Other skin cancer (non-melanoma, non BCC, non SCC)

Skin Cancer (Non-Melanoma)

Epidemiology:

Non-melanoma skin cancer (NMSC) is broadly characterized by two primary subtypes: basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). These malignancies are the most prevalent forms of skin cancer globally, with estimates indicating that over 5 million cases are diagnosed annually in the United States alone^1,2. Notably, spontaneous remission (SR) in NMSC is exceptionally rare. SR events are often unrecognized unless dramatic, making precise prevalence estimates challenging; it has been reported that instances of SR may account for less than 1% of NMSC cases³. Such sporadic occurrences have raised interest in the immunological mechanisms and environmental factors that may contribute to spontaneous remission, despite limited evidence and rare reports⁴.

Clinical Characteristics:

To date, 43 well-documented SR cases involving primary cutaneous or metastatic skin malignancies have been reported in the literature between 1961 and 2025. Reported patient ages ranged from 20 to 96 years, with most cases occurring in the sixth to ninth decades of life. A slight female predominance was noted (approximately 1.3:1), indicating a marginally higher incidence of SR among women. Overall, SR was most frequently observed in older individuals, typically involving lesions of the skin or facial regions, and was occasionally associated with localized immune stimulation, including biopsy, infection, or vaccination. See table 1 below for further information.

Histological Characteristics:

Patients who experienced SR of cutaneous malignancies commonly presented with visible skin nodules or plaques, often located on the face, scalp, or lower limbs. Diagnosis was typically established through clinical evaluation and histopathological examination of skin biopsy specimens. In most cases, the disease was localized or regionally advanced, occasionally involving lymph nodes or distant cutaneous sites. Remission was generally verified by clinical or histologic assessment, often revealing complete disappearance of the lesion or replacement by fibrotic tissue. Nearly all reported SR cases were associated with prolonged remission or sustained regression, occasionally persisting for months to years, markedly exceeding the expected course of cutaneous malignancy.

Proposed Contributing Mechanisms:

Multiple mechanisms have been proposed to explain SR in cutaneous malignancies. The most frequently cited involve immune-mediated tumor destruction, often triggered by infection, biopsy, or vaccination, which may enhance tumor antigen recognition and activate cytotoxic T-cell responses. Other suggested factors include ischemic necrosis and reactive inflammatory processes that compromise tumor viability. Overall, SR in cutaneous malignancies appears to result from a complex interaction between immune activation and local microenvironmental changes leading to tumor regression.

Site and Extent of Remission:

Most documented SR cases in cutaneous malignancies involved complete disappearance of the lesions, while a smaller number exhibited partial or localized regression. Regression affected both primary and metastatic sites in several instances, most frequently involving the skin, lymph nodes, or lungs. Reported follow-up durations ranged from weeks to several years, with many patients maintaining long-term remission. Compared with other tumor types, SR in cutaneous malignancies has sometimes led to durable remission and extended survival.

Table 1: Skin Cancer SR Cases and Clinical Characteristics

Author–year	Age/sex	Primary site	Remission site	Proposed mechanisms	Follow-up
Khader et al., 2015⁵	40/F	Left knee	Left knee	Immunologic reaction to biopsy	2 years
Cirillo, 2015⁶	89/M	Scalp (left temporal, vertex)	Scalp (left temporal, vertex)	Immunologic reaction to biopsy	24 months
Terui et al., 2016⁷	94/F	Left cheek	Left cheek	CD8+ immune cell infiltration	20 days
Branch et al., 2018⁸	96/F	Suprasternal notch	Suprasternal notch	T-cell–mediated immunity	8 weeks
Nagase et al., 2018⁹	83/F	Nose	Nose	Ischemic factors	Not reported
Longo et al., 2018¹⁰	69/M	Lymph node	Lymph node	Not reported	Not reported
Marcoval et al., 2018¹¹	69/M	Parietal scalp	Parietal scalp	Immune response to viral infection	Not reported
Marcoval et al., 2018¹¹	72/F	Left pretibial region	Left pretibial region	Immune response to viral infection	4 weeks
Bystricky et al., 2021¹²	88/F	Right cheek	Right cheek	Biopsy-related immune response	3 months
Leung et al., 2021¹³	71/F	Left lower eyelid and cheek	Left lower eyelid and cheek	Not reported	5 weeks
Bellot et al., 2023¹⁴	76/Not reported	Left leg	Left leg	T-cell–mediated immune response	3 weeks
Wesselmann et al., 2024¹⁵	84/M	Right forearm	Forearm Lymph Node	Vaccine–induced antiviral immune response	3 months
Castano et al., 2012¹⁶	93 -year-old male	left cheek mass	Primary reduced in size over several weeks with CR sattelite lesions. CR 2 yaers out from biopsy	none offrerred	Primary reduced in size over several weeks with CR sattelite lesions. CR 2 yaers out from biopsy
Mulder et al., 2010¹⁷	78-year-old man	left parotid gland	after 10 weeks he noticed a slow but consistent regression of the lesion. Clinical follow-up 5 months later showed no trace of the tumour.		after 10 weeks he noticed a slow but consistent regression of the lesion. Clinical follow-up 5 months later showed no trace of the tumour.
Ishikawa et al., 2004¹⁸	24 years old Japanese woman	Blood vessels, Right aural region	After a follow-up period of 2 years, the nodules totally dissapeared		After a follow-up period of 2 years, the nodules totally dissapeared
Mckenna, 2000¹⁹	2‐month‐old female	blood vessels of the skin	The lesion gradually regressed over a 14-month period.	none reported	The lesion gradually regressed over a 14-month period.
Schwartz, 2020²⁰	2-day-old boy	skin	Four years later, the child had been healthy and developing appropriately since diagnosis.	none reported	Four years later, the child had been healthy and developing appropriately since diagnosis.
Kaneshima, 2019²¹	3-month-old boy	skin	The skin rashes started regressing 3 months after onset and had completely disappeared 6 months later	none reported	The skin rashes started regressing 3 months after onset and had completely disappeared 6 months later
Fukumoto, 2018²²	76-year-old man	skin	14 days after biopsy, the remaining nodule disappeared completely without additional therapy	None reported	14 days after biopsy, the remaining nodule disappeared completely without additional therapy
Martin, 2018²³	10-year-old girl	skin	Ten days after receiving the first dose of the human papillomavirus (HPV) bivalent vaccine, total remission of the wart was noted	In addition to an immune response to the L1 capsid protein, a nonspecific effect related to locally released chemokines could also be involved	Ten days after receiving the first dose of the human papillomavirus (HPV) bivalent vaccine, total remission of the wart was noted
Álvarez-Chinchilla, 2018²⁴	42-year-old woman. History of several autoimmune processes, including HLA-B27-positive sacroiliitis, ANA-positive peripheral arthritis, and autoimmune hypothyroidism that was treated with supplemental L- tyrosine.	skin	the patient’s melanocytic lesions pro- gressively disappeared and were practically absent by the end of a 3-year period	the mechanism underlying nevus disappearance in this case was most likely immune in nature	the patient’s melanocytic lesions pro- gressively disappeared and were practically absent by the end of a 3-year period
Li, 2018²⁵	79‐year‐old male	skin	The lesions regressed spontaneously after one month	The predominantly increasing dendritic cells in the epidermis, which stained CD1a, accompanied with multiple histiocytes in deep dermis probably indicated the underlying immunological mechanism.	The lesions regressed spontaneously after one month
Albayyat, 2019²⁶	83-year-old man. History of cataract extraction with insertion of intraocular lenses in both eyes. renal cell carcinoma	conjunctiva	Five weeks after the onset of the lesion while waiting for surgery and without any intervention, the patient noted a sudden spontaneous bleeding from the mass and associated decrease in the size of the lesion	The regression process is thought to be driven by Wnt and retinoic acid signalling pathways.	Five weeks after the onset of the lesion while waiting for surgery and without any intervention, the patient noted a sudden spontaneous bleeding from the mass and associated decrease in the size of the lesion
Amagai, 2018²⁷	26-year-old Japanese female	skin	her nodule rapidly regressed with hyperkeratosis, central depression and prominent erythema around the tumor	antitumor immune response was suppressed at the tumor site.	her nodule rapidly regressed with hyperkeratosis, central depression and prominent erythema around the tumor
Nanda, 2024²⁸	58-year-old woman. history of allergic rhinitis and zoster	skin	The lesions shrank in size over the subsequent weeks. At the 6-week post-laser visit, the eruptive papules had spontaneously completely resolved, with excellent cosmetic results	None reported	The lesions shrank in size over the subsequent weeks. At the 6-week post-laser visit, the eruptive papules had spontaneously completely resolved, with excellent cosmetic results
Hu, 2021²⁹	62-year-old woman	skin	On the 4th week follow-up visit, the nodule on her left nose almost disappeared and the characteristic dermoscopic patterns, including yellowish follicular plugs and white cotton materials with linear- irregular vessels, were gone.	None reported	On the 4th week follow-up visit, the nodule on her left nose almost disappeared and the characteristic dermoscopic patterns, including yellowish follicular plugs and white cotton materials with linear- irregular vessels, were gone.
Heath, 2018³⁰	71-year-old Caucasian male. History of non-melanoma skin cancer	skin	The presence of surrounding dermal fibrosis and inflammation in combination with the clinical presentation suggest spontaneous involution (regression)	None reported	The presence of surrounding dermal fibrosis and inflammation in combination with the clinical presentation suggest spontaneous involution (regression)
Nijar, 2018³¹	77-year-old gentleman	breast	FDG PET/CT performed two weeks after biopsy did not show any FDG-avid lesion, except for a nonspecific uptake in multiple mediastinal lymph nodes. The tumor was staged as IIA (T2N0).	the role of T cell-mediated immune response in the development of tumor regression resulting in apoptosis and cellular necrosis	FDG PET/CT performed two weeks after biopsy did not show any FDG-avid lesion, except for a nonspecific uptake in multiple mediastinal lymph nodes. The tumor was staged as IIA (T2N0).
Collins, 1894³²	Mr. M., had a small elevation on the right cheek twenty years ago, which frequently formed a scab		As the erysipelas faded out, the desquamations following the ulcer seemed to assume a more healthy appearance. Granulations of a more normal character developed and in about two weeks the ulcer was entirely healed. The cicatrix on March 1 is slightly indurated, but smooth and firm, presenting the appearance of normal cicatricial tissue		As the erysipelas faded out, the desquamations following the ulcer seemed to assume a more healthy appearance. Granulations of a more normal character developed and in about two weeks the ulcer was entirely healed. The cicatrix on March 1 is slightly indurated, but smooth and firm, presenting the appearance of normal cicatricial tissue
Ronchese, 1953³³			spontaneous involution		spontaneous involution
Obermayer, 1949³⁴	21-year-old unmarried woman		Two weeks after the last consultation, all verrucae had disappeared	Posthypnotic suggestion	Two weeks after the last consultation, all verrucae had disappeared
Tagami et al., 1977³⁵			Within two to six weeks, all the warts completely involuted	a mononuclear cell infiltration with epidermal invasion	Within two to six weeks, all the warts completely involuted
Aiba et al., 1986³⁶			the presence of HPV antigen using papilloma virus genus-specific antiserum in 31 cases of regressing flat warts was not found, whereas it was demonstrated in the nuclei of upper epidermal cells of ordinary flat warts in 12 of 19 cases (63%)	T-cell-mediated immune attack against tumor cells, and not against intranuclear HPV antigen, induces the systemic spontaneous regression of numerous flat warts in humans	the presence of HPV antigen using papilloma virus genus-specific antiserum in 31 cases of regressing flat warts was not found, whereas it was demonstrated in the nuclei of upper epidermal cells of ordinary flat warts in 12 of 19 cases (63%)
Bowling et al., 2005³⁷
Ciudad et al., 2010³⁸
Holak et al., 2008³⁹
Mancini, 2008⁴⁰
Maruo et al., 2000⁴¹
Missotten et al., 2008⁴²
Nihei et al., 2004⁴³
Sais et al., 2002⁴⁴
Turk et al., 2009⁴⁵
Val-Bernal et al., 2011⁴⁶
Furue et al., 2001⁴⁷

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