Keywords
How to Cite
Abstract
Aim. To correlate ultrasonographic features of uveal melanoma with histopathological findings following photodynamic therapy (PDT) with chlorin e6.
Materials and Methods. The study included 19 patients with uveal melanoma. For patients who were initially recommended for enucleation due to the large size of the neoplasm but refused, PDT was performed as the first stage of combined treatment (transscleral in 1 patient, hybrid in 5, transpupillary in 13). In the absence of positive dynamics or upon the patient's change of decision, secondary enucleation was performed within 0.25 to 1.5 (0.85 ± 0.49) months. To assess treatment efficacy, a comprehensive ultrasound examination with color Doppler imaging (CDI) and acoustic densitometry was performed. Histopathological examination of the melanoma included assessment of the morphological type, degree of necrosis, identification of signs of circulatory disturbance (thrombi), scleral invasion, mitotic activity, and degree of tumor vascularization.
Results. Histology revealed spindle cell (n=14), epithelioid (n=2), and mixed (n=3) cell types. Ultrasound and histopathological measurements showed excellent correlation (rₛ = 0.89 for tumor height, and rₛ = 0.91 and diameter, p<0.001). Necrosis was present in all cases; fibrin-erythrocyte thrombi were found in 17 eyes (89.5%). Significant correlations were identified between: baseline acoustic density and degree of necrosis (rₛ = -0.59, p=0.02); hypervascular pattern on CDI and a pronounced vascular network on histology (rₛ = 0.56, p=0.03); and the magnitude of decrease in acoustic density post-PDT (from 30.53 ± 1.26 dB to 25.97 ± 0.83 dB; Δ = -6.56 ± 1.12 dB) and the degree of necrosis (rₛ = -0.52, p=0.04). In transscleral and hybrid PDT, necrotic zones were adjacent to the sclera (0.3–0.5 mm), while thrombi were located up to 6.0 mm from the sclera.
Conclusion. The comparison of ultrasound and morphological data shows that a dynamic decrease in acoustic density and the initial hypervascular nature of blood flow are significant predictors of necrotic changes and intratumoral vessel thrombosis after PDT. The obtained results justify the possibility of using acoustic densitometry and Doppler ultrasound as objective criteria for the early assessment of the response to PDT.
References
Бровкина А.Ф. Локальное лечение меланом хориоидеи: возможности и ограничения. Вестник офтальмологии. 2018; 134(4): 52-60. -DOI: https://doi.org/10.17116/oftalma201813404152. [Brovkina A.F. Local treatment of choroidal melanoma: possibilities and limitations. Russian Annals of Ophthalmology. 2018; 134(4): 52-60. -DOI: https://doi.org/10.17116/oftalma201813404152 (In Rus)].
Shields C.L., Kaliki S., Furuta M., et al. American joint committee on cancer classification of uveal melanoma (anatomic stage) predicts prognosis in 7731 patients. Ophthalmology. 2015; 122(6): 1180-1186.-DOI: https://doi.org/10.1016/j.ophtha.2015.01.026.
Панова И.Е., Бойко Э.В., Самкович Е.В., Гвазава В.Г. Изолированная транспупиллярная фотодинамическая терапия в локальном лечении меланомы хориоидеи. Офтальмология. 2025; 22(1): 159-168-DOI: https://doi.org/10.18008/1816-5095-2025-1-159-168. [Panova I.E., Boiko E.V., Samkovich E.V., Gvazavа V.G. Isolated transpupillary photodynamic therapy in local treatment of choroidal melanoma. Ophthalmology in Russia. 2025; 22(1): 159-168-DOI: https://doi.org/10.18008/1816-5095-2025-1-159-168 (In Rus)].
Терещенко А.В., Белый Ю.А., Володин П.Л., Каплан М.А. Фотодинамическая терапия с фотосенсибилизатором «Фотодитазин» в офтальмологии. Под ред. проф. Х.П. Тахчиди. Калуга: МНТК «Микрохирургия глаза». 2008; 288(ил.). [Tereshchenko A.V., Beliy Yu.A., Volodin P.L., Kaplan M.A. Photodynamic therapy with photosensitizer ‘Photoditazine’ in ophthalmology. Ed. by Prof. H.P. Takhchidi. Kaluga: ISTC ‘Eye Microsurgery’. 2008; 288(ill.) (In Rus)].
Kessel D. Photodynamic therapy: critical PDT theory. Photochem Photobiol. 2023; 99(2): 199-203.-DOI: https://doi.org/10.1111/php.13616.
Самкович Е.В., Бойко Э.В., Панова И.Е., et al. Экспериментально-морфологическое обоснование подходов к гибридной фотодинамической терапии увеальной меланомы. Вопросы онкологии. 2025; 71(2): 325-333.-DOI: https://doi.org/10.37469/0507-3758-2025-71-2-325-333. [Samkovich E.V., Boiko E.V., Panova I.E., et al. Experimental and morphological justification of approaches to hybrid photodynamic therapy of uveal melanoma. Voprosy Onkologii = Problems in Oncology. 2025; 71(2): 325-333.-DOI: https://doi.org/10.37469/0507-3758-2025-71-2-325-333 (In Rus)].
Саакян С.В., Амирян А.Г., Вальский В.В., et al. Причины энуклеации после брахитерапии увеальных меланом. Российский офтальмологический журнал. 2016; 9(4): 46-51-DOI: https://doi.org/10.21516/2072-0076-2016-9-4-46-51. [Saakyan S.V., Amiryan A.G., Valskiy V.V., Mironova I.S., Tsygankov A.Yu. Indications for enucleation after uveal melanoma brachytherapy. Russian Ophthalmological Journal. 2016; 9(4): 46-51-DOI: https://doi.org/10.21516/2072-0076-2016-9-4-46-51 (In Rus)].
Pham C.M., Custer P.L., Couch S.M. Comparison of primary and secondary enucleation for uveal melanoma. Orbit. 2017; 36(6): 422-427.-DOI: https://doi.org/10.1080/01676830.2017.1337183.
Fabian I.D., Tomkins-Netzer O., Stoker I., et al. Secondary enucleation for uveal melanoma: a 7-year retrospective analysis. Am J Ophthalmol. 2015; 160(6): 1104-1110.e1.-DOI: https://doi.org/10.1016/j.ajo.2015.08.034.
Панова И.Е., Свистунова Е.М., Самкович Е.В., et al. Оценка постлучевого патоморфоза меланомы хориоидеи в клинической практике. Архив патологии. 2025; 87(3): 33-39-DOI: https://doi.org/10.17116/patol20258703133. [Panova I.E., Svistunova E.M., Samkovich E.V., et al. Post-radiation choroidal melanoma pathomorphosis assessment in clinical practice. Russian Journal of Archive of Pathology. 2025; 87(3): 33-39-DOI: https://doi.org/10.17116/patol20258703133 (In Rus)].
Белый Ю.А., Терещенко А.В., Володин П.Л., et al. Морфологическое изучение фотодинамических эффектов с фотосенсибилизатором «Фотодитазин» на структуру меланомы сосудистой оболочки глаза человека. Вестник ОГУ. 2007; 78: 19-22.-URL: http://vestnik.osu.ru/2007_12/38.pdf. [Beliy Yu.A., Tereshchenko A.V., Volodin P.L., et al. Morphological study of photodynamic effects with photosensitizer “Photoditazine” on the structure of melanoma of the human ocular vasculature. Vestnik OGU. 2007; 78: 19-22.-URL: http://vestnik.osu.ru/2007_12/38.pdf (In Rus)].
Ferreira T.A., Jaarsma-Coes M.G., Marinkovic M., et al. MR imaging characteristics of uveal melanoma with histopathological validation. Neuroradiology. 2022; 64(1): 171-184.-DOI: https://doi.org/10.1007/s00234-021-02825-5.
Mandard A.M., Dalibard F., Mandard J.C., et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994; 73(11): 2680-2686.-DOI: https://doi.org/10.1002/1097-0142(19940601)73:11<2680::aid-cncr2820731105>3.0.co;2-c.
Becker K., Mueller J.D., Schulmacher C., et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer. 2003; 98(7): 1521-1530.-DOI: https://doi.org/10.1002/cncr.11660.
Ростовцев Н.М., Пастернак А.Е., Котляров Н.А. Морфологические изменения в экспериментальной опухоли при фотодинамической терапии. Педиатрический вестник Южного Урала. 2015; 5: 46-49.-EDN: VDOYVL.-URL: www.elibrary.ru/download/elibrary_25114267_94308755.pdf. [Rostovtsev N.M., Pasternak А.Е., Kotliarov N.A. Morphological changes in experimental tumors in photodynamic therapy. Pediatric Bulletin of the South Ural. 2015; 5: 46-49.-EDN: VDOYVL.-URL: www.elibrary.ru/download/elibrary_25114267_94308755.pdf (In Rus)].
Корчагина К.С., Гамаюнов С.В., Воропаева Л.А., Шахова Н.М. Патоморфологические изменения тканей после проведения ФДТ (обзор литературы). Поволжский онкологический вестник. 2017; 3(30): 64-68.-EDN: YMPRYP.-URL: www.elibrary.ru/download/elibrary_32323612_75254342.pdf. [Korchagina K.S., Gamayunov S.V., Voropaeva L.A., Shakhova N.M. Pathomorphological changes in tissues after PDT (Literature review). Oncology Bulletin of the Volga region. 2017; 3(30): 64-68.-EDN: YMPRYP.-URL: www.elibrary.ru/download/elibrary_32323612_75254342.pdf (In Rus)].
Панова И.Е., Самкович Е.В., Нечипоренко П.А. Ультразвуковая допплерография в оценке кровоснабжения меланомы хориоидеи: параллели с контрастной ангиографией и гистографией. Вестник офтальмологии. 2023; 139(1): 27‑34.-DOI: https://doi.org/10.17116/oftalma202313901127. [Panova I.E., Samkovich E.V., Nechiporenko P.A. Doppler ultrasound in the assessment of blood supply to choroidal melanoma: parallels with contrast angiography and histography. Russian Annals of Ophthalmology. 2023; 139(1): 27‑34.-DOI: https://doi.org/10.17116/oftalma202313901127 (In Rus)].
Нероев В.В., Саакян С.В., Амирян А.Г., Кружкова Г.В. Ультразвуковой денситометрический анализ структуры увеальной меланомы. Российский офтальмологический журнал. 2012; 2: 45–48.-EDN: QCLKTV.-URL: www.elibrary.ru/download/elibrary_19121658_57354867.pdf. [Neroev V.V., Saakyan S.V., Amiryan A.G., Kruzhkova G.V. Ultrasonographic densitometry analysis of the structure of uveal melanoma. Russian Ophthalmological Journal. 2012; 2: 45–48.-EDN: QCLKTV.-URL: www.elibrary.ru/download/elibrary_19121658_57354867.pdf (In Rus)].
Харлап С.И., Лихванцева В.Г., Ручко Т.А. Дифференциальная диагностика опухолей хориоидеи на основе пространственного ультразвукового анализа их ангиоархитектоники. Вестник офтальмологии. 2007; 123(2): 3–9.-EDN: UIZNUX. [Kharlap S.I., Likhvantseva V.G., Ruchko T.A. Differential diagnosis of choroidal tumors on the basis of spatial ultrasound analysis of their angioarchitectonics. Russian Annals of Ophthalmology. 2007; 123(2): 3–9.-EDN: UIZNUX (In Rus)].
Амирян А.Г., Бровкина А.Ф., Лелюк В.Г. Ангиоархитектоника увеальных меланом. Офтальмология. 2005; 2(1): 37-40. [Amiryan A.G., Brovkina A.F., Lelyuk V.G. Angioarchitectonics of uveal melanomas. Ophthalmology. 2005; 2(1): 37-40 (In Rus)].
Boiko E.V., Samkovich E.V., Panova I.E., et al. Transscleral photodynamic therapy with a chlorin e6 photosensitizer in a rabbit experimental model of an intraocular mass lesion. J Lasers Med Sci. 2025; 16: e26.-DOI: https://doi.org/10.34172/jlms.2025.26.
Boiko E.V., Samkovich E.V., Panova I.E., et al. Transscleral photodynamic therapy with a chlorin e6: An experimental study of exposure parameters and therapeutic window. PLoS One. 2026; 21(1): e0341058.-DOI: https://doi.org/10.1371/journal.pone.0341058.
Mroz P., Hashmi J.T., Huang Y.Y., Lange N., Hamblin M.R. Stimulation of anti-tumor immunity by photodynamic therapy. Expert Rev Clin Immunol. 2011; 7(1): 75-91.-DOI: https://doi.org/10.1586/eci.10.81.
Kabingu E., Vaughan L., Owczarczak B., et al. CD8+ T cell-mediated control of distant tumours following local photodynamic therapy is independent of CD4+ T cells and dependent on natural killer cells. Br J Cancer. 2007; 96(12): 1839-1848.-DOI: https://doi.org/10.1038/sj.bjc.6603792.
Hendrzak-Henion J.A., Knisely T.L., Cincotta L., et al. Role of the immune system in mediating the antitumor effect of benzophenothiazine photodynamic therapy. Photochem Photobiol. 1999; 69(5): 575-581.-DOI: https://doi.org/10.1111/j.1751-1097.1999.tb03330.x.
Oh D.S., Kim H.G., Oh J.E., et al. Intratumoral depletion of regulatory T cells using anti-CD25-conjugated chlorin e6 and photodynamic therapy. Oncotarget. 2017; 8(46): 80465-80478.-DOI: https://doi.org/10.18632/oncotarget.17663.
Николаева Е.Ю., Капинус В.Н., Гривцова Л.Ю., et al. Ключевые иммунологические факторы, опосредующие эффекты внутривенной системной ФДТ у онкологических больных. Лазерная медицина. 2024; 28(3): 40.-EDN: TEQZOQ. [Nikolaeva E.Yu., Kapinus V.N., Grivtsova L.Yu., et al. Key immunological factors mediating the effects of intravenous systemic PDT in cancer patients. Laser Medicine. 2024; 28(3): 40.-EDN: TEQZOQ (In Rus)].
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
© АННМО «Вопросы онкологии», Copyright (c) 2026