Squamous cell carcinoma (skin)

Squamous Cell Carcinoma (Skin)

Epidemiology:

Squamous cell carcinoma (SCC) of the skin is recognized as the second most prevalent nonmelanoma skin cancer, with an estimated annual incidence in the United States exceeding 1.5 million cases ¹. While the vast majority of cases are treated successfully through local excision, spontaneous remission (SR), characterized by an unexpected resolution of cancer without treatment, is exceedingly rare, with reports indicating it occurs in less than 1% of cases ². This complexity is further compounded by the generally limited clinical awareness and documentation of subtle or complete remissions, thus complicating the understanding of their true prevalence in the population ³.

Clinical Characteristics:

To date, nine cases of spontaneous remission (SR) of cutaneous squamous cell carcinoma have been reported in the medical literature. These cases collectively emphasize the exceptional rarity of this phenomenon and its occurrence across a wide age spectrum, ranging from the third to the tenth decade of life. The reported cases included both male and female patients, comprising five males and four females, indicating no significant gender predilection (male-to-female ratio 5:4). See Table 1 for detailed case information.

Histological Characteristics:

Of the cases analyzed, the tumors were exclusively reported as originating from cutaneous sites, most frequently in sun-exposed regions such as the face, scalp, and extremities. Remission occurred predominantly at the same cutaneous sites, although in some instances, regional lymph node involvement was also noted. No cases involving distant metastases or extra-cutaneous origins were included, as only those demonstrating definitive spontaneous remission of primary cutaneous squamous cell carcinoma were considered. This selection ensured diagnostic precision and preserved the clinical specificity of spontaneous remission in cutaneous squamous cell carcinoma.

Proposed Contributing Mechanisms:

Among the reported cases, proposed mechanisms for spontaneous remission included immune response, hormonal influences, psychological factors, ischemic necrosis, and tumor maturation, although several reports did not specify an underlying cause. Overall, immune-mediated activity, local ischemic injury, and tumor differentiation are thought to play pivotal roles in facilitating spontaneous remission in cutaneous squamous cell carcinoma.

Site and Extent of Remission:

The majority of documented cases demonstrated complete remission localized to the primary cutaneous sites, most frequently involving the face, scalp, and extremities, including regions such as the nose, temporal area, lip, leg, and parietal scalp. In a few cases, remission extended to regional lymph nodes, including the inguinal, cervical, axillary, and epitrochlear nodes, reflecting localized immune activity or inflammatory mechanisms contributing to tumor clearance. Reported follow-up durations ranged from several weeks to years, with the longest observed remission lasting for multiple years, indicating durable disease control without therapeutic intervention. Collectively, these observations suggest that spontaneous remission in cutaneous squamous cell carcinoma, though exceedingly rare, may occasionally result in sustained and clinically meaningful resolution of lesions across diverse anatomical sites.

Table 1: Squamous cell carcinoma SR Cases and Clinical Characteristics

References:

1. Marcil I. , Stern R. Risk of developing a subsequent nonmelanoma skin cancer in patients with a history of nonmelanoma skin cancer. Arch Dermatol. 2000;136(12). doi:10.1001/archderm.136.12.1524
2. Thrift A., Hughes M., Muranushi C., et al. A model to predict the risk of keratinocyte carcinomas. Journal of Investigative Dermatology. 2016;136(6):1247-1254. doi:10.1016/j.jid.2016.02.008
3. Amin A., Küçük Ö., Khuri F., & Shin D. Perspectives for cancer prevention with natural compounds. JCO. 2009;27(16):2712-2725. doi:10.1200/jco.2008.20.6235
4. Smith JF. A Case of Multiple Primary Squamous-Celled Carcinomata of Skin in a Young Man. Br J Dermatol. 1934;46(6):267–272.
5. Dunn JS, Smith JF. Self-Healing Primary Squamous Carcinoma of the Skin. Br J Dermatol. 1934;46:519–523.
6. Smith JF. Multiple Primary, Self-Healing Squamous Epithelioma of Skin. Br J Dermatol. 1948;60:315–318.
7. Sommerville J, Milne JA. Familial Primary Self-Healing Squamous Epithelioma of the Skin (Ferguson Smith Type). Br J Dermatol. 1950;62:485–490.
8. Schnapp AC, Blake WJ. Spontaneous Cure of Epidermoid Carcinoma with Widespread Metastases. Wis Med J. 1961;60(12):633–636.
9. Foley C, Moran B, McMenamin M, McDermott R, Ormond P, Irvine AD. Spontaneous regression of cutaneous metastases of squamous cell carcinoma. QJM. 2014;107(1):61–63. doi:10.1093/qjmed/hct162
10. Misago N, Takai T, Murata Y, Nagase K, Narisawa Y. Cases with a spontaneous regression of an infiltrating non-crateriform keratoacanthoma and squamous cell carcinoma with a keratoacanthoma-like component. J Dermatol. 2014;41(5):430–434. doi:10.1111/1346-8138.12454
11. Brufau-Cochs M, Sandoval-Clavijo A, García-Herrera A, Toll-Abelló A. Spontaneous regression of aggressive cutaneous squamous cell carcinoma. Indian J Dermatol Venereol Leprol. 2025;91(3):386–388. doi:10.25259/IJDVL_1205_2023
12. Sipaul, F., Ling, B., Mason, C., & Keast, A. (2015). spontaneous regression of laryngeal squamous cell carcinoma. The Journal of laryngology and otology, 129(12), 1248–1250. https://doi.org/10.1017/S0022215115002595
13. de Andrade Sousa, A., Lopes Rena, R., Souza Silva, G., Marcos Arantes Soares, J., Porcaro-Salles, J. M., Nunes, L., Alves Mesquita, R., & Jham, B. C. (2014). spontaneous remission of a squamous cell carcinoma of the floor of the mouth. Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery, 42(7), 1536–1539. https://doi.org/10.1016/j.jcms.2014.04.026
14. Choi, N., Cho, J. K., Baek, C. H., Ko, Y. H., & Jeong, H. S. (2014). spontaneous regression of metastatic cancer cells in the lymph node: a case report. BMC research notes, 7, 293. https://doi.org/10.1186/1756-0500-7-293
15. Depierre, A., Breton, J. L., & Garnier, G. (1984). Régression spotaneousanée d'un cancer bronchique épidermoïde [spontaneous regression of a bronchial epidermoid cancer]. Revue des maladies respiratoires, 1(2), 113–117.
16. Kumaresan, T., Rodriguez, D., Preece, J., Kmeid, M., Foulke, L., & Gildener-Leapman, N. (2025). Oral Tongue Spontaneous Tumor Regression after Biopsy: A Case Report and Genomic Profile. Ear, nose, & throat journal, 104(3), 151–154. https://doi.org/10.1177/01455613221100034
17. Watkins, M. O., Tate, A. D., Lewis, J. S., Jr, & Garrett, C. G. (2022). Spontaneous Regression of Laryngeal Squamous Cell Carcinoma After Biopsy. Ear, nose, & throat journal, 101(1), 59–61. https://doi.org/10.1177/0145561320939834
18. Kim, Y., Helm, K. F., Billingsley, E. M., & Lam, C. (2019). Spontaneous Regression of a Keratoacanthoma Centrifugum Marginatum. Dermatology practical & conceptual, 9(2), 157–159. https://doi.org/10.5826/dpc.0902a16