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Mitoses in melanoma: Is there really a meaning?


Mark A. Hurt MD

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Just this month there are two interesting articles published on the issue of mitosis in melanoma and whether they confer diagnostic or prognostic meaning.

The first is by Gori et al. (1), who make the argument that the presence of greater than 1 mitosis/mm[sup]2[/sup] should not necessarily result in sentinel node biopsy in pregnant women. Their reasoning, based on a single case, was:

[indent=1]"to minimize the risk to the fetus, especially with respect to potential risks to the growing brain and development of the fetus due to general anesthesia, SLNB [sentinel lymph node biopsy] was postponed until after delivery."[/indent]

They state further that:

[indent=1]"On the basis of our limited experience and according to the literature, it is hard to conclude that pregnant women with thin melanomas presenting an MR of 1/mm[sup]2[/sup] would benefit from SLNB in pregnancy or in the postpartum period. SLNB is a procedure with a low but not negligible morbidity and high economic cost; moreover, it results in negative psychological effect on pregnant women."[/indent]

Of course, I can think of another argument against doing a sentinel node biopsy: it has no proven survival benefit. It might offer a benefit for knowing something about [i]prognosis[/i], but not survival. On this basis alone, it would seem that pursuing SLNB during pregnancy is a bad idea.


The second article is by Cooper et al. (2), and it explores their 10-year experience with thin melanomas and SNLB at a single institution. What was interesting to me about this is they found that:

[indent=1]"Our data confirm a statistically significant relationship between SLNB result and likelihood for distant metastasis in thin melanoma. There was a trend for a relationship between mitotic rate and clinical outcome. This relationship reached statistical significance at a mitotic rate of greater than 3 mitoses/mm[sup]2[/sup]."[/indent]


This kind of study brings to bear whether the mitotic index in melanoma is really relevant as a guide to anything except, possibly, the diagnosis. I have always argued that finding mitoses in a melanocytic lesion might aid in establishing the [i]diagnosis[/i] of melanoma in some cases, but I have little confidence that it should be used to target patients for lymph node dissection.


Let me know what you think -- and why.



[center]References[/center]

[url="http://www.ncbi.nlm.nih.gov/pubmed/?term=23852163"]1. Gori A, Salvini C, Fabroni C, Lo Scocco G. Is the mitotic rate of 1/mm2 the correct cutoff point for performing sentinel lymph node biopsy in pregnant patients with thin melanoma? Melanoma Res. 2013; 23:420-421; 2013 Jul 10. [Epub ahead of print] PubMed PMID: 23852163.[/url]

[url="http://www.ncbi.nlm.nih.gov/pubmed/?term=23978604"]2. Cooper C, Wayne JD, Damstetter EM, Martini M, Gordon J, Guitart J, West DP, Nardone B, Rademaker A, Gerami P. A 10-year, single-institution analysis of clinicopathologic features and sentinel lymph node biopsy in thin melanomas. J Am Acad Dermatol. 2013 Aug 23. doi:pii: S0190-9622(13)00768-8. 10.1016/j.jaad.2013.07.016. [Epub ahead of print] PubMed PMID: 23978604.[/url]
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I agree, Mark! You are quite right.
There are several issues at hand. For me, tthe main one - often overlooked - is that, based on currently available evidence, a survival benefit of ELND (elective lymph node disseaction) after positive SN, remains a contended issue. This is not at all a rearguard struggle: many very experienced and intelligent clinicians and pathologists are unconvinced that a survival benefit has been demonstrated convincingly. I hope that FU data of the very few relevant PRT conducted so far, will be of help to settle this matter.
Still further away lies the answer to the question whether SN in [i]very thin[/i] melanoma, or in special groups such as pregnant women and children, is a good idea. Prognostic relevance of the path diagnosis of the SN is beyond doubt (except in children), it is substantial. But [i]if a positive SN means that an ELND will be performed, then I am hesitant[/i], and would point out the pain-in-the-neck uncertainties rather than the longed-for benefits.
Regarding the usefulness of intradermal mitotic activity in the distinction of nevus and melanoma: there is absolutely a place for that, but only when one realises that occasional mitotic figures are seen in nevi NOS (mostly, but by no means exclusively, in women of fertile age), and they are a regular feature of some nevus variants, especially those of the wide and varied spectrum of blue nevi.
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Mark A. Hurt MD

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I agree completely, Wolter. Thank you for your insightful commentary. You are absolutely right about the issue of mitotic figures in nevi. I see them not uncommonly in classic nevus patterns.

As for sentinel node biopsy and ELND, I'm going to have to be convinced about survival benefit before I'll sign on to using either as the standard of care for these patients.
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