Clinical and histopathological classification of feline intraocular lymphoma.

This retrospective study aimed to describe and classify cats with intraocular lymphoma, determine the proportion of cases with presumed solitary ocular lymphoma (PSOL) compared with ocular manifestations of multicentric disease and assess the clinical outcomes of these patients. One hundred seventy-two cases identified through biopsy submissions were reviewed histologically; 163 of these cases were subtyped according to the WHO classification system. Cases were categorized as having PSOL or ocular lymphoma with suspected systemic involvement (SSI) based on submission forms and follow-up data. The majority of cases exhibited concurrent uveitis (75%) and secondary glaucoma (58%). Diffuse large B-cell lymphoma was the most common subtype (n = 86; 53%), followed by peripheral T-cell lymphoma (n = 44; 27%). Other subtypes included anaplastic large T- (n = 8; 5%) and B-cell (n = 4; 2.5%) lymphomas, and 15 cases (9%) were negative for all immunohistochemical markers. In sixty-nine cases (40%), adequate clinical data and sufficient survival data were obtained to distinguish PSOL from SSI. PSOL comprised the majority of cases (64%), while 36% had SSI. When covarying for age at diagnosis, the median survival time was significantly higher (P = 0.003) for cases of PSOL (154 days) versus those with SSI (69 days); hazards ratio of 0.47 for PSOL (95% CI: 0.241-0.937). The subtype of lymphoma did not affect survival time. Cats with PSOL represent a greater proportion of the disease population, and this subset of cats with intraocular lymphoma has a better clinical outcome.

Ocular surface squamous neoplasia: analysis based on the 8th American Joint Committee on Cancer classification.

PURPOSE: To evaluate outcomes of ocular surface squamous neoplasia (OSSN) based on American Joint Committee on Cancer (AJCC), 8th edition classification. METHODS: Retrospective, non-randomized interventional case series of 127 patients (136 eyes) with OSSN. RESULTS: On the basis of the AJCC (eighth edition), OSSN was classified as per T category as Tis (n = 14, 10%), T1 (n = 0), T2 (n = 4, 3%), T3 (n = 113, 83%), and T4 (n = 5, 4%). The following parameters increased with increasing T category: mean age at presentation at 37 years for Tis, 43 years for T2, 46 years for T3, and 55 years for T4 (p = 0.04); mean tumor basal diameter of 4 mm for Tis, not applicable (na) for T1, 6 mm for T2, 7 mm for T3, 20 mm for T4 (p = 0.001); extent of clock hours of corneal involvement (0, na, 0, 4, 8; p = 0.02), and conjunctival involvement (1, na, 2, 3, 9; p = 0.0005); involvement of adjacent structures including fornix (0%, na, 0, 9, 80%; p < 0.001), and caruncle (0%, na, 0, 3, 60%; p < 0.001) for Tis, T1, T2, T3, and T4, respectively. Overall, of the 136 eyes, 19 (14%) had tumor recurrence, and all tumor recurrences were seen in T3. Regional lymph node metastasis was noted in 4 (3%) patients. No systemic metastasis or death occurred in any patient during the mean follow-up period of 15 months (median, 11 months; range 6-55 months). CONCLUSION: Increasing T category based on AJCC 8th edition classification is associated with increasing severity of disease, tumor recurrence rate, and the rate of regional lymph node metastasis.

Clinical and pathological classification of canine intraocular lymphoma.

The objectives of this retrospective study of 100 dogs with intraocular lymphoma were to describe the histomorphologic and immunohistochemical features of canine intraocular lymphoma, determine the proportion of cases with presumed solitary ocular lymphoma (PSOL) compared to multicentric disease, and assess the clinical outcomes of these patients. Selected cases from Penn Vet Diagnostic Laboratory and Comparative Ocular Pathology Lab of Wisconsin (2004-2015) were evaluated and subtyped using the WHO classification system. Peripheral T-cell lymphoma and diffuse large B-cell lymphoma were the two most common subtypes. Questionnaires were distributed to the referring veterinarians and veterinary ophthalmologists inquiring about clinical signs at time of enucleation, staging, patient outcome, treatment, and disease progression. Cases were categorized as PSOL if only ocular involvement was noted at the time of diagnosis based on the clinical staging criteria. The majority of cases (61%) did not have systemic involvement at the time of diagnosis, and these cases did not progress postoperatively. Median survival time (MST) was significantly higher for the presumed solitary intraocular cases: 769 vs. 103 days, hazard ratio of 0.23 (95% CI: 0.077-0.68). The subtype of lymphoma did not affect survival time. The results of this study suggest two significant points of clinical interest: the majority of dogs (61%) presented without signs of systemic involvement of lymphoma at the time of enucleation, and dogs with only ocular involvement showed no disease progression postenucleation.

Ocular adnexal lymphomas: An eye care service experience in Turkey.

AIM: This study aimed to evaluate the clinical and pathological features of ocular adnexal lymphoma (OAL) and the treatment results in an eye care service center in Turkey. MATERIALS AND METHODS: The data sets of the patients diagnosed with OAL acquired between January 2008 and January 2016 were collected and analyzed. RESULTS: Fifteen patients were included in our study. The mean age was 55.80 ± 17.85 years. The age range was 7-85 years. Most of the lesions originated from orbital tissue, and histopathological and immunohistochemistry examinations of the lesions were consistent with non-Hodgkin's lymphoma in 14 patients and Hodgkin's lymphoma in 1 patient. The most common subtype of OAL, accounting for 40% of cases, is extranodular marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type. CONCLUSION: Most of our patients' histopathological and immunohistochemistry examinations are non-Hodgkin's type and also involve the orbits. Ocular adnexal lymphomatosis is not a rare disorder and could be treated if there is no systemic involvement at first diagnosis.

Favorable outcome of alternate systemic and intra-arterial chemotherapy for retinoblastoma.

The recent trend of treatment for retinoblastoma is to salvage the eye globes as well as achieving patients' survival. Intra-arterial chemotherapy (IAC) is one of the current standard treatment; however, it cannot exclude the risk of occult micrometastases in the central nervous system in advanced-stage retinoblastoma. Alternate fashion of intravenous chemotherapy (IVC) and IAC strategy was developed to increase the eye salvage rate and to reduce the metastatic risk. Between January 2012 and December 2014, 13 eyes of 12 patients with newly diagnosed retinoblastoma received alternate chemotherapy using IVC and IAC in Yonsei Cancer Center. Eye salvage rate was assessed by the eye preservation time, which was defined as the duration from the diagnosis to the time of enucleation. Total 13 eyes were classified according to the International Classification of Retinoblastoma (ICRB) as group B (n = 1, 7.7%), group C (n = 2, 15.4%), group D (n = 5, 38.5%), or group E (n = 5, 38.5%). IAC was performed, 3 to 5 times (median: 4 times) for each eye, total 54 times. Five to 15 courses (median: 8 courses) of systemic chemotherapy were performed in the patients. During the median follow-up period of 30.4 months, overall eye salvage rate was 63.9 ± 14.7%. All patients survived. The treatment was tolerable without significant complications. These results showed that primary alternate IVC-IAC was tolerable and effective for retinoblastoma.

The classification of vitreous seeds in retinoblastoma and response to intravitreal melphalan.

PURPOSE: To evaluate the clinical characteristics of the 3 classifications of vitreous seeds in retinoblastoma-dust (class 1), spheres (class 2), and clouds (class 3)-and their responses to intravitreal melphalan. DESIGN: Retrospective, bi-institutional cohort study. PARTICIPANTS: A total of 87 patient eyes received 475 intravitreal injections of melphalan (median dose, 30 µg) given weekly, a median of 5 times (range, 1-12 times). METHODS: At presentation, the vitreous seeds were classified into 3 groups: dust, spheres, and clouds. Indirect ophthalmoscopy, fundus photography, ultrasonography, and ultrasonic biomicroscopy were used to evaluate clinical response to weekly intravitreal melphalan injections and time to regression of vitreous seeds. Kaplan-Meier estimates of time to regression and ocular survival, patient survival, and event-free survival (EFS) were calculated and then compared using the Mantel-Cox test of curve. MAIN OUTCOME MEASURES: Time to regression of vitreous seeds, patient survival, ocular survival, and EFS. RESULTS: The difference in time to regression was significantly different for the 3 seed classes (P < 0.0001): the median time to regression was 0.6, 1.7, and 7.7 months for dust, spheres, and clouds, respectively. Eyes with dust received significantly fewer injections and a lower median and cumulative dose of melphalan, whereas eyes with clouds received significantly more injections and a higher median and cumulative dose of melphalan. Overall, the 2-year Kaplan-Meier estimates for ocular survival, patient survival, and EFS (related to target seeds) were 90.4% (95% confidence interval [CI], 79.7-95.6), 100%, and 98.5% (95% CI, 90-99.7), respectively. CONCLUSIONS: The regression and response of vitreous seeds to intravitreal melphalan are different for each seed classification. The vitreous seed classification can be predictive of time to regression, number, median dose, and cumulative dose of intravitreal melphalan injections required.

Comparative integrated molecular analysis of intraocular medulloepitheliomas and central nervous system embryonal tumors with multilayered rosettes confirms that they are distinct nosologic entities.

Intraocular medulloepithelioma (IO MEPL) is an uncommon embryonal neuroepithelial neoplasm of the eye. These ocular neoplasms have been compared with intracranial medulloepitheliomas or other histologic variants of CNS embryonal tumor with multilayered rosettes (CNS ETMR) due to their morphological mimicry. We performed comprehensive molecular analysis to explore the histogenetic and biologic relationships between 22 IO MEPL and 68 CNS ETMR. Routinely prepared paraffin-embedded samples were assessed for genome-wide methylation profiles using the Illumina Methylation 450k BeadChip array. We identified strong cytogenetic and epigenetic differences between ocular neoplasms and CNS ETMR. None of the IO MEPL cases displayed the ETMR-specific amplification of the C19MC locus. Instead, cytogenetic analysis of the IO MEPL showed numerous copy number aberrations which involved either whole chromosomes or chromosomal arms; recurrent aberrations in these tumors affected chromosomes 1p, 4, 8 and 16p. DNA methylation patterns were also strikingly different between these two tumor entities, suggesting that they do not share common origins and biological behaviors. Comparative cluster analysis of 198 pediatric CNS tumors and 22 IO MEPL revealed a clear demarcation of the CNS ETMR and IO MEPL profiles from other CNS entities. In conclusion, although IO MEPL shares some histopathological features with CNS ETMR, they manifest striking molecular diversity at the cytogenetic and epigenetic levels. Consequently they deserve a separate nosologic designation in future tumor classifications, where CNS MEPL could be designated as a histological variant of CNS ETMR.

Hydroa vacciniforme-like lymphoma with primarily periorbital swelling: 7 cases of an atypical clinical manifestation of this rare cutaneous T-cell lymphoma.

Hydroa vacciniforme-like lymphoma (HVL) is a rare cutaneous T-cell lymphoma that is usually seen in children of Hispanic or Asian origin. Association between chronic latent Epstein-Barr virus infection in both hydroa vacciniforme (HV) and HVL has been demonstrated and has recently been categorized by the World Health Organization as one of the Epstein Barr virus-positive lymphoproliferative disorders of childhood. Patients with HVL present with a cutaneous rash characterized by edema, blisters, ulcers, and scars mainly seen on the face and extremities that mimic HV; however, unlike in HV, the lesions tend to be extensive and deeper and are associated with severe scarring, necrosis, and systemic manifestations. We are reporting 7 cases of an unusual clinical variant of HVL with primarily periorbital edema. All of our patients in this series presented with progressive periorbital edema that was accompanied with systemic symptoms including fever, malaise, and lymphadenopathy. Most cases were initially misinterpreted as inflammatory processes including cellulitis, arthropod bite reactions, and periorbital lupus erythematosus. The biopsy of these lesions revealed an atypical lymphocytic infiltrate predominantly distributed in the deep dermis and in subcutaneous fat. Immunohistochemistry studies revealed a cytotoxic T-cell (CD8) profile. All cases were associated with Epstein-Barr virus infection. Our study presents a rare clinical variant of HVL with predominant periorbital edema. This variant could potentially be overlooked and misdiagnosed as an inflammatory condition; thus, it needs to be included in the differential diagnosis of periorbital edema in young patients.

Intraocular and periocular lymphoma in dogs and cats: a retrospective review of 21 cases (2001-2012).

OBJECTIVE: To immunologically phenotype and histologically classify canine and feline intraocular and periocular lymphomas. METHODS: The databases of four veterinary medical diagnostic laboratories were searched to identify cases of intraocular or periocular lymphoma in dogs and cats between 2001 and 2012. Hematoxylin and eosin (H&E) stained slides were reviewed for confirmation and classification of lymphoma, and immunohistochemistry for CD3 (T-cell marker) and CD79a and/or CD20 (B-cell markers) was examined to determine the lineage of the neoplastic lymphocytes. RESULTS: Six canine and 15 feline cases of ocular lymphoma were identified. In the canine cases, there were three intraocular and three periocular lymphomas where two intraocular and one periocular lymphomas were B-cell, one of each intraocular and periocular lymphomas were T-cell and one periocular lymphoma was nonreactive with CD3, CD79a or CD20. In the feline cases, there were six intraocular and nine periocular lymphomas where five intraocular and six periocular lymphomas were B-cell, and one intraocular and three periocular lymphomas were T-cell. Only one canine case had concurrent generalized lymphadenopathy, only one canine conjunctival lymphoma had simultaneous cutaneous lymphoma, and only one feline case had bilateral ocular involvement when they were diagnosed. CONCLUSION: Canine and feline intraocular and periocular lymphomas are often of B-cell phenotype. Although in general terms lymphoma is not considered a primary tumor when it occurs in or adjacent to the globe, these tumors frequently first become evident in the globe and/or periocular area. An accurate early diagnostic approach is crucial for the patient's quality of life because B-cell lymphomas are generally more amenable to chemotherapy than T-cell lymphomas.

[Ophthalmic oncology: achievements over the last two decades].

The article describes current trends in scientific research, especially those that concern treatment of the most common cancers. The latter include malignant eyelid and conjunctiva tumors, retinoblastoma and choroidal melanoma. Relevant publications in Russian and foreign journals demonstrate a progressive advance in treatment approaches: from radical methods associated with surrounding tissue damage to local tumor destruction. Comparative analysis of the methods and their effectiveness suggest that Russian ophthalmic oncology meets state-of-the-art international criteria.

[The pathological analysis of 213 children with ocular tumor].

OBJECTIVE: To analyze the pathological classification of ocular tumor in children. METHODS: 213 cases (214 eyes) of ocular tumor in children below 14 years old between January 2001 and December 2007 in Henan Eye Institute were reviewed retrospectively, the pathological classification were made according to the location and nature of the tumor. RESULTS: There were 17 eyes (7.94%) of 214 eyes with benign tumor of eyelid, the leading two tumor were 4 eyes with cyst, in which 1 eye with epidermoid cyst and 3 eyes with dermoid cyst were included, and 3 eyes with squamous papilloma. There were 84 eyes (39.25%) of 214 eyes with conjunctival and corneal tumor, 1 eye with intraepithelial tumor was found, other tumors were all benign tumor, the leading three tumors were corneal dermoid (64 eyes), conjunctival nevus (10 eyes) and squamous papilloma (4 eyes). There were 73 eyes (34.11%) with intraocular tumor including 66 eyes (90.41%) with retinoblastoma, 6 eyes (8.22%) with iris cyst and 1 eye (1.37%) with iris melanoma. Of 38 eyes of orbital tumor, cyst (16 eyes), vascular hamartoma (7 eyes) and inflammatory pseudotumor (4 eyes) were the most common benign tumors, there were 3 eyes (7.89%) with orbital extension of retinoblastoma and 2 eyes (5.26%) with rhabdosarcoma. There were 2 eyes with scleral tumor, including 1 eye with scleral bony choristoma and 1 eye with congenital scleral cyst. Altogether, there are 135 eyes (63.08%) with benign tumor and 79 eyes (36.92%) with malignant tumors. CONCLUSIONS: Most children's ocular tumors are congenital and embryonic tumors. Retinoblastoma is the most common malignant ocular tumor in children, then is corneal dermoid.

A child with leukocoria.

Leukocoria, meaning "white pupil," describes the clinical finding of a white pupillary reflex on examination. It may be discovered through an asymmetric red reflex using direct ophthalmoscopy, or it may be seen incidentally on flash photography. It results from an abnormality of the eyeball that interferes with the normal reflective process. We report a case of a 3-year-old boy who presents with leukocoria found to be caused by a retinoblastoma and discuss the differential diagnosis of this uncommon presentation to the pediatric emergency department.

Prognostic factors for relapse and survival among patients with ocular adnexal lymphoma: validation of the eighth edition of the American Joint Committee on Cancer (AJCC) TNM classification.

BACKGROUND/AIMS: To validate the prognostic performance of the American Joint Committee on Cancer (AJCC) eighth edition classification for ocular adnexal lymphoma (OAL). METHODS: We performed a retrospective review of 140 consecutive patients treated for primary OAL between March 2010 and September 2017. Associations between T/N/M categories at presentation and disease-related outcomes, including relapse, progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Seventy-nine women and 61 men (median age, 52 (range 20-84) years; median follow-up, 57 (range 7-131) months) were included. Histological subtypes included mucosa-associated lymphoid tissue lymphoma (92.1%, n=129), diffuse large B-cell lymphoma (5.0%, n=7), follicular lymphoma (1.4%, n=2) and mantle cell lymphoma (1.4%, n=2). Patients with ≥T2 disease had significantly higher risks of overall relapse (unadjusted HR)=4.32, p=0.016), decreased PFS (uHR=5.19, p=0.004) and decreased OS (uHR=9.21, p=0.047). Patients with ≥N1 disease had significantly higher risks of overall relapse (uHR=9.17, p<0.001) and decreased PFS (uHR=9.24, p<0.001). M1 disease was significantly associated with higher risks of overall relapse (uHR=3.62, p=0.036), decreased PFS (uHR=5.13, p=0.001) and decreased OS (uHR=9.24, p=0.013). On considering TNM categories as continuous data, the uHRs for per level increase in T, N and M categories were 1.77, 1.83 and 2.30 for overall relapse and 1.72, 1.87 and 2.78 for decreased PFS, respectively (p<0.05 for each comparison). CONCLUSION: The T, N and M categories of the AJCC eighth edition classification have prognostic value for relapse and survival among patients with primary OAL. Particularly, nodal/metastatic involvement at presentation indicated less favourable outcome.

Tumors of the lacrimal drainage system.

Tumors of the lacrimal drainage system are rare, but potentially life-threatening. They comprise a large and variable spectrum of entities grouped into three major categories of primary epithelial, primary nonepithelial and inflammatory lesions. The most common primary epithelial tumors include papilloma, squamous cell carcinoma and transitional cell carcinoma, the most frequent primary nonepithelial tumors fibrous histiocytoma, malignant lymphoma and malignant melanoma, and the most common inflammatory lesions sarcoidosis, Wegener granulomatosis and pyogenic granuloma. This review outlines the incidence, types, management and prognosis of tumors affecting the lacrimal drainage system.

American Joint Committee on Cancer classification predicts outcome of patients with lacrimal gland adenoid cystic carcinoma.

PURPOSE: To investigate whether American Joint Committee on Cancer (AJCC) classification at initial diagnosis of lacrimal gland adenoid cystic carcinoma predicts outcome of treatment on local recurrence. DESIGN: Retrospective chart review. PARTICIPANTS: Consecutive patients with adenoid cystic carcinoma of the lacrimal gland treated at 8 institutions between January 1986 and December 2007. METHODS: Clinical records, including pathology reports and imaging studies, were reviewed. MAIN OUTCOME MEASURES: AJCC classification, histologic subtype, local recurrence rate, and survival. RESULTS: AJCC classification at initial diagnosis was assessable for 53 patients and was as follows: T1N0M0, 7 patients; T2N0M0, 8 patients; T3aN0M0, 14 patients; T3aNxM0, 1 patient; T3aN0M1, 1 patient; T3bN0M0, 13 patients; T3bN0M1, 1 patient; T4aN0M0, 2 patients; T4bN0M0, 4 patients; T4bN0M1, 1 patient; and T4bNXM0, 1 patient. Thirty-eight (72%) of the 53 patients had >T3 tumors at presentation. Of the 38 patients with >T3 tumors, 20 were treated with orbital exenteration and postoperative adjuvant radiotherapy (RT), 6 were treated with orbital exenteration without RT, and 12 were treated with globe-preserving surgery (10 with RT and 2 without RT). Of the 15 patients with T3 tumors, the risk of local recurrence (in the orbit or skull base) was higher in patients treated with conservative surgery as opposed to orbital exenteration and RT. Only 4 (20%) of the 20 patients treated with orbital exenteration and RT had local recurrence, compared with 3 (50%) of the 6 patients treated with orbital exenteration without RT and 8 (67%) of the 12 patients treated with globe-preserving surgery. Overall, 17 (45%) of the 38 patients with >T3 tumors and only 1 (7%) of the 15 patients with T3 disease at initial diagnosis correlates with worse outcomes than does AJCC

Epithelial tumors of the lacrimal gland: an update.

PURPOSE OF REVIEW: The goal of this article is to offer an update on the treatment and prognosis of the most common epithelial tumors of the lacrimal gland, report on new pathological entities and offer a review of the classification of lacrimal gland tumors. RECENT FINDINGS: Improvements have been made in the understanding of lacrimal gland lesions with the knowledge that lacrimal gland tumors compare to the more common counterparts of the major salivary glands. Therefore, the WHO's classification of salivary gland tumors has been adapted to the lacrimal gland pathology. Until recently, primary adenocarcinomas of the lacrimal gland were not further subclassified, but they can now be divided into low-grade and high-grade malignancies. The adjunctive use of intra-arterial cytoreductive chemotherapy for the management of adenoid cystic carcinoma is one of the most important advancements on the management of these aggressive tumors. Another important step forward has been taken on carcinoma ex pleomorphic adenoma of the lacrimal gland, which is subclassified into noninvasive carcinoma, with an excellent prognosis after complete excision and invasive carcinoma for which the prognosis is still guarded despite adjunctive radiotherapy. SUMMARY: This article offers an update on diagnosis, classification and treatment of common and rare epithelial lacrimal gland tumors.

Understanding intraocular lymphomas.

The purpose of this review is to describe the clinical features, pathology and molecular biology of intraocular lymphomas, which represent a heterogenous group of malignant neoplasms; to propose an anatomical classification of these tumours according to whether they occur in the retina or uvea; and to overview laboratory investigations and highlight factors required for successful biopsy. Recent findings show that retinal lymphomas are high-grade (i.e. aggressive), B-cell malignancies and are associated with a poor prognosis, with most patients dying of central nervous system disease. Immunophenotyping and somatic mutation analyses indicate that these lymphomas are probably derived from early post-germinal centre cells. Primary choroidal lymphomas are typically low-grade (i.e. indolent), B-cell tumours with morphological, immunophenotypical and genotypic features similar to extranodal marginal zone B-cell lymphomas (EMZL) elsewhere in the body. The putative cell of origin is the post-germinal centre (memory) B cell. Primary iridal lymphomas are very rare, with an equal distribution of B- and T-cell types and with a variable clinical course, most patients succumbing to their disease as a result of systemic dissemination. Primary lymphomas limited to the ciliary body are exceptionally rare. Secondary uveal lymphomas/leukaemias occur in patients with advanced systemic lymphoma or leukaemia, respectively. In summary, the term 'primary intraocular lymphoma (PIOL)' is imprecise. It would be preferable to refer to the various forms of intraocular lymphoma according to whether they are retinal, choroidal, ciliary or iridal and whether they are primary or secondary in these locations.