Is there a relation between type of primary melanoma treatment and the development of intralymphatic metastasis? A review of the literature

Background: Intralymphatic metastases (ILM) originate from tumor cell emboli entrapped in dermal lymphatics between primary tumor and regional lymph node basin. Because of this origin, sentinel lymph node biopsy (SLNB) might increase ILM by restricting lymph flow.

Methods: Pubmed, Embase, Cochrane and Medline were searched for articles on ILM between 1980 and September 2014. ILM Incidences were calculated after wide local excision (WLE), excision with elective lymph node dissection (ELND) or therapeutic lymph node dissection (TLND), WLE with SLNB with or without completion lymph node dissection (CLND) and delayed lymph node dissection (DLND) for patients developing nodal metastasis during follow-up.

Results: In 36 studies, 14,729 patients underwent WLE, 1682 patients WLE/ELND, 362 patients WLE/DLND and 11,201 patients WLE/SLNB. On meta-analysis, ILM occurrence was 3.4% (95% CI 2.8-4.2%). ILM occurred most frequently in the WLE/DLND group (5.5%, 95% CI 3.5-8.7%), followed by WLE/ELND (4.7%, 95% CI 3.1-7.0%), WLE/SLNB (4.5%, 95% CI 3.5-5.7%) and WLE alone (1.9%, 95% CI 1.4-2.7%). 1330 SLNB+ patients were identified and 5783 SLNB- patients. For these groups, on meta-analysis, ILM recurrence was 13.2% (95% CI 10.8-16.2%) and 3.4% (95% CI 2.5-4.5%), respectively (p=0.01).

Conclusion: In this review SLNB is associated with an increase of ILM with an incidence of 1.9% for WLE vs. 3.4% for SNLB-. Selection bias in this review cannot be excluded. However, ILM occur four times more frequently after SLNB+ than SLNB- procedures and more often after SLNB+/CLND than WLE/DLND or WLE/ELND. ILM should therefore be viewed as a bio-marker of aggressive primary disease.

Synopsis: Sentinel lymph node biopsy is thought to increase intralymphatic metastasis by restricting lymph flow. This review demonstrates that there is an increase in metastasis, but this result has to be interpreted with caution due to possible selection bias. Aggressive tumor characteristics are likely the cause of this increase.