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IMPORTANCE: Ocular surface squamous neoplasia (OSSN) is a spectrum of malignancies that generally includes conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC). OSSN can be treated with topical therapies including interferon α-2b (IFN), mitomycin C (MMC), or 5-fluorouracil 1% (5FU). Recently, due to unavailability of IFN and toxicity associated with MMC, therapy has shifted towards 5FU. OBJECTIVE: Herein, we compare the use of 5FU 1% as a primary versus (vs) secondary treatment regimen in eyes with moderate to extensive OSSN. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study of 73 consecutive patients with unilateral moderate to extensive OSSN treated at a single tertiary ocular oncology center from 2016 to 2023. Mean follow up time was 478.2 days overall, with 283.0 days for primary 5FU group and 860.3 days for secondary 5FU group. INTERVENTION: Topical 5FU 1% 4 times daily for 2 weeks with option for 2-weekly extension until tumor control, either as primary treatment or as secondary treatment to surgical resection, topical IFN or topical MMC, or cryotherapy. MAIN OUTCOMES: Outcome measures included tumor response, need for additional surgery, complications, and visual outcomes. RESULTS: A comparison (primary vs secondary treatment) revealed no difference in mean tumor basal dimension (19.6 vs 17.2 mm, P = 0.46), thickness (3.7 vs 3.4 mm, P = 0.64), or tumor extent (4.4 vs 4.5 clock hours, P = 0.92). The primary treatment group showed greater complete tumor control (77% vs 38%, P = 0.04). Multivariable analysis comparison (primary vs secondary treatment) showed primary treatment more likely to achieve complete tumor control (P = 0.01). There was no difference in the complication rate from 5FU treatment between the groups. There was no difference in visual outcome, and no tumor-related metastasis (0%) or death (0%). CONCLUSION AND RELEVANCE: Topical 5FU 1% is efficacious and safe as a primary or secondary treatment for moderate to extensive OSSN. Tumors treated with primary 5FU 1% demonstrated more complete resolution. In patients with moderate to extensive OSSN, primary treatment with topical 5FU 1% may be warranted.
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Antimetabolitos Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias de la Conjuntiva , Fluorouracilo , Humanos , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias de la Conjuntiva/tratamiento farmacológico , Neoplasias de la Conjuntiva/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Antimetabolitos Antineoplásicos/administración & dosificación , Soluciones Oftálmicas/administración & dosificación , Adulto , Anciano de 80 o más Años , Administración Tópica , Resultado del Tratamiento , Estudios de SeguimientoRESUMEN
Indeterminate melanocytic proliferations of the conjunctiva have both benign and malignant features that previously made these lesions nearly impossible to categorize in existing classification schemes. With the evolution of immunohistochemistry and molecular genetics, however, subclassifications have emerged that allow for a more tailored diagnosis and management. These conjunctival melanocytic proliferations include deep penetrating nevus, granular cell nevus, and nevoid melanoma. There remains a small subset of conjunctival melanocytic proliferations that defy precise characterization as nevi, primary acquired melanosis, or melanomas despite currently available ancillary diagnostic modalities and remain indeterminate. We highlight these unusual types of nevi and melanomas, with an update on their morphologic, immunohistochemical, and molecular genetic characteristics.
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Neoplasias de la Conjuntiva , Melanoma , Nevo , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Neoplasias de la Conjuntiva/diagnóstico , Neoplasias de la Conjuntiva/patología , Nevo/diagnóstico , Nevo/metabolismo , Nevo/patología , Neoplasias Cutáneas/patología , Conjuntiva/metabolismo , Conjuntiva/patologíaRESUMEN
Conjunctival melanoma is quite rare, estimated at approximately 0.5 incidence per 1 million persons per year. This malignancy arises from a pre-existing nevus (7%), primary acquired melanosis (74%), or de novo without pre-existing condition (19%) and develops most often in patients with Fitzpatrick skin types I (23%) and II (62%). At initial presentation, the tumor size is approximately 13 mm in cross-sectional diameter and has 3-mm thickness, involving the bulbar (97%), forniceal (30%), tarsal (28%), or caruncular (11%) regions, often with corneal (54%) and rarely with orbital (4%) involvement. According to the eighth edition of the American Joint Committee on Cancer (AJCC), the tumor is classified as T1 (63%), T2 (18%), T3 (20%), and T4 (0%). Outcomes depend on several factors including patient age, AJCC classification, orbital invasion, and type of initial surgery, whereas tumor origin and Fitzpatrick skin type do not appear to impact outcomes. Older patients (≥70 years of age) demonstrate larger tumors, greater recurrence, and greater vision loss. Analysis of 425 patients by AJCC classification (T1 versus T2 versus T3) revealed increasing T category with greater lymph node metastasis (3% versus 13% versus 25%; P < .001), tumor-related systemic metastasis (13% versus 45% versus 40%; P < .001), and tumor-related death (8% versus 22% versus 37%; P < .001). Data of patients with orbital invasion revealed significantly greater 10-year rates of exenteration (P < .001), distant metastasis (P = .0005), and death (P = .001). Studies have demonstrated biomarkers related to conjunctival melanoma include mutations in BRAF, NRAS, ATRX, and NF1. Future therapies might be directed against these mutations or with small-molecule inhibitors and/or immunotherapy. In summary, conjunctival melanoma is a rare but ominous malignancy, imparting moderate risk for lymph node and systemic metastasis as well as death, depending on tumor features and classification. The first surgery is highly important in prevention of tumor seeding, recurrence, and metastasis.
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Neoplasias de la Conjuntiva , Melanoma , Humanos , Melanoma/terapia , Melanoma/patología , Recurrencia Local de Neoplasia/patología , Neoplasias de la Conjuntiva/patología , Neoplasias de la Conjuntiva/cirugía , Metástasis Linfática , Biomarcadores , Estudios Retrospectivos , Estadificación de NeoplasiasRESUMEN
Purpose: To evaluate cumulative incidence of metastasis at specific timepoints after treatment of uveal melanoma in a large cohort of patients and to provide comparison of conditional outcomes in the youngest and oldest cohorts (extremes of age). Methods: Retrospective analysis of 8091 consecutive patients with uveal melanoma at a single center over a 51-year period. The patients were categorized by age at presentation (0-29 years [n = 348, 4%], 30-59 years [n = 3859, 48%], 60-79 years [n = 3425, 42%], 80 to 99 years [n = 459, 6%]) and evaluated for nonconditional (from presentation date) and conditional (from specific timepoints after presentation) cumulative incidence of metastasis at five, 10, 20, and 30 years. Results: For the entire population of 8091 patients, five-year/10-year/20-year/30-year nonconditional cumulative incidence of metastasis was 15%/23%/32%/36%, and the conditional incidence improved to 6%/15%/25%/30% for patients who did not develop metastasis in the first three years. For the extremes of age (0-29 years and 80-99 years), the nonconditional cumulative incidence of metastasis revealed the younger cohort with superior outcomes at 8%/15%/19%/27% and 21%/29%/29%/29%, respectively (P < 0.001). The conditional incidence (at one-year and two-year timepoints with metastasis-free survival) showed persistent superior younger cohort survival (P < 0.001, P = 0.001), but no further benefit for patients with three-year metastasis-free survival at 4%/12%/16%/24% and 7%/18%/18%/18%, respectively (P = 0.09). Conclusions: Non-conditional metastasis-free survival analysis for patients with uveal melanoma revealed the youngest cohort to have significantly better survival than the oldest cohort, and this persisted into one-year and two-year conditional metastasis-free survival but diminished at the three-year conditional timepoint.
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Melanoma , Neoplasias de la Úvea , Humanos , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Estudios Retrospectivos , Neoplasias de la Úvea/patología , Melanoma/patología , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
A 53-year-old Caucasian male presented with an inflamed-appearing limbal nodule in his OD, clinically compatible with nodular episcleritis, that was unresponsive to topical corticosteroid therapy. Excisional biopsy of the lesion was performed and histopathological examination revealed foci of necrotizing vasculitis and granulomatous inflammation in a background of intense actinic elastosis. Infectious stains for organisms were negative. A comprehensive systemic evaluation for vasculitides was negative. Three years later, the patient returned with a clinically and histopathologically identical lesion in his OS. Systemic evaluation was noncontributory again, and a diagnosis of bilateral conjunctival actinic granuloma with necrobiotic vasculitic pattern was made.
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Enfermedades de la Piel , Vasculitis , Humanos , Masculino , Persona de Mediana Edad , Granuloma/diagnóstico , Granuloma/patología , Diagnóstico Diferencial , BiopsiaRESUMEN
A 58-year-old female with a 3-year history of adult-onset asthma, bilateral blepharoptosis, dry eye, and yellow-orange xanthelasma-like plaques extensively involving both upper eyelids presented with a diagnosis of adult-onset asthma with periocular xanthogranuloma (AAPOX) and systemic IgG4-related disease. Over the next 8 years, she received 10 intralesional triamcinolone injections (40-80 mg) in the right upper eyelid, 7 intralesional triamcinolone injections (30-60 mg) in the left upper eyelid, underwent right anterior orbitotomy twice followed by 4 doses of rituximab (1000 mg intravenous infusion) without regression of the AAPOX. The patient was then treated with 2 monthly doses of Truxima (1000 mg intravenous infusion), a biosimilar to rituximab. At the most recent follow-up, 13 months later, the xanthelasma-like plaques and orbital infiltration had markedly improved. To the best of the authors' knowledge, this is the first report of Truxima being used to treat AAPOX with systemic IgG4-related disease and to generate a sustained clinical response.
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Asma , Enfermedad Relacionada con Inmunoglobulina G4 , Neoplasias de los Tejidos Blandos , Xantomatosis , Femenino , Adulto , Humanos , Persona de Mediana Edad , Rituximab/uso terapéutico , Granuloma/diagnóstico , Xantomatosis/complicaciones , Xantomatosis/diagnóstico , Xantomatosis/tratamiento farmacológico , Asma/complicaciones , Asma/diagnóstico , Asma/tratamiento farmacológico , TriamcinolonaAsunto(s)
Efusiones Coroideas , Linfangiectasia Intestinal , Enteropatías Perdedoras de Proteínas , Desprendimiento de Retina , Humanos , Enteropatías Perdedoras de Proteínas/complicaciones , Enteropatías Perdedoras de Proteínas/diagnóstico , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/etiología , Linfangiectasia Intestinal/complicaciones , Linfangiectasia Intestinal/diagnósticoRESUMEN
Purpose: Retinoblastoma (RB) is most often diagnosed with clinical features and not diagnosed with tumor biopsy. This study describes tumor-derived analyte concentrations from aqueous humor (AH) liquid biopsy and its use in clinical assays. Design: Case series study. Participants: Sixty-two RB eyes from 55 children and 14 control eyes from 12 children from 4 medical centers. Methods: This study included 128 RB AH samples including: diagnostic (DX) samples, samples from eyes undergoing treatment (TX), samples after completing treatment (END), and during bevacizumab injection for radiation therapy after completing RB treatment (BEV). Fourteen-control AH were analyzed for unprocessed analytes (double-stranded DNA [dsDNA], single-stranded DNA [ssDNA], micro-RNA [miRNA], RNA, and protein) with Qubit fluorescence assays. Double-stranded DNA from 2 RB AH samples underwent low-pass whole-genome sequencing to detect somatic copy number alterations. Logistic regression was used to predict disease burden given analyte concentrations. Main Outcome Measures: Unprocessed analyte (dsDNA, ssDNA, miRNA, RNA and protein) concentrations. Results: Results revealed dsDNA, ssDNA, miRNA, and proteins, but not RNA, were quantifiable in most samples (up to 98%) with Qubit fluorescence assays. Median dsDNA concentration was significantly higher in DX (3.08 ng/µl) compared to TX (0.18 ng/µl; P < 0.0001) at an order of 17 times greater and 20 times greater than END samples (0.15 ng/µl; P = 0.001). Using logistic regression, nucleic acid concentrations were useful in predicting higher versus lower RB disease burden. Retinoblastoma somatic copy number alterations were identified in a TX, but not in a BEV sample, indicating the correlation with RB activity. Conclusions: Aqueous humor liquid biopsy in RB is a high-yield source of dsDNA, ssDNA, miRNA, and protein. Diagnostic samples are most useful for RB 1 gene mutational analyses. Genomic analysis may be more informative of tumor activity status than quantification alone and can be performed even with smaller analyte concentrations obtained from TX samples. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.
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Conjunctival melanoma, a rare malignancy of the ocular surface, is increasing in incidence. When small, straightforward excision with "no touch" surgery and cryotherapy at an experienced centre can provide excellent outcomes. When advanced, management is more complex and highly individualized. The risk of metastatic disease from conjunctival melanoma is as high as 30% and depends on tumour origin, American Joint Committee on Cancer (AJCC) classification, biomarkers, and perhaps most important, management technique. Metastatic disease can result in melanoma-associated death. Therefore, early detection and prompt directed treatment at an experienced centre are important for protection from metastasis. In this review, we provide an update on conjunctival melanoma clinical features, diagnostic modalities, AJCC staging, genetic markers, and the most critical, controlled management with minimization of tumour seeding. We detail the new era of characterization of conjunctival melanoma with molecular biomarkers that predict melanoma prognosis. This could lead to precision medicine with targeted approaches to specific mutations that improve patient survival. As we work together, the field of conjunctival melanoma is moving forward.
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PURPOSE: To compare the clinical features at presentation and treatment outcomes of conjunctival melanoma by absence/presence of orbital invasion. METHODS: A retrospective review of patients with conjunctival melanoma managed at a single tertiary referral center from April 18, 1974, to September 9, 2019. RESULTS: Of 430 patients with conjunctival melanoma, 21 (5%) had orbital invasion at presentation. A comparison between the 2 groups (orbital invasion absent vs. present) revealed that the orbital invasion group had a higher frequency of prior eyelid incisional biopsy (5% vs. 24%, P = 0.006), greater tumor basal diameter (12.2 vs. 17.3, P = 0.009), greater tumor thickness (2.4 vs. 7.0, P < 0.001), more quadrants involved (1.8 vs. 2.5, P = 0.002), and more clock hours involved (4.4 vs. 5.8, P = 0.037). In addition, those with orbital invasion were more likely to undergo exenteration as primary treatment (1% vs. 24%, P < 0.001). Multivariate relative risk regression analysis revealed that variables predictive of orbital invasion included greater tumor thickness (P < 0.001) and greater involvement of the fornix (P = 0.031) and tarsus (P = 0.033). Outcomes revealed orbital invasion group with greater 5-year/10-year distant metastatic rate (16%/21% vs. 63%/63%, P = 0.005), and greater melanoma-related death rate (7%/13% vs. 38%/53%, P = 0.001). CONCLUSIONS: Conjunctival melanoma with orbital invasion at presentation demonstrate larger, more extensive tumors involving the fornix or tarsus, and with greater rate of melanoma-related metastasis and death.
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Neoplasias Óseas , Neoplasias de la Conjuntiva , Melanoma , Humanos , Recurrencia Local de Neoplasia , Neoplasias de la Conjuntiva/patología , Melanoma/patología , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
In this review we discuss several recent concepts regarding retinoblastoma control and its impact. In a cohort of 482 patients with solitary unilateral retinoblastoma revealed germline mutation in 16% and the likelihood of germline retinoblastoma was greater for younger children (≤1 year versus (vs.) >1 year at presentation) with odds ratio (OR) 2.96 (p = 0.001), and greatest for the youngest infants (≤3 months vs. >3-12 months) (OR 5.52) (p = 0.002). Retinocytoma/retinoma, a benign variant of retinoblastoma, was studied in 78 tumours and demonstrated transformation into retinoblastoma in 9.2% by 5 years and 15.3% by 10 years and 20 years. An international global study on retinoblastoma over 1.5 years revealed 4351 new patients and 85% from low- and middle-income countries, notably with older age at detection and greater risk for metastasis. Management of retinoblastoma in 964 eyes using intravenous chemotherapy showed 20-year globe salvage at 96% in group A, 90% in group B, 90% in group C, 68% in group D, and 32% in group E eyes. The 5-year globe salvage with intra-arterial chemotherapy for 160 eyes (655 infusions) with retinoblastoma showed success in 100% for group B, 80% for group C, 78% for group D, and 55% for group E. The psychological impact of retinoblastoma on the parents revealed depression (73%), anxiety (64%), and/or stress (100%), and on the patient revealed deficits in quality of life issues. Retinoblastoma is a challenging disease and chemotherapy provides reliable tumour control and globe salvage. Continuing efforts to improve quality of life issues is important.
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Neoplasias del Ojo , Neoplasias de la Retina , Retinoblastoma , Niño , Lactante , Humanos , Retinoblastoma/tratamiento farmacológico , Retinoblastoma/genética , Retinoblastoma/diagnóstico , Neoplasias de la Retina/tratamiento farmacológico , Neoplasias de la Retina/genética , Neoplasias de la Retina/diagnóstico , Carga Global de Enfermedades , Calidad de Vida , Protocolos de Quimioterapia Combinada Antineoplásica , Infusiones Intraarteriales , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Metastasis to the eye can involve the choroid (90%), ciliary body (2%), iris (8%), and retina, optic disc, vitreous, and/or lens capsule (<1-4%). The mean number of uveal metastasis per eye (1.7), mean tumour base (11.6 mm) and thickness (3.2 mm), tumour colour (86% yellow), and presence of subretinal fluid (72%), are all clinical features suggestive of the diagnosis. Imaging with ultrasonography demonstrates an echodense mass (80%) and optical coherence tomography shows a "lumpy bumpy" choroidal surface (64%), both important diagnostic features. Uveal metastases typically emanate from primary cancer of the breast (37%), lung (27%), kidney (4%), gastrointestinal tract (4%), cutaneous melanoma (2%), lung carcinoid (2%), prostate (2%), thyroid (1%), pancreas (1%), and other sites (3%). Occasionally, fine needle aspiration biopsy is employed if the primary site is not known. In 16% of cases, the primary site remains unknown. Rarely, metastases affect the retina, vitreous, and lens capsule, most often originating from cutaneous melanoma and in patients previously treated with checkpoint inhibitor therapy. Kaplan-Meier analysis in a series of 1111 patients with uveal metastasis revealed 32% survival at 3 years and 24% at 5 years. Patients with uveal metastasis from carcinoid tumour showed most favourable survival at 5-years (92%), whereas pancreatic and kidney cancer demonstrated least favourable survival (0%). The 5-year survival was better for females (versus (vs.) males) (31% vs. 21%) and older adults (vs. children) (40% vs. 0%). In this review, we examine several large-cohort publications on the topic of ocular metastasis.
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Melanoma , Disco Óptico , Neoplasias Cutáneas , Neoplasias de la Úvea , Masculino , Femenino , Niño , Humanos , Anciano , Melanoma/patología , Cuerpo Ciliar/patología , Neoplasias Cutáneas/patología , Neoplasias de la Úvea/diagnóstico , Disco Óptico/patología , Iris/patología , Coroides/patología , Retina/patología , Melanoma Cutáneo MalignoRESUMEN
Purpose: The aims of this study were to study use of tissue glue instead of conventional suturing and to secure I-125 plaque in human eyes with uveal melanoma. Methods: We studied 6 patients with choroidal melanoma undergoing plaque radiotherapy who were found to have thin sclera intraoperatively. Following tumor localization and plaque placement, tissue glue was applied over and around the plaque surface. The plaque was held securely in all cases. Conjunctivoplasty was performed with 7-0 vicryl sutures to ensure complete coverage and stability of the plaque. At the time of plaque removal, the tissue glue clot was in place with plaque secured. The clot and plaque were removed without difficulty. Results: In all 6 cases, the tissue glue secured the plaque in place for the required radiation duration (mean 117.6 h (hrs), median 103.1 h, range 101.6-162.5 h) delivering a tumor apex dose (mean 63.6 cGy/h, median 69.6 cGy/h, range 44.7-70.5 cGy/h). At the time of plaque removal, the plaque was in the designated position without displacement in all cases. There were no toxicities from the tissue glue. Conclusions: Tissue glue can serve as an alternative for fixation of plaque radiotherapy to the sclera without the need for suturing. This technique might be useful in eyes with thin sclera.
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BACKGROUND/AIMS: To evaluate the likelihood of germline mutation in patients presenting with solitary retinoblastoma based on tumour location at first examination. METHODS: Retrospective analysis of solitary unilateral retinoblastoma for likelihood of germline mutation (family history of retinoblastoma and/or genetic testing indicating germline RB1 mutation and/or development of additional new or bilateral tumours) based on tumur location at presentation (macular vs extramacular). RESULTS: Of 480 consecutive patients with solitary retinoblastoma, 85 were in the macula (18%) and 395 were extramacular (82%). By comparison (macular vs extramacular tumours), macular tumours had smaller basal diameter (12.7 mm vs 18.9 mm, p<0.001) and smaller tumour thickness (6.1 mm vs 10.7 mm, p<0.001). Patients with macular tumours demonstrated greater likelihood for germline mutation (23% vs 12%, OR=2.18, p=0.011), specifically based on family history of retinoblastoma (13% vs 2%, OR=4.64, p=0.004), genetic testing showing germline RB1 mutation (27% vs 15%, OR=2.04 (95% CI 1.04 to 4.01), p=0.039), development of new tumours (13% vs 3%, OR=5.16 (95% CI 2.06 to 12.87), p=0.001) and/or development of bilateral disease (9% vs 2%, OR=4.98 (95% CI 1.70 to 14.65), p=0.004). CONCLUSIONS: Among patients with solitary unilateral retinoblastoma, those presenting with macular tumour (compared with extramacular tumour) show 2.18 times greater likelihood for germline mutation and an even higher likelihood of development of subsequent tumours. Solitary macular retinoblastoma should raise an index of suspicion for likely germline mutation and multifocal disease.
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PURPOSE: To understand conditional prognostic value of the Cancer Genome Atlas (TCGA) for uveal melanoma metastasis based on event-free survival at 1, 2, 3, 4, and 5 years. METHODS: A retrospective study of eyes with uveal melanoma categorized according to TCGA and studied for nonconditional and conditional risks for metastasis at 5 and 10 years. RESULTS: Of 1001 eyes with uveal melanoma, the nonconditional (standard, at presentation) 5-year/10-year metastatic rate was 18%/25%. The conditional 5-year/10-year metastatic rate (for those without metastasis at 2 years) revealed 10%/18% and the conditional 10-year metastatic rate (for those without metastasis at 5 years) revealed 9%. The TCGA categories included Group A (n = 486, 49%), B (n = 141, 14%), C (n = 260, 26%), and D (n = 114, 11%). The non-conditional 5-year/10-year metastatic rate revealed Group A (4%/6%), Group B (12%/20%), Group C (23%/49%), and Group D (60%/68%). The conditional 5-year/10-year metastatic rate (for those without metastasis at 2 years) revealed Group A (2%/5%), Group B (8%/18%), Group C (21%/40%), and Group D (38%/50%). The conditional 10-year metastatic rate (for those without metastasis at 5 years) revealed Group A (2%), Group B (10%), Group C (33%), and Group D (20%). The peak incidence of metastasis for Groups A and B occurred during years 5-6, C during years 4-6, and D during years 1-2. CONCLUSION: Survival outcomes for uveal melanoma as non-conditional (at presentation) and conditional (event-free survival during follow-up) reveal reduction in metastatic rate over time. For those with 5-year metastasis-free survival, the 10-year conditional risk for metastasis was 9%.
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Myxomas are a heterogeneous group of mesenchymal tumors. Soft tissue myxomas are divided into myocardial, intramuscular, juxta-articular, superficial, aggressive, and nerve sheath myxomas. Although benign, myxomas have site-specific biologic behavior and syndromic associations, which can influence prognosis and management. In addition, myxomas need to be distinguished from malignant neoplasms, such as myxofibrosarcomas, low-grade fibromyxoid sarcomas, myxoid liposarcomas, and peripheral nerve sheath tumors. While myxomas can occur throughout the body, these tumors arise more commonly in the thigh, shoulder, buttocks, and upper extremity, and less often in the head and neck. Rarely, myxomas can arise in a periocular location, typically in the conjunctiva and eyelid skin. In this case report, we present a patient with recurrent intramuscular myxoma of the eyelid and discuss the differential diagnosis and syndromic associations of this neoplasm. To our knowledge, there have been no prior reports of intramuscular myxoma of the eyelid and orbit.
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Fibrosarcoma , Mixoma , Neoplasias de la Vaina del Nervio , Adulto , Humanos , Mixoma/diagnóstico , Mixoma/cirugía , Mixoma/patología , Fibrosarcoma/diagnóstico , Diagnóstico Diferencial , Neoplasias de la Vaina del Nervio/diagnóstico , Párpados/patologíaRESUMEN
PURPOSE: Frequent activating mutations in the mitogen-activated protein kinase (MAPK) pathway genes have been identified in histiocytoses. MAPK signaling consistently upregulates cyclin D1. The goal of this study was to determine whether cyclin D1 expression by immunohistochemistry is a useful diagnostic marker for periocular histiocytoses and to further characterize their genetic basis. DESIGN: Retrospective observational case series. METHODS: Pathology records were searched for all patients with histiocytoses diagnosed between 1995 and 2020. Eleven histiocyte-rich inflammatory lesions and 10 xanthelasma served as controls. Cyclin D1 immunohistochemistry was performed on all tissues. A subset of histiocytoses was evaluated by next-generation sequencing (NGS) and droplet digital PCR (ddPCR). RESULTS: There were 36 patients, 15 males (42%) and 21 females (58%), with histiocytoses: 9 juvenile xanthogranuloma (25%), 8 adult-onset asthma and periocular xanthogranuloma (22%), 7 Langerhans cell histiocytosis (19%), 5 Rosai-Dorfman disease (14%), 5 xanthogranuloma-not otherwise specified (14%), 1 Erdheim-Chester disease (3%), and 1 histiocytic sarcoma (3%). Moderate to strong nuclear cyclin D1 expression was present in ≥50% of lesional cells in histiocytoses (23/36, 64%), significantly more when compared to histiocyte-rich inflammatory lesions (0/11, 0%, P<.001) and xanthelasma (0/10, 0%, P<.001). Cyclin D1 was expressed in <10% of lesional cells in all 11 histiocyte-rich inflammatory lesions (P<.001) and all 10 xanthelasma lesions (P<.001). MAPK pathway gene mutations were detected in 12 of 14 (86%) histiocytoses successfully assayed by NGS and/or ddPCR. CONCLUSIONS: Our study confirms that the cyclin D1 immunohistochemical stain is a useful diagnostic marker for periocular histiocytoses, correlating with underlying mutations in MAPK pathway genes.