Werdich XQ, Jakobiec FA, Curtin HD, Fay A.
A clinical, radiologic, and immunopathologic study of five periorbital intraosseous cavernous vascular malformations. Am J Ophthalmol 2014;158(4):816-826.e1.
AbstractPURPOSE: To correlate the clinical, radiographic, histopathologic, and immunohistochemical features of 5 primary periorbital intraosseous cavernous vascular malformations. DESIGN: Retrospective interventional case series. METHODS: Clinical and operative records and radiographic images were reviewed. Histopathologic slides were evaluated with hematoxylin-eosin, trichrome, and elastin stains. Immunohistochemical studies were performed with a spectrum of monoclonal antibodies directed at antigens of vascular cells. RESULTS: Three men and 2 women ranged in age from 36 to 64 years. Vision was unaffected and there was no proptosis or globe displacement. The slow-growing lesions measured 13-25 mm in greatest diameter (mean 16.4 mm). Computed tomographic studies revealed that 2 lesions were situated in the maxillary bone, 2 in the frontal, and 1 in the zygoma, all anteriorly and with circumscribed, lucent, honeycombed, or sunburst characteristics. Histopathologically the lesions were composed of cavernous or telangiectatic channels; 1 showed advanced fibrotic vascular involution. Immunohistochemistry demonstrated CD31/34 positivity for vascular endothelium and D2-40 negativity for lymphatic endothelium. A typically thin mural myofibroblastic cuff was smooth muscle actin positive, weakly calponin positive, and desmin negative. Glucose transporter-1 and Ki-67 were negative in the endothelium. CONCLUSIONS: Intraosseous vascular lesions resemble orbital cavernous venous malformations (not true hemangiomas), except that their vascular walls are thinner owing to the constraints imposed by neighboring bone spicules, which limit the amount of interstitium from which mural myofibroblasts can be recruited. The bony trabeculae conferred the honeycomb or sunburst appearances observed radiographically. En bloc excision of these lesions was successful and avoided complications (mean follow-up, 46 months).
Wolkow N, Jakobiec FA, Afrogheh AH, Eagle RC, Pai SI, Faquin WC.
Programmed Cell Death 1 Ligand 1 and Programmed Cell Death 1 Ligand 2 Are Expressed in Conjunctival Invasive Squamous Cell Carcinoma: Therapeutic Implications. Am J Ophthalmol 2019;200:226-241.
AbstractPURPOSE: Novel cancer immunotherapies, called immune checkpoint inhibitors, have demonstrated clinical efficacy in the treatment of squamous cell carcinomas of the head and neck. Tissue expression of programmed cell death 1 ligand 1 (PD-L1) and programmed cell death 1 ligand 2 (PD-L2) has been shown to predict tumor response to these drugs. We examine the expression of prognostic immune biomarkers, PD-L1 and PD-L2, in invasive ocular surface squamous neoplasia. DESIGN: Retrospective case series. METHODS: Eighteen cases of ocular surface or ocular adnexal invasive squamous cell carcinomas were identified in pathology case files of the Massachusetts General Hospital/Massachusetts Eye and Ear Infirmary and at the Wills Eye Hospital accessioned between January 1, 2014 and January 1, 2017. Immunohistochemical staining for PD-L1, PD-L2, CD8, and p16 was performed and graded in a standardized fashion. RESULTS: PD-L1 and PD-L2 were expressed on tumor cells to varying degrees, and also on some stromal cells and endothelial cells. Stromal and endothelial cell expression was also seen in control conjunctival specimens. Tumor expression of PD-L1 and PD-L2 was present on the cell membranes. All 18 (100%) of the tumors expressed PD-L1: 7 (39%) expressed a high level, 3 (17%) expressed a medium level, and 8 (44%) expressed a low level. Only 9 (50%) tumors expressed PD-L2 and it was at a low level. The expression of PD-L1 in tumor cells correlated with the presence of CD8-positive cytotoxic T lymphocytes among tumor cells (P < .01) and with the presence of CD8-positive cells in the surrounding stroma (P = .04). CONCLUSIONS: A subset of ocular invasive conjunctival squamous carcinomas express high levels of PD-L1 and CD8 and therefore may respond therapeutically to immune checkpoint inhibition.
Wolkow N, Jakobiec FA, Afrogheh AH, Pai SI, Faquin WC.
High Expression of Programmed Death Ligand 1 and Programmed Death Ligand 2 in Ophthalmic Sebaceous Carcinoma: The Case for a Clinical Trial of Checkpoint Inhibitors. Am J Ophthalmol 2020;220:128-139.
AbstractPURPOSE: To evaluate the expression of programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) in ocular adnexal sebaceous carcinoma (OASC), and to appraise these findings within the context of recent comparable studies. DESIGNS: Retrospective case series. METHODS: Twenty cases of primary OASC were immunostained for PD-L1, PD-L2 and CD8. PD-L1 and PD-L2 expression were graded with both the combined positive score (CPS) and the tumor proportion score (TPS). Both raw CPS and TPS were reported, as well as positivity with TPS and CPS ≥1. CD8 expression was graded on a 0-3 scale. Charts were reviewed for clinical correlations. The results of the current study were compared with results of similar recent investigations. RESULTS: For the 20 cases, mean expression of PD-L1 with CPS was 29.7 (range 0-101.5) and with TPS was 12.2 (range 0-95.8); mean expression of PD-L2 with CPS was 7.9 (range 0-37.3) and with TPS was 1.9 (range 0-12.9). PD-L1 CPS ≥1 was detected in 95% of OASC, while PD-L1 TPS ≥1 was found in 75%. PD-L2 CPS ≥1 was present in 60%, while only 20% had PD-L2 TPS ≥1. Immune cells appeared to contribute to a substantial proportion of PD-L1 and PD-L2 positivity, and a conspicuous CD8-positive T-lymphocytic infiltrate was present in most tumors. Significant correlations were identified between tissue expression of PD-L1, PD-L2, and CD8. Tissues with greater levels of PD-L1 tended to express higher levels of PD-L2 and CD8. The degree of PD-L1 and PD-L2 expression was also associated with the area in millimeters squared of the immunostained tumor, suggesting that tumor sampling may influence interpretation of PD-L1 and PD-L2 expression in ocular adnexal tumors. CONCLUSIONS: The current and preceding studies confirm that PD-L1 and PD-L2 are expressed in a high percentage of OASCs. These results support the premise that checkpoint inhibitor drugs hold considerable therapeutic promise for patients with OASC and stimulate the institution of clinical trials.
Wolkow N, Jakobiec FA, Lee H, Sutula FC.
Long-term Outcomes of Globe-Preserving Surgery With Proton Beam Radiation for Adenoid Cystic Carcinoma of the Lacrimal Gland. Am J Ophthalmol 2018;195:43-62.
AbstractPURPOSE: To describe outcomes of globe-preserving surgery combined with high-dose proton beam radiation (PBR) in treating primary adenoid cystic carcinoma (ACC) of the lacrimal gland. DESIGN: Retrospective case series. METHODS: Twenty-nine patients with primary ACC of the lacrimal gland were identified in the records of a single institution between 1990 and 2017. Patients with nonorbital primary tumor origins or with inadequate follow-ups were excluded. Eighteen patients met inclusion criteria. Clinical data, imaging studies, histopathology, treatment modality, local recurrences, visual outcomes, metastases, and survivals were assessed. Disease-free survivals for the current patients were measured and compared to those of other studies. RESULTS: The eighteen patients (14 female, 4 male) were followed for a median of 12.9 years (range 0.6-22.3 years) after treatment completion. Their median age was 40 years. Four were children (median age 12 years). All were treated with globe-preserving tumor resection and radiation (median dose of 72 cobalt gray equivalents). Three adult patients died of metastatic disease (median of 4.2 years after treatment). Four had local recurrences. Useful vision (20/40 or better) was retained for a median 3 years (range 1-12.9 years). Radiation morbidity included brain injury, retinopathy, optic neuropathy, keratopathy, and cataract. Overall and disease-free survivals were significantly better compared to historical treatments, but did not differ statistically from other modern approaches. CONCLUSIONS: Globe-preserving surgery with PBR, although imperfect, has a favorable long-term survival compared to other modern modalities, and offers a variable period of useful vision.
Wolkow N, Jakobiec FA, Gragoudas ES.
LONG-TERM OBSERVATION OF MULTIFOCAL METASTATIC INTRAOCULAR CARCINOID WITH ACQUIRED IRIS HETEROCHROMIA. Retin Cases Brief Rep 2020;14(3):265-267.
AbstractBACKGROUND/PURPOSE: To report a unique case of a pulmonary carcinoid tumor unilaterally metastatic to the iris and ciliary body and bilaterally to the choroid that was conservatively followed. METHODS: A 46-year-old woman presented with bilateral choroidal lesions and a left iris tumor. Ultrasound biomicroscopy disclosed a ciliary body component. A diagnosis of metastatic carcinoid tumor was made based on the clinical features. Rather than an excision, photodynamic therapy, or radiation treatment, as has been reported in all previous cases of carcinoid tumor metastatic to the iris, the patient was observed. RESULTS: Excellent vision was maintained for 8 years. The iris tumor gradually enlarged, but the choroidal lesions remained unchanged. The iris with the carcinoid tumor gradually acquired a brown pigmentation; this is the first reported case of acquired iris heterochromia in the setting of carcinoid tumor. CONCLUSION: We conclude, in cases of metastatic carcinoid in which visual acuity is excellent and the patient is asymptomatic, that observation of the ocular lesions is an acceptable course of action. The iris heterochromia is believed to have been caused by secretory factors produced by the tumor.
Wolkow N, Yoon MK.
Seborrheic Keratosis Concealing a Basal Cell Carcinoma. Ophthalmic Plast Reconstr Surg 2020;
