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Molecular Pathology of Cutaneous Melanoma and Nonmelanoma Skin Cancer

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Molecular Surgical Pathology

Abstract

Recent data indicate that the dramatic rise in incidence of skin cancers recorded in the last decades is still in progress. According to the National Cancer Institute, more than one million cases of cutaneous malignancies were diagnosed in the USA in 2009, with these estimates likely to be exceedingly conservative. Analogous trends have been observed worldwide, posing a considerable socioeconomic burden especially in Western countries; these numbers are all the more striking as incidence rates for the majority of other cancers are either steady or decreasing. Although nonmelanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), accounts for up to 90 % of all skin cancer cases, also cutaneous melanoma (CM) incidence is constantly on the rise; importantly, prognosis of advanced melanoma is still dismal, with 5-year survival rates for patients with metastatic disease below 10 %. Meanwhile, substantial scientific advances have been made in pathology, genetics, and basic research of skin cancer, dramatically altering the approach in diagnosing and treating both CM and NMSC. Novel insights have been gained regarding inherited determinants of predisposition to skin neoplasms, mechanisms of ultraviolet light (UV)-induced oncogenesis, and molecular pathways regulating cutaneous cancer onset and progression; sizeable progress has been made also in understanding the pathogenesis of less common cutaneous malignancies, including adnexal neoplasms, Merkel cell carcinoma (MCC), and dermatofibrosarcoma protuberans (DFSP). The once prevailing concept that cancer simply stems from the unregulated proliferation of a monoclonal and homogenous cell population is being replaced by a more complex notion, viewing tumors as heterogeneous collections of multiple subpopulations with different genetic background, molecular features, and responsiveness to external stimuli. Accordingly, established diagnostic classifications and prognostic schemes are being revisited in light of recent molecular discoveries, new therapeutic agents are being developed targeting key drivers in skin cancer pathogenesis, and molecular diagnostics are becoming integral part of patients’ management. The recent introduction of next generation genomics techniques and their rapid diffusion are destined to further revolutionize this field. We propose an extensive overview of the molecular pathways involved in UV-induced oncogenesis as well as pathogenesis of CM; further, we offer a comprehensive synopsis of the molecular pathology of NMSC (including BCC as well as SCC and related precursors), selected adnexal neoplasms, MCC, and DFSP.

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Suggested Reading

Ultraviolet Light and Skin Cancer

  • Abdel-Malek ZA, Kadekaro AL, Swope VB (2010) Stepping up melanocytes to the challenge of UV exposure. Pigment Cell Melanoma Res 23:171–86

    Article  CAS  PubMed  Google Scholar 

  • Autier P, Dore JF, Eggermont AM et al (2011) Epidemiological evidence that UVA radiation is involved in the genesis of cutaneous melanoma. Curr Opin Oncol 23:189–96

    Article  PubMed  Google Scholar 

  • Gerstenblith MR, Shi J, Landi MT (2010) Genome-wide association studies of pigmentation and skin cancer: a review and meta-analysis. Pigment Cell Melanoma Res 23:587–606

    Article  CAS  PubMed  Google Scholar 

  • Kappes UP, Luo D, Potter M et al (2006) Short- and ­long-wave UV light (UVB and UVA) induce similar mutations in human skin cells. J Invest Dermatol 126:667–75

    Article  CAS  PubMed  Google Scholar 

  • Narayanan DL, Saladi RN, Fox JL (2010) Ultraviolet radiation and skin cancer. Int J Dermatol 49:978–86

    Article  PubMed  Google Scholar 

  • Runger TM (2007) How different wavelengths of the ultraviolet spectrum contribute to skin carcinogenesis: the role of cellular damage responses. J Invest Dermatol 127:2103–5

    Article  PubMed  CAS  Google Scholar 

  • Runger TM (2008) C–  >  T transition mutations are not solely UVB-signature mutations, because they are also generated by UVA. J Invest Dermatol 128:2138–40

    Article  CAS  PubMed  Google Scholar 

  • Runger TM (2011) Is UV-induced mutation formation in melanocytes different from other skin cells? Pigment Cell Melanoma Res 24:10–2

    Article  PubMed  CAS  Google Scholar 

  • Runger TM, Kappes UP (2008) Mechanisms of mutation formation with long-wave ultraviolet light (UVA). Photodermatol Photoimmunol Photomed 24:2–10

    Article  CAS  PubMed  Google Scholar 

  • von Thaler AK, Kamenisch Y, Berneburg M (2010) The role of ultraviolet radiation in melanomagenesis. Exp Dermatol 19:81–8

    Article  CAS  Google Scholar 

Melanoma

  • Barrett JH, Iles MM, Harland M et al (2011) Genome-wide association study identifies three new melanoma susceptibility loci. Nat Genet 43:1108–13

    Article  CAS  PubMed  Google Scholar 

  • Bastian BC, Kashani-Sabet M, Hamm H et al (2000a) Gene amplifications characterize acral melanoma and permit the detection of occult tumor cells in the surrounding skin. Cancer Res 60:1968–73

    CAS  PubMed  Google Scholar 

  • Bastian BC, LeBoit PE, Pinkel D (2000b) Mutations and copy number increase of HRAS in Spitz nevi with distinctive histopathological features. Am J Pathol 157:967–72

    Article  CAS  PubMed  Google Scholar 

  • Bastian BC, Olshen AB, LeBoit PE et al (2003) Classifying melanocytic tumors based on DNA copy number changes. Am J Pathol 163:1765–70

    Article  CAS  PubMed  Google Scholar 

  • Bastian BC, Xiong J, Frieden IJ et al (2002) Genetic changes in neoplasms arising in congenital melanocytic nevi: differences between nodular proliferations and melanomas. Am J Pathol 161:1163–9

    Article  CAS  PubMed  Google Scholar 

  • Bauer J, Bastian BC (2006) Distinguishing melanocytic nevi from melanoma by DNA copy number changes: comparative genomic hybridization as a research and diagnostic tool. Dermatol Ther 19:40–9

    Article  PubMed  Google Scholar 

  • Bauer J, Buttner P, Murali R et al (2011) BRAF mutations in cutaneous melanoma are independently associated with age, anatomic site of the primary tumor, and the degree of solar elastosis at the primary tumor site. Pigment Cell Melanoma Res 24:345–51

    Article  CAS  PubMed  Google Scholar 

  • Bauer J, Curtin JA, Pinkel D et al (2007) Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations. J Invest Dermatol 127:179–82

    Article  CAS  PubMed  Google Scholar 

  • Bertolotto C, Lesueur F, Giuliano S et al (2011) A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma. Nature 480:94–8

    Article  CAS  PubMed  Google Scholar 

  • Bogenrieder T, Herlyn M (2011) The molecular pathology of cutaneous melanoma. Cancer Biomark 9:267–86

    Google Scholar 

  • Broekaert SM, Roy R, Okamoto I et al (2010) Genetic and morphologic features for melanoma classification. Pigment Cell Melanoma Res 23:763–70

    Article  CAS  PubMed  Google Scholar 

  • Busam KJ (2011) Desmoplastic melanoma. Clin Lab Med 31:321–30

    Article  PubMed  Google Scholar 

  • Carvajal RD, Antonescu CR, Wolchok JD et al (2011) KIT as a therapeutic target in metastatic melanoma. JAMA 305:2327–34

    Article  CAS  PubMed  Google Scholar 

  • Cerroni L, Barnhill R, Elder D et al (2010) Melanocytic tumors of uncertain malignant potential: results of a tutorial held at the XXIX Symposium of the International Society of Dermatopathology in Graz, October 2008. Am J Surg Pathol 34:314–26

    Article  PubMed  Google Scholar 

  • Cheli Y, Ohanna M, Ballotti R et al (2010) Fifteen-year quest for microphthalmia-associated transcription ­factor target genes. Pigment Cell Melanoma Res 23:27–40

    Article  CAS  PubMed  Google Scholar 

  • Cronin JC, Wunderlich J, Loftus SK et al (2009) Frequent mutations in the MITF pathway in melanoma. Pigment Cell Melanoma Res 22:435–44

    Article  CAS  PubMed  Google Scholar 

  • Curtin JA, Busam K, Pinkel D et al (2006) Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol 24:4340–6

    Article  CAS  PubMed  Google Scholar 

  • Curtin JA, Fridlyand J, Kageshita T et al (2005) Distinct sets of genetic alterations in melanoma. N Engl J Med 353:2135–47

    Article  CAS  PubMed  Google Scholar 

  • Duffy DL, Iles MM, Glass D et al (2010) IRF4 variants have age-specific effects on nevus count and predispose to melanoma. Am J Hum Genet 87:6–16

    Article  CAS  PubMed  Google Scholar 

  • Dutton-Regester K, Hayward NK (2012) Reviewing the somatic genetics of melanoma: from current to future analytical approaches. Pigment Cell Melanoma Res 25:144–54

    Article  CAS  PubMed  Google Scholar 

  • Fargnoli MC, Pike K, Pfeiffer RM et al (2008) MC1R variants increase risk of melanomas harboring BRAF mutations. J Invest Dermatol 128:2485–90

    Article  CAS  PubMed  Google Scholar 

  • Flaherty KT, Hodi FS, Bastian BC (2010) Mutation-driven drug development in melanoma. Curr Opin Oncol 22:178–83

    Article  CAS  PubMed  Google Scholar 

  • Gammon B, Beilfuss B, Guitart J et al (2012) Enhanced detection of spitzoid melanomas using fluorescence in situ hybridization with 9p21 as an adjunctive probe. Am J Surg Pathol 36:81–8

    Article  PubMed  Google Scholar 

  • Garrido MC, Bastian BC (2010) KIT as a therapeutic target in melanoma. J Invest Dermatol 130:20–7

    Article  CAS  PubMed  Google Scholar 

  • Gerami P, Jewell SS, Morrison LE et al (2009) Fluorescence in situ hybridization (FISH) as an ancillary diagnostic tool in the diagnosis of melanoma. Am J Surg Pathol 33:1146–56

    Article  PubMed  Google Scholar 

  • Gerami P, Jewell SS, Pouryazdanparast P et al (2011) Copy number gains in 11q13 and 8q24 [corrected] are highly linked to prognosis in cutaneous malignant melanoma. J Mol Diagn 13:352–8

    Article  CAS  PubMed  Google Scholar 

  • Gerami P, Zembowicz A (2011) Update on fluorescence in situ hybridization in melanoma: state of the art. Arch Pathol Lab Med 135:830–7

    PubMed  Google Scholar 

  • Harbour JW (2012) The genetics of uveal melanoma: an emerging framework for targeted therapy. Pigment Cell Melanoma Res 25:171–81

    Article  CAS  PubMed  Google Scholar 

  • Harbour JW, Onken MD, Roberson ED et al (2010) Frequent mutation of BAP1 in metastasizing uveal melanomas. Science 330:1410–3

    Article  CAS  PubMed  Google Scholar 

  • Hill SJ, Delman KA. Pediatric melanomas and the atypical spitzoid melanocytic neoplasms. Am J Surg. 2011 [Epub ahead of print].

    Google Scholar 

  • Macgregor S, Montgomery GW, Liu JZ et al (2011) Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3. Nat Genet 43:1114–8

    Article  CAS  PubMed  Google Scholar 

  • Maize JC Jr, McCalmont TH, Carlson JA et al (2005) Genomic analysis of blue nevi and related dermal melanocytic proliferations. Am J Surg Pathol 29:1214–20

    Article  PubMed  Google Scholar 

  • Murali R, Zannino D, Synnott M et al (2011) Clinical and pathological features of metastases of primary cutaneous desmoplastic melanoma. Histopathology 58:886–95

    Article  PubMed  Google Scholar 

  • Newton-Bishop J, Gruis N (2010) Melanoma susceptibility genes. Melanoma Res 20:161–2

    Article  PubMed  Google Scholar 

  • North JP, Kageshita T, Pinkel D et al (2008) Distribution and significance of occult intraepidermal tumor cells surrounding primary melanoma. J Invest Dermatol 128:2024–30

    Article  CAS  PubMed  Google Scholar 

  • North JP, Vetto JT, Murali R et al (2011) Assessment of copy number status of chromosomes 6 and 11 by FISH provides independent prognostic information in primary melanoma. Am J Surg Pathol 35:1146–50

    Article  PubMed  Google Scholar 

  • Pouryazdanparast P, Cowen DP, Beilfuss BA et al (2012) Distinctive clinical and histologic features in cutaneous melanoma with copy number gains in 8q24. Am J Surg Pathol 36:253–64

    Article  PubMed  Google Scholar 

  • Prickett TD, Agrawal NS, Wei X et al (2009) Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4. Nat Genet 41:1127–32

    Article  CAS  PubMed  Google Scholar 

  • Scolyer RA, Long GV, Thompson JF (2011) Evolving concepts in melanoma classification and their relevance to multidisciplinary melanoma patient care. Mol Oncol 5:124–36

    Article  PubMed  Google Scholar 

  • Stark MS, Woods SL, Gartside MG et al (2011) Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing. Nat Genet 44:165–9

    Article  PubMed  CAS  Google Scholar 

  • Thomas AJ, Erickson CA (2008) The making of a melanocyte: the specification of melanoblasts from the neural crest. Pigment Cell Melanoma Res 21:598–610

    Article  CAS  PubMed  Google Scholar 

  • Van Raamsdonk CD, Bezrookove V, Green G et al (2009) Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 457:599–602

    Article  PubMed  CAS  Google Scholar 

  • Van Raamsdonk CD, Griewank KG, Crosby MB et al (2010) Mutations in GNA11 in uveal melanoma. N Engl J Med 363:2191–9

    Article  PubMed  Google Scholar 

  • Viros A, Fridlyand J, Bauer J et al (2008) Improving melanoma classification by integrating genetic and morphologic features. PLoS Med 5:e120

    Article  PubMed  CAS  Google Scholar 

  • Walia V, Mu EW, Lin JC, Samuels Y (2012) Delving into somatic variation in sporadic melanoma. Pigment Cell Melanoma Res 25:155–70

    Article  CAS  PubMed  Google Scholar 

  • Wei X, Walia V, Lin JC et al (2011) Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat Genet 43:442–6

    Article  CAS  PubMed  Google Scholar 

  • Whiteman DC, Pavan WJ, Bastian BC (2011) The melanomas: a synthesis of epidemiological, clinical, histopathological, genetic, and biological aspects, supporting distinct subtypes, causal pathways, and cells of origin. Pigment Cell Melanoma Res 24:879–97

    Article  CAS  PubMed  Google Scholar 

  • Wiesner T, Obenauf AC, Murali R et al (2011) Germline mutations in BAP1 predispose to melanocytic tumors. Nat Genet 43:1018–21

    Article  CAS  PubMed  Google Scholar 

  • Williams PF, Olsen CM, Hayward NK et al (2011) Melanocortin 1 receptor and risk of cutaneous melanoma: a meta-analysis and estimates of population burden. Int J Cancer 129:1730–40

    Article  CAS  PubMed  Google Scholar 

  • Worley LA, Onken MD, Person E et al (2007) Transcriptomic versus chromosomal prognostic markers and clinical outcome in uveal melanoma. Clin Cancer Res 13:1466–71

    Article  CAS  PubMed  Google Scholar 

  • Yokoyama S, Woods SL, Boyle GM et al (2011) A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma. Nature 480:99–103

    Article  CAS  PubMed  Google Scholar 

Nonmelanoma Skin Cancer

  • Arnault JP, Mateus C, Escudier B et al (2012) Skin tumors induced by sorafenib; paradoxic RAS-RAF pathway activation and oncogenic mutations of HRAS, TP53, and TGFBR1. Clin Cancer Res 18:263–72

    Article  CAS  PubMed  Google Scholar 

  • Arron ST, Ruby JG, Dybbro E et al (2011) Transcriptome sequencing demonstrates that human papillomavirus is not active in cutaneous squamous cell carcinoma. J Invest Dermatol 131:1745–53

    Article  CAS  PubMed  Google Scholar 

  • Barakat MT, Humke EW, Scott MP (2010) Learning from Jekyll to control Hyde: Hedgehog signaling in development and cancer. Trends Mol Med 16:337–48

    Article  CAS  PubMed  Google Scholar 

  • Botti E, Spallone G, Moretti F et al (2011) Developmental factor IRF6 exhibits tumor suppressor activity in squamous cell carcinomas. Proc Natl Acad Sci USA 108:13710–5

    Article  CAS  PubMed  Google Scholar 

  • Durinck S, Ho C, Wang NJ et al (2011) Temporal dissection of tumorigenesis in primary cancers. Cancer Discov 1:137–43

    Article  CAS  PubMed  Google Scholar 

  • Epstein EH (2008) Basal cell carcinomas: attack of the hedgehog. Nat Rev Cancer 8:743–54

    Article  CAS  PubMed  Google Scholar 

  • Epstein EH Jr (2011) Mommy - where do tumors come from? J Clin Invest 121:1681–3

    Article  CAS  PubMed  Google Scholar 

  • Han J, Qureshi AA, Nan H et al (2011) A germline variant in the interferon regulatory factor 4 gene as a novel skin cancer risk locus. Cancer Res 71:1533–9

    Article  CAS  PubMed  Google Scholar 

  • Hooper JE, Scott MP (2005) Communicating with Hedgehogs. Nat Rev Mol Cell Biol 6:306–17

    Article  CAS  PubMed  Google Scholar 

  • Kasper M, Jaks V, Hohl D et al (2012) Basal cell carcinoma - molecular biology and potential new therapies. J Clin Invest 122:455–63

    Article  CAS  PubMed  Google Scholar 

  • Marchetti A, Felicioni L, Malatesta S et al (2011) Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J Clin Oncol 29:3574–9

    Article  CAS  PubMed  Google Scholar 

  • Marinari B, Ballaro C, Koster MI et al (2009) IKKalpha is a p63 transcriptional target involved in the pathogenesis of ectodermal dysplasias. J Invest Dermatol 129:60–9

    Article  CAS  PubMed  Google Scholar 

  • Mikkola ML, Costanzo A, Thesleff I et al (2010) Treasure or artifact: a decade of p63 research speaks for itself. Cell Death Differ 17:180–3

    Article  CAS  PubMed  Google Scholar 

  • Nan H, Kraft P, Hunter DJ et al (2009) Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians. Int J Cancer 125:909–17

    Article  CAS  PubMed  Google Scholar 

  • Nan H, Xu M, Kraft P et al (2011) Genome-wide association study identifies novel alleles associated with risk of cutaneous basal cell carcinoma and squamous cell carcinoma. Hum Mol Genet 20:3718–24

    Article  CAS  PubMed  Google Scholar 

  • Park E, Liu B, Xia X et al (2011) Role of IKKalpha in skin squamous cell carcinomas. Future Oncol 7:123–34

    Article  CAS  PubMed  Google Scholar 

  • Ratushny V, Gober MD, Hick R et al (2012) From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma. J Clin Invest 122:464–72

    Article  CAS  PubMed  Google Scholar 

  • Sellheyer K (2011) Basal cell carcinoma: cell of origin, cancer stem cell hypothesis and stem cell markers. Br J Dermatol 164:696–711

    Article  CAS  PubMed  Google Scholar 

  • Tang T, Tang JY, Li D et al (2011) Targeting superficial or nodular basal cell carcinoma with topically formulated small molecule inhibitor of smoothened. Clin Cancer Res 17:3378–87

    Article  CAS  PubMed  Google Scholar 

  • Wang GY, Wang J, Mancianti ML et al (2011a) Basal cell carcinomas arise from hair follicle stem cells in Ptch1(+/−) mice. Cancer Cell 19:114–24

    Article  CAS  PubMed  Google Scholar 

  • Wang NJ, Sanborn Z, Arnett KL et al (2011b) Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma. Proc Natl Acad Sci U S A 108:17761–6

    Article  CAS  PubMed  Google Scholar 

  • Wu X, Nguyen BC, Dziunycz P et al (2010) Opposing roles for calcineurin and ATF3 in squamous skin cancer. Nature 465:368–72

    Article  CAS  PubMed  Google Scholar 

Cutaneous Adnexal Neoplasms

  • Almeida S, Maillard C, Itin P et al (2008) Five new CYLD mutations in skin appendage tumors and evidence that aspartic acid 681 in CYLD is essential for deubiquitinase activity. J Invest Dermatol 128:587–93

    CAS  PubMed  Google Scholar 

  • Fehr A, Kovacs A, Loning T et al (2011) The MYB-NFIB gene fusion-a novel genetic link between adenoid cystic carcinoma and dermal cylindroma. J Pathol 224:322–7

    Article  CAS  PubMed  Google Scholar 

  • Gaskin BJ, Fernando BS, Sullivan CA et al (2011) The significance of DNA mismatch repair genes in the diagnosis and management of periocular sebaceous cell carcinoma and Muir-Torre syndrome. Br J Ophthalmol 95:1686–90

    Article  PubMed  Google Scholar 

  • Hafner C, Schmiemann V, Ruetten A et al (2007) PTCH mutations are not mainly involved in the pathogenesis of sporadic trichoblastomas. Hum Pathol 38:1496–500

    Article  CAS  PubMed  Google Scholar 

  • Kazakov DV, Sima R, Vanecek T et al (2009a) Mutations in exon 3 of the CTNNB1 gene (beta-catenin gene) in cutaneous adnexal tumors. Am J Dermatopathol 31:248–55

    Article  PubMed  Google Scholar 

  • Kazakov DV, Vanecek T, Zelger B et al (2011) Multiple (familial) trichoepitheliomas: a clinicopathological and molecular biological study, including CYLD and PTCH gene analysis, of a series of 16 patients. Am J Dermatopathol 33:251–65

    Article  PubMed  Google Scholar 

  • Kazakov DV, Zelger B, Rutten A et al (2009b) Morphologic diversity of malignant neoplasms arising in preexisting spiradenoma, cylindroma, and spiradenocylindroma based on the study of 24 cases, sporadic or occurring in the setting of Brooke-Spiegler syndrome. Am J Surg Pathol 33:705–19

    Article  PubMed  Google Scholar 

  • Ko CJ (2010) Muir-Torre syndrome: facts and controversies. Clin Dermatol 28(3):324–9

    Article  PubMed  Google Scholar 

  • Krahl D, Sellheyer K (2010) Basal cell carcinoma and pilomatrixoma mirror human follicular embryogenesis as reflected by their differential expression patterns of SOX9 and beta-catenin. Br J Dermatol 162:1294–301

    Article  CAS  PubMed  Google Scholar 

  • Landis MN, Davis CL, Bellus GA, et al. Immunosuppression and sebaceous tumors: a confirmed diagnosis of Muir-Torre syndrome unmasked by immunosuppressive therapy. J Am Acad Dermatol. 2011;65:1054–8 e1051.

    Google Scholar 

  • Massoumi R, Paus R (2007) Cylindromatosis and the CYLD gene: new lessons on the molecular principles of epithelial growth control. Bioessays 29:1203–14

    Article  CAS  PubMed  Google Scholar 

  • Mitani Y, Rao PH, Futreal PA et al (2011) Novel chromosomal rearrangements and break points at the t(6;9) in salivary adenoid cystic carcinoma: association with MYB-NFIB chimeric fusion, MYB expression, and clinical outcome. Clin Cancer Res 17:7003–14

    Article  CAS  PubMed  Google Scholar 

  • Niemann C, Owens DM, Schettina P et al (2007) Dual role of inactivating Lef1 mutations in epidermis: tumor promotion and specification of tumor type. Cancer Res 67:2916–21

    Article  CAS  PubMed  Google Scholar 

  • Rajan N, Langtry JA, Ashworth A et al (2009) Tumor mapping in 2 large multigenerational families with CYLD mutations: implications for disease management and tumor induction. Arch Dermatol 145:1277–84

    Article  CAS  PubMed  Google Scholar 

  • Shalin SC, Lyle S, Calonje E et al (2010) Sebaceous neoplasia and the Muir-Torre syndrome: important connections with clinical implications. Histopathology 56:133–47

    Article  PubMed  Google Scholar 

  • Sima R, Vanecek T, Kacerovska D et al (2010) Brooke-Spiegler syndrome: report of 10 patients from 8 families with novel germline mutations: evidence of diverse somatic mutations in the same patient regardless of tumor type. Diagn Mol Pathol 19:83–91

    Article  PubMed  Google Scholar 

  • Takeda H, Lyle S, Lazar AJ et al (2006) Human sebaceous tumors harbor inactivating mutations in LEF1. Nat Med 12:395–7

    Article  CAS  PubMed  Google Scholar 

  • Xia J, Urabe K, Moroi Y et al (2006) beta-Catenin mutation and its nuclear localization are confirmed to be frequent causes of Wnt signaling pathway activation in pilomatricomas. J Dermatol Sci 41:67–75

    Article  CAS  PubMed  Google Scholar 

Merkel Cell Carcinoma

  • Houben R, Adam C, Baeurle A et al (2012a) An intact retinoblastoma protein-binding site in Merkel cell polyomavirus large T antigen is required for promoting growth of Merkel cell carcinoma cells. Int J Cancer 130:847–56

    Article  CAS  PubMed  Google Scholar 

  • Houben R, Grimm J, Willmes C et al (2012b) Merkel cell carcinoma and Merkel cell polyomavirus: evidence for hit-and-run oncogenesis. J Invest Dermatol 132:254–6

    Article  CAS  PubMed  Google Scholar 

  • Houben R, Shuda M, Weinkam R et al (2010) Merkel cell polyomavirus-infected Merkel cell carcinoma cells require expression of viral T antigens. J Virol 84:7064–72

    Article  CAS  PubMed  Google Scholar 

  • Paulson KG, Carter JJ, Johnson LG et al (2010) Antibodies to merkel cell polyomavirus T antigen oncoproteins reflect tumor burden in merkel cell carcinoma patients. Cancer Res 70:8388–97

    Article  CAS  PubMed  Google Scholar 

  • Rollison DE, Giuliano AR, Becker JC (2010) New virus associated with merkel cell carcinoma development. J Natl Compr Canc Netw 8:874–80

    PubMed  Google Scholar 

  • Schrama D, Becker JC (2011) Merkel cell carcinoma–pathogenesis, clinical aspects and treatment. J Eur Acad Dermatol Venereol 25:1121–9

    Article  CAS  PubMed  Google Scholar 

  • Schrama D, Peitsch WK, Zapatka M et al (2011) Merkel cell polyomavirus status is not associated with clinical course of Merkel cell carcinoma. J Invest Dermatol 131:1631–8

    Article  CAS  PubMed  Google Scholar 

  • Schrama D, Ugurel S, Becker JC (2012) Merkel cell carcinoma: recent insights and new treatment options. Curr Opin Oncol 24:141–9

    Article  PubMed  Google Scholar 

  • Wang TS, Byrne PJ, Jacobs LK et al (2011c) Merkel cell carcinoma: update and review. Semin Cutan Med Surg 30:48–56

    Article  PubMed  CAS  Google Scholar 

  • Wong HH, Wang J (2010) Merkel cell carcinoma. Arch Pathol Lab Med 134:1711–6

    PubMed  Google Scholar 

Dermatofibrosarcoma Protuberans

  • Bogucki B, Neuhaus I, Hurst EA. Dermatofibrosarcoma protuberans: a review of the literature. Dermatol Surg. 2012 [Epub ahead of print].

    Google Scholar 

  • Llombart B, Monteagudo C, Sanmartin O et al (2011) Dermatofibrosarcoma protuberans: a clinicopathological, immunohistochemical, genetic (COL1A1-PDGFB), and therapeutic study of low-grade versus high-grade (fibrosarcomatous) tumors. J Am Acad Dermatol 65:564–75

    Article  CAS  PubMed  Google Scholar 

  • Llombart B, Sanmartin O, Lopez-Guerrero JA et al (2009) Dermatofibrosarcoma protuberans: clinical, pathological, and genetic (COL1A1-PDGFB ) study with therapeutic implications. Histopathology 54:860–72

    Article  PubMed  Google Scholar 

  • Salgado R, Llombart B, Ramon MP et al (2011) Molecular diagnosis of dermatofibrosarcoma protuberans: a comparison between reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization methodologies. Genes Chromosomes Cancer 50:510–7

    Article  CAS  PubMed  Google Scholar 

  • Segura S, Salgado R, Toll A et al (2011) Identification of t(17;22)(q22;q13) (COL1A1/PDGFB) in dermatofibrosarcoma protuberans by fluorescence in situ hybridization in paraffin-embedded tissue microarrays. Hum Pathol 42:176–84

    Article  CAS  PubMed  Google Scholar 

  • Tardio JC (2009) CD34-reactive tumors of the skin. An updated review of an ever-growing list of lesions. J Cutan Pathol 36:89–102

    Article  PubMed  Google Scholar 

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Saggini, A., Bastian, B. (2013). Molecular Pathology of Cutaneous Melanoma and Nonmelanoma Skin Cancer. In: Cheng, L., Eble, J. (eds) Molecular Surgical Pathology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4900-3_13

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