884 Correspondence

(PCR) with a primer pair for exon 5, as previously described.1 PCR products were separated by agarose gel electrophoresis, ren, puried with NucleoSpin Extract II (Macherey-Nagel, Du Germany), and directly sequenced with an ABI 3130 Genetic Analyzer (Life Technologies Applied Biosystems, Monza, Italy). We documented a rate of 100% sequence alignment in all samples, conrming the absence of the c.794T>C substitution and other major alterations. Even though we cannot rule out concurrent anomalies in the structural domains coded by the remaining four exons, our data suggest that BPDCN cases do not carry a mutation affecting TIR activity of MYD88. This observation parallels the absence of L265P mutations reported for acute myeloid leukaemia, myelomonocytic leukaemia, acute lymphoblastic leukaemia and multiple myeloma.13 Therefore, we think that the likely activation of NF-jB in BPDCN is MYD88 independent.

11 Shieh MP, Reisian N, Walavalkar V et al. Excessive therapeutic response in a case of blastic plasmacytoid dendritic cell neoplasm. Clin Adv Hematol Oncol 2012; 10:569. 12 Lucioni M, Novara F, Fiandrino G et al. Twenty-one cases of blastic plasmacytoid dendritic cell neoplasm: focus on biallelic locus 9p21.3 deletion. Blood 2011; 118:45914. 13 Je EM, Yoo NJ, Lee SH. Absence of MYD88 gene mutation in acute leukemias and multiple myelomas. Eur J Haematol 2012; 88:2734. Funding sources: Research Fund Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Conicts of interest: none declared.

Disparities in melanoma incidence rates in Europe

DOI: 10.1111/bjd.12054 MADAM, There has been an ongoing debate over the reasons for the rapid increase in incidence rates for cutaneous malignant melanoma over the past seven decades. Melanoma incidence rates have risen by a factor of 10 since 1940 in the U.S.A., and by a factor of ve since the mid-1950s in Northern Europe.1 Incidence rates appear to be still rising in Europe but may be stabilizing in some countries.2 However, melanoma mortality rates in Europe and elsewhere changed little between 1990 and 2006.3 Several papers have suggested that incidence rates have risen rapidly due to more frequent screening and identication of melanoma in situ. In the U.S.A., melanoma in situ comprised about 40% of melanoma incidence in 2006.4 In Germany, median tumour thickness decreased from 181 mm in 1976 to 053 mm in 2000 (P < 00001).5 However, as of 2008, the rate of in situ melanoma among diagnosed melanoma cases was only 15%.6 Indeed, a recent paper calls the recent trends in melanoma incidence a pseudo-epidemic due to improved criteria for diagnosis that allow melanomas to be recognized far more accurately and at earlier stages, and to overdiagnosis of melanoma.7 The recent paper by Forsea et al.8 suggested that countries in Central and Eastern Europe (CEE) may have missed opportunities for early melanoma diagnosis, compared with countries in the rest of Europe, although incomplete reporting in Eastern Europe cannot be ruled out. This suggestion is based on the fact that CEE had much lower melanoma incidence rates than most other European countries. While this suggestion is likely correct, it is questionable whether increasing screening in CEE would reduce melanoma mortality rates. Data from GLOBOCAN 2008 indicate that melanoma mortality rates for women in the CEE countries studied had very nearly the same latitudinal distribution as for the rest of Europe, with a slope of 00074 deaths per 100 000 per year per
2012 The Authors BJD 2012 British Association of Dermatologists

Anatomia Patologica, Dipartimento di Medicina ` di Pavia, and Fondazione Molecolare, Universita IRCCS Policlinico San Matteo, Pavia, Italy 2 Divisione di Ematologia, Department of Molecular ` di Pavia, Pavia, Italy Medicine, Universita 3 ` degli Studi Divisione di Dermatologia, Universita Milano-Bicocca, Milan, Italy E-mail: giacomo.andrino@gmail.com

G. FIANDRINO1 M. ARRA1 R. RIBONI1 M. LUCIONI1 E. DALLERA1 L. ARCAINI2 E. BERTI3 M. PAULLI1

References
1 Barchet W, Cella M, Colonna M. Plasmacytoid dendritic cells virus experts of innate immunity. Semin Immunol 2005; 17:25361. 2 Ngo VN, Young RM, Schmitz R et al. Oncogenically active MYD88 mutations in human lymphoma. Nature 2011; 470:11519. 3 Pham-Ledard A, Cappellen D, Martinez F et al. MYD88 somatic mutation is a genetic feature of primary cutaneous diffuse large B-cell lymphoma, leg type. J Invest Dermatol 2012; 132:211820. 4 Montesinos-Rongen M, Godlewska E, Brunn A et al. Activating L265P mutations of the MYD88 gene are common in primary central nervous system lymphoma. Acta Neuropathol 2011; 122:7912. 5 Yan Q, Huang Y, Watkins AJ et al. BCR and TLR signaling pathways are recurrently targeted by genetic changes in splenic marginal zone lymphomas. Haematologica 2012; 97:5958. 6 Wang L, Lawrence MS, Wan Y et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med 2011; 365:2497506. 7 Demchenko YN, Glebov OK, Zingone A et al. Classical and or alternative NF-kappaB pathway activation in multiple myeloma. Blood 2010; 115:354152. 8 Chanan-Khan AA, Giralt S. Importance of achieving a complete response in multiple myeloma, and the impact of novel agents. J Clin Oncol 2010; 28:261224. 9 Dalle S, Beylot-Barry M, Bagot M et al. Blastic plasmacytoid dendritic cell neoplasm: is transplantation the treatment of choice? Br J Dermatol 2010; 162:749. 10 Jegalian AG, Facchetti F, Jaffe ES. Plasmacytoid dendritic cells: physiologic roles and pathologic states. Adv Anat Pathol 2009; 16:392404.

British Journal of Dermatology (2013) 168, pp871914

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degree, and zero degree intercept of 09 deaths per 100 000 year for the rest of Europe; and 00093 deaths per 100 000 year degree, and zero degree intercept of 069 deaths per 100 000 per year for CEE countries.9 For men, with Russia and Ukraine omitted, the corresponding values were 0069, zero degree intercept of )11; and 0042, zero degree intercept of )0027. When Russia and Ukraine are included, the CEE slope changes to )00052 with zero degree intercept of 22. Thus, the lower melanoma incidence rates for CEE did not seem to have any inuence on melanoma mortality rates. This analysis adds to the evidence that the trends of rapidly rising melanoma incidence rates in the rest of Europe, North America, and Australia and New Zealand may be due to higher diagnosis rates for melanomas that are not life threatening. Indeed, analyses of survival rates with respect to Breslow thickness indicate that survival rates for thinner melanomas are much higher than for thicker melanomas.10 One suggestion for reducing the burden of melanoma is to encourage people not to burn while in the sun, but not to avoid the sun. It is sporadic, not chronic, ultraviolet irradiance that is strongly correlated with the risk of melanoma. For example, a recent ecological study of cancer incidence based on occupation in Nordic countries found reduced incidence rates for melanoma for those with outdoor occupations, and reduced risk of many types of internal cancers due to production of vitamin D.11 Sunlight, Nutrition, and Health Research Center, W.B. GRANT PO Box 641603, San Francisco, CA 94164-1603, U.S.A. E-mail: wbgrant@inonline.net

9 Ferlay J, Shin HR, Bray C et al. GLOBOCAN 2008 v1.2, cancer incidence and mortality worldwide. Lyon: IARC, 2010 (CancerBase no. 10). Available at: http://globocan.iarc.fr/ (last accessed 2 October 2012). 10 Green AC, Baade P, Coory M et al. Population-based 20-year survival among people diagnosed with thin melanomas in Queensland, Australia. J Clin Oncol 2012; 30:14627. 11 Grant WB. Role of solar UV irradiance and smoking in cancer as inferred from cancer incidence rates by occupation in Nordic countries. Dermatoendocrinol 2012; 4:20311.

Characterization of a malignant T-cell line established from a rare case of CD8+CD56+ zary syndrome Se
DOI: 10.1111/bjd.12058 MADAM, The majority of cell lines derived from mycosis zary syndrome (SS), representatives of cutafungoides and Se neous T-cell lymphoma (CTCL), are positive for CD4, and CD8+ cases are rare.1 Here, we established a CD8+CD56+ skin-inltrating tumour cell line from skin blisters of a patient with CD8+ SS. Using this cell line, the peculiar features of CD8+ CTCL cells were studied. The patients clinical information has been described elsewhere.2 Briey, a 26-year-old woman had erythroderma with conspicuous blister formation and lymphocytosis (25 109 cells L)1). Approximately 40% of peripheral blood mononuclear cells (PBMCs) had a CD2highCD3lowCD8+CD56+CLA+ CD4) phenotype and expressed CXCR3 at an intermediate level and CCR10 at a high level, but did not express CCR4. CD8+CD56+CLA+ tumour cells inltrated the skin with marked epidermotropism. Blood and lymph node involvement was conrmed by demonstration of identical clonal rearrangment of the T-cell receptor Cb1 gene. After informed consent and approval by the ethical committee of our university, we established a tumour T-cell line. More than 3 months after termination of substantial treatments, including interferon (IFN)-c and radiation, skin-inltrating cells were obtained by aspiration of the blister uid without an invasive procedure, and subsequent purication by Ficoll Hypaque. Cells were cultured with 10 ng mL)1 interleukin (IL)-7 in complete RPMI-1640, and expanded to 200 lL per well in round-bottom 96-well plates. Fresh culture medium was added to the well every 2 days, and the cells were collected each week. A long-term tumour T-cell line, termed CD8SSC, was established by maintaining it over 6 months. DNAs extracted from a skin specimen and CD8SSC were subjected to Southern blotting analysis for Cb1 after digestion with BamHI restriction enzyme. The same rearranged nongerm line band was detected in both samples. The patient had no antihuman T-cell lymphotropic virus 1 (HTLV-1) antibody, and there was no monoclonal integration of HTLV-1 proviral DNA into blood or CD8SSC.
British Journal of Dermatology (2013) 168, pp871914

References
1 Godar DE. Worldwide increasing incidences of cutaneous malignant melanoma. J Skin Cancer 2011; 2011:858425. z J et al. International trends in 2 Erdmann F, Lortet-Tieulent J, Schu the incidence of malignant melanoma 19532008 are recent generations at higher or lower risk? Int J Cancer 2012; (in press). 3 Marugame T, Zhang MJ. Comparison of time trends in melanoma of skin cancer mortality (19902006) between countries based on the WHO mortality database. Jpn J Clin Oncol 2010; 40:710. 4 Criscione VD, Weinstock MA. Melanoma thickness trends in the United States, 19882006. J Invest Dermatol 2010; 130:7937. 5 Buettner PG, Leiter U, Eigentler TK, Garbe C. Development of prognostic factors and survival in cutaneous melanoma over 25 years: an analysis of the Central Malignant Melanoma Registry of the German Dermatological Society. Cancer 2005; 103:61624. s Z, Ka sler M. [Epidemiology of malig6 Balatoni T, Liszkay G, Miklo nant melanoma (Clinical experience at the National Institute of Oncology in Hungary)]. Orv Hetil 2011; 152:10006(in Hungarian). 7 Weyers W. The epidemic of melanoma between under- and overdiagnosis. J Cutan Pathol 2012; 39:916. 8 Forsea AM, Del Marmol V, de Vries E et al. Melanoma incidence and mortality in Europe: new estimates, persistent disparities. Br J Dermatol 2012; DOI: 10.1111/j.1365-2133.2012.11125.x.

2012 The Authors BJD 2012 British Association of Dermatologists