Specific location of ocular adnexal lymphoma and mortality: an international multicentre retrospective study.

AIMS: To examine whether the specific location of ocular adnexal lymphoma (OAL) and the American Joint Committee on Cancer (AJCC) TNM tumour stage are prognostic factors for mortality in the main OAL subtypes. METHODS: Clinical and survival data were retrospectively collected from seven international eye cancer centres. All patients from 1980 to 2017 with histologically verified primary or secondary OAL were included. Cox regression was used to compare the ocular adnexal tumour locations on all-cause mortality and disease-specific mortality. RESULTS: OAL was identified in 1168 patients. The most frequent lymphoma subtypes were extranodal marginal zone B-cell lymphoma (EMZL) (n=688, 59%); follicular lymphoma (FL) (n=150, 13%); diffuse large B-cell lymphoma (DLBCL) (n=131, 11%); and mantle cell lymphoma (MCL) (n=89, 8%). AJCC/TNM tumour-stage (T-stage) was significantly associated with disease-specific mortality in primary ocular adnexal EMZL and increased through T-categories from T1 to T3 disease. No associations between AJCC/TNM T-stage and mortality were found in primary ocular adnexal FL, DLBCL, or MCL. EMZL located in the eyelid had a significantly increased disease-specific mortality compared with orbital and conjunctival EMZL, in both primary EMZL and the full EMZL cohort. In DLBCL, eyelid location had a significantly higher disease-specific mortality compared with an orbital or lacrimal gland location. CONCLUSION: Disease-specific mortality is associated with AJCC/TNM T-stage in primary ocular adnexal EMZL patients. Lymphoma of the eyelid has the highest disease-specific mortality in primary EMZL, and in the full cohort of EMZL and DLBCL patients.

Epstein-Barr virus-associated lymphoma of the orbit: Case report and review of the literature.

Purpose: Herein, the authors describe an unusual presentation of EBV-associated diffuse large B-cell lymphoma in the bilateral orbits of an immunocompetent woman. Observations: An elderly, immunocompetent woman presented with an orbital mass which was biopsied and proven to be EBV-associated lymphoma. The authors then performed a literature search and review which suggested this presentation to be rare as it has been infrequently reported in the ophthalmic literature. Conclusions and importance: More research is needed to fully ascertain the importance of EBV in ocular adnexal lymphoma. The authors hope this case report adds to the body of literature a different presentation of EBV-associated ocular adnexal lymphoma.

Malignant peripheral nerve sheath tumor of the orbit: a case report and review of the literature.

Malignant peripheral nerve sheath tumor is a rare tumor which infrequently involves the orbit. They occur most often in the setting of neurofibromatosis 1 (NF1), and therefore the involvement of the orbit without a history of NF1 is even less common. Management of this tumor is fraught with a high rate of recurrences and metastases, with a high mortality rate. Primary surgical excision with tumor-free margins remains the primary treatment, while adjuvant modalities such as radiation and chemotherapy play a more minor role.

Overlapping Immunohistochemical Features of Adenocarcinoma of the Nonpigmented Ciliary Body Epithelium and Renal Cell Carcinoma.

PURPOSE: To find immunohistochemical markers that distinguish adenocarcinoma of the nonpigmented ciliary epithelium (NPCE) from metastatic carcinoma, especially metastatic renal cell carcinoma. DESIGN: Retrospective case series. METHODS: Three cases of adenocarcinoma of the NPCE were examined histologically with hematoxylin-eosin stain and immunohistochemical stains including vimentin, AE1/AE3, Cam 5.2, CK7, PAX2, PAX8, AMACR, and CAIX. We also reviewed previously reported cases of this tumor. RESULTS: We found that the immunohistochemical profile of adenocarcinoma of the NPCE can overlap with renal cell carcinoma. Both tumors can express vimentin, cytokeratin AE1/AE3, Cam 5.2, PAX2, PAX8, and AMACR. One of the adenocarcinomas of the NPCE in our series also expressed CD10 and the renal cell carcinoma marker (RCC Ma). Carbonic anhydrase IX (CAIX) was not detected in any of the 3 tumors. CONCLUSIONS: Adenocarcinomas arising in phthisic eyes can be diagnostically challenging. We have found it particularly difficult to distinguish adenocarcinoma of the NPCE from metastatic carcinoma, especially metastatic clear cell renal cell carcinoma and papillary renal cell carcinoma. Because of the immunophenotypic overlap, most patients will require systemic workup including imaging of the kidneys to be certain of the diagnosis.

Lymphoma of the Lacrimal Gland - An International Multicenter Retrospective Study.

PURPOSE: To characterize the clinical features of subtype-specific lacrimal gland lymphoma and their effect on patient survival. DESIGN: Multicenter retrospective interventional case series. METHODS: Patient data were collected from 6 international eye cancer centers from January 1, 1980, through December 31, 2017. All patients with histologically verified primary or secondary lymphoma of the lacrimal gland were included. Primary endpoints were overall survival (OS) and disease-specific survival (DSS). RESULTS: A total of 260 patients with lacrimal gland lymphoma were identified. The median age was 58 years and 52% of patients were men. Non-Hodgkin B-cell lymphomas constituted 99% (n = 258) and T-cell lymphomas constituted 1% (n = 2). The most frequent lymphoma subtypes were extranodal marginal zone B-cell lymphoma (EMZL) (n = 177, 68%), follicular lymphoma (FL) (n = 26, 10%), diffuse large B-cell lymphoma (DLBCL) (n = 25, 10%), and mantle cell lymphoma (MCL) (n = 17, 7%). Low-grade lymphomas (EMZL and FL) were most commonly treated with external beam radiotherapy (EBRT), whereas high-grade lymphomas (DLBCL and MCL) were treated with chemotherapy in combination with rituximab and/or EBRT. The prognosis was relatively good with a 5-year OS and DSS of 73.8% and 87.5%, respectively. Lymphoma subtype was a statistically significant predictor for DSS, with EMZL (5-year DSS: 93.4%) having the best prognosis and DLBCL (5-year DSS: 52.6%) having the poorest. CONCLUSIONS: This is the largest reported collection of data of subtype-specific lacrimal gland lymphoma. The subtype distribution of lacrimal gland lymphoma resembles that of the ocular adnexa. Prognosis is good and the histologic subtype is a significant predictor for disease-specific survival.

International multicentre retrospective cohort study of ocular adnexal marginal zone B-cell lymphoma.

BACKGROUNDS/AIMS: To date, this is the largest cohort study on extranodal marginal zone B-cell lymphoma (EMZL) of the ocular adnexa (OA). The aim of the study was to characterise the clinical features of OA-EMZL. METHODS: A retrospective multicentre study involving seven international eye cancer centres. Data were collected from 1 January 1980 through 31 December 2017. A total of 689 patients with OA-EMZL were included. RESULTS: The median follow-up time was 42 months. The median age was 62 years (range, 8-100 years), and 55 % (378/689 patients) of patients were women. The majority of patients (82%, 558/680 patients) were diagnosed with primary OA-EMZL with Ann Arbor stage IE (90%, 485/541 patients) and American Joint Committee on Cancer stage T2 (61%, 340/557 patients) at the time of diagnosis. The orbit (66%, 452/689 patients) and the conjunctiva (37%, 255/689 patients) were the most frequently involved anatomical structures. The 5-year, 10-year and 20-year disease-specific survival (DSS) were 96%, 91% and 90%, respectively. Stage IE patients treated with external beam radiation therapy (EBRT) as monotherapy (10-year DSS, 95%) were found to have a better DSS than stage IE patients treated with chemotherapy (10-year DSS, 86%). Stage IIIE/IVE patients treated with chemotherapy and rituximab had a better DSS (10-year DSS, 96%) than stage IIIE/IVE patients treated with chemotherapy without rituximab (10-year DSS, 63%). CONCLUSIONS AND RELEVANCE: EMZL is a slow-growing tumour with an excellent long-term survival. Low-dose EBRT as monotherapy should be considered in localised OA-EMZL. Rituximab-based chemotherapy should be chosen in those patients with disseminated disease.

Extraocular Muscle Enlargement and Thyroid Eye Disease-like Orbital Inflammation Associated with Immune Checkpoint Inhibitor Therapy in Cancer Patients.

PURPOSE: To describe thyroid eye disease (TED)-like orbital inflammatory syndrome in 3 cancer patients treated with immune checkpoint inhibitors. METHODS: All consecutive patients treated by the senior author who were receiving immune checkpoint inhibitors and developed TED-like orbital inflammation were included. RESULTS: Three cancer patients treated with immune checkpoint inhibitors developed orbital inflammation. The first patient was treated with a combination of a cytotoxic T-lymphocyte antigen-4 inhibitor and a programmed cell death protein 1 inhibitor and developed TED-like orbital inflammation with normal thyroid function and antibody levels. The second patient had a previous diagnosis of Graves disease without TED, and developed TED soon after initiating treatment with a programmed cell death protein 1 inhibitor. The third patient developed acute hyperthyroidism with symptomatic TED following treatment with an investigational cytotoxic T-lymphocyte antigen-4 inhibitor agent. All 3 patients were managed with either systemic steroids or observation, with resolution of their symptoms and without the need to halt immune checkpoint inhibitor treatment for their cancer. DISCUSSION AND CONCLUSIONS: TED-like orbital inflammation may occur as a side effect of immune checkpoint inhibitor therapy with anti-cytotoxic T-lymphocyte antigen-4 or anti-PD-1 inhibitors. To the best of their knowledge, this is the first reported case of TED as a result of programmed cell death protein 1 inhibitor monotherapy. All 3 patients were treated with systemic steroids and responded quickly while continuing treatment with immune checkpoint inhibitors for their cancer. With increasing use of this class of drugs, clinicians should be familiar with the clinical manifestations and treatments for this adverse reaction.

Orbital Lymphoma-An International Multicenter Retrospective Study.

PURPOSE: To investigate and characterize the clinical features of subtype-specific orbital lymphoma. DESIGN: Retrospective, interventional case series. METHODS: The study included 7 international eye cancer centers. Patient data were collected from January 1, 1980 through December 31, 2017. A total of 797 patients with a histologically verified orbital lymphoma were included. The primary endpoints were overall survival, disease-specific survival, and progression-free survival. RESULTS: The median age was 64 years, and 51% of patients (n = 407) were male. The majority of lymphomas were of B-cell origin (98%, n = 779). Extranodal marginal zone B-cell lymphoma (EMZL) was the most frequent subtype (57%, n = 452), followed by diffuse large B-cell lymphoma (DLBCL) (15%, n = 118), follicular lymphoma (FL) (11%, n = 91), and mantle cell lymphoma (MCL) (8%, n = 66). Localized Ann Arbor stage IE EMZL and FL were frequently treated with external beam radiation therapy. DLBCL, MCL, and disseminated EMZL and FL were primarily treated with chemotherapy. EMZL and FL patients had a markedly better prognosis (10-year disease-specific survival of 92% and 71%, respectively) than DLBCL and MCL patients (10-year disease-specific survival of 41% and 32%, respectively). CONCLUSIONS: Four lymphoma subtypes were primarily found in patients with orbital lymphoma: EMZL, DLBCL, FL, and MCL. The histologic subtype was found to be the main predictor for outcome, with EMZL and FL patients having a markedly better prognosis than DLBCL and MCL.

Clinical Presentation and Anatomical Location of Orbital Plasmacytomas.

PURPOSE: To evaluate the clinical and anatomical location of orbital plasmacytomas and assess local control following therapy. METHODS: The American Society of Ophthalmic Plastic and Reconstructive Surgery Oncology Database was queried to identify patients diagnosed with orbital plasmacytoma. These patients' records were reviewed for demographic characteristics, clinical and radiologic findings, treatments, and outcomes. RESULTS: Thirty patients from 4 institutions (24 from MD Anderson Cancer Center, 3 from SUNY Downstate Medical Center, 2 from University of California, Los Angeles, and 1 from Oregon Health and Science University) were identified. Eighteen patients (60%) were diagnosed with multiple myeloma (MM) before and 11 (37%) were diagnosed with MM immediately after orbital plasmacytoma. Based on imaging, 4 distinct anatomical patterns were identified: 1) bony plasmacytoma affecting the superotemporal orbit, epidural space, and temporal fossa (15 patients; 50%); 2) discrete orbital plasmacytoma (7 patients; 23%); 3) infiltrative plasmacytoma either originating from a sinus (4 patients; 13%); or 4) originating from the orbital floor and infiltrating facial soft tissue (4 patients; 13%). Of the 29 patients with available treatment data, 2 had radiation only, 3 had chemotherapy only, 6 had chemoradiation, and 18 had stem cell transplant following chemoradiation (n = 17) or only chemotherapy (n = 1). Following treatment, 10 patients achieved complete and 11 achieved partial responses. CONCLUSION: Orbital plasmacytomas were found exclusively in patients with MM diagnosed before or immediately after orbital plasmacytoma. Plasmacytomas can have 4 distinct anatomical patterns of origin. Following treatment, all patients had good to excellent local control of their orbital lesions.

Clinicopathological Features of Ocular Adnexal Mantle-Cell Lymphoma in an International Multicenter Cohort.

Importance: To our knowledge, the clinical features of ocular adnexal mantle-cell lymphoma (OA-MCL) have not previously been evaluated in a large multicenter cohort. Objective: To characterize the clinical features of OA-MCL. Design, Setting, and Participants: This retrospective multicenter study included patient data collected from January 1, 1980, through December 31, 2015, at 6 eye cancer centers in 4 countries. Medical records of 55 patients with OA-MCL were reviewed; the median length of follow-up was 33 months. Main Outcomes and Measures: Overall survival, disease-specific survival, and progression-free survival were the primary end points. Results: Fifty-five patients were included; ocular adnexal MCL was found to be most common in older individuals (mean age, 70 years) and men (n = 42 of 55; 76%). Patients with OA-MCL frequently presented with disseminated lymphoma (n = 34 of 55; 62%), and were likely to experience stage IVE disease (n = 35 of 55; 64%), with bilateral involvement (n = 27 of 55; 47%), tumor masses (n = 27 of 36; 75%), and involvement of the orbit (n = 32 of 55; 58%). Chemotherapy with or without external beam radiation therapy was the most frequently used treatment. Overall survival rates for the entire cohort were 65% at 3 years (95% CI, 52%-78%) and 34% at 5 years (95% CI, 21%-47%). Disease-specific survival after 5 years was 38% for the entire cohort (95% CI, 25%-51%); the disease-specific survival adjusted by eye cancer center was better in patients who had received rituximab in addition to the chemotherapy regimen (hazard ratio, 3.3; 95% CI, 1.0-14.7; P = .06). The median progression-free survival was 2.3 years (95% CI, 1.8-2.7 years) in patients who experienced recurrence after primary treatment, and 4.1 years (95% CI, 3.9-4.3 years) in patients who presented with a relapse of systemic lymphoma in the ocular adnexal region. Conclusions and Relevance: These results suggest that the distinctive features of OA-MCL are its appearance in older male individuals, advanced stage and bilateral manifestation at the time of diagnosis, and aggressive course. The prognosis of patients with OA-MCL might be improved by addition of rituximab to chemotherapy treatment.

Lymphoma of the Eyelid - An International Multicenter Retrospective Study.

PURPOSE: To document subtype-specific clinical features of lymphoma of the eyelid, and their effect on patient outcome. DESIGN: Retrospective observational case series. METHODS: Patient data were collected from 7 international eye cancer centers from January 1, 1980 through December 31, 2015. The cases included primary and secondary lymphomas affecting the eyelid. Overall survival, disease-specific survival (DSS), and progression-free survival were the primary endpoints. RESULTS: Eighty-six patients were included. Mean age was 63 years and 47 (55%) were male. Non-Hodgkin B-cell lymphomas constituted 83% (n = 71) and T-cell lymphomas constituted 17% (n = 15). The most common subtypes were extranodal marginal-zone lymphoma (EMZL) (37% [n = 32]), follicular lymphoma (FL) (23% [n = 20]), diffuse large B-cell lymphoma (DLBCL) (10% [n = 9]), mantle cell lymphoma (MCL) (8% [n = 7]), and mycosis fungoides (MF) (9% [n = 8]). EMZL had a female predilection (69% [22 of 32]), whereas MCL (71% [5 of 7]) and MF (88% [7 of 8]) had a male predominance. MCL (57% [4 of 7]), DLBCL (56% [5 of 9]), and MF (88% [7 of 8]) were frequently secondary lymphomas. Localized EMZL and FL were mostly treated with external beam radiation therapy, whereas DLBCL, MCL, and high Ann Arbor stage EMZL and FL were frequently treated with chemotherapy. DLBCL and MCL had a poor prognosis (5-year DSS, 21% and 50%, respectively), whereas EMZL, FL, and MF had a good prognosis (5-year DSS, 88%, 88% and 86%, respectively). CONCLUSIONS: Lymphoma of the eyelid consists mainly of the lymphoma subtypes EMZL, FL, DLBCL, MCL, and MF. High-grade DLBCL and MCL, as well as MF, are frequently secondary eyelid lymphomas. The main predictor of outcome was the histologic subtype: EMZL, FL, and MF had a significantly better prognosis than MCL and DLBCL.

Rates of Positive Findings on Positron Emission Tomography and Bone Marrow Biopsy in Patients With Ocular Adnexal Lymphoma.

PURPOSE: The aim of this study was to determine rates of positive findings on positron emission tomography (PET) and bone marrow biopsy performed during staging workup for ocular adnexal lymphoma (OAL). METHODS: A retrospective review of OAL patients was conducted. Demographics, primary versus secondary OAL, histologic subtype, and findings on PET and bone marrow biopsy performed as part of the initial staging workup for OAL were recorded. RESULTS: The study included 119 patients with OAL. There were 85 primary and 34 secondary OALs. The main histologic subtypes of lymphoma were mucosa-associated lymphoid tissue (n = 61), follicular (n = 26), diffuse large B-cell (n = 17), and mantle cell (n = 10). Positive PET findings were seen in 42 of 68 patients (62%) with primary OAL and 19 of 24 (79%) with secondary OAL. Positive PET findings were seen in 24 of 47 patients (51%) with mucosa-associated lymphoid tissue, 13 of 17 (76%) with follicular, 14 of 15 (93%) with diffuse large B-cell, and 9 of 10 (90%) with mantle cell lymphoma. Positive findings on bone marrow biopsy were seen in 7 of 59 patients (12%) with mucosa-associated lymphoid tissue, 4 of 23 (17%) with follicular, 1 of 17 (6%) with diffuse large B-cell, and 2 of 9 (22%) with mantle cell lymphoma. CONCLUSIONS: Our findings suggest that a significant proportion of patients with primary and secondary OAL have positive findings on PET and bone marrow biopsy at initial diagnosis, suggesting a reasonable yield for these tests as part of the initial staging workup in patients with a new diagnosis of OAL.

Immune Checkpoint Inhibitors for Treatment of Metastatic Melanoma of the Orbit and Ocular Adnexa.

Programmed cell death 1 (PD-1) inhibitors are members of a new class of drugs known as immune checkpoint inhibitors and have proven efficacy in the treatment of metastatic melanoma. Herein, the authors report the use of nivolumab and pembrolizumab, 2 recently Food and Drug Administration-approved PD-1 inhibitors, in 3 patients: 1 with metastatic conjunctival melanoma and 2 with metastatic cutaneous melanoma and orbital involvement. The patients' metastatic disease responded well to drug treatment. As of this writing, 2 patients have completed therapy and remain disease free at least 1 year after treatment completion; the other patient is still receiving treatment, and his orbital disease is responding. The authors herein describe the use of PD-1 inhibitors as a new alternative in the treatment of metastatic melanoma to the orbit or metastatic ocular adnexal melanomas in these clinical settings.

Resveratrol targeting of AKT and p53 in glioblastoma and glioblastoma stem-like cells to suppress growth and infiltration.

OBJECTIVE Glioblastoma multiforme (GBM) is an aggressive brain cancer with median survival of less than 2 years with current treatment. Glioblastomas exhibit extensive intratumoral and interpatient heterogeneity, suggesting that successful therapies should produce broad anticancer activities. Therefore, the natural nontoxic pleiotropic agent, resveratrol, was studied for antitumorigenic effects against GBM. METHODS Resveratrol's effects on cell proliferation, sphere-forming ability, and invasion were tested using multiple patient-derived GBM stem-like cell (GSC) lines and established U87 glioma cells, and changes in oncogenic AKT and tumor suppressive p53 were analyzed. Resveratrol was also tested in vivo against U87 glioma flank xenografts in mice by using multiple delivery methods, including direct tumor injection. Finally, resveratrol was delivered directly to brain tissue to determine toxicity and achievable drug concentrations in the brain parenchyma. RESULTS Resveratrol significantly inhibited proliferation in U87 glioma and multiple patient-derived GSC lines, demonstrating similar inhibitory concentrations across these phenotypically heterogeneous lines. Resveratrol also inhibited the sphere-forming ability suggesting anti-stem cell effects. Additionally, resveratrol blocked U87 glioma and GSC invasion in an in vitro Matrigel Transwell assay at doses similar to those mediating antiproliferative effects. In U87 glioma cells and GSCs, resveratrol reduced AKT phosphorylation and induced p53 expression and activation that led to transcription of downstream p53 target genes. Resveratrol administration via oral gavage or ad libitum in the water supply significantly suppressed GBM xenograft growth; intratumoral or peritumoral resveratrol injection further suppressed growth and approximated tumor regression. Intracranial resveratrol injection resulted in 100-fold higher local drug concentration compared with intravenous delivery, and with no apparent toxicity. CONCLUSIONS Resveratrol potently inhibited GBM and GSC growth and infiltration, acting partially via AKT deactivation and p53 induction, and suppressed glioblastoma growth in vivo. The ability of resveratrol to modulate AKT and p53, as well as reportedly many other antitumorigenic pathways, is attractive for therapy against a genetically heterogeneous tumor such as GBM. Although resveratrol exhibits low bioavailability when administered orally or intravenously, novel delivery methods such as direct injection (i.e., convection-enhanced delivery) could potentially be used to achieve and maintain therapeutic doses in the brain. Resveratrol's nontoxic nature and broad anti-GBM effects make it a compelling candidate to supplement current GBM therapies.

Fibrous Hamartoma of Infancy in the Eyelid: A Rare Presentation.

A 6-year-old girl presented with a left nodular mass around the punctum. Previous debulking in a similar location at 10 weeks and 8 months of age confirmed fibrous hamartoma of infancy. Pathology at the initial surgery revealed benign-appearing fibroadipose tissue, vasculature, and smooth muscle. Pathologic examination from the third debulking illustrated less fibrous trabeculae extending into increased amounts of mature-appearing adipocytes with collections of immature-appearing fibrocytes. The lesion had slight differences in pathology compared with prior surgical specimens; however, was still consistent with fibrous hamartoma of infancy. No recurrence has been reported since the last surgery.

Conjunctival Lymphoma--An International Multicenter Retrospective Study.

IMPORTANCE: To date, the clinical features of the various subtypes of conjunctival lymphoma (CL) have not been previously evaluated in a large cohort. OBJECTIVE: To characterize subtype-specific clinical features of CL and their effect on patient outcome. DESIGN, SETTING, AND PARTICIPANTS: A retrospective multicenter study was performed. Patient data were collected from January 1, 1980, through December 31, 2010. The dates of the analysis were May 15, 2015, to August 20, 2015. The median follow-up period was 43 months. Seven eye cancer centers were involved in the study. In total, 268 patients with CL were identified, 5 of whom were excluded because of missing clinical data. MAIN OUTCOMES AND MEASURES: Overall survival, disease-specific survival, and progression-free survival were the primary end points. RESULTS: Two hundred sixty-three patients with CL were included in the study. Their mean age was 61.3 years, and 55.1% (145 of 263) were female. All lymphomas were of B-cell type. The most frequent subtype was extranodal marginal zone lymphoma (EMZL) (68.4% [180 of 263]), followed by follicular lymphoma (FL) (16.3% [43 of 263]), mantle cell lymphoma (MCL) (6.8% [18 of 263]), and diffuse large B-cell lymphoma (DLBCL) (4.6% [12 of 263). Conjunctival lymphoma commonly manifested in elderly individuals (age range, 60-70 years old), with EMZL having a female predilection (57.8% [104 of 180]) and MCL having a marked male predominance (77.8% [14 of 18]). Unlike EMZL and FL, DLBCL and MCL were frequently secondary diseases (41.7% [5 of 12] and 88.9% [16 of 18], respectively), with MCL showing a frequent occurrence of stage IVE lymphoma (61.1% [11 of 18]) and bilateral manifestation (77.8% [14 of 18]). Localized disease (stage IE or IIE) was commonly treated with external beam radiation therapy (EBRT) with or without chemotherapy, while widespread lymphoma (stage IIIE or IVE) and MCL of any stage were managed with chemotherapy with or without EBRT. Diffuse large B-cell lymphoma and MCL had a poor prognosis, with 5-year disease-specific survival of 55.0% and 9.0%, respectively, in contrast to EMZL (97.0%) and FL (82.0%). Further survival predictors included age (EMZL), sex (FL), and Ann Arbor staging classification (EMZL and FL). The American Joint Committee on Cancer TNM staging showed limited prognostic usefulness, only being able to predict survival for patients with DLBCL. CONCLUSIONS AND RELEVANCE: Conjunctival lymphoma consists of mainly 4 subtypes of B-cell non-Hodgkin lymphoma: EMZL, FL, MCL, and DLBCL. Mantle cell lymphoma is characterized by a particularly high frequency of secondary disease of stage IVE and bilateral manifestation. The histological subtype is the main outcome predictor, with MCL and DLBCL having a markedly poorer prognosis than EMZL and FL.

The Significance of the Discordant Occurrence of Lens Tumors in Humans versus Other Species.

PURPOSE: The purpose of this study was to determine in which species and under what conditions lens tumors occur. DESIGN: A review of databases of available human and veterinary ocular pathologic material and the previously reported literature. PARTICIPANTS: Approximately 18 000 patients who had ocular surgical specimens submitted and studied at the University of Wisconsin School of Medicine and Public Health between 1920 and 2014 and 45 000 ocular veterinary cases from the Comparative Ocular Pathology Laboratory of Wisconsin between 1983 and 2014. METHODS: Material in 2 major archived collections at the University of Wisconsin medical and veterinary schools were studied for occurrence of lens tumors. Tumor was defined as a new growth of tissue characterized by progressive, uncontrolled proliferation of cells. In addition, cases presented at 3 major eye pathologic societies (Verhoeff-Zimmerman Ophthalmic Pathology Society, Eastern Ophthalmic Pathology Society, and The Armed Forces Institute of Pathology Ophthalmic Alumni Society) from 1975 through 2014 were reviewed. Finally, a careful search of the literature was carried out. Approval from the institutional review board to carry out this study was obtained. MAIN OUTCOME MEASURES: The presence of tumors of the lens. RESULTS: The database search and literature review failed to find an example of a lens tumor in humans. In contrast, examples of naturally occurring lens tumors were found in cats, dogs, rabbits, and birds. In the veterinary school database, 4.5% of feline intraocular and adnexal neoplasms (234/5153) were designated as feline ocular posttraumatic sarcoma, a tumor previously demonstrated to be of lens epithelial origin. Similar tumors were seen in rabbit eyes, a bird, and in a dog. All 4 species with lens tumors had a history of either ocular trauma or protracted uveitis. The literature search also revealed cases where lens tumors were induced in zebrafish, rainbow trout, hamsters, and mice by carcinogenic agents (methylcholanthrene, thioacetamide), oncogenic viruses (SV40, HPV-16), and genetic manipulation. CONCLUSIONS: Our results suggest that lens tumors do not occur in humans. In contrast, after lens capsule rupture, a lens tumor can occur in other species. We hypothesize that a genetic mechanism exists that prevents lens tumors in humans.

Hedgehog Pathway Inhibition for Locally Advanced Periocular Basal Cell Carcinoma and Basal Cell Nevus Syndrome.

PURPOSE: To review our experience treating patients with the Hedgehog pathway inhibitor, vismodegib, in patients with orbital or periocular locally advanced or metastatic basal cell carcinoma (BCC) or basal cell nevus syndrome. DESIGN: Retrospective interventional case series. METHODS: We reviewed all patients with locally advanced or metastatic orbital or periocular BCC or basal cell nevus syndrome treated with the Hedgehog pathway inhibitor, vismodegib, at a comprehensive cancer center from 2009 through 2015. Reviewed data included age; sex; American Joint Commission on Cancer tumor, node, metastasis staging system designation; type and grade of drug-related side effects; response to treatment; duration of follow-up, and status at last follow-up. RESULTS: The study included 10 white men and 2 white women; the median age was 64.5 years. Ten patients had locally advanced BCC; 2 had basal cell nevus syndrome. Among the patients with locally advanced BCC, 5 had T3bN0M0 disease at presentation; 1 each had T3aN0M0, T3bN1M0, T2N1M1, T4N1M1, and T4N2cM1 disease. Overall, 3 patients had a complete response, 6 had a partial response, and 3 had stable disease at last follow-up. Two patients developed progressive disease after a complete response for 38 months and stable disease for 16 months, respectively. All patients developed grade I drug-related adverse effects, most commonly muscle spasms (12 patients), weight loss (10), dysgeusia (9), alopecia (9), decreased appetite (5), and fatigue (4). Five patients developed grade II adverse effects. At last follow-up, none of the 5 patients presenting with T3bN0M0, nor the patient with T3bN1M0 disease, had required orbital exenteration. CONCLUSION: Hedgehog pathway inhibition produces a significant clinical response in most patients with locally advanced or metastatic orbital or periocular BCC or basal cell nevus syndrome and can obviate orbital exenteration in some patients. Drug-related adverse effects are manageable in most patients.

Investigating the role of metal fatigue in a case of ritleng probe fracture: its causes and prevention.

Complications with the Ritleng probe have not been reported previously. Herein, we report a case in which the Ritleng probe tip fractured during use on a patient undergoing nasolacrimal duct intubation requiring subsequent retrieval. A root-cause analysis was conducted which help to elicit possible ways to prevent such a complication in the future. Most notably the use of the stylet, documented as a cleaning device, seems to offer additional support to prevent metal fatigue and tip fracture.