Squamous cell carcinoma (skin) - Spontaneous Remission Database

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

Author–year	Age/sex	Primary site	Remission site	Proposed mechanisms	Follow-up
Smith, 1934⁴	23/M	Skin	Legs, face, neck, hand, calf	Not reported	Several months to years
Dunn & Smith, 1934⁵	42/M	Skin (right thigh)	Right thigh	Not reported	Not reported
Smith, 1948⁶	Not reported	Skin (right leg, face, nose)	Not reported	Not reported	Not reported
Sommerville & Milne, 1950⁷	34/F	Skin (nose, leg, chin, ears, scalp, forearms, buttock)	Nose, leg, forearm, buttock	Not reported	4 months
Schnapp & Blake, 1961⁸	40/M	Skin (back, leg, arm, forearm, shoulder)	Lymph nodes (inguinal, cervical, axillary, epitrochlear)	Not reported	Not reported
Foley et al., 2014⁹	74/F	Skin (right lower extremity)	Right lower extremity	Immune response, Hormonal factors, Psychological factors	18 months
Misago et al., 2014¹⁰	43/F	Skin (right temporal region)	Right temporal region	Not reported	7 weeks
Misago et al., 2014¹⁰	84/F	Skin (upper lip)	Upper lip	Not reported	4 weeks
Brufau-Cochs et al., 2025¹¹	90s/M	Skin (left parietal area)	Skin (parietal and temporal regions)	Not reported	12 weeks
Deandrade et al., 2014¹²	62 -year-old male, ETOH/Tob HX	Oral cavity, floor mouth	CR at 3 months follow up	None reported	CR at 3 months follow up
Choi et al., 2014¹³	52 -year-old female asian	right buccal area	aspiration found no malignancy and she has remained in a disease-free state for 4 years total regression was revealed after salvage neck dissection and surgical pathology of recurrence that occurred 4 years and 6 months after treatment. I.e. Total regression of metastatic squamous cell carcinoma cell sin the left level V LN and there was no malignancy of other lymph nodes * the left level V lymph nodes were not involved in pervious surgeries or radiation * complete tumor regression was confirmed by cytokeratin and Ki-67 staining, high levels of cytokeratin and Ki-67 were observed in the tumor cells cytokeratin was noted in the keratin debris Marked differences between the metastatic node and tumor-regressed node were in the incidence of Foxp3+ regulatory T cells and CD56+ natural killer cells. There was nearly 2-fold in the metastatic node a noticeable infiltration of CD56+ NK cells was found in the keratin debris in the tumor-regressed LN	immunological events or unknown etiology the interaction between Treg and Nk cells may be an imporightant phenomenon in SR	aspiration found no malignancy and she has remained in a disease-free state for 4 years total regression was revealed after salvage neck dissection and surgical pathology of recurrence that occurred 4 years and 6 months after treatment. I.e. Total regression of metastatic squamous cell carcinoma cell sin the left level V LN and there was no malignancy of other lymph nodes * the left level V lymph nodes were not involved in pervious surgeries or radiation * complete tumor regression was confirmed by cytokeratin and Ki-67 staining, high levels of cytokeratin and Ki-67 were observed in the tumor cells cytokeratin was noted in the keratin debris Marked differences between the metastatic node and tumor-regressed node were in the incidence of Foxp3+ regulatory T cells and CD56+ natural killer cells. There was nearly 2-fold in the metastatic node a noticeable infiltration of CD56+ NK cells was found in the keratin debris in the tumor-regressed LN
Depierre et al., 1984¹⁴	57-year-old male Heavy tobacco & liquor usage	Carina of middle lobe	Bronchial aspiration produced a muco-inflammatory substance rich in alveolar macrophages Immunologic study performed on patient in 1983 showed increase in fraction C3: 165 (normal 15-120) and C4 : 61 (normal 20-50)	Possible factor is the notable rise in NK cells	Bronchial aspiration produced a muco-inflammatory substance rich in alveolar macrophages Immunologic study performed on patient in 1983 showed increase in fraction C3: 165 (normal 15-120) and C4 : 61 (normal 20-50)
Kumaresan, 2025¹⁵	77-year-old woman. Past medical history included active Meniere’s disease and trigeminal neuralgia.	Tongue, lymph nodes	Two weeks later, the tongue mass had almost completely regressed. One month later, the tongue had a stable 4-mm deep pocket with some thickened tissue, but no tumor was visible.	None reported	Two weeks later, the tongue mass had almost completely regressed. One month later, the tongue had a stable 4-mm deep pocket with some thickened tissue, but no tumor was visible.
Kumaresan, 2025¹⁵	77-year-old woman. active Meniere’s disease and trigeminal neuralgia.	Tongue	Approximately two weeks after the PET scan, the tongue mass had almost completely regressed. Pathology demonstrated marked tumor regression with only a minute focus of residual invasive SCC with surrounding chronic inﬂammatory cells and tumor apoptotic ﬁgures	None reported	Approximately two weeks after the PET scan, the tongue mass had almost completely regressed. Pathology demonstrated marked tumor regression with only a minute focus of residual invasive SCC with surrounding chronic inﬂammatory cells and tumor apoptotic ﬁgures
Watkins, 2022¹⁶	62-year-old male	Vocal cord	Two weeks after MDL a repeat clinical examination by a laryngologist revealed significant improvement. There was almost complete regression of the exophytic SCC. Three weeks later a new MDL revealed a nearly normal in appearance left true vocal fold. There was a small focal area of mucosal irregularity on the left superior surface. Histopathological examination reported inflamed squamous mucosa with reactive and regenerative changes that were negative for malignancy.	Biopsy to the cancerous area led to an antitumor immune response, causing regression of the remaining tumor.	Two weeks after MDL a repeat clinical examination by a laryngologist revealed significant improvement. There was almost complete regression of the exophytic SCC. Three weeks later a new MDL revealed a nearly normal in appearance left true vocal fold. There was a small focal area of mucosal irregularity on the left superior surface. Histopathological examination reported inflamed squamous mucosa with reactive and regenerative changes that were negative for malignancy.
Kim, 2019¹⁷	Caucasian man in his 70s	skin	the patient subsequently noticed flattening and reduction in size of the lesion. Three months after initial presentation, physical examination showed a 4 × 5 cm, nontender, nonmalodorous thin plaque with a minor amount of friable tissue and clinically normal skin in the center. A third biopsy was consistent with a regressing KCM	None reported	the patient subsequently noticed flattening and reduction in size of the lesion. Three months after initial presentation, physical examination showed a 4 × 5 cm, nontender, nonmalodorous thin plaque with a minor amount of friable tissue and clinically normal skin in the center. A third biopsy was consistent with a regressing KCM
Oya et al., 2004¹⁸
Ramos et al., 2009¹⁹
Ansai et al., 2005²⁰
Batinac et al., 2006²¹
Hedayati, 2024²²
Marcil²³
Thrift et al.²⁴
Amin et al.²⁵

References:

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
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
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
Smith JF. A Case of Multiple Primary Squamous-Celled Carcinomata of Skin in a Young Man. Br J Dermatol. 1934;46(6):267–272.
Dunn JS, Smith JF. Self-Healing Primary Squamous Carcinoma of the Skin. Br J Dermatol. 1934;46:519–523.
Smith JF. Multiple Primary, Self-Healing Squamous Epithelioma of Skin. Br J Dermatol. 1948;60:315–318.
Sommerville J, Milne JA. Familial Primary Self-Healing Squamous Epithelioma of the Skin (Ferguson Smith Type). Br J Dermatol. 1950;62:485–490.
Schnapp AC, Blake WJ. Spontaneous Cure of Epidermoid Carcinoma with Widespread Metastases. Wis Med J. 1961;60(12):633–636.
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
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
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
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
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
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.
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
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
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
Oya, R., & Ikemura, K. (2004). Spontaneous regression of recurrent squamous cell carcinoma of the tongue. International Journal of Clinical Oncology / Japan Society of Clinical Oncology, 9(4), 339-342. doi:10.1007/s10147-004-0404-6
Ramos, L. M., Cardoso, S. V., Loyola, A. M., Rocha, M. A., & Durighetto-Junior, A. F. (2009). Keratoacanthoma of the inferior lip: Review and report of case with spontaneous regression. Journal of Applied Oral Science : Revista FOB, 17(3), 262-265.
Ansai, S., & Manabe, M. (2005). Possible spontaneous regression of a metastatic lesion of keratoacanthoma-like squamous cell carcinoma in a regional lymph node. The Journal of Dermatology, 32(11), 899-903.
Batinac, T., Zamolo, G., Coklo, M., & Hadzisejdic, I. (2006). Possible key role of granzyme B in keratoacanthoma regression. Medical Hypotheses, 66(6), 1129-1132. doi:10.1016/j.mehy.2005.12.035
Hedayati, M. 2024. Identifying SCC Lesions Capable of Spontaneous Regression by Using Immunohistochemistry: A Systematic Review and Meta-Analysis
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)
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
Amin A., Küçük Ö., Khuri F., & Shin D. Perspectives for cancer prevention with natural compounds. JCO. 2009;27(16):2712-2725

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