Cellular heterogeneity in vertical growth phase melanoma.
BACKGROUND
Melanoma growing as a tumorigenic nodule is one of the most virulent neoplasms to which the flesh is heir. At a considerably small tumor size, it incurs significant risk for widespread metastatic dissemination. There are no effective means of surgical intervention, chemical therapy, or immunologic therapy for advanced and metastatic melanoma.


OBJECTIVE
To review the literature and highlight recent cardinal advances in the understanding of melanoma vertical growth, with specific emphasis on how its recognition and characterization may be applied to diagnostic practice and development of novel investigative approaches.


METHODS
Literature review, archival material, personal experience, and research collaborators.


CONCLUSIONS
The study of tumorigenic melanoma, both in primary lesions and in metastases, is the key to the eventual eradication of this highly virulent neoplasm that may disseminate widely when only occupying the volume of a grain of rice. Morphology often provides the first insight into structure and function. A growing database using meticulous and inclusive criteria to define tumor stem cells in the context of clinically relevant models now indicates that the key to melanoma heterogeneity may reside in a small subpopulation with the ability to self-renew and form tumors despite most cells present being significantly less virulent. Hopefully, from these insights into melanoma tumor progression from radial growth phase to heterogeneous and tumorigenic vertical growth phase will come additional answers to how smart therapies may be developed that specifically target those vertical growth phase cells that most pertain to patient survival.
Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. alaga@rics.bwh.harvard.edu
Alvaro C
AC
Laga
George F
GF
Murphy
D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000473:pathology; D009389:Neovascularization, Pathologic; D012878:Skin Neoplasms / Q000473:pathology*