The biology of micrometastases from uveal melanoma

Borthwick, Nicola; Thombs, Jasmine; Polak, Marta E.; Gabriel, Francis G.; Hungerford, J. L.; Damato, Bertil; Rennie, I G; Jager, Martine J.; Cree, Ian A.

doi:10.1136/jcp.2010.087999

Cited by 26 publications

(30 citation statements)

References 43 publications

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“…Stage 1 and stage 2 metastases may be inconspicuous on hematoxylin-eosin stains and may become apparent with immunohisto-chemical staining for HMB45. Both the previous study 12 and the present study showed a conspicuous absence of inflammatory cells in the liver associated with the melanoma metastases. Although the present study could not evaluate individual metastatic melanoma cell survival in the liver, the previous autopsy study 12 and experimental models indicate that few melanoma cells can survive in the liver for prolonged periods to spawn metastases.…”

Section: Commentsupporting

confidence: 78%

“…There are similarities and differences between the present study and the only previous study 12 of the his tological features of metastatic uveal melanoma to the liver. The prior study 12 found a collection of 1 to 3 melanoma cells in the liver in 1 of 6 patients with uveal melanoma who died of nonmelanoma causes.…”

Section: Commentsupporting

confidence: 46%

“…The prior study 12 found a collection of 1 to 3 melanoma cells in the liver in 1 of 6 patients with uveal melanoma who died of nonmelanoma causes. Metastatic melanomas that measured 200 to 2000 μm in diameter were found in the livers of 16 patients who died of metastatic uveal melanoma.…”

Section: Commentmentioning

confidence: 99%

“…Metastatic melanomas that measured 200 to 2000 μm in diameter were found in the livers of 16 patients who died of metastatic uveal melanoma. 12 The prior study 12 used a panmelanoma immunohistochemical antibody, whereas, in the present study, I used S100 and HMB45. In the present study, HMB45 was strongly positive in 9 of 10 patients, and S100 was positive in 2 of 10 patients, with HMB45 being more sensitive than S100 for detecting all stages of the melanomas in the liver.…”

Section: Commentmentioning

confidence: 99%

“…In a single study 12 of postmortem liver tissue samples obtained from patients with uveal melanoma, tumors 200 to 2000 μm in diameter were found in patients who died of metastases, and, in one instance, a single collection of 1 to 3 melanoma cells was found in the liver of a patient who died of a myocardial infarction. In the present study, I examined postmortem hepatic biopsy specimens obtained from 10 patients who succumbed to liver metastases of uveal melanoma in order to assess the histologic growth patterns, immunohistochemical features, vascularity, and mitotic rates of the tumors.…”

mentioning

confidence: 99%

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Progression of Ocular Melanoma Metastasis to the Liver

Grossniklaus

2013

JAMA Ophthalmol

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Section: Commentsupporting

confidence: 78%

Section: Commentsupporting

confidence: 46%

Section: Commentmentioning

confidence: 99%

Section: Commentmentioning

confidence: 99%

mentioning

confidence: 99%

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Progression of Ocular Melanoma Metastasis to the Liver

Grossniklaus

2013

JAMA Ophthalmol

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Replacement and desmoplastic histopathological growth patterns: A pilot study of prediction of outcome in patients with uveal melanoma liver metastases

Barnhill

Vermeulen

Daelemans

et al. 2018

The Journal of Pathology CR

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Up to 50% of uveal melanomas (UM) metastasise to the liver within 10 years of diagnosis, and these almost always prove rapidly fatal. As histopathological growth patterns (HGPs) of liver metastases of the replacement and desmoplastic type, particularly from colon and breast carcinoma, may import valuable biological and prognostic information, we have studied HGP in a series of 41 UM liver metastases originating from 41 patients from the period 2006–2017. Twenty patients underwent enucleation while 21 had radiation therapy. Analysis of UM by array comparative genomic hybridisation revealed: 25 (64%) patients with high risk (monosomy3/8q gain); 13 (33%) intermediate risk (M3/8normal or disomy3/8q gain); and 1 low risk (disomy3/8normal). The principal HGP was replacement in 30 (73%) cases and desmoplastic in 11 (27%) cases. Cases with replacement demonstrated striking vascular co‐option/angiotropism. With the development of liver metastasis, only the replacement pattern, largest primary tumour diameter, and R2 (incomplete resection) status predicted diminished overall survival (OS; p < 0.041, p < 0.017, p < 0.047, respectively). On multivariate analysis, only HGP (hazard ratio; HR = 6.51, p = 0.008) and resection status remained significant. The genomic high‐risk variable had no prognostic value at this stage of liver metastasis. Chi‐square test showed no association of HGP with monosomy 3 or 8q gain. Eighteen of 41 (44%) patients are alive with disease and 23 (56%) patients died with follow‐up ranging from 12 to 318 months (mean: 70 months, median: 47 months). In conclusion, we report for the first time the frequency of the replacement and desmoplastic HGPs in liver UM metastases resected from living patients, and their potential important prognostic value for UM patients, as in other solid cancers. These results may potentially be utilised to develop radiological correlates and therapeutic targets for following and treating patients with UM metastases.

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