Introduction: The rate of squamous cell carcinoma spontaneous regression (SR) remains unknown because incidences are rare and underreported. Case Report: We present a case of a 92-year-old Caucasian female who was found to have a 1 cm lesion on her nose. Pathologic evaluation supported the diagnosis of a moderately-differentiated squamous cell carcinoma. The patient refused treatment and returned with no clinical evidence of disease several months later. The lesion spontaneously regressed without excision. Discussion: Frequency of SR of malignancies has been estimated to occur 1 in 80,000 to 100,000 cases [1]. The biologic mechanisms of SR in malignancies remain unclear. Further investigations into the mechanisms of SR may identify potential treatment strategies for cancer.
Currently, the rate of squamous cell carcinoma spontaneous regression (SR) remains unknown. There has been much speculation as to mechanisms of SR. An immunologic mechanism has been proposed from clinical observations of an increased incidence of malignancies seen in immunosuppressed patients. Both in vivo and in vitro evidence supports an immunologic and hormonal mechanism in tumor regression. Alterations affecting apoptotic pathways of squamous cell carcinomas have been proposed as a mechanism for carcinogenesis and SR via T cell-mediated apoptosis. Both Cytotoxic T lymphocytes (CTLs) and Natural Killer cells (NK) can identify and induce apoptosis of cancer cells [
A 92-year-old Caucasian female presented to her local dermatologist with a non-tender, one centimeter, centrally ulcerated lesion with raised margins arising on the nose (
Cases of spontaneous remissions are rare and as a result, the rate among the general population remains unknown. “Spontaneous remission” can be defined as an incomplete or complete regression of a malignant growth in the absence of treatment or presence of treatment known to have no effect on cancer progression [
The clinical presentation and histopathologic findings supported the diagnosis of squamous cell carcinoma in our patient. Our sample demonstrated numerous mitosis, marked pleomorphism, and moderate differentiation, favoring squamous cell carcinoma over keratoacanthoma. Keratoacanthomas represent a well-differentiated variant.
Cells are equipped to handle DNA damage and decrease chance of cancer progression via photoreactivation, base excision, mismatch, double-stranded break, and nucleotide excision repair [
More evidence of the role of the immune system is demonstrated following organ transplantation. Immunosuppressed patients have a high incidence of squamous cell carcinoma development and lower rates of regression [
Mechanistically, SR can occur via T-cell mediated apoptosis. In vitro investigation of immunomodulation of neoplastic cells have been successful. Particularly, CTLs, leukocytes, monocytes, natural killer cells, lymphokineactivated killer cells, and rare plasma and mast cells have all been found to infiltrate tumors. Specifically, MHC class I Cytotoxic T lymphocytes have been found to have the greatest specificity for cancer cells [
Squamous cell cancer is traditionally treated with surgical excision and intractable cases with surgery and platinum-based chemotherapy. Locally advanced, metastatic, and unresectable cases provide a greater challenge to treat. Targeting immunotherapies has demonstrated tremendous promise with treating intractable cases. Case reports of cetuximab, a monoclonal antibody targeting Epidermal Growth Factor Receptor (EGFR) has been associated with prolonged survival and is “well-tolerated” [
While significant evidence validates the immunological basis for cancer remission, regression may be nonimmunologic, as well. Elimination of carcinogens has been shown to result in cancer remission in certain cancers. However, this theory is incomplete. A prime example is smoking’s influence on lung cancer. Smoking cessation does not induce cancer remission [
Hormones and trophic factors can have an effect on squamous cell cancer. In a Mancuso et al. study of two mice models, ovariectomized mice (with diminished estradiol and progesterone levels) have increased tumorogenesis and decreased tumor latency when compared to control mice. One theory is that estrogen is thought to bind with ERβ, which downregulates proto-oncogenic cyclin D1 transcription and ERα’s “proliferative action” on cancer cells [
Other potential factor in inducing spontaneous remission, include cell re-differentiation via retinoic acids, growth factors, and other substances, natural killer cells, modulation of oncogene and tumor suppressors, anti-angiogenesis factors, apoptosis, and withdrawal of cellular stresses [
Further research into the underpinnings of spontaneous regression in malignancies may identify potential therapeutic treatment strategies for the prevention and treatment of malignancies.
Luckey Dunn M. D., Dana V. Ferrence, R. N.