Pathogenic Germline Variants in Uveal Melanoma Driver and BAP1-Associated Genes in Finnish Patients with Uveal Melanoma.

Uveal melanoma (UM) is a rare yet aggressive eye cancer causing over 50% mortality from metastasis. Familial UM, amounting to 1%-6% of patients in Finland and the United States, mostly lack identified genetic cause, while 8% show associations with other cancer syndromes. We searched novel genetic associations for predisposition to UM, additional to already studied BAP1 and MBD4, by using targeted amplicon sequencing of 19 genes associated with UM, BAP1, or renal cell carcinoma in 270 consecutively enrolled Finnish patients with UM.

The Pediatric and Young Adult Choroidal and Ciliary Body Melanoma Genetic Study, A Survey by the European Ophthalmic Oncology Group.

Purpose: To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group.

Methods: Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor.

Pediatric ocular melanoma: a collaborative multicenter study and meta-analysis.

Purpose: To investigate clinical manifestations and prognoses in pediatric patients (≤12 years old) with ocular melanoma.

Methods: This was a retrospective, multicenter cohort study with individual participant data (IPD) meta-analysis pooling available published cases, and unpublished cases from an international collaboration of seven ocular oncology centers.

Results: There were 133 eyes of 133 pediatric patients with choroidal or ciliary body (n = 66 [50%]), iris (n = 33 [25%]), conjunctival (n = 26 [19%]), and eyelid (n = 8 [6%]) melanoma.

Presumed incipient choroidal melanoma: proposed diagnostic criteria and management.

Aims: To propose diagnostic criteria for a presumed incipient choroidal melanoma based on tumour growth rate and tumour doubling time (TDT) and to describe management of such tumours with transpupillary thermotherapy (TTT).

Methods: Retrospective interventional case series of nine consecutive presumed incipient uveal melanomas diagnosed and treated with TTT in 2010-2017. Growth rate in mm/year and per cent/year in largest basal diameter (LBD) and TDT were compared with published data for uveal melanomas and growing naevi that did not transform to melanoma under long-term follow-up.

Very late orbital recurrence of choroidal melanoma four decades post enucleation.

Orbital recurrence of malignant choroidal melanoma is quite uncommon, occurring in about 3% of patients undergoing enucleation for large tumors. Orbital recurrences after more than 10 years from enucleation are even rarer. In literature, only few reports described orbital recurrence that occurred between 10 and 40 years after primary diagnosis.

Iris extramedullary hematopoiesis in choroidal melanoma.

Purpose: Extramedullary hematopoiesis (EMH) usually occurs in patients with loss of bone marrow hematopoietic function, and in a vast majority of cases, it involves the liver, the spleen, or the lymph nodes. We report EMH in the iris of patients enucleated for choroidal melanoma (CM).

Methods: We report a series of three patients with CM, two treated with primary enucleation and one with secondary enucleation.

Ultra-wide-field imaging assessment of small choroidal pigmented lesions using red and green colour channels.

Background: Diagnosis of small choroidal melanoma is mainly based on tumour thickness, subretinal fluid, or lipofuscin pigment. Ultra-wide-field imaging (UWF) allows depiction of choroidal lesions through a red (RC) and a green channel (GC). Aim of the study was to determine the utility of this tool in the detection of small choroidal melanoma.

Very late recurrence of iris melanoma: 45 years after treatment.

Iris melanoma is a rare tumour that accounts for ~3-4% of all uveal melanoma cases. In the past, surgical resection was the sole treatement option, whereas nowadays, it has been replaced by brachytherapy as treatment of choice. Surgical resection is still in use in selected cases but combined with adjuvant radiotherapy in cases of incomplete resection.

Comprehensive Study of the Clinical Phenotype of Germline BAP1 Variant-Carrying Families Worldwide.

Background: The BRCA1-associated protein-1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is a hereditary tumor syndrome caused by germline pathogenic variants in BAP1 encoding a tumor suppressor associated with uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and cutaneous BAP1-inactivated melanocytic tumors. However, the full spectrum of tumors associated with the syndrome is yet to be determined. Improved understanding of the BAP1-TPDS is crucial for appropriate clinical management of BAP1 germline variant carriers and their families, including genetic counseling and surveillance for new tumors.

Conjunctival Melanoma during Pregnancy.

Purpose: To describe the clinical and histopathological features of a conjunctival melanoma (CM) during early pregnancy.

Procedures: A 37-year-old, 20-week pregnant primigravida was referred to the Sheffield Ocular Oncology Service with a rapidly growing lesion arising from the right superior conjunctival fornix, noted from the first trimester of pregnancy. This was associated with pain and bloody discharge.

The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group.

Purpose: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI.

Design: Retrospective, multicenter observational study.

Participants: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.

Uveal melanoma among Finnish children and young adults.

Purpose: To characterize uveal melanoma (UM) among children and young adults in a high-risk region for this cancer.

Methods: The medical records of consecutive patients <25 years of age with UM treated from 1962 to 2009 were retrospectively reviewed. The following data were collected: sex, tumor location and size, tumor node metastasis (TNM) stage, vision, and survival.

Prognostic associations of insulin-like growth factor-1 receptor in primary uveal melanoma.

Objective: To study the association between immunoreactivity for insulin-like growth factor-1 receptor (IGF-1R) in primary ciliary body and choroidal melanoma and metastatic death in a consecutive, population-based data set.

Design: Retrospective, consecutive, population-based cohort study.

Participants: A total of 167 patients with choroidal and ciliary body melanoma, enucleated from 1972 to 1981, with long-term survival data.

Nucleolar size in choroidal and ciliary body melanomas and corresponding hepatic metastases.

Purpose: This study aimed to investigate the relationship between hepatic metastasis and the mean diameter of the 10 largest nucleoli (MLN) in uveal melanoma.

Methods: A cross-sectional histopathological analysis of 37 metastases (13 surgical or needle biopsies, 24 autopsies) and corresponding primary choroidal and ciliary body melanomas was conducted, using statistical tests appropriate for paired data. The largest nucleoli were measured from digital photographs of silver-stained sections along a 5-mm-wide linear field.

KI-67 immunopositivity in choroidal and ciliary body melanoma with respect to nucleolar diameter and other prognostic factors.

Purpose: To study the association of cell proliferation in uveal melanoma with the mean of the 10 largest nucleoli (MLN), microvascular prognostic factors, and survival.

Methods: Population-based, retrospective cohort study of 167 choroidal and ciliary body melanomas enucleated from 1972 to 1981. Mouse monoclonal antibody Ki-67 (clone 7B11) was used to identify proliferating cells.

Microvascular loops and networks in uveal melanoma.

Microvascular patterns--three-dimensional architectural arrangements of microvessels and extravascular matrix in uveal melanoma--were discovered when investigators were looking for histopathological features of sufficient size to be imaged clinically. Evidence that these patterns may be formed by tumour cells and that they may be able to conduct plasma and blood as well as discovery of similar elements in other cancers make them of general importance. Of nine different patterns described, closed microvascular loops and networks have been studied most extensively.

Nucleolar diameter and microvascular factors as independent predictors of mortality from malignant melanoma of the choroid and ciliary body.

Purpose: To determine whether nucleolar diameter and microvascular factors are independent predictors of mortality in malignant uveal melanoma of the choroid and ciliary body.

Method: A population-based retrospective cohort study was conducted of melanoma-specific and all-cause mortality in 167 consecutive patients who had an eye enucleated because of choroidal and ciliary body melanoma from 1972 through 1981. The largest nucleoli were measured from digital photographs of silver-stained tumors along a central 5-mm-wide linear field parallel to the base of the tumor.