Skip to main content
SpringerLink
Log in

Systemic Associations

  • Chapter
  • First Online:
Clinical Ophthalmic Oncology

  • 453 Accesses

Abstract

Several rare eyelid tumors may be manifestations of a systemic disease. It is imperative for ophthalmologists to recognize their systemic associations and initiate appropriate systemic and genetic evaluation. In this review, we describe eyelid tumors with associated systemic diseases (Table 11.1). Where applicable, the inheritance pattern of the syndromic association and its molecular genetics are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AVM:

Arteriovenous malformation

BCC:

Basal cell carcinoma

CHRPE:

Congenital hypertrophy of retinal pigment epithelium

CM:

Capillary malformations

CNC:

Carney complex

CS:

Cowden syndrome

FDA:

Food Drug Administration

HNPCC:

Hereditary nonpolyposis colorectal cancer

MRI:

Magnetic resonance imaging

MTS:

Muir-Torre syndrome

NBCCS:

Nevoid basal cell carcinoma syndrome

NF1:

Neurofibromatosis type 1

PDL:

Pulsed dye laser

PDT:

Photodynamic therapy

RPE:

Retinal pigment epithelium

SWS:

Sturge-Weber syndrome

References

  1. Ponder B. Inherited cancer syndromes. In: Carney D, Sikora K, editors. Genes and cancer. New York: John Wiley & Sons; 1990. p. 99–106.

    Google Scholar 

  2. Bianciotto C, Demirci H, Shields CL, et al. Metastatic tumors to the eyelid: report of 20 cases and review of the literature. Arch Ophthalmol. 2009;127(8):999–1005.

    PubMed  Google Scholar 

  3. Boyd KP, Korf BR, Theos A. Neurofibromatosis type 1. J Am Acad Dermatol. 2009;61(1):1–14.

    PubMed  PubMed Central  Google Scholar 

  4. Avery RA, Katowitz JA, Fisher MJ, et al. Orbital/periorbital plexiform neurofibromas in children with neurofibromatosis type 1: multidisciplinary recommendations for care. Ophthalmology. 2017;124(1):123–32.

    PubMed  Google Scholar 

  5. Zhang ML, Suarez MJ, Bosley TM, et al. Clinicopathological features of peripheral nerve sheath tumors involving the eye and ocular adnexa. Hum Pathol. 2017;63:70–8.

    PubMed  PubMed Central  Google Scholar 

  6. Pai HV, Abbagani S, Jaishankar PP. Isolated neurofibroma of the eyelid mimicking recurrent chalazion. Indian J Ophthalmol. 2018;66(3):451–3.

    PubMed  PubMed Central  Google Scholar 

  7. Chen N, Hsu Y-H, Lee Y-C. Solitary neurofibroma of eyelid masquerading as chalazion. Int Med Case Rep J. 2017;10:177–9.

    PubMed  PubMed Central  Google Scholar 

  8. Savar A, Cestari DM. Neurofibromatosis type I: genetics and clinical manifestations. Semin Ophthalmol. 2008;23(1):45–51.

    PubMed  Google Scholar 

  9. Jain G, Jain VK, Sharma IK, et al. Neurofibromatosis type 1 presenting with ophthalmic features: a case series. J Clin Diagn Res. 2016;10(11):SR01–3.

    PubMed  PubMed Central  Google Scholar 

  10. Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol. 2014;13(8):834–43.

    PubMed  Google Scholar 

  11. Avery RA, Dombi E, Hutcheson KA, et al. Visual outcomes in children with neurofibromatosis type 1 and orbitotemporal plexiform neurofibromas. Am J Ophthalmol. 2013;155(6):1089–1094.e1.

    PubMed  Google Scholar 

  12. Altan-Yaycioglu R, Hintschich C. Clinical features and surgical management of orbitotemporal neurofibromatosis: a retrospective interventional case series. Orbit. 2010;29(5):232–8.

    PubMed  Google Scholar 

  13. Gandhi NG. Treatment of neuro-ophthalmic and orbitofacial manifestations of neurofibromatosis type 1. Curr Opin Ophthalmol. 2013;24(5):506–11.

    PubMed  Google Scholar 

  14. Rasmussen SA, Yang Q, Friedman JM. Mortality in neurofibromatosis 1: an analysis using U.S. death certificates. Am J Hum Genet. 2001;68(5):1110–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Higham CS, Dombi E, Rogiers A, et al. The characteristics of 76 atypical neurofibromas as precursors to neurofibromatosis 1 associated malignant peripheral nerve sheath tumors. Neuro Oncol. 2018;

    Google Scholar 

  16. Kehrer-Sawatzki H, Vogt J, Mußotter T, et al. Dissecting the clinical phenotype associated with mosaic type-2 NF1 microdeletions. Neurogenetics. 2012;13(3):229–36.

    CAS  PubMed  Google Scholar 

  17. Nguyen R, Jett K, Harris GJ, et al. Benign whole body tumor volume is a risk factor for malignant peripheral nerve sheath tumors in neurofibromatosis type 1. J Neuro-Oncol. 2014;116(2):307–13.

    CAS  Google Scholar 

  18. Lee JW, Chung HY. Capillary malformations (Portwine Stains) of the head and neck. Otolaryngol Clin N Am. 2018;51(1):197–211.

    Google Scholar 

  19. Mills CM, Lanigan SW, Hughes J, et al. Demographic study of port wine stain patients attending a laser clinic: family history, prevalence of naevus anaemicus and results of prior treatment. Clin Exp Dermatol. 1997;22(4):166–8.

    CAS  PubMed  Google Scholar 

  20. Parsa CF. Focal venous hypertension as a pathophysiologic mechanism for tissue hypertrophy, port-wine stains, the Sturge-Weber syndrome, and related disorders: proof of concept with novel hypothesis for underlying etiological cause (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2013;111:180–215.

    PubMed  PubMed Central  Google Scholar 

  21. Shirley MD, Tang H, Gallione CJ, et al. Sturge–Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013;368(21):1971–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Frigerio A, Wright K, Wooderchak-Donahue W, et al. Genetic variants associated with port-wine stains. Rieux-Laucat F, editor. PLoS One. 2015;10(7):e0133158.

    PubMed  PubMed Central  Google Scholar 

  23. Yadav P, De Castro DK, Waner M, et al. Vascular anomalies of the head and neck: a review of genetics. Semin Ophthalmol. 2013;28(5–6):257–66.

    PubMed  Google Scholar 

  24. Sivarajan V, Maclaren WM, Mackay IR. The effect of varying pulse duration, wavelength, spot size, and fluence on the response of previously treated capillary vascular malformations to pulsed-dye laser treatment. Ann Plast Surg. 2006;57(1):25–32.

    CAS  PubMed  Google Scholar 

  25. Thomson J, Greig A, Lloyd C, et al. PHACE syndrome misdiagnosed as a port-wine stain. BMJ Case Rep. 2015;2015:bcr2015209889.

    PubMed  PubMed Central  Google Scholar 

  26. Haggstrom AN, Lammer EJ, Schneider RA, et al. Patterns of infantile hemangiomas: new clues to hemangioma pathogenesis and embryonic facial development. Pediatrics. 2006;117(3):698–703.

    PubMed  Google Scholar 

  27. Tallman B, Tan OT, Morelli JG, et al. Location of port-wine stains and the likelihood of ophthalmic and/or central nervous system complications. Pediatrics. 1991;87(3):323–7.

    CAS  PubMed  Google Scholar 

  28. Singh AK, Keenaghan M, Sturge-Weber syndrome. [Updated 2018 Oct 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459163/.

  29. Dymerska M, Kirkorian AY, Offermann EA, et al. Size of facial port-wine birthmark may predict neurologic outcome in Sturge-Weber syndrome. J Pediatr. 2017;188:205–209.e1.

    PubMed  Google Scholar 

  30. Pascual-Castroviejo I, Pascual-Pascual S-I, Velazquez-Fragua R, et al. Sturge-Weber syndrome: study of 55 patients. Can J Neurol Sci. 2008;35(3):301–7.

    PubMed  Google Scholar 

  31. Zallmann M, Leventer RJ, Mackay MT, et al. Screening for Sturge-Weber syndrome: a state-of-the-art review. Pediatr Dermatol. 2018;35(1):30–42.

    PubMed  Google Scholar 

  32. Abdolrahimzadeh S, Scavella V, Felli L, et al. Ophthalmic Alterations in the Sturge-Weber Syndrome, Klippel-Trenaunay Syndrome, and the Phakomatosis Pigmentovascularis: An Independent Group of Conditions? Biomed Res Int. 2015;2015:786519.

    PubMed  PubMed Central  Google Scholar 

  33. Panjwani S, Bagewadi A, Keluskar V, et al. Gardner’s syndrome. J Clin Imaging Sci. 2011;1(1):65.

    PubMed  PubMed Central  Google Scholar 

  34. Blair NP, Trempe CL. Hypertrophy of the retinal pigment epithelium associated with Gardner’s syndrome. Am J Ophthalmol. 1980;90(5):661–7.

    CAS  PubMed  Google Scholar 

  35. Gardner EJ, Richards RC. Multiple cutaneous and subcutaneous lesions occurring simultaneously with hereditary polyposis and osteomatosis. Am J Hum Genet. 1953;5(2):139–47.. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1716470/

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Gardner EJ. Follow-up study of a family group exhibiting dominant inheritance for a syndrome including intestinal polyps, osteomas, fibromas and epidermal cysts. Am J Hum Genet. 1962;14:376–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Whitson WE, Orcutt JC, Walkinshaw MD. Orbital osteoma in Gardner’s syndrome. Am J Ophthalmol. 1986;101(2):236–41.

    CAS  PubMed  Google Scholar 

  38. Lewis RA, Crowder WE, Eierman LA, et al. The Gardner syndrome. Significance of ocular features. Ophthalmology. 1984;91(8):916–25.

    CAS  PubMed  Google Scholar 

  39. Gorlin RJ, Goltz RW. Multiple Nevoid basal-cell epithelioma, Jaw Cysts and Bifid Rib. N Engl J Med. 1960;262(18):908–12.

    CAS  PubMed  Google Scholar 

  40. Gorlin RJ. Nevoid basal cell carcinoma (Gorlin) syndrome. Genet Med. 2004;6(6):530–9.

    PubMed  Google Scholar 

  41. Akbari DMDM, Chen H, Guo G, et al. Basal cell nevus syndrome (Gorlin syndrome): genetic insights, diagnostic challenges, and unmet milestones. Pathophysiology. 2017;

    Google Scholar 

  42. Farndon PA, Del Mastro RG, Evans DG, et al. Location of gene for Gorlin syndrome. Lancet. 1992;339(8793):581–2.

    CAS  PubMed  Google Scholar 

  43. Hahn H, Wicking C, Zaphiropoulous PG, et al. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell. 1996;85(6):841–51.

    CAS  PubMed  Google Scholar 

  44. Pan S, Dong Q, Sun L-S, et al. Mechanisms of inactivation of PTCH1 gene in nevoid basal cell carcinoma syndrome: modification of the two-hit hypothesis. Clin Cancer Res. 2010;16(2):442–50.

    CAS  PubMed  Google Scholar 

  45. Reinders MG, van Hout AF, Cosgun B, et al. New mutations and an updated database for the patched-1 ( PTCH1 ) gene. Mol Genet Genomic Med. 2018;6:409.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Fan Z, Li J, Du J, et al. A missense mutation in PTCH2 underlies dominantly inherited NBCCS in a Chinese family. J Med Genet. 2008;45(5):303–8.

    CAS  PubMed  Google Scholar 

  47. Pastorino L, Ghiorzo P, Nasti S, et al. Identification of a SUFU germline mutation in a family with Gorlin syndrome. Am J Med Genet A. 2009;149A(7):1539–43.

    CAS  PubMed  Google Scholar 

  48. Rouhani B, Ramasubramanian A. Pediatric genetic ocular tumors. J Pediatr Genet. 2014;3:259–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Evans DG, Ladusans EJ, Rimmer S, et al. Complications of the naevoid basal cell carcinoma syndrome: results of a population based study. J Med Genet. 1993;30(6):460–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Springate JE. The nevoid basal cell carcinoma syndrome. J Pediatr Surg. 1986;21(10):908–10.

    CAS  PubMed  Google Scholar 

  51. Rahbari H, Mehregan AH. Basal cell epithelioma (carcinoma) in children and teenagers. Cancer. 1982;49(2):350–3.

    CAS  PubMed  Google Scholar 

  52. Solis DC, Kwon GP, Ransohoff KJ, et al. Risk factors for basal cell carcinoma among patients with basal cell nevus syndrome. JAMA Dermatology. 2017;153(2):189.

    Google Scholar 

  53. Shanley S, Ratcliffe J, Hockey A, et al. Nevoid basal cell carcinoma syndrome: review of 118 affected individuals. Am J Med Genet. 1994;50(3):282–90.

    CAS  PubMed  Google Scholar 

  54. Honavar SG, Shields JA, Shields CL, et al.  Basal cell carcinoma of the eyelid associated with Gorlin-Goltz syndrome. Ophthalmology. 2001;108(6):1115–23.

    CAS  PubMed  Google Scholar 

  55. Nerad JA, Whitaker DC. Periocular basal cell carcinoma in adults 35 years of age and younger. Am J Ophthalmol. 1988;106(6):723–9.

    CAS  PubMed  Google Scholar 

  56. Ragge NK, Salt A, Collin JRO, et al. Gorlin syndrome: the PTCH gene links ocular developmental defects and tumour formation. Br J Ophthalmol. 2005;89(8):988–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Sánchez-Vicente JL, Contreras-Díaz M, Rueda T, et al. Combined hamartoma of the retina and retinal pigment epithelium in a patient with Gorlin syndrome: spontaneous partial resolution of traction caused by epiretinal membrane. Case Rep Ophthalmol Med. 2016;2016:1–5.

    Google Scholar 

  58. Black GCM, Mazerolle CJ, Wang Y, et al. Abnormalities of the vitreoretinal interface caused by dysregulated Hedgehog signaling during retinal development. Hum Mol Genet. 2003;12(24):3269–76.

    CAS  PubMed  Google Scholar 

  59. De Craene S, Batteauw A, Van Lint M, et al. Subconjunctival epidermoid cysts in Gorlin-Goltz syndrome. Orbit. 2014;33(4):280–2.

    PubMed  Google Scholar 

  60. Rodrigues AL, Carvalho A, Cabral R, et al. Case Report Multiple nevoid basal cell carcinoma syndrome associated with congenital orbital teratoma, caused by a PTCH1 frameshift mutation. Genet Mol Res. 2014;13(3):5654–63.

    CAS  PubMed  Google Scholar 

  61. Knowlton PB, Mawn LA, Atkinson JB, et al. Strabismus resulting from an anomalous extraocular muscle in Gorlin syndrome. J AAPOS. 2014;18(5):495–8.

    PubMed  Google Scholar 

  62. Farley ND, Sassalos TM, Ober MD. Basal cell nevus syndrome presenting as epiretinal membrane and myelinated nerve fiber layer. Retin Cases Brief Rep. 2017;11:S151–4.

    PubMed  Google Scholar 

  63. Romano M, lacovello D, Cascone NC, et al. Identification of a novel mutation in the PTCH gene in a patient with Gorlin-Goltz syndrome with unusual ocular disorders. Eur J Ophthalmol. 2011;21(4):516–9.

    PubMed  Google Scholar 

  64. Yin VT, Pfeiffer ML, Esmaeli B. Targeted therapy for orbital and periocular basal cell carcinoma and squamous cell carcinoma. Ophthal Plast Reconstr Surg. 2013;29(2):87–92.

    PubMed  Google Scholar 

  65. Chen JJ, Sartori J, Aakalu VK, et al. Review of ocular manifestations of Nevoid basal cell carcinoma syndrome: what an ophthalmologist needs to know. Middle East Afr J Ophthalmol. 2015;22(4):421–7.

    PubMed  PubMed Central  Google Scholar 

  66. Tang JY, Ally MS, Chanana AM, et al. Inhibition of the hedgehog pathway in patients with basal-cell nevus syndrome: final results from the multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016;17(12):1720–31.

    CAS  PubMed  Google Scholar 

  67. Jain S, Song R, Xie J. Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas. Onco Targets Ther. 2017;10:1645–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Bettoli V, Zauli S, Virgili A. Retinoids in the chemoprevention of non-melanoma skin cancers: why, when and how. J Dermatolog Treat. 2013;24(3):235–7.

    CAS  PubMed  Google Scholar 

  69. Figueira JA, Batista FR de S, Rosso K, et al. Delayed diagnosis of Gorlin–Goltz syndrome. J Craniofac Surg. 2018;29:e530.

    PubMed  Google Scholar 

  70. Lloyd KM, Dennis M. Cowden’s disease. A possible new symptom complex with multiple system involvement. Ann Intern Med. 1963;58:136–42.

    PubMed  Google Scholar 

  71. Mester J, Eng C. Cowden syndrome: recognizing and managing a not-so-rare hereditary cancer syndrome. J Surg Oncol. 2015;111(1):125–30.

    PubMed  Google Scholar 

  72. Schrager CA, Schneider D, Gruener AC, et al. Clinical and pathological features of breast disease in Cowden’s syndrome: an underrecognized syndrome with an increased risk of breast cancer. Hum Pathol. 1998;29(1):47–53.

    CAS  PubMed  Google Scholar 

  73. Liaw D, Marsh DJ, Li J, et al. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet. 1997;16(1):64–7.

    CAS  PubMed  Google Scholar 

  74. Pilarski R, Burt R, Kohlman W, et al. Cowden Syndrome and the PTEN Hamartoma tumor syndrome: systematic review and revised diagnostic criteria. J Natl Cancer Inst. 2013;105(21):1607–16.

    CAS  PubMed  Google Scholar 

  75. Pilarski R. Cowden syndrome: a critical review of the clinical literature. J Genet Couns. 2009;18(1):13–27.

    PubMed  Google Scholar 

  76. Zhou X-P, Marsh DJ, Morrison CD, et al. Germline inactivation of PTEN and dysregulation of the phosphoinositol-3-kinase/Akt pathway cause human Lhermitte-Duclos disease in adults. Am J Hum Genet. 2003;73(5):1191–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Weary PE, Gorlin RJ, Gentry WC, et al. Multiple hamartoma syndrome (Cowden’s disease). Arch Dermatol. 1972;106(5):682–90.

    CAS  PubMed  Google Scholar 

  78. Tan M-H, Mester JL, Ngeow J, et al. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res. 2012;18(2):400–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Bardenstein DS, McLean IW, Nerney J, et al. Cowden’s disease. Ophthalmology. 1988;95(8):1038–41.

    CAS  PubMed  Google Scholar 

  80. Al-Zaid T, Ditelberg JS, Prieto VG, et al. Trichilemmomas show loss of PTEN in Cowden syndrome but only rarely in sporadic tumors. J Cutan Pathol. 2012;39(5):493–9.

    PubMed  Google Scholar 

  81. Sbordone S, Savastano A, Savastano MC, et al. Corneal confocal microscopy anomalies associated with Cowden syndrome: a case report. Case Rep Ophthalmol. 2013;4(2):76–80.

    PubMed  PubMed Central  Google Scholar 

  82. Suaiti L, Al-Haseni A, Lee H, et al. Iris mammillations in a pair of twins with Cowden syndrome. JAAD Case Rep. 2016;2(4):323–5.

    PubMed  PubMed Central  Google Scholar 

  83. DeParis SW, Bloomer M, Han Y, et al. Uveal ganglioneuroma due to germline PTEN mutation (Cowden syndrome) presenting as unilateral infantile glaucoma. Ocul Oncol Pathol. 2017;3(2):122–8.

    PubMed  Google Scholar 

  84. Sellitto C, Li L, Gao J, et al. AKT activation promotes PTEN hamartoma tumor syndrome–associated cataract development. J Clin Invest. 2013;123(12):5401–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Gicquel J-J, Vabres P, Bonneau D, et al. Retinal angioma in a patient with Cowden disease. Am J Ophthalmol. 2003;135(3):400–2.

    PubMed  Google Scholar 

  86. Venturini G, Moulin AP, Deprez M, et al. Clinicopathologic and molecular analysis of a choroidal pigmented Schwannoma in the context of a PTEN hamartoma tumor syndrome. Ophthalmology. 2012;119(4):857–64.

    PubMed  Google Scholar 

  87. Mansoor Q, Steel DHW. Proliferative retinopathy in Cowden syndrome. Case Rep. 2012;2012(mar08 1):bcr1120115273.

    Google Scholar 

  88. Gama I, Almeida L. Optic nerve head drusen as a rare manifestation of Cowden syndrome: multimodal imaging. Ophthalmology. 2017;124(8):1164.

    PubMed  Google Scholar 

  89. Brownstein MH, Wolf M, Bikowski JB. Cowden’s disease: a cutaneous marker of breast cancer. Cancer. 1978;41(6):2393–8.

    CAS  PubMed  Google Scholar 

  90. Harach HR, Soubeyran I, Brown A, et al. Thyroid pathologic findings in patients with Cowden disease. Ann Diagn Pathol. 1999;3(6):331–40.

    CAS  PubMed  Google Scholar 

  91. Tan M-H, Mester J, Peterson C, et al. A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands. Am J Hum Genet. 2011;88(1):42–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Gosein MA, Narinesingh D, Nixon CA-AC, et al. Multi-organ benign and malignant tumors: recognizing Cowden syndrome: a case report and review of the literature. BMC Res Notes. 2016;9:388.

    PubMed  PubMed Central  Google Scholar 

  93. Carney JA, Gordon H, Carpenter PC, et al. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore). 1985;64(4):270–83.

    CAS  Google Scholar 

  94. Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab. 2001;86(9):4041–6.

    CAS  PubMed  Google Scholar 

  95. Carney JA. The triad of gastric epithelioid leiomyosarcoma, pulmonary chondroma, and functioning extra-adrenal paraganglioma: a five-year review. Medicine (Baltimore). 1983;62(3):159–69.

    CAS  Google Scholar 

  96. Carney JA, Hruska LS, Beauchamp GD, et al. Dominant inheritance of the complex of myxomas, spotty pigmentation, and endocrine overactivity. Mayo Clin Proc. 1986;61(3):165–72.

    CAS  PubMed  Google Scholar 

  97. Bertherat J, Horvath A, Groussin L, et al. Mutations in regulatory subunit type 1A of cyclic adenosine 5′-monophosphate-dependent protein kinase (PRKAR1A): phenotype analysis in 353 patients and 80 different genotypes. J Clin Endocrinol Metab. 2009;94(6):2085–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Stratakis CA, Kirschner LS, Carney JA, et al. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet. 2000;26(1):89–92.

    PubMed  Google Scholar 

  99. Salpea P, Horvath A, London E, et al. Deletions of the PRKAR1A locus at 17q24.2-q24.3 in Carney complex: genotype-phenotype correlations and implications for genetic testing. J Clin Endocrinol Metab. 2014;99(1):E183–8.

    PubMed  Google Scholar 

  100. Anselmo J, Medeiros S, Carneiro V, et al. A large family with carney complex caused by the S147G PRKAR1A mutation shows a unique spectrum of disease including adrenocortical cancer. J Clin Endocrinol Metab. 2012;97(2):351–9.

    CAS  PubMed  Google Scholar 

  101. Liu Q, Tong D, Liu G, et al. Carney complex with PRKAR1A gene mutation: a case report and literature review. Medicine (Baltimore). 2017;96(50):e8999.

    CAS  Google Scholar 

  102. Cohen C, Turner ML, Stratakis CA. Pigmented lesions of the conjunctiva in Carney’s complex. J Am Acad Dermatol. 2000;42(1 Pt 1):145.

    CAS  PubMed  Google Scholar 

  103. Kennedy RH, Waller RR, Carney JA. Ocular pigmented spots and eyelid myxomas. Am J Ophthalmol. 1987;104(5):533–8.

    CAS  PubMed  Google Scholar 

  104. Horvath A, Stratakis CA. Carney complex and lentiginosis. Pigment Cell Melanoma Res. 2009;22(5):580–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Boikos SA, Stratakis CA. Carney complex: the first 20 years. Curr Opin Oncol. 2007;19(1):24–9.

    CAS  PubMed  Google Scholar 

  106. Carney JA. Psammomatous melanotic schwannoma. A distinctive, heritable tumor with special associations, including cardiac myxoma and the Cushing syndrome. Am J Surg Pathol. 1990;14(3):206–22.

    CAS  PubMed  Google Scholar 

  107. Stratakis CA. Carney complex: a familial lentiginosis predisposing to a variety of tumors. Rev Endocr Metab Disord. 2016;17(3):367–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Carney JA. Carney complex: the complex of myxomas, spotty pigmentation, endocrine overactivity, and schwannomas. Semin Dermatol. 1995;14(2):90–8.

    CAS  PubMed  Google Scholar 

  109. Muir EG, Bell AJ, Barlow KA. Multiple primary carcinomata of the colon, duodenum, and larynx associated with kerato-acanthomata of the face. Br J Surg. 1967;54(3):191–5.

    CAS  PubMed  Google Scholar 

  110. Hampel H, Peltomaki P. Hereditary colorectal cancer: risk assessment and management. Clin Genet. 2000;58(2):89–97.

    CAS  PubMed  Google Scholar 

  111. Cohen PR, Kohn SR, Kurzrock R. Association of sebaceous gland tumors and internal malignancy: the Muir-Torre syndrome. Am J Med. 1991;90(5):606–13.

    CAS  PubMed  Google Scholar 

  112. Ponti G, de Leon MP. Muir-Torre syndrome. Lancet Oncol. 2005;6(12):980–7.

    PubMed  Google Scholar 

  113. Lehrer MD, Lynch H, Glembocki DJ, et al. Glioblastoma multiforme as initial internal malignancy in Muir-Torre syndrome (MTS). JAAD Case Rep. 2015;1(6):381–3.

    PubMed  PubMed Central  Google Scholar 

  114. South CD, Hampel H, Comeras I, et al. The frequency of Muir-Torre syndrome among Lynch syndrome families. J Natl Cancer Inst. 2008;100(4):277–81.

    CAS  PubMed  Google Scholar 

  115. Ponti G, Pellacani G, Seidenari S, et al. Cancer-associated genodermatoses: skin neoplasms as clues to hereditary tumor syndromes. Crit Rev Oncol Hematol. 2013;85(3):239–56.

    PubMed  Google Scholar 

  116. John AM, Schwartz RA. Muir-Torre syndrome (MTS): an update and approach to diagnosis and management. J Am Acad Dermatol. 2016;74(3):558–66.

    PubMed  Google Scholar 

  117. Coldron J, Reid I. Muir-Torre syndrome. J R Coll Surg Edinb. 2001;46(3):178–9.

    CAS  PubMed  Google Scholar 

  118. Tay E, Schofield JB, Rowell NP, et al. Ophthalmic presentation of the Muir Torre syndrome. Ophthalmic Plast Reconstr Surg. 2003;19(5):402–4.

    PubMed  Google Scholar 

  119. Singh AD, Mudhar HS, Bhola R, et al. Sebaceous adenoma of the eyelid in Muir-Torre syndrome. Arch Ophthalmol. 2005;123(4):562.

    PubMed  Google Scholar 

  120. Burgdorf WH, Pitha J, Fahmy A. Muir-Torre syndrome. Histologic spectrum of sebaceous proliferations. Am J Dermatopathol. 1986;8(3):202–8.

    CAS  PubMed  Google Scholar 

  121. Gauthier A-S, Campolmi N, Tumahai P, et al. Sebaceous carcinoma of the eyelid and Muir-Torre syndrome. JAMA Ophthalmol. 2014;132(8):1025.

    PubMed  Google Scholar 

  122. Propeck PA, Warner T, Scanlan KA. Sebaceous carcinoma of the breast in a patient with Muir-Torre syndrome. AJR Am J Roentgenol. 2000;174(2):541–2.

    CAS  PubMed  Google Scholar 

  123. Mencía-Gutiérrez E, Gutiérrez-Díaz E, Santos-Briz A, et al. Sebaceous gland carcinoma of the eyelid and palpebral conjunctiva in a patient with Muir-Torre syndrome. Br J Ophthalmol. 2000;84(11):1325–6.

    PubMed  Google Scholar 

  124. Rustgi AK. Hereditary gastrointestinal polyposis and nonpolyposis syndromes. N Engl J Med. 1994;331(25):1694–702.

    CAS  PubMed  Google Scholar 

  125. Kruse R, Rütten A, Lamberti C, et al. Muir-Torre phenotype has a frequency of DNA mismatch-repair-gene mutations similar to that in hereditary nonpolyposis colorectal cancer families defined by the Amsterdam criteria. Am J Hum Genet. 1998;63(1):63–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Umar A, Risinger JI, Hawk ET, et al. Testing guidelines for hereditary non-polyposis colorectal cancer. Nat Rev Cancer. 2004;4(2):153–8.

    CAS  PubMed  Google Scholar 

  127. Umar A, Boland CR, Terdiman JP, et al. Revised bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96(4):261–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Roberts ME, Riegert-Johnson DL, Thomas BC, et al. A clinical scoring system to identify patients with sebaceous neoplasms at risk for the Muir–Torre variant of Lynch syndrome. Genet Med. 2014;16(9):711–6.

    PubMed  Google Scholar 

  129. Jones B, Oh C, Mangold E, et al. Muir-Torre syndrome: diagnostic and screening guidelines. Australas J Dermatol. 2006;47(4):266–9.

    PubMed  Google Scholar 

  130. Le S, Ansari U, Mumtaz A, et al. Lynch syndrome and Muir-Torre syndrome: an update and review on the genetics, epidemiology, and management of two related disorders. Dermatol Online J. 2017;23(11)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatric Ophthalmology and Strabismus, Center for Genetic Eye Diseases, Cole Eye Institute (i-32), Cleveland Clinic Foundation, Cleveland, OH, USA

    Matteo Scaramuzzi & Elias I. Traboulsi

  2. Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA

    Lucy T. Xu & Arun D. Singh

Authors
  1. Matteo Scaramuzzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lucy T. Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arun D. Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elias I. Traboulsi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elias I. Traboulsi .

Editor information

Editors and Affiliations

  1. Ocular Onocology Service and Ophthalmic Pathology Laboratory, Department of Ophthalmology, Hadassah - Hebrew University Medical Center, Jerusalem, Israel

    Jacob Pe'er

  2. Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA

    Arun D. Singh

  3. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK

    Bertil E. Damato

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Scaramuzzi, M., Xu, L.T., Singh, A.D., Traboulsi, E.I. (2019). Systemic Associations. In: Pe'er, J., Singh, A., Damato, B. (eds) Clinical Ophthalmic Oncology. Springer, Cham. https://doi.org/10.1007/978-3-030-06046-6_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-06046-6_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-06045-9

  • Online ISBN: 978-3-030-06046-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation