epidermis. These features might be related to a block in the S phase of the cell cycle. On the other hand, the calprotectin immu- nolabelling throughout the epidermis appeared strikingly moth- eaten indicating severe vacuolar alterations. As seen in other disor- ders, the Mac 387-positive keratinocytes were either metabolically altered or engaged in a regenerative phase. The combination of these features was interpreted as a sublethal sign. The dermal den- drocyte alterations were reminiscent of the methotrexate-induced changes. 6 In some instances, CAR associated with anti-cancer treatment may be predictive for the drug efficacy. 7 Such a feature has not been evaluated so far for pemetrexed. M. Sabatiello, † V. Willemaers, † M. Lesuisse, † G.-E. Pie´ rard ‡, * † Department of Dermatology, Regional Hospital Citadelle, Lie` ge, Belgium, and ‡ Department of Dermatopathology, University Hospital Sart Tilman, Lie` ge, Belgium *Correspondence: G.-E. Pie´ rard. E-mail: gerald.pierard@ulg.ac.be References 1 Dubey S, Schiller JH. The emerging new drugs for NSCLC: pemetrexed, bortezomib and cetuximab. Oncologist 2005; 10: 282–291. 2 Franchimont C, Pie´rard GE. Cutaneous pathobiology mediated by chemotherapy. J Cutan Pathol 1980; 7: 387–393. 3 Gaigl Z, Seitz CS, Bro¨cker EB et al. Methotrexate-induced toxic epider- mal necrolysis-like skin toxicity. Eur J Dermatol 2007; 17: 168–169. 4 Sawada Y, Kawakami C, Nakamura M et al. Toxic epidermal necrosis- like dermatosis induced by the first course of methotrexate. Eur J Dermatol 2009; 19: 397–398. 5 Bunn P, Paoletti P, Niyikiza C et al. Vitamin B 12 and folate reduce toxoicity of Alimta TM (pemetrexed disodium, LY231514, MTA) a novel antifolate / antimetabolite. Proc Am Soc Clin Oncol 2001; 20: 76a. 6 Quatresooz P, Pie´rard GE. Dermal dendrocyte ballooning. Am J Clin Dermatol 2006; 7: 391–392. 7 Quatresooz A, Rorive P, Paquet P et al. Cutaneous adverse effects predicting the efficacity of targeted antineoplastic therapies. Rev Med Lie`ge 2009; 64: 247–350. DOI: 10.1111/j.1468-3083.2011.04027.x Report of 27 cases of naevus spilus in 2134 patients with melanoma: is naevus spilus a risk marker of cutaneous melanoma? Editor We reported the experience of the Melanoma Unit of University Hospital of Spedali Civili of Brescia about the incidence of naevus spilus (NS) in the 2134 patients in follow-up for melanoma and the analysis of the risk that melanoma originated in NS, especially in patients who were already affected by this cutaneous tumour, with the intent to underline the importance of clinical monitoring. Naevus spilus is characterized by numerous small, darkly pigmented speckles, which could appear on a background of tarnish-brown hyperpigmentation. There are numerous different denominations for this skin lesion: ‘naevus spilus’, ‘naevus on nae- vus’, ‘spotty naevus’, ‘speckled lentiginous naevus’, ‘speckled nae- vus spilus’. It is a relatively uncommon condition, it appeared in 2% of the population. Lesions are benign and they may be noted at birth or have their onset in early infancy or childhood. NS range in size from less than 1 cm to more than 10 cm in diameter, it may have zosteriform or regional distribution. The lesions involve especially the trunk and upper and lower extremities. Microscopi- cally, the background pigmentation corresponds to the features of a lentigo simplex, whereas the dark speckles usually show a junc- tional proliferation of melanocytes. Dermatoscopy reveals darker brown areas with a reticulo-globular pattern in favour of melano- cytic nevi. The background is usually light brown and reticular. Malignant melanoma has been reported as a very rare complica- tion, but a renewed interest in this entity has occurred following the report, in the last 5 years, of 12 cases of malignant melanoma in NS previously considered as benign naevus, besides the previous 19 case reports of malignant melanoma on NS since the 1970s. 1–10 We evaluated 2134 patients with melanoma, 27 of them pre- sented NS in a different body region. The patients referred the NS as congenital. The median range at melanoma’s diagnosis was 42 years (range 22–77 years), 17 were women and 10 men. Ana- tomically, the lesions were localized most frequently on lower extremities, followed by the trunk, the upper extremities and the head. In 24 patients, the darkly pigmented speckles were on a hyperpigmented background, but in three patients there wasn’t the cafe´-au-lait macule. One patient presented two NS in two different body regions. All the NS were small except in three cases, Figure 1 Naevus spilus with an hyperpigmented area with an irregular pattern: histology excluded atypia. ª 2011 The Authors JEADV 2012, 26, 122–130 Journal of the European Academy of Dermatology and Venereology ª 2011 European Academy of Dermatology and Venereology Letters to the Editor 129