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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Latest Research Publications
Prevention of Skin Cancer
Melanoma
Non Melanoma Skin Cancer
-- Basal Cell Carcinoma
-- Squamous Cell Carcinoma
Cutaneous T-cell Lymphoma
Dermatofibrosarcoma Protuberans
Merkel Cell Cancer

Information Patients and the Public (9 links)


Information for Health Professionals / Researchers (6 links)

Latest Research Publications

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

Belkin DA, Mitsui H, Wang CQ, et al.
CD200 upregulation in vascular endothelium surrounding cutaneous squamous cell carcinoma.
JAMA Dermatol. 2013; 149(2):178-86 [PubMed]
OBJECTIVE: To characterize the presence of CD200 and CD200 receptor (CD200R) in the human cutaneous squamous cell carcinoma (SCC) microenvironment and to define a possible role for the CD200 axis in immune evasion by SCC.
DESIGN: Gene expression in SCC vs normal skin was studied. Laser capture microdissection was used to determine differential expression of CD200 in normal skin vs actinic keratosis vs SCC in situ vs invasive SCC. Immunofluorescence microscopy was used to define expression of CD200R on macrophages, myeloid dendritic cells, natural killer cells, and T cells in SCC vs normal skin. The effects of SCC supernatant on induction of CD200 in human blood endothelial cells was also examined.
SETTING: Academic Medical Center with an established Section of Mohs and Dermatologic Surgery and an active Cutaneous Biology Research Program.
PARTICIPANTS: Surgical discard tissue from deidentified patients and samples of normal skin from healthy volunteers were used in this study.
MAIN OUTCOME MEASURES: Expression of CD200 on SCC-associated blood vessels; expression of CD200 receptor on SCC-associated macrophages and T cells; and induction of CD200 on endothelial cells by SCC supernatants.
RESULTS: CD200 gene and message were upregulated in SCC stroma. Immunostaining revealed a higher number of CD200(+) cells in SCC stroma than in normal dermis (180.8 cells/mm(2) vs 24.6 cells/mm(2)) (P<.01). CD200 was further identified mainly on blood vessel endothelium in SCC. Tumor supernatant was able to induce CD200 expression on human dermal blood endothelial cells in culture. CD200R was identified on macrophages and dendritic cells in SCC microenvironment.
CONCLUSIONS: CD200 expression on local blood vessels may promote tumor progression by suppressing CD200R myeloid cells during diapedesis. These data highlight a previously unrecognized mechanism of immune evasion by SCC and may provide guidance for the development of targeted therapy.


Burusapat C, Satayasoontorn K, Nelson SD
Clinicopathological study of primary superficial leiomyosarcomas.
J Med Assoc Thai. 2013; 96(3):294-301 [PubMed]
BACKGROUND: Primary superficial leiomyosarcomas (PSL) are rare malignant lesions that are subdivided into cutaneous and subcutaneous tumors. Primary cutaneous and subcutaneous leiomyosarcomas differ not only as to primary site of origins, but also to differences in prognosis. Guidelines for management and follow-up are not clearly defined in the literature.
MATERIAL AND METHOD: Retrospective review was conducted from the patient's chart between January 2000 and December 2009. Histopathology, immunohistochemistry, and clinical and surgical records were reviewed.
RESULTS: The authors found five cases of PSL and divided them into two cases of cutaneous leiomyosarcomas and three cases ofsubcutaneous leiomyosarcomas. Overall, mean age of the patients was 42.4 years, male: female ratio was 4:1. Clinical presentations were painless mass. Wide excisions were performed in three cases with 2 cm margins. No local recurrence was found in the period of follow-up (6 months to 3 years). One case presented with bony metastasis five years after operation.
CONCLUSION: PSL are rare tumors. Surgical resection remains the main option for curative treatment. Wide excision with at least 2 cm peripheral margins and a depth that includes subcutaneous tissue and fascia are recommended. The natural history of these tumors is not clearly defined. All patients should be followed-up for a period of at least five years after treatments. The authors hoped that further study of these tumors would result in better treatments and follow-up guidelines to be a benefit to such patients in the future.


Sarantopoulos GP, Palla B, Said J, et al.
Mimics of cutaneous lymphoma: report of the 2011 Society for Hematopathology/European Association for Haematopathology workshop.
Am J Clin Pathol. 2013; 139(4):536-51 [PubMed]
The Society for Hematopathology and European Association for Haematopathology workshop, from October 27 to 29, 2011, in Los Angeles, CA, exhibited many exemplary skin biopsy specimens with interesting inflammatory changes mimicking features of cutaneous lymphoma. This article reviews features observed in cutaneous lymphoid hyperplasia, cutaneous drug reactions, lupus-associated panniculitis, pityriasis lichenoides, hypereosinophilic syndrome, histiocytic necrotizing lymphadenitis, traumatic ulcerative granuloma with stromal eosinophils, and pigmented purpuric dermatosis, as well as a brief review of the pertinent literature and discussion of submitted conference cases. For the pathologist, it is important to be aware of diagnostic pitfalls as well as the limitations of ancillary testing (eg, clonality studies). Finally, correlation with total clinical information, good communication with clinical colleagues, close clinical follow-up with rebiopsy, and prudent use of laboratory studies are vital and will likely offer the best path toward a correct diagnosis.


Swerdlow SH, Quintanilla-Martinez L, Willemze R, Kinney MC
Cutaneous B-cell lymphoproliferative disorders: report of the 2011 Society for Hematopathology/European Association for Haematopathology workshop.
Am J Clin Pathol. 2013; 139(4):515-35 [PubMed]
The diagnosis and classification of the cutaneous B-cell lymphomas can be quite a challenge, with a definitive diagnosis sometimes being elusive, even when an extensive workup has been performed. Distinction of benign from neoplastic disorders can be difficult, with some hyperplasias mimicking lymphomas and vice versa. There are only a limited number of skin-specific B-cell lymphomas, including primary cutaneous follicle center lymphoma and primary cutaneous diffuse large B-cell lymphoma, leg type. Cutaneous marginal zone lymphomas have distinctive features but are classified with the other mucosa-associated lymphoid tissue lymphomas. It is important, however, to also remember that many other B-cell lymphomas/ plasma cell neoplasms can primarily, or more often secondarily, involve the skin. Some may mimic one of the skin-specific lymphomas but have very different clinical implications. Iatrogenic and senescent immunodeficiency-associated lymphoproliferative disorders that are often Epstein-Barr virus (EBV) positive can also primarily involve the skin, including cases also known as EBV-positive mucocutaneous ulcer.


Quintanilla-Martinez L, Jansen PM, Kinney MC, et al.
Non-mycosis fungoides cutaneous T-cell lymphomas: report of the 2011 Society for Hematopathology/European Association for Haematopathology workshop.
Am J Clin Pathol. 2013; 139(4):491-514 [PubMed]
Primary cutaneous T-cell lymphomas (CTCL) excluding mycosis fungoides (MF) were discussed in 2 sessions of the 2011 Society for Hematopathology/ European Association of Haematopathology Workshop, Los Angeles, CA. Session 2 focused on primary cutaneous CD30+ T-cell lymphoproliferative disorders and their differential diagnosis, including systemic CD30+ T-cell lymphoma secondarily infiltrating the skin. Interesting features like special morphologic variants and atypical phenotypes were presented. In addition, the possibility of rare ALK+ primary cutaneous lymphomas was discussed. Session 3 examined other more uncommon non-MF CTCLs, including subcutaneous panniculitis-like T-cell lymphoma, extranodal NK/T-cell lymphoma, hydroa vacciniforme-like T-cell lymphoma, and rare subtypes of primary cutaneous peripheral T-cell lymphoma, not otherwise specified. In addition, systemic T-cell lymphomas involving the skin secondarily, such as angioimmunoblastic T-cell lymphoma, were included in this session. In this report, novel findings, areas of special interest, and diagnostic challenges emerging from the cases submitted to the workshop will be highlighted. The necessity to integrate histologic, immunophenotypical, genetic, and in particular, clinical data to arrive at the correct diagnosis, and subsequently provide adequate treatment, is emphasized.


Song SX, Willemze R, Swerdlow SH, et al.
Mycosis fungoides: report of the 2011 Society for Hematopathology/European Association for Haematopathology workshop.
Am J Clin Pathol. 2013; 139(4):466-90 [PubMed]
Session 1 of the 2011 Workshop of the Society for Hematopathology and European Association for Haematopathology focused on mycosis fungoides (MF), the most common cutaneous lymphoma. The 62 cases in this case group demonstrated a wide spectrum of clinicopathologic features, including those seen in typical cases as well as those, by contrast, with atypical clinical history, morphology, immunophenotype, and/or genotype. Of the 62 cases, 27 (44%) were presented at the workshop and highlighted diagnostic challenges plus related issues. This report summarizes the approach recommended for making a confident diagnosis of MF and its clinically significant variants; emphasizes pitfalls in evaluating early MF, assessing nodal involvement, and diagnosing transformed MF; and discusses the relationship between MF and primary cutaneous CD30+ T-cell lymphoproliferative disorders. Last, Sézary syndrome is discussed, with concentration on those features distinct from MF.


Griffin JR, Wriston CC, Peters MS, Lehman JS
Decreased expression of intercellular adhesion molecules in acantholytic squamous cell carcinoma compared with invasive well-differentiated squamous cell carcinoma of the skin.
Am J Clin Pathol. 2013; 139(4):442-7 [PubMed]
Intercellular adhesion proteins are poorly characterized in acantholytic squamous cell carcinoma (ASCC), a more aggressive tumor than nonacantholytic invasive well-differentiated squamous cell carcinoma (SCC) of the skin. In this study we compared expression of Dsg3, E-cadherin, and syndecan-1 in ASCC and SCC. Immunohistochemical detection of Dsg3, E-cadherin, and syndecan-1 in 22 ASCCs and 22 SCCs was graded on a semiquantitative scale for intensity of staining (SI) and degree of circumferential staining (CS) about the cell membrane. Results were assessed by means of conditional logistic regression and χ(2) analysis. Dsg3 and E-cadherin expression (SI, CS) was significantly decreased (P < .05) in ASCC compared with SCC, whereas staining for syndecan-1 was similar in the 2 tumor types. Differences in expression of adhesion markers between ASCC and SCC may contribute to the development of acantholysis in ASCC and its more aggressive biologic behavior.


Heidari M, Najafi F
Trends of skin cancer incidence in 6 geographical regions of the Islamic Republic of Iran, 2000-2005.
East Mediterr Health J. 2013; 19(1):59-65 [PubMed]
Data about the incidence of skin cancer in the Islamic Republic of Iran are lacking. This study investigated trends in the incidence of skin cancer (lCD-10 category C44, other malignant neoplasms of skin) in 6 regions using data from the Iranian cancer registry from 2000 to 2005. The standardized incidence rates in each year were calculated by the direct method using the standard World Health Organization population and a Poisson regression model was applied to analyse trends. Over the study period, 30 701 cases of cancer were identified, rising from 2353 in 2000 to 8484 in 2005. The male-to-female ratio was 1.6. The age-standardized incidence rose significantly from 3.8 cases per 100 000 in 2000 to 13.0 in 2005 (slope = 0.26), and the same trend was seen in all regions except the region to the east of the Caspian Sea. This increasing incidence of skin cancer in the Islamic Republic of Iran is similar to that reported in other countries.


Sartorelli P, Romeo R, Paolucci V, et al.
Skin photoaging in farmers occupationally exposed to ultraviolet radiation.
Med Lav. 2013 Jan-Feb; 104(1):24-9 [PubMed]
BACKGROUND: Most personal exposures to UV radiations occur from outdoor activities and several studies detected a significant association between skin cancer and outdoor occupation.
OBJECTIVE: The aim of the study was to ascertain the prevalence of photoaging signs in a population of Italian farmers and in a population of indoor workers taking account of confounding factors.
METHODS: 169 farmers and 198 indoor workers were classified for skin phototype and for skin photoaging, moreover 13 variables were taken into account. Marginal permutation tests were adopted for statistical analysis.
RESULTS: Farmers were significantly older than the indoor workers. In workers occupationally exposed to UV photoaging increased with increasing age and years of occupational exposure to sunlight The distribution of skin phototype did not show significant differences in the two populations, while farmer showed a higher degree of photoaging than indoor workers.
CONCLUSIONS: Even if farmers were older than the in door workers it seems that outdoor work produces a higher degree of photoaging.


Gaba S, Chopra P, Pankaj P, et al.
Merkel cell carcinoma--a rare cause of non-healing skin ulcer: a case report.
J Indian Med Assoc. 2012; 110(7):496-8 [PubMed]
Merkel cell carcinoma (MCC) is a rare tumour of skin which needs to be differentiated from other small cell tumours like small-cell carcinoma of lung, melanoma, and lymphoma. Definitive diagnosis is made by immunohistochemistry and staining positively with cytokeratin. There is very little data regarding treatment of metastatic MCC and many questions remain unanswered. MCC is a chemosensitive tumour and many different chemotherapeutic regimens have been used alone or in combination with radiotherapy to treat metastatic MCC. Although complete and partial responses are achieved, they are mostly short lived and tumour usually recurs. Here a case is reported who had partial remission with chemotherapy (etoposide and cisplatin) and radiation therapy in a patient with metastatic MCC.


Balk SJ, Fisher DE, Geller AC
Teens and indoor tanning: a cancer prevention opportunity for pediatricians.
Pediatrics. 2013; 131(4):772-85 [PubMed]
In October 2011, California became the first US state to ban indoor tanning for minors under age 18 years. Vermont followed in May 2012. Increasingly, scientific evidence shows that artificial tanning raises the risk of skin cancer, including melanoma, a common cancer in adolescents and young adults and the type most likely to result in death. The World Health Organization, the American Academy of Pediatrics, the American Academy of Dermatology, the American Medical Association, and other organizations strongly recommend legislation to ban minors under age 18 from indoor tanning. Several nations have banned teen tanning. Yet, tanning in salons is still a prevalent practice in the United States, especially among teen girls, where rates for the oldest teens approach 40%. There is no federal legislation to restrict minors from salon tanning. More than 60% of states have some kind of legislation regarding minors' use of tanning salons, but only California and Vermont have passed complete bans of indoor tanning for minors. The Indoor Tanning Association, an industry advocacy group, has vigorously opposed legislative efforts. Pediatricians can play key roles in counseling families and with legislative efforts. In this update, we review the prevalence of salon tanning, association with skin cancer risk, tanning addiction, the roles of the federal and state governments in regulation and legislation, and responses to arguments created by industry to oppose legislation. Preventing exposure to artificial tanning may save lives, including young lives, and is a key cancer prevention opportunity for pediatricians.


Dong Y, Zhuang L, Ma W
Comprehensive assessment of the association of ERCC2 Lys751Gln polymorphism with susceptibility to cutaneous melanoma.
Tumour Biol. 2013; 34(2):1155-60 [PubMed]
Previous studies evaluating the association between excision repair cross-complimentary group 2 (ERCC2) Lys751Gln polymorphism and susceptibility to cutaneous melanoma reported conflicting findings. We searched PubMed and Wangfang Medical databases up to October 16, 2012 to identify eligible studies. A total of 8 case-control studies including 3,492 cases and 5,381 controls were included in the meta-analysis. Statistical analysis was performed with Review Manage version 5.1. Odds ratios (ORs) with 95 % confidence intervals (95 %CIs) were used to assess the strength of the association. There was no obvious between-study heterogeneity among those eight studies under all four comparison models. Overall, there was a significant association between ERCC2 Lys751Gln polymorphism and susceptibility to cutaneous melanoma under three genetic models (for Gln versus Lys: OR = 1.08, 95 % CI = 1.01-1.15, P = 0.02; for GlnGln versus LysLys: OR = 1.16, 95 % CI = 1.01-1.33, P = 0.03; for GlnGln/LysGln versus LysLys: OR = 1.10, 95 % CI = 1.01-1.21, P = 0.04). Sensitivity analysis by omitting one study a time showed the significance of the pooled ORs was stable under all those three genetic models above. Therefore, the meta-analysis suggests that there is a significant association between ERCC2 Lys751Gln polymorphism and susceptibility to cutaneous melanoma.


Fink EC, Fisher DE
BRAF and MC1R in melanoma: different in head and neck tumors?
J Invest Dermatol. 2013; 133(4):878-80 [PubMed]
In this issue, Hacker et al. (2012) report the largest study to date on the association between MC1R variants and BRAF mutant melanoma. Although they did not observe a significant overall correlation, there was a significant negative association between BRAF and MC1R mutations for head/neck melanomas. This suggests a fundamental difference in pathogenesis between head/neck and truncal melanomas, which could contribute to their divergent prognoses.


Metcalf RA, Bashey S, Wysong A, et al.
Intravascular ALK-negative anaplastic large cell lymphoma with localized cutaneous involvement and an indolent clinical course: toward recognition of a distinct clinicopathologic entity.
Am J Surg Pathol. 2013; 37(4):617-23 [PubMed]
Intravascular large T-cell or NK-cell lymphomas rarely present with cutaneous involvement. Intravascular cytotoxic T or NK lymphomas presenting in the skin (cIT/NKL) are often EBV, and reported cases follow a highly aggressive clinical course. Intravascular anaplastic large cell lymphoma (ALCL) by contrast is extraordinarily rare and, when it presents in the skin, raises the question of aggressive clinical behavior in the manner of cIT/NKL versus indolent clinical behavior in the manner of primary cutaneous ALCL. Here we describe a case of localized cutaneous intravascular anaplastic lymphoma kinase-negative ALCL (cIALCL) with a very indolent clinical course. The patient experienced a single cutaneous relapse and remains alive without disease 4 years after diagnosis. Review of the literature reveals multiple clinicopathologic differences between cIALCL and cIT/NKL: distribution (cIALCL, single skin region, P=0.021, Fisher exact test); histology (cIALCL, cohesive with necrosis, P=0.005); immunophenotype (cIALCL, strongly CD30, P=0.021; cIT/NKL, CD56 and/or EBV, P=0.003); and indolent clinical behavior with a trend toward better overall survival (P=0.067, Kaplan-Meier survival analysis). Our index case of cIALCL and 1 other tested case were immunohistochemically confirmed to be intralymphatic (contained within D2-40+vessels) as compared with the blood vessel localization of cIT/NKL. Recognition of cIALCLs as a distinct clinicopathologic entity, and in particular their distinction from aggressive, usually EBV cIT/NKLs, may be possible on the basis of a combination of clinicopathologic criteria, allowing for localized therapy in a subset of patients.


DeCaprio JA, Garcea RL
A cornucopia of human polyomaviruses.
Nat Rev Microbiol. 2013; 11(4):264-76 [PubMed]
During the past 6 years, focused virus hunting has led to the discovery of nine new human polyomaviruses, including Merkel cell polyomavirus, which has been linked to Merkel cell carcinoma, a lethal skin cell cancer. The discovery of so many new and highly divergent human polyomaviruses raises key questions regarding their evolution, tropism, latency, reactivation, immune evasion and contribution to disease. This Review describes the similarities and differences among the new human polyomaviruses and discusses how these viruses might interact with their human host.


Maurice PD, Fenton T, Cross N, et al.
A dedicated dermatology clinic for renal transplant recipients: first 5 years of a New Zealand experience.
N Z Med J. 2013; 126(1369):27-33 [PubMed]
AIM: Cancer following organ transplantation is a growing public health concern. We describe the first 5 years' experience of a dedicated dermatology clinic for renal transplant recipients, the first of its type in New Zealand.
METHODS: Data from patients seen in the clinic were collected on a nephrology/dermatology database.
RESULTS: 86 of 99 transplant recipients had a baseline dermatology assessment. Seventy-one skin cancers (45 squamous, 25 basal cell carcinomas, 1 melanoma) were found in 17 patients. Eighteen of these were an incidental finding at the baseline post-transplant examination of 7 patients: they had not been noted either by the patient or by their nephrologist. A further 44 cancers were found in 13 patients at follow-up examinations in the dedicated clinic. Squamous and basal cell carcinomas received definitive treatment after 26 and 38 days (median) respectively. A brief analysis showed this to be a cost-effective way of diagnosing and treating skin cancer in this cohort of patients.
CONCLUSION: The clinic is enabling prompt diagnosis and cost-effective treatment of skin cancers developing in renal transplant recipients and is also identifying significant numbers of pre-existing skin cancers in these patients.


Olaofe OO, Omoniyi-Esan GO, Omonisi AE, Alakinyoola AL
Pseudoangiosarcomatous squamous cell carcinoma in an old surgical scar of an African woman.
Afr J Med Med Sci. 2012; 41(3):317-20 [PubMed]
BACKGROUND: Squamous cell carcinoma, a malignant proliferation of keratinocytes, can be found in many regions of the body covered by stratified squamous epithelium and in areas covered by other epithelia but which had undergone squamous metaplasia. Squamous cell carcinoma has many variants.
METHODOLOGY: We, retrospectively, reviewed the case file and histological features of a 75 year old trader with a rare variant of squamous cell carcinoma arising from an old surgical scar.
CASE REPORT: The 75-year-old African female trader presented to the hospital with three and a-half month history of a swelling in the anterior aspect of the left leg arising from an old surgical scar. Clinical examination showed an irregularly shaped ulcer measuring 14 x 16 cm with an everted edge and a hyperpigmented floor. Histologic sections of the specimen showed the infiltration of the papillary and reticular dermis of the skin by sheets of atypical spindle cells with areas of squamous differentiation. There was a contiguous area of capillary-like structures constituting about 30% of the sections examined. The neoplastic cells were positive for vimentin and cytokeratin but were negative for CD34. The diagnosis was pseudoangiosarcomatous squamous cell carcinoma.
CONCLUSION: This tumour can be found in Africans and in an old surgical scar. It can coexist with other variants of squamous cell carcinoma. There may be need in the future to add a new mixed variant to the current classification scheme.


Karagiannis P, Gilbert AE, Josephs DH, et al.
IgG4 subclass antibodies impair antitumor immunity in melanoma.
J Clin Invest. 2013; 123(4):1457-74 [PubMed] Free Access to Full Article
Host-induced antibodies and their contributions to cancer inflammation are largely unexplored. IgG4 subclass antibodies are present in IL-10-driven Th2 immune responses in some inflammatory conditions. Since Th2-biased inflammation is a hallmark of tumor microenvironments, we investigated the presence and functional implications of IgG4 in malignant melanoma. Consistent with Th2 inflammation, CD22+ B cells and IgG4(+)-infiltrating cells accumulated in tumors, and IL-10, IL-4, and tumor-reactive IgG4 were expressed in situ. When compared with B cells from patient lymph nodes and blood, tumor-associated B cells were polarized to produce IgG4. Secreted B cells increased VEGF and IgG4, and tumor cells enhanced IL-10 secretion in cocultures. Unlike IgG1, an engineered tumor antigen-specific IgG4 was ineffective in triggering effector cell-mediated tumor killing in vitro. Antigen-specific and nonspecific IgG4 inhibited IgG1-mediated tumoricidal functions. IgG4 blockade was mediated through reduction of FcγRI activation. Additionally, IgG4 significantly impaired the potency of tumoricidal IgG1 in a human melanoma xenograft mouse model. Furthermore, serum IgG4 was inversely correlated with patient survival. These findings suggest that IgG4 promoted by tumor-induced Th2-biased inflammation may restrict effector cell functions against tumors, providing a previously unexplored aspect of tumor-induced immune escape and a basis for biomarker development and patient-specific therapeutic approaches.


Kent R, Glorioso S, Nordberg ML
A model for cutaneous squamous cell carcinoma in vemurafenib therapy.
J La State Med Soc. 2012 Nov-Dec; 164(6):311-3 [PubMed]
Vemurafenib is a chemotherapeutic BRAF inhibitor, or dabrafenib, that has been FDA-approved for treatment in metastatic melanoma positive for the V600E mutation. BRAF inhibitors, including vemurafenib, are linked to the development of cutaneous squamous cell carcinoma and keratoacanthoma. Furthermore, pathological analysis has shown these secondary tumors do not harbor the same mutations as the primary cancer, suggesting de novo pathogenesis. In accordance, patients require close dermatological follow-up due to the high prevalence rates of these tumors. This paper takes the form of an extensive case-and-review article exploring the development of these tumors and their management.


Doyle LA, Fletcher CD
Metastasizing "benign" cutaneous fibrous histiocytoma: a clinicopathologic analysis of 16 cases.
Am J Surg Pathol. 2013; 37(4):484-95 [PubMed]
Cutaneous fibrous histiocytoma (FH) is considered a benign tumor; however, certain types of FH have been shown to have a tendency for local recurrence, and there are rare reported cases of metastasis. In this study, 16 cases of morphologically benign FH with locoregional or distant metastasis were identified in consult files. Pathologic features of primary, recurrent, and metastatic tumors, as well as clinical outcome, were evaluated. Nine were male and 7 were female patients; mean age was 42 years (range, 3 to 68 y). Primary tumors arose on the leg in 5 patients, buttock in 1, trunk in 3, shoulder in 3, neck in 2, and finger in 1. The primary site in 1 case was unknown. Fifteen primary tumors available for review involved the dermis; 6 extended into the superficial subcutis. Tumor size ranged from 1 to 5 cm (median 3.2 cm). Histologically, primary tumors showed characteristic features of FH, being composed in most cases of a polymorphous population of bland spindle and histiocytoid cells in a mixed storiform and fascicular growth pattern with admixed foam cells, multinucleate cells, and inflammatory cells in varying proportions. Histologic variants included 11 cellular (2 with mixed atypical and cellular features), 2 aneurysmal, 1 atypical, and 1 epithelioid type. All tumors showed entrapment of hyalinized collagen bundles. Mitotic activity ranged from <1 to 13/10 HPF. Focal necrosis was seen in 1 primary tumor. Ten patients had local tumor recurrence; 4 patients had multiple local recurrences. Time to first recurrence ranged from 6 weeks to 13 years. The local recurrences of 1 tumor showed increased cytologic atypia, but recurrences were otherwise morphologically similar to primary tumors. Metastases occurred 0 to 180 months after diagnosis (median 17 mo) and involved the lungs (12 patients), lymph nodes (8), soft tissues (6), and liver (1). Five patients developed multiple satellite nodules in the region of the primary tumor. Metastases were morphologically similar to the primary tumors. So far, 6 patients died of disease, with a median time to death of 64 months (range, 10 to 168 mo). Four patients are alive with metastatic disease. Two patients are disease free at last follow-up, and 1 patient died of unrelated disease. Metastasis of morphologically benign cutaneous FH is an extremely rare but clinically aggressive event. Primary tumors tend to be large and cellular, but aggressive behavior cannot be predicted on morphologic grounds alone; however, early or frequent local recurrence may warrant closer clinical follow-up.


Pailoor J, Mun KS, Leow M
Cutaneous malignant melanoma: clinical and histopathological review of cases in a Malaysian tertiary referral centre.
Malays J Pathol. 2012; 34(2):97-101 [PubMed]
Melanoma is a lethal skin cancer that occurs predominantly among Caucasians. In Malaysia, the incidence of melanoma is low. This is a retrospective study of clinical and histopathological features of patients with cutaneous melanoma who were seen at the University Malaya Medical Centre from 1998 to 2008. Thirty-two patients with cutaneous melanoma were recorded during that period. Of these, 24 had sought treatment at the onset of disease at our centre. Chinese patients constituted the largest group (19 cases). The median age of these 24 patients at the time of presentation was 62 years. 16 patients had melanoma involving the lower limb with 12 affecting the sole of the foot. None had melanoma arising from the face. Histopathology showed nodular melanoma in 22 cases (91.6%), with superficial spreading and acral lentiginous melanoma diagnosed in 1 case each. The majority of patients (62.5%) were found to be in Stage III of the disease at the time of diagnosis.


Ibrahim ZA, Narihan MZ, Ojep DN, et al.
Cyclin D1 expression in acral melanoma: a case control study in Sarawak.
Malays J Pathol. 2012; 34(2):89-95 [PubMed]
Acral melanoma has been reported to have distinctive clinical presentation and ethnic distribution compared to other histological types of malignant melanoma. Acral melanoma also exhibits distinctive focused gene amplifications, including cyclin D1 overexpression. We reviewed archived histological material of malignant melanoma in the Sarawak General Hospital from year 2004 to 2010. 43 tumours, comprising 28 acral melanoma and 15 non-acral melanoma, had sufficient material to be included in the study. The majority (36%) of acral melanoma tumours occurred in the heel. The tumours were analyzed for cyclin D1 expression by immunohistochemistry. 68% of acral melanoma were cyclin D1 positive compared to a positivity of 33% in non-acral tumours. This difference was statistically significant (p < 0.05). This finding may improve the histological diagnosis of acral melanoma and detection of positive resection margins.


Matin RN, Chikh A, Chong SL, et al.
p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis.
J Exp Med. 2013; 210(3):581-603 [PubMed] Article available free on PMC after 11/09/2013
The role of apoptosis in melanoma pathogenesis and chemoresistance is poorly characterized. Mutations in TP53 occur infrequently, yet the TP53 apoptotic pathway is often abrogated. This may result from alterations in TP53 family members, including the TP53 homologue TP63. Here we demonstrate that TP63 has an antiapoptotic role in melanoma and is responsible for mediating chemoresistance. Although p63 was not expressed in primary melanocytes, up-regulation of p63 mRNA and protein was observed in melanoma cell lines and clinical samples, providing the first evidence of significant p63 expression in this lineage. Upon genotoxic stress, endogenous p63 isoforms were stabilized in both nuclear and mitochondrial subcellular compartments. Our data provide evidence of a physiological interaction between p63 with p53 whereby translocation of p63 to the mitochondria occurred through a codependent process with p53, whereas accumulation of p53 in the nucleus was prevented by p63. Using RNA interference technology, both isoforms of p63 (TA and ΔNp63) were demonstrated to confer chemoresistance, revealing a novel oncogenic role for p63 in melanoma cells. Furthermore, expression of p63 in both primary and metastatic melanoma clinical samples significantly correlated with melanoma-specific deaths in these patients. Ultimately, these observations provide a possible explanation for abrogation of the p53-mediated apoptotic pathway in melanoma, implicating novel approaches aimed at sensitizing melanoma to therapeutic agents.


Shenoy S, Cassim R
Metastatic melanoma to the gastrointestinal tract: role of surgery as palliative treatment.
W V Med J. 2013 Jan-Feb; 109(1):30-3 [PubMed]
BACKGROUND: Malignant melanoma is an uncommon metastatic tumor found in the gastrointestinal tract but most commonly involves the small bowel. Less than 5% of patients with metastases to the gastrointestinal tract are diagnosed antemortem. Clinical presentation could be an acute abdominal emergency such as a bowel obstruction, intussusception, bleeding and perforation or chronic symptoms with weight loss, abdominal pain and anemia.
METHODS: We report two unusual cases with acute gastrointestinal complications related to metastatic melanoma. Case 1 developed acute upper gastrointestinal bleeding and was diagnosed with gastric mass. Biopsy revealed metastatic melanoma. The patient died of his advanced disease. Case 2 with unknown primary melanoma presented with acute abdomen secondary to small bowel perforation. He underwent laparotomy and small bowel resection with palliative intent. The patient remains alive and free of symptoms at 4 year follow up.
CONCLUSIONS: Metastatic melanoma of the gastrointestinal tract should be suspected in any patient with history of cutaneous melanoma and new gastrointestinal symptoms. Surgical interventions for symptomatic patients with melanoma of the gastrointestinal tract significantly relieve pain and improve quality of life and may confer a survival advantage.


Koo E, Walsh A, Dickson H
Red flags and alarm bells: an atypical lesion masquerading as a diabetic foot ulcer.
J Wound Care. 2012; 21(11):550, 552 [PubMed]
An 88-year-old male presented at a high-risk foot service with a non-healing, plantar wound on his right foot, which had the appearance of a neuropathic ulcer. On further examination, the lesion was confirmed asymmetrical in shape and atypical in appearance. It also presented with surrounding violaceous, pigmented nodules in the arch of the foot, and several small, similar nodules on the plantar surface of the contralateral foot, giving the appearance of an exophytic lesion and suggesting melanoma. Following biopsy, it was diagnosed as classic Kaposi sarcoma.


Yao Y, Mark LA
Woringer-Kolopp disease mimicking foot dermatitis.
Cutis. 2012; 90(6):307-9, 316 [PubMed]
Woringer-Kolopp disease, also known as localized pagetoid reticulosis, is a rare cutaneous lymphoproliferative disorder classified as a solitary variant of mycosis fungoides (MF). Despite the indolent and benign nature of the disease, misdiagnosis and inappropriate treatment may result in years of debilitating symptoms and even loss of function. We present the case of a patient with long-standing Woringer-Kolopp disease that mimicked foot dermatitis. Histopathologic examination demonstrated epidermotropic infiltration of atypical lymphocytes that were CD3+ CD4- CD8-. The patient was successfully treated with topical keratolytics and bexarotene gel 1% with minimal residual lesions after 8 years of follow-up. We discuss the characteristics of this rare disease in contrast with localized MF as well as more aggressive forms of epidermotropic T-cell lymphoma.


de Morais OO, de Araújo LC, Gomes CM, et al.
Congenital dermatofibrosarcoma protuberans.
Cutis. 2012; 90(6):285-8 [PubMed]
Congenital dermatofibrosarcoma protuberans (DFSP) is a rare dermal and subcutaneous neoplasm of low-grade malignant behavior that is characterized by a low frequency of metastases with locally invasive growth. Its occurrence at birth and during childhood is rare. We present a case of a patient who was born with a light brown macule on his right buttock that was misdiagnosed as localized scleroderma. The lesion progressed into reddish atrophic plaques and nodules extending to the iliac region and the gluteal fold. At 5 years of age, a diagnosis of congenital DFSP was made based on clinical and immunohistochemical characteristics (CD34 positivity and spindle cell proliferation). Although there was a delay in diagnosis, a 3-step excision was proposed with a final step of Mohs micrographic surgery (MMS).


O'Day SJ, Eggermont AM, Chiarion-Sileni V, et al.
Final results of phase III SYMMETRY study: randomized, double-blind trial of elesclomol plus paclitaxel versus paclitaxel alone as treatment for chemotherapy-naive patients with advanced melanoma.
J Clin Oncol. 2013; 31(9):1211-8 [PubMed]
PURPOSE: Elesclomol, an investigational first-in-class compound, induces oxidative stress, triggers mitochondrial-induced apoptosis in cancer cells, and shows synergy with taxanes in tumor models. Following completion of a phase II trial of elesclomol in combination with paclitaxel that met its primary end point of progression-free survival (PFS), this randomized, double-blind, controlled phase III study was conducted to confirm the efficacy and tolerability of elesclomol in combination with paclitaxel versus paclitaxel alone in patients with advanced melanoma.
PATIENTS AND METHODS: Patients with stage IV chemotherapy-naive melanoma (n = 651) were randomly assigned 1:1 to paclitaxel 80 mg/m(2) either alone or in combination with elesclomol 213 mg/m(2) administered weekly for 3 weeks of a 4-week cycle. Patients were stratified by prior systemic treatment, M1 subclass, and baseline lactate dehydrogenase (LDH) levels. The primary end point was PFS.
RESULTS: The study did not achieve its PFS end point (hazard ratio, 0.89; P = .23). The study was stopped when an early overall survival data analysis indicated an imbalance in total deaths favoring paclitaxel, predominantly in patients with high LDH levels. A prospectively defined subgroup analysis revealed a statistically significant improvement in median PFS for the combination in patients with normal baseline LDH.
CONCLUSION: The addition of elesclomol to paclitaxel did not significantly improve PFS in unselected patients with advanced melanoma. The association between baseline LDH and clinical outcomes suggests that LDH may be a predictive factor for treatment with this combination, consistent with recent findings on the association between elesclomol anticancer activity and cellular metabolic state.


Müller D, Manojlović S, Luksić I, Grgurević J
Calcifying epithelial odontogenic tumor of the maxilla (Pindborg tumor).
Coll Antropol. 2012; 36 Suppl 2:205-8 [PubMed]
Calcifying epithelial odontogenic tumor (CEOT), or the Pindborg tumor, is very rare neoplasm, which accounts up to 1% of all odontogenic tumors. These tumors involve mandible almost twice as common as the maxillary bone, mostly in the premolar and molar region and present at first with local swelling. There is no gender predilection and the tumor usually appears between 2nd and 6th decade of life. We report the case of a 36-year-old male patient with a Pindborg tumor in the maxillary region on the right side, also involving the adjacent maxillary sinus, with destroying of the local anatomical structures. Complete surgical excision of the tumor has been performed and four years after surgical treatment, there is no sign of recurrence.


Hyter S, Indra AK
Nuclear hormone receptor functions in keratinocyte and melanocyte homeostasis, epidermal carcinogenesis and melanomagenesis.
FEBS Lett. 2013; 587(6):529-41 [PubMed]
Skin homeostasis is maintained, in part, through regulation of gene expression orchestrated by type II nuclear hormone receptors in a cell and context specific manner. This group of transcriptional regulators is implicated in various cellular processes including epidermal proliferation, differentiation, permeability barrier formation, follicular cycling and inflammatory responses. Endogenous ligands for the receptors regulate actions during skin development and maintenance of tissue homeostasis. Type II nuclear receptor signaling is also important for cellular crosstalk between multiple cell types in the skin. Overall, these nuclear receptors are critical players in keratinocyte and melanocyte biology and present targets for cutaneous disease management.


This page last updated: 22nd May 2013
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