Intraocular Tumor-Associated Lymphangiogenesis

Heindl, Ludwig M.; Hofmann, Torsten; Adler, Werner; Knorr, H. L. J.; Holbach, Leonard M.; Naumann, Gottfried O.H.; Kruse, Friedrich E.; Cursiefen, Claus

doi:10.1016/j.ophtha.2009.06.057

Cited by 47 publications

(18 citation statements)

References 29 publications

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“…Additionally, it should be mentioned when obtaining informed consent from patients. That is because both local recurrence and extraocular extension, which may result from iatrogenic tumor cell seeding, decrease the patients' chance of a tumor-free survival [12,13]. Fortunately in our case, and despite recurrence and monosomy 3, neither hepatic nor other distant metastases have been detected during the 5-year follow-up period since the initial diagnosis.…”

Section: Discussionmentioning

confidence: 66%

Uveal Melanoma Cell Seeding after Transretinal Tumor Biopsy

Koch¹,

Hishmi²,

Ortmann³

et al. 2017

Ocul Oncol Pathol

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Background/Aims: To report a case and the histopathology of uveal melanoma cell seeding following transretinal tumor biopsy for a suspected uveal lesion. Methods: Interventional case report. Results: A 66-year-old male presented with a pigmented perilimbal episcleral lesion overlying an intraocular mass at the pars plana, 3.5 years after transretinal biopsy and ruthenium plaque brachytherapy for a choroidal melanoma at the posterior pole. The patient underwent enucleation of the eye. Histopathology confirmed a recurrence of uveal melanoma with intra- and extrascleral tumor portions. Serial sections revealed the posterior border of this newfound pars plana melanoma separated from the radiation scar by a viable and tumor-free choroidal area, thus failing to establish a continuity between secondary and primary tumor. Conclusion: Transretinal tumor biopsy is of high diagnostic and prognostic value in the management of uveal lesions, but also bears the potential risk for tumor cell seeding.

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Section: Discussionmentioning

confidence: 66%

Uveal Melanoma Cell Seeding after Transretinal Tumor Biopsy

Koch¹,

Hishmi²,

Ortmann³

et al. 2017

Ocul Oncol Pathol

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“…The presence or absence of “true” lymphatic vessels in the human eye is still a controversial topic. Heindl et al pointed out that there is no sufficient evidence that ciliary body lymphatic vessels are true lymphatic vessels without extraocular extension 226 and that the presence of intraocular lymphangiogenesis in ciliary body melanomas with extraocular extensions is associated with a poorer prognosis 227 . In addition, immunohistochemical staining for LYVE-1 on postmortem human adult eyes reveals the absence of lymphatic vessels.…”

Section: Diseases Associated With Corneal Lymphangiogenesismentioning

confidence: 99%

“…233 In another study, Heindl et al reported that intraocular lymphangiogenesis increases tumor size and metastasis, and is thus correlated with mortality in patients with malignant melanoma and extraocular extensions. 227 Recently, Hos et al described the role of tumor-associated lymphangiogenesis in ocular malignancies and its potential role in future therapeutic development. 20 …”

Section: Diseases Associated With Corneal Lymphangiogenesismentioning

confidence: 99%

Understanding lymphangiogenesis in knockout models, the cornea, and ocular diseases for the development of therapeutic interventions

Yang

Walia

Huang

et al. 2016

Survey of Ophthalmology

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A major focus of cancer research for several decades has been understanding the ability of tumors to induce new blood vessel formation, a process known as angiogenesis. Unfortunately, only limited success has been achieved in the clinical application of angiogenesis inhibitors. We now know that lymphangiogenesis, the growth of lymphatic vessels, likely also plays a major role in tumor progression. Thus, therapeutic strategies targeting lymphangiogenesis or both lymphangiogenesis and angiogenesis may represent promising approaches for treating cancer and other diseases. Importantly, research progress toward understanding lymphangiogenesis is significantly behind that related to angiogenesis. A PubMed search of ‘angiogenesis’ returns nearly 80,000 articles, whereas a search of ‘lymphangiogenesis’ returns approximately 2,635 articles. This stark contrast can be explained by the lack of molecular markers for identifying the invisible lymphatic vasculature that persisted until less than two decades ago combined with the intensity of research interest in angiogenesis during the past half-century. Still, significant strides have been made in developing strategies to modulate lymphangiogenesis, largely using ocular disease models. Here, we review the current knowledge of lymphangiogenesis in the context of knockout models, ocular diseases, the biology of activators and inhibitors, and the potential for therapeutic interventions targeting this process.

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“…In case of metastasis, both types of tumor usually spread to the regional lymph nodes first, while UM primarily metastasizes hematogenously to the liver [5,8,9,10,27,28,29,30,31,32,33]. Both CM and skin melanoma are highly positive for S100 on immunohistochemical staining.…”

Section: Introductionmentioning

confidence: 99%

“…In UM, however, S100 expression has been shown to be significantly lower than in CM. Furthermore, serum levels of S100 can also serve as a prognostic marker in skin melanoma [27,28,29,30,31,32,33,34,35,36]. Other pigment markers that have been assessed with regard to their labeling of skin melanoma, CM, or UM are tyrosinase, p75 NTR (p75 neurotrophin receptor), HMB (human melanoma black)-45, HMB-50, melan-A, and microphthalmia-associated transcription factor [34,36].…”

Section: Introductionmentioning

confidence: 99%

Systemic BRAF/MEK Inhibitors as a Potential Treatment Option in Metastatic Conjunctival Melanoma

Mor

Heindl

2016

Ocul Oncol Pathol

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Aim: In this review, we outline similarities between conjunctival and skin melanoma as well as the effectiveness of combined BRAF/MEK inhibition in melanoma, and discuss the applicability of these agents in conjunctival melanoma. Methods: The study provides a PubMed literature review. Results: Conjunctival melanoma and skin melanoma are genetically and phenotypically related. Both tumors typically harbor BRAF mutations in more than 50% of cases. New targeted therapies in metastatic skin melanoma include selective inhibition of BRAF and MEK. Combined BRAF/MEK inhibition has revolutionized the treatment of metastatic skin melanoma, significantly improving patients' prognoses. While these new substances have been investigated extensively in the treatment of skin melanoma, comparable studies in conjunctival melanoma do not exist owing to the rarity of the malignancy. Conclusions: The application of combined BRAF/MEK inhibition in metastatic or unresectable conjunctival melanoma shows great potential for improving patients' prognoses. Future studies are needed to investigate the assumed benefit.

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Intraocular Tumor-Associated Lymphangiogenesis

Cited by 47 publications

References 29 publications

Uveal Melanoma Cell Seeding after Transretinal Tumor Biopsy

Uveal Melanoma Cell Seeding after Transretinal Tumor Biopsy

Understanding lymphangiogenesis in knockout models, the cornea, and ocular diseases for the development of therapeutic interventions

Systemic BRAF/MEK Inhibitors as a Potential Treatment Option in Metastatic Conjunctival Melanoma

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