title: Is there a relation between type of primary melanoma treatment and the development of intralymphatic metastasis? A review of the literature.
abstract: 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).
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgical Oncology, University Groningen, University Medical Centre Groningen, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Sloot
authors.affiliation: Department of Surgical Oncology, University Groningen, University Medical Centre Groningen, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Speijers
authors.affiliation: Department of Surgical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Bastiaannet
authors.affiliation: Department of Surgical Oncology, University Groningen, University Medical Centre Groningen, The Netherlands. Electronic address: h.j.hoekstra@umcg.nl.
authors.forename: H J
authors.initials: HJ
authors.lastname: Hoekstra
mesh_terms: D006801:Humans; D008197:Lymph Node Excision / Q000009:adverse effects / Q000379:methods; D008198:Lymph Nodes / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis / Q000517:prevention & control*; D008545:Melanoma / Q000473:pathology / Q000601:surgery; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000517:prevention & control; D017063:Outcome Assessment, Health Care; D021701:Sentinel Lymph Node Biopsy / Q000009:adverse effects / Q000379:methods; D012878:Skin Neoplasms / Q000473:pathology / Q000601:surgery; D061665:Time-to-Treatment
keywords: Lymph node excision; Melanoma; Neoplasm metastasis; Recurrence; Review; Sentinel lymph node biopsy; Surgery