Pathology of the Eyelids

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Albert and Jakobiec's Principles and Practice of Ophthalmology
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Abstract

The eyelid is a complex structure, composed of skin, orbicularis muscle, tarsus, and conjunctiva. Bordered by the eyebrow superiorly and cheek inferiorly, the eyelids are split into an upper and lower eyelids. With its numerous appendages and glands, the eyelid protects the eye from the external environment and helps maintain the ocular surface.

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References

  1. Elder DE. Lever’s histopathology of the skin. 11th ed. Philadelphia: Wolters Kluwer; 2014.

    Google Scholar 

  2. Font R. In: Spencer W, editor. Ophthalmic pathology. Philadelphia: WB Saunders; 1996.

    Google Scholar 

  3. Burgeson RE. Type VII collagen, anchoring fibrils, and epidermolysis bullosa. J Invest Dermatol. 1993;101(3):252–5.

    Article  CAS  PubMed  Google Scholar 

  4. Chung HJ, Uitto J. Type VII collagen: the anchoring fibril protein at fault in dystrophic epidermolysis bullosa. Dermatol Clin. 2010;28(1):93–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Jakobiec FA, Qureshi S, Zakka FR, Tu Y, Lee NG. Eyelid eccrine cyst: an exceptional lesion among dominant apocrine cysts. Ophthal Plast Reconstr Surg. 2017;33(5):e128–31.

    Article  PubMed  Google Scholar 

  6. Duncan K, Jeng BH. Medical management of blepharitis. Curr Opin Ophthalmol. 2015;26(4):289–94.

    Article  PubMed  Google Scholar 

  7. Burkat CN, Hossain K, Marcet MM, Silkiss RZ, Baharestani S. Stye [Internet]. EyeWiki; 2019. Available from: https://eyewiki.aao.org/Stye

  8. Steffen C, Markman J. Spontaneous disappearance of molluscum contagiosum. Arch Dermatol. 1980;116:923.

    Article  CAS  PubMed  Google Scholar 

  9. Redfield RR, James WD, Wright DC, Brown C, Salahuddin SZ, Markham PD, et al. Severe molluscum contagiosum infection in a patient with human T cell lymphotrophic (HTLV-III) disease. J Am Acad Dermatol. 1985;13(5):821–4.

    Article  CAS  PubMed  Google Scholar 

  10. Meza-Romero R, Navarrete-Dechent C, Downey C. Molluscum contagiosum: an update and review of new perspectives in etiology, diagnosis, and treatment. Clin Cosmet Investig Dermatol. 2019;12:373–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Leung AKC, Barankin B, Hon KLE. Molluscum contagiosum: an update. Recent Pat Inflamm Allergy Drug Discov [Internet]. 2017 17 [cited 2019 Jul 21];11(1). Available from: http://www.eurekaselect.com/152545/article

  12. Shisler JL. Immune evasion strategies of molluscum contagiosum virus. Adv Virus Res. 2015;92:201–52.

    Article  CAS  PubMed  Google Scholar 

  13. Goette DK. Carcinoma in situ in verruca vulgaris. Int J Dermatol. 1980;19(2):98–101.

    Article  CAS  PubMed  Google Scholar 

  14. Zaesim A, Jackson AC, Lee SW, Price SA. Squamous cell carcinoma arising within verruca vulgaris on the nipple. Case Rep Dermatol Med. 2018;2018:1–4.

    Google Scholar 

  15. Berman A, Winkelmann RK. Involuting common warts. J Am Acad Dermatol. 1980;3(4):356–62.

    Article  CAS  PubMed  Google Scholar 

  16. Eyzaguirre E, Haque AK. Application of immunohistochemistry to infections. Arch Pathol Lab Med. 2008;132(3):424–31.

    Article  PubMed  Google Scholar 

  17. Burkat CN, Vaidya N. Mucormycosis [Internet]. EyeWiki. Available from: https://eyewiki.aao.org/Mucormycosis

  18. Rudramurthy S, Singh M, Parashar A, Chakrabarti A, Zaman K, Kaur H. Cutaneous mucormycosis of scalp and eyelids in a child with type I diabetes mellitus. Indian J Dermatol Venereol Leprol. 2015;81(3):275.

    Article  PubMed  Google Scholar 

  19. Baima B, Sticherling M. Demodicidosis revisited. Acta Derm Venereol. 2002;82(1):3–6.

    Article  CAS  PubMed  Google Scholar 

  20. Karincaoglu Y, Bayram N, Aycan O, Esrefoglu M. The clinical importance of Demodex folliculorum presenting with nonspecific facial signs and symptoms. J Dermatol. 2004;31(8):618–26.

    Article  PubMed  Google Scholar 

  21. Bonnar E, Eustace P, Powell FC. The demodex mite population in rosacea. J Am Acad Dermatol. 1993;28(3):443–8.

    Article  CAS  PubMed  Google Scholar 

  22. Aylesworth R, Vance JC. Demodex folliculorum and Demodex brevis in cutaneous biopsies. J Am Acad Dermatol. 1982;7(5):583–9.

    Article  CAS  PubMed  Google Scholar 

  23. Vollmer RT. Demodex-associated folliculitis. Am J Dermatopathol. 1996;18(6):589–91.

    Article  CAS  PubMed  Google Scholar 

  24. Cheng AMS, Sheha H, Tseng SCG. Recent advances on ocular demodex infestation. Curr Opin Ophthalmol. 2015;26(4):295–300.

    Article  PubMed  Google Scholar 

  25. Straatsma BR. Meibomian gland tumors. Arch Ophthalmol. 1956;56(1):71–93.

    Article  CAS  Google Scholar 

  26. Kaliki S, Ayyar A, Dave TV, Ali MJ, Mishra DK, Naik MN. Sebaceous gland carcinoma of the eyelid: clinicopathological features and outcome in Asian Indians. Eye. 2015;29(7):958–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Flux K. Sebaceous neoplasms. Surg Pathol Clin. 2017;10(2):367–82.

    Article  PubMed  Google Scholar 

  28. 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.

    Article  CAS  PubMed  Google Scholar 

  29. 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.

    Article  PubMed  Google Scholar 

  30. Font RL, Rishi K. Sebaceous gland adenoma of the tarsal conjunctiva in a patient with Muir-Torre syndrome. Ophthalmology. 2003;110(9):1833–6.

    Article  PubMed  Google Scholar 

  31. Mathiak M, Rütten A, Mangold E, Fischer H-P, Ruzicka T, Friedl W, et al. Loss of DNA mismatch repair proteins in skin tumors from patients with Muir-Torre syndrome and MSH2 or MLH1 germline mutations: establishment of immunohistochemical analysis as a screening test. Am J Surg Pathol. 2002;26(3):338–43.

    Article  PubMed  Google Scholar 

  32. Ponti G, Manfredini M, Tomasi A, Pellacani G. Muir-Torre syndrome and founder mismatch repair gene mutations: a long gone historical genetic challenge. Gene. 2016;589(2):127–32.

    Article  CAS  PubMed  Google Scholar 

  33. Shields JA, Demirci H, Marr BP, Eagle RC, Shields CL. Sebaceous carcinoma of the ocular region: a review. Surv Ophthalmol. 2005;50(2):103–22.

    Article  PubMed  Google Scholar 

  34. Milman T, Schear MJ, Eagle RC. Diagnostic utility of adipophilin immunostain in periocular carcinomas. Ophthalmology. 2014;121(4):964–71.

    Article  PubMed  Google Scholar 

  35. Doxanas MT, Green WR. Sebaceous gland carcinoma. Review of 40 cases. Arch Ophthalmol Chic Ill 1960. 1984;102(2):245–9.

    Article  CAS  Google Scholar 

  36. Folberg R, Whitaker DC, Tse DT, Nerad JA. Recurrent and residual sebaceous carcinoma after Mohs’ excision of the primary lesion. Am J Ophthalmol. 1987;103(6):817–23.

    Article  CAS  PubMed  Google Scholar 

  37. Boniuk M, Zimmerman LE. Sebaceous carcinoma of the eyelid, eyebrow, caruncle, and orbit. Trans – Am Acad Ophthalmol Otolaryngol. 1968;72(4):619–42.

    CAS  PubMed  Google Scholar 

  38. Wolfe JT, Yeatts RP, Wick MR, Campbell RJ, Waller RR. Sebaceous carcinoma of the eyelid. Errors in clinical and pathologic diagnosis. Am J Surg Pathol. 1984;8(8):597–606.

    Article  PubMed  Google Scholar 

  39. Lemos LB, Santa Cruz DJ, Baba N. Sebaceous carcinoma of the eyelid following radiation therapy. Am J Surg Pathol. 1978;2(3):305–11.

    Article  CAS  PubMed  Google Scholar 

  40. Kivelä T, Asko-Seljavaara S, Pihkala U, Hovi L, Heikkonen J. Sebaceous carcinoma of the eyelid associated with retinoblastoma. Ophthalmology. 2001;108(6):1124–8.

    Article  PubMed  Google Scholar 

  41. Rao NA, Hidayat AA, McLean IW, Zimmerman LE. Sebaceous carcinomas of the ocular adnexa: a clinicopathologic study of 104 cases, with five-year follow-up data. Hum Pathol. 1982;13(2):113–22.

    Article  CAS  PubMed  Google Scholar 

  42. Hashimoto K, Lever WF. Histogenesis of skin appendage tumors. Arch Dermatol. 1969;100(3):356–69.

    Article  CAS  PubMed  Google Scholar 

  43. Asai Y, Ishii M, Hamada T. Acral syringoma: electron microscopic studies on its origin. Acta Derm Venereol. 1982;62(1):64–8.

    CAS  PubMed  Google Scholar 

  44. Grossniklaus HE, Knight SH. Eccrine acrospiroma (clear cell hidradenoma) of the eyelid. Immunohistochemical and ultrastructural features. Ophthalmology. 1991;98(3):347–52.

    Article  CAS  PubMed  Google Scholar 

  45. Headington JT, Niederhuber JE, Beals TF. Malignant clear cell acrospiroma. Cancer. 1978;41(2):641–7.

    Article  CAS  PubMed  Google Scholar 

  46. Hirsch P, Helwig EB. Chondroid syringoma. Mixed tumor of skin, salivary gland type. Arch Dermatol. 1961;84:835–47.

    Article  CAS  PubMed  Google Scholar 

  47. Headington JT. Mixed tumors of skin: eccrine and apocrine types. Arch Dermatol. 1961;84:989–96.

    Article  CAS  PubMed  Google Scholar 

  48. Grizzard WS, Torezynski E, Edwards WC. Adenocarcinoma of eccrine sweat glands. Arch Ophthalmol Chic Ill 1960. 1976;94(12):2119–23.

    Article  CAS  Google Scholar 

  49. Kramer TR, Grossniklaus HE, McLean IW, Orcutt J, Green WR, Iliff NT, et al. Histiocytoid variant of eccrine sweat gland carcinoma of the eyelid and orbit: report of five cases. Ophthalmology. 2002;109(3):553–9.

    Article  PubMed  Google Scholar 

  50. Jakobiec FA, Austin P, Iwamoto T, Trokel SL, Marquardt MD, Harrison W. Primary infiltrating signet ring carcinoma of the eyelids. Ophthalmology. 1983;90(3):291–9.

    Article  CAS  PubMed  Google Scholar 

  51. Rollins-Raval M, Chivukula M, Tseng GC, Jukic D, Dabbs DJ. An immunohistochemical panel to differentiate metastatic breast carcinoma to skin from primary sweat gland carcinomas with a review of the literature. Arch Pathol Lab Med. 2011;135(8):975–83.

    Article  CAS  PubMed  Google Scholar 

  52. Segal A, Segal N, Gal A, Tumuluri K. Mucinous sweat gland adenocarcinoma of the eyelid – current knowledge of a rare tumor. Orbit. 2010;29(6):334–40.

    Article  PubMed  Google Scholar 

  53. Wright JD, Font RL. Mucinous sweat gland adenocarcinoma of eyelid: a clinicopathologic study of 21 cases with histochemical and electron microscopic observations. Cancer. 1979;44(5):1757–68.

    Article  CAS  PubMed  Google Scholar 

  54. Cohen KL, Peiffer RL, Lipper S. Mucinous sweat gland adenocarcinoma of the eyelid. Am J Ophthalmol. 1981;92(2):183–8.

    Article  CAS  PubMed  Google Scholar 

  55. Holds JB, Haines JH, Mamalis N, Anderson RL, Wolin MJ. Mucinous adenocarcinoma of the orbit arising from a stable, benign-appearing eyelid nodule. Ophthalmic Surg. 1990;21(3):163–6.

    CAS  PubMed  Google Scholar 

  56. Lahav M, Albert DM, Bahr R, Craft J. Eyelid tumors of sweat gland origin. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1981;216(4):301–11.

    Article  CAS  PubMed  Google Scholar 

  57. Netland PA, Townsend DJ, Albert DM, Jakobiec FA. Hidradenoma papilliferum of the upper eyelid arising from the apocrine gland of moll. Ophthalmology. 1990;97(12):1593–8.

    Article  CAS  PubMed  Google Scholar 

  58. Ni C, Wagoner M, Kieval S, Albert DM. Tumours of the Moll’s glands. Br J Ophthalmol. 1984;68(7):502–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Böni R, **n H, Hohl D, Panizzon R, Burg G. Syringocystadenoma papilliferum: a study of potential tumor suppressor genes. Am J Dermatopathol. 2001;23(2):87–9.

    Article  PubMed  Google Scholar 

  60. Menzies S, McKenna D, Hartel P. Periocular cutaneous oncocytoma. Clin Exp Dermatol. 2018;43(1):97–9.

    Article  CAS  PubMed  Google Scholar 

  61. Say EAT, Shields CL, Bianciotto C, Eagle RC, Shields JA. Oncocytic lesions (oncocytoma) of the ocular adnexa: report of 15 cases and review of literature. Ophthal Plast Reconstr Surg. 2012;28(1):14–21.

    Article  PubMed  Google Scholar 

  62. Simpson W, Garner A, Collin JR. Benign hair-follicle derived tumours in the differential diagnosis of basal-cell carcinoma of the eyelids: a clinicopathological comparison. Br J Ophthalmol. 1989;73(5):347–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Bardenstein DS, McLean IW, Nerney J, Boatwright RS. Cowden’s disease. Ophthalmology. 1988;95(8):1038–41.

    Article  CAS  PubMed  Google Scholar 

  64. Yanoff M, Sassani JW. Ocular pathology. 7th ed. London/New York: Saunders/ Elsevier; 2015. 701p.

    Google Scholar 

  65. Jakobiec FA, Zakka FR. A reappraisal of eyelid eccrine and apocrine hidrocystomas: microanatomic and immunohistochemical studies of 40 lesions. Am J Ophthalmol. 2011;151(2):358–374.e2.

    Article  CAS  PubMed  Google Scholar 

  66. Font RL, Stone MS, Schanzer MC, Lewis RA. Apocrine hidrocystomas of the lids, hypodontia, palmar-plantar hyperkeratosis, and onychodystrophy. A new variant of ectodermal dysplasia. Arch Ophthalmol Chic Ill 1960. 1986;104(12):1811–3.

    Article  CAS  Google Scholar 

  67. Kersten RC, Ewing-Chow D, Kulwin DR, Gallon M. Accuracy of clinical diagnosis of cutaneous eyelid lesions. Ophthalmology. 1997;104(3):479–84.

    Article  CAS  PubMed  Google Scholar 

  68. Margo CE. Eyelid tumors: accuracy of clinical diagnosis. Am J Ophthalmol. 1999;128(5):635–6.

    Article  CAS  PubMed  Google Scholar 

  69. Lever WF. Inverted follicular keratosis is an irritated seborrheic keratosis. Am J Dermatopathol. 1983;5(5):474.

    Article  CAS  PubMed  Google Scholar 

  70. Liddell K, White JE, Caldwell IW. Seborrhoeic keratoses and carcinoma of the large bowel: three cases exhibiting the sign of Leser-Trelat. Br J Dermatol. 1975;92(4):449–52.

    Article  CAS  PubMed  Google Scholar 

  71. Wick MR, Patterson JW. Cutaneous paraneoplastic syndromes. Semin Diagn Pathol [Internet]. 2019 Jan [cited 2019 Jul 20]; Available from: https://linkinghub.elsevier.com/retrieve/pii/S0740257019300085

  72. Kincaid MC, Green WR, Hoover RE, Farmer ER. Iododerma of the conjunctiva and skin. Ophthalmology. 1981;88(12):1216–20.

    Article  CAS  PubMed  Google Scholar 

  73. Barr CC, Gamel JW. Blastomycosis of the eyelid. Arch Ophthalmol. 1986;104(1):96–7.

    Article  CAS  PubMed  Google Scholar 

  74. Siegel JA, Korgavkar K, Weinstock MA. Current perspective on actinic keratosis: a review. Br J Dermatol. 2017;177(2):350–8.

    Article  CAS  PubMed  Google Scholar 

  75. Quaedvlieg PJF, Tirsi E, Thissen MRTM, Krekels GA. Actinic keratosis: how to differentiate the good from the bad ones? Eur J Dermatol. 2006;16(4):335–9.

    CAS  PubMed  Google Scholar 

  76. Møller R, Reymann F, Hou-Jensen K. Metastases in dermatological patients with squamous cell carcinoma. Arch Dermatol. 1979;115(6):703–5.

    Article  PubMed  Google Scholar 

  77. Fernandez Figueras MT. From actinic keratosis to squamous cell carcinoma: pathophysiology revisited. J Eur Acad Dermatol Venereol. 2017;31:5–7.

    Article  PubMed  Google Scholar 

  78. Brownstein MH, Rabinowitz AD. The precursors of cutaneous squamous cell carcinoma. Int J Dermatol. 1979;18(1):1–16.

    Article  CAS  PubMed  Google Scholar 

  79. Andersen SL, Nielsen A, Reymann F. Relationship between Bowen disease and internal malignant tumors. Arch Dermatol. 1973;108(3):367–70.

    Article  CAS  PubMed  Google Scholar 

  80. Reymann F, Ravnborg L, Schou G, Engholm G, Osterlind A, Thestrup-Pedersen K. Bowen’s disease and internal malignant diseases. A study of 581 patients. Arch Dermatol. 1988;124(5):677–9.

    Article  CAS  PubMed  Google Scholar 

  81. Chuang TY, Reizner GT. Bowen’s disease and internal malignancy. A matched case-control study. J Am Acad Dermatol. 1988;19(1 Pt 1):47–51.

    Article  CAS  PubMed  Google Scholar 

  82. Martin H, Strong E, Spiro RH. Radiation-induced skin cancer of the head and neck. Cancer. 1970;25(1):61–71.

    Article  CAS  PubMed  Google Scholar 

  83. Hegedus F, Mathew LM, Schwartz RA. Radiation dermatitis: an overview. Int J Dermatol. 2017;56(9):909–14.

    Article  PubMed  Google Scholar 

  84. Gaasterland DE, Rodrigues MM, Moshell AN. Ocular involvement in xeroderma pigmentosum. Ophthalmology. 1982;89(8):980–6.

    Article  CAS  PubMed  Google Scholar 

  85. Cleaver JE, Lam ET, Revet I. Disorders of nucleotide excision repair: the genetic and molecular basis of heterogeneity. Nat Rev Genet. 2009;10(11):756–68.

    Article  CAS  PubMed  Google Scholar 

  86. DiGiovanna JJ, Kraemer KH. Shining a light on xeroderma pigmentosum. J Invest Dermatol. 2012;132(3 Pt 2):785–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Brooks BP, Thompson AH, Bishop RJ, Clayton JA, Chan C-C, Tsilou ET, et al. Ocular manifestations of xeroderma pigmentosum: long-term follow-up highlights the role of DNA repair in protection from sun damage. Ophthalmology. 2013;120(7):1324–36.

    Article  PubMed  Google Scholar 

  88. Loeffler M, Hornblass A. Characteristics and behavior of eyelid carcinoma (basal cell, squamous cell sebaceous gland, and malignant melanoma). Ophthalmic Surg. 1990;21(7):513–8.

    CAS  PubMed  Google Scholar 

  89. Wu A, Sun MT, Huilgol SC, Madge S, Selva D. Histological subtypes of periocular basal cell carcinoma: periocular basal cell carcinoma subtypes. Clin Exp Ophthalmol. 2014;42(7):603–7.

    Article  PubMed  Google Scholar 

  90. Pellegrini C, Maturo M, Di Nardo L, Ciciarelli V, Gutiérrez García-Rodrigo C, Fargnoli M. Understanding the molecular genetics of basal cell carcinoma. Int J Mol Sci. 2017;18(11):2485.

    Article  PubMed Central  CAS  Google Scholar 

  91. Gailani MR, Ståhle-Bäckdahl M, Leffell DJ, Glynn M, Zaphiropoulos PG, Pressman C, et al. The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat Genet. 1996;14(1):78–81.

    Article  CAS  PubMed  Google Scholar 

  92. **e J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C, et al. Activating smoothened mutations in sporadic basal-cell carcinoma. Nature. 1998;391(6662):90–2.

    Article  CAS  PubMed  Google Scholar 

  93. Epstein EH. Basal cell carcinomas: attack of the hedgehog. Nat Rev Cancer. 2008;8(10):743–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Jayaraman SS, Rayhan DJ, Hazany S, Kolodney MS. Mutational landscape of basal cell carcinomas by whole-exome sequencing. J Invest Dermatol. 2014;134(1):213–20.

    Article  CAS  PubMed  Google Scholar 

  95. Borel DM. Cutaneous basosquamous carcinoma. Review of the literature and report of 35 cases. Arch Pathol. 1973;95(5):293–7.

    CAS  PubMed  Google Scholar 

  96. Puig S, Berrocal A. Management of high-risk and advanced basal cell carcinoma. Clin Transl Oncol. 2015;17(7):497–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Doxanas MT, Green WR, Iliff CE. Factors in the successful surgical management of basal cell carcinoma of the eyelids. Am J Ophthalmol. 1981;91(6):726–36.

    Article  CAS  PubMed  Google Scholar 

  98. Basset-Seguin N, Sharpe HJ, de Sauvage FJ. Efficacy of hedgehog pathway inhibitors in basal cell carcinoma. Mol Cancer Ther. 2015;14(3):633–41.

    Article  CAS  PubMed  Google Scholar 

  99. Pe’er J. Pathology of eyelid tumors. Indian J Ophthalmol. 2016;64(3):177.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Damasceno JC, Isenberg J, Lopes LR, Hime B, Fernandes BF, Lowen M, et al. Largest case series of Latin American eyelid tumors over 13-Years from a single center in Sao Paulo, Brazil. Arq Bras Oftalmol [Internet]. 2018 [cited 2019 Jul 20];81(1). Available from: http://www.gnresearch.org/doi/10.5935/0004-2749.20180004

  101. Behshad R, Garcia-Zuazaga J, Bordeaux JS. Systemic treatment of locally advanced nonmetastatic cutaneous squamous cell carcinoma: a review of the literature. Br J Dermatol. 2011;165(6):1169–77.

    Article  CAS  PubMed  Google Scholar 

  102. Choi FD, Kraus CN, Elsensohn AN, Carley SK, Lehmer LM, Nguyen RT, et al. PD-1 and PD-L1 inhibitors in the treatment of non-melanoma skin cancer: a systematic review. J Am Acad Dermatol [Internet]. 2019 Jun [cited 2019 Jul 20]; Available from: https://linkinghub.elsevier.com/retrieve/pii/S0190962219308813

  103. Kwiek B, Schwartz RA. Keratoacanthoma (KA): an update and review. J Am Acad Dermatol. 2016;74(6):1220–33.

    Article  PubMed  Google Scholar 

  104. Takai T. Advances in histopathological diagnosis of keratoacanthoma. J Dermatol. 2017;44(3):304–14.

    Article  PubMed  Google Scholar 

  105. Misago N, Takai T, Toda S, Narisawa Y. The histopathologic changes in keratoacanthoma depend on its stage. J Cutan Pathol. 2014;41(7):617–9.

    Article  PubMed  Google Scholar 

  106. Urmacher C. Histology of normal skin. Am J Surg Pathol. 1990;14(7):671–86.

    Article  CAS  PubMed  Google Scholar 

  107. Gottlieb B, Brown AL, Winkelmann RK. Fine structure of the nevus cell. Arch Dermatol. 1965;92(1):81–7.

    Article  CAS  PubMed  Google Scholar 

  108. DeLellis RA, Dayal Y. The role of immunohistochemistry in the diagnosis of poorly differentiated malignant neoplasms. Semin Oncol. 1987;14(2):173–92.

    CAS  PubMed  Google Scholar 

  109. Sheffield MV, Yee H, Dorvault CC, Weilbaecher KN, Eltoum IA, Siegal GP, et al. Comparison of five antibodies as markers in the diagnosis of melanoma in cytologic preparations. Am J Clin Pathol. 2002;118(6):930–6.

    Article  PubMed  Google Scholar 

  110. Busam KJ, Chen YT, Old LJ, Stockert E, Iversen K, Coplan KA, et al. Expression of melan-A (MART1) in benign melanocytic nevi and primary cutaneous malignant melanoma. Am J Surg Pathol. 1998;22(8):976–82.

    Article  CAS  PubMed  Google Scholar 

  111. Argenyi ZB, Cain C, Bromley C, Nguyen AV, Abraham AA, Kerschmann R, et al. S-100 protein-negative malignant melanoma: fact or fiction? A light-microscopic and immunohistochemical study. Am J Dermatopathol. 1994;16(3):233–40.

    Article  CAS  PubMed  Google Scholar 

  112. Mohamed A, Gonzalez RS, Lawson D, Wang J, Cohen C. SOX10 expression in malignant melanoma, carcinoma, and normal tissues. Appl Immunohistochem Mol Morphol. 2013;21(6):506–10.

    Article  CAS  PubMed  Google Scholar 

  113. Vollmer RT. Use of Bayes rule and MIB-1 proliferation index to discriminate Spitz nevus from malignant melanoma. Am J Clin Pathol. 2004;122(4):499–505.

    Article  PubMed  Google Scholar 

  114. McNeal AS, Liu K, Nakhate V, Natale CA, Duperret EK, Capell BC, et al. CDKN2B loss promotes progression from benign melanocytic nevus to melanoma. Cancer Discov. 2015;5(10):1072–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Taylor LA, O’Day C, Dentchev T, Hood K, Chu EY, Ridky TW, et al. p15 expression differentiates nevus from melanoma. Am J Pathol. 2016;186(12):3094–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Ma SA, O’Day CP, Dentchev T, Takeshita J, Ridky TW, Seykora JT, et al. Expression of p15 in a spectrum of spitzoid melanocytic neoplasms. J Cutan Pathol. 2019;46(5):310–6.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Breathnach AS. Melanocyte distribution in forearm epidermis of freckled human subjects. J Invest Dermatol. 1957;29(4):253–61.

    Article  CAS  PubMed  Google Scholar 

  118. Bastiaens M, ter Huurne J, Gruis N, Bergman W, Westendorp R, Vermeer BJ, et al. The melanocortin-1-receptor gene is the major freckle gene. Hum Mol Genet. 2001;10(16):1701–8.

    Article  CAS  PubMed  Google Scholar 

  119. Ackerman AB. Histologic diagnosis of inflammatory skin diseases: a method by pattern analysis. Philadelphia: Lea & Febiger; 1978. 863p.

    Google Scholar 

  120. Murphy GF. Dermatopathology: a practical guide to common disorders. Philadelphia: W.B Saunders; 1995. 505p.

    Google Scholar 

  121. Ortonne J-P, Bissett DL. Latest insights into skin hyperpigmentation. J Investig Dermatol Symp Proc. 2008;13(1):10–4.

    Article  PubMed  Google Scholar 

  122. Rhodes AR, Silverman RA, Harrist TJ, Melski JW. A histologic comparison of congenital and acquired nevomelanocytic nevi. Arch Dermatol. 1985;121(10):1266–73.

    Article  CAS  PubMed  Google Scholar 

  123. Bauer J, Curtin JA, Pinkel D, Bastian BC. Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations. J Invest Dermatol. 2007;127(1):179–82.

    Article  CAS  PubMed  Google Scholar 

  124. Walsh N, Crotty K, Palmer A, McCarthy S. Spitz nevus versus spitzoid malignant melanoma: an evaluation of the current distinguishing histopathologic criteria. Hum Pathol. 1998;29(10):1105–12.

    Article  CAS  PubMed  Google Scholar 

  125. Cesinaro AM, Schirosi L, Bettelli S, Migaldi M, Maiorana A. Alterations of 9p21 analysed by FISH and MLPA distinguish atypical spitzoid melanocytic tumours from conventional Spitz’s nevi but do not predict their biological behaviour. Histopathology. 2010;57(4):515–27.

    Article  PubMed  Google Scholar 

  126. Dorsey CS, Montgomery H. Blue nevus and its distinction from Mongolian spot and the nevus of Ota. J Invest Dermatol. 1954;22(3):225–36.

    Article  CAS  PubMed  Google Scholar 

  127. Goldenhersh MA, Savin RC, Barnhill RL, Stenn KS. Malignant blue nevus. Case report and literature review. J Am Acad Dermatol. 1988;19(4):712–22.

    Article  CAS  PubMed  Google Scholar 

  128. Kopf AW, Weidman AI. Nevus of ota. Arch Dermatol. 1962;85:195–208.

    Article  CAS  PubMed  Google Scholar 

  129. Hidano A, Kajima H, Ikeda S, Mizutani H, Miyasato H, Niimura M. Natural history of nevus of Ota. Arch Dermatol. 1967;95(2):187–95.

    Article  CAS  PubMed  Google Scholar 

  130. Toivonen P, Kivelä T. Unusual tumors involving the head and neck region: case 2. Malignant uveal melanoma in ocular melanocytosis. J Clin Oncol. 2001;19(21):4174–7.

    Article  CAS  PubMed  Google Scholar 

  131. Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O’Brien JM, et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2009;457(7229):599–602.

    Article  PubMed  CAS  Google Scholar 

  132. Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore). 1985;64(4):270–83.

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Kirschner LS, Carney JA, Pack SD, Taymans SE, Giatzakis C, Cho YS, 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.

    Article  CAS  PubMed  Google Scholar 

  135. Conley J, Lattes R, Orr W. Desmoplastic malignant melanoma (a rare variant of spindle cell melanoma). Cancer. 1971;28(4):914–36.

    Article  CAS  PubMed  Google Scholar 

  136. Reed RJ, Leonard DD. Neurotropic melanoma. A variant of desmoplastic melanoma. Am J Surg Pathol. 1979;3(4):301–11.

    Article  CAS  PubMed  Google Scholar 

  137. Gibson LE, Goellner JR. Amelanotic melanoma: cases studied by Fontana stain, S-100 immunostain, and ultrastructural examination. Mayo Clin Proc. 1988;63(8):777–82.

    Article  CAS  PubMed  Google Scholar 

  138. Muhlbauer JE, Margolis RJ, Mihm MC, Reed RJ. Minimal deviation melanoma: a histologic variant of cutaneous malignant melanoma in its vertical growth phase. J Invest Dermatol. 1983;80(1 Suppl):63s–5s.

    Article  CAS  PubMed  Google Scholar 

  139. Niven J, Lubin J. Pedunculated malignant melanoma. Arch Dermatol. 1975;111(6):755–6.

    Article  CAS  PubMed  Google Scholar 

  140. Gardner WA, Vazquez MD. Balloon cell melanoma. Arch Pathol. 1970;89(5):470–2.

    PubMed  Google Scholar 

  141. Candido S, Rapisarda V, Marconi A, Malaponte G, Bevelacqua V, Gangemi P, et al. Analysis of the B-RafV600E mutation in cutaneous melanoma patients with occupational sun exposure. Oncol Rep. 2014;31(3):1079–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353(20):2135–47.

    Article  CAS  PubMed  Google Scholar 

  143. Leonardi G, Falzone L, Salemi R, Zanghì A, Spandidos D, Mccubrey J, et al. Cutaneous melanoma: from pathogenesis to therapy (Review). Int J Oncol [Internet]. 2018 Feb 27 [cited 2019 Jul 20]; Available from: http://www.spandidos-publications.com/10.3892/ijo.2018.4287

  144. McGovern VJ, Mihm MC, Bailly C, Booth JC, Clark WH, Cochran AJ, et al. The classification of malignant melanoma and its histologic reporting. Cancer. 1973;32(6):1446–57.

    Article  CAS  PubMed  Google Scholar 

  145. Clark WH, Mihm MC. Lentigo maligna and lentigo-maligna melanoma. Am J Pathol. 1969;55(1):39–67.

    PubMed  PubMed Central  Google Scholar 

  146. Mancera N, Smalley KSM, Margo CE. Melanoma of the eyelid and periocular skin: histopathologic classification and molecular pathology. Surv Ophthalmol. 2019;64(3):272–88.

    Article  PubMed  Google Scholar 

  147. Pollack LA, Li J, Berkowitz Z, Weir HK, Wu X-C, Ajani UA, et al. Melanoma survival in the United States, 1992 to 2005. J Am Acad Dermatol. 2011;65(5 Suppl 1):S78–86.

    PubMed  PubMed Central  Google Scholar 

  148. Clark WH, Elder DE, Guerry D, Braitman LE, Trock BJ, Schultz D, et al. Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst. 1989;81(24):1893–904.

    Article  PubMed  Google Scholar 

  149. Lang J, MacKie RM. Prevalence of exon 15 BRAF mutations in primary melanoma of the superficial spreading, nodular, acral, and lentigo maligna subtypes. J Invest Dermatol. 2005;125(3):575–9.

    Article  CAS  PubMed  Google Scholar 

  150. Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg. 1970;172(5):902–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Gershenwald JE, Scolyer RA. Melanoma staging: American Joint Committee on Cancer (AJCC) 8th edition and beyond. Ann Surg Oncol. 2018;25(8):2105–10.

    Article  PubMed  Google Scholar 

  152. Keung EZ, Gershenwald JE. The eighth edition American Joint Committee on Cancer (AJCC) melanoma staging system: implications for melanoma treatment and care. Expert Rev Anticancer Ther. 2018;18(8):775–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Amin MB, American Joint Committee on Cancer, American Cancer Society, editors. AJCC cancer staging manual. Eight edition / editor-in-chief, Mahul B. Amin, MD, FCAP; editors, Stephen B. Edge, MD, FACS [and 16 others] ; Donna M. Gress, RHIT, CTR-Technical editor; Laura R. Meyer, CAPM-Managing editor. Chicago: American Joint Committee on Cancer, Springer; 2017. 1024p.

    Google Scholar 

  154. Rigel DS, Russak J, Friedman R. The evolution of melanoma diagnosis: 25 years beyond the ABCDs. CA Cancer J Clin. 2010;60(5):301–16.

    Article  PubMed  Google Scholar 

  155. Kelly JW, Chamberlain AJ, Staples MP, McAvoy B. Nodular melanoma. No longer as simple as ABC. Aust Fam Physician. 2003;32(9):706–9.

    PubMed  Google Scholar 

  156. Fu Q, Chen N, Ge C, Li R, Li Z, Zeng B, et al. Prognostic value of tumor-infiltrating lymphocytes in melanoma: a systematic review and meta-analysis. OncoImmunology. 2019;8(7):1593806.

    Article  PubMed  PubMed Central  Google Scholar 

  157. Khair DO, Bax HJ, Mele S, Crescioli S, Pellizzari G, Khiabany A, et al. Combining immune checkpoint inhibitors: established and emerging targets and strategies to improve outcomes in melanoma. Front Immunol [Internet]. 2019 Mar 19 [cited 2019 Jul 23];10. Available from: https://www.frontiersin.org/article/10.3389/fimmu.2019.00453/full

  158. van Vugt LJ, van der Vleuten CJM, Flucke U, Blokx WAM. The utility of GLUT1 as a diagnostic marker in cutaneous vascular anomalies: a review of literature and recommendations for daily practice. Pathol – Res Pract. 2017;213(6):591–7.

    Article  PubMed  CAS  Google Scholar 

  159. Ferry AP. Pyogenic granulomas of the eye and ocular adnexa: a study of 100 cases. Trans Am Ophthalmol Soc. 1989;87:327–43; discussion 343–347.

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Jakobiec FA, Zakka FR, Yoon MK. Complex orbital angiomyoma with features of a lymphangiohemangioma. Ophthal Plast Reconstr Surg. 2013;29(2):e61–5.

    Article  PubMed  Google Scholar 

  161. Curragh DS, Chang S, Selva D. Kaposi sarcoma of the upper eyelid: a rare occurrence. Clin Exp Ophthalmol. 2018;46(9):1097–8.

    Article  PubMed  Google Scholar 

  162. Serraino D, Angeletti C, Carrieri MP, Longo B, Piche M, Piselli P, et al. Kaposi’s sarcoma in transplant and HIV-infected patients: an epidemiologic study in Italy and France. Transplantation. 2005;80(12):1699–704.

    Article  PubMed  Google Scholar 

  163. Beral V, Peterman TA, Berkelman RL, Jaffe HW. Kaposi’s sarcoma among persons with AIDS: a sexually transmitted infection? Lancet. 1990;335(8682):123–8.

    Article  CAS  PubMed  Google Scholar 

  164. Safai B, Johnson KG, Myskowski PL, Koziner B, Yang SY, Cunningham-Rundles S, et al. The natural history of Kaposi’s sarcoma in the acquired immunodeficiency syndrome. Ann Intern Med. 1985;103(5):744–50.

    Article  CAS  PubMed  Google Scholar 

  165. Hoover DR, Black C, Jacobson LP, Martinez-Maza O, Seminara D, Saah A, et al. Epidemiologic analysis of Kaposi’s sarcoma as an early and later AIDS outcome in homosexual men. Am J Epidemiol. 1993;138(4):266–78.

    Article  CAS  PubMed  Google Scholar 

  166. Yarchoan R, Uldrick TS. HIV-associated cancers and related diseases. In: Longo DL, editor. N Engl J Med. 2018;378(11):1029–41.

    Google Scholar 

  167. Shuler JD, Holland GN, Miles SA, Miller BJ, Grossman I. Kaposi sarcoma of the conjunctiva and eyelids associated with the acquired immunodeficiency syndrome. Arch Ophthalmol Chic Ill 1960. 1989;107(6):858–62.

    Article  CAS  Google Scholar 

  168. Baykal C, Polat Ekinci A, Yazganoglu KD, Buyukbabani N. The clinical spectrum of xanthomatous lesions of the eyelids. Int J Dermatol. 2017;56(10):981–92.

    Article  PubMed  Google Scholar 

  169. Alper MG, Zimmerman LE, Piana FG. Orbital manifestations of Erdheim-Chester disease. Trans Am Ophthalmol Soc. 1983;81:64–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  170. Valdez MA, Isamah N, Northway RM. Dermatologic manifestations of systemic diseases. Prim Care. 2015;42(4):607–30.

    Article  PubMed  Google Scholar 

  171. Callen JP. Chronic cutaneous lupus erythematosus. Clinical, laboratory, therapeutic, and prognostic examination of 62 patients. Arch Dermatol. 1982;118(6):412–6.

    Article  CAS  PubMed  Google Scholar 

  172. Kearns W, Wood W, Marchese A. Chronic cutaneous lupus involving the eye lid. Ann Ophthalmol. 1982;14(11):1009–10.

    CAS  PubMed  Google Scholar 

  173. Silpa-archa S, Lee JJ, Foster CS. Ocular manifestations in systemic lupus erythematosus. Br J Ophthalmol. 2016;100(1):135–41.

    Article  PubMed  Google Scholar 

  174. DeWane ME, Waldman R, Lu J. Dermatomyositis part I: clinical features and pathogenesis. J Am Acad Dermatol [Internet]. 2019 Jul [cited 2019 Jul 19]; Available from: https://linkinghub.elsevier.com/retrieve/pii/S0190962219323096

  175. Santoro FA, Huang J. Ocular involvement in cutaneous connective tissue disease. Clin Dermatol. 2016;34(2):138–45.

    Article  PubMed  Google Scholar 

  176. El-Baba F, Frangieh GT, Iliff WJ, Hood AB, Green WR. Morphea of the eyelids. Ophthalmology. 1982;89(11):1285–8.

    Article  CAS  PubMed  Google Scholar 

  177. Breathnach SM. Amyloid and amyloidosis. J Am Acad Dermatol. 1988;18(1 Pt 1):1–16.

    Article  CAS  PubMed  Google Scholar 

  178. Stack RR, Vote BJT, Evans JL, Elder MJ. Bilateral ptosis caused by localized superficial eyelid amyloidosis. Ophthal Plast Reconstr Surg. 2003;19(3):239–40.

    Article  PubMed  Google Scholar 

  179. Pelton RW, Desmond BP, Mamalis N, Pratt DV, Patel BC, Anderson RL. Nodular cutaneous amyloid tumors of the eyelids in the absence of systemic amyloidosis. Ophthalmic Surg Lasers. 2001;32(5):422–4.

    Article  CAS  PubMed  Google Scholar 

  180. Howie AJ, Brewer DB, Howell D, Jones AP. Physical basis of colors seen in Congo red-stained amyloid in polarized light. Lab Investig. 2008;88(3):232–42.

    Article  CAS  PubMed  Google Scholar 

  181. Chan I, Liu L, Hamada T, Sethuraman G, McGrath JA. The molecular basis of lipoid proteinosis: mutations in extracellular matrix protein 1. Exp Dermatol. 2007;16(11):881–90.

    Article  CAS  PubMed  Google Scholar 

  182. Hamada T. Lipoid proteinosis. Clin Exp Dermatol. 2002;27(8):624–9.

    Article  CAS  PubMed  Google Scholar 

  183. Uchida T, Hayashi H, Inaoki M, Miyamoto T, Fujimoto W. A failure of mucocutaneous lymphangiogenesis may underlie the clinical features of lipoid proteinosis. Br J Dermatol. 2007;156(1):152–7.

    Article  CAS  PubMed  Google Scholar 

  184. Jensen AD, Khodadoust AA, Emery JM. Lipoid proteinosis. Report of a case with electron microscopic findings. Arch Ophthalmol Chic Ill 1960. 1972;88(3):273–7.

    Article  CAS  Google Scholar 

  185. Davies G, Dymock I, Harry J, Williams R. Deposition of melanin and iron in ocular structures in haemochromatosis. Br J Ophthalmol. 1972;56(4):338–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Buckley WR. Localized argyria. Arch Dermatol. 1963;88:531–9.

    Article  CAS  PubMed  Google Scholar 

  187. Wolkow N, Li Y, Maminishkis A, Song Y, Alekseev O, Iacovelli J, et al. Iron upregulates melanogenesis in cultured retinal pigment epithelial cells. Exp Eye Res. 2014;128:92–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Wolf R, Orion E, Tüzün Y. Periorbital (eyelid) dermatides. Clin Dermatol. 2014;32(1):131–40.

    Article  PubMed  Google Scholar 

  189. Zaba LC, Krueger JG, Lowes MA. Resident and “inflammatory” dendritic cells in human skin. J Invest Dermatol. 2009;129(2):302–8.

    Article  CAS  PubMed  Google Scholar 

  190. Haniffa M, Gunawan M, Jardine L. Human skin dendritic cells in health and disease. J Dermatol Sci. 2015;77(2):85–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Lee, V., Seykora, J.T. (2022). Pathology of the Eyelids. In: Albert, D.M., Miller, J.W., Azar, D.T., Young, L.H. (eds) Albert and Jakobiec's Principles and Practice of Ophthalmology. Springer, Cham. https://doi.org/10.1007/978-3-030-42634-7_127

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