the larger right pupil most noticeable in light. Ocular motility was normal. F, magnetic resonance imaging axial scan of the brain showing scattered subcortical foci in the peritrigonal white matter bilaterally (arrows), which were hypointense on T1, hyperintense on T2, and nonenhancing, consistent with white matter dysgenesis or scar.
A
B
C
D
E eye. The limbal mass was excised, and a free-hand peripheral lamellar keratoplasty was performed. Histopathologic examination of the excised tumor showed a nonkeratinizing stratified squamous epithelium covering densely packed and disorganized collagenous connective tissue. Adipose tissue, dilated capillaries, and ectopic lacrimal gland also were present (Fig 1C). The scalp lesion was excised at the same time as the limbal tumor and showed keratinizing stratified squamous epithelium with mild hyperkeratosis, papillomatosis, and acanthosis covering a disorganized collagenous connective tissue, which contained primitive mesenchymal cells, immature hair structures, and sebaceous glands (Fig 1D). Nine months after surgery, the patient developed right-sided ptosis and mydriasis, with the larger right pupil most noticeable in light (Fig 1E). Ocular motility was normal. A partial right thirdnerve paresis was diagnosed. A magnetic resonance imaging scan of the brain showed no abnormalities in the region of the oculomotor nucleus, fasciculus, or nerve but did show scattered abnormal foci in the peritrigonal white matter bilaterally (Fig 1F). These subcortical foci were hypointense on T1, hyperintense on T2, and nonenhancing, consistent with white matter dysgenesis or scar. With time, the ptosis and anisocoria resolved, but the patient developed both superficial and deep corneal vascularization of the
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F lamellar graft, associated with mild-to-moderate graft haze. Visual acuity in the right eye decreased to 20/100, and esotropia developed despite aggressive patching and refractive management of the residual irregular astigmatism. Case 2. AE was the female product of a normal full-term pregnancy. There was no family history of consanguinity or birth defects. Delivery was vaginal and uncomplicated. Shortly after birth, the patient was noted to have limbal tumors on the right eye, a right upper eyelid defect (Fig 2A), and a linear nevus and patchy alopecia on her scalp (Fig 2B), consistent with the diagnosis of LNSS. Postnatal development was normal with no evidence of seizures. The patient was referred to the pediatric ophthalmology service at UCSF at 9 months of age for evaluation and treatment of her right limbal tumors. Examination at that time showed a large superotemporal limbal mass involving the central cornea and a second, smaller superonasal limbal mass on the right. The limbal masses were excised and a penetrating keratoplasty was performed. Examination of the right eye at the time of surgery showed optic disc tilting and temporal peripapillary chorioretinal atrophy consistent with myopia. Histopathologically, the right limbal masses all were similar and showed nonkeratinizing stratified squamous epithelium covering a loose connective tissue that contained lacrimal gland, adipose tissue, lymphoid follicles, and smooth muscle tissue (Figs 2C, 2D). The
Duncan et al 䡠 Complex Limbal Choristomas in LNSS
Figure 2. A, limbal tumors, right eye, with right upper eyelid coloboma. B, linear nevus and patchy alopecia, anterior scalp (arrows). C, low-power view of excised limbal lesion (A). Nodular aggregates of lymphocytes are apparent just beneath the epithelium (arrow). As in the first case, lacrimal gland and adipose tissue are prominent (arrowheads). In addition, bands of smooth muscle can be identified at the base of the lesion (open arrow) (stain, hematoxylin– eosin; magnification, ⫻40). D, higher power view of (C). Glandular tissue (arrowhead), fat (open arrow), and bundles of smooth muscle (arrows) (stain, hematoxylin– eosin; magnification, ⫻200). E, an immunoperoxidase stain for smooth muscle actin. The interlacing bands are strongly positive. An S-100 stain for peripheral nerve was negative (stain, hematoxylin– eosin; magnification, ⫻200).
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Figure 3. A, linear nevus, scalp (arrowheads). B, superotemporal and inferotemporal limbal masses and a nasal limbal mass associated with scleral ectasia, right eye. C, a coloboma of the left upper eyelid with trichiasis and flesh-colored mass at the lid margin also was present. The limbal tumors are poorly visualized but evident inferonasally. D, histopathologic findings in excised limbal tumor (A). Epithelium is artifactitiously folded on itself (top of photograph). Fibroadipose tissue surrounds a large plaque of hyaline cartilage (lower portion of photograph) (stain, hematoxylin– eosin; magnification, ⫻50).
presence of smooth muscle was confirmed immunohistochemically using smooth muscle actin antiserum (Fig 2E). An S-100 immunoperoxidase stain, used to identify neural tissue, was negative. One month after removal of the limbal masses, the patient developed graft vascularization. Repeat penetrating keratoplasty was performed, but the graft revascularized 18 months after the second surgery. Vision was light perception at last follow-up, and the patient was using a scleral prosthesis. The right upper eyelid coloboma noted at birth was repaired with a right posterior auricular skin graft at 3 months of age. Subsequent keloid formation necessitated two additional eyelid reconstructive procedures at 2 and 8 years of age. Results from punch biopsy of the linear nevus on the anterior scalp showed few hair follicles and no sebaceous gland abnormalities. The linear nevus has been monitored closely but has shown no evidence of malignant transformation. Case 3. HS was the male product of a full-term pregnancy complicated by prolonged rupture of membranes and group B streptococcal pneumonia. There was no family history of consanguinity or birth defects. Shortly after birth, the patient was noted to have bilateral limbal tumors, a linear nevus on his scalp (Fig 3A), developmental delay, and seizures, all consistent with the diagnosis of LNSS. The patient was referred to the pediatric ophthalmology service at UCSF for evaluation of bilateral limbal masses at the age of 27 months. Examination of the right eye showed superotemporal and inferotemporal limbal masses and a nasal limbal mass associated with scleral ectasia (Fig 3B). Examination of the left eye showed nasal and superotemporal limbal tumors (Fig 3C). Vision was central, steady, and maintained bilaterally, but with-the-rule astigmatism was present in the right eye. Other ocular findings included a coloboma of the left upper eyelid with trichiasis, a flesh-colored mass at the lid margin, and a left inferonasal chorioretinal coloboma with peripapillary atrophy. By 5 years of age, the patient began to develop amblyopia and esotropia in the right eye. The superotemporal and inferotemporal right limbal masses were removed, and the right lateral rectus muscle was resected. Scleral ectasia prohibited removal of the
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nasal limbal mass or recession of the medial rectus muscle. The patient subsequently underwent resection of the left limbal masses and repair of the left upper eyelid coloboma with resection of the left upper eyelid tumor. Right esotropia persisted, and the patient developed amblyopia despite aggressive postoperative patching. The patient was lost to follow-up at 5 years of age. Histopathologically, the right limbal mass showed a nonkeratinizing stratified squamous epithelium over a loose connective tissue containing lacrimal gland, cartilage, and adipose tissue (Fig 3D). The left upper eyelid mass showed keratinizing stratified squamous epithelium with hair follicles covering striated muscle, adipose tissue, sweat glands, and lacrimal gland tissue (not shown). The patient had been noted at birth to have a linear nevus present on the scalp (Fig 3A), confirmed histologically (not shown). The linear nevus was monitored closely until age 5 years and showed no evidence of malignant transformation. Case 4. NR was the male product of a pregnancy complicated by parvovirus infection with documented maternal seroconversion at 15 weeks’ gestation, a right pleural effusion drained in utero, onset of preterm labor at 28 weeks, and an emergency Cesarean section delivery performed for breech presentation at 30 weeks. There was no family history of consanguinity or birth defects. The patient required prolonged hospitalization with respiratory support because of severe respiratory distress syndrome and bronchopulmonary dysplasia. Shortly after birth, the patient was noted to have a right eyelid defect with a prolapsing mass, a left limbal mass, extensive skin abnormalities, and a seizure disorder, consistent with the diagnosis of LNSS. The patient was referred to the pediatric ophthalmology service on the third day of life. Examination showed a coloboma of the right upper eyelid extending from the midline to the medial canthus, a pedunculated superotemporal limbal mass, and microphthalmia with a corneal diameter of 8 mm. Dilated fundus examination of the right eye showed a large inferonasal chorioretinal coloboma involving the posterior pole and a tilted optic disc. Examination of the left eye showed a superotemporal limbal mass. The left anterior segment and fundus were otherwise normal. The right superotemporal mass was removed and a tarsorrhaphy per-
Duncan et al 䡠 Complex Limbal Choristomas in LNSS
Figure 4. Histopathologic changes of the excised superotemporal limbal tumor (right eye). The appearance is that of skin with an overlying epidermis, primitive hair follicles, and dermis-like connective tissue. A large nerve bundle is seen to the right (arrowheads) (stain, hematoxylin– eosin; magnification, ⫻40).
formed on the third day of life. Histopathologically, the pedunculated mass was covered with keratinizing stratified squamous epithelium and included skin adnexal structures and neural tissue (Fig 4). Release of the tarsorrhaphy and examination of the right eye at 13 months of age showed an unreactive right pupil and immobilization of the globe by dense conjunctival scarring. The patient was noted to fix and follow well with the left eye, which showed a visual acuity of approximately 20/300 using Teller acuity cards. Neurologic imaging showed occipital cortical dysgenesis with right ventricular dilation. Definitive repair of the right upper eyelid defect was performed at 18 months of age. Skin findings included patchy alopecia; a linear, raised, fleshcolored lesion on the midline of the forehead and the chin; and raised white streaky lesions from the right ear down the right neck as well as on the inner right arm and inner right thigh. Skin biopsy results of a lesion showed papillated epidermal hyperplasia with inflamed vascular proliferation, consistent with linear nevus sebaceous (not shown). Additional systemic findings included supraventricular tachycardia, coarctation of the aorta with hypertension, pulmonary lymphangiectasis, right hemihypertrophy, right inguinal hernia, cryptorchidism, micropenis, and bilateral renal cystic dysplasia.
Discussion We have presented the clinical characteristics of four patients with LNSS and complex limbal choristomas. The limbal tumors most often were superotemporal, although inferior and nasal masses also were present. The choristomas were bilateral in two patients. Three patients required surgical removal of their choristomas, either because of astigmatism or involvement of the central cornea. The fourth patient’s tumor was removed at the time of a lid coloboma repair. Removal of one choristoma was accompanied by a lamellar keratoplasty and a second by two consecutive penetrating keratoplasties. Each graft eventually vascularized, reducing vision. One patient’s vision was limited by amblyopia and another by occipital cortical dysgenesis with visual impairment. Although not part of the original description by Feuerstein and Mims,1 associated ocular anomalies occur in up to 50% of patients with LNSS,2 most commonly limbal
tumors.3–26 Several histopathologic types of limbal tumors have been described, including dermoids, lipodermoids, and single-tissue and complex choristomas.27 Complex choristomas are rare and are characterized by the presence of two or more ectopic tissues.27 All four of the choristomas in our cases were histopathologically complex, showing foci of lacrimal gland (3 of 4), adipose tissue (3 of 4), neural tissue (1 of 4), cartilage (1 of 4), lymphoid follicles (1 of 4), skin adnexal tissue (1 of 4), and smooth muscle (1 of 4). Ectopic tissues reported previously in complex choristomas included lacrimal or serous gland,5–10,12–16,18 –20,25,28 neural tissue,5,7,13,14,16,21,22,28 cartilage,5,7,8,10 –15,18,19,21 smooth muscle,7 fat,7,8,11–15,17,20,24,25,28 hair follicles,9,21 sebaceous glands,9,12,21 bone,13,14,21,22 sweat glands,12,21 lymphoid follicles,12 and bone marrow.21,22 The surgical treatment of patients with limbal choristomas has not been well addressed.29 In general, superficial lamellar keratectomy with lamellar keratoplasty is preferred to penetrating keratoplasty, since lamellar graft vascularization tends to produce only mild haze and irregular astigmatism, whereas vascularization after penetrating keratoplasty more often results in complete graft opacification, frequently from endothelial decompensation and corneal edema.15,30 –34 Mansour and associates15 reported a patient with LNSS and bilateral total conjunctival choristomas who underwent lamellar keratectomy complicated by corneal perforation requiring penetrating keratoplasty. The corneal graft vascularized after 4 months. In this series, the first patient (case 1) underwent lamellar keratoplasty with poor resultant vision due to irregular astigmatism and amblyopia, whereas the second patient (case 2) underwent two consecutive penetrating keratoplasties with graft failure after each procedure. Associated ocular findings present in our cases included an eyelid mass (1 of 4), colobomas of the eyelid (3 of 4), colobomas of the choroid and retina (2 of 4), nonparalytic strabismus (2 of 4), partial oculomotor palsy with ptosis and anisocoria (1 of 4), microphthalmia (1 of 4), hypertelorism (1 of 4), and cortical visual impairment (1 of 4). Previously reported ocular findings associated with LNSS in addition to the complex limbal choristomas discussed above have included microphthalmia,14,23,35–37 macrophthalmia,38 eyelid coloboma,6,10,19,23,24,37,39 – 42 eyelid angiolipoma,38 ptosis,16,21,28,35,43– 46 corneal vascularization,9,13,14,21,24, 36,37,41,42,47,48 iris coloboma,9,47,49,50 cataract,46,50 Coats’ disease,51 chorioretinal coloboma,2,9,13,17,18,21,47 staphyloma,5,13,48,52 choroidal osteoma,19 optic disc coloboma,17– 19,42,49,53,54 optic nerve glioma,55 nystagmus,9,18,23,35, 47,51,56 –58 strabismus,13,16,19,23,24,28,41,46,49,51,54,59 – 64 pseudopapilledema,64 and cortical visual impairment.56,58 Unilateral third cranial nerve palsy has been reported twice before in the literature,16,28 sparing the pupil in one case.28 To our knowledge, transient partial third-nerve palsy as occurred in our case 1 has not been reported. The skin abnormalities were the first findings to be described in LNSS and have been characterized most extensively. In 1895, Jadassohn65 described “Talgdru¸sen– naevi” or sebaceous-gland nevi consisting entirely of large but histologically normal sebaceous lobules. Robinson66 introduced the term “naevus sebaceous of Jadassohn” in 1932 and presented the first histologic evidence of the
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Ophthalmology Volume 105, Number 8, August 1998 association of the nevus with malignancy in a patient with basal cell epithelioma. Mehregan and Pinkus67 presented a comprehensive analysis of the histologic characteristics of nevus sebaceous in patients of different ages and divided the natural history of nevus sebaceous into three phases. They described nevus sebaceous as a skin lesion found primarily on the face or scalp, characterized histopathologically by papillomatous hyperplasia of the epidermis, large sebaceous glands of normal structure, small malformed hair roots, and hyperplastic, cystic apocrine glands.67 In young patients, the sebaceous gland abnormalities can be minimal to absent and can show nonspecific histopathologic changes on biopsy. Such nonspecific changes were observed in punch biopsy specimens taken from two patients in the current series, both of whom were very young. In the second and most characteristic phase, large sebaceous glands and hyperplastic apocrine glands predominate, whereas in the third phase, the skin lesions may undergo malignant transformation.27 For this reason, linear sebaceous nevi should be excised or monitored closely for evidence of growth or change. Neurologic disorders were part of the original description of LNSS by Feuerstein and Mims,1 which included nevus sebaceous, seizures, and mental retardation. A number of other neurologic abnormalities have been reported, most related to abnormal central nervous system development.26 Commonly reported disorders include hemiparesis,2,20,23,40,41,43,45,54,68 –70 quadriparesis,47,71 hypotonia,14,18,42,43,49,50,53,54,56,58,72–74 reflex abnormalities,2,23,43,45,47,58,63,72 gait disorders,23,41 diencephalic syndrome,47,75 and microcephaly.49,70 Frequently reported neurologic imaging results include cortical atrophy,7,13,19,22,41 dilated ventricles,13,23,41,42,47,53,63 and hemimegalencephaly.54,55,58,74 Two of our four cases presented with neurologic involvement, including developmental delay and seizures. Over the past 35 years, numerous systemic abnormalities have been described in association with LNSS, none of which is either common or specific.9,11,39,40,44,47,50,52,54,56,70,76,77 The patient in case 4 in our study presented with a number of systemic findings, including pulmonary lymphangiectasis, supraventricular tachycardia, coarctation of the aorta, renal cystic dysplasia, right inguinal hernia, cryptorchidism, micropenis, and right hemihypertrophy. The patient in case 1 had frontal bossing and hypoplastic ears. Ocular findings have been reported frequently in patients with LNSS and often alert the physician to the diagnosis. Although limbal tumors are the most common ocular manifestation of LNSS,3–26 complex limbal choristomas are rare. Visual prognosis in patients with LNSS and complex limbal choristomas appears guarded, despite aggressive treatment.
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