Uveal melanoma
Uveal melanoma is the most common primary intraocular cancer in adults with an incidence of less than one individual per 100,000 per year. Uveal melanoma can arise in the choroid, the ciliary body or the iris.
In almost 50% of patients the tumour disseminates to the liver and other parts of the body. Clinical and histopathological features associated with metastatic uveal melanoma include: large tumour diameter; epithelioid cytomorphology; closed connective tissue loops; and high mitotic rate. UM is also an unusual solid tumour in that gross chromosomal abnormalities are strongly associated with the development of metastasis and patient mortality.
In particular metastatic disease occurs almost exclusively in patients whose tumour shows chromosome 3 loss. In the absence of this abnormality, the prognosis for survival is extremely good.
Our laboratory research into uveal melanoma focusses on understanding the biological and genetic processes that make this cancer behave so aggressively. Our work has already enhanced prognostication, making it possible to predict the future health of our patients. We hope to gain a better understanding of tumour behaviour so that more effective treatments can be developed, thereby prolonging life.
Our clinical research has made it possible to save useful vision in eyes that would previously have been lost and treatment methods we have developed are now being adopted around the world. These include: various methods of local resection of choroidal melanoma; proton beam radiotherapy of iris melanoma; eccentric placement of ruthenium plaque in the treatment of choroidal melanoma; and biopsy of choroidal melanoma.
We are also investigating quality of life in patients with intraocular melanoma so that we can understand how patients react to their disease and its treatment and such insights will help us to anticipate and avert psychological difficulties.
Conjunctival melanoma
Melanomas of the conjunctiva (the transparent sheath that covers the eyeball and the inner surface of the eyelid) are very rare; occurring in less than one individual per million people every year, most commonly in the Caucasian population. These melanomas usually appear in adulthood with the mean age of incidence being around 60 years. Conjunctival melanomas can appear spontaneously or following the development of intra-epithelial neoplasia, rarely they develop from an already existing mole or naevus.
One fifth of patients develop metastatic disease within 2-3 years of diagnosis with an estimated one third of these patients dying within ten years of the onset of symptoms. Approximately half of all conjunctival melanomas recur.
Standardised documentation to record the presentation and treatment of conjunctival melanomas has been developed by the Liverpool Ocular Oncology Centre (LOOC) in order to facilitate better collection of data for this rare tumour in multicentre studies. This system was used to successfully audit treatment of conjunctival melanomas at the LOOC.
Studies of the aetiology and pathogenesis of conjunctival melanoma have been hampered by the rarity of the disease resulting in many investigations analysing a limited number of patient samples. Despite this several genetic studies have revealed the presence of frequent BRAF mutation; in addition, the common, non-random genetic abnormalities of chromosomes 3, 6 and 8, that occur in uveal melanomas, are not found in conjunctival melanoma suggesting, a more similar pathogenesis to cutaneous melanoma. Studies performed by LOORG demonstrated common amplification of CDKN1A and RUNX2 in primary conjunctival melanomas. In metastases amplification of MLH1, TIMP2 and chromosome 20q were also common in addition to deletion of MGMT and ECHS1.
Ocular adnexal lymphoma
Ocular adnexa lymphomas (OAL) represent 8% of all extranodal non-Hodgkin lymphomas (NHL), which develop as primary or secondary tumour manifestations in the orbit, conjunctiva, eyelids, and lacrimal glands and drainage system. OAL are sub-typed according to the World Health Organisation Classification, with extranodal marginal zone B-cell lymphoma of the ocular adnexa (EMZL-OA) accounting for 60-70% of these tumours. The remaining 30-40% of OALs comprise diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), plasmacytoma, mantle cell lymphoma (MCL) and T-cell lymphomas, in decreasing frequency. The incidence of EMZL-OA has inexplicably increased over the last two decades at a rate of 6% annually.
Although most EMZL-OA patients present initially with limited disease, up to 1/3 subsequently develop disseminated lymphoma. Currently it is difficult to predict disease course both clinically and histopathologically, although various parameters, such as anatomical location, serum lactate dehydrogenase levels, patient age and gender as well as tumour cell Ki-67 growth fraction have been suggested to be of prognostic value.
The pathogenesis of OAL is currently poorly understood. Previous studies have suggested infection with Chlamydia could contribute to the development of OAL in some countries, however this remains controversial. Recently, deletion of 6q23.3-24.1 with loss of A20, a putative tumour suppressor gene and a negative regulator of the NF-kB signalling pathway, has been described as a predictive biomarker for EMZL-OA recurrence and systemic dissemination. Promoter hypermethylation and inactivating mutations of A20 are reported to exist in about one third of EMZL-OA cases.
More specific information on the research being undertaken within LOORG can be found under Research Team
Uveal melanoma is the most common primary intraocular cancer in adults with an incidence of less than one individual per 100,000 per year. Uveal melanoma can arise in the choroid, the ciliary body or the iris.
In almost 50% of patients the tumour disseminates to the liver and other parts of the body. Clinical and histopathological features associated with metastatic uveal melanoma include: large tumour diameter; epithelioid cytomorphology; closed connective tissue loops; and high mitotic rate. UM is also an unusual solid tumour in that gross chromosomal abnormalities are strongly associated with the development of metastasis and patient mortality.
In particular metastatic disease occurs almost exclusively in patients whose tumour shows chromosome 3 loss. In the absence of this abnormality, the prognosis for survival is extremely good.
Our laboratory research into uveal melanoma focusses on understanding the biological and genetic processes that make this cancer behave so aggressively. Our work has already enhanced prognostication, making it possible to predict the future health of our patients. We hope to gain a better understanding of tumour behaviour so that more effective treatments can be developed, thereby prolonging life.
Our clinical research has made it possible to save useful vision in eyes that would previously have been lost and treatment methods we have developed are now being adopted around the world. These include: various methods of local resection of choroidal melanoma; proton beam radiotherapy of iris melanoma; eccentric placement of ruthenium plaque in the treatment of choroidal melanoma; and biopsy of choroidal melanoma.
We are also investigating quality of life in patients with intraocular melanoma so that we can understand how patients react to their disease and its treatment and such insights will help us to anticipate and avert psychological difficulties.
Conjunctival melanoma
Melanomas of the conjunctiva (the transparent sheath that covers the eyeball and the inner surface of the eyelid) are very rare; occurring in less than one individual per million people every year, most commonly in the Caucasian population. These melanomas usually appear in adulthood with the mean age of incidence being around 60 years. Conjunctival melanomas can appear spontaneously or following the development of intra-epithelial neoplasia, rarely they develop from an already existing mole or naevus.
One fifth of patients develop metastatic disease within 2-3 years of diagnosis with an estimated one third of these patients dying within ten years of the onset of symptoms. Approximately half of all conjunctival melanomas recur.
Standardised documentation to record the presentation and treatment of conjunctival melanomas has been developed by the Liverpool Ocular Oncology Centre (LOOC) in order to facilitate better collection of data for this rare tumour in multicentre studies. This system was used to successfully audit treatment of conjunctival melanomas at the LOOC.
Studies of the aetiology and pathogenesis of conjunctival melanoma have been hampered by the rarity of the disease resulting in many investigations analysing a limited number of patient samples. Despite this several genetic studies have revealed the presence of frequent BRAF mutation; in addition, the common, non-random genetic abnormalities of chromosomes 3, 6 and 8, that occur in uveal melanomas, are not found in conjunctival melanoma suggesting, a more similar pathogenesis to cutaneous melanoma. Studies performed by LOORG demonstrated common amplification of CDKN1A and RUNX2 in primary conjunctival melanomas. In metastases amplification of MLH1, TIMP2 and chromosome 20q were also common in addition to deletion of MGMT and ECHS1.
Ocular adnexal lymphoma
Ocular adnexa lymphomas (OAL) represent 8% of all extranodal non-Hodgkin lymphomas (NHL), which develop as primary or secondary tumour manifestations in the orbit, conjunctiva, eyelids, and lacrimal glands and drainage system. OAL are sub-typed according to the World Health Organisation Classification, with extranodal marginal zone B-cell lymphoma of the ocular adnexa (EMZL-OA) accounting for 60-70% of these tumours. The remaining 30-40% of OALs comprise diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), plasmacytoma, mantle cell lymphoma (MCL) and T-cell lymphomas, in decreasing frequency. The incidence of EMZL-OA has inexplicably increased over the last two decades at a rate of 6% annually.
Although most EMZL-OA patients present initially with limited disease, up to 1/3 subsequently develop disseminated lymphoma. Currently it is difficult to predict disease course both clinically and histopathologically, although various parameters, such as anatomical location, serum lactate dehydrogenase levels, patient age and gender as well as tumour cell Ki-67 growth fraction have been suggested to be of prognostic value.
The pathogenesis of OAL is currently poorly understood. Previous studies have suggested infection with Chlamydia could contribute to the development of OAL in some countries, however this remains controversial. Recently, deletion of 6q23.3-24.1 with loss of A20, a putative tumour suppressor gene and a negative regulator of the NF-kB signalling pathway, has been described as a predictive biomarker for EMZL-OA recurrence and systemic dissemination. Promoter hypermethylation and inactivating mutations of A20 are reported to exist in about one third of EMZL-OA cases.
More specific information on the research being undertaken within LOORG can be found under Research Team
