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Skin Cancer

Skin cancer is the most common type of cancer and accounts for half of all new cancers in Western populations. It occurs more often in people with light coloured skin who have had a high exposure to sunlight. The two most frequent types of skin cancer are Basal Cell Carcinomas and Squamous Cell Carcinoma (often grouped under "non-melanoma skin cancer"). The third most frequent skin cancer is Melanoma, this is a malignancy of the cells which give the skin it's colour (melanocytes). In addition there are a number of other, less common cancers starting in the skin including Merkel cell tumours, cutaneous lymphomas, and sarcomas (see the pages on sarcoma and lymphoma in this guide).

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Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Prevention of Skin Cancer
Non Melanoma Skin Cancer
-- Basal Cell Carcinoma
-- Squamous Cell Carcinoma
Cutaneous T-cell Lymphoma
Dermatofibrosarcoma Protuberans
Merkel Cell Cancer

Information Patients and the Public (10 links)

Information for Health Professionals / Researchers (6 links)

  • PubMed search for publications about Skin Cancer - Limit search to: [Reviews]

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    MeSH term: Skin Neoplasms
    International US National Library of Medicine
    qualityPubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.

Latest Research Publications

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

Rohatgi S, Naveen S, Salunke P, et al.
The story of a deformed leprous foot.
Lepr Rev. 2016; 87(1):104-8 [PubMed] Related Publications
Eccrine syringofibroadenoma (ESFA) is a rare adnexal tumour of eccrine ductal proliferation. A 50 year old treated case of leprosy presented with a chronic non healing ulcer of 5 years duration on the deformity laden right foot. Multiple verrucous papules and plaques were seen surrounding the ulcer which showed histopathological findings consistent with ESFA. Although ESFA constitutes a rare association with leprosy, considering the load of treated cases in our country and elsewhere, it may represent an under-reported entity which requires more attention in the post elimination era.

Agarwala SS
The Role of Intralesional Therapies in Melanoma.
Oncology (Williston Park). 2016; 30(5):436-41 [PubMed] Related Publications
The US Food and Drug Administration has been rapidly approving new checkpoint inhibitors and targeted therapies for melanoma and other tumors. Recently, it approved the first intralesional therapy, talimogene laherparepvec (T-VEC), for the treatment of metastatic melanoma lesions in the skin and lymph nodes. Several other intralesional therapies (PV-10, interleukin-12 electroporation, coxsackievirus A21 [CVA21]) are entering later-stage testing. Locally injected agents have clearly shown their ability to produce local responses that can be durable. The possibility that they also stimulate a regional and even systemic immune response is exciting, as this potential effect may have utility in combination regimens; such regimens are an area of active research. Favorable responses with minimal toxicities in monotherapy trials have led to the first melanoma studies of T-VEC in combination with the cytotoxic T-lymphocyte-associated antigen 4 inhibitor ipilimumab and, separately, with the programmed death 1-blocking antibody pembrolizumab. Studies of PV-10 with pembrolizumab and of CVA21 with pembrolizumab are also being initiated. Preliminary analyses of the results of the first combination trials, which show higher response rates than with either agent alone, offer some optimism that these locoregional therapies will find application--as treatment for patients who cannot tolerate systemic immunotherapies, to alleviate locoregional morbidity, and perhaps even to "prime" the immune system.

Manciuc C, Filip-Ciubotaru F, Badescu A, et al.
Rev Med Chir Soc Med Nat Iasi. 2016 Jan-Mar; 120(1):119-23 [PubMed] Related Publications
In the last two years the Romanian adult population infected with the human immunodeficiency virus (HIV) has increased due to sexual transmission, both heterosexual and homosexual. The case presented is that of a 33 year-old man, admitted to the Infectious Diseases Hospital in Iasi with acute respiratory failure and a confirmation of Kaposi's sarcoma. Tests later proved positive for HIV, the patient being included in the stage AIDS C3 (acute immunodeficiency syndrome). The respiratory failure was suspected to be caused by Pneumocystis carinii and cotrimoxazol therapy, oxygen therapy and anti-retroviral therapy were established. He was also referred to the oncology hospital for treatment of Kaposi's sarcoma. The patient's adherence to therapy was influenced by a strong doctor-patient relationship, as well as by psychological counseling and support. Creating a functional doctor-patient-psychologist team is key throughout the HIV-positive patient's existence, for supporting long term adherence to therapy and acceptance of the diagnosis. This case highlights the need for a strong psychosocial compartment in every medical center that deals with HIV-infected individuals.

Tirosh I, Izar B, Prakadan SM, et al.
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq.
Science. 2016; 352(6282):189-96 [PubMed] Related Publications
To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells. Malignant cells within the same tumor displayed transcriptional heterogeneity associated with the cell cycle, spatial context, and a drug-resistance program. In particular, all tumors harbored malignant cells from two distinct transcriptional cell states, such that tumors characterized by high levels of the MITF transcription factor also contained cells with low MITF and elevated levels of the AXL kinase. Single-cell analyses suggested distinct tumor microenvironmental patterns, including cell-to-cell interactions. Analysis of tumor-infiltrating T cells revealed exhaustion programs, their connection to T cell activation and clonal expansion, and their variability across patients. Overall, we begin to unravel the cellular ecosystem of tumors and how single-cell genomics offers insights with implications for both targeted and immune therapies.

Nghiem PT, Bhatia S, Lipson EJ, et al.
PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma.
N Engl J Med. 2016; 374(26):2542-52 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Merkel-cell carcinoma is an aggressive skin cancer that is linked to exposure to ultraviolet light and the Merkel-cell polyomavirus (MCPyV). Advanced Merkel-cell carcinoma often responds to chemotherapy, but responses are transient. Blocking the programmed death 1 (PD-1) immune inhibitory pathway is of interest, because these tumors often express PD-L1, and MCPyV-specific T cells express PD-1.
METHODS: In this multicenter, phase 2, noncontrolled study, we assigned adults with advanced Merkel-cell carcinoma who had received no previous systemic therapy to receive pembrolizumab (anti-PD-1) at a dose of 2 mg per kilogram of body weight every 3 weeks. The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1. Efficacy was correlated with tumor viral status, as assessed by serologic and immunohistochemical testing.
RESULTS: A total of 26 patients received at least one dose of pembrolizumab. The objective response rate among the 25 patients with at least one evaluation during treatment was 56% (95% confidence interval [CI], 35 to 76); 4 patients had a complete response, and 10 had a partial response. With a median follow-up of 33 weeks (range, 7 to 53), relapses occurred in 2 of the 14 patients who had had a response (14%). The response duration ranged from at least 2.2 months to at least 9.7 months. The rate of progression-free survival at 6 months was 67% (95% CI, 49 to 86). A total of 17 of the 26 patients (65%) had virus-positive tumors. The response rate was 62% among patients with MCPyV-positive tumors (10 of 16 patients) and 44% among those with virus-negative tumors (4 of 9 patients). Drug-related grade 3 or 4 adverse events occurred in 15% of the patients.
CONCLUSIONS: In this study, first-line therapy with pembrolizumab in patients with advanced Merkel-cell carcinoma was associated with an objective response rate of 56%. Responses were observed in patients with virus-positive tumors and those with virus-negative tumors. (Funded by the National Cancer Institute and Merck; ClinicalTrials.gov number, NCT02267603.).

Ribas A, Hamid O, Daud A, et al.
Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma.
JAMA. 2016; 315(15):1600-9 [PubMed] Related Publications
IMPORTANCE: The programmed death 1 (PD-1) pathway limits immune responses to melanoma and can be blocked with the humanized anti-PD-1 monoclonal antibody pembrolizumab.
OBJECTIVE: To characterize the association of pembrolizumab with tumor response and overall survival among patients with advanced melanoma.
DESIGN, SETTINGS, AND PARTICIPANTS: Open-label, multicohort, phase 1b clinical trials (enrollment, December 2011-September 2013). Median duration of follow-up was 21 months. The study was performed in academic medical centers in Australia, Canada, France, and the United States. Eligible patients were aged 18 years and older and had advanced or metastatic melanoma. Data were pooled from 655 enrolled patients (135 from a nonrandomized cohort [n = 87 ipilimumab naive; n = 48 ipilimumab treated] and 520 from randomized cohorts [n = 226 ipilimumab naive; n = 294 ipilimumab treated]). Cutoff dates were April 18, 2014, for safety analyses and October 18, 2014, for efficacy analyses.
EXPOSURES: Pembrolizumab 10 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, or 2 mg/kg every 3 weeks continued until disease progression, intolerable toxicity, or investigator decision.
MAIN OUTCOMES AND MEASURES: The primary end point was confirmed objective response rate (best overall response of complete response or partial response) in patients with measurable disease at baseline per independent central review. Secondary end points included toxicity, duration of response, progression-free survival, and overall survival.
RESULTS: Among the 655 patients (median [range] age, 61 [18-94] years; 405 [62%] men), 581 had measurable disease at baseline. An objective response was reported in 194 of 581 patients (33% [95% CI, 30%-37%]) and in 60 of 133 treatment-naive patients (45% [95% CI, 36% to 54%]). Overall, 74% (152/205) of responses were ongoing at the time of data cutoff; 44% (90/205) of patients had response duration for at least 1 year and 79% (162/205) had response duration for at least 6 months. Twelve-month progression-free survival rates were 35% (95% CI, 31%-39%) in the total population and 52% (95% CI, 43%-60%) among treatment-naive patients. Median overall survival in the total population was 23 months (95% CI, 20-29) with a 12-month survival rate of 66% (95% CI, 62%-69%) and a 24-month survival rate of 49% (95% CI, 44%-53%). In treatment-naive patients, median overall survival was 31 months (95% CI, 24 to not reached) with a 12-month survival rate of 73% (95% CI, 65%-79%) and a 24-month survival rate of 60% (95% CI, 51%-68%). Ninety-two of 655 patients (14%) experienced at least 1 treatment-related grade 3 or 4 adverse event (AE) and 27 of 655 (4%) patients discontinued treatment because of a treatment-related AE. Treatment-related serious AEs were reported in 59 patients (9%). There were no drug-related deaths.
CONCLUSIONS AND RELEVANCE: Among patients with advanced melanoma, pembrolizumab administration was associated with an overall objective response rate of 33%, 12-month progression-free survival rate of 35%, and median overall survival of 23 months; grade 3 or 4 treatment-related AEs occurred in 14%.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01295827.

Sofoudis C, Salakos N, Tolia M, et al.
Skin metastases of vulvar squamous cell carcinoma. Presentation of a rare case.
Eur J Gynaecol Oncol. 2016; 37(1):126-8 [PubMed] Related Publications
Skin metastases secondary to vulvar carcinoma is an infrequent clinical entity. The authors describe a case of squamous vulvar carcinoma, which presented with cutaneous involvement as a part of distant spread. After a radical vulvectomy, bilateral inguino-femoral lymphadenectomy, and adjuvant radiotherapy, the patient developed multiple cutaneous metastases in lower extremities. This case was unique in presentation, with skin metastases secondary from vulvar carcinoma, and indicated advance disease and poor prognosis.

Bonaventura A, Liberale L, Hussein El-Dib N, et al.
Anemia Due to Inflammation in an Anti-Coagulated Patient with Blue Rubber Bleb Nevus Syndrome.
Clin Lab. 2016; 62(1-2):241-3 [PubMed] Related Publications
BACKGROUND: Blue rubber bleb nevus syndrome (BRBNS) is a rare disease characterized by vascular malformations mostly involving skin and gastrointestinal tract. This disease is often associated with sideropenic anemia and occult bleeding.
METHODS: We report the case of chronic severe anemia in an old patient under oral anticoagulation treatment for chronic atrial fibrillation.
RESULTS: At admission, the patient also presented fever and increased laboratory parameters of systemic inflammation (ferritin 308 mcg/L, C-reactive protein (CRP) 244 mg/L). A small bluish-colored lesion over the left ear lobe was observed. Fecal occult blood test was negative as well as other signs of active bleeding. Lower gastrointestinal endoscopy revealed internal hemorrhoids and multiple teleangiectasias that were treated with argon plasma coagulation. Videocapsule endoscopy demonstrated multiple bluish nodular lesions in the small intestine. Unexpectedly, chronic severe anemia due to systemic inflammation was diagnosed in an old anticoagulated patient with BRNBS. The patient was treated with blood transfusions, hydration, antibiotic treatment, and long-acting octreotide acetate, without stopping warfarin. Fever and inflammation disappeared without any acute gastrointestinal bleeding and improvement of hemoglobin levels at three-month follow up.
CONCLUSIONS: This is the oldest patient presenting with chronic anemia, in which BRNBS was also diagnosed. Surprisingly, anemia was mainly caused by systemic inflammation instead of chronic gastrointestinal bleeding. However, we would recommend investigating this disease also in old subjects with mild signs and symptoms.

Cheema AM, Hayat N
J Ayub Med Coll Abbottabad. 2015 Oct-Dec; 27(4):927-9 [PubMed] Related Publications
Naevus Sebaceous of Jadassohn is a rarely seen hamartomatous lesion and is a fourth type of sebaceous gland tumour, in which sebaceous glands show nevoid character of growth composed partly or completely of sebaceous glands. A detailed research revealed that very little data is available; no case of this disorder has been reported as an isolated eye lid lesion. Majority of the published cases are associated with systemic involvement. We present here a case report of this rare disorder. A middle age female patient presented with a mass of left lower lid since childhood without any other ocular and systemic abnormality. Excision biopsy along with rotation flap surgery was done. Histopathological examination of the specimen revealed the diagnosis. To our best of knowledge this is a unique presentation of naevus sebaceous of Jadassohn on eye lid which has not been documented till yet anywhere.

Pelak MJ, Śnietura M, Lange D, et al.
The prognostic significance of indoleamine-2,3-dioxygenase and the receptors for transforming growth factor β and interferon γ in metastatic lymph nodes in malignant melanoma.
Pol J Pathol. 2015; 66(4):376-82 [PubMed] Related Publications
We analyzed the prognostic significance of indoleamine-2,3-dioxygenase (IDO) and type 1 receptors for transforming growth factor beta (TGF-βR1) and interferon gamma (IFN-γR1) in resected nodal metastases of 48 malignant melanoma patients. In 32 cases the corresponding skin tumors were available. We used immunohistochemical (IHC) staining which was assessed by pathologists and by a computer-aided algorithm that yielded quantitative results, both absolute and relative. We correlated the results with the patient outcome. We identified absolute computer-assessed IDO levels as positively correlated with increased risk of death in a multivariate model (HR = 1.02; 95% CI: 1.002-1.04; p = 0.03). In univariate analysis, patients with IDO levels below the median had a better overall survival time (30.3 vs. 17.5 months; p = 0.03). TGF-βR1 and IFN-γR1 expression was modestly correlated (R = 0.34; p lt; 0.05) and TGF-βR1 expression was lower in lymph nodes than in matched primary skin tumors (Z = 2.87; p = 0.004). The pathologists' and computer-aided IHC assessment demonstrated high correlation levels (R = 0.61, R = 0.74 and R = 0.88 for IDO, TGF-βR1 and IFN-γR1, respectively). Indoleamine-2,3-dioxygenase is prognostic for the patient outcome in melanoma with nodal involvement and should be investigated prospectively for its predictive significance. IHC assessment by computer-aided methods is recommended as its gives IHC more objectivity and reproducibility. ecting mismatch repair deficiency. Association of CDX2 and PMS2 in the present study is necessary to conduct further genetic and pathological studies focusing on these two markers together.

Mohan P, Yuvaraj A, Abraham G, et al.
Occurrence of double primary malignancies in an African renal transplant recipient.
Saudi J Kidney Dis Transpl. 2016; 27(2):377-80 [PubMed] Related Publications
A 63-year-old African male with end stage renal disease who received a renal transplantation from his daughter after successful treatment of hepatitis C virus, type 1 genotype developed metastatic Kaposi's sarcoma and subsequently adenocarcinoma of the prostate. He was successfully treated with chemotherapy and reduction of immunosuppression and switch over to rapamycin.

Pucci F, Garris C, Lai CP, et al.
SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions.
Science. 2016; 352(6282):242-6 [PubMed] Related Publications
Tumor-derived extracellular vesicles (tEVs) are important signals in tumor-host cell communication, yet it remains unclear how endogenously produced tEVs affect the host in different areas of the body. We combined imaging and genetic analysis to track melanoma-derived vesicles at organismal, cellular, and molecular scales to show that endogenous tEVs efficiently disseminate via lymphatics and preferentially bind subcapsular sinus (SCS) CD169(+) macrophages in tumor-draining lymph nodes (tdLNs) in mice and humans. The CD169(+) macrophage layer physically blocks tEV dissemination but is undermined during tumor progression and by therapeutic agents. A disrupted SCS macrophage barrier enables tEVs to enter the lymph node cortex, interact with B cells, and foster tumor-promoting humoral immunity. Thus, CD169(+) macrophages may act as tumor suppressors by containing tEV spread and ensuing cancer-enhancing immunity.

Voinea S, Sandru A, Gherghe M,
Pitfalls in Cutaneous Melanoma Lymphatic Drainage.
Chirurgia (Bucur). 2016 Jan-Feb; 111(1):87-9 [PubMed] Related Publications
Sentinel node (SN) biopsy has become standard in staging of cutaneous melanoma. As skin lymphatic drainage is complex, preoperative empirical assessment of SN localization is virtually impossible. Therefore in order to identify all regional lymphatic basins corresponding to a specific primary tumor is mandatory to carry out preoperative lymphoscintigraphy. In this paper we present a clinical case that highlights the importance of identifying, biopsy and histological analysis of all SN in order to achieve a correct staging of the patient, followed by appropriate treatment according to the real clinical stage of the disease.

Meuris F, Gaudin F, Aknin ML, et al.
Symptomatic Improvement in Human Papillomavirus-Induced Epithelial Neoplasia by Specific Targeting of the CXCR4 Chemokine Receptor.
J Invest Dermatol. 2016; 136(2):473-80 [PubMed] Related Publications
Human papillomavirus (HPV) infection is estimated to be the causal agent in 5% of all human cancers and is the leading cause of genital warts, which is the most common sexually transmitted viral disease. Currently, there are no medications to treat HPV infection, and therapeutic strategies primarily target HPV-related cancer rather than viral infection. HPV infection has severe effects on patients who display selective susceptibility to the virus in the context of primary immunodeficiencies, such as the warts, hypogammaglobulinemia, infections, and myelokathexis syndrome, which is caused by dysfunctions of CXCR4, the receptor for the CXCL12 chemokine. In this study we showed in a transgenic mouse model of HPV-induced epidermal neoplasia the beneficial effects of Cxcl12/Cxcr4 pathway blockade with the selective CXCR4 antagonist AMD3100. Daily treatment with AMD3100 for 28 days potently reduced the abnormal ear epidermal thickening in all mice. This effect was associated with reductions in keratinocyte hyperproliferation and immune cell infiltration, both of which are linked to neoplastic progression. Moreover, we observed the abnormal coordinate expression of Cxcl12 and p16INK4a (a surrogate marker of HPV-induced cancers) in dysplastic epidermal keratinocytes, which was inhibited by AMD3100 treatment. These results provide strong evidence for the therapeutic potential of CXCL12/CXCR4 pathway blockade in HPV-induced pathogenesis.

Zhang K, Wong P, Salvaggio C, et al.
Synchronized Targeting of Notch and ERBB Signaling Suppresses Melanoma Tumor Growth through Inhibition of Notch1 and ERBB3.
J Invest Dermatol. 2016; 136(2):464-72 [PubMed] Free Access to Full Article Related Publications
Despite significant advances in melanoma therapy, melanoma remains the deadliest form of skin cancer, with a 5-year survival rate of only 15%. Thus, novel treatments are required to address this disease. Notch and ERBB are evolutionarily conserved signaling cascades required for the maintenance of melanocyte precursors. We show that active Notch1 (Notch1(NIC)) and active (phosphorylated) ERBB3 and ERBB2 correlate significantly and are similarly expressed in both mutated and wild-type BRAF melanomas, suggesting these receptors are co-reactivated in melanoma to promote survival. Whereas blocking either pathway triggers modest effects, combining a ?-secretase inhibitor to block Notch activation and a tyrosine kinase inhibitor to inhibit ERBB3/2 elicits synergistic effects, reducing cell viability by 90% and hampering melanoma tumor growth. Specific inhibition of Notch1 and ERBB3 mimics these results, suggesting these are the critical factors triggering melanoma tumor expansion. Notch and ERBB inhibition blunts AKT and NF?B signaling. Constitutive expression of NF?B partially rescues cell death. Blockade of both Notch and ERBB signaling inhibits the slow cycling JARID1B-positive cell population, which is critical for long-term maintenance of melanoma growth. We propose that blocking these pathways is an effective approach to treatment of melanoma patients regardless of whether they carry mutated or wild-type BRAF.

Belkin DA, Wysong A
Radiographic imaging for skin cancer.
Semin Cutan Med Surg. 2016; 35(1):42-8 [PubMed] Related Publications
Radiographic imaging is important for the full evaluation of high-risk cutaneous tumors. The correct modality should be chosen based on tumor subtype and clinical question. Locally advanced tumors may require imaging to evaluate the extent of disease, such as bony involvement, orbital infiltration, or perineural invasion. Tumors at high risk for regional and distant metastasis require imaging to identify local and distant tumor burden.

Giavedoni P, Puig S, Carrera C
Noninvasive imaging for nonmelanoma skin cancer.
Semin Cutan Med Surg. 2016; 35(1):31-41 [PubMed] Related Publications
The development of noninvasive optical technologies is revolutionizing the diagnosis of skin tumors. Nonmelanoma skin cancer, the most frequent neoplasm, has become an important health and economic issue, and proper management can avoid unnecessary morbidity and mutilating treatment or relapses. Noninvasive treatment modalities and the recently approved systemic therapies for advanced basal cell carcinoma cases make noninvasive monitoring techniques necessary. Current knowledge, applications, and limitations of the tools most clinically implemented, such as dermoscopy, reflectance confocal microscopy, high frequency ultrasonography, and optical coherence tomography will be reviewed in this article. In addition to the improvement of diagnostic accuracy of skin cancer, using these tools individually or in combination facilitates better management of certain patients and tumors.

Fuller C, Cellura AP, Hibler BP, Burris K
Computer-assisted diagnosis of melanoma.
Semin Cutan Med Surg. 2016; 35(1):25-30 [PubMed] Related Publications
The computer-assisted diagnosis of melanoma is an exciting area of research where imaging techniques are combined with diagnostic algorithms in an attempt to improve detection and outcomes for patients with skin lesions suspicious for malignancy. Once an image has been acquired, it undergoes a processing pathway which includes preprocessing, enhancement, segmentation, feature extraction, feature selection, change detection, and ultimately classification. Practicality for everyday clinical use remains a vital question. A successful model must obtain results that are on par or outperform experienced dermatologists, keep costs at a minimum, be user-friendly, and be time efficient with high sensitivity and specificity.

Menge TD, Pellacani G
Advances in noninvasive imaging of melanoma.
Semin Cutan Med Surg. 2016; 35(1):18-24 [PubMed] Related Publications
Melanoma is the most dangerous type of skin cancer and its incidence has risen sharply in recent decades. Early detection of disease is critical for improving patient outcomes. Any pigmented lesion that is clinically concerning must be removed by biopsy for morphologic investigation on histology. However, biopsies are invasive and can cause significant morbidity, and their accuracy in detecting melanoma may be limited by sampling error. The advent of noninvasive imaging devices has allowed for assessment of intact skin, thereby minimizing the need for biopsy; and these technologies are increasingly being used in the diagnosis and management of melanoma. Reflectance confocal microscopy, optical coherence tomography, ultrasonography, and multispectral imaging are noninvasive imaging techniques that have emerged as diagnostic aids to physical exam and/or conventional dermoscopy. This review summarizes the current knowledge about these techniques and discusses their practical applications and limitations.

Jellinek NJ, Lipner SR
Longitudinal Erythronychia: Retrospective Single-Center Study Evaluating Differential Diagnosis and the Likelihood of Malignancy.
Dermatol Surg. 2016; 42(3):310-9 [PubMed] Related Publications
BACKGROUND: Longitudinal erythronychia (LE) is an underappreciated and understudied clinical diagnosis. The rates of malignancy and prevalence within the differential diagnosis are not well-established.
OBJECTIVE: To examine the prevalence of biopsy-proven diagnoses in patients presenting with LE.
METHODS: Retrospective single-center study of 65 consecutive patients undergoing biopsy of LE.
RESULTS: Malignancy was identified in only 3 of 65 cases (in situ carcinoma in 2 and melanoma in 1). Onychopapilloma was the most common diagnosis in cases of localized LE. Lichen planus was the most common diagnosis in cases of polydactylous (generalized) LE.
CONCLUSION: Longitudinal erythronychia is not a rare clinical finding. The differential diagnosis includes neoplasms, inflammatory conditions, infectious conditions, and scar. Clinicopathologic correlation is required to make the diagnosis in many cases. Malignancy is uncommon, but not rare, with squamous cell carcinoma in situ representing the most common malignancy.

Fitzmaurice S, Eisen DB
Daylight Photodynamic Therapy: What is Known and What is Yet to be Determined.
Dermatol Surg. 2016; 42(3):286-95 [PubMed] Related Publications
BACKGROUND: Photodynamic therapy (PDT) has been used extensively to treat actinic keratoses (AKs) and less so nonmelanoma skin cancers (NMSC). Conventional in-office treatment is limited by intensive time requirements and patient discomfort. A new trend toward the use of daylight as a light source either clinically monitored or self-supervised is gaining acceptance.
OBJECTIVE: To assess the current published data on daylight photodynamic therapy (dPDT) and identify knowledge gaps.
METHODS AND MATERIALS: A systematic search of the PubMed archives using the terms daylight PDT, daylight-PDT, daylight photodynamic therapy, and ambient light and photodynamic therapy was conducted on May 18, 2015. No restrictions were used for the search string.
RESULTS: Seventeen published works were identified on the use of dPDT; 8 randomized studies, 4 prospective cohort studies, 1 case series, 1 case report, and 3 retrospective studies. Complete response rates for treatment of AKs from randomized trials range from 46% to 89.2%.
CONCLUSION: Daylight PDT has been demonstrated to have high efficacy with results similar to conventional PDT for the treatment of AKs. Initial reports regarding treatment of NMSC indicate recurrence rates much higher than other accepted therapies. Pain associated with treatment seems to be significantly less than for conventional PDT.

Curković D, Pastar Z, Kostović K
Dermoscopy and Early Melanoma.
Coll Antropol. 2015; 39(3):791-5 [PubMed] Related Publications
The lack of effective therapies for patients with advanced melanoma establishes an early recognition as the aim of clinical and dermoscopic examination, which is the most important factor for improving patient survival and decreases the treatment and management costs. Melanoma in situ is the earliest stage of melanoma. The features of early melanomas, especially in those lesions smaller than 3mm, can be very subtle clinically, dermoscopically and pathohistologically, and it is often impossible to discriminate between a melanoma and nevus. Clinically, de novo melanomas are small brown to black macula with an irregular outline. In melanomas developing in a nevus, there is an asymmetry of the lesion with marked change in color and/or shape of the pre-existing nevus. Dermoscopically, early stages of melanoma show the same global features as thicker melanomas, but in a more subtle way. Asymmetry is the most important parameter; multiple colors are rare. Significant local melanoma-specific criteria, especially when present at the periphery, are irregular pigment network, irregular streaks, and irregular dots/globules, while blue-white structures are rarely found.

John AM, Schwartz RA
Muir-Torre syndrome (MTS): An update and approach to diagnosis and management.
J Am Acad Dermatol. 2016; 74(3):558-66 [PubMed] Related Publications
Muir-Torre syndrome (MTS) is a rare genetic condition that predisposes individuals to skin tumors and visceral malignancies. Because of the potentially aggressive nature of internal malignancies and sebaceous carcinoma, and the tendency to have multiple low-grade visceral cancers, close cancer surveillance is required in individuals and their families with this usually autosomal dominant disorder. Although the majority of MTS is caused by mutations in DNA mismatch repair genes resulting in microsatellite instability, a newly described subtype of MTS does not demonstrate microsatellite instability and may be inherited in an autosomal recessive pattern. In addition, MTS may be unmasked in transplant recipients taking specific immunosuppressant drugs or other immunosuppressed patients. Neoplasms may be subject to immunohistochemistry or both immunohistochemistry and genetic testing to confirm the diagnosis of MTS. Here, we offer an update and an approach to the diagnosis and management of MTS with a particular emphasis on the role of immunohistochemistry and genetic testing.

Jaju PD, Ransohoff KJ, Tang JY, Sarin KY
Familial skin cancer syndromes: Increased risk of nonmelanotic skin cancers and extracutaneous tumors.
J Am Acad Dermatol. 2016; 74(3):437-51; quiz 452-4 [PubMed] Related Publications
Nonmelanoma skin cancers (NMSCs) represent the most common malignancies worldwide, with reported incidence rising each year. Both cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), as well as other NMSCs, represent complex diseases with a combination of environmental and genetic risk factors. In general, hereditary cancer syndromes that increase the risk of NMSC fall under several broad categories: those associated with immunodeficiencies, those that affect skin pigmentation, and those that perturb key molecular pathways involved in the pathogenesis of NMSCs. Many of the syndromes are also associated with extracutaneous manifestations, including internal malignancies; therefore, most require a multidisciplinary management approach with a medical geneticist. Finally, dermatologists play a critical role in the diagnosis and management of these conditions, because cutaneous findings are often the presenting manifestations of disease.

Ransohoff KJ, Jaju PD, Jaju PD, et al.
Familial skin cancer syndromes: Increased melanoma risk.
J Am Acad Dermatol. 2016; 74(3):423-34; quiz 435-6 [PubMed] Related Publications
Phenotypic traits, such as red hair and freckling, increase melanoma risk by 2- to 3-fold. In addition, approximately 10% of melanomas are caused by inherited germline mutations that increase melanoma risk from 4- to >1000-fold. This review highlights the key genes responsible for inherited melanoma, with an emphasis on when a patient should undergo genetic testing. Many genetic syndromes associated with increased melanoma risk are also associated with an increased risk of other cancers. Identification of these high-risk patients is essential for preventive behavior reinforcement, genetic counseling, and ensuring other required cancer screenings.

Soura E, Eliades PJ, Shannon K, et al.
Hereditary melanoma: Update on syndromes and management: Emerging melanoma cancer complexes and genetic counseling.
J Am Acad Dermatol. 2016; 74(3):411-20; quiz 421-2 [PubMed] Article available free on PMC after 01/03/2017 Related Publications
Recent advances in cancer genomics have enabled the discovery of many cancer-predisposing genes that are being used to classify new familial melanoma/cancer syndromes. In addition to CDKN2A and CDK4, germline variants in TERT, MITF, and BAP1 have been added to the list of genes harboring melanoma-predisposing mutations. These newer entities may have escaped earlier description in part because of more advanced technologies now being used and in part because of their mixed cancer phenotype as opposed to a melanoma-focused syndrome. Dermatologists should be aware of (and be able to recognize) the clinical signs in high-risk patients in different contexts. Personal and family histories of cancer should always be sought in patients with multiple nevi or a positive history for melanoma, and should be updated annually. Various features that are unique to specific disorders, such as the appearance of melanocytic BAP1-mutated atypical intradermal tumors in cases of BAP1 melanoma syndrome, should also be recognized early. These patients should be offered regular screenings with the use of dermoscopy and total body photography, as needed. More importantly, referral to other specialists may be needed if a risk for internal malignancy is suspected. It is important to have in mind that these patients tend to develop multiple melanomas, along with various internal organ malignancies, often at younger ages; a multidisciplinary approach to their cancer screening and treatment is ideal.

Soura E, Eliades PJ, Shannon K, et al.
Hereditary melanoma: Update on syndromes and management: Genetics of familial atypical multiple mole melanoma syndrome.
J Am Acad Dermatol. 2016; 74(3):395-407; quiz 408-10 [PubMed] Article available free on PMC after 01/03/2017 Related Publications
Malignant melanoma is considered the most lethal skin cancer if it is not detected and treated during its early stages. About 10% of melanoma patients report a family history of melanoma; however, individuals with features of true hereditary melanoma (ie, unilateral lineage, multigenerational, multiple primary lesions, and early onset of disease) are in fact quite rare. Although many new loci have been implicated in hereditary melanoma, CDKN2A mutations remain the most common. Familial melanoma in the presence of multiple atypical nevi should raise suspicion for a germline CDKN2A mutation. These patients have a high risk of developing multiple primary melanomas and internal organ malignancies, especially pancreatic cancer; therefore, a multidisciplinary approach is necessary in many cases. The value of dermoscopic examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first-degree relatives. In addition, genetic counseling with the possibility of testing can be a valuable adjunct for familial melanoma patients. This must be performed with care, however, and only by qualified individuals trained in cancer risk analysis.

Wang KR, Jia YJ, Zhou SH, et al.
Cutaneous and Subcutaneous Metastases From Atypical Laryngeal Carcinoids: Case Report and Review of the Literature.
Medicine (Baltimore). 2016; 95(7):e2796 [PubMed] Related Publications
The incidence of cutaneous and subcutaneous metastases from atypical laryngeal carcinoids is approximately 20%. However, the pathogenesis and natural history of, and prognostic factors for, the condition remain poorly understood. We reported a 54-year-old female presented with cutaneous and subcutaneous metastases from atypical laryngeal carcinoid. Laryngoscopy revealed a 0.5 × 1.5-cm reddish mass on the laryngeal surface of the epiglottis. Under general anesthesia, a biopsy sample was obtained via suspension laryngoscopy. Routine pathology revealed atypical laryngeal carcinoid. Immunohistochemical staining of the sections of primary tumor was positive for cytokeratin, chromogranin A, synaptophysin, hypoxia-inducible factor-1α, P53, and CD56. GLUT-1, p-Akt, and PI3K were negative. The Ki-67 index was 15%. Supraglottic laryngectomy and selective right-neck dissection were performed. After 6 months, the patient complained of pain in the right wall of the chest; multiple cutaneous and subcutaneous nodules were evident at that site and in the abdomen. An abdominal nodule was biopsied and pathology revealed that the atypical metastatic carcinoid had metastasized to both cutaneous and subcutaneous areas of the abdomen. Chemotherapy was then prescribed. Currently, the intrathecal drug delivery system remains in place. No local recurrence has been detected. Furthermore, we systematically reviewed clinical manifestations of the disease, pathogenesis, prognostic factors, and treatment. The metastasis rate (cutaneous and subcutaneous) was approximately 12.2%. Thirty patients (62.5%) with cutaneous and subcutaneous metastases exhibited contemporaneous lymph node invasion. The 3-, 5-, and 10-year survival rates were 44.0%, 22.0%, and 13.0%, respectively. The prognosis of patients with atypical laryngeal carcinoids was poor. Relevant prognostic factors included the level of p53, human papilloma virus status, certain hypoxic markers, and distant metastasis. No optimal treatment for such metastases has yet been defined.

Turnis ME, Sawant DV, Szymczak-Workman AL, et al.
Interleukin-35 Limits Anti-Tumor Immunity.
Immunity. 2016; 44(2):316-29 [PubMed] Article available free on PMC after 16/02/2017 Related Publications
Regulatory T (Treg) cells pose a major barrier to effective anti-tumor immunity. Although Treg cell depletion enhances tumor rejection, the ensuing autoimmune sequelae limits its utility in the clinic and highlights the need for limiting Treg cell activity within the tumor microenvironment. Interleukin-35 (IL-35) is a Treg cell-secreted cytokine that inhibits T cell proliferation and function. Using an IL-35 reporter mouse, we observed substantial enrichment of IL-35(+) Treg cells in tumors. Neutralization with an IL-35-specific antibody or Treg cell-restricted deletion of IL-35 production limited tumor growth in multiple murine models of human cancer. Limiting intratumoral IL-35 enhanced T cell proliferation, effector function, antigen-specific responses, and long-term T cell memory. Treg cell-derived IL-35 promoted the expression of multiple inhibitory receptors (PD1, TIM3, LAG3), thereby facilitating intratumoral T cell exhaustion. These findings reveal previously unappreciated roles for IL-35 in limiting anti-tumor immunity and contributing to T cell dysfunction in the tumor microenvironment.

Botar-Jid CM, Cosgarea R, Bolboacă SD, et al.
Assessment of Cutaneous Melanoma by Use of Very- High-Frequency Ultrasound and Real-Time Elastography.
AJR Am J Roentgenol. 2016; 206(4):699-704 [PubMed] Related Publications
OBJECTIVE: The primary objective of this study was to evaluate the usefulness of very-high-frequency ultrasound as tool for assessment of skin melanoma by investigation of the correlation between the ultrasound measurement of the thickness of a melanoma and the histopathologically measured Breslow index. The secondary objective was to assess the potential role of real-time elastography in the preoperative evaluation of skin melanoma.
SUBJECTS AND METHODS: The study included 42 cutaneous melanoma lesions in 39 adult subjects examined in the division of ultrasound of a department of radiology between September 2011 and January 2015. Gray-scale sonographic features at 40 MHz (thickness, echogenicity, contour) and real-time strain elastographic (qualitative and semiquantitative, strain ratio) characteristics were evaluated and compared with the pathologic results.
RESULTS: The melanoma lesions had a homogeneous hypoechoic appearance with a regular contour and stiff or medium consistency. The mean difference between Breslow index and ultrasound thickness was -0.05 mm (95% CI, -0.24 to 0.13 mm), sustaining the absence of significant differences between these two measurements. A strong relation was identified between real-time elastographic appearance and strain ratio for the relations between lesion and hypodermis and between lesion and neighboring dermis (p < 0.002) or hypodermis.
CONCLUSION: Our study showed that very-high-frequency ultrasound and real-time elastography can be useful examinations for comprehensive preoperative evaluation of cutaneous melanoma.

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