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Non-Melanoma Skin Cancer

Basal Cell Carcinoma is the most common type of skin cancer, it occurs when basal cells (round cells found in the outer layer of skin) become cancerous. The second most common type of skin cancer is Squamous Cell Carcinoma, this is where squamous cells (the flat, scaly cells on the surface of the skin) become malignant . Cure rates are very high for both basal cell carcinoma and squamous cell carcinoma. In addition there are a number of other, less common cancers starting in the skin including Merkel cell tumours and cutaneous lymphomas and sarcomas (see the sections on sarcoma and lymphoma for more information about these).

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Basal Cell Carcinoma
Squamous Cell Carcinoma
Cutaneous T-cell Lymphoma
Dermatofibrosarcoma Protuberans
Merkel Cell Cancer
Prevention of Skin Cancer
Skin Cancer

Information Patients and the Public (12 links)

Information for Health Professionals / Researchers (9 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Bashline B
Skin Cancer: Squamous and Basal Cell Carcinomas.
FP Essent. 2019; 481:17-22 [PubMed] Related Publications
Approximately 1 in 5 Americans will develop skin cancer during their lifetime; 97% of these cancers will be nonmelanoma skin cancers (NMSCs). Basal cell carcinoma (BCC) comprises approximately 80% of NMSCs and most of the remainder are cutaneous squamous cell carcinomas (SCCs). The predominant risk factor for NMSC is exposure to solar UV radiation. Skin type also plays a role, with a higher incidence of NMSCs among fairer-skinned individuals. Immunocompromise can increase the risk. Biopsy of suspicious lesions should be obtained to determine histologic subtype and guide treatment. Surgical techniques include excision, curettage and electrodessication, and Mohs micrographic surgery. Nonsurgical therapies such as topical therapy or photodynamic therapy may be used for BCC lesions if surgical techniques are not appropriate. Staging and sentinel lymph node biopsy are reserved for patients with large infiltrative lesions. The prognosis for patients with NMSC is extremely favorable. Because of the low risk of metastasis, significant morbidity or mortality is rare. The American Academy of Dermatology recommends skin examinations for all patients with NMSC at least annually. Primary interventions for prevention include counseling on reducing sun exposure, use of UV-protective clothing and sunscreen, and discouragement of tanning bed use.

Hu M, Tang Y, Long G, et al.
Primary Extracranial Meningioma of Mastoid in a Patient With History of Skin Squamous Cell Carcinoma, Lung Adenocarcinoma and Prostatic Carcinoma.
Anticancer Res. 2019; 39(6):3197-3201 [PubMed] Related Publications
BACKGROUND: Meningiomas are the most common benign intracranial tumors and frequently develop in the parasagittal region, but can also present extracranially. Rarely, meningiomas may involve the middle ear and mastoid, resulting from contiguous spread of adjacent intracranial tumor, or extremely rarely, as an isolated primary tumor, which is frequently misdiagnosed and unrecognized, resulting in inappropriate clinical management.
CASE REPORT: Herein we report such a case of an 80-year-old man with history of multiple cancer who presented with ear pain, vertigo and hearing loss. Audiometry demonstrated bilateral sensorineural hearing loss. Contrast-enhanced temporal bone computed tomography revealed a soft-tissue mass in the right epitympanum without bone erosion or any intracranial involvement. Radiological and operative findings were suspicious for cholesteatoma. Histological examination showed an epithelial neoplasm arranged in nests and whorls with intranuclear inclusions. No psammoma bodies, mitotic figures, or tumor necrosis were identified. The tumor cells were positive for epithelial membrane antigen, vimentin, progesterone receptor and CD56; and negative for synaptophysin, chromogranin, pancytokeratin (AE1/AE3), cytokeratin 7, prostate-specific antigen, inhibin, S100, P63, and P40. Ki67 highlighted about 2% of the tumor cells. Based on the morphological features and immunohistochemical profile, the tumor was diagnosed as primary extracranial meningioma of the mastoid, meningothelial subtype, World Health Organization grade 1.
CONCLUSION: To the best of our knowledge, primary mastoid meningioma clinically mimicking a cholesteatoma presenting in a patient with a history of multiple primary carcinomas has not been previously reported. The pathogenesis, diagnosis and treatment of this entity are discussed.

Оshyvalova ОО, Ziukov OL, Gurianov VG
Prognostic model of skin cancer risk assessment.
Wiad Lek. 2019; 72(5 cz 1):817-822 [PubMed] Related Publications
OBJECTIVE: Introduction: Early detection of people at risk of skin cancer will reduce the incidence of disease, lower the cost of health technologies and decrease anxiety level in patients. The aim of the work is to create a prognostic model for identifying people at increased risk of skin cancer development.
PATIENTS AND METHODS: Material and methods: We used the results of our previous research on identifying risk factors in patients with actinic keratosis (AK), squamous cell carcinoma in situ (SCCis) and cutaneous squamous cell carcinoma (cSCC), who were under dynamic observation at the State Institution of Science "Research and Practical Centre of Preventive and Clinical Medicine" State Administrative Department (hereinafter SIS) in 2014-2017.
RESULTS: Results: The prognostic model is valid, AUC = 0.97 (95% CI 0.96 - 0.99) showing a significant association of the risk of skin cancer development with the following factors: patient's age, sunburns, using skin sunscreens, exposure to the sun in recent times, exposure to radiological materials, drug administration (antiarrhythmic drugs, antihypertensive medications, hormonal contraceptives, antibiotics), burdened family history (melanoma, squamous cell cancer). Model sensitivity was 95.1% (95% CI 91.6% - 97.4%), specificity - 88.5% (95% CI 84.6% - 91.8%).
CONCLUSION: Conclusions: The developed and analysed mathematical risk prediction system made it possible to identify 11 factors which are significantly associated with risk of skin cancer development. The prognostic model might be offered for specialists in taking decision at the stage of primary and secondary prevention of skin cancer.

Lin RL, Wu EM, Hale EK
Use of a Buried Intradermal (Subcutaneous) Running Suture for Superficial Repair to Optimize Cosmetic Outcome
J Drugs Dermatol. 2019; 18(5):481-482 [PubMed] Related Publications
Superficial repair after excisions helps to optimize cosmetic outcomes. Possibly due to how wound closures are traditionally taught in dermatology, simple interrupted or continuous sutures are overwhelmingly favored by dermatologic surgeons in superficial repair, especially on cosmetically sensitive areas such as face and ears. However, this repair method risks wound overgrowth around the points where the suture traverses through the epidermis, and long-term postsurgical healing frequently leaves behind scars with ‘railroad track’ suture marks rather than a fine line. Here, we present buried intradermal running suture technique as an alternative superficial repair method compared to the simple interrupted or running suture techniques. We demonstrate the superior cosmetic outcome offered by buried intradermal suture with 2 patient cases, who had defects on the temple and shin. While dermatologists can now offer energy-based devices and neuromodulators to improve cosmesis, our approach helps optimize scar appearance so that patients can have the best possible surgical outcome without necessitating further interventions. J Drugs Dermatol. 2019;18(5):481-482.

Verhave B, Goldberg M, Hashim P, Levitt J
Treatment of Arsenic-Induced Bowen’s Disease With Topical 5-Fluorouracil
J Drugs Dermatol. 2019; 18(5):477-479 [PubMed] Related Publications
Here, we present a case of arsenic-induced Bowen’s disease treated with a regimen consisting of topical 5-fluouracil and oral nicotinamide. The use of this therapy modality resulted in near complete resolution of all of the patient’s lesions except for those on her palms, soles, and scalp. Excellent wound care and treatment adherence were major factors contributing to the success of this treatment option. Our results ultimately provide an alternative approach to treating multiple arsenical keratoses in patients who are limited to a drug plan involving 5-FU and oral nicotinamide and who are able to be rigorously compliant with application of medication and wound care. J Drugs Dermatol. 2019;18(5):477-479.

Cavalieri S, Perrone F, Milione M, et al.
PD-L1 Expression in Unresectable Locally Advanced or Metastatic Skin Squamous Cell Carcinoma Treated with Anti-Epidermal Growth Factor Receptor Agents.
Oncology. 2019; 97(2):112-118 [PubMed] Related Publications
BACKGROUND: Recurrent or metastatic (R/M) skin squamous cell carcinoma (sSCC) not amenable of surgery or irradiation may benefit from systemic therapies. Epidermal growth factor receptor (EGFR) inhibitors and, more recently, immune checkpoint blockers (ICBs) showed activity in R/M sSCC. In this study, we aimed at exploring the possible role of PD-L1 expression in predicting response to anti-EGFR agents.
METHODS: Patients affected by R/M sSCC, treated with pan-HER inhibitor dacomitinib or with platinum-based chemotherapy with cetuximab (CT-cet) from 2010 to 2016, were considered. PD-L1 expression was assessed with immunohistochemistry on tumor cells (TCs) and on microenvironment (TC and tumor-infiltrating lymphocyte [IC] scores, respectively). Prognostic role of PD-L1 and the correlation with response to EGFR inhibitors and survival were analyzed.
RESULTS: Twenty-eight R/M sSCCs were analyzed (19 treated with dacomitinib, 9 with CT-cet). TC and IC were negative in 82 and 45% of cases, respectively; 15% sSCCs were both TC and IC positive. Progression-free survival (PFS) was longer in IC-positive cases (median 7.5 months vs. 2.1 in IC0, p = 0.02). No statistically significant differences were observed between PD-L1 expression and both overall survival and response rates.
CONCLUSION: PD-L1 expression in microenvironment predicted better PFS. The combination of EGFR inhibitors and ICB could help deepening the knowledge about the interrelations between the EGFR and PD-1/PD-L1 pathways.

Miolo N, Rodrigues RF, Silva ERD, et al.
Skin cancer incidence in rural workers at a reference hospital in western Paraná.
An Bras Dermatol. 2019 Mar-Apr; 94(2):157-163 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Skin cancer is common in Brazil and is related to sun exposure, among other risk factors. There are no data on the incidence of malignant skin neoplasm in rural workers in western Paraná.
OBJECTIVE: To analyze the incidence and profile of rural workers who were diagnosed with skin cancer at a reference service in Cascavel, western Paraná, in the last five years (2011-2016).
METHODS: This retrospective cross-sectional study was carried out through a review of the anatomopathological reports of rural workers diagnosed with skin cancer at Cascavel Oncology Center (CEONC), in Cascavel. The following variables were collected: year of diagnosis, age, gender, injury location and histological subtype.
RESULTS: A total of 681 cases of malignant epithelial neoplasia were identified, with a higher frequency in the 61-70 age group. Data analysis showed an increase of about 210% in the occurrence of skin cancers in the last 5 years. The cephalic region was the most affected, and the most common histological subtype was nodular basal cell carcinoma. There was no association between gender and location.
STUDY LIMITATIONS: This is a retrospective study and analysis of a secondary data bank.
CONCLUSION: This study is a regional estimation of the incidence of cutaneous neoplasms and provides evidence of a considerable increase in the number of diagnoses in rural workers from western Paraná, Brazil. Moreover, it is possible to conclude that the sample group studied is at risk of developing skin cancer.

Mikami E, Kudo M, Ohashi R, et al.
Toll‑like receptor 4 plays a tumor‑suppressive role in cutaneous squamous cell carcinoma.
Int J Oncol. 2019; 54(6):2179-2188 [PubMed] Related Publications
Toll‑like receptor 4 (TLR4), a key regulator of the innate immune system, is expressed not only in immune cells, but also in a number of cancer cells. A biological role for TLR4 in cutaneous squamous cell carcinoma (SCC), however, is unclear. In this study, we first examined TLR4 expression and localization in cases of SCC, actinic keratosis (AK) and Bowen's disease (BD) by immunohistochemistry. TLR4 expression was significantly higher in the SCC than in the AK or BD tissues. We then determined the TLR4 expression level in vivo, in 3 histological subtypes of SCC. TLR4 expression in poorly differentiated SCC was significantly lower compared with that of the moderately and well‑differentiated type. In addition, the CD44 immunoreactivity tended to be high in the cell membrane of poorly differentiated SCC. Of note, poorly differentiated SCC is a risk factor of unfavorable outcomes in affected patients. We then assessed the biological role of TLR4 in HSC‑1 and HSC‑5 SCC cells and HaCaT human keratinocytes. TLR4 knockdown by transfection with siRNA accelerated HSC‑1 and HaCaT cell migration and invasion compared to the control siRNA‑transfected cells. TLR4 knockdown resulted in an increased CD44 expression and in an enhanced filopodia protrusion formation, particularly in HSC‑1. On the whole, these results suggest that a reduced TLR4 expression enhances the malignant features in SCC cases and cultured SCC cell lines. TLR4 may thus play an anti‑tumor role in cutaneous SCC.

Tampucci S, Carpi S, Digiacomo M, et al.
Diclofenac-Derived Hybrids for Treatment of Actinic Keratosis and Squamous Cell Carcinoma.
Molecules. 2019; 24(9) [PubMed] Free Access to Full Article Related Publications
In this work, hybrid compounds

Goldie SJ, Chincarini G, Darido C
Targeted Therapy Against the Cell of Origin in Cutaneous Squamous Cell Carcinoma.
Int J Mol Sci. 2019; 20(9) [PubMed] Free Access to Full Article Related Publications
Squamous cell carcinomas (SCC), including cutaneous SCCs, are by far the most frequent cancers in humans, accounting for 80% of all newly diagnosed malignancies worldwide. The old dogma that SCC develops exclusively from stem cells (SC) has now changed to include progenitors, transit-amplifying and differentiated short-lived cells. Accumulation of specific oncogenic mutations is required to induce SCC from each cell population. Whilst as fewer as one genetic hit is sufficient to induce SCC from a SC, multiple events are additionally required in more differentiated cells. Interestingly, the level of differentiation correlates with the number of transforming events required to induce a stem-like phenotype, a long-lived potential and a tumourigenic capacity in a progenitor, a transient amplifying or even in a terminally differentiated cell. Furthermore, it is well described that SCCs originating from different cells of origin differ not only in their squamous differentiation status but also in their malignant characteristics. This review summarises recent findings in cutaneous SCC and highlights transforming oncogenic events in specific cell populations. It underlines oncogenes that are restricted either to stem or differentiated cells, which could provide therapeutic target selectivity against heterogeneous SCC. This strategy may be applicable to SCC from different body locations, such as head and neck SCCs, which are currently still associated with poor survival outcomes.

Abenavoli FM, Inchingolo AD, Inchingolo AM, et al.
A technical note for the use of small-diameter cannula for lipoaspiration technique in aesthetic reconstructive post-oncological surgery.
J Biol Regul Homeost Agents. 2019 May-Jun,; 33(3):1011-1013 [PubMed] Related Publications
Skin cancer basal cell carcinoma (BCC) is a quite common lesion with a worldwide annual incidence between 3% and 8%. Tissue reconstruction should be biologically driven: nowadays, the naso-genial flap is one of the safest and usable flaps for the reconstruction of the labial and nasal region after invasive surgery aimed at a full BCC excision. In fact, the proximity of this flap to the area to be treated, the similar colour of the skin and the technical possibility to perform a single surgery to both harvest the flap and remove the lesion in the area to be then reconstructed, make it highly preferred by surgeons. In order to prevent the most severe swelling, the Authors started to use a novel method consisting in the use of the small-diameter cannula for lipoaspiration technique (SDCL). The correct use of SDCL allows to aspirate the adipose tissue, thus obtaining an available adipose-based scaffold, highly compatible with the area in which the flap is to be placed.

García-Sancha N, Corchado-Cobos R, Pérez-Losada J, Cañueto J
MicroRNA Dysregulation in Cutaneous Squamous Cell Carcinoma.
Int J Mol Sci. 2019; 20(9) [PubMed] Free Access to Full Article Related Publications
Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and it can be locally invasive and metastatic to distant sites. MicroRNAs (miRNAs or miRs) are endogenous, small, non-coding RNAs of 19-25 nucleotides in length, that are involved in regulating gene expression at a post-transcriptional level. MicroRNAs have been implicated in diverse biological functions and diseases. In cancer, miRNAs can proceed either as oncogenic miRNAs (onco-miRs) or as tumor suppressor miRNAs (oncosuppressor-miRs), depending on the pathway in which they are involved. Dysregulation of miRNA expression has been shown in most of the tumors evaluated. MiRNA dysregulation is known to be involved in the development of cutaneous squamous cell carcinoma (CSCC). In this review, we focus on the recent evidence about the role of miRNAs in the development of CSCC and in the prognosis of this form of skin cancer.

Bottomley MJ, Thomson J, Harwood C, Leigh I
The Role of the Immune System in Cutaneous Squamous Cell Carcinoma.
Int J Mol Sci. 2019; 20(8) [PubMed] Free Access to Full Article Related Publications
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. In immunosuppressed populations it is a source of considerable morbidity and mortality due to its enhanced recurrence and metastatic potential. In common with many malignancies, leucocyte populations are both protective against cancer development and also play a role in 'sculpting' the nascent tumor, leading to loss of immunogenicity and tumor progression. UV radiation and chronic viral carriage may represent unique risk factors for cSCC development, and the immune system plays a key role in modulating the response to both. In this review, we discuss the lessons learned from animal and ex vivo human studies of the role of individual leucocyte subpopulations in the development of cutaneous SCC. We then discuss the insights into cSCC immunity gleaned from studies in humans, particularly in populations receiving pharmacological immunosuppression such as transplant recipients. Similar insights in other malignancies have led to exciting and novel immune therapies, which are beginning to emerge into the cSCC clinical arena.

Amiraraghi N, Scott RA, Balaji N, Yaneza MMC
Human papillomavirus 16 and p16 positive nasal cutaneous squamous cell carcinoma in immunocompetent men in their twenties.
J Laryngol Otol. 2019; 133(4):348-352 [PubMed] Related Publications
BACKGROUND: Cutaneous squamous cell carcinoma is usually associated with long-term ultraviolet light exposure. Human papillomavirus 16 is a high-risk mucosal human papillomavirus type, usually associated with anogenital and oropharyngeal cancer. This paper describes the first two cases of human papillomavirus 16 and p16 related nasal cutaneous squamous cell carcinoma.
METHOD: Prospective case series from December 2015.
RESULTS: Two young, male, fair-skinned patients had large (greater than 20 mm), rapidly growing, ulcerated lesions of the nasal tip. The tumours were excised, with at least a 6 mm margin, and the patients' noses were subsequently reconstructed. Neither patient had cervical lymphadenopathy or underwent adjuvant radiotherapy. Both patients were registered at the same general practice. The tumours were human papillomavirus 16 and p16 positive; the latter indicated that the virus was driving the disease process. Except for superficial burns, neither patient had other risk factors.
CONCLUSION: Changes in sexual practices have led to an increase in human papillomavirus positive oropharyngeal carcinoma and there may be an associated increase in human papillomavirus type 16 positive nasal cutaneous squamous cell carcinoma.

Zhao G, Bae JY, Zheng Z, et al.
Overexpression and Implications of Melanoma-associated Antigen A12 in Pathogenesis of Human Cutaneous Squamous Cell Carcinoma.
Anticancer Res. 2019; 39(4):1849-1857 [PubMed] Related Publications
BACKGROUND/AIM: Melanoma-associated antigen A12 (MAGEA12) has recently been reported as a repressor of tumor-suppressor genes. This study aimed to investigate the implications of MAGEA12 expression in the pathogenesis of cutaneous squamous cell carcinoma (cSCC).
MATERIALS AND METHODS: MAGEA12 and p21 expression were investigated in 15 samples of normal skin and 111 of cSCC tissues by immunohistochemistry. The biological functions of MAGEA12 in cSCC were also investigated both in vitro and in vivo.
RESULTS: Expression of both MAGEA12 and p21 was significantly increased in cSCC. MAGEA12 expression showed a positive correlation, while p21 expression showed negative correlation with the recurrence-free survival of patients with cSCC. In addition, MAGEA12 knockdown significantly attenuated proliferative, migratory, invasive, and tumorigenic activities of cSCC cells and was negatively correlated with p21 expression both in vitro and in vivo.
CONCLUSION: MAGEA12-mediated down-regulation of p21 may be involved in cSCC pathogenesis and MAGEA12 may serve as a molecular biomarker in cSCC.

Donaldson MR, Weber A
Dual Immunostaining With SOX10 and AE1/AE3 to Confirm Perineural Invasion on Mohs Sections
J Drugs Dermatol. 2019; 18(3):262-264 [PubMed] Related Publications
Perineural invasion (PNI) is associated with high risk keratinocyte carcinomas. Identification of PNI during Mohs surgery is important for staging and post-adjuvant treatment decisions but can be challenging. To confirm or exclude PNI suspected on hematoxylin and eosin sections, we performed immunohistochemical double staining on Mohs frozen sections. Neural marker SOX10 and pan-cytokeratin marker AE1/AE3 were combined in a simultaneous assay using species-specific (mouse and rabbit) antibodies and horseradish peroxidase and alkaline phosphatase detection systems. Of 23 Mohs cases with suspected PNI, 18 were confirmed to have definitive nerve involvement by tumor using double staining. Double staining frozen tissue is feasible and can be beneficial for real time confirmation of PNI during Mohs. J Drugs Dermatol. 2019;18(3):262-264.

Hu SC, Su YS, Lai YC, et al.
Liposomal Avicequinone-B formulations: Aqueous solubility, physicochemical properties and apoptotic effects on cutaneous squamous cell carcinoma cells.
Phytomedicine. 2019; 58:152870 [PubMed] Related Publications
BACKGROUND: Avicequinone-B (Naphtho[2,3-b]furan-4,9-dione) is a furanonaphthoquinone derivative. It is a hydrophobic compound with poor aqueous solubility, which may restrict its potential pharmaceutical and biomedical applications.
PURPOSE: We synthesized different liposomal formulations of Avicequinone-B, and measured their particle size, aqueous solubility, and physicochemical properties. In addition, we investigated the anticancer activity of liposomal Avicequinone-B in human cutaneous squamous cell carcinoma (SCC) cells.
METHODS: Liposomal Avicequinone-B formulations were synthesized using the thin-film hydration method. Drug yield, encapsulation efficiency and aqueous solubility were determined by high performance liquid chromatography. Particle size and polydispersity index were measured by submicron particle size analyzer, and ultrastructural morphology was visualized by transmission electron microscopy. Thermal transitions were determined by differential scanning calorimetry. Anti-skin cancer activity was determined in HSC-1 cells (human cutaneous SCC cell line) using the MTS cytotoxicity assay, apoptosis was assessed by caspase-3/7 activity assay, mitochondrial membrane potential was determined by JC-10 assay, and signal transduction pathways were evaluated by Western blot analysis.
RESULTS: Liposomal Avicequinone-B formulations showed adequate yield and high encapsulation efficiency. These liposomal formulations produced small, uniformly sized nanoparticles, and greatly increased the aqueous solubility of Avicequinone-B. Differential scanning calorimetry showed loss of thermal phase transitions. In addition, liposomal Avicequinone-B showed significant cytotoxic effect on HSC-1 cells, through reduction of mitochondrial membrane potential, increased cytosolic cytochrome-c level, increased cleaved caspase 8 level, and induction of apoptosis. This was mediated through activation of ERK, p38 and JNK signaling pathways.
CONCLUSION: Liposomal Avicequinone-B demonstrated improved aqueous solubility and physicochemical characteristics, and induced apoptosis in cutaneous SCC cells. Therefore, liposomal Avicequinone-B may have potential uses as a topical anti-skin cancer drug formulation in the future.

Thompson JD, Avey GD, Wieland AM, et al.
Auriculotemporal Nerve Involvement in Parotid Bed Malignancy.
Ann Otol Rhinol Laryngol. 2019; 128(7):647-653 [PubMed] Related Publications
OBJECTIVE: To identify and evaluate patients with parotid bed malignancy demonstrating radiographic findings of auriculotemporal (AT) nerve involvement.
METHODS: A retrospective review of patients with parotid bed malignancy was performed to identify patients with imaging findings of AT nerve involvement and record associated clinical findings, symptoms, and pathology information. Independent, blinded review of radiographic images by a senior neuroradiologist was performed to identify imaging characteristics and categorize patients into highly likely or possible involvement groups.
RESULTS: Of 547 patients identified with parotid bed malignancy, 23 patients exhibited radiographic findings suggestive of AT nerve involvement. Thirteen patients met criteria for highly likely involvement, and 10 patients met criteria for possible involvement. Cutaneous malignancy with metastasis to the parotid bed accounted for 11 of 23 patients, and the most common histology was squamous cell carcinoma (9 patients). Primary parotid malignancy accounted for 12 of 23 patients, and the most common histology was salivary ductal carcinoma (3 patients). All 13 highly likely patients reported periauricular pain, and 11 of 13 demonstrated facial weakness. Features suggesting advanced disease included radiographic findings of intracranial involvement (10/23 patients), nonsurgical primary treatment (13/23 patients), and positive margins on pathology report (7/10 patients).
CONCLUSION: AT nerve involvement is an uncommon but important phenomenon that often occurs in the setting of advanced disease and is commonly associated with periauricular pain and coexisting facial weakness. Awareness of the associated clinical features and imaging patterns can allow for appropriate identification of this pattern of spread and help to optimize treatment planning.

Gong ZH, Zhou F, Shi C, et al.
miRNA-221 promotes cutaneous squamous cell carcinoma progression by targeting PTEN.
Cell Mol Biol Lett. 2019; 24:9 [PubMed] Free Access to Full Article Related Publications
Background: Cutaneous squamous cell carcinoma (CSCC) is a common type of skin malignancy. MicroRNA-221 (miRNA-221) is a critical non-coding RNA in tumor initiation and progression. However, the molecular mechanisms of miRNA-221 in the development of CSCC remain unknown. This study investigated the expression of miRNA-221 in CSCC and its potential tumor biological functions.
Methods: MTT assay, colony assay, PCR, and Western blot were adopted.
Results: In this study, miRNA-221 expression was significantly higher in CSCC tissues and cell lines than in normal tissues and cells (
Conclusions: Taken together, the obtained results indicated that miR-221 plays an oncogenic function in CSCC by targeting PTEN and further suggest that miR-221 may be a potential target for CSCC diagnosis and treatment.

Chaabane A, Bacha D, Ayachi K, et al.
Metatypical Basal Cell Carcinoma: A 6-Year Retrospective Study.
Skinmed. 2019; 17(1):24-28 [PubMed] Related Publications
Metatypical basal cell carcinoma (MBCC) represents a high-risk type of cutaneous tumor and has characteristics similar to basal cell carcinoma and squamous cell carcinoma. We report a retrospective study of 13 patients who presented with cervicofacial MBCC. Our study found an increased prevalence of aggressive clinicohistologic features and showed disease recurrences in more than one-third of the patients; therefore, we conclude that MBCC is an aggressive variant that requires a complex surgical approach for achieving a stable and complete remission. (

Ventura A, Pellegrini C, Cardelli L, et al.
Telomeres and Telomerase in Cutaneous Squamous Cell Carcinoma.
Int J Mol Sci. 2019; 20(6) [PubMed] Free Access to Full Article Related Publications
The role of telomere biology and telomerase activation in skin cancers has been investigated in melanoma and basal cell carcinoma but limited evidence is available for cutaneous squamous cell carcinoma (cSCC). We will review the current knowledge on the role of telomere and telomerase pathway in cSCC pathogenesis. At the somatic level, both long and short telomere lengths have been described in cSCC. This telomere dichotomy is probably related to two different mechanisms of tumour initiation which determines two tumour subtypes. Telomere shortening is observed during the invasive progression from in situ forms of cSCC, such as Bowen's disease (BD) and actinic keratosis (AK), to invasive cSCC. At the germline level, controversial results have been reported on the association between constitutive telomere length and risk of cSCC. Approximately 75⁻85% of cSCC tumours are characterized by a high level of telomerase activity. Telomerase activation has been also reported in AKs and BD and in sun-damaged skin, thus supporting the hypothesis that UV modulates telomerase activity in the skin. Activating

Mohammadipour K, Mansouri R, Salmanpour R, et al.
Investigation of Interleukin-17 Gene Polymorphisms and Serum Levels in Patients with Basal Cell Carcinoma of the Skin.
Iran J Immunol. 2019; 16(1):53-61 [PubMed] Related Publications
BACKGROUND: Interleukin 17 (IL-17) is a pro-inflammatory cytokine that plays an important role in cancer pathogenesis.
OBJECTIVE: To investigate the association of two IL-17 gene polymorphisms (rs2275913 and rs763780), as well as IL-17 serum levels with susceptibility to Basal Cell Carcinoma (BCC) of skin.
METHODS: Two hundred subjects with BCC and 200 healthy controls were recruited. DNA was extracted from peripheral blood leukocytes and genotypes were determined using PCR-RFLP methods. Serum levels were assessed by ELISA.
RESULTS: At position rs2275913 in IL-17A, the frequencies of GG, AG and AA genotypes were 99 (49.5%), 76 (38%) and 25 (12.5%) in patients and 97 (48.5%), 84 (42%) and 19 (9.5%) in the control group. The distribution of AA, GA and GG genotypes at position rs763780 in IL-17F were 166 (83%), 34 (17%) and 0 (0%) in patients and 158 (79%), 40 (20%) and 2 (1%) in the control group. Haplotype analysis by Arlequin software package revealed that GA haplotype was the most frequent haplotype in both groups. No significant differences were found in alleles, genotypes, and haplotypes frequencies between study groups at both positions (P>0.05). While no difference in IL-17 serum levels was observed between individuals with different genotypes, statistical analysis showed higher IL-17A serum levels, but not IL-17F, in patients compared to controls (0.65 ± 0.11 and 0.03 ± 0.02 pg/ml), respectively, (P<0.001).
CONCLUSION: Our findings do not support the association of rs763780 and rs2275913 gene polymorphisms in IL-17gene with susceptibility of Iranians with BCC. Increased IL-17A serum levels may still play a role in pathogenesis of BCC.

Orangi M, Dyson ME, Goldberg LH, Kimyai-Asadi A
Repair of Apical Triangle Defects Using Melolabial Rotation Flaps.
Dermatol Surg. 2019; 45(3):358-362 [PubMed] Related Publications
BACKGROUND: The apical triangle of the upper cutaneous lip, also known as the alar-facial sulcus, is an anatomical structure bound medially by the nasal ala, laterally by the medial cheek, and inferiorly by the remainder of the upper cutaneous lip. During reconstruction, retaining the central concavity and the convex lateral and medial outlines of this location is required to maintain midfacial symmetry.
OBJECTIVE: This is a retrospective study of our use of the melolabial rotation flap for reconstruction of surgical defects of the apical triangle.
METHODS AND MATERIALS: Eighty-six surgical defects involving the apical triangle that were repaired with melolabial rotation flaps were included. All tumors were treated with Mohs micrographic surgery before reconstruction. Preoperative, intraoperative, and postoperative details of each case were analyzed.
RESULTS: Of the 86 defects included in the study, 68 (79%) were evaluated postoperatively. The apical triangle was preserved in all cases. Clinical asymmetry was noted in 3 patients (3.4%). No major complications were noted, and no patient required surgical revision.
CONCLUSION: Melolabial rotation flaps may be considered for single-stage reconstruction of surgical defects involving the apical triangle.

Feng J, LaChance A, Sinclair DA, Asgari MM
Multiple basal cell carcinomas in a patient with myotonic dystrophy type 1.
BMJ Case Rep. 2019; 12(3) [PubMed] Article available free on PMC after 08/03/2020 Related Publications
A man in his early 60s with myotonic dystrophy type 1 (DM1) and an extensive history of non-melanoma skin cancer presented with multiple pearly, erythematous papules on his face, head, trunk and extremities, clinically consistent with basal cell carcinoma (BCC). Due to the numerous BCC and history of multiple and early-onset BCC, examination was concerning for a hereditary BCC syndrome. Subsequent histopathology confirmed BCC. Genetic testing was negative for basal cell nevus syndrome and clinical findings were inconsistent with other known hereditary BCC syndromes. There have been reports of an association between DM1 and BCC, however, it is not well known among clinicians. We hope to raise awareness among clinicians about this association.

Pandey A, Liaukovich M, Joshi K, et al.
Uncommon Presentation of Metastatic Squamous Cell Carcinoma of the Skin and Treatment Challenges.
Am J Case Rep. 2019; 20:294-299 [PubMed] Article available free on PMC after 08/03/2020 Related Publications
BACKGROUND Squamous cell carcinoma is one of the most common keratinocytic skin cancers, the other being basal cell carcinoma. It is the second most common skin cancer after melanoma. Cutaneous squamous cell carcinoma is mostly a localized disease. The metastatic presentation is rare even in the presence of invasive disease. The metastatic potential depends on the presence of high-risk features at the time of diagnosis. Lung, liver, and bone are the frequent sites of metastasis. Local and locoregional disease undergoes excision with or without adjuvant radiation. However, we lack proper treatment paradigms for this metastatic disease. CASE REPORT We are reporting a case of an elderly female with a history of high-risk localized cutaneous squamous cell carcinoma treated with complete local excision and radiation presenting 5 years later with extensive disease to the lung and liver, abdominal nodes, and spinal fracture. The patient was not a candidate for chemotherapy due to kidney failure. On the basis of ongoing separate trials on different immunotherapies, she was started on nivolumab. CONCLUSIONS Treating metastatic cutaneous squamous cell carcinoma is a challenge considering the absence of phase III trials due to the rarity of this disease. Historically, platinum with or without 5-FU (fluorouracil), bleomycin, doxorubicin, and retinoic acid were used with variable responses. Data on epidermal growth factor receptor (EGFR) inhibitors on EGFR expressing tumors are available. However, even with the most recent reports on immunotherapy in patients with high programmed death-1 expression or high mutation burden, it is difficult to achieve good response.

Yom SS
Integrating the Management of Nodal Metastasis Into the Treatment of Nonmelanoma Skin Cancer.
Semin Radiat Oncol. 2019; 29(2):171-179 [PubMed] Related Publications
The two types of nonmelanoma skin cancer most apt to metastasize to lymph nodes are cutaneous squamous cell carcinoma and Merkel cell carcinoma. The clinical impact of nodal metastases of these cancers is substantial, resulting in intensification of treatment and morbidity and worsened cancer outcomes. Exact best practices are challenging to define as many specific clinical scenarios remain incompletely catalogued, characterized, or studied. In general, the role of radiation therapy is indisputably established as part of the treatment of both of these diseases although its success depends on the best available assessment of extent of disease and appropriate integration into the multimodality care plan.

Baltz GC, Chi PM, Wong PF, et al.
Development and validation of a 3D-printed bolus cap for total scalp irradiation.
J Appl Clin Med Phys. 2019; 20(3):89-96 [PubMed] Article available free on PMC after 08/03/2020 Related Publications
PURPOSE: The goal of total scalp irradiation (TSI) is to deliver a uniform dose to the scalp, which requires the use of a bolus cap. Most current methods for fabricating bolus caps are laborious, yet still result in nonconformity and low reproducibility, which can lead to nonuniform irradiation of the scalp. We developed and validated patient-specific bolus caps for TSI using three-dimensional (3D) printing.
METHODS AND MATERIALS: 3D-printing materials were radiologically analyzed to identify a material with properties suitable for use as a bolus cap. A Python script was developed within a commercial treatment planning system to automate the creation of a ready-to-print, patient-specific 3D bolus cap model. A bolus cap was printed for an anthropomorphic head phantom using a commercial vendor and a computed tomography simulation of the anthropomorphic head phantom and bolus cap was used to create a volumetric-modulated arc therapy TSI treatment plan. The planned treatment was delivered to the head phantom and dosimetric validation was performed using thermoluminescent dosimeters (TLD). The developed procedure was used to create a bolus cap for a clinical TSI patient, and in vivo TLD measurements were acquired for several fractions.
RESULTS: Agilus-60 was validated as a new 3D-printing material suitable for use as bolus. A 3D-printed Agilus-60 bolus cap had excellent conformality to the phantom scalp, with a maximum air gap of 4 mm. TLD measurements showed that the bolus cap generated a uniform dose to the scalp within a 2.7% standard deviation, and the delivered doses agreed with calculated doses to within 2.4% on average. The patient bolus was conformal and the average difference between TLD measured and planned doses was 5.3%.
CONCLUSIONS: We have developed a workflow to 3D-print highly conformal bolus caps for TSI and demonstrated these caps can reproducibly generate a uniform dose to the scalp.

Marka A, Carter JB, Toto E, Hassanpour S
Automated detection of nonmelanoma skin cancer using digital images: a systematic review.
BMC Med Imaging. 2019; 19(1):21 [PubMed] Article available free on PMC after 08/03/2020 Related Publications
BACKGROUND: Computer-aided diagnosis of skin lesions is a growing area of research, but its application to nonmelanoma skin cancer (NMSC) is relatively under-studied. The purpose of this review is to synthesize the research that has been conducted on automated detection of NMSC using digital images and to assess the quality of evidence for the diagnostic accuracy of these technologies.
METHODS: Eight databases (PubMed, Google Scholar, Embase, IEEE Xplore, Web of Science, SpringerLink, ScienceDirect, and the ACM Digital Library) were searched to identify diagnostic studies of NMSC using image-based machine learning models. Two reviewers independently screened eligible articles. The level of evidence of each study was evaluated using a five tier rating system, and the applicability and risk of bias of each study was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool.
RESULTS: Thirty-nine studies were reviewed. Twenty-four models were designed to detect basal cell carcinoma, two were designed to detect squamous cell carcinoma, and thirteen were designed to detect both. All studies were conducted in silico. The overall diagnostic accuracy of the classifiers, defined as concordance with histopathologic diagnosis, was high, with reported accuracies ranging from 72 to 100% and areas under the receiver operating characteristic curve ranging from 0.832 to 1. Most studies had substantial methodological limitations, but several were robustly designed and presented a high level of evidence.
CONCLUSION: Most studies of image-based NMSC classifiers report performance greater than or equal to the reported diagnostic accuracy of the average dermatologist, but relatively few studies have presented a high level of evidence. Clinical studies are needed to assess whether these technologies can feasibly be implemented as a real-time aid for clinical diagnosis of NMSC.

Chu Z, Zhang X, Li Q, et al.
CDC20 contributes to the development of human cutaneous squamous cell carcinoma through the Wnt/β‑catenin signaling pathway.
Int J Oncol. 2019; 54(5):1534-1544 [PubMed] Article available free on PMC after 08/03/2020 Related Publications
Cell division cycle 20 (CDC20) is a regulatory molecule and serves critical roles at multiple points of the cell cycle. Recent evidence indicates that CDC20 may serve an oncogenic role in a number of human cancer types. However, the role of CDC20 in primary cutaneous squamous cell carcinoma (cSCC) has not been studied, to the best of our knowledge. The aim of the present study was to investigate whether and how CDC20 is involved in the tumorigenesis of cSCC. The results revealed that CDC20 expression was significantly increased in cSCC tissues and cell lines, and its expression was associated with pathological differentiation. Downregulation of CDC20 inhibited cell proliferation, induced cell cycle arrest, promoted apoptosis and reduced migratory ability through inhibition of the Wnt/β‑catenin signaling pathway. Furthermore, all‑trans‑retinoic acid treatment significantly downregulated CDC20 expression in cSCC. The present results revealed that CDC20 may serve a crucial role in human cSCC, and suggested that CDC20 may be a novel biomarker for the prevention, diagnosis and treatment of cSCC.

Gandini S, Doré JF, Autier P, et al.
Epidemiological evidence of carcinogenicity of sunbed use and of efficacy of preventive measures.
J Eur Acad Dermatol Venereol. 2019; 33 Suppl 2:57-62 [PubMed] Related Publications
The International Agency for Research on Cancer classified, in July 2009, exposure to artificial tanning devices (sunbeds) as carcinogenic to humans. This classification was based on evidence from epidemiological and experimental animal studies. The present chapter will review these epidemiological evidences. The summary risk estimates from 27 epidemiological studies obtained through a meta-analysis showed an increased risk of melanoma: summary relative risk (SRR) = 1.20 [95% confidence interval (CI) 1.08-1.34]. The risk was higher when exposure took place at younger age (SRR = 1.59; 95% CI 1.36-1.85). The risk was independent of skin sensitivity or population and a dose response was evident. A meta-analysis of 12 studies was conducted for non-melanoma skin cancers and showed a significantly increased risk for basal cell carcinoma (SRR = 1.29; 95% CI 1.08-1.53) and for squamous cell carcinoma (SRR = 1.67; 95% CI 1.29-2.17). As for melanoma, the risk for other skin cancers increased for first exposures at young age. Epidemiological studies have gradually strengthened the evidence for a causal relationship between indoor tanning and skin cancer and they fit with prior knowledge on relationship between UV exposure and skin cancer. Additionally, several case-control studies provided consistent evidence of a positive association between use of sunbed and ocular melanoma, also with greater risk for first exposures at younger age. Preventive measures based on information on risk or by requiring parental authorization for young users proved to be inefficient in several studies. The significant impact of strong actions or total ban, such as performed in Iceland, or a total ban of sunbed use, as in Brazil or Australian states, needs to be further assessed.

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