Analysis of the mortality by eye cancer from 2010 to 2019 in Brazil / Análise da mortalidade no Brasil por câncer ocular de 2010 a 2019

ABSTRACT Objective: To assess the deaths caused by eye cancer from 2010 to 2019 in Brazil. Methods: Data were selected from SUS' Computer Department platform at the Ministry of Health, including death certificates, from 2010 to 2019, from all Brazilian states and the Federal District, filtering the codes C69.0 to C69.9 as the cause of death, according to the International Classification of Diseases, Tenth Revision. Results: There were 1,859 deaths from malignant neoplasm of eye and adnexa (C69), in Brazil, from 2010 to 2019, affecting 1,062 (57.1%) men. The site of neoplasm was unspecified (C69.9) in 719 cases, representing the most frequent etiology in the C69 group (38.67%). The malignant neoplasm of the orbit (C69.6) was the second most common cause of death (22.59%), followed by malignant neoplasm of retina (C69.2) (14.73%). Conclusion: The number of deaths due to malignant neoplasm of eye and adnexa slightly increased through the years of 2010 to 2019, in Brazil.

RESUMO Objetivo: Avaliar os óbitos causados por câncer ocular durante os anos de 2010 a 2019 no Brasil. Métodos: Os dados foram selecionados na plataforma do Departamento de Informática do SUS do Ministério da Saúde, incluindo declarações de óbito, durante os anos de 2010 a 2019, de todos os estados brasileiros e do Distrito Federal, filtrando os códigos C69.0 a C69.9 como causa básica de óbito, de acordo com a Classificação Internacional de Doenças e Problemas Relacionados à Saúde - 10ᵃ Revisão. Resultados: Houve 1.859 óbitos por neoplasia maligna de olho e anexos (C69), no Brasil, no período de 2010 a 2019, acometendo 1.062 (57,1%) homens. O sítio da neoplasia não foi especificado (C69.9) em 719 casos, representando a etiologia mais frequente no grupo C69 (38,67%). A neoplasia maligna da órbita (C69.6) foi a segunda causa mais comum de óbito (22,59%), seguida pela neoplasia maligna da retina (C69.2) (14,73%). Conclusão: O número de óbitos por neoplasia maligna de olho e anexos aumentou discretamente ao longo dos anos de 2010 a 2019, no Brasil.

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.

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.

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.

Cell of origin and mutation pattern define three clinically distinct classes of sebaceous carcinoma.

Sebaceous carcinomas (SeC) are cutaneous malignancies that, in rare cases, metastasize and prove fatal. Here we report whole-exome sequencing on 32 SeC, revealing distinct mutational classes that explain both cancer ontogeny and clinical course. A UV-damage signature predominates in 10/32 samples, while nine show microsatellite instability (MSI) profiles. UV-damage SeC exhibited poorly differentiated, infiltrative histopathology compared to MSI signature SeC (p = 0.003), features previously associated with dissemination. Moreover, UV-damage SeC transcriptomes and anatomic distribution closely resemble those of cutaneous squamous cell carcinomas (SCC), implicating sun-exposed keratinocytes as a cell of origin. Like SCC, this UV-damage subclass harbors a high somatic mutation burden with >50 mutations per Mb, predicting immunotherapeutic response. In contrast, ocular SeC acquires far fewer mutations without a dominant signature, but show frequent truncations in the ZNF750 epidermal differentiation regulator. Our data exemplify how different mutational processes convergently drive histopathologically related but clinically distinct cancers.

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.

Lacrimal Sac Tumors--A Review.

Tumors of the lacrimal sac are rare but their recognition and early management are imperative, as they are locally invasive and potentially life-threatening. Because of their rarity, large clinical studies with statistically significant data on the natural course, management, and prognosis of these neoplasms are unavailable. Current practices are therefore based on a few case series and a small number of isolated case reports. Most tumors are primary and of epithelial origin (60-94%), of which 55% are malignant. Lacrimal sac tumors typically present with epiphora and a palpable mass over the medial canthus and are thus often erroneously diagnosed as chronic dacryocystitis. A full history with clinical and diagnostic workup is essential to plan treatment, which is often multi-disciplinary. Statistically significant associations have been shown with higher tumor staging and size with increased metastatic risk and lower survival rates. Management usually involves complete surgical resection with adjuvant radiotherapy and/or chemotherapy for malignant lesions. Long-term follow-up is required, as recurrences and metastases can occur many years after initial treatment.

An Update on Tumors of the Lacrimal Gland.

Lacrimal gland tumors are rare and constitute a wide spectrum of different entities ranging from benign epithelial and lymphoid lesions to high-grade carcinomas, lymphomas, and sarcomas with large differences in prognosis and clinical management. The symptoms and findings of a lacrimal gland lesion are a growing mass at the site of the lacrimal gland, including displacement of the eyeball, decreased motility, diplopia, and ptosis. Pain is the cardinal symptom of an adenoid cystic carcinoma. Radiological findings characteristically include an oval, well-demarcated mass for benign lesions whereas malignant lesions typically display calcifications, destruction of bone, and invasion of adjacent structures. The diagnosis ultimately relies on histology, as does the choice of treatment and the prognosis. In recent years, the understanding of the biology of numerous types of lacrimal gland neoplasia has improved and the choice of treatment has changed accordingly and holds further promise for future targeted therapies. Treatment of benign epithelial lesions is surgical excision whereas carcinomas often require adjuvant radiotherapy and/or chemotherapy. In contrast, the cornerstone in management of lymphoid lesions is chemotherapy, often including a monoclonal antibody. This article presents an update on the clinical, radiological, histological, and molecular features, along with treatment strategies for tumors of the lacrimal gland.

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.

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.

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.

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.

The impact of growth patterns of retinoblastoma (endophytic, exophytic, and mixed patterns).

OBJECTIVE: To study the impact of the retinoblastoma growth pattern (endophytic vs. exophytic) on the clinical and pathological features after primary enucleation. MATERIAL AND METHOD: A retrospective case series of 42 eyes of 41 patients who had pathologically confirmed retinoblastoma. The main outcome measures included demographics, laterality, international intraocular retinoblastoma (IIRC) group, vitreous seeding, neovascular glaucoma, choroid invasion, optic nerve invasion, metastasis, and survival. RESULTS: The median age at diagnosis was 30 months. Nineteen (46%) patients were males, and 17(41%) patients had bilateral retinoblastomas. Eight (19%) eyes were IIRC group C, 20 (48%) eyes were IIRC group D, and 14 (33%) eyes were IIRC group E. Nineteen (45%) tumors were endophytic, 14 (33%) were exophytic, and 9 (21%) were mixed. Choroid invasion was seen in 4 (21%) of the endophytic tumors, 5 (36%) of the exophytic tumors, and 8 (89%) of the mixed tumors (p=0.025). A mixed growth pattern was associated with massive choroid invasion in 5 (56%) of eyes. Neovascular glaucoma was seen in 5 (56%) of the mixed tumors (p=0.0376). Vitreous seeds were seen in 6 (67%) of the mixed tumors (p=0.0448). Optic nerve invasion as well as patients' age at diagnosis, gender, and tumor laterality had no correlation with tumor growth pattern. At a median follow up of 36 months, no single case had metastasis or was dead. CONCLUSION: Exophytic tumors have higher risk of choroid invasion, while endophytic tumors have higher risk of vitreous seeding. The mixed tumor growth pattern is associated with more advanced IIRC group, more risk of neovascular glaucoma, and more risk of massive choroid invasion.

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.