Prolonging the debate about precursors of invasive squamous cell carcinoma.
A busy Friday prevented me from participating in Case 875 of spot diagnosis, but I make a point of getting into the relevant discussion brought up by Dr. Sasi Attili. Foresseing my comment could be the last one, I thought it was a good idea prolong the debate in my own blog.
A number of key principles are enshrined in the medical science, and the fact that tumors are monoclonal proliferations is one of them. That implies any tumor arise from the clonal expansion of a single cell which has undergone nonlethal genetic damage.
An inescapable conclusion can be drawn from this principle of the oncogenesis: lesions, even the so-called preneoplastic ones, do not transform into tumors. Only individual cells do.
It turns out that some lesions may result from the action of factors capable of creating a favorable intrinsic environment for the emergence of neoplastic-related mutations in individual cells, or from the action of factors capable themselves to induce directly these mutations.
Several factors are known to be associated with neoplastic-related mutations in individual cells of the epidermis, including, first and foremost, sunlight, arsenic, psoralens and ultraviolet-A radiation (PUVA), and human papillomavirus (HPV). Thus, lesions may crop up in the epidermis due to long-term exposure to these factors or to other lesser-known agents. Even though designated according to the causative factor as actinic keratosis, arsenical keratosis, PUVA keratosis, Bowen disease, and so forth, such lesions are composed of cells with neoplastic-related mutations, i.e., they all are already neoplastic lesions. They are not keratinocytic dysplasia or intraepidermal squamous precursor lesions. Each of them is early squamous cell carcinoma since the clone that compose these lesions is the very same clone that will compose the advanced squamous cell carcinoma after the progression of the disease.
Probably the theory that the so-called keratinocytic dysplasias are precursors of invasive squamous cell carcinoma emerged from the ascertainment that, in the majority of cases, actinic keratosis, arsenical keratosis, PUVA keratosis, Bowen disease, and so forth, do not evolve, inexorably, into a frankly aggressive squamous cell carcinoma characterized by rapid growth, infiltration of underlying tissues like subcutaneous fat or bone, and distant metastasis. This happens just because early squamous cell carcinoma may remit spontaneously, remain unchanged for many years even without treatment, or have its progress halted by an effective therapeutic intervention.
Moreover, it's impossible to unequivocally establish, both clinically and microscopically, from when the so-called keratinocytic dysplasias must be referred as invasive squamous cell carcinoma. There's no reliable criteria to distinguish one from the other just because they are a single process that begins superficially and may progress.
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