Lindsay K. Klofas,Carley M. Bogan,Alice C. Coogan,Stephen J. Schultenover,Vivian L. Weiss,Anthony B. Daniels
To systematically evaluate and compare the effects of using small-gauge needles and vitrectors on the ability to obtain adequate diagnostic and prognostic uveal melanoma biopsy specimens.
Comparative evaluation of biopsy instruments.
Survival of uveal melanoma cells was evaluated in vitro following needle aspiration. Five therapeutically enucleated eyes were sampled in triplicate for ex vivo diagnostic biopsy experiments with 25 gauge (25 G) needle, 27 gauge (27 G) needle, and 27 G vitrector. During surgery in 8 patients, paired diagnostic transscleral fine needle aspiration biopsies were performed using both 25 G and 27 G needles. A review of cytologic specimens was performed by a panel of 3 expert cytopathologists. A retrospective chart review was performed to evaluate 100 consecutive tumors undergoing prognostic biopsy for gene expression profiling to assess the relationship between needle gauge and prognostic adequacy.
No significant cell shearing of uveal melanoma cells occurred in vitro with 25 G, 27 G, or 30 G needles. For ex vivo biopsy samples, diagnostic yield was 100% using 25 G needle (5/5) or 27 G vitrector (5/5) but 60% using a 27 G needle (3/5). For in vivo samples, no difference in diagnostic yield was found between 25 G (75%, 6/8) or 27 G (75%, 6/8) needle sizes. Of 100 molecular prognostic biopsy samples evaluated, 65 were obtained using 27 G needles; for these biopsies, the prognostic yield was 65/65 (100%).
For diagnostic biopsy of uveal melanoma, a larger-gauge needle or a 27 G vitrector may have better overall cellularity and diagnostic yield when compared to a 27 G needle. However, for much more common molecular prognostic testing, a 27 G needle provided adequate sample in 100% (65/65) of cases, and a larger needle provided no additional benefit.
Michael Kinori,Sharon Armarnik,Robert Listernick,Joel Charrow,Janice Lasky Zeid
This study reports on neurofibromatosis type 1 (NF1)-associated optic pathway gliomas (OPGs) and a follow-up period of at least 10 years in a cohort of children. OPGs are a common manifestation of NF1 and can cause significant visual morbidity. Long-term follow-up in children with NF1-associated OPGs has not been reported previously.
Retrospective observational case series.
This study included children with a documented follow-up of at least 10 years. Three final outcomes were evaluated: visual acuity (VA) per eye (i.e., in the more severely affected eye), VA per patient (i.e., VA when both eyes were open), and the presence of optic nerve head pallor.
A total of 45 children were included, followed for a mean of 14 years (range, 10-21 years). At the end of follow-up, abnormal VA (considered moderate to severe impairment) in the more severely affected eye was present in 36% of the patients and in both eyes in 11%. Optic nerve head pallor of 1 or both nerves was present in 62%. In multivariate analysis, only initial VA and optic nerve head appearance at presentation were found to predict the final outcomes. All patients, except for 1, were asymptomatic at presentation and had normal VA and nerves that appeared normal, preserved their good vision in both eyes. Only 1 patient, who had normal VA and normal appearing nerves at presentation, had moderate to severe VA loss at long term follow-up.
In this study, children with NF1-associated OPG whose examination signs and symptoms were normal had a normal initial examination and excellent long-term visual and anatomical outcomes. VA and the appearance of the optic nerve head at presentation predict long-term outcome.
Fausto de Souza D. · Tsering T. · Burnier M.N. · Bravo-Filho V. · Dias A.B.T. · Abdouh M. · Goyeneche A. · Burnier J.V.
Introduction: Acetylsalicylic acid (ASA) has been investigated for a potential anticancer role in several cancers, such as colorectal, ovarian, and endometrial cancer. Moreover, ASA has been shown to abrogate various processes that contribute to tumor growth and progression. Objective: The aim of this study was to evaluate the effects of ASA on cutaneous melanoma (CM) and uveal melanoma (UM). Methods: Human CM and UM cells were treated with 5 mM ASA and assessed for changes in cellular functions. Antiangiogenic effects of ASA were determined using an ELISA-based assay for 10 proangiogenic cytokines, and then validated by Western blot. Finally, proteomic analysis of ASA-treated cells was performed to elucidate the changes that may be responsible for ASA-mediated effects in melanoma cells. Results: Treatment with ASA significantly inhibited the proliferation, invasion, and migration capabilities, and caused a significant decrease in angiogenin and PIGF secretion in both CM and UM. Mass spectrometry revealed 179 protein changes associated with ASA in the CM and UM cell lines. Conclusions: These results suggest that ASA may be effective as an adjuvant therapy in metastatic CM and UM. Future studies are needed to determine the regulating targets that are responsible for the antitumor effects of ASA.
Kasturi N. · Gera P. · Panicker G. · Jossy A. · Rangarajan V. · Hanuman S.B.
Primary rhabdoid tumors are highly malignant, rare tumors occurring in the renal, extrarenal soft tissue or central nervous system. They have non-specific radiological features and present with several histological components that create a problem in differential diagnosis with other embryonal tumors. We report a rare case of malignant rhabdoid tumor of the retina that presented with clinical features like those of retinoblastoma.
Martino F. · Gelmi M.C. · Galluzzi P. · De Francesco S. · Miracco C. · Hadjistilianou D.
Introduction: A masquerade syndrome is an atypical presentation of a neoplastic process that mimics an inflammatory condition. In this paper, we focus on orbital pseudocellulitis. Case Series: Our case series includes 5 retinoblastoma patients with orbital pseudocellulitis at presentation. In 3 patients the disease was bilateral, in 1 trilateral, and in 1 unilateral. The eyes with pseudocellulitis were enucleated, while the fellow eyes were treated conservatively, when affected. Four patients responded well to the therapy and showed remission of the tumor. The patient with trilateral retinoblastoma did not respond to therapy and died of disease. Discussion: Differential diagnosis with infectious orbital cellulitis is extremely important. Patients with orbital cellulitis present with fever, sinusitis, leukocytosis, and raised inflammatory markers, while ophthalmoscopic examination is negative and imaging studies show sinus involvement. On the contrary, patients with retinoblastoma do not show systemic inflammation, while ophthalmoscopic examination reveals leukocoria, buphthalmos, and an intraocular tumor mass associated with retinal detachment. Magnetic resonance imaging shows intralesional calcifications and soft tissue edema without sinus involvement. Histology confirms the diagnosis. Conclusions: Medical history, physical examination, and imaging studies are crucial in the diagnosis of retinoblastoma-associated orbital pseudocellulitis. Retinoblastoma should be excluded in all patients with signs of pre-septal orbital cellulitis through fundoscopy and/or imaging studies
Yadav S. · Gupta N. · Singh R. · Patil M. · Meel R. · Vanathi M. · Kashyap S. · Tandon R.
Objective: To evaluate the adjunctive role of conjunctival autofluorescence in the management of ocular surface squamous neoplasia (OSSN). Materials and Methods: Seventeen patients with clinically diagnosed OSSN were included. Morphological characteristics, type of OSSN, and autofluorescence photographs of the lesion were captured. Presence and area of conjunctival ultraviolet autofluorescence (CUVAF) were the main outcome measures. Results: Overall, 17 patients with 15 (88%) primary and 2 (12%) recurrent OSSN were included. Common locations were temporal (n = 10), nasal (n = 5), and diffuse variety (n = 2). Morphologically, there were 4 (22.2%) nodular, 4 (22.2%) leucoplakic, 3 (16.7%) gelatinous, and 1 (5.5%) each of papillary, nodulo-ulcerative, and diffuse variety. Mixed morphology was present in 4 eyes (22.2%). Sixteen of 18 eyes (88.9%) with OSSN displayed autofluorescence on CUVAF images. The mean area of CUVAF was 15.82 mm2 (10.77–19.59 mm2). Autofluorescence was reported in 8 eyes (44.4%) which had negative reports on impression cytology. Conclusions: Conjunctival autofluorescence was seen in the majority of cases with OSSN, in spite of negative cytology reports. Our study demonstrates that CUVAF may serve as an effective ancillary, non-invasive, and resource-friendly tool for supplementing the clinical diagnosis of OSSN, especially in diffuse and recurrent lesions that are not amenable to surgical intervention.
Van Ly D. · Wang D. · Conway R.M. · Giblin M. · Liang S. · Lukeis R. · Lim L.-A. · Hesson L. · Cherepanoff S.
Uveal melanoma (UM) is the commonest primary intraocular malignancy in adults. There is limited published data on lipid production in UM. Here, we describe the clinical, histological, immunohistochemical, and molecular findings in a ciliochoroidal melanoma with lipid production and expression of the enzyme HMG-CoA reductase. This case highlights an unusual UM tumour phenotype with a high-risk molecular metastatic profile and discusses tumour lipogenesis and activation of the mevalonate pathway as a potential therapeutic target in managing lipidised ciliochoroidal UM.
Binkley E.M. · Sampson A.D. · Syed N.A. · Boldt H.C.
We describe a case of a 53-year-old man with a history of metastatic squamous cell carcinoma of the tonsil who presented with a large, dome-shaped, choroidal mass in the left eye with concern for extra-ocular extension. Standardized echography showed a choroidal mass with low-to-medium internal reflectivity, pockets of very low reflectivity, positive angle kappa, and 1+ vascularity that were concerning for primary choroidal melanoma. Biopsy of the lesion was consistent with metastatic squamous cell carcinoma of the tonsil rather than melanoma. This is only the second reported case of metastatic squamous cell carcinoma to the choroid presenting with a large vascular tumor with echographic characteristics consistent with choroidal melanoma. The unique vascularity present in some cases of squamous cell carcinoma of the tonsil may explain the vascularity and large height of this patient’s lesion. Tumor fine-needle aspiration biopsy can play an important role in patients with choroidal lesions in the setting of unusual primary tumors.
Meel R · Kashyap S. · Bakhshi S. · Singh Bajaj M. · Wadhwani M.
Objective: The aim of this work was to study the clinical and histopathology features and treatment outcome in retinoblastoma cases presenting at an older age (>6 years). Design: This was a retrospective study. We recruited 48 retinoblastoma patients who were treated at our institute over 7 consecutive years and were older than 6 years at presentation. Methods: Medical records were reviewed for data, including age at diagnosis, gender, laterality, family history, lag time, first symptom, misdiagnosis, clinical findings, grade and stage of disease at diagnosis, treatment, outcome, and follow-up status. Histopathology slides were reviewed and assessed for the presence of histopathological high-risk features (HRF) for metastasis. The main outcome measures were the frequency of atypical clinical features like hyphema, pseudohypopyon, glaucoma, cataract, vitreous hemorrhage, and phthisis, and misdiagnosis, prior intervention, stage of disease at presentation, and treatment outcome. Results: In total, 48/610 (7.8%) patients were older than 6 years, with a median age of 7 years (range 6–31). Retinoblastoma was bilateral in 7 cases. The most common initial symptom was white reflex followed by a decrease in vision. The median lag time was 9 months. Fourteen cases (29.2%) were misdiagnosed, with endophthalmitis the most common misdiagnosis. Twenty-six (54%) patients had intraocular disease, 12 (25%) had locally advanced disease, and 10 (21%) had metastatic disease at presentation. Overall, 67% (14/21) of the eyes that were enucleated upfront for presumed intraocular disease had histopathological HRF. At last follow-up, 31/36 (86%) who were treated were alive and healthy, while 5 (14%) patients had disease progression. Conclusions: This is the largest study of older age retinoblastoma and shows that it forms a significant percentage of retinoblastoma in developing countries, is misdiagnosed in one-third of cases, and may present at an advanced stage in 46% of cases.
Berry J.L. · Kim M.E. · Pefkianaki M. · Reid M. · Shah R. · Jubran R. · Kim J.W.
Introduction: Intravitreal melphalan (IVM) has emerged as an efficacious treatment for vitreous seeding in retinoblastoma. Although rarely severe, IVM-related toxicity may be treatment limiting. There is paucity of data on the impact of IVM toxicity on new tumor formation and ultimate globe salvage. Objectives: To investigate whether the grade of retinal toxicity post-IVM impacts retinal and seeding tumor recurrence, as well as the overall ability to salvage the eye. Methods: A single-institution retrospective chart review was performed on 47 eyes of 42 patients who received systemic intravenous chemotherapy followed by IVM as salvage treatment for persistent or recurrent vitreous seeding. Chorioretinal toxicity was graded from 0 to 5. Results: Toxicity grade was inversely associated with the risk of recurrence, where a one-unit increase in toxicity grade correlated with nearly a 54% reduction in the odds of tumor recurrence (OR 0.46 [0.25–0.84], p = 0.01). Similarly, toxicity grade was related to enucleation, where a one-unit increase in toxicity grade was associated with a 31% reduction in the odds of undergoing enucleation (OR 0.69 [0.40–1.18], p = 0.17). Conclusions: While retinoblastoma therapy aims to limit toxicity, especially visually significant toxicity, eyes with higher grades of post-IVM toxicity are less likely to have retinal and seeding tumor recurrence.