Alec L Amram1, Grecia Rico2, Jonathan W Kim3, Murali Chintagumpala4, Cynthia E Herzog5, Dan S Gombos6, Patricia Chévez-Barrios7. 1. Department of Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, Texas. 2. Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas. 3. Retinoblastoma Service, Children's Hospital Los Angeles, Los Angeles, California; USC Roski Eye Institute, Keck School of Medicine of USC, Los Angeles, California. 4. Retinoblastoma Center of Houston, Houston, Texas; Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas. 5. Retinoblastoma Center of Houston, Houston, Texas; Department of Pediatrics Patient Care, Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas. 6. Retinoblastoma Center of Houston, Houston, Texas; Department of Ophthalmology, Baylor College of Medicine, Houston, Texas; Section of Ophthalmology, Department of Head and Neck Surgery, University of Texas, MD Anderson Cancer Center, Houston, Texas. 7. Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas; Retinoblastoma Center of Houston, Houston, Texas; Department of Ophthalmology, Baylor College of Medicine, Houston, Texas; Pathology and Laboratory Medicine and Ophthalmology, Weill Cornell Medical College of Cornell University, New York, New York; Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Department of Pathology and Laboratory Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas. Electronic address: pchevez-barrios@houstonmethodist.org.
Abstract
PURPOSE: A recent classification scheme for retinoblastoma vitreous seeds has shown promise in predicting treatment response. For the first time, we correlate this clinical classification scheme with its histopathologic features. DESIGN: Retrospective review. PARTICIPANTS: Enucleated eyes received at the pathology department of the Retinoblastoma Center of Houston from 2010 to 2015. METHODS: Macroscopic photographs of the enucleated eyes of patients with retinoblastoma were analyzed to select those with vitreous seeds. Cases with adequate material for clinicopathologic correlation were selected for further analysis, and clinical photographs were reviewed. Routine histopathologic slides were reviewed and compared with the clinical and macroscopic photographs. Seeds were classified as type 1 ("dust"), type 2 ("sphere"), or type 3 ("cloud"). To confirm the presence of macrophages, CD68 immunohistochemical staining was used. Synaptophysin was used to stain retinoblastoma cells. MAIN OUTCOME MEASURES: To correlate clinical vitreous seed type with histopathologic features. RESULTS: A total of 14 eyes with adequate amounts of tumor seeds along with clinical and macroscopic photographic correlation were selected from a total of 138 eyes reviewed. Type 1 seeds consisted of individual viable tumor cells and scattered macrophages. Type 2 seeds consisted of 2 submorphologies: spheres with viable cells throughout and spheres with an outer rim of viable cells but necrotic cells centrally. Type 3 seeds were composed of more than 90% necrotic material admixed with few macrophages and viable cells at their outer rim. Untreated (8/14) and previously treated (6/14) eyes showed similar histopathologic features for each type of seeds. Treated eyes had more type 1 and 3 seeds. CONCLUSIONS: We provide the first histopathologic correlation of the clinical classification scheme for vitreous seeds in retinoblastoma. "Dust" is formed by scattered single cells alternating with macrophages. "Spheres" with translucent centers contain multiple layers of viable tumor cells that shed single cells and may be more clinically aggressive. "Cloud" seeds are mostly composed of necrotic material, explaining their lack of therapeutic response. Pretreated eyes showed tumor seeds morphologically similar to untreated eyes. Knowledge of the underlying histopathology of vitreous seed types is a fundamental component of classification and may aid in understanding clinical response to treatment.
PURPOSE: A recent classification scheme for retinoblastoma vitreous seeds has shown promise in predicting treatment response. For the first time, we correlate this clinical classification scheme with its histopathologic features. DESIGN: Retrospective review. PARTICIPANTS: Enucleated eyes received at the pathology department of the Retinoblastoma Center of Houston from 2010 to 2015. METHODS: Macroscopic photographs of the enucleated eyes of patients with retinoblastoma were analyzed to select those with vitreous seeds. Cases with adequate material for clinicopathologic correlation were selected for further analysis, and clinical photographs were reviewed. Routine histopathologic slides were reviewed and compared with the clinical and macroscopic photographs. Seeds were classified as type 1 ("dust"), type 2 ("sphere"), or type 3 ("cloud"). To confirm the presence of macrophages, CD68 immunohistochemical staining was used. Synaptophysin was used to stain retinoblastoma cells. MAIN OUTCOME MEASURES: To correlate clinical vitreous seed type with histopathologic features. RESULTS: A total of 14 eyes with adequate amounts of tumor seeds along with clinical and macroscopic photographic correlation were selected from a total of 138 eyes reviewed. Type 1 seeds consisted of individual viable tumor cells and scattered macrophages. Type 2 seeds consisted of 2 submorphologies: spheres with viable cells throughout and spheres with an outer rim of viable cells but necrotic cells centrally. Type 3 seeds were composed of more than 90% necrotic material admixed with few macrophages and viable cells at their outer rim. Untreated (8/14) and previously treated (6/14) eyes showed similar histopathologic features for each type of seeds. Treated eyes had more type 1 and 3 seeds. CONCLUSIONS: We provide the first histopathologic correlation of the clinical classification scheme for vitreous seeds in retinoblastoma. "Dust" is formed by scattered single cells alternating with macrophages. "Spheres" with translucent centers contain multiple layers of viable tumor cells that shed single cells and may be more clinically aggressive. "Cloud" seeds are mostly composed of necrotic material, explaining their lack of therapeutic response. Pretreated eyes showed tumor seeds morphologically similar to untreated eyes. Knowledge of the underlying histopathology of vitreous seed types is a fundamental component of classification and may aid in understanding clinical response to treatment.
Authors: Zachary K Goldsmith; William Coppess; Andrew S Irvine; Kelley Yuan; Samuel R Barsh; Madison K Ritter; Matthew W McEwen; Jacqueline Flores-Otero; Aileen Garcia-Vargas; Magaly Martinez-Ferrer; Rachel C Brennan; Vanessa M Morales-Tirado; Matthew W Wilson Journal: Invest Ophthalmol Vis Sci Date: 2018-09-04 Impact factor: 4.799
Authors: Michelle G Zhang; Jeffim N Kuznetsoff; Dawn A Owens; Ryan A Gallo; Karthik Kalahasty; Anthony M Cruz; Stefan Kurtenbach; Zelia M Correa; Daniel Pelaez; J William Harbour Journal: Cancers (Basel) Date: 2022-10-10 Impact factor: 6.575
Authors: Mary E Kim; Ashley Polski; Liya Xu; Rishvanth K Prabakar; Chen-Ching Peng; Mark W Reid; Rachana Shah; Peter Kuhn; David Cobrinik; James Hicks; Jesse L Berry Journal: Cancers (Basel) Date: 2021-07-03 Impact factor: 6.639
Authors: Ankit Singh Tomar; Paul T Finger; Brenda Gallie; Tero Kivelä; Ashwin Mallipatna; Chengyue Zhang; Junyang Zhao; Matthew Wilson; Rachel Brennan; Michala Burges; Jonathan Kim; Jesse L Berry; Rima Jubran; Vikas Khetan; Suganeswari Ganeshan; Andrey Yarovoy; Vera Yarovaya; Elena Kotova; Denis Volodin; Yacoub Yousef; Kalle Nummi; Tatiana L Ushakova; Olga V Yugay; Vladimir G Polyakov; Marco Antonio Ramirez-Ortiz; Elizabeth Esparza-Aguiar; Guillermo L Chantada; Paula Schaiquevich; Adriana C Fandiño; Jason C Yam; Winnie W Lau; Carol P Lam; Phillipa Sharwood; Sonia Moorthy; Quah Boon Long; Vera Adobea Essuman; Lorna A Renner; Ekaterina Semenova; Jaume Català-Mora; Maria Correa Llano; Elisa Carreras Journal: Br J Ophthalmol Date: 2021-08-02 Impact factor: 5.908