Lymphatic invasion predicts sentinel lymph node metastasis and adverse outcome in primary cutaneous melanoma

Moy, Andrea P.; Mochel, Mark C.; Muzikansky, Alona; Duncan, Lyn M.; Kraft, Stefan

doi:10.1111/cup.12969

Cited by 15 publications

(19 citation statements)

References 18 publications

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“…In comparison, in our current study, we observed a strong correlation between angiotropism and lymphatic invasion. This partial discrepancy may be due, in part, to our use of a more sensitive method of detecting lymphatic invasion with S100/D240 double stains as compared to H&E analysis alone . The association of angiotropism and lymphatic invasion in this study does not necessarily suggest that there is a direct relationship between angiotropism and vascular invasion, as angiotropic foci were predominantly detected in association with CD31+ blood vessels and vascular invasion was typically identified within D240+ lymphatic vessels, and we did not observe vascular invasion in CD31+ vessels.…”

Section: Discussioncontrasting

confidence: 63%

Angiotropism in primary cutaneous melanoma is associated with disease progression and distant metastases: A retrospective study of 179 cases

et al. 2019

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Background: Angiotropism is the histopathological correlate of pericytic mimicry and extravascular migratory metastasis (EVMM), a mechanism of melanoma spread by migration along the external surface of blood and lymphatic vessels. The frequency of angiotropism in primary cutaneous melanoma and the clinical utility of its detection remain unclear.Methods: We investigated angiotropism in 179 primary cutaneous melanomas by hematoxylin and eosin (H&E), CD31, and S100/D240 stains.Results: We detected angiotropism in 31 cases (17%) by H&E. CD31 immunohistochemistry increased detection to 59 cases (33%). When lymphatic vessels were included by using S100/D240 stains, 67 cases (37%) cases were positive. Angiotropism was associated with lymphatic invasion and mitotic rate with all detection methods. There was an association with increased tumor thickness when detected by H&E and CD31. No association with sentinel lymph node status was seen. By H&E and CD31 staining, angiotropism was associated with disease progression and distant metastases by univariate, but not multivariate analysis. Overall survival was not affected by the presence of angiotropism.Conclusions: Angiotropism is relatively common in primary melanoma when immunohistochemical stains are used for detection and associated with mitotic rate and intravascular lymphatic invasion. The association with disease progression and distant metastasis suggests that it represents an alternative pathway of metastasis, that is, EVMM/pericytic mimicry vs intravascular spread. K E Y W O R D Sangiotropism, melanoma, metastasis, pericytic mimicry, survival

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Section: Discussioncontrasting

confidence: 63%

Angiotropism in primary cutaneous melanoma is associated with disease progression and distant metastases: A retrospective study of 179 cases

et al. 2019

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“…In our recent analysis of melanomas from patients who underwent SLN biopsy, we found the sensitivity and specificity of predicting SLN metastasis with lymphatic invasion on dual S100/D2-40 IHC were 44% and 82%, respectively. 32 In addition, patients without lymphatic invasion were more likely to be disease free at last follow-up (79%) than patients with lymphatic invasion (54%) detected on S100/D2-40 IHC (average followup = 22 months and 24 months, respectively).…”

Section: Lymphatic Invasion and Metastasismentioning

confidence: 92%

“…We recently studied 105 melanomas with dual S100/D2-40 IHC and detected lymphatic invasion in 23%. 32 Unequivocal lymphatic invasion can be recognized when S100-positive cytologically atypical cells, stained with a red chromogen, are seen circumferentially surrounded by a thin D2-40-positive lymphatic endothelium, stained with a brown chromogen. Either solid tumor emboli or single tumor cells may be seen within the lymphatic spaces.…”

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confidence: 99%

Lymphatic invasion and angiotropism in primary cutaneous melanoma

Moy

Duncan

Kraft

2017

Laboratory Investigation

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Access of melanoma cells to the cutaneous vasculature either via lymphatic invasion or angiotropism is a proposed mechanism for metastasis. Lymphatic invasion is believed to be a mechanism by which melanoma cells can disseminate to regional lymph nodes and to distant sites and may be predictive of adverse outcomes. Although it can be detected on hematoxylin-and eosin-stained sections, sensitivity is markedly improved by immunohistochemistry for lymphatic endothelial cells. Multiple studies have reported a significant association between the presence of lymphatic invasion and sentinel lymph node metastasis and survival. More recently, extravascular migratory metastasis has been suggested as another means by which melanoma cells can spread. Angiotropism, the histopathologic correlate of extravascular migratory metastasis, has also been associated with melanoma metastasis and disease recurrence. Although lymphatic invasion and angiotropism are not currently part of routine melanoma reporting, the detection of these attributes using ancillary immunohistochemical stains may be useful in therapeutic planning for patients with melanoma.

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“…The present study has several limitations. Lymphatic invasion is a known prognostic factor in melanoma, but could unfortunately not be assessed reliably in this study because there were too many missing values (30·3 per cent). The retrospective design and short follow‐up of some patients are other limitations.…”

Section: Discussionmentioning

confidence: 96%

External validation of a prognostic model to predict survival of patients with sentinel node-negative melanoma

Ipenburg

Nieweg

Ahmed

et al. 2019

British Journal of Surgery

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Background Identifying patients with sentinel node‐negative melanoma at high risk of recurrence or death is important. The European Organisation for Research and Treatment of Cancer (EORTC) recently developed a prognostic model including Breslow thickness, ulceration and site of the primary tumour. The aims of the present study were to validate this prognostic model externally and to assess whether it could be improved by adding other prognostic factors. Methods Patients with sentinel node‐negative cutaneous melanoma were included in this retrospective single‐institution study. The β values of the EORTC prognostic model were used to predict recurrence‐free survival and melanoma‐specific survival. The predictive performance was assessed by discrimination (c‐index) and calibration. Seeking to improve the performance of the model, additional variables were added to a Cox proportional hazards model. Results Some 4235 patients with sentinel node‐negative cutaneous melanoma were included. The median follow‐up time was 50 (i.q.r. 18·5–81·5) months. Recurrences and deaths from melanoma numbered 793 (18·7 per cent) and 456 (10·8 per cent) respectively. Validation of the EORTC model showed good calibration for both outcomes, and a c‐index of 0·69. The c‐index was only marginally improved to 0·71 when other significant prognostic factors (sex, age, tumour type, mitotic rate) were added. Conclusion This study validated the EORTC prognostic model for recurrence‐free and melanoma‐specific survival of patients with negative sentinel nodes. The addition of other prognostic factors only improved the model marginally. The validated EORTC model could be used for personalizing follow‐up and selecting high‐risk patients for trials of adjuvant systemic therapy.

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Lymphatic invasion predicts sentinel lymph node metastasis and adverse outcome in primary cutaneous melanoma

Abstract: The detection of LI is improved by dual immunohistochemistry and predicts SLN metastasis. The presence of LI may impact therapeutic planning in melanoma, such as the decision to perform a SLN biopsy.

Cited by 15 publications

References 18 publications

Angiotropism in primary cutaneous melanoma is associated with disease progression and distant metastases: A retrospective study of 179 cases

Angiotropism in primary cutaneous melanoma is associated with disease progression and distant metastases: A retrospective study of 179 cases

Lymphatic invasion and angiotropism in primary cutaneous melanoma

External validation of a prognostic model to predict survival of patients with sentinel node-negative melanoma

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