Publications by authors named "Sara E Lally"

84 Publications

Conjunctival melanoma: outcomes based on tumour origin in 629 patients at a single ocular oncology centre.

Eye (Lond) 2021 Mar 26. Epub 2021 Mar 26.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

Purpose: To investigate clinical features and outcomes of conjunctival melanoma classified by tumour origin.

Methods: Retrospective review of conjunctival melanoma patients at a single ocular oncology centre between April 18, 1974 and September 9, 2019. Lesions were divided into three tumour origin groups (primary acquired melanosis [PAM], nevus, and de novo) and clinical features and outcomes were compared.

Results: There were 629 patients with conjunctival melanoma that arose from PAM (n = 476, 76%), nevus (n = 59, 9%), or de novo (n = 94, 15%). A comparison (PAM vs. nevus vs. de novo) revealed patients with tumours arising from PAM presented with older mean age (62 vs. 52 vs. 55 years, p < 0.001), worse initial logMAR visual acuity (Snellen equivalent 20/30 vs. 20/25 vs. 20/25, p = 0.03), and greater clock hour involvement (4.8 vs. 4.0 vs. 3.2, p < 0.001). Tumours arising from nevus had lower frequency of fornix (31% vs. 9% vs. 24%, p = 0.02) and tarsal involvement (29% vs. 9% vs. 26%, p = 0.046) and more frequent classification as AJCC category T1 (60% vs. 89% vs. 62%, p = 0.01). After follow-up of (57.2 vs. 68.2 vs. 51.7 months, p = 0.35), tumours arising from PAM had worse mean final visual acuity (20/50 vs. 20/40 vs. 20/40, p = 0.02) and greater frequency of visual acuity loss ≥3 lines (25% vs. 15% vs. 10%, p = 0.02). Kaplan-Meier estimates for 5-year risk showed no difference by tumour origin for visual acuity loss ≥3 lines, local tumour recurrence, exenteration, metastasis, or death.

Conclusions: Conjunctival melanoma most often arose from PAM, and tumour origin did not affect clinical outcomes.
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http://dx.doi.org/10.1038/s41433-021-01508-yDOI Listing
March 2021

Primary treatment of ocular surface squamous neoplasia with topical interferon alpha-2b: Comparative analysis of outcomes based on original tumor configuration.

Indian J Ophthalmol 2021 Mar;69(3):563-567

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

Purpose: The aim of this study was to evaluate tumor control of OSSN with topical IFNα2b alone based on tumor configuration (flat versus (vs.) dome-shaped).

Methods: Retrospective, nonrandomized, interventional cohort study on 64 consecutive tumors in 63 patients with OSSN treated with topical IFNα2b. Topical IFNα2b (1 million international units/cc) was compounded and provided by the Thomas Jefferson University Hospital Pharmacy to be refrigerated and applied 4 times daily until biomicroscopic evidence of tumor resolution was observed.

Results: The tumor configuration was flat (n = 15, 23%) or dome-shaped (n = 49, 77%). A comparison (flat vs. dome-shaped) revealed dome-shaped with older mean patient age at presentation (62 vs. 70 years, P = 0.04), greater patient history of smoking (13% vs. 42%, P = 0.04), greater corneal involvement (7% vs. 82%, P < 0.001), larger mean basal diameter (5.5 vs. 12.4 mm, P = 0.001) and mean thickness (1.9 vs. 4.3, P = 0.002), and longer mean duration IFNα2b therapy (3.7 vs. 6.3 months, P = 0.002). There was no difference in mean follow-up time (22.2 vs 23.1 months) or time to complete response (5.0 vs. 6.1 months). There was no difference in achievement of complete tumor control with IFNα2b alone (93% vs. 96%). There were no cases with metastasis or death.

Conclusion: Topical IFNα2b alone shows excellent overall tumor control of 95% with no difference in efficacy based on tumor configuration.
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http://dx.doi.org/10.4103/ijo.IJO_1665_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942118PMC
March 2021

Conjunctival Melanoma: Outcomes based on the American Joint Committee on Cancer Clinical Classification (8th Edition) of 425 Patients at a Single Ocular Oncology Center.

Asia Pac J Ophthalmol (Phila) 2020 Dec 9;10(2):146-151. Epub 2020 Dec 9.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA.

Purpose: The aim of this study was to evaluate outcomes of conjunctiva melanoma based on the American Joint Committee on Cancer Classification (AJCC) 8th edition.

Design: Retrospective interventional case series.

Methods: Outcomes analysis of 425 patients.

Results: In this analysis of 425 patients with conjunctival melanoma, there were 266 (63%) patients classified as T1, 75 (18%) as T2, 84 (20%) as T3, and 0 (0%) as T4. A comparison (T1 vs T2 vs T3) revealed that history of primary acquired melanosis was more common in T2 (81% vs 96% vs 81%; P = 0.01) and conjunctival nevus more common in T1 (20% vs 9% vs 11%; P = 0.03). Of 381 patients with follow-up (mean of 57.6 months), comparison revealed higher T category with increasing local recurrence/new tumor (30% vs 43% vs 49%; P = 0.004), increasing exenteration (3% vs 9% vs 28%; P < 0.001), increasing melanoma-related locoregional lymph node metastasis (2% vs 7% vs 12%; P = 0.001), increasing melanoma-related systemic metastasis (9% vs 25% vs 23%; P < 0.001), and increasing melanoma-related death (4% vs 12% vs 18%; P < 0.001). A comparison at 10 years revealed visual acuity loss of >3 lines (32% vs 42% vs 63%; P < 0.001), melanoma recurrence/new tumor (47% vs 70% vs 74%; P < 0.001), exenteration (4% vs 24% vs 46%; P < 0.001), melanoma-related locoregional lymph node metastasis (3% vs 13% vs 25%; P < 0.001), melanoma-related systemic metastasis (13% vs 45% vs 40%; P < 0.001), and melanoma-related death (8% vs 22% vs 37%; P < 0.001).

Conclusions: Based on the AJCC 8th edition of conjunctival melanoma, the 10-year risk per T category significantly increased for visual acuity loss of >3 lines, recurrence/new tumor, exenteration, locoregional and systemic melanoma-related metastasis, and melanoma-related death.
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http://dx.doi.org/10.1097/APO.0000000000000343DOI Listing
December 2020

Ocular Surface Squamous Neoplasia Managed With Primary Interferon α2b: A Comparative Analysis of 212 Tumors in Smokers Versus Nonsmokers.

Cornea 2020 Dec 3. Epub 2020 Dec 3.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA.

Purpose: To explore clinical features and outcomes of ocular surface squamous neoplasia (OSSN) treated with primary interferon (IFN)-α2b, based on patient cigarette smoking status.

Methods: Retrospective nonrandomized, interventional cohort study on 212 consecutive tumors in 194 patients, all of whom were treated with topical and/or injection IFNα2b.

Results: There were 88 tumors in 76 patients with current or past smoking history (smokers) and 124 tumors in 118 nonsmoking patients (nonsmokers). A comparison (smokers vs. nonsmokers) revealed smokers with more frequent bilateral disease (16% vs. 3%, P = 0.003), more frequent involvement of inferior forniceal (34% vs. 21%, P = 0.03) and inferior tarsal conjunctiva (38% vs. 24%, P = 0.04), greater mean number of clock hour involvement (4.1 vs. 3.5 clock hours, P = 0.04), and greater dome growth pattern (30% vs. 15%, P = 0.01). There was no difference regarding method of IFNα2b administration as topical (61% vs. 71%, P = 0.14), injection (10% vs. 6%, P = 0.32), or combination topical/injection (28% vs. 23%, P = 0.33). A comparison revealed smokers with more frequent recurrence after initial response (23% vs. 13%, P = 0.04). There was no difference regarding initial tumor response or time to response, treatment side effects, or systemic outcomes.

Conclusions: Regarding ocular surface squamous neoplasia, smokers more often display bilateral, dome-shaped tumors with inferior forniceal or tarsal involvement, and greater extent than nonsmokers. After treatment with topical and/or injection IFNα2b, control is equivalent, but smokers show greater recurrence.
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http://dx.doi.org/10.1097/ICO.0000000000002615DOI Listing
December 2020

Conjunctival melanoma: Risk factors for recurrent or new tumor in 540 patients at a single ocular oncology center.

Eur J Ophthalmol 2020 Nov 11:1120672120970393. Epub 2020 Nov 11.

Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

Purpose: To investigate risk factors for recurrent or new tumor in patients with conjunctival melanoma.

Methods: Retrospective review of patients with conjunctival melanoma managed on the Ocular Oncology Service, Wills Eye Hospital from 1974 to 2019.

Results: There were 540 patients with mean follow-up of 57.6 months, of whom 176 (33%) had recurrent or new tumor formation. Risk factors for recurrent or new tumor on univariate analysis included presentation at older age (OR: 1.02 [1.01-1.03] per 1-year increase in age,  = 0.002), history of prior conjunctival surgery (OR: 1.62 [1.05-2.49],  = 0.03), worse visual acuity at presentation (OR: 1.76 [1.04-2.98] per 1 log-unit increase,  = 0.04), more advanced AJCC clinical T-subcategory (OR: 1.08 [1.02-1.14] per 1 subcategory increase,  = 0.01), tumor primary location in tarsal conjunctiva (OR: 1.80 [1.09-2.98],  = 0.02), and secondary tumor involvement of the fornix (OR: 1.68 [1.06-2.65],  = 0.03), and eyelid (OR: 1.92 [1.07-3.43],  = 0.03). Risk factors on multivariate analysis using all demographics, clinical features, and tumor location included presentation at older age (OR: 1.02 [1.00-1.03],  = 0.01), history of prior conjunctival surgery (OR: 1.84 [1.16-2.94],  = 0.01), and more advanced AJCC clinical T-subcategory (OR: 1.07 [1.01-1.13] per one subcategory increase,  = 0.03).

Conclusion: On multivariate analysis, the strongest predictors of recurrent or new tumor formation following treatment of conjunctival melanoma included older age, history of prior conjunctival surgery, and advanced AJCC T-subcategory. These results suggest that earlier detection and the first surgery in conjunctival melanoma management are critical for prevention of recurrent or new tumor, and we recommend prompt referral to an experienced surgeon.
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http://dx.doi.org/10.1177/1120672120970393DOI Listing
November 2020

Photopsia and visual loss in a patient with lung cancer.

Indian J Ophthalmol 2020 Nov;68(11):2348

Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, United States.

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http://dx.doi.org/10.4103/ijo.IJO_58_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774178PMC
November 2020

Muir-Torre Syndrome Associated Periocular Sebaceous Neoplasms: Screening Patterns in the Literature and in Clinical Practice.

Ocul Oncol Pathol 2020 Aug 15;6(4):226-237. Epub 2020 Jan 15.

Department of Ophthalmic Pathology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Background: Muir-Torre syndrome (MTS) is defined clinically as the association of cutaneous sebaceous neoplasm and visceral malignancy. Ancillary tests are considered crucial for diagnosis. Although screening guidelines for MTS, including the Mayo MTS scoring system, have been proposed, there are no ophthalmic site-specific guidelines.

Summary: A literature review conducted by PubMed search for articles describing patients with periocular sebaceous neoplasm and MTS disclosed 31 publications describing 60 patients, 36 (60%) of whom fulfilled clinical criteria for MTS, 6 (10%) whose diagnosis was based on screening ancillary studies, 14 (23%) who fulfilled clinical criteria and had supporting screening ancillary studies, and 4 (7%) who fulfilled clinical criteria and had supporting diagnostic genetic testing. Most patients were male (34 vs. 15 females), with a median age of 59 years (range 37-79 years). The most common diagnosis was sebaceous carcinoma (40/60, 67%), followed by sebaceous adenoma (16/60, 27%), followed by other tumors with sebaceous differentiation (4/60, 6%). The periocular lesions were identified prior to visceral malignancy in 10 out of 45 (22%) cases, after visceral malignancy in 34 out of 45 (76%) cases, and concurrently with visceral malignancy in 1 out of 45 (2%) cases. Immunohistochemistry for mismatch repair proteins was performed in 41 out of 60 (68%) and 14 out of 38 (37%) of the tumors had lost MSH2. Based on Mayo-MTS scores of 2 or greater, and after removing visceral malignancies not included in their scoring algorithm, 26 out of 30 of patients (87%) with complete data were considered to be appropriate candidates for further work-up. A survey of current practice was conducted by questionnaires, distributed to ophthalmic pathologists, ocular oncologists, and oculoplastic surgeons from national and international professional societies. Of the 103 physicians who participated in the survey, 91 (88%) felt that MTS evaluation guidelines were not sufficiently clear.

Key Messages: Our findings suggest that Mayo MTS screening guidelines may be applicable to periocular sebaceous neoplasms. The uncertainty of ophthalmic specialists about optimal screening guidelines for MTS reflects the heterogeneity of defining criteria for MTS and limited molecular genetic data. Larger studies with detailed clinical, histopathologic, and molecular genetic data are required to formally assess screening guidelines for MTS in patients with periocular sebaceous neoplasms.
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http://dx.doi.org/10.1159/000504984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506251PMC
August 2020

Immunohistochemical Profiling of Conjunctival Melanocytic Intraepithelial Lesions, Including SOX10, HMB45, Ki67, and P16.

Am J Ophthalmol 2021 02 28;222:148-156. Epub 2020 Sep 28.

Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Department of Pathology, Wills Eye Hospital, Philadelphia, Pennsylvania, USA.

Purpose: To determine the usefulness of melan-A, SOX10, HMB45, and p16 immunohistochemical stains in the distinction between the low-grade and high-grade conjunctival melanocytic intraepithelial lesions, either independently or as components of an immunohistochemical panel.

Design: Retrospective observational case series.

Methods: Institutional pathology records between 2014 and 2018 were searched for all patients with conjunctival melanocytic intraepithelial lesions. Biopsies without supporting clinical history or tissue available for review and immunohistochemical analysis were excluded. Clinical, histopathologic, and immunohistochemical (p16, SOX10, HMB45, and Ki-67) findings were recorded.

Results: Thirty-one patients underwent 47 biopsies for conjunctival melanocytic lesions between 2014 and 2018. Pathologic diagnoses were low-grade conjunctival melanocytic intraepithelial lesion (n = 18, 38%) and high-grade conjunctival melanocytic intraepithelial lesion/melanoma in situ (n = 29, 62%). The addition of melan-A and SOX10 immunohistochemical stains resulted in an upgrade of conjunctival melanocytic intraepithelial lesion from low-grade to high-grade in 2 (4%) of 47 cases. The addition of melan-A and SOX10 immunohistochemical stains did not downgrade any of the histomorphologically high-grade lesions. In a clinical-pathologic multivariable model, the parameters most predictive of high-grade melanocytic intraepithelial lesion/melanoma in situ were involvement of the caruncle (odds ratio [OR] = 19, confidence interval [CI] 1.6-212; P = .02] and p16 cytoplasmic H-score >30 (OR = 81, CI 2.7 to >999; P = .01) CONCLUSION: Although the stains for melanocytic markers melan-A and SOX10 facilitate assessment of melanocytic intraepithelial lesions, the current immunohistochemical panels have limited value in distinction between the low-grade and high-grade intraepithelial melanocytic proliferations and need to be used judiciously.
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http://dx.doi.org/10.1016/j.ajo.2020.09.033DOI Listing
February 2021

In the Context of Cicatricial Disease.

JAMA Ophthalmol 2020 10;138(10):1095-1096

Department of Ophthalmology, Wills Eye Hospital, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1001/jamaophthalmol.2020.1606DOI Listing
October 2020

Ophthalmic Manifestations of Rosai-Dorfman Disease in Five Patients.

J Curr Ophthalmol 2020 Jul-Sep;32(3):238-243. Epub 2020 Jul 4.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

Purpose: To report clinical features, pathology characteristics, and treatment outcomes of five patients with Rosai-Dorfman disease (RDD).

Methods: A retrospective case series of patients with RDD from the Ocular Oncology Service of Wills Eye Hospital between 1974 and 2018.

Results: There were six eyes of five patients (3 males, 2 females) with ophthalmic manifestations of RDD. The mean age at the initial presentation was 33 years (median 35, range 10-52 years). Before referral, the tumor was initially suspected to be lymphoma ( = 3), idiopathic orbital inflammation ( = 2), or pterygium ( = 1). The disease was unilateral ( = 4) or bilateral ( = 1). The mean duration of symptoms was 9 months (median 8, range 5-24 months). The disease produced nodules in the conjunctiva ( = 4) or orbit ( = 2). Two patients with conjunctival involvement had corneal involvement. One patient with bilateral conjunctiva lesions demonstrated bilateral orbital involvement and bilateral anterior uveitis. The mean tumor basal dimension was 13 mm (median 9, range 6-27 mm) for conjunctiva lesions and 37 mm (median 37, range 34-40 mm) for orbital lesions. The main symptom (per patient) included proptosis ( = 2), palpable mass ( = 1), and foreign body sensation ( = 2). No patient experienced pain or tenderness. Palpable, nontender lymphadenopathy was detectable in two patients in the cervical and inguinal lymph nodes. Systemic involvement with paranasal sinusitis and mediastinal/pulmonary lymphadenopathy occurred in two patients, both with orbital involvement. Surgical resection was performed for all patients. At a mean follow-up of 31 months (median 12, range, 10-76 months) after the surgery, tumor control was achieved in all six eyes without local recurrence.

Conclusion: In this series of six eyes with RDD, patients with orbital and/or intraocular disease were more likely to demonstrate lymphadenopathy and systemic involvement, while those with unilateral perilimbal conjunctival tumors remained localized.
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http://dx.doi.org/10.4103/JOCO.JOCO_84_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382521PMC
July 2020

Conjunctival Melanoma: Outcomes Based on Age at Presentation in 629 Patients at a Single Ocular Oncology Center.

Cornea 2021 May;40(5):554-563

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA. Dr. Dalvin has an appointment with the Department of Ophthalmology, Mayo Clinic, Rochester, MN.

Purpose: To investigate the clinical features and outcomes for conjunctival melanoma based on patient age.

Methods: A retrospective review of patients with conjunctival melanoma managed at a single tertiary referral center from April 18, 1974, to September 9, 2019. Clinical features and outcomes were compared by patient age category at presentation (young ≤45 years, middle-aged 46-69 years, and older ≥70 years), with Kaplan-Meier and Cox proportional hazard analysis [hazard ratio (95% confidence interval)].

Results: There were 629 patients categorized as young in 130 (21%), middle-aged in 278 (44%), and older in 221 (35%). A comparison by age category (young vs. middle-aged vs. older) revealed that older patients had melanoma with greater number of affected quadrants (1.7 vs. 1.8 vs. 2.0, P = 0.001) and clock hours (3.9 vs. 4.2 vs. 5.2, P = 0.001). All patients were treated with surgical excision, with no difference in requirement for additional medical or radiation therapy. By 10-year Kaplan-Meier outcomes, older patients had more frequent visual acuity loss ≥3 lines (11% vs. 28% vs. 64%, P < 0.001) and local tumor recurrence (38% vs. 46% vs. 70%, P < 0.001). Hazard ratio for the oldest age group (age ≥70) revealed a 7.76-fold (3.33-18.09) increased risk for visual acuity loss (P < 0.001), and a 2.08-fold (1.32-3.28) increased risk of local tumor recurrence (P = 0.002). There was no difference by age in risk for enucleation, exenteration, locoregional lymph node involvement, distant systemic metastasis, or death.

Conclusions: Older patients with conjunctival melanoma present with more extensive disease and have increased risk for visual acuity loss and local tumor recurrence.
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http://dx.doi.org/10.1097/ICO.0000000000002449DOI Listing
May 2021

Eye cancer in a young male with a vaping history.

Indian J Ophthalmol 2020 Aug;68(8):1699-1701

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

We report a new observation of conjunctival intraepithelial neoplasia (CIN) in a young man following years of electronic cigarette use. A 22-year-old man with a 5-year electronic cigarette use (vaping) developed painless unilateral blurred vision in the right eye from mild superficial corneal opacification, unresponsive to topical antiviral therapy. Corneal scraping documented no infectious etiology. The abnormality persisted for 1 year and superficial keratectomy revealed high-grade CIN with enlarged pleomorphic and dyskeratotic cells. Interferon-alpha-2b was instituted. In this case, chronic exposure to electronic cigarette vapors (vaping) could have been associated with CIN in this young patient.
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http://dx.doi.org/10.4103/ijo.IJO_27_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640851PMC
August 2020

Conjunctival nevi and melanoma: multiparametric immunohistochemical analysis, including p16, SOX10, HMB45, and Ki-67.

Hum Pathol 2020 09 21;103:107-119. Epub 2020 Jul 21.

Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, 19107, USA; Department of Pathology, Wills Eye Hospital, Philadelphia, PA, 19107, USA.

The role of p16 in the diagnosis and prognosis of conjunctival melanocytic lesions in the context of other clinical and immunohistochemical parameters has not been systematically explored. This study was conducted to determine whether p16 is a useful parameter in the diagnosis and prognosis of conjunctival melanocytic nevi and melanoma, either independently or as a component of immunohistochemical panels. Sixty-one patients underwent 61 biopsies for conjunctival melanocytic lesions between 2014 and 2018. Pathologic diagnoses were melanoma (n = 25, 41%), nevus (n = 21, 34%), and conjunctival melanocytic lesion of uncertain malignant potential (n = 15, 25%). The biopsies were assessed for expression of p16, SOX10, HMB45, and Ki-67. In a multivariable model, the parameters most predictive of melanoma versus nevus were diffuse HMB45 staining (odds ratio [OR] = 45, confidence interval [CI] = 4.4-457, P = .02] and p16 nuclear H-score≤115 (OR = 9.5, CI = 1.2-77; P = .04). There was no association of p16 expression with melanoma thickness. Next-generation sequencing identified no CDKN2A mutations or copy number alterations in 12 conjunctival melanomas, including the tumors with absent p16 expression. This study demonstrates that p16 immunohistochemical stain is useful in distinguishing conjunctival melanocytic nevi from melanoma, particularly in combination with HMB45. P16 expression does not appear to correlate with CDKN2A status and melanoma thickness.
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http://dx.doi.org/10.1016/j.humpath.2020.07.020DOI Listing
September 2020

Lacrimal Gland Hamartoma (Formerly Termed Dacryoadenoma).

Am J Ophthalmol 2020 09 29;217:189-197. Epub 2020 Apr 29.

Department of Pathology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA.

Purpose: Since the original description of "dacryadenoma" by Jakobiec and associates, the data on this unusual epibulbar lacrimal gland lesion remain sparse. The aim of this study was to characterize clinically, morphologically, and immunohistochemically this isolated epibulbar lacrimal gland lesion.

Design: Retrospective observational case series.

Methods: Institutional pathology records between 2000 and 2019 were searched for all cases of isolated epibulbar lacrimal gland lesions. Tissue from 3 normal lacrimal glands and 1 complex choristoma were included for comparative analysis. Clinical, histopathologic, and immunohistochemical findings were recorded.

Results: Four patients with isolated epibulbar lacrimal gland lesions, 2 male and 2 female, with a median age of 18 years (range, 12-57) were identified. All patients presented with recent onset of unilateral pink-to-orange, well-circumscribed subepithelial juxtaforniceal (3/4, 75%), or nasal (1/4, 25%) bulbar conjunctival nodules, which were asymptomatic (3/4, 75%) or associated with foreign body sensation (1/4, 25%). When compared with the normal lacrimal gland and complex choristoma, all isolated epibulbar lacrimal gland lesions were composed predominantly of variably dilated, branching tubular structures with pseudo-apocrine snouts, and either totally absent (2/2, 50%) or rare (2/2, 50%) ducts and rare acinar zymogen granules (3/4, 75%).

Conclusion: Our study confirms that a subset of isolated epibulbar lacrimal gland lesions differs morphologically and immunohistochemically from normal lacrimal gland tissue and the lacrimal gland in a complex choristoma. These differences range from subtle to overt, suggesting that isolated epibulbar lacrimal gland lesions may have originated from precursor cellular elements indigenous to the conjunctiva (hamartia) and grew into disorganized lacrimal gland tissue.
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http://dx.doi.org/10.1016/j.ajo.2020.04.015DOI Listing
September 2020

Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma with Myxoid Stroma in a Hereditary Retinoblastoma Survivor.

Ocul Oncol Pathol 2020 Mar 8;6(2):79-86. Epub 2019 Aug 8.

Department of Ophthalmology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) is an indolent, locally aggressive mesenchymal neoplasm, most often confined to the lower extremities and retroperitoneum and rarely identified in the orbit. Diagnosis of ALT/WDL can be challenging due to its frequent morphologic overlap with benign adipose lesions and other more aggressive liposarcoma subtypes, including myxoid liposarcoma. We describe a 26-year-old female with a history of hereditary retinoblastoma and external-beam radiotherapy to the orbit, who developed orbital liposarcoma. Although initial morphologic assessment raised the consideration of myxoid liposarcoma, subsequent fluorescein in situ hybridization studies demonstrated and coamplification without rearrangement, supporting the diagnosis of ALT/WDL with myxoid stroma. The literature review of previously reported orbital myxoid liposarcomas revealed a morphologic overlap of documented tumors with ALT/WDL, dedifferentiated liposarcoma, and pleomorphic liposarcoma with myxoid stroma as well as an absence of immunohistochemical and molecular genetic data supportive of the diagnosis of myxoid liposarcoma. This case emphasizes the potential overlap of ALT/WDL with myxoid liposarcoma and the increasing importance of molecular genetic studies in the diagnosis, prognosis, and management of orbital liposarcoma.
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http://dx.doi.org/10.1159/000501523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109428PMC
March 2020

Controlling Conjunctival Melanoma-To Infinity and Beyond.

JAMA Ophthalmol 2020 06;138(6):608-609

Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1001/jamaophthalmol.2020.0522DOI Listing
June 2020

Conjunctival Melanoma: Features and Outcomes Based on the Fitzpatrick Skin Type in 540 Patients at a Single Ocular Oncology Center.

Ophthalmic Plast Reconstr Surg 2020 Sep/Oct;36(5):490-496

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.

Purpose: To determine the association of Fitzpatrick skin type (FST) with conjunctival melanoma.

Methods: Retrospective case series of 540 patients with conjunctival melanoma to assess clinical features and outcomes per FST.

Results: The FST was Type I (n = 126, 23%), II (n = 337, 62%), III (n = 56, 10%), IV (n = 8, 2%), V (n = 12, 2%), and VI (n = 1, <1%). A comparison (FST I vs. II vs. III, IV, V, and VI) revealed Types I and II associated with older mean patient age (63.9 vs. 60.7 vs. 51.1 years, p < 0.001), greater percentage of female patients (68% vs. 44% vs. 42%, p < 0.001), lower frequency of complexion associated melanosis (1% vs. 2% vs. 13%, p < 0.001), smaller tumor thickness (2.1 vs. 2.8 vs. 3.6 mm, p = 0.01), and less eyelid involvement (13% vs. 13% vs. 28%, p = 0.02). Kaplan-Meier estimates for 5-year risk showed no difference by Types for visual acuity loss ≥3 lines, local tumor recurrence, exenteration, metastasis, or death.

Conclusion And Relevance: Most patients with conjunctival melanoma show FST I or II, and this demonstrated no association with 5-year rate of vision loss, tumor recurrence, exenteration, metastasis, or death.
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http://dx.doi.org/10.1097/IOP.0000000000001624DOI Listing
March 2021

Long-term (20-year) real-world outcomes of intravenous chemotherapy (chemoreduction) for retinoblastoma in 964 eyes of 554 patients at a single centre.

Br J Ophthalmol 2020 11 12;104(11):1548-1555. Epub 2020 Feb 12.

Department of Pediatric Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Background: Intravenous chemotherapy (IVC) remains an important globe salvage therapy for retinoblastoma.

Methods: Evaluation of long-term globe salvage at 5, 10, 15 and 20 years following frontline IVC for retinoblastoma.

Results: Of 994 eyes, comparison by International Classification of Retinoblastoma group (A vs B vs C vs D vs E) revealed more advanced group with older mean age at presentation (8 vs 7 vs 10 vs 11 vs 15 months, p<0.001). By clinical features, more advanced group demonstrated greater mean tumour diameter (3.2 vs 6.8 vs 9.4 vs 14.3 vs 16.4, p<0.001) and thickness (2.0 vs 3.7 vs 4.4 vs 7.3 vs 9.3, p<0.001), and greater frequency of vitreous seeds ≥1 quadrant (0% vs 0% vs 44% vs 42% vs 57%, p<0.001) and subretinal seeds (0% vs 0% vs 22% vs 65% vs 54%, p<0.001). By outcomes, less advanced group demonstrated greater tumour control (without need for enucleation or external beam radiotherapy (EBRT)) by year 2 (96% vs 91% vs 91% vs 71% vs 32%, p<0.001), and with minimal change up to 20 years. In order to achieve globe salvage, additional intra-arterial chemotherapy (IAC) or plaque radiotherapy was employed by year 2 (5% vs 26% vs 28% vs 27% vs 19%, p<0.001), with little further need up to 20 years. Pinealoblastoma (2%), metastasis (2%) and death (1%) were infrequent.

Conclusion: Frontline IVC (plus additional IAC and/or plaque radiotherapy) for retinoblastoma provided complete tumour control for groups A (96%), B (91%), C (91%), D (71%) and E (32%), avoiding enucleation or EBRT and was lasting for up to 20 years.
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http://dx.doi.org/10.1136/bjophthalmol-2019-315572DOI Listing
November 2020

Conjunctival 'mucoepidermoid carcinoma' revisited: a revision of terminology, based on morphologic, immunohistochemical and molecular findings of 14 cases, and the 2018 WHO Classification of Tumours of the Eye.

Mod Pathol 2020 07 13;33(7):1242-1255. Epub 2020 Jan 13.

Sheffield Ocular Oncology Service, Department of Ophthalmology, A-Floor, Royal Hallamshire Hospital, Sheffield, S10 2JF, UK.

In 2018, the consensus meeting for the WHO Classification of Tumours of the Eye decided that conjunctival mucoepidermoid carcinoma should be reclassified as adenosquamous carcinoma, as this represented a better morphological fit. To examine the applicability of this terminology, we studied the clinical, histopathological, immunohistochemical and molecular pathology of 14 cases that were originally diagnosed as conjunctival mucoepidermoid carcinoma. There were 7 (50%) females and 7 (50%) males. The median age was 64 years. The left eye was affected in 8 and the right eye in 6 patients. In-situ carcinoma was present in 11/14 (79%) cases and comprised in-situ squamous cell carcinoma (SCC) and conjunctival intraepithelial neoplasia with mucinous differentiation (CIN-Muc). Invasive carcinoma was present in 11/14 (79%) cases. Group 1 (1/11 cases, 9%) comprised invasive SCC only. Group 2 (6/11 cases, 55%) comprised SCC with mucinous differentiation, manifesting as scattered intracellular mucin, occasionally together with intercellular mucin, with no evidence of true glandular differentiation. Group 3 (3/11 cases. 27%) comprised true adenosquamous carcinoma. Group 4 (1/11 cases, 9%) comprised pure adenocarcinoma. Thirteen of 14 cases (93%) underwent FISH for MAML2 translocation and none were rearranged. Two cases harboured high-risk HPV (type 16 and 18). The combined findings confirm that all lesions in our study were not mucoepidermoid carcinoma, but represented predominantly SCC with mucinous differentiation and adenosquamous carcinoma. We, therefore, recommend future revision of the WHO classification to include SCC with mucinous differentiation alongside adenosquamous carcinoma.
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http://dx.doi.org/10.1038/s41379-020-0456-9DOI Listing
July 2020

Conjunctival melanoma with orbital invasion and liver metastasis managed with systemic immune checkpoint inhibitor therapy.

Indian J Ophthalmol 2019 12;67(12):2071-2073

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

A 60-year-old Caucasian female was referred for biopsy-proven amelanotic orbito-conjunctival melanoma. Map biopsies revealed residual invasive melanoma on the deep tarsal margin at the site of previous surgery. Repeat excisions were required after recurrence was detected following 3 months and 7 months. Positron emission tomography scan detected liver metastasis and additional orbito-conjunctival melanoma recurrence. Biomarker testing showed NRAS mutation without BRAF or c-KIT mutations and without PD-L1 expression. Systemic checkpoint inhibitor therapy was initiated with regression of both the orbito-conjunctival melanoma and liver metastasis. Invasive, non resectable orbito-conjunctival melanoma with liver metastasis can demonstrate a response to systemic checkpoint inhibitor therapy.
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http://dx.doi.org/10.4103/ijo.IJO_663_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896557PMC
December 2019

Idiopathic Orbital Pseudotumor Preceding Systemic Inflammatory Disease in Children.

J Pediatr Ophthalmol Strabismus 2019 Nov;56(6):373-377

Purpose: To describe four pediatric cases in which isolated orbital pseudotumor preceded the development of a systemic inflammatory disease by months to years.

Methods: The medical records of all patients with the clinical diagnosis of orbital pseudotumor seen at the Ocular Oncology Service of Wills Eye Hospital and Northern Virginia Ophthalmology Associates from 2010 to 2015 were reviewed retrospectively, and those associated with systemic inflammatory disease were selected for further study. Data were retrospectively collected from medical record review regarding patient demographics and clinical features, time to development of systemic inflammatory disease, and medical management.

Results: In four pediatric patients, isolated orbital pseudotumor preceded the development of a systemic inflammatory disease, including pauciarticular juvenile idiopathic arthritis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), and Crohn's disease.

Conclusions: Orbital pseudotumor may be an antecedent to systemic inflammatory disease in children. Because this was a small case series, the authors are not ready to suggest that a full systemic work-up for systemic inflammatory disease is warranted for every patient with orbital pseudotumor. However, close observation and suspicion for systemic inflammatory conditions may be reasonable in children who present with idiopathic orbital pseudotumor. [J Pediatr Ophthalmol Strabismus. 2019;56(6):373-377.].
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http://dx.doi.org/10.3928/01913913-20190923-02DOI Listing
November 2019

Tubular apocrine adenoma of the eyelid - A case report and literature review.

Saudi J Ophthalmol 2019 Jul-Sep;33(3):304-307. Epub 2019 Jul 26.

Department of Pathology, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

Tubular apocrine adenoma is a rare benign adnexal neoplasm most commonly identified in the scalp, composed of a dermal proliferation of apocrine tubules in a background of hyalinized stroma. Tubular apocrine adenoma can be a component of various sweat gland tumors and can also morphologically overlap with other sweat gland neoplasms. Isolated tubular apocrine adenoma arising in the glands of Moll is exceedingly rare, with only 4 previously reported cases. We present a 63-year-old male with tubular apocrine adenoma of the left upper eyelid, which recurred following initial incomplete excision. Although the lesion showed focal morphologic similarity to the apocrine variant of pleomorphic adenoma (chondroid syringoma), the diagnosis of tubular apocrine adenoma was supported by fluorescence in situ hybridization studies, which demonstrated absence of and gene rearrangements seen in pleomorphic adenoma. This case illustrates the clinical, microscopic and immunohistochemical features of tubular apocrine adenoma. The recent advances in our understanding of the molecular genetics of tubular apocrine adenoma and related tumors, and how these advances shape the evolving classification of sweat gland tumors are reviewed.
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http://dx.doi.org/10.1016/j.sjopt.2019.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819710PMC
July 2019

A simple pingueculum or not?

Indian J Ophthalmol 2019 11;67(11):1792

Wills Eye Hospital, Philadelphia, PA, USA.

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http://dx.doi.org/10.4103/ijo.IJO_1831_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836611PMC
November 2019

Eyelid chalazion or not?

Indian J Ophthalmol 2019 10;67(10):1519

Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

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http://dx.doi.org/10.4103/ijo.IJO_1620_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786182PMC
October 2019

Conjunctival Melanocytic Nevi With Granular Cell Change.

Arch Pathol Lab Med 2020 04 30;144(4):457-465. Epub 2019 Aug 30.

From the Department of Ophthalmic Pathology (Drs Eiger-Moscovich, Eagle, and Milman) and the Ocular Oncology Service (Drs Lally, C. L. Shields, and J. A. Shields), Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania; the Institute of Ophthalmology and Visual Science, Rutgers University, Newark, New Jersey (Dr Langer); the Department of Ophthalmology, University of Washington, Seattle (Dr Sheehan); and the Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia (Dr Milman).

Context.—: Granular cell change in melanocytic nevus is underrepresented in the literature with only 4 well-documented cases, 1 described in the conjunctiva. Unfamiliarity with the clinical and pathologic features of these lesions contributes to the diagnostic difficulty.

Objective.—: To delineate the clinical and histopathologic features of conjunctival nevi with granular cell change.

Design.—: In a retrospective observational case series, the medical records of all patients with conjunctival nevi and granular cell change diagnosed between December 2016 and October 2018 were reviewed. Data collected included age, sex, clinical presentation, pathologic findings, and follow-up.

Results.—: Twelve patients, 6 males and 6 females, with a median age of 14 years (range, 8-82 years) were identified. The nevus manifested as a pigmented, well-circumscribed nodule (7 of 9; 78%) or patch (2 of 9; 22%) in the bulbar and limbal conjunctiva (7 of 9; 78%) or in the plica semilunaris/caruncle (2 of 9; 22%). Cysts were noted in 7 of 9 lesions (78%). Features prompting surgical excision included atypical pigmentation (8 of 9; 89%), growth (7 of 9; 78%), and atypical vascularity (4 of 9; 44%). Microscopically, all lesions comprised a conventional melanocytic nevus with focal granular cell change and immunoreactivity for Melan-A, SOX10, and HMB-45, with Ki-67 proliferative index of less than 2%. Of the 9 lesions with follow-up information, there were no recurrences over mean follow-up of 11.2 months (range, 1-23 months).

Conclusions.—: Granular cell change in melanocytic nevi is an underrecognized finding that can simulate melanoma clinically and histopathologically. Young age at diagnosis, lack of associated conjunctival melanosis, bulbar location, cysts, and the absence of mitotic figures with a low Ki-67 proliferative index are helpful clinical and pathologic diagnostic clues.
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http://dx.doi.org/10.5858/arpa.2019-0053-OADOI Listing
April 2020

Unilateral enophthalmos.

Indian J Ophthalmol 2019 08;67(8):1264

Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

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http://dx.doi.org/10.4103/ijo.IJO_1019_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677040PMC
August 2019

IsomiRs and tRNA-derived fragments are associated with metastasis and patient survival in uveal melanoma.

Pigment Cell Melanoma Res 2020 01 16;33(1):52-62. Epub 2019 Aug 16.

Computational Medicine Center, Thomas Jefferson University, Philadelphia, Pennsylvania.

Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults. With over 50% of patients developing metastatic disease, there is an unmet need for improved diagnostic and therapeutic options. Efforts to understand the molecular biology of the disease have revealed several markers that correlate with patient prognosis, including the copy number of chromosome 3, genetic alterations in the BAP1, EIF1AX and SF3B1 genes, and other transcriptional features. Here, we expand upon previous reports by comprehensively characterizing the short RNA-ome in 80 primary UVM tumor samples. In particular, we describe a previously unseen complex network involving numerous regulatory molecules that comprise microRNA (miRNAs), novel UVM-specific miRNA loci, miRNA isoforms (isomiRs), and tRNA-derived fragments (tRFs). Importantly, we show that the abundance profiles of isomiRs and tRFs associate with various molecular phenotypes, metastatic disease, and patient survival. Our findings suggest deep involvement of isomiRs and tRFs in the disease etiology of UVM. We posit that further study and characterization of these novel molecules will improve understanding of the mechanisms underlying UVM, and lead to the development of new diagnostic and therapeutic approaches.
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http://dx.doi.org/10.1111/pcmr.12810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928426PMC
January 2020

Authors' Reply.

Middle East Afr J Ophthalmol 2019 Jan-Mar;26(1):53

Ocular Oncology Service and Department of Pathology, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

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http://dx.doi.org/10.4103/meajo.MEAJO_294_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507375PMC
February 2020

Heterochromia following intravitreal chemotherapy in two cases.

J AAPOS 2019 08 27;23(4):241-243. Epub 2019 Apr 27.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address:

Intravitreal chemotherapy is recognized as an effective treatment for retinoblastoma with vitreous (and occasionally subretinal) seeding refractory to intravenous or intra-arterial chemotherapy. However, this treatment carries with it the risk of toxicity to both the posterior and anterior segments of the eye, including retinal pigment epithelial mottling, ischemic/hemorrhagic retinopathy, posterior synechia, cataract, scleral necrosis, and focal iris depigmentation. We report 2 cases of iris heterochromia secondary to profound iris stromal depigmentation following intravitreal melphalan and topotecan injections.
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http://dx.doi.org/10.1016/j.jaapos.2019.03.002DOI Listing
August 2019

Delayed implant infection with () 30 years after silicone sheet orbital floor implant.

Orbit 2020 Apr 25;39(2):139-142. Epub 2019 Apr 25.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

: To report a case of delayed implant infection with (, previously known as ) 30 years after silicone sheet orbital floor implant.: Case report with orbital imaging.: A 61-year-old male with a history of traumatic orbital floor fracture right eye (OD) repaired using a silicone sheet orbital floor implant 30 years prior, presented with 6 months of painless blepharoptosis and diplopia OD. On examination, there was 3 mm right upper eyelid blepharoptosis and hyperglobus. There was no globe proptosis, dysmotility, or compression and no cutaneous erythema, hyperthermia, discharge, or tenderness to palpation. Orbital magnetic resonance imaging (MRI) revealed a cystic mass in the inferior orbit in the region of the floor implant, measuring 25 mm in diameter and 10 mm in thickness. By MRI, T1-weighted images revealed a hypointense signal within the mass and T2-weighted images showed hyperintense signal with a flat hypointensity centrally representing the floor implant. Microbiologic cultures grew .: can manifest several decades after placement of an orbital prosthetic implant, leading to delayed infection.
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http://dx.doi.org/10.1080/01676830.2019.1605613DOI Listing
April 2020