Vinodh Kakkassery MD, PhD,Sarah E. Coupland MD, PhD,Ludwig M. Heindl MD, PhD, MSc
Iris lymphomas are rare malignant neoplasms arising either as primary tumors in the iris or as secondary tumors involving the iris. We summarize previously published data and make recommendations for work-up strategies for cases of suspected iris lymphoma. Our objective is to provide a structured overview of the typical clinical symptoms and signs, the pathologic, ophthalmic, as well as hematologic work-up for diagnosis, treatment, and follow-up of iris lymphomas and offer a flowchart on how to diagnose and treat these tumors.
Ingvild Ramberg, Peter Bjerre Toft, Steffen Heegaard
Malignant tumors of epithelial origin are the most frequent neoplasms of the lacrimal drainage system (LDS). A total of 539 cases are reported in the literature from 1960 to 2019. LDS carcinoma is a disease of the middle-aged and elderly population, with a median age at diagnosis of 57 years. Overall, there is a slight male predominance. Reported risk factors are chronic inflammation, LDS papilloma, and infection with oncogenic viruses. Symptoms of an LDS carcinoma resemble those of benign, inflammatory diseases, with epiphora from obstruction of the LDS as the most frequently encountered symptom. The median time from symptoms to diagnosis is 12 months and even longer for patients reporting epiphora as the only initial symptom. This diagnostic delay leads to a substantial fraction of patients with locally advanced tumors and lymph node spread at the time of diagnosis. Surgery with adjuvant radiotherapy is the treatment of choice for most patients; however, the extension and aggressiveness of the disease and the patient’s general health and preferences determine the definite treatment. Five-year overall survival is reported to range from 61 to 87.6%. A large tumor size and positive lymph node status correlate with a decreased overall and disease-free survival.
Alexandra L. Farrall, Justine R. Smith
Primary central nervous system lymphoma (PCNSL) may manifest initially in the eye (termed vitreoretinal lymphoma or VRL) or in non-ocular CNS compartments, or in both. The nature of the onset of PCNSL implies two clinical specialists — ophthalmologists and neuro-oncologists — independently may assess the primary presentation of this rare malignancy. Clinically relevant perspectives on expectations of PCNSL manifestation in both ocular and non-ocular CNS compartments would help inform management practices in each specialty, which should impact clinical outcomes. A recent increase in the number of published PCNSL cohort studies provides new opportunity to review the current prevalence rates of ocular involvement, and the timing of this involvement over the course of disease. In PCNSL cohorts defined by non-ocular CNS compartment involvement, with or without ocular involvement (termed “PCNSL ± ocular involvement” cohorts), mean rates of concomitant VRL at diagnosis, or at any time during the course, are 10% and 16%, respectively. Only a few individuals within this cohort group present with exclusive eye disease (<5%), and the rate of secondary ocular involvement is only 5–9%. In PCNSL cohorts defined by the involvement of the ocular compartment, with or without non-ocular CNS involvement (termed “VRL ± non-ocular CNS involvement” cohorts), 58% of persons have a primary ocular diagnosis, which carries a 50% risk of secondary involvement in the CNS beyond the eye. Rates of non-ocular CNS involvement with VRL at diagnosis or over the course of disease are 41% and 69%, respectively.
Ankit Singh Tomar, Paul T. Finger, Codrin E. Iacob
Intraocular leiomyoma is a benign smooth muscle tumor. First recognized before the era of immunohistochemistry, uveal leiomyomas have been described in case reports and small case series. We add 3 new cases, for a total of 80. Of these, there were 29 men and 51 women. The mean and median ages were 35.8 and 30.5 years respectively, with a range of 8 to 80 years. Curiously, ciliary body tumors were more common in females, whereas iris and posterior choroidal leiomyomas were more prevalent in males. Infrequently associated with systemic fibroids, nuclear expression of sex steroid receptors was inconsistent. Iris and posterior choroidal leiomyoma were predominantly amelanotic, while 40% of ciliary body leiomyomas were brown. Two-thirds of the leiomyomas blocked transillumination partially or completely, a feature shared by uveal melanoma. In general, low-frequency ultrasound imaging reveals low to moderate internal reflectivity; however, high-frequency anterior uveal ultrasound was used to localize a leiomyoma as resident in the suprachoroidal space with an overlying layer of intact choroid. In the few cases examined by physiologic imaging, increased metabolic activity (typically associated with malignancy and inflammation) has been noted. We found that pigmented uveal leiomyomas can be clinically identical to melanoma. Therefore, histopathology with immunohistochemical staining for smooth muscle actin was the most reliable diagnostic method to differentiate pigmented uveal leiomyoma from melanoma. Treatment is governed by the clinical diagnosis, tumor size and location, as well as prognosis for vision and globe preservation.
Juan Valenzuela, Gabrielle A. Yeaney, Eric D. Hsi, Elizabeth M. Azzato, David M. Peereboom, Arun D. Singh
Twenty-eight patients were identified with large B-cell lymphoma of the uvea. Uveal involvement was iris (1 case), ciliary body (1 case), or choroidal in 14 cases. Panuveal involvement was observed in 12 cases. The clinical presentation could be categorized into uveitis (8), intraocular mass (9), neovascular glaucoma (4), and vascular disorders (4). The majority (21 cases, 77%) were diagnosed at autopsy (11) or after enucleation (10). Only 7 were diagnosed with conservative techniques. Histopathologically, 3 distinct subgroups of large B-cell lymphoma could be identified: 15 were characterized as diffuse large B-cell lymphoma, 11 as intravascular large B-cell lymphoma, and 2 as plasmablastic lymphoma. All cases had a poor prognosis, with a median survival of 14 months. Most cases (19, 67%) represented secondary uveal involvement with widespread systemic lymphoma at ophthalmic presentation. Six cases were treated with radiotherapy, most of these diagnosed before the 1990s (4). Subsequent cases (9) received systemic or local chemotherapy and adjunct radiotherapy, depending on the organs affected. Two cases were treated only with enucleation, and systemic treatment was not specified in 13 cases. Large B-cell lymphoma can rarely involve the uvea. The presenting features are nonspecific, often leading to enucleation. Effective therapy is not known. In all 3 variants, the aggressive nature and widespread involvement at ophthalmic presentation is associated with short survival.
Thonnie Rose O. See, Gustav Stålhammar, Tina Tang, Joshua S. Manusow, David R. Jordan, Jeffrey A. Nerad, Robert C. Kersten, Marc Yonkers, Nasreen A. Syed, Seymour Brownstein, Hans E. Grossniklaus
Primary ductal adenocarcinoma (PDA) is a rare epithelial tumor of the lacrimal gland. Herein we report 5 cases and review 29 published cases of PDA of the lacrimal gland. Among these 5 cases, the most common clinical presentation was painless swelling and/or proptosis of their eye. The size of the lesions ranged from 1.6 to 2.5 cm. Histopathologic examination revealed proliferations of ductal or gland-like cells with vesiculated pleomorphic nuclei and prominent nucleoli. Tumor cells stained positive for epithelial and apocrine differentiation markers. Immunohistochemistry for human epidermal growth factor 2 was positive in 2 of the 4 cases. Four of the five patients were alive at the last follow-up visit. One died with bone metastases, which were diagnosed 25 months after exenteration and then survived an additional 51 months. On reviewing of twenty-nine previously published cases of PDA, the mean age of diagnosis was 58 years, with a male predominance (75%). Fifteen patients (54%) had distant metastases, 1 (4%) had local recurrence, and 10 (37%) suffered from a PDA-related death. PDA is a high-grade aggressive epithelial tumor of the lacrimal gland. Although rare, awareness and recognition of this malignancy are important to help determine prognosis and treatment options.
Matthew A. DelMauro, Danielle C. Kalberer, I Rand Rodgers
Mohs micrographic surgery and reconstruction is considered by many as the gold standard for treatment of cutaneous malignancies arising in the periorbital region. It has a high rate of tumor clearance and a low rate of postsurgical complications. One of the most common complications is surgical site infection. Although surgical site infection occurs in less than 3% of patients, it may result in significant morbidity. Considerable research efforts have been devoted to identifying risk factors associated with the development of a postsurgical infection. We examine the impact of endogenous factors (which determine the efficacy of a patient’s immune system), exogenous factors (which influence a patient’s exposure to bacterial pathogens), and antimicrobial interventions on the incidence of surgical site infection and propose evidence-based recommendations.
Inbal Avisar, Yoav Nahum, Michael Mimouni, Israel Kremer, Raman Malhotra
The normal structure and function of the eyelids, eyelashes, conjunctival fornices, and lacrimal system are essential for the health of the ocular surface, and abnormalities of these structures accompany many cases of ocular surface disease. We describe the role of oculoplastic intervention in the context of ocular surface disease, focusing on blink disorders, lagophthalmos, entropion, lid scarring and keratinization, trichiasis, and punctal and lacrimal sac disease.
Frederick A. Jakobiec, Paula Cortes Barrantes, Daniel R. Lefebvre, Tatyana Milman
Over several months, a painless, multinodular, non-erythematous swelling of the deep tissues of his left upper eyelid developed in a 63-year-old man. An excisional biopsy with histopathologic evaluation disclosed a unique sebaceous papilloma within a cyst lined by non-keratinizing squamous epithelium that focally displayed a variably thick, superficial, eosinophilic cuticular layer. Immunohistochemical staining demonstrated that the tumor and its epithelial cystic lining had a profile consistent with Meibomian gland duct epithelium. Adipophilin highlighted cytoplasmic vacuolar lipid positivity. The encapsulation of the lesion, absence of nuclear atypia, and Ki-67 nuclear positivity restricted to the basilar cells established its intrinsically benign nature. The patient’s clinical history was remarkable for pulmonary and colonic carcinomas resected, respectively, 20 years and 8 years earlier. DNA mismatch repair protein expression studies disclosed loss of nuclear immunostaining of MSH6 protein, pointing to the possibility of an underlying rare MSH6 variant of the Muir-Torre syndrome, not yet described in the ophthalmic literature. p16 nuclear positivity was also found in the tumor cells, indicating the possible role of high-risk human papillomavirus as an additional factor in the genesis of the tumor. Genetic evaluation of normal and tumoral tissues in future similar cases will detect if there is an underlying germline mutation versus a somatic mutation limited to the tumor. This will be required to fully establish a predictable linkage with this new subtype of the Muir-Torre syndrome.
Lucio De Maria, Paolo De Sanctis, Megha Tollefson, Samir Mardini, James A. Garrity, Pearse P. Morris, Emily Bendel, Waleed Brinjikji
Percutaneous sclerotherapy is an alternative strategy for the treatment of vascular malformations of the orbital and periorbital regions. The safety and efficacy of sclerotherapy in this setting have not been fully established. We present the results of a systematic review and meta-analysis examining the safety and efficacy of percutaneous sclerotherapy for the treatment of vascular malformations of the orbit. We searched PubMed, MEDLINE, and EMBASE from 2000 to 2018 for studies evaluating the safety and efficacy of percutaneous sclerotherapy for orbital and periorbital vascular malformations. Two independent reviewers selected studies and abstracted data. The primary outcome of this study is the efficacy of sclerotherapy which includes complete response, partial response, or no response to sclerotherapy. Data were analyzed using random-effects meta-analysis. Thirteen studies reporting on 154 patients were included. The rate of complete cure after percutaneous sclerotherapy was 54.9% (95% confidence interval [CI] = 34.2%-75.7%). The rate of emergent decompressive surgery was 3.4% (95% CI = 0.5%-6.2%), and the rate of vision loss was 2.7% (95% CI = 0.1%-5.3%). I2 values were above 50% for most outcomes indicating substantial heterogeneity. Our systematic review and meta-analysis of 13 studies and over 150 patients found that percutaneous sclerotherapy is a safe and effective treatment modality for the treatment of low-flow vascular malformations of the orbit.