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European Journal of Cancer (Oxford,... May 2021The rising interest for precise characterization of the tumour immune contexture has recently brought forward the high potential of RNA sequencing (RNA-seq) in... (Review)
Review
The rising interest for precise characterization of the tumour immune contexture has recently brought forward the high potential of RNA sequencing (RNA-seq) in identifying molecular mechanisms engaged in the response to immunotherapy. In this review, we provide an overview of the major principles of single-cell and conventional (bulk) RNA-seq applied to onco-immunology. We describe standard preprocessing and statistical analyses of data obtained from such techniques and highlight some computational challenges relative to the sequencing of individual cells. We notably provide examples of gene expression analyses such as differential expression analysis, dimensionality reduction, clustering and enrichment analysis. Additionally, we used public data sets to exemplify how deconvolution algorithms can identify and quantify multiple immune subpopulations from either bulk or single-cell RNA-seq. We give examples of machine and deep learning models used to predict patient outcomes and treatment effect from high-dimensional data. Finally, we balance the strengths and weaknesses of single-cell and bulk RNA-seq regarding their applications in the clinic.
Topics: Artificial Intelligence; Biomarkers, Tumor; Clinical Decision-Making; Gene Expression Profiling; Humans; Neoplasms; Precision Medicine; Predictive Value of Tests; Prognosis; RNA, Neoplasm; RNA-Seq; Single-Cell Analysis; Transcriptome; Tumor Microenvironment
PubMed: 33866228
DOI: 10.1016/j.ejca.2021.03.005 -
Eye (London, England) Feb 2017Although it is a relatively rare disease, primarily found in the Caucasian population, uveal melanoma is the most common primary intraocular tumor in adults with a mean... (Review)
Review
Although it is a relatively rare disease, primarily found in the Caucasian population, uveal melanoma is the most common primary intraocular tumor in adults with a mean age-adjusted incidence of 5.1 cases per million per year. Tumors are located either in iris (4%), ciliary body (6%), or choroid (90%). The host susceptibility factors for uveal melanoma include fair skin, light eye color, inability to tan, ocular or oculodermal melanocytosis, cutaneous or iris or choroidal nevus, and BRCA1-associated protein 1 mutation. Currently, the most widely used first-line treatment options for this malignancy are resection, radiation therapy, and enucleation. There are two main types of radiation therapy: plaque brachytherapy (iodine-125, ruthenium-106, or palladium-103, or cobalt-60) and teletherapy (proton beam, helium ion, or stereotactic radiosurgery using cyber knife, gamma knife, or linear accelerator). The alternative to radiation is enucleation. Although these therapies achieve satisfactory local disease control, long-term survival rate for patients with uveal melanoma remains guarded, with risk for liver metastasis. There have been advances in early diagnosis over the past few years, and with the hope survival rates could improve as smaller tumors are treated. As in many other cancer indications, both early detection and early treatment could be critical for a positive long-term survival outcome in uveal melanoma. These observations call attention to an unmet medical need for the early treatment of small melanocytic lesions or small melanomas in the eye to achieve local disease control and vision preservation with the possibility to prevent metastases and improve overall patient survival.
Topics: Age Distribution; Combined Modality Therapy; Humans; Incidence; Iridectomy; Melanoma; Radiosurgery; Radiotherapy; Risk Factors; Sex Distribution; Tumor Suppressor Proteins; Ubiquitin Thiolesterase; Ultraviolet Rays; Uveal Neoplasms
PubMed: 27911450
DOI: 10.1038/eye.2016.275 -
Ugeskrift For Laeger May 2023Melanoma isolated to the iris is rare and can present with a distorted pupil. This is a case report of an 81-year-old asymptomatic man, who had a large pigmented element...
Melanoma isolated to the iris is rare and can present with a distorted pupil. This is a case report of an 81-year-old asymptomatic man, who had a large pigmented element in his left iris through 30 years. Because of involvement of the angle the tumour was excised with the ciliary body, and histopathologic examination revealed an iris melanoma. The aim of this report is to underscore the clinical signs of an iris melanoma and when surgery is needed.
Topics: Male; Humans; Aged, 80 and over; Pupil; Iris Neoplasms; Iris; Melanoma
PubMed: 37170744
DOI: No ID Found -
Archives of Pathology & Laboratory... Feb 2008The iris is the least common site of primary uveal melanoma. The prognosis of iris melanoma is better than that of melanoma of the ciliary body and choroid, but the... (Review)
Review
The iris is the least common site of primary uveal melanoma. The prognosis of iris melanoma is better than that of melanoma of the ciliary body and choroid, but the reason for this difference is unclear. One possible explanation is that iris melanoma is smaller than its posterior segment counterparts at the time of diagnosis. Most iris melanomas are spindle cell types, according to a modified Callender classification system. There is evidence that the proliferation of melanocytes of the anterior iris surface (iris plaque) and diffuse stromal invasion may be risk factors for local recurrence and metastasis, respectively.
Topics: Biomarkers, Tumor; Humans; Immunohistochemistry; Iris Neoplasms; Melanoma; Middle Aged; Prognosis; Survival Rate
PubMed: 18251588
DOI: 10.5858/2008-132-268-IM -
Survey of Ophthalmology 2020Intraocular leiomyoma is a benign smooth muscle tumor. First recognized before the era of immunohistochemistry, uveal leiomyomas have been described in case reports and... (Review)
Review
Intraocular leiomyoma is a benign smooth muscle tumor. First recognized before the era of immunohistochemistry, uveal leiomyomas have been described in case reports and small case series. We add 3 new cases, for a total of 80. Of these, there were 29 men and 51 women. The mean and median ages were 35.8 and 30.5 years respectively, with a range of 8 to 80 years. Curiously, ciliary body tumors were more common in females, whereas iris and posterior choroidal leiomyomas were more prevalent in males. Infrequently associated with systemic fibroids, nuclear expression of sex steroid receptors was inconsistent. Iris and posterior choroidal leiomyoma were predominantly amelanotic, while 40% of ciliary body leiomyomas were brown. Two-thirds of the leiomyomas blocked transillumination partially or completely, a feature shared by uveal melanoma. In general, low-frequency ultrasound imaging reveals low to moderate internal reflectivity; however, high-frequency anterior uveal ultrasound was used to localize a leiomyoma as resident in the suprachoroidal space with an overlying layer of intact choroid. In the few cases examined by physiologic imaging, increased metabolic activity (typically associated with malignancy and inflammation) has been noted. We found that pigmented uveal leiomyomas can be clinically identical to melanoma. Therefore, histopathology with immunohistochemical staining for smooth muscle actin was the most reliable diagnostic method to differentiate pigmented uveal leiomyoma from melanoma. Treatment is governed by the clinical diagnosis, tumor size and location, as well as prognosis for vision and globe preservation.
Topics: Adult; Eye Neoplasms; Female; Humans; Leiomyoma; Male; Middle Aged; Uvea
PubMed: 31923479
DOI: 10.1016/j.survophthal.2019.12.008 -
Orphanet Journal of Rare Diseases Aug 2006Retinoblastoma is a rare eye tumor of childhood that arises in the retina. It is the most common intraocular malignancy of infancy and childhood; with an incidence of... (Review)
Review
Retinoblastoma is a rare eye tumor of childhood that arises in the retina. It is the most common intraocular malignancy of infancy and childhood; with an incidence of 1/15,000-20,000 live births. The two most frequent symptoms revealing retinoblastoma are leukocoria and strabismus. Iris rubeosis, hypopyon, hyphema, buphthalmia, orbital cellulites and exophthalmia may also be observed. Sixty per cent of retinoblastomas are unilateral and most of these forms are not hereditary (median age at diagnosis two years). Retinoblastoma is bilateral in 40% of cases (median age at diagnosis one year). All bilateral and multifocal unilateral forms are hereditary. Hereditary retinoblastoma constitutes a cancer predisposition syndrome: a subject constitutionally carrying an RB1 gene mutation has a greater than 90% risk of developing retinoblastoma but is also at increased risk of developing other types of cancers. Diagnosis is made by fundoscopy. Ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) scans may contribute to diagnosis. Management of patients with retinoblastoma must take into account the various aspects of the disease: the visual risk, the possibly hereditary nature of the disease, the life-threatening risk. Enucleation is still often necessary in unilateral disease; the decision for adjuvant treatment is taken according to the histological risk factors. Conservative treatment for at least one eye is possible in most of the bilateral cases. It includes laser alone or combined with chemotherapy, cryotherapy and brachytherapy. The indication for external beam radiotherapy should be restricted to large ocular tumors and diffuse vitreous seeding because of the risk of late effects, including secondary sarcoma. Vital prognosis, related to retinoblastoma alone, is now excellent in patients with unilateral or bilateral forms of retinoblastoma. Long term follow-up and early counseling regarding the risk of second primary tumors and transmission should be offered to retinoblastoma patients.
Topics: Child, Preschool; Diagnosis, Differential; Eye Diseases; Female; Humans; Infant; Pregnancy; Prenatal Diagnosis; Prognosis; Rare Diseases; Retinal Neoplasms; Retinoblastoma; Retinoblastoma Protein
PubMed: 16934146
DOI: 10.1186/1750-1172-1-31 -
BMC Ophthalmology Jan 2022To characterise the topographical and clinical features of primary iris melanoma and to visualise the patterns of tumour extent in the iris.
BACKGROUND
To characterise the topographical and clinical features of primary iris melanoma and to visualise the patterns of tumour extent in the iris.
METHODS
Clinical characteristics of iris melanomas were analysed, and data on their size, shape, and location were converted into a database of two-dimensional iris charts by means of computer-drawing software. The geometric centre of each tumour was entered into corresponding sectors of the chart. The extent of the melanomas was computationally visualised by merging the iris drawings and displaying the number of overlapping tumours on colour-coded iris maps.
RESULTS
Twenty-nine patients (18 females and 11 males) with a mean age of 52 years met the inclusion criteria. The mean largest tumour diameter was 6.1 mm (range, 1.8-11.0 mm). Five tumours (17%) involved the pupillary margin, 10 (34%) involved the iris root, and 10 (34%) involved both sites. The hemispheric location of the tumour centroid was superior in 3 eyes (11%) and inferior in 25 (89%) (p < 0.0001), and the distribution between the temporal and nasal hemispheres was 17 (61%) and 11 (39%), respectively (p = 0.26). In females, the iris melanomas were located more temporally (p = 0.02) and had more often originated from a pre-existing naevus (p = 0.03), than in males. There was also shift towards more temporally located melanomas in younger patients.
CONCLUSIONS
The lower temporal iris quadrant is the preferential area of melanoma occurrence and growth. Iris melanoma tends to be more temporally located in females, who compared with males also have a higher proportion of melanomas arising from a pre-existing naevus.
Topics: Female; Humans; Iris; Iris Neoplasms; Male; Melanoma; Middle Aged; Uveal Neoplasms
PubMed: 34980044
DOI: 10.1186/s12886-021-02236-3 -
International Journal of Molecular... Sep 2020Uveal melanoma (UM) is a global disease which especially occurs in elderly people. Its incidence varies widely between populations, with the highest incidence among... (Review)
Review
Uveal melanoma (UM) is a global disease which especially occurs in elderly people. Its incidence varies widely between populations, with the highest incidence among Caucasians, and a South-to-North increase in Europe. As northern Europeans often have blond hair and light eyes, we wondered whether iris colour may be a predisposing factor for UM and if so, why. We compared the distribution of iris colour between Dutch UM patients and healthy Dutch controls, using data from the Rotterdam Study (RS), and reviewed the literature regarding iris colour. We describe molecular mechanisms that might explain the observed associations. When comparing a group of Dutch UM patients with controls, we observed that individuals from Caucasian ancestry with a green/hazel iris colour (Odds Ratio (OR) = 3.64, 95% Confidence Interval (CI) 2.57-5.14) and individuals with a blue/grey iris colour (OR = 1.38, 95% CI 1.04-1.82) had a significantly higher crude risk of UM than those with brown eyes. According to the literature, this may be due to a difference in the function of pheomelanin (associated with a light iris colour) and eumelanin (associated with a brown iris colour). The combination of light-induced stress and aging may affect pheomelanin-carrying melanocytes in a different way than eumelanin-carrying melanocytes, increasing the risk of developing a malignancy.
Topics: Aged; Aged, 80 and over; Aging; Cohort Studies; Eye Color; Female; Humans; Incidence; Iris; Light; Male; Melanins; Melanocytes; Melanoma; Middle Aged; Netherlands; Odds Ratio; Uveal Neoplasms; White People
PubMed: 32998469
DOI: 10.3390/ijms21197172 -
Oman Journal of Ophthalmology Sep 2013Iris tumors are broadly classified into cystic or solid lesions. The cystic lesions arise from iris pigment epithelium (IPE) or iris stroma. IPE cysts classically remain... (Review)
Review
Iris tumors are broadly classified into cystic or solid lesions. The cystic lesions arise from iris pigment epithelium (IPE) or iris stroma. IPE cysts classically remain stable without need for intervention. Iris stromal cyst, especially those in newborns, usually requires therapy of aspiration, possibly with alcohol-induced sclerosis, or surgical resection. The solid tumors included melanocytic and nonmelanocytic lesions. The melanocytic iris tumors include freckle, nevus (including melanocytoma), Lisch nodule, and melanoma. Information from a tertiary referral center revealed that transformation of suspicious iris nevus to melanoma occurred in 4% by 10 years and 11% by 20 years. Risk factors for transformation of iris nevus to melanoma can be remembered using the ABCDEF guide as follows: A=age young (<40 years), B=blood (hyphema) in anterior chamber, C=clock hour of mass inferiorly, D=diffuse configuration, E=ectropion, F=feathery margins. The most powerful factors are diffuse growth pattern and hyphema. Tumor seeding into the anterior chamber angle and onto the iris stroma are also important. The nonmelanocytic iris tumors are relatively uncommon and included categories of choristomatous, vascular, fibrous, neural, myogenic, epithelial, xanthomatous, metastatic, lymphoid, leukemic, secondary, and non-neoplastic simulators. Overall, the most common diagnoses in a clinical series include nevus, IPE cyst, and melanoma. In summary, iris tumors comprise a wide spectrum including mostly iris nevus, IPE cyst, and iris melanoma. Risk factors estimating transformation of iris nevus to melanoma can be remembered by the ABCDEF guide.
PubMed: 24379549
DOI: 10.4103/0974-620X.122269