Fine-Needle Aspirates of Uveal Melanomas and Prognosis

Folberg, Robert; Augsburger, James J.; Gamel, John W.; Shields, Jerry A.; Lang, Warren R.

doi:10.1016/0002-9394(85)90619-1

Cited by 41 publications

(16 citation statements)

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“…Several groups have reported the cytopathological classification of the tumor cells they obtained during FNAB (13,15,16,18) , and occasional groups have also reported cytopathological versus histopathological classification of tumors evaluated by FNAB and managed by enucleation and transcleral resection (10,15,17,22,35) . Although reported studies of cytopathological classification of tumor cells obtained by FNAB and histopathological classification of the entire tumor evaluated following enucleation show reasonably good agreement between these assignments (10,17,19,22,35) , many clinicians and ophthalmic pathologists remain skeptical about the reliability and prognostic value of melanoma pathological classification based on FNAB.…”

Section: Discussionmentioning

confidence: 99%

“…Although reported studies of cytopathological classification of tumor cells obtained by FNAB and histopathological classification of the entire tumor evaluated following enucleation show reasonably good agreement between these assignments (10,17,19,22,35) , many clinicians and ophthalmic pathologists remain skeptical about the reliability and prognostic value of melanoma pathological classification based on FNAB. This skepticism seems to stem from concern about the potential for FNAB to yield non-representative tumor specimens, recognition that cytology provides only cellular features and not tissue features of the tumors (which are important for histopathological classification), and realization that there is considerable variability in histopathological classification of uveal melanomas by ophthalmic pathologists who analyze the same microslides of selected tumors (43,44) .…”

Section: Discussionmentioning

confidence: 99%

“…In most of these early cases, the objective of the FNAB was to establish, confirm, or refute the clinical diagnosis of the evaluated intraocular tumor and direct baseline systemic evaluation of the patient, treatment of the primary intraocular tumor, and post-treatment follow-up (1,4,5,9,(13)(14)(15) . Over the years, various authors have described and illustrated the cytomorphological and immunocytochemical features of melanocytic uveal tumor cells obtained by FNAB (1,13,(15)(16)(17)(18)(19)(20)(21) and the relative frequencies of spindle, epithelioid, mixed and necrotic tumor cells in the obtained specimens (13,15,17) . A few groups of investigators have described the correlation between cytopathological and histopathological classification of the uveal me lanoma cells in cases treated by enucleation or transcleral tumor resection, (4,10,15,17,22) and some investigators have also reported the frequency of insufficient aspirates for cytopathological diagnosis in their series and factors associated with this result (3,8,10,(21)(22)(23)(24)(25)(26)(27) .…”

Section: Introductionmentioning

confidence: 99%

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Prognostic implications of cytopathologic classification of melanocytic uveal tumors evaluated by fine-needle aspiration biopsy

Augsburger¹,

Corrêa²,

Trichopoulos³

2013

Arq. Bras. Oftalmol.

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Purpose: Determine whether cytopathologic classification of melanocytic uveal tumors evaluated by fine-needle aspiration biopsy (FNAB) is a significant prognostic factor for death from metastasis. Methods: Retrospective analysis of cases of clinically diagnosed uveal melanoma evaluated by fine-needle aspiration biopsy from 1980 to 2006. Main outcome evaluated was death from metastasis. Associations between baseline clinical variables and cytopathologic classification were evaluated using cross-tabulation. Prognostic significance of cytopathologic classification was evaluated by Ka planMeier and Cox proportional hazards analysis. Results: Of 302 studied biopsies, 260 (86.1%) yielded sufficient cells for cytopathologic classification. Eighty of the 260 patients who had a sufficient specimen have already died (P=0.021), 69 from metastatic uveal melanoma. Cell type assigned by cytopathology was strongly associated with metastasis/metastatic death in this series (P=0.0048). Multivariate analysis showed cytopathologic classification to be an independently significant prognostic factor for metastatic death (P=0.0006). None of the 42 patients whose tumor yielded insufficient aspirates (sampled in at least two sites) have developed metastasis or died of metastasis thus far. Conclusion: In this series, cytopathology of fine-needle aspiration biopsy samples obtained from uveal melanomas was strongly prognostic of death from metastasis. Insufficiently aspirates (2 or more sites sampled) proved to be prognostic of a favorable outcome (i.e., not developing metastasis). Keywords

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prognostic implications of cytopathologic classification of melanocytic uveal tumors evaluated by fine-needle aspiration biopsy

Augsburger¹,

Corrêa²,

Trichopoulos³

2013

Arq. Bras. Oftalmol.

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“…The ophthalmic one-pass FNAB sampling of intraocular tumors does not yield material that is satisfactory for prognostication in cytologically heterogeneous neoplasms. [17][18][19] It is possible for a patient to harbor a significant quantity of metastatic disease to the liver and maintain normal hepatic enzymes. 20 Therefore, the application of any new therapy likely to be effective in treating metastatic melanoma would be most efficacious if applied before the metastatic tumor burden is great.…”

Section: Introductionmentioning

confidence: 99%

Vasculogenic Mimicry and Tumor Angiogenesis

Folberg

Hendrix

Maniotis

2000

The American Journal of Pathology

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632

434

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Tumors require a blood supply for growth and hematogenous dissemination. Much attention has been focused on the role of angiogenesis-the recruitment of new vessels into a tumor from pre-existing vessels. However, angiogenesis may not be the only mechanism by which tumors acquire a microcirculation. Highly aggressive and metastatic melanoma cells are capable of forming highly patterned vascular channels in vitro that are composed of a basement membrane that stains positive with the periodic acid-Schiff (PAS) reagent in the absence of endothelial cells and fibroblasts. These channels formed in vitro are identical morphologically to PAS-positive channels in histological preparations from highly aggressive primary uveal melanomas, in the vertical growth phase of cutaneous melanomas, and in metastatic uveal and cutaneous melanoma. The generation of microvascular channels by genetically deregulated, aggressive tumor cells was termed "vasculogenic mimicry" to emphasize their de novo generation without participation by endothelial cells and independent of angiogenesis. Techniques designed to identify the tumor microcirculation by the staining of endothelial cells may not be applicable to tumors that express vasculogenic mimicry. Although it is not known if therapeutic strategies targeting endothelial cells will be effective in tumors whose blood supply is formed by tumor cells in the absence of angiogenesis, the biomechanical and molecular events that regulate vasculogenic mimicry provide opportunities for the development of novel forms of tumor-targeted treatments. The unique patterning characteristic of vasculogenic mimicry provides an opportunity to design noninvasive imaging techniques to detect highly aggressive neoplasms and their metastases. Tumors require a blood supply to sustain growth. The tumor microcirculation plays a central role in the hematogenous dissemination of cancers. Considerable attention has been focused on the mechanisms by which tumors acquire their blood supply. It is a well-accepted paradigm that tumors recruit new blood vessels from the existing circulation 1 -angiogenesis-either from factors secreted by the tumor cells, as Folkman 2,3 has emphasized, or from surrounding stromal cells. 4 There are two variations on the theme of tumor angiogenesis: augmentation of the angiogenic response by progenitor endothelial cells, and vessel cooption. Asahara and associates 5 described the incorporation of endothelial cell progenitors (or angioblasts) from circulating peripheral blood into sites of ischemic-driven angiogenesis. Holash and associates 6 described a process of "vessel cooption" in which tumors coopt the existing vasculature, which regresses leading to massive necrosis, and the tumor is then vascularized at the periphery by tumor angiogenesis as described above.We 7 recently described a novel process by which tumors develop a highly patterned microcirculation that is independent of angiogenesis: in aggressive primary and metastatic melanomas, the tumor cells generate acellular microcirculat...

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“…The problem of sampling error and misclassification is thought to be less important if larger enucleation specimens are used, as these are more representative of the tumor than biopsies. 21,23 In this study, larger enucleation specimens were used from the patient tumors, minimizing the risk of misclassification.…”

Section: 12mentioning

confidence: 99%

Higher Percentage of FISH-Determined Monosomy 3 and 8q Amplification in Uveal Melanoma Cells relate to Poor Patient Prognosis

Bosch

Beek²,

Vaarwater³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To investigate the relation between patient survival and incrementally increasing percentages of fluorescence in situ hybridization-determined complete loss of chromosome 3 (monosomy 3) and gain of chromosome 8q in primary uveal melanoma cells.METHODS. Clinicopathological factors were related to diseasefree survival. Fluorescence in situ hybridization was performed using probes on chromosomes 1, 3, 6, and 8. The percentages of UM cells with monosomy 3 or chromosome 8q gain were classified in groups with incrementally increasing percentages and related to disease-free survival. Correlations between clinical factors and cytogenetic aberrations were also analyzed.RESULTS. Two-hundred twenty choroidal and ciliary body melanomas were analyzed. The following proved to be significant predictors of survival in univariate analysis: older patient age (P ¼ 0.003); large tumor diameter (P < 0.001); mixed cell type (P ¼ 0.001); presence of closed microvascular loops (P < 0.001); loss of chromosome 1p (P ¼ 0.006); monosomy 3 (P < 0.001); gain of 6p (P < 0.001); and gain of chromosome 8q (P < 0.001). Multivariate Cox analysis displayed monosomy 3 (Hazard ratio [HR] 2.83, P ¼ 0.002) and gain of chromosome 8q (HR 3.13, P ¼ 0.002) as the most important independent prognostic factors of poor survival, followed by older patient age (HR 1.02, P ¼ 0.017). Increasing percentages of monosomy 3 and gain of chromosome 8q in tumor cells showed a correlation with worse prognosis (Logrank test 49.9 and 40.4, both P < 0.001) and increased number of additional copies of 8q correlated with shorter disease-free interval (Log-rank test 45.7, P < 0.001). CONCLUSIONS.A high percentage monosomy 3 and chromosome 8q gain in primary UM cells showed a strong relation with poor disease-free survival compared with low percentage aberrations. (Invest Ophthalmol Vis Sci.

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Fine-Needle Aspirates of Uveal Melanomas and Prognosis

Cited by 41 publications

References 6 publications

Prognostic implications of cytopathologic classification of melanocytic uveal tumors evaluated by fine-needle aspiration biopsy

Prognostic implications of cytopathologic classification of melanocytic uveal tumors evaluated by fine-needle aspiration biopsy

Vasculogenic Mimicry and Tumor Angiogenesis

Higher Percentage of FISH-Determined Monosomy 3 and 8q Amplification in Uveal Melanoma Cells relate to Poor Patient Prognosis

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