Spotlight on ocular Kaposi’s sarcoma: an update on the presentation, diagnosis, and management options

References

• Schwartz RA. Kaposi’s sarcoma: an update. J Surg Oncol. 2004;87(3):146–151.
   PubMed Web of Science ®Google Scholar
• Alluhaybi AF, Hatatah NM. HIV-associated cutaneous Kaposi’s sarcoma. Cureus. 2021;13(2):e13544.
   PubMed Web of Science ®Google Scholar
• **Kaposi M. Idiopathisces multiples Pigmentsarkom der Haut. Archiv fur Dermatologi und Syphilis. 1872;3:265–273.
   Google Scholar
• Shuler JD, Holland GN, Miles SA, et al. Kaposi sarcoma of the conjunctiva and eyelids associated with the acquired immunodeficiency syndrome. Arch Ophthalmol. 1989;107(6):858–862.
   PubMedGoogle Scholar
• **Brun SC, Jakobiec FA. Kaposi’s sarcoma of the ocular adnexa. Int Ophthalmol Clin. 1997;37(4):25–38.
   PubMedGoogle Scholar
• Donovan C, Patel H, Shetty S, et al. Aggressive conjunctival Kaposi sarcoma as the initial manifestation of acquired immunodeficiency syndrome. Am J Ophthalmol Case Rep. 2020;19:100832.
   PubMedGoogle Scholar
• Steuer AB, Cohen JM, Christman MP, et al. Acquired immune deficiency syndrome-related epidemic Kaposi sarcoma. Dermatol Online J. 2018;24(12):12.
   Google Scholar
• **Weinstein JE, Karp CL. Ocular surface neoplasias and human immunodeficiency virus infection. Curr Opin Infect Dis. 2013;26(1):58–65.
   PubMed Web of Science ®Google Scholar
• Crum-Cianflone NF, Hullsiek KH, Ganesan A, et al. Is Kaposi’s sarcoma occurring at higher CD4 cell counts over the course of the HIV epidemic? AIDS. 2010;24(18):2881–2883.
   PubMed Web of Science ®Google Scholar
• *Mosam A, Aboobaker J, Shaik F. Kaposi’s sarcoma in sub-Saharan Africa: a current perspective. Curr Opin Infect Dis. 2010;23(2):119–123.
   PubMed Web of Science ®Google Scholar
• **Ramdass P, Mullick S, Farber HF. Viral skin diseases. Prim Care. 2015;42(4):517–567.
   PubMed Web of Science ®Google Scholar
• **Ulloa-Padilla JP, Ghassibi MP, Dubovy SR, et al. Clinicopathologic correlation of Kaposi sarcoma involving the ocular adnexa: immunophenotyping of diagnostic and therapeutic targets. Ophthalmic Plast Reconstr Surg. 2020;36(2):185–190.
   PubMed Web of Science ®Google Scholar
• *Yang J, Yin XF, Li YP, et al. Case report of ocular Kaposi’s sarcoma. BMC Ophthalmol. 2017;17(1):143.
   PubMedGoogle Scholar
• *Coblentz J, Park JY, Discepola G, et al. Conjunctival Kaposi’s sarcoma with orbital extension in an HIV-negative man. Can J Ophthalmol. 2018;53(3):e111–e3.
   PubMed Web of Science ®Google Scholar
• Schmid K, Wild T, Bolz M, et al. Kaposi’s sarcoma of the conjunctiva leads to a diagnosis of acquired immunodeficiency syndrome. Acta Ophthalmol Scand. 2003;81(4):411–413.
   PubMedGoogle Scholar
• Chang Y, Cesarman E, Pessin MS, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science. 1994;266(5192):1865–1869.
   PubMed Web of Science ®Google Scholar
• Chen J, Dai L, Goldstein A, et al., Identification of new antiviral agents against Kaposi’s sarcoma-associated herpesvirus (KSHV) by high-throughput drug screening reveals the role of histamine-related signaling in promoting viral lytic reactivation. PLoS Pathog. 15(12): e1008156. 2019.
   PubMed Web of Science ®Google Scholar
• Mesri EA, Cavallin LE, Ashlock BM, et al. Molecular studies and therapeutic targeting of Kaposi’s sarcoma herpesvirus (KSHV/HHV-8) oncogenesis. Immunol Res. 2013;57(1–3):159–165.
   PubMed Web of Science ®Google Scholar
• Dollard SC, Butler LM, Jones AM, et al. Substantial regional differences in human herpesvirus 8 seroprevalence in sub-Saharan Africa: insights on the origin of the “Kaposi’s sarcoma belt”. Int J Cancer. 2010;127(10):2395–2401.
   PubMed Web of Science ®Google Scholar
• **Lisitsyn NA. Representational difference analysis: finding the differences between genomes. Trends Genet. 1995;11(8):303–307.
   PubMed Web of Science ®Google Scholar
• Saha A, Kaul R, Murakami M, et al. Tumor viruses and cancer biology: modulating signaling pathways for therapeutic intervention. Cancer Biol Ther. 2010;10(10):961–978.
   PubMed Web of Science ®Google Scholar
• Yasunaga JI, Matsuoka M. Oncogenic spiral by infectious pathogens: cooperation of multiple factors in cancer development. Cancer Sci. 2018;109(1):24–32.
   PubMed Web of Science ®Google Scholar
• Speck SH, Ganem D. Viral latency and its regulation: lessons from the gamma-herpesviruses. Cell Host Microbe. 2010;8(1):100–115.
   PubMed Web of Science ®Google Scholar
• Zhi H, Zahoor MA, Shudofsky AM, et al. KSHV vCyclin counters the senescence/G1 arrest response triggered by NF-κB hyperactivation. Oncogene. 2015;34(4):496–505.
   PubMed Web of Science ®Google Scholar
• Leidal AM, Cyr DP, Hill RJ, et al. Subversion of autophagy by Kaposi’s sarcoma-associated herpesvirus impairs oncogene-induced senescence. Cell Host Microbe. 2012;11(2):167–180.
   PubMed Web of Science ®Google Scholar
• Moses AV, Jarvis MA, Raggo C, et al. Kaposi’s sarcoma-associated herpesvirus-induced upregulation of the c-kit proto-oncogene, as identified by gene expression profiling, is essential for the transformation of endothelial cells. J Virol. 2002;76(16):8383–8399.
   PubMed Web of Science ®Google Scholar
• Fukumoto H, Kanno T, Hasegawa H, et al. Pathology of Kaposi’s sarcoma-associated herpesvirus infection. Front Microbiol. 2011;2:175.
   PubMed Web of Science ®Google Scholar
• Hong YK, Foreman K, Shin JW, et al. Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus. Nat Genet. 2004;36(7):683–685.
   PubMed Web of Science ®Google Scholar
• Human herpesvirus-8 disease. AidsInfo. 2018.
   Google Scholar
• Pauk J, Huang ML, Brodie SJ, et al. Mucosal shedding of human herpesvirus 8 in men. N Engl J Med. 2000;343(19):1369–1377.
   PubMed Web of Science ®Google Scholar
• Casper C, Krantz E, Selke S, et al. Frequent and asymptomatic oropharyngeal shedding of human herpesvirus 8 among immunocompetent men. J Infect Dis. 2007;195(1):30–36.
   PubMed Web of Science ®Google Scholar
• Campbell DM, Rappocciolo G, Jenkins FJ, et al. Dendritic cells: key players in human herpesvirus 8 infection and pathogenesis. Front Microbiol. 2014;5:452.
   PubMed Web of Science ®Google Scholar
• Douglas JL, Gustin JK, Dezube B, et al. Kaposi’s sarcoma: a model of both malignancy and chronic inflammation. Panminerva Med. 2007;49(3):119–138.
   PubMed Web of Science ®Google Scholar
• Cai Q, Verma SC, Lu J, et al. Molecular biology of Kaposi’s sarcoma-associated herpesvirus and related oncogenesis. Adv Virus Res. 2010;78:87–142.
   PubMed Web of Science ®Google Scholar
• Curtis TH, Durairaj VD. Conjunctival Kaposi sarcoma as the initial presentation of human immunodeficiency virus infection. Ophthalmic Plast Reconstr Surg. 2005;21(4):314–315.
   PubMed Web of Science ®Google Scholar
• Sousa Neves F, Braga J, Cardoso da Costa J. Kaposi’s sarcoma of the conjunctiva and the eyelid leads to the diagnosis of human immunodeficiency virus infection - a case report. BMC Cancer. 2018;18(1):708.
   PubMedGoogle Scholar
• Rossetto JD, Molles S, Gracitelli CPB. Extensive bulbar conjunctival Kaposi’s sarcoma as initial symptom of human immunodeficiency virus. Arq Bras Oftalmol. 2019;82(5):429–431.
   PubMed Web of Science ®Google Scholar
• Soll DB, Redovan EG. Kaposi’s sarcoma of the eyelid as the initial manifestation of AIDS. Ophthalmic Plast Reconstr Surg. 1989;5(1):49–51.
   PubMedGoogle Scholar
• Kurumety UR, Lustbader JM. Kaposi’s sarcoma of the bulbar conjunctiva as an initial clinical manifestation of acquired immunodeficiency syndrome. Arch Ophthalmol. 1995;113(8):978.
   PubMedGoogle Scholar
• Teixeira AI, Neno M, Badura R, et al. Kaposi Sarcoma of the eyelid as an initial manifestation of AIDS. Dermatol Online J. 2016;22:7.
   Google Scholar
• Weinstein JE, Mears KA. Periocular Kaposi sarcoma as the initial presentation of human immunodeficiency virus. JAMA Ophthalmol. 2016;134(10):e162139.
   PubMed Web of Science ®Google Scholar
• *Moore PS, Chang Y. Detection of herpesvirus-like DNA sequences in Kaposi’s sarcoma in patients with and those without HIV infection. N Engl J Med. 1995;332(18):1181–1185.
   PubMed Web of Science ®Google Scholar
• Gao SJ, Kingsley L, Li M, et al. KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi’s sarcoma. Nat Med. 1996;2(8):925–928.
   PubMed Web of Science ®Google Scholar
• Antman K, Chang Y. Kaposi’s sarcoma. N Engl J Med. 2000;342(14):1027–1038.
   PubMed Web of Science ®Google Scholar
• Radu O, Pantanowitz L. Kaposi sarcoma. Arch Pathol Lab Med. 2013;137(2):289–294.
   PubMed Web of Science ®Google Scholar
• Friedman-Kien AE, Saltzman BR. Clinical manifestations of classical, endemic African, and epidemic AIDS-associated Kaposi’s sarcoma. J Am Acad Dermatol. 1990;22(6 Pt 2):1237–1250.
   PubMed Web of Science ®Google Scholar
• Etemad SA, Dewan AK. Kaposi sarcoma updates. Dermatol Clin. 2019;37(4):505–517.
   PubMed Web of Science ®Google Scholar
• **Qureshi YA, Karp CL, Dubovy SR. Intralesional interferon alpha-2b therapy for adnexal Kaposi sarcoma. Cornea. 2009;28(8):941–943.
   PubMed Web of Science ®Google Scholar
• **Dugel PU, Gill PS, Frangieh GT, et al. Ocular adnexal Kaposi’s sarcoma in acquired immunodeficiency syndrome. Am J Ophthalmol. 1990;110(5):500–503.
   PubMed Web of Science ®Google Scholar
• **Kohanim S, Daniels AB, Huynh N, et al. Local treatment of Kaposi sarcoma of the conjunctiva. Int Ophthalmol Clin. 2011;51(4):183–192.
   PubMedGoogle Scholar
• **Dugel PU, Gill PS, Frangieh GT, et al. Treatment of ocular adnexal Kaposi’s sarcoma in acquired immune deficiency syndrome. Ophthalmology. 1992;99(7):1127–1132.
   PubMed Web of Science ®Google Scholar
• **Rosado FG, Itani DM, Coffin CM, et al. Utility of immunohistochemical staining with FLI1, D2-40, CD31, and CD34 in the diagnosis of acquired immunodeficiency syndrome-related and non-acquired immunodeficiency syndrome-related Kaposi sarcoma. Arch Pathol Lab Med. 2012;136(3):301–304.
   PubMed Web of Science ®Google Scholar
• Minoda H, Usui N, Sata T, et al. Human herpesvirus-8 in Kaposi’s sarcoma of the conjunctiva in a patient with AIDS. Jpn J Ophthalmol. 2006;50(1):7–11.
   PubMed Web of Science ®Google Scholar
• Patel RM, Goldblum JR, Hsi ED. Immunohistochemical detection of human herpes virus-8 latent nuclear antigen-1 is useful in the diagnosis of Kaposi sarcoma. Mod Pathol. 2004;17(4):456–460.
   PubMed Web of Science ®Google Scholar
• Robin YM, Guillou L, Michels JJ, et al. Human herpesvirus 8 immunostaining: a sensitive and specific method for diagnosing Kaposi sarcoma in paraffin-embedded sections. Am J Clin Pathol. 2004;121(3):330–334.
   PubMed Web of Science ®Google Scholar
• Murray N, McCluskey P, Wakefield D, et al. Isolated bulbar conjunctival Kaposi’s sarcoma. Aust N Z J Ophthalmol. 1994;22(1):81–82.
   PubMedGoogle Scholar
• Izquierdo Rodriguez C, Cordova JM. Conjunctival Kaposi’s sarcoma as the initial manifestation of acquired inmunodeficiency syndrome. Nepal J Ophthalmol. 2013;5(2):265–267.
   PubMedGoogle Scholar
• Mikropoulos D, Mavrikakis I, Ziakas NG, et al. Kaposi’s sarcoma of the bulbar conjunctiva in an immunocompetent patient. Case Rep Ophthalmol. 2011;2(2):193–197.
   PubMedGoogle Scholar
• Fogt F, Sulewski M, Meralli F, et al. Conjunctival Kaposi’s sarcoma in a nonimmunocompromised patient. Can J Ophthalmol. 2007;42(2):310–311.
   PubMed Web of Science ®Google Scholar
• Rodríguez-Pérez C, Gris-Castellón O, Soler-Lluis N, et al. [Amniotic membrane transplantation after surgical resection in conjunctival Kaposi’s sarcoma]. Arch Soc Esp Oftalmol. 2005;80(9):525–528.
   PubMedGoogle Scholar
• Marino D, Calabrese F, Ottaviano G, et al. Recurrent Kaposi sarcoma associated with Koebner phenomenon in two HIV-seronegative patients: two case reports and a review of the literature. Medicine (Baltimore). 2017;96(52):e9467.
   PubMed Web of Science ®Google Scholar
• Reiser BJ, Mok A, Kukes G, et al. Non-AIDS-related Kaposi sarcoma involving the tarsal conjunctiva and eyelid margin. Arch Ophthalmol. 2007;125(6):838–840.
   PubMedGoogle Scholar
• Maia S, Gomes M, Oliveira L, et al. Isolated bulbar conjunctival Kaposi’s sarcoma as a primary presentation of AIDS: a case report. Case Rep Ophthalmol Med. 2013;2013:469195.
   PubMedGoogle Scholar
• *Gunay E, Oncul H. Successful treatment of conjunctival kaposi sarcoma in a human immunodeficiency virus-negative kidney transplant recipient: a case report. Transplant Proc. 2020;52(2):622–624.
   PubMed Web of Science ®Google Scholar
• Ron IG, Kremer I, Lowenstein A, et al. Conjunctival involvement in classic (indolent) HIV negative Kaposi’s sarcoma. Br J Ophthalmol. 1994;78(6):488–489.
   PubMed Web of Science ®Google Scholar
• Jonasch E, Haluska FG. Interferon in oncological practice: review of interferon biology, clinical applications, and toxicities. Oncologist. 2001;6(1):34–55.
   PubMed Web of Science ®Google Scholar
• Dupuy J, Price M, Lynch G, et al. Intralesional interferon-alpha and zidovudine in epidemic Kaposi’s sarcoma. J Am Acad Dermatol. 1993;28(6):966–972.
   PubMed Web of Science ®Google Scholar
• Aldenhoven M, Barlo NP, Sanders CJ. Therapeutic strategies for epidemic Kaposi’s sarcoma. Int J STD AIDS. 2006;17(9):571–578.
   PubMed Web of Science ®Google Scholar
• Hummer J, Gass JD, Huang AJ. Conjunctival Kaposi’s sarcoma treated with interferon alpha-2a. Am J Ophthalmol. 1993;116(4):502–503.
   PubMed Web of Science ®Google Scholar
• Munteanu G, Munteanu M, Giuri S. [Conjunctival-palpebral Kaposi’s angiosarcoma: report of a case]. J Fr Ophtalmol. 2003;26(10):1059–1062.
   PubMed Web of Science ®Google Scholar
• **Korn BS, Park DJ, Kikkawa DO. Intralesional mitomycin-C for the treatment of conjunctival Kaposi sarcoma. Ophthalmic Plast Reconstr Surg. 2011;27(4):e88–90.
   PubMed Web of Science ®Google Scholar
• **Dupont C, Vasseur E, Beauchet A, et al., Long-term efficacy on Kaposi’s sarcoma of highly active antiretroviral therapy in a cohort of HIV-positive patients. CISIH 92. Centre d’information et de soins de l’immunodéficience humaine. Aids. 14(8): 987–993. 2000.
   PubMedGoogle Scholar
• **Mosam A, Shaik F, Uldrick TS, et al., A randomized controlled trial of highly active antiretroviral therapy versus highly active antiretroviral therapy and chemotherapy in therapy-naive patients with HIV-associated Kaposi sarcoma in South Africa. J Acquir Immune Defic Syndr. 60(2): 150–157. 2012.
   PubMed Web of Science ®Google Scholar
• Bower M, Weir J, Francis N, et al. The effect of HAART in 254 consecutive patients with AIDS-related Kaposi’s sarcoma. Aids. 2009;23(13):1701–1706.
   PubMed Web of Science ®Google Scholar
• Loke WC, Spittle MF, Mitchell S, et al. Timing of highly active antiretroviral therapy and chemotherapy for Kaposi’s sarcoma in patients with HIV infection. Int J STD AIDS. 2006;17(8):565–566.
   PubMed Web of Science ®Google Scholar
• **Leder HA, Galor A, Peters GB, et al. Resolution of conjunctival Kaposi sarcoma after institution of highly active antiretroviral therapy alone. Br J Ophthalmol. 2008;92(1):151.
   Web of Science ®Google Scholar
• Yeak J, Iqbal T, Zahari M, et al. Total resolution of ocular Kaposi sarcoma with different treatment approaches - a case series and review of literature. Int J STD AIDS. 2019;30(8):802–809.
   PubMed Web of Science ®Google Scholar
• Shields JA, Mashayekhi A, Kligman BE, et al. Vascular tumors of the conjunctiva in 140 cases. Ophthalmology. 2011;118(9):1747–1753.
   PubMed Web of Science ®Google Scholar
• Jin C, Minhas H, Kaur A, et al. A case of ocular kaposi’s sarcoma successfully treated with highly active antiretroviral therapy (HAART) combined with docetaxel. Am J Case Rep. 2018;19:1074–1077.
   PubMed Web of Science ®Google Scholar
• Segura LC, Goel A. Rare ocular involvement in a newly diagnosed AIDS patient with diffuse Kaposi’s sarcoma. Cureus. 2020;12(6):e8502.
   PubMed Web of Science ®Google Scholar
• Eduardo-Sánchez YW, Fernández-Agrafojo D. Human immunodeficiency virus-associated giant conjunctival Kaposi’s sarcoma: complete remission with antiretroviral therapy and systemic chemotherapy. Arch Soc Esp Oftalmol. 2018;93(6):310–312.
   PubMedGoogle Scholar
• **Ghabrial R, Quivey JM, Dunn JP Jr., et al. Radiation therapy of acquired immunodeficiency syndrome-related Kaposi’s sarcoma of the eyelids and conjunctiva. Arch Ophthalmol. 1992;110(10):1423–1426.
   PubMedGoogle Scholar
• Cianfrocca M, Lee S, Von Roenn J, et al. Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcoma: evidence of symptom palliation from chemotherapy. Cancer. 2010;116(16):3969–3977.
   PubMed Web of Science ®Google Scholar
• *Cooper JS, Fried PR. Defining the role of radiation therapy in the management of epidemic Kaposi’s sarcoma. Int J Radiat Oncol Biol Phys. 1987;13(1):35–39.
   PubMed Web of Science ®Google Scholar
• **Kirova YM, Belembaogo E, Frikha H, et al., Radiotherapy in the management of epidemic Kaposi’s sarcoma: a retrospective study of 643 cases. Radiother Oncol. 46(1): 19–22. 1998.
   PubMed Web of Science ®Google Scholar
• Geara F, Le Bourgeois JP, Piedbois P, et al. Radiotherapy in the management of cutaneous epidemic Kaposi’s sarcoma. Int J Radiat Oncol Biol Phys. 1991;21(6):1517–1522.
   PubMed Web of Science ®Google Scholar
• *Cooper JS, Fried PR. Case report. Treatment of aggressive epidemic Kaposi’s sarcoma of the conjunctiva by radiotherapy. Arch Ophthalmol. 1988;106(1):20–21.
   PubMedGoogle Scholar
• **Brambilla L, Tourlaki A, Genovese G. Iatrogenic Kaposi’s sarcoma: a retrospective cohort study in an Italian tertiary care centre. Clin Oncol (R Coll Radiol). 2017;29(10):e165–e71.
   PubMed Web of Science ®Google Scholar
• Stallone G, Schena A, Infante B, et al. Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. N Engl J Med. 2005;352(13):1317–1323.
   PubMed Web of Science ®Google Scholar
• Campistol JM, Schena FP. Kaposi’s sarcoma in renal transplant recipients–the impact of proliferation signal inhibitors. Nephrol Dial Transplant. 2007;22(Suppl 1):i17–22.
   PubMedGoogle Scholar
• **Dalla Pria A, Pinato DJ, Bracchi M, et al. Recent advances in HIV-associated Kaposi sarcoma. F1000Res. 2019;8. https://doi.org/https://doi.org/10.12688/f1000research.17401.1
   Google Scholar
• Reid EG, Suazo A, Lensing SY, et al. AIDS malignancy consortium (AMC). Pilot trial AMC-063: safety and efficacy of bortezomib in AIDS-associated Kaposi sarcoma. Clin Cancer Res. 2020 Feb 1;26(3):558–565.
   PubMed Web of Science ®Google Scholar
• Masood R, Xia G, Smith DL, et al. Ephrin B2 expression in Kaposi sarcoma is induced by human herpesvirus type 8: phenotype switch from venous to arterial endothelium. Blood. 2005 Feb 1;105(3):1310–1318.
   PubMed Web of Science ®Google Scholar
• **Ceccarelli M, Facciolà A, Taibi R, et al. The treatment of Kaposi’s sarcoma: present and future options, a review of the literature. Eur Rev Med Pharmacol Sci. 2019;23(17):7488–7497.
   PubMed Web of Science ®Google Scholar
• *Li H, Zhong C, Wang Q, et al. Curcumin is an APE1 redox inhibitor and exhibits an antiviral activity against KSHV replication and pathogenesis. Antiviral Res. 2019;167:98–103.
   PubMed Web of Science ®Google Scholar
• Uldrick TS, Wyvill KM, Kumar P, et al. Phase II study of bevacizumab in patients with HIV-associated Kaposi’s sarcoma receiving antiretroviral therapy. J Clin Oncol. 2012;30(13):1476–1483.
   PubMed Web of Science ®Google Scholar
• Ardavanis A, Doufexis D, Kountourakis P, et al. A Kaposi’s sarcoma complete clinical response after sorafenib administration. Ann Oncol. 2008;19(9):1658–1659.
   PubMed Web of Science ®Google Scholar
• Delyon J, Bizot A, Battistella M, et al. PD-1 blockade with nivolumab in endemic Kaposi sarcoma. Ann Oncol. 2018;29(4):1067–1069.
   PubMed Web of Science ®Google Scholar
• Liu Z, Karp CL, Galor A, et al. Role of optical coherence tomography angiography in the characterization of vascular network patterns of ocular surface squamous neoplasia. Ocul Surf. 2020;18(4):926–935.
   Web of Science ®Google Scholar
• Karp CL, Mercado C, Venkateswaran N, et al. Use of high-resolution optical coherence tomography in the surgical management of ocular surface squamous neoplasia: a pilot study. Am J Ophthalmol. 2019;206:17–31.
   PubMed Web of Science ®Google Scholar