Selective Pathology of Intraocular Tumors

  • Patricia Chévez-BarriosEmail author
  • Linda Alejandra Cernichiaro Espinosa


Retinoblastoma represents the most common intraocular malignant tumor in children and worldwide is the most common intraocular malignancy. Uveal melanomas are the most common malignant intraocular tumors in adults. This review chapter includes key clinical features and important histopathologic findings for diagnosis and prognosis of both entities.


Intraocular tumor Retinoblastoma Malignant tumor Uveal melanomas 


  1. 1.
    Nork TM, Schwartz TL, Doshi HM, Millecchia LL. Retinoblastoma. Cell of origin. Arch Ophthalmol. 1995;113:791–802.CrossRefGoogle Scholar
  2. 2.
    Albert DM. Wardrop Lecture, 1974. James Wardrop: a brief review of his life and contributions. Trans Ophthalmol Soc UK. 1974;94:892–908.PubMedGoogle Scholar
  3. 3.
    Albert DM. Historic review of retinoblastoma. Ophthalmology. 1987;94:654–62.CrossRefGoogle Scholar
  4. 4.
    Gallie BL, Phillips RA, Ellsworth RM, et al. Significance of retinoma and phthisis bulbi for retinoblastoma. Ophthalmology. 1982;89:1393–9.CrossRefGoogle Scholar
  5. 5.
    McLean IW. Retinoblastoma, retinocytomas, and pseudoretinoblastomas. In: Spencer WH, editor. Ophthalmic pathology. An atlas and textbook. Philadelphia: American Academy of Ophthalmology/WB Saunders Company; 1990. p. 1332–438.Google Scholar
  6. 6.
    Zhang J, Schweers B, Dyer MA. The first knockout mouse model of retinoblastoma. Cell Cycle. 2004;3(7):952–9.CrossRefGoogle Scholar
  7. 7.
    Squire J, Gallie BL, Phillips RA. A detailed analysis of chromosomal changes in heritable and non- heritable retinoblastoma. Hum Genet. 1985;70:291–301.CrossRefGoogle Scholar
  8. 8.
    Classon M, Harlow E. The retinoblastoma tumor suppressor in development and cancer. Nat Rev Cancer. 2002;2:910–7.CrossRefGoogle Scholar
  9. 9.
    Skalet AH, Gombos DS, Gallie BL, Kim JW, Shields CL, Marr BP, Plon SE, Chevez-Barrios P. Screening children at risk for retinoblastoma: consensus report from the American Association of Ophthalmic Oncologists and Pathologists. Ophthalmology. 2018;125(3):453–8.CrossRefGoogle Scholar
  10. 10.
    Sastre X, Chantada GL, Doz F, Wilson MW, de Davila MT, Rodríguez-Galindo C, Chintagumpala M, Chévez-Barrios P, International Retinoblastoma Staging Working Group. Proceedings of the consensus meetings from the International Retinoblastoma Staging Working Group on the pathology guidelines for the examination of enucleated eyes and evaluation of prognostic risk factors in retinoblastoma. Arch Pathol Lab Med. 2009;133(8):1199–202. Scholar
  11. 11.
    Hurwitz RL, Chévez-Barrios P, Chintagumpala M, Shields C, Shields J. Retinoblastoma. In: Pizzo PA, Poplack D, editors. Principles and practice of pediatric oncology. 6th ed. Philadelphia: Lippincott-Raven; 2002. p. 825–46.Google Scholar
  12. 12.
    Wong FL, Boice JD Jr, Abramson DH, et al. Cancer incidence after retinoblastoma: radiation dose and sarcoma risk. JAMA. 1997;278:1262–7.CrossRefGoogle Scholar
  13. 13.
    Chantada GL, Doz F, Orjuela M, Qaddoumi I, Sitorus RS, Kepak T, Furmanchuk A, Castellanos M, Sharma T, Chevez-Barrios P, Rodriguez-Galindo C, International Retinoblastoma Staging Working Group. World disparities in risk definition and management of retinoblastoma: a report from the International Retinoblastoma Staging Working Group. Pediatr Blood Cancer. 2008;50(3):692–4.CrossRefGoogle Scholar
  14. 14.
    Ghisoli ML, Zage PE, Herzog C, Chevez-Barrios P, Chintagumpala M, Hurwitz RL, Gombos DS. Multidisciplinary management of retinoblastoma: diagnosis, treatment, and future direction. Ophthalmic Oncol. 2011:179.Google Scholar
  15. 15.
    Chintagumpala M, Chevez-Barrios P, Paysse EA, Plon SE, Hurwitz R. Retinoblastoma: review of current management. Oncologist. 2007 Oct;12(10):1237–46.CrossRefGoogle Scholar
  16. 16.
    Gombos DS, Chevez-Barrios AP. Current treatment and management of retinoblastoma. Curr Oncol Rep. 2007 Nov;9(6):453–8.CrossRefGoogle Scholar
  17. 17.
    Chévez-Barrios P, Eagle R, Marback E. Histopathologic features and prognostic factors. Clin Ophthalmic Oncol Retinoblastoma [serial online]. 2015:167.Google Scholar
  18. 18.
    Chévez-Barrios P, Eagle RC, Marbach. Histological features and risks for metastatic spread of retinoblastoma. In: Singh AD, Damato B, Pe’er J, Murphree AL, Perry JD, editors. Clinical Ocular Oncology. 1st ed. London: Elsevier/Saunders; 2007. Section 6–77.Google Scholar
  19. 19.
    Chong EM, Coffee RE, Chintagumpala M, Hurwitz RL, Hurwitz MY, Chévez-Barrios P. Extensively necrotic retinoblastoma is associated with high-risk prognostic factors. Arch Pathol Lab Med. 2006 Nov;130(11):1669–72.PubMedGoogle Scholar
  20. 20.
    Shields CL, Shields JA, Baez K, et al. Optic nerve invasion of retinoblastoma: metastatic potential and clinical risk factors. Cancer. 1994;73:692–8.CrossRefGoogle Scholar
  21. 21.
    Magramm I, Abramson DH, Ellsworth RM. Optic nerve involvement in retinoblastoma. Ophthalmology. 1989;96:217–22.CrossRefGoogle Scholar
  22. 22.
    Chantada GL, de Davila MT, Fandino A, et al. Retinoblastoma with low risk for extraocular relapse. Ophthalmic Genet. 1999;20:133–40.CrossRefGoogle Scholar
  23. 23.
    Retinoblastoma. In: Amin MB, Edge S, Greene F, Byrd DR. Brookland RK, Washingont ML. Gershenwald JE, Compton CC, Hess KR, Sullivan DC, Jessup JM, Brierley JD, Gaspar LE, Schilsky RL, Balch CM, Winchester DP, Asare EA, Madera M, Gress DM, Meyer LR, editors. AJCC Cancer Staging Manual. 8th ed. New York: Springer; 2017. Chapter 68. p. 819–831.Google Scholar
  24. 24.
    Amram AL, Rico G, Kim JW, Chintagumpala M, Herzog CE, Gombos DS, Chévez-Barrios P. Vitreous seeds in retinoblastoma. Clinicopathologic classification and correlation. Ophthalmology. 2017;124:1540–7.CrossRefGoogle Scholar
  25. 25.
    Singh AD, Topham A. Incidence of uveal melanoma in the United States: 1973–1997. Ophthalmology. 2003;11(5):956–61.CrossRefGoogle Scholar
  26. 26.
    Singh AD, Bergman L, Seregard S. Uveal melanoma: epidemiologic aspects. Ophthalmol Clin N Am. 2005;18(1):75–84.CrossRefGoogle Scholar
  27. 27.
    Kujala E, Damato B, Coupland SE, Desjardins L, Bechrakis NE, Grange JD, Kivelä T. Staging of ciliary body and choroidal melanomas based on anatomic extent. J Clin Oncol. 2013;31(22):2825–31.CrossRefGoogle Scholar
  28. 28.
    Haugh AM, Njauw CN, Bubley JA, Verzì AE, Zhang B, Kudalkar E, VandenBoom T, Walton K, Swick BL, Kumar R, Rana HQ, Cochrane S, McCormick SR, Shea CR, Tsao H, Gerami P. Genotypic and phenotypic features of BAP1 cancer syndrome: a report of 8 new families and review of cases in the literature. JAMA Dermatol. 2017;153(10):609–18.CrossRefGoogle Scholar
  29. 29.
    Kaliki S, Shields CL, Shields JA. Uveal melanoma: estimating prognosis. Indian J Ophthalmol. 2015;63(2):93–102.CrossRefGoogle Scholar
  30. 30.
    McLean IW, Foster WD, Zimmerman LE, Gamel JW. Modifications of Callender’s classification of uveal melanoma at the Armed Forces Institute of Pathology. Am J Ophthalmol. 1983;96(4):502–9.CrossRefGoogle Scholar
  31. 31.
    Zhao M, Mu Y, Dang Y, Zhu Y. Secondary glaucoma as initial manifestation of ring melanoma: a case report and review of literature. Int J Clin Exp Pathol. 2014;7(11):8163–9.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Burris CK, Rodriguez ME, Raven ML. Melanomalytic Glaucoma. Ophthalmology. 2015;122(12):2422.CrossRefGoogle Scholar
  33. 33.
    Rummelt V, Folberg R, Woolson RF, Hwang T, Pe'er J. Relation between the microcirculation architecture and the aggressive behavior of ciliary body melanomas. Ophthalmology. 1995;102(5):844–51.CrossRefGoogle Scholar
  34. 34.
    Folberg R, Rummelt V, Parys-Van Ginderdeuren R, Hwang T, Woolson RF, Pe'er J, Gruman LM. The prognostic value of tumor blood vessel morphology in primary uveal melanoma. Ophthalmology. 1993;100(9):1389–98.CrossRefGoogle Scholar
  35. 35.
    Tschentscher F, Hüsing J, Hölter T, Kruse E, Dresen IG, Jöckel KH, Anastassiou G, Schilling H, Bornfeld N, Horsthemke B, Lohmann DR, Zeschnigk M. Tumor classification based on gene expression profiling shows that uveal melanomas with and without monosomy 3 represent two distinct entities. Cancer Res. 2003;63(10):2578–84.PubMedGoogle Scholar
  36. 36.
    Onken MD, Worley LA, Ehlers JP, Harbour JW. Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death. Cancer Res. 2004;64(20):7205–9.CrossRefGoogle Scholar
  37. 37.
    Mäkitie T, Summanen P, Tarkkanen A, Kivelä T. Tumor-infiltrating macrophages (CD68(+) cells) and prognosis in malignant uveal melanoma. Invest Ophthalmol Vis Sci. 2001;42(7):1414–21.PubMedGoogle Scholar
  38. 38.
    Field MG, Decatur CL, Kurtenbach S, Gezgin G, van der Velden PA, Jager MJ, Kozak KN, Harbour JW. PRAME as an independent biomarker for metastasis in uveal melanoma. Clin Cancer Res. 2016;22(5):1234–42.CrossRefGoogle Scholar
  39. 39.
    The Collaborative Ocular Melanoma Study (COMS) randomized trial of preenucleation radiation of large choroidal melanoma I: characteristics of patients enrolled and not enrolled. COMS report no. 9. Am J Ophthalmol. 1998;125(6):767.Google Scholar
  40. 40.
    Li W, Gragoudas ES, Egan KM. Metastatic melanoma death rates by anatomic site after proton beam irradiation for uveal melanoma. Arch Ophthalmol. 2000;118(8):1066–70.CrossRefGoogle Scholar
  41. 41.
    Krema H, Simpson ER, Pavlin CJ, Payne D, Vasquez LM, McGowan H. Management of ciliary body melanoma with iodine-125 plaque brachytherapy. Can J Ophthalmol. 2009;44(4):395–400.CrossRefGoogle Scholar
  42. 42.
    International Validation of the American Joint Committee on Cancer’s 7th Edition Classification of Uveal Melanoma. JAMA Ophthalmol. 2015;133(4):376–83.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Patricia Chévez-Barrios
    • 1
    • 2
    Email author
  • Linda Alejandra Cernichiaro Espinosa
    • 3
  1. 1.Department of Pathology and Genomic MedicineHouston Methodist HospitalHoustonUSA
  2. 2.Department of Pathology & Laboratory Medicine and OphthalmologyHouston Methodist-Weill Cornell Medical CollegeNew YorkUSA
  3. 3.Hospital para Evitar la Ceguera en Mexico “Dr. Luis Sanchez Bulnes”CoyoacánMexico

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