Histogenesis of malignant melanoma of the skin: the role of lymphocytes in the transformation of tissue developmental units.
It is proposed that the completion of both growth and differentiation, in highly specialized progressively evolving multicellular organisms, is achieved throughout two separated but sexually interacting populations of cells (bi-clonal model): 1) the germ line, seated in an obligatory axial position, required for the generation of cytoplasmic replicons, is the source of travelling vectors (spermatozoa, lymphocytes ...) endowed with these potentially transforming nucleoproteins. 2) The centrifugally growing somatic tissues subjected to mitotic senescence. The progressive loss of replicons probably triggers meiotic-like recombinations and differentiation in distal tissues. The shedding of axial replicons to distal meiotic targets seems to be instrumental in transformation, initiating both, embryogenesis and cancer. This theoretical approach is applied to the histogenetic model of malignant melanoma of the skin. In this setting, the axial population is identified as lymphocytes involved in a process of extrathymic maturation (lichenoid lesions), in the same field where melanoma would arise. Pagetoid nests of melanocytes are considered to be the expression of TDUs evolving in a distal population of senescent neurocristic cells. This situation establishes the likelihood of mixing between potentially transforming lymphocytes and the meiotic melanocytes resulting in a transformed hybrid, the earliest cellular expression of malignant melanoma.
Palacios Llopis
S
S
Department Anatomia Patológica, Hospital Nacional Marqués de Valdecilla, Santander, Spain.
D002454:Cell Differentiation; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D004848:Epithelium / Q000473:pathology; D006801:Humans; D008214:Lymphocytes / Q000473:pathology; D008544:Melanocytes / Q000473:pathology; D008545:Melanoma / Q000209:etiology* / Q000473:pathology; D008938:Mitosis; D008954:Models, Biological; D010641:Phenotype; D012878:Skin Neoplasms / Q000209:etiology* / Q000473:pathology