Skin Cancer
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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)

Latest Research Publications

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

Vogel RI, Ahmed RL, Nelson HH, et al.
Exposure to indoor tanning without burning and melanoma risk by sunburn history.
J Natl Cancer Inst. 2014; 106(6):dju112 [PubMed] Related Publications
Indoor tanning is carcinogenic to humans. Individuals report that they tan indoors before planning to be in the sun to prevent sunburns, but whether skin cancer is subsequently reduced is unknown. Using a population-based case-control study, we calculated the association between melanoma and indoor tanning after excluding exposed participants reporting indoor tanning-related burns, stratified by their number of lifetime sunburns (0, 1-2, 3-5, >5). Confounding was addressed using propensity score analysis methods. All statistical tests were two-sided. We observed increased risk of melanoma across all sunburn categories for participants who had tanned indoors without burning compared with those who never tanned indoors, including those who reported zero lifetime sunburns (odds ratio = 3.87; 95% confidence interval = 1.68 to 8.91; P = .002). These data provide evidence that indoor tanning is a risk factor for melanoma even among persons who reported never experiencing burns from indoor tanning or outdoor sun exposure.

Related: Melanoma USA

Kaiser S, Vassell R, Pinckney RG, et al.
Clinical impact of biopsy method on the quality of surgical management in melanoma.
J Surg Oncol. 2014; 109(8):775-9 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: Though guidelines recommend excisional biopsy for diagnosing melanoma, partial biopsy techniques are commonly performed, risking underestimation of Breslow depth and altering surgical management. Biopsy choice patterns by specialty and subsequent impact on surgical management was examined.
METHODS: Retrospective review of the University of Vermont Cancer Registry. All patients with a single, primary cutaneous melanoma from 1/02 to 6/12 analyzed.
RESULTS: Among 853 lesions analyzed, 606 had Breslow depth <1 mm. Dermatologists perform 62.6% of biopsies, favoring shave biopsies; surgeons favor excisional biopsies (48%), and primary care doctors favor punch biopsies (44.8%), (P < 0.001). Final Breslow depth was upstaged in 107 (12.5%); however, only 23 of 488 partial biopsies (4.7%) displayed a discrepancy great enough to change surgical recommendations (P < 0.001). There was no statistically significant relationship with presence of ulceration, regression, high Clark level, or high mitotic index.
CONCLUSIONS: Partial biopsy techniques are commonly performed in diagnosing melanoma; especially among dermatologists, who perform the majority of biopsies. Though partial biopsies were less accurate in determining Breslow thickness; they rarely alter recommendations for surgical management. Predictive features could not be determined to identify the few cases where a Breslow discrepancy was clinically relevant.

Related: Melanoma

Frankel TL, Bamboat ZM, Ariyan C, et al.
Predicting the development of brain metastases in patients with local/regional melanoma.
J Surg Oncol. 2014; 109(8):770-4 [PubMed] Related Publications
BACKGROUND: The brain is a common site of recurrence in melanoma patients. Brain recurrence may present as a seizure, hemorrhage, or death. We sought to determine predictors of brain metastases in patients with primary and regional melanoma in order to facilitate targeted screening.
METHODS: Prospectively maintained databases were used to identify patients treated for local or regional melanoma who developed stage IV melanoma with and without brain metastasis at initial recurrence. One hundred twenty patients were identified with brain relapse and compared to 487 patients without brain recurrence.
RESULTS: On univariate analysis, patients with brain metastases were younger (55 vs. 59yrs, P = 0.04) but did not differ in primary site (head and neck 23% vs. 21%, P = 0.20). Brain metastasis patients had thinner primaries (mean 3.4 vs. 4.5 mm, P = 0.01). There were no other pathologic differences including ulceration (55% vs. 53%, P = 0.75), mitoses (7 vs.7.5, P = 0.61) or histologic subtype. Younger age and decreased Breslow thickness were independently associated with brain metastases at stage IV recurrence (OR = 1.10 P = 0.01 and OR = 1.02 P = 0.02, respectively).
CONCLUSIONS: Our analysis, the largest to date, demonstrates that thinner Breslow depth and younger age were associated with brain recurrence at first presentation with Stage IV disease.

Ellis H
Edward Cock: Cock's 'peculiar tumour'.
J Perioper Pract. 2014; 24(4):87-8 [PubMed] Related Publications
I must first apologise to my readers for including in this series a condition which I have never personally seen in 40 years of general surgery, nor, I believe, have any of the readers of this article. My excuse is that the condition has such a charming name and that the surgeon, Edward Cock, was such an interesting character.

Dubravcić ID, Brozić JM, Aljinović A, Sindik J
Quality of life in Croatian metastatic melanoma patients.
Coll Antropol. 2014; 38(1):69-74 [PubMed] Related Publications
The aim of this study was to examine the quality of life (QoL) in 40 Croatian metastatic melanoma patients who had completed at least first-line treatment and to see if there was a correlation between QoL parameters and serum lactate dehydrogenase (LDH). LDH levels were measured and all patients clinically examined between April and September 2013. Two QoL questionnaires were used for patient self-evaluation: the European Organization for Research and Treatment of Cancer Quality of life Questionnaire (EORTC QLQ-C30) and the Dartmouth Primary Care Cooperative Research Network and the World Organization of National Colleges, Academies, and Academic Associations of General Practitioners/Family Physicians (COOP/WONCA) charts. The average EORTC QLQ-C30 score for global health status (GHS) was 41.204. The average scores for functional scales were high, with the exception of emotional functioning (65.02). Blood LDH levels positively correlated with the Eastern Cooperative Oncology Group (ECOG) status (r = 0.415; p < 0.01) and pain (r = 0.345; p < 0.05), but not with any functional or COOP/WONCA scores. Global health status (GHS) positively correlated with patient age at the time of evaluation (r = 0.386; p < 0.05) and age at the time when metastatic disease had been diagnosed (r = 0.366; p < 0.05). Quality of life for the studied group of metastatic melanoma patients in Croatia can be considered generally good, with the exception of emotional functioning and symptoms of fatigue, dispnoea, insomnia, and financial difficulties.

Aydin IT, Melamed RD, Adams SJ, et al.
FBXW7 mutations in melanoma and a new therapeutic paradigm.
J Natl Cancer Inst. 2014; 106(6):dju107 [PubMed] Related Publications
BACKGROUND: Melanoma is a heterogeneous tumor with subgroups requiring distinct therapeutic strategies. Genetic dissection of melanoma subgroups and identification of therapeutic agents are of great interest in the field. These efforts will ultimately lead to treatment strategies, likely combinatorial, based on genetic information.
METHODS: To identify "driver" genes that can be targeted therapeutically, we screened metastatic melanomas for somatic mutations by exome sequencing followed by selecting those with available targeted therapies directed to the gene product or its functional partner. The FBXW7 gene and its substrate NOTCH1 were identified and further examined. Mutation profiling of FBXW7, biological relevance of these mutations and its inactivation, and pharmacological inhibition of NOTCH1 were examined using in vitro and in vivo assays.
RESULTS: We found FBXW7 to be mutated in eight (8.1%) melanoma patients in our cohort (n = 103). Protein expression analysis in human tissue samples (n = 96) and melanoma cell lines (n = 20) showed FBXW7 inactivation as a common event in melanoma (40.0% of cell lines). As a result of FBXW7 loss, we observed an accumulation of its substrates, such as NOTCH1. Ectopic expression of mutant forms of FBXW7 (by 2.4-fold), as well as silencing of FBXW7 in immortalized melanocytes, accelerated tumor formation in vivo (by 3.9-fold). Its inactivation led to NOTCH1 activation, upregulation of NOTCH1 target genes (by 2.6-fold), and promotion of tumor angiogenesis and resulted in tumor shrinkage upon NOTCH1 inhibition (by fivefold).
CONCLUSIONS: Our data provides evidence on FBXW7 as a critical tumor suppressor mutated and inactivated in melanoma that results in sustained NOTCH1 activation and renders NOTCH signaling inhibition as a promising therapeutic strategy in this setting.

Related: Melanoma Signal Transduction NOTCH1 gene FBXW7 gene

Kramer E, Herman O, Frand J, et al.
Ki67 as a biologic marker of basal cell carcinoma: a retrospective study.
Isr Med Assoc J. 2014; 16(4):229-32 [PubMed] Related Publications
BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in humans. Several factors have been associated with the biological behavior of these tumors, including histopathologic type, depth of tumor invasion, perineural invasion, and the expression of several biological markers including Ki67, a proliferative marker. Previous studies assessing the relationship between the proliferative fraction, as expressed by Ki67, and the histological variants of BCC as well as its association with the tendency to recur, failed to illustrate significant statistical correlation.
OBJECTIVES: To examine the proliferative index, as expressed by Ki67, in various subtypes of basal cell carcinoma, and to assess its relationship to various histological and clinical variables.
METHODS: In this retrospective study 51 lesions of BCC were examined. In each case, the following data were gathered: demographic (age and gender), anatomic location, size of the lesion, and clinical follow-up. Each case was stained immunohistochemically with anti-Ki67 antigen (MIB-1), and the proliferative index was determined. Histological analysis was performed for the following data: presence of an ulcer, intensity of inflammatory infiltrate, histologic subtype, mitotic count, and the presence of perineural invasion.
RESULTS: Basal cell carcinoma exhibited a wide variation of proliferative indices, ranging from 1% to 61%. A significant statistical correlation was observed between the proliferative index and the mitotic activity, tumor ulceration and brisk tumor-infiltrating lymphocytes.
CONCLUSIONS: The wide variation in the degree of proliferation (from almost no activity to highly proliferative tumors) suggests that basal cell carcinoma exhibits a wide spectrum of biological characteristics. Ulcerated lesions were characterized by high proliferative index. No true correlation was demonstrated between the proliferative index and the aggressive histological subtypes, implying that other factors were more biologically significant. The degree of proliferation also showed significant statistical correlation with the degree of tumor infiltration by lymphocytes. The significance of this proliferation-associated increased immunogenicity needs to be further studied.

Related: Basal Cell Carcinoma MKI67

Micali G, Lacarrubba F, Nasca MR, et al.
Topical pharmacotherapy for skin cancer: part II. Clinical applications.
J Am Acad Dermatol. 2014; 70(6):979.e1-12; quiz 9912 [PubMed] Related Publications
The purpose of the paper is to provide an in-depth, evidence-based analysis of the clinical use of topical treatments for skin cancer. A comprehensive review of topical drugs has been performed, including 5-fluorouracil, imiquimod, diclofenac, ingenol mebutate, retinoids, resiquimod, piroxicam, dobesilate, and betulinic acid. The evaluated studies were rated according to their level of evidence level (I-V), as indicated by recent guidelines for evidence-based medicine, The Oxford 2011 Levels of Evidence. Therapeutic response is generally related to tumor type, extent, and localization, and also to patient compliance. Careful patient selection is required in order to achieve the desired goal of complete tumor clearance.

Related: Basal Cell Carcinoma

Micali G, Lacarrubba F, Nasca MR, Schwartz RA
Topical pharmacotherapy for skin cancer: part I. Pharmacology.
J Am Acad Dermatol. 2014; 70(6):965.e1-12; quiz 977-8 [PubMed] Related Publications
Topical pharmacotherapy represents an effective alternative treatment for superficial skin cancer, primarily actinic keratoses and basal cell carcinomas. We provide an in-depth analysis of the pharmacologic aspects of available topical drugs for the treatment of primary skin tumors. In particular, we evaluate the mechanisms of action, formulations and indications, side effects, and contraindications of 5-fluorouracil, imiquimod, diclofenac, ingenol mebutate, and retinoids. Moreover, the characteristics of some investigational molecules (ie, resiquimod, piroxicam, dobesilate, and betulinic acid) are presented.

Related: Basal Cell Carcinoma

Dixon AJ, Anderson SJ, Mazzurco JD, Steinman HK
Novel photodynamic therapy does not prevent new skin cancers--randomized controlled trial.
Dermatol Surg. 2014; 40(4):412-9 [PubMed] Related Publications
OBJECTIVES: To determine whether field photodynamic therapy (PDT) of actinic keratoses using a novel preparation of 5-aminolevulonic acid (novel ALA) results in fewer subsequent invasive skin cancers developing on the face of individuals with previous facial cutaneous malignancy in a prospective randomized controlled trial.
METHODS AND MATERIALS: Intervention patients received two treatments of novel ALA 2 weeks apart. Controls were observed. Patients were followed up with biopsy of any suspicious lesions for 3 years.
RESULTS: The trial was suspended early because of problems with trial governance and the reporting of severe adverse events. Sixty-four patients who were recruited at that time at one center were monitored. Their average age was 71, and 57% were male. Patients were randomized to intervention (n = 34) or observation (n = 29). Over the subsequent 3 years, 13 intervention patients (38%) developed 30 new cutaneous malignancies in the field treated, and 11 control patients (38%) developed 22 new malignancies. Some intervention patients experienced prolonged adverse events, including permanent scarring.
CONCLUSION: Novel ALA made no difference in the likelihood of new malignancies developing. The risks without benefit of this novel ALA are troubling. Lack of efficacy and safety of novel ALA cannot be extrapolated to other PDT products.

Related: Basal Cell Carcinoma Melanoma

Lee C, Duffy SA, Louzon SA, et al.
The impact of Sun Solutions educational interventions on select health belief model constructs.
Workplace Health Saf. 2014; 62(2):70-9 [PubMed] Related Publications
The purpose of this study was to offer the Sun Solutions intervention to operating engineers (N = 232) to decrease sun exposure and skin cancer. The majority (82%) of the engineers worked outside between 10 a.m. and 3 p.m., 4 to 5 hours a day; 81.4% reported more than one sunburn during the past year and 70% sometimes or never used sunscreen compared to 30% who wore sunscreen approximately 50% or more of the time. Most reported that the intervention was helpful (97%), most were satisfied (96%) with the intervention, and 84% expressed a future intention to use sunscreen. Regarding sun protective behaviors, the intervention significantly improved perceived self-efficacy (p < .05) and increased perceived barriers (p < .05). Regarding sunburn and skin cancer, the intervention increased perceived benefits (p < .05), susceptibility (p < .05), and severity (p < .05) for sunburning, but not skin cancer (p > .10). The Sun Solutions intervention showed the potential to increase sunscreen use and decrease the risk of sunburn and skin cancer among operating engineers.

Related: USA

Foo TA, Dellavalle RP
Tanning bed legislation and the dermatologist.
Semin Cutan Med Surg. 2013; 32(4):217-23 [PubMed] Related Publications
Indoor ultraviolet (UV) tanning correlates with increased risk of developing melanoma and other skin cancers. Because of the limited scope of individual counseling by physicians and other health care providers, prevention efforts now encompass population-based interventions in the form of legislation to discourage and decrease access to indoor tanning facilities. Legislation increasingly restricts indoor UV tanning at the national, territory, state, or local level and draws attention to the complexities surrounding enforcement and infraction penalties. Further research needs to better define the effect of decreased indoor UV tanning access on skin cancer incidence.

Related: USA

White I, Fortino J, Curti B, Vetto J
Clinical impact of sentinel lymph node biopsy in patients with thick (>4 mm) melanomas.
Am J Surg. 2014; 207(5):702-7; discussion 707 [PubMed] Related Publications
BACKGROUND: The role of sentinel lymph node status (SLNS) in thick melanoma is evolving. The purpose of this study was to determine the prognostic value of SLNS in thick melanoma.
METHODS: A retrospective analysis of 120 prospectively collected clinically node-negative thick melanomas over 5 years was performed. Patient (age/sex) and tumor (thickness, ulceration, SLNS, mitoses, metastases, and recurrence) features were collected. Multivariate analysis was performed using Cox proportional hazard model.
RESULTS: Factors predictive of positive SLN included male sex, ulceration, and high mitoses. Factors associated with positive SLN had higher local-regional recurrence and metastases than negative SLN. SLNS and tumor thickness impacted 5-year disease-free survival (DFS) and overall survival (OS). Positive SLN, ulceration, age, and mitoses were independent predictors of DFS/OS.
CONCLUSIONS: Nonulcerated/lower mitoses thick melanomas had lower positive SLN rates. Positive SLN develop recurrence and metastases and have worse OS/DFS. SLNS is an important prognosticator for OS/DFS. Sentinel lymph node biopsy delineates prognostic groups in thick melanomas and can impact management.

Related: Melanoma

Main B, Felstead A, Hughes C, Thomas S
A guide to skin cancer of the face for the dental team.
Dent Update. 2014; 41(2):111-2, 114-6, 118 [PubMed] Related Publications
The incidence of skin cancer in the United Kingdom is increasing and is associated with an ageing population and increasing lifetime exposure to sunlight. The three most common types of skin cancer are basal cell carcinoma, squamous cell carcinoma and malignant melanoma, all three of which may present on the skin of the face. The dental team are, therefore, well-placed to recognize suspicious lesions and arrange for further advice or assessment. This paper outlines the epidemiology, important clinical features and principles of modern management of facial skin cancers to aid dental practitioners in the recognition of suspicious lesions. In addition, some of these treatments have side-effects which have the potential to affect a patient's oral health or its management and these aspects are also discussed. Clinical Relevance: The dental surgeon is ideally placed to recognize malignant or potentially malignant lesions on patients'faces and to advise on seeking further advice or refer for assessment, as appropriate. Dental practitioners will increasingly encounter patients who have undergone surgical or non-surgical management of facial skin cancer and should understand the potential oro-facial side-effects of such treatment.

Related: Basal Cell Carcinoma Melanoma

Cleavenger J, Johnson SM
Non melanoma skin cancer review.
J Ark Med Soc. 2014; 110(11):230-4 [PubMed] Related Publications
The diagnosis of skin cancer is often distressing for the individual patient even though 20% of the population may develop a skin cancer during their life. As with most conditions, an ounce of prevention is worth a pound of cure. Employing sun smart behaviors in childhood that last into adulthood is a good place to start. Regularly scheduled full body skin exams by a health care provider in addition to monthly self skin check exams allow for early detection.

Related: Basal Cell Carcinoma

Hoch S, Franke N, Katabi N, et al.
The value of elective parotidectomy in advanced squamous cell carcinoma of the skin of the head.
Anticancer Res. 2014; 34(5):2433-6 [PubMed] Related Publications
BACKGROUND: Parotid metastases from cutaneous squamous cell carcinoma (CSCC) are associated with poor prognosis. However, the incidence of occult parotid lymph node metastases in high-risk CSCC is unclear. Therefore, the role of elective parotidectomy is still controversial. The purpose of the present study was to analyze the value of elective parotidectomy in patients with high-risk CSCC.
PATIENTS AND METHODS: The clinical data including histological and radiological results, as well as surgery-related complications, of 13 patients with high-risk CSCC who underwent elective parotidectomy were retrospectively analyzed.
RESULTS: Occult parotid lymph node metastases were detected by histological examination in only 1 out of 13 patients after elective parotidectomy. Surgery-related complications and morbidity were not observed.
CONCLUSION: In the absence of clinical disease in the parotid gland, the risk of occult metastases is not high enough to warrant for elective parotidectomy in patients with CSCC.

Related: Head and Neck Cancers Head and Neck Cancers - Molecular Biology

Deaver D, Cauthen A, Cohen G, et al.
Excimer laser in the treatment of mycosis fungoides.
J Am Acad Dermatol. 2014; 70(6):1058-60 [PubMed] Related Publications
BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, which typically presents as a patch or plaque in early-stage disease. Phototherapy including psoralen plus ultraviolet A and ultraviolet B are well-established treatment modalities in management of early-stage MF. Only a limited number of reports have evaluated the efficacy of 308-nm excimer laser in therapy of cutaneous T-cell lymphoma.
OBJECTIVE: We sought to evaluate the efficacy of 308-nm excimer laser (XTRAC, PhotoMedex, Montgomeryville, PA) in patients with stage IA to IIA MF.
METHODS: We reviewed the clinical and laboratory characteristics of 6 consecutive patients given the diagnosis of refractory MF who underwent treatment with excimer laser.
RESULTS: We found that the 308-nm excimer laser is a safe and well-tolerated alternative therapy for early-stage MF. In addition, we were able to delineate criteria to help predict treatment response. Our data showed that 4 (66%) patients achieved clinical improvement (3 complete responses, 1 partial response), 1 had stable disease, and 1 had progressive disease.
LIMITATIONS: This was a retrospective study consisting of 6 patients. A prospective study with a larger sample size would be desirable for future studies.
CONCLUSION: The use of 308-nm excimer laser in the treatment of stage IA to IIA MF showed clinical and pathological benefit for patients with isolated lesions or lesions in areas that may be difficult to treat because of anatomic location.

Related: Cutaneous T-cell lymphoma

Juan YH, Saboo SS, Tirumani SH, et al.
Malignant skin and subcutaneous neoplasms in adults: multimodality imaging with CT, MRI, and 18F-FDG PET/CT.
AJR Am J Roentgenol. 2014; 202(5):W422-38 [PubMed] Related Publications
OBJECTIVE: The purpose of this article is to enlighten radiologists with the clinical presentation, multimodality imaging features, local recurrence, distant spread, differential diagnosis, and prognosis of skin and subcutaneous malignancies.
CONCLUSION: Cutaneous and subcutaneous malignancies represent the most common type of cancer and frequently present with overlapping imaging appearances. CT, MRI, and (18)F-FDG PET/CT are commonly used for staging, preoperative planning, and posttreatment assessment. Knowledge of the multimodality imaging features can narrow down the differential diagnosis and elucidate their metastatic pattern.

Glover AR, Allan CP, Wilkinson MJ, et al.
Outcomes of routine ilioinguinal lymph node dissection for palpable inguinal melanoma nodal metastasis.
Br J Surg. 2014; 101(7):811-9 [PubMed] Related Publications
BACKGROUND: Patients who present with palpable inguinal melanoma nodal metastasis have two surgical options: inguinal or ilioinguinal lymph node dissection. Indications for either operation remain controversial. This study examined survival and recurrence outcomes following ilioinguinal dissection for patients with palpable inguinal nodal metastasis, and assessed the incidence and preoperative predictors of pelvic nodal metastasis.
METHODS: This was a retrospective clinicopathological analysis of consecutive surgical patients with stage III malignant melanoma. All patients underwent a standardized ilioinguinal dissection at a specialist tertiary oncology hospital over a 12-year period (1998-2010).
RESULTS: Some 38.9 per cent of 113 patients had metastatic pelvic nodes. Over a median follow-up of 31 months, the 5-year overall survival rate was 28 per cent for patients with metastatic inguinal and pelvic nodes, and 51 per cent for those with inguinal nodal metastasis only (P = 0.002). The nodal basin control rate was 88.5 per cent. Despite no evidence of pelvic node involvement on preoperative computed tomography (CT), six patients (5.3 per cent) with a single metastatic inguinal lymph node had metastatic pelvic lymph nodes. Logistic regression analysis showed that the number of metastatic inguinal nodes (odds ratio 1.56; P = 0.021) and suspicious CT findings (odds ratio 9.89; P = 0.001) were both significantly associated with metastatic pelvic nodes. The specificity of CT was good (89.2 per cent) in detecting metastatic pelvic nodes, but the sensitivity was limited (57.9 per cent).
CONCLUSION: Metastatic pelvic nodes are common when palpable metastatic inguinal nodes are present. Long-term survival can be achieved following their resection by ilioinguinal dissection. As metastatic pelvic nodes cannot be diagnosed reliably by preoperative CT, patients presenting with palpable inguinal nodal metastasis should be considered for ilioinguinal dissection.

Related: Cancer of Unknown Primary

Lee JJ, Mochel MC, Piris A, et al.
p40 exhibits better specificity than p63 in distinguishing primary skin adnexal carcinomas from cutaneous metastases.
Hum Pathol. 2014; 45(5):1078-83 [PubMed] Related Publications
The histopathologic distinction between primary adnexal carcinomas and metastatic adenocarcinoma to the skin from sites such as the breast, lung, and others often presents a diagnostic dilemma. Current markers of diagnostic utility include p63 and cytokeratin 5/6; however, their expression has been demonstrated in 11% to 22% and 27% of cutaneous metastases, respectively. Furthermore, the immunoreactivity of p40 and GATA3 in various cutaneous adnexal carcinomas has not been previously reported. In the present study, we compared the expression of p40, p63, cytokeratin 5/6, and GATA3 in a total of 143 cases, including 67 primary adnexal carcinomas and 76 cutaneous metastases. p40, p63, cytokeratin 5/6, and GATA3 expression was observed in 80%, 84%, 86%, and 47% of primary adnexal carcinoma, respectively, and in 8%, 17%, 26%, and 40% of cutaneous metastases, respectively. χ(2) Analysis revealed statistically significant P values (<.0001) for p40, p63, and cytokeratin 5/6 in distinguishing primary adnexal carcinoma from cutaneous metastases. In summary, while p63 and cytokeratin 5/6 have similar sensitivity (84% and 86%, respectively) in detecting primary adnexal carcinomas, p40 appeared to be the most specific marker (92%) with the best positive predictive value (90%). Since breast and lung are the most common sites of origin for cutaneous metastases, p40 is the best distinguishing marker in these settings. None of the four studied markers (p40, p63, cytokeratin 5/6, and GATA3) are helpful in distinguishing between primary adnexal carcinomas from cutaneous metastases of salivary gland or bladder malignancies.

Related: GATA3 gene

Fleming KE, Ly TY, Pasternak S, et al.
Support for p63 expression as an adverse prognostic marker in Merkel cell carcinoma: report on a Canadian cohort.
Hum Pathol. 2014; 45(5):952-60 [PubMed] Related Publications
Recent evidence has invoked immunohistochemical expression of p63 in Merkel cell carcinoma as an adverse prognostic factor. Conflicting data led us to evaluate this. An Eastern Canadian cohort diagnosed between 1990 and 2012 was studied. Demographic and clinical data were obtained from pathology records and Provincial Cancer Registries. Pathological features were evaluated by the investigators. Merkel cell polyomavirus status was known in a subset of cases. Clinicopathological features were correlated with overall survival. The cohort consisted of 83 patients (mean age, 75.8 ± 11.7 years) with a male/female ratio of 1.24:1. In a mean follow-up period of 175 weeks (±177), 51 patients died (61.4%). Of several parameters examined, 6 showed significant adverse associations with survival on univariate analysis: age (hazard ratio [HR], 1.05 [1.02-1.08]), clinical stage (III/IV versus I/II; HR, 2.24 [1.18-4.27]), tumor size (HR, 1.16 [1.05-1.28]), combined versus pure morphology (HR, 1.82 [1.04-3.18]), minimal tumor-infiltrating lymphocytes (HR, 2.23 [1.04-4.78]), and expression of p63 (positive in 49.4%; HR, 1.93 [1.09-3.43]). In the stage I/II subgroup, p63 expression was associated with a trend toward poor survival. On multivariate analysis, p63 expression was not significantly associated with reduced survival. Our data support existing evidence that p63 expression in Merkel cell carcinoma carries adverse implications for survival. That it was not an independent prognostic factor may be due to study size and/or its potential as a confounding variable with clinical stage. Of clinical importance is its association with a trend toward a poor outcome in early stage disease.

Related: Canada Merkel Cell Carcinoma

Corrie PG, Marshall A, Dunn JA, et al.
Adjuvant bevacizumab in patients with melanoma at high risk of recurrence (AVAST-M): preplanned interim results from a multicentre, open-label, randomised controlled phase 3 study.
Lancet Oncol. 2014; 15(6):620-30 [PubMed] Related Publications
BACKGROUND: Bevacizumab, a monoclonal antibody that targets VEGF, has shown restricted activity in patients with advanced melanoma. We aimed to assess the role of bevacizumab as adjuvant treatment for patients with resected melanoma at high risk of recurrence. We report results from the preplanned interim analysis.
METHODS: We did a multicentre, open-label, randomised controlled phase 3 trial at 48 centres in the UK between July 18, 2007, and March 29, 2012. Patients aged 16 years or older with American Joint Committee on Cancer stage (AJCC) stage IIB, IIC, and III cutaneous melanoma were randomly allocated (1:1), via a central, computer-based minimisation procedure, to receive intravenous bevacizumab 7.5 mg/kg, every 3 weeks for 1 year, or to observation. Randomisation was stratified by Breslow thickness of the primary tumour, N stage according to AJCC staging criteria, ulceration of the primary tumour, and patient sex. The primary endpoint was overall survival; secondary endpoints included disease-free interval, distant-metastases interval and quality of life. Analysis was by intention-to-treat. This trial is registered as an International Standardised Randomised Controlled Trial, number ISRCTN81261306.
FINDINGS: 1343 patients were randomised to either the bevacizumab group (n=671) or the observation group (n=672). Median follow-up was 25 months (IQR 16-37) in the bevacizumab group and 25 months (17-37) in the observation group. At the time of interim analysis, 286 (21%) of 1343 enrolled patients had died: 140 (21%) of 671 patients in the bevacizumab group, and 146 (22%) of 672 patients in the observation group. 134 (96%) of patients in the bevacizumab group died because of melanoma versus 139 (95%) in the observation group. We noted no significant difference in overall survival between treatment groups (hazard ratio [HR] 0.97, 95% CI 0.78-1.22; p=0.76); this finding persisted after adjustment for stratification variables (HR 1.03; 95% CI 0.81-1.29; p=0.83). Median duration of treatment with bevacizumab was 51 weeks (IQR 21-52) and dose intensity was 86% (41-96), showing good tolerability. 180 grade 3 or 4 adverse events were recorded in 101 (15%) of 671 patients in the bevacizumab group, and 36 (5%) of 672 patients in the observation group. Bevacizumab resulted in a higher incidence of grade 3 hypertension than did observation (41 [6%] vs one [<1%]). There was an improvement in disease-free interval for patients in the bevacizumab group compared with those in the observation group (HR 0.83, 95% CI 0.70-0.98, p=0.03), but no significant difference between groups for distant-metastasis-free interval (HR 0.88, 95% CI 0.73-1.06, p=0.18). No significant differences were noted between treatment groups in the standardised area under the curve for any of the quality-of-life scales over 36 months. Three adverse drug reactions were regarded as both serious and unexpected: one patient had optic neuritis after the first bevacizumab infusion, a second patient had persistent erectile dysfunction, and a third patient died of a haemopericardium after receiving two bevacizumab infusions and was later identified to have had significant predisposing cardiovascular risk factors.
INTERPRETATION: Bevacizumab has promising tolerability. Longer follow-up is needed to identify an effect on the primary endpoint of overall survival at 5 years.

Related: Melanoma Bevacizumab (Avastin)

Mazeron R, Oberlin O, Dumas I, et al.
Brachytherapy in children with rhabdomyosarcomas of the nasolabial fold.
Pediatr Blood Cancer. 2014; 61(7):1162-7 [PubMed] Related Publications
BACKGROUND: Rhabdomyosarcomas (RMS) of the nasolabial fold can be difficult to manage surgically due to functional and cosmetic limitations. Therefore, brachytherapy (BT) has been proposed to improve local control while limiting the volume of irradiation as well as the extent of the surgical excision.
MATERIALS AND METHODS: Sixteen pediatric cases with RMS of the nasolabial fold treated from 1971 to 2005 were retrospectively reviewed.
RESULTS: Median follow-up was 4.4 years (1.7-33). Half of the patients were male and their age at diagnosis ranged from 4 months to 13.5 years. Histological subtypes included 10 embryonal and 6 alveolar RMS. Initial treatment consisted of induction multi-agent chemotherapy in all cases. In 12 patients, BT was combined with local excision (4 complete resections, 1 with macroscopic residual disease, and 7 with microscopic disease). Low dose-rate brachytherapy was performed in all cases according to the Paris system, using plastic catheters implanted per-operatively. The doses delivered ranged from 50 to 70 Gy, depending on chemotherapy response, and surgical margin status. 10 patients relapsed: 4 local, 6 regional, and 2 metastatic failures were reported. The median time to relapse was 6.5 months. At the time of analysis eight patients were alive and four had died. Four cases, under palliative care at last check-up, were lost to follow-up.
CONCLUSION: BT provided an acceptable local control rate, but the poor regional control of these cases may suggest a need for more aggressive management of cervical regional lymph node regions in RMS of the nasolabial fold.

Related: Brachytherapy Rhabdomyosarcoma

Gordon R
Skin cancer: increasing awareness and screening in primary care.
Nurse Pract. 2014; 39(5):48-54 [PubMed] Related Publications
Skin cancer screening (SCS) promotes early detection and improves treatment. Primary care providers are strategically positioned to provide screenings, yet the frequency is low. Strategies to improve SCS include increasing skin cancer awareness, targeting high-risk patient populations, and advocating for primary care providers to conduct screenings.

Related: Cancer Screening and Early Detection

Dummer R, Goldinger SM, Widmer D, et al.
To B-(RAF) or not to be.
J Invest Dermatol. 2014; 134(5):1200-1 [PubMed] Related Publications
The identification of targetable mutations has revolutionized the therapy of metastatic melanoma. In particular, BRAF and MEK inhibitors have a well-documented impact on overall survival in metastatic disease. However, therapeutic success is highly dependent on the correct identification of these mutations. We discuss the impact of molecular heterogeneity in this context.

Related: Melanoma BRAF gene Vemurafenib (Zelboraf)

Somasundaram R, Herlyn M
Indomethacin to the rescue of TRAIL-resistant melanomas.
J Invest Dermatol. 2014; 134(5):1198-9 [PubMed] Related Publications
Patients with melanomas develop resistance to both conventional- and targeted-therapy drugs. Promising clinical responses with immune checkpoint reagents have resulted in renewed interest in the use of biological therapies, although only subsets of individuals are known to respond to these reagents. Tse et al. now report on the use of indomethacin, an anti-inflammatory drug, to sensitize therapy-resistant melanoma cells.

Related: Melanoma BIRC5 TNFSF10

Argenziano G, Lallas A, Longo C, et al.
Dormant melanomas or changing nevi?
J Invest Dermatol. 2014; 134(5):1196-8 [PubMed] Related Publications
The development of new primary melanomas in patients treated with vemurafenib has been reported recently in a study by Perier-Muzet et al. The primary outcome of the study was to describe the dermoscopic changes that prompted excision of those melanomas. However, the crucial point raised by the study is the large number of melanomas that were detected.

Related: Melanoma Vemurafenib (Zelboraf)

D'Andrea M, Reggiani C, Fasano D, et al.
Tumours of the skin adnexa: a case series with focus on multiple segmental forms.
Pathologica. 2013; 105(6):337-41 [PubMed] Related Publications
OBJECTIVE: Skin adnexal tumours (SAT) as a whole are rare tumours, and most of our current knowledge on SAT is from single case reports or small series focused on single histotypes. The purpose of this paper is to review a series of benign and malignant SAT diagnosed in a 20-year period.
METHODS: All consecutive cases of SAT diagnosed between January 1992 and Dicember 2011 were retrieved. All slides were reviewed and diagnosed according to currently accepted criteria.
RESULTS: 281 consecutive cases of SAT were found. The majority of cases (94.3%) were benign, the most frequent histotypes were eccrine spiradenoma, hidrocystoma, eccrine poroma, syringoma, sebaceous adenoma and trichofolliculoma. Benign SAT affected adult males more frequently (M/F = 153/112) (mean age 59 years). Recurrences were rare (2/265). Three cases of multiple segmental spiroadenoma were observed. Malignant SAT consituted only 5.7% of all cases comprising sebaceous carcinoma, extramammary Paget disease and apocrine carcinoma. There was a slight female predilection (M/F = 7/9) (mean age 72 years), although patients were older than those affected by benign SAT. All neoplasms were small and no recurrences were recorded.
CONCLUSION: SAT are rare and most frequently benign. Correct diagnosis and complete surgical removal are important.

Hirako Y, Yonemoto Y, Yamauchi T, et al.
Isolation of a hemidesmosome-rich fraction from a human squamous cell carcinoma cell line.
Exp Cell Res. 2014; 324(2):172-82 [PubMed] Related Publications
Hemidesmosomes are cell-to-matrix adhesion complexes anchoring keratinocytes to basement membranes. For the first time, we present a method to prepare a fraction from human cultured cells that are highly enriched in hemidesmosomal proteins. Using DJM-1 cells derived from human squamous cell carcinoma, accumulation of hemidesmosomes was observed when these cells were cultured for more than 10 days in a commercial serum-free medium without supplemental calcium. Electron microscopy demonstrated that numerous electron-dense adhesion structures were present along the basal cell membranes of DJM-1 cells cultured under the aforementioned conditions. After removing cellular materials using an ammonia solution, hemidesmosomal proteins and deposited extracellular matrix were collected and separated by electrophoresis. There were eight major polypeptides, which were determined to be plectin, BP230, BP180, integrin α6 and β4 subunits, and laminin-332 by immunoblotting and mass spectrometry. Therefore, we designated this preparation as a hemidesmosome-rich fraction. This fraction contained laminin-332 exclusively in its unprocessed form, which may account for the promotion of laminin deposition, and minimal amounts of Lutheran blood group protein, a nonhemidesmosomal transmembrane protein. This hemidesmosome-rich fraction would be useful not only for biological research on hemidesmosomes but also for developing a serum test for patients with blistering skin diseases.

Tuominen R, Jönsson G, Enerbäck C, et al.
Investigation of a putative melanoma susceptibility locus at chromosome 3q29.
Cancer Genet. 2014; 207(3):70-4 [PubMed] Related Publications
Malignant melanoma, the most fatal form of skin cancer, is currently increasing in incidence in many populations. Approximately 10% of all cases occur in families with an inherited predisposition for melanoma. In Sweden, only a minor portion of such melanoma families carry a mutation in the known melanoma gene CDKN2A, and there is a need to identify additional melanoma susceptibility genes. In a recently performed genome-wide linkage screen, novel loci with suggestive evidence of linkage to melanoma were detected. In this study, we have further analyzed one region on chromosome 3q29. In all, 89 affected and 15 nonaffected family members from 42 melanoma-prone families were genotyped for 34 genetic markers. In a pooled linkage analysis of all 42 families, we detected significant evidence of linkage, with a maximum heterogeneity logarithm of odds (HLOD) score of 3.1 with 83% of the families contributing to the linkage score. The minimum critical region of linkage (defined by a 1LOD score support interval) maps to chromosome 3q29, spans 3.5 Mb of genomic sequence, and harbors 44 identified genes. Sequence variants within this region have previously been associated with cancer susceptibility. This study reports the presence of a putative novel melanoma susceptibility locus in the Swedish population, a finding that needs to be replicated in an independent study on other individuals with familial melanoma. Sequencing of genes in the region may identify novel melanoma-associated mutations.

Related: Chromosome 3 Melanoma

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