Cutaneous Angiomyolipoma of the Eyelid in a 2-Year-Old With Tuberous Sclerosis Complex

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Cutaneous Angiomyolipoma of the Eyelid in a 2-Year-Old With Tuberous Sclerosis Complex Lauren C. Ditta, MD, Jie Zhang, MD, Wafi Bibars, MD, John Bissler, MD CASE REPORT Downloaded from http://journals.lww.com/jneuro-ophthalmology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 05/04/2022 A 2-year-old boy diagnosed with tuberous sclerosis complex (TSC) was referred to pediatric neuroophthalmology as part of a multi-disciplinary workup. The mother expressed concern about the appearance of the child’s left upper eyelid, which for the past year, was more full and discolored compared with the right eyelid (Fig. 1). On neuro-ophthalmic examination, the child demonstrated verbal delay, but he cooperated for the examination. Vision was normal for age, pupils were equally reactive without an afferent pupillary defect, sensorimotor examination was unremarkable, and his cycloplegic refraction demonstrated low hyperopia. On external examination, there was fullness of the left upper eyelid with irregular skin changes and discoloration. There was no significant blepharoptosis. Levator function appeared equal and normal. No discrete mass could be firmly palpated; however, the eyelid had a palpable irregular superficial and deep texture. The remainder of his anterior segment examination was unremarkable. Dilated examination revealed healthy optic nerves with no peripheral retinal pigment changes or retinal astrocytic hamartomas (RAHs). An ultrasound of the left upper eyelid was performed revealing a well-circumscribed solid-appearing, superficial soft tissue lesion, slightly hypoechoic relative to the adjacent adipose tissue and demonstrated mild vascularity on Doppler interrogation. The Department of Ophthalmology (LCD), University of Tennessee Health Science Center, Hamilton Eye Institute, Memphis, Tennessee; Department of Neuro-Ophthalmology (LCD), Le Bonheur Children’s Hospital Neuroscience Institute, Memphis, Tennessee; Department of Ophthalmology (LCD), St. Jude Children’s Research Hospital, Memphis, Memphis Tennessee; Le Bonheur Tuberous Sclerosis Center of Excellence (LCD, JB), Le Bonheur Children’s Hospital, Memphis, Tennessee; Department of Pathology (JZ, WB), University of Tennessee Health Science Center, Memphis, Tennessee; Department of Pathology (JZ), Le Bonheur Children’s Hospital, Memphis, Tennessee; Department of Pediatrics (JB), Le Bonheur Children’s Hospital, Memphis, Tennessee; Division Chief, Department of Nephrology (JB), Le Bonheur Children’s Hospital, Memphis, Tennessee; and Division Chief, Department of Nephrology (JB), St. Jude Children’s Research Hospital, Memphis, Tennessee. The authors report no conflicts of interest. lesion measured approximately 3 mm in thickness · 1 mm in transverse width. The mother elected to proceed with resection of the left upper eyelid lesion. Informed consent was obtained and general anesthesia commenced without complication. Lidocaine with 2% epinephrine was infused in the left upper eyelid. An ellipse incision was made over the abnormal skin, sharp scissors were used to dissect down to the levator aponeurosis, and the orbital septum was visualized. There was abnormal tissue with lobulated areas that were easily removed in one piece. Healthy, normal tissue surrounded the abnormal tissue with no evidence of infiltration. The subcutaneous tissue and skin were closed in an interrupted fashion and the eyelid was dressed with ointment and a patch. On pathologic assessment, the gross pathology specimen was a yellow-tan lobulated lesion measuring 1.0 · 0.7 · 0.5 cm. Microscopically, the dermis showed mild fibrosis with scattered dilated venules. A few thick-walled blood vessels and adjacent mature adipose tissue was seen between dermis and orbicular muscles. The thickened vascular wall lacked an elastic lamina and was composed of spindled or epithelioid cells. Those cells were immunoreactive to smooth muscle actin in a diffuse pattern and to HMB-45 in a patchy pattern (Fig. 2), and immunonegative to S-100 protein. Adjacent mature adipose cells are immunoreactive to S-100 protein. Such morphologic and immunophenotypic features are similar to renal angiomyolipoma (AML). TSC is a rare multi-systemic genetic disease characterized by the presence of benign tumors in different organ systems. Of the ophthalmic manifestations, RAHs are the most common, which are benign glial tumors of the inner retina. In addition, retinal achromic patches, refractive error, eyelid angiofibromas, This case study was HIPAA compliant and performed after parental consent. Address correspondence to Lauren C. Ditta, MD, Le Bonheur Children’s Hospital, Neuroscience Institute, 848 Adams Avenue, Memphis, Tennessee 38103; E-mail: [e-mail] Ditta et al: J Neuro-Ophthalmol 2021; 41: e69-e70 FIG. 1. External photograph showing an elevated, irregular, poorly circumscribed lesion near the left brow. Note the overlying, superficial skin changes. e69 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence theloid cells, in particular, produce a basal lamina extracellular matrix such as that of endothelial cells and pericytes in the vasculature. Most cutaneous angiomyolipomata have no association with TSC, are HMB-45 negative and more commonly are named as a mesenchymal lesion of fat. However, in the setting of TSC, these lesions are not fatty tumors such as cutaneous angiomyolipomas, but rather vascular tumors of anomalous vascular development (3–5). Herein, we report a child with a cutaneous angiomyolipoma of the eyelid with tumor markers positive for HMB-45, consistent with a diagnosis of TSC. Although AML have been reported in various extrarenal locations throughout the body, including the skin, the cutaneous form of this lesion is uncommon. To date, fewer than 50 cases have been reported in the literature since cutaneous AML were first described in 1990 (4,5). To our knowledge, the is the first documented case of cutaneous AML in the eyelid. Treatment strategies in the pediatric age group include simple excision for amblyopia risk factors, such as blepharoptosis or astigmatism, and to improve cosmesis. In addition, systemic agents (i.e., rapamycin), may be a reasonable modality to reduce the size of both cutaneous (AML) and other TSC lesions throughout the body in patients who have mutations in TSC1 and TSC2 tumor suppressor genes, leading to hyperactivation of the mTOR (Mammalian Target of Rapamycin) pathway. FIG. 2. Thick-walled vessel is immunoreactive to HMB-45 in a patchy pattern (·400). nonparalytic strabismus, and colobomas can also be seen (1). Angiomyolipomata are a type of perivascular epithelioid cell tumor. They are the most common benign renal tumors, occurring in 0.2% and 0.6% of the population, and in 80% of cases is sporadic. The remaining 20% of AML found in the kidney are associated with TSC (2). AML of the kidney develop in approximately 80% of patients with diagnosis of TSC (3). As the name would imply, TSC-associated AML are comprised of different cellular components, including blood vessels, spindle (or smooth muscle-like) cells, epithelioid cells, and fat-like cells (3). This tumor is not of adipocyte origin, as it is consistently negative for S-100 immunohistochemistry. Angiomyolipomata are rare, benign, vascular tumors, demonstrating microscopic, histochemical, and morphological findings of a vascular cell of origin. Electron microscopy has demonstrated that angiomyolipoma spindle and epi- e70 STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: L. C. Ditta, J. Zhang, W. Bibars, J. Bissler; b. Acquisition of data: L. C. Ditta, J. Zhang, W. Bibars, J. Bissler; c. Analysis and interpretation of data: L. C. Ditta, J. Zhang, W. Bibars, J. Bissler. Category 2: a. Drafting the manuscript: L. C. Ditta, J. Zhang, W. Bibars, J. Bissler; b. Revising it for intellectual content: L. C. Ditta, J. Zhang, W. Bibars, J. Bissler. Category 3: a. Final approval of the completed manuscript: L. C. Ditta, J. Zhang, W. Bibars, J. Bissler. REFERENCES 1. Rowley SA, O’Callaghan FJ, Osborne JP. Ophthalmic manifestations of tuberous sclerosis: a population-based study. Br J Ophthalmic. 2001;85:420–423. 2. Fittschen A, Wendlik I, Oeztuerk S, Kratzer W, Akinli AS, Haenle MM, Graeter T. Prevalence of sporadic renal angiomyolipoma: a retrospective analysis of 61,389 in- and out-patients. Abdom Imaging. 2014;39:1009–1013. 3. Bissler JJ, Kingswood JC. Renal angiomyolipomata. Kidney Int. 2004;66:924–934. 4. Fitzpatrick JE, Mellette JR Jr, Hwang RJ, Golitz LE, Zaim MT, Clemons D. Cutaneous angiolipoleiomyoma. J Am Acad Dermatol. 1990;23:1093–1098. 5. Mannan AASR, Khandakar B, Yuan S. Cutaneous angiomyolipoma of the ear: a case report and literature review. Am J Dermatopathol. 2019:144–147. Ditta et al: J Neuro-Ophthalmol 2021; 41: e69-e70 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.