Expression of endoglin in human melanocytic lesions

Angiogenesis plays an important role in progression of various tumours including malignant melanoma. It is possible that the immunostaining of angiogenic markers could differentiate benign and malignant melanocytic lesions or that the immunostaining pattern with angiogenic markers could vary with tumour thickness and thus be a prognostic marker. We were interested to see whether there was any correlation between endoglin (CD 105; EDG) expression with tumour thickness in primary cutaneous malignant melanomas (MM), any correlation between EDG expression and clinical outcome in patients with primary cutaneous MMs and any difference in staining pattern between cutaneous MMs and Spitz naevi which could be of diagnostic value. Tissue sections from 14 primary cutaneous MM lesions with a Breslow thickness of > 2 mm, 10 primary cutaneous MM lesions with a Breslow thickness of 1-2 mm, and six Spitz and 10 compound naevi were stained for EDG. EDG expression was compared with survival in patients with primary cutaneous MMs. Overall, EDG staining was positive in 96% of MMs and 94% of benign melanocytic naevi. Very strong (++++) and strong (+++) EDG staining was found in 58% of MMs and 56% of benign melanocytic lesions. EDG expression did not vary significantly with the thickness of the lesion in primary cutaneous melanoma. Survival of melanoma patients did not correlate with the degree of EDG expression. Therefore, expression of this marker alone is not sufficient to differentiate benign and malignant melanocytic lesions.     

The carcinoembryonic antigen (CEA) family (CD66) expressed in melanocytic naevi is not expressed in blue naevuscell naevi in dendritic type

BACKGROUND: Although sporadic reports have regarded the expression of the carcinoembryonic antigen (CEA) family in melanoma, there has been no information about the expression in precursor lesions of melanoma such as melanocytic naevi and blue naevi. METHODS: The expression was immunohistochemically studied in frozen biopsy specimens of 45 acquired and 16 congenital melanocytic naevi and 20 blue naevi, using a panel of monoclonal and polyclonal antibodies that recognize different epitopes of CEA and related molecules. RESULTS: Members of the CEA glycoprotein family were strongly expressed in all of the subtypes of melanocytic naevus. A reduced expression of the CEA glycoproteins with increased dermal depth or acquisition of a spindled morphology of naevus cells was apparent. The expression was not seen in the present blue naevi and normal epidermal melanocytes. CONCLUSIONS: Although the significance of the expression was not clarified, this report has clearly demonstrated that the CEA family is strongly expressed in melanocytic naevi and immunoreactivity is divergent between melanocytic naevi and blue naevi and between dermal naevus cell types, suggesting that the expression may be altered with architectural changes in the melanocyte-lineage cells.     

Digital dermatoscopic follow‐up of 1027 melanocytic lesions in 121 patients at risk of malignant melanoma

Objective  The aim of the presented prospective study was to use a digital dermatoscopic system to follow‐up patients with multiple melanocytic naevi, and to evaluate the frequency and character of dermatoscopic changes. Methods  We monitored selected melanocytic lesions with the use of a 6‐month follow‐up interval between check‐ups. We searched for changes in size, shape, symmetry, structure and colour. We defined the criteria for surgical excision and histopathological examination of changing lesions. We created a small group of excised unchanged atypical melanocytic naevi. Results  We completed dermatoscopic monitoring of 1027 melanocytic lesions in 121 patients at risk of developing malignant melanoma. The average total follow‐up interval was 21.0 months. We noticed a substantial enlargement of monitored lesions in 4.5% of cases, and there was a change of shape in 1.3% and change of asymmetry in 2.0%. The appearance of new structures, frequently being associated with malignant melanoma, was observed in 10 lesions, and it was predictive for the histopathological confirmation of this diagnosis in all cases. About 80% of monitored lesions remained unchanged. We excised 38 monitored lesions (seven melanomas in situ, four thin invasive melanomas and 27 melanocytic naevi). There was no melanoma excised in the group of unchanged atypical melanocytic lesions. Conclusion  Digital dermatoscopic follow‐up facilitates the recognition of thin malignant melanomas and helps to reduce the number of unnecessary excisions.     

Proposal of a new classification system for melanocytic naevi

The lack of consensus among clinicians and pathologists due to the mixture of clinical and histopathological features used to define the various melanocytic naevi underscores the need of a better classification system for these benign lesions. We describe a dermoscopic classification system for melanocytic naevi that is directed to clinicians dealing with the early diagnosis of melanoma, as well to pathologists, in order to promote better communication between these different specialists.     

Immunohistochemical expression of cyclooxygenage-2 in melanocytic skin lesions

Background Several reports have shown expression of cyclooxygenase‐2 (COX‐2) in malignant skin tumors. COX‐2 has also recently been reported as a marker of malignant melanoma (MM). Objective Our aim was to investigate whether there is a difference in the immunohistochemical expression of COX‐2 between malignant and benign melanocytic lesions of the skin. Methods We selected 40 archival cases of MM including 10 cases of superficial spreading melanoma, 10 of lentigo maligna melanoma, 10 of nodular melanoma, and 10 of acral lentiginous melanoma. For comparison, we also selected 35 benign melanocytic lesions, which included 15 nonatypical nevi and 10 atypical nevi. The remaining 10 cases were Spitz nevi. COX‐2 immunohistochemical staining was performed, and intensities were assessed quantitatively. Results The MM group and the benign melanocytic nevi group showed a highly statistically significant difference in the intensity of COX‐2 expression (P < 0.0001). Staining intensity in the dermal component of MM cases also showed a tendency to increase with increasing tumor depth. By contrast, the intensity of the dermal component in the melanocytic nevi group decreased with increasing depth as the nevus cells matured from type A to type C cells. No statistical difference was noted between the MM and Spitz nevi cases (P = 0.20). Conclusions Malignant melanoma shows stronger immunohistochemical expression of COX‐2 than benign melanocytic nevi. Although COX‐2 cannot be used alone to differentiate MM from melanocytic nevi, it may serve as an aid in the differential diagnosis of melanocytic skin lesions.     

Clinically equivocal melanocytic skin lesions with features of regression: a dermoscopic-pathological study

BACKGROUND: Benign melanocytic skin lesions may be difficult to differentiate from melanoma both clinically and dermoscopically. One of the most confounding dermoscopic features, commonly seen in melanoma but in our experience also in melanocytic naevi, is represented by the so-called blue-white structures (BWS). OBJECTIVES: To evaluate diagnostic significance and histopathological correlates of BWS seen by dermoscopy in a series of clinically equivocal melanocytic skin lesions that were excised. METHODS: Patients were recruited from six specialized pigmented lesion clinics in Austria, Italy and Spain over a period of 9 months. All consecutive patients showing one or more melanocytic lesions with BWS, but not classified as melanoma dermoscopically, were included. Each lesion was photographed clinically and dermoscopically. All images were reviewed by one of us and the degree, type and location of BWS evaluated for each lesion. A panel of four experienced dermatopathologists independently reviewed all specimens for diagnosis and one of them evaluated presence and degree of melanosis and/or fibrosis. The main outcome measures were the percentage and histopathological correlates of lesions with different degree, type and location of BWS. RESULTS: All included lesions with BWS (n = 158) showed partial or focal regression histopathologically. One hundred and thirty-five (85.4%) lesions were diagnosed as melanocytic naevi (complete histopathological interobserver agreement), whereas 23 (14.6%) were defined as equivocal because at least one of four pathologists diagnosed the given lesion as melanoma. Only one lesion was diagnosed as melanoma by all four pathologists. The majority of naevi exhibited blue areas (84.4%) with a central distribution (57%) and involving < 50% of the lesion surface (89.6%). By contrast, 78.3% of equivocal lesions revealed a combination of white and blue areas with an irregular distribution (60.9%) and involving > 50% of the lesion surface (47.8%). CONCLUSIONS: Using degree and type of BWS, an algorithm was constructed that can be applied for the management of lesions exhibiting dermoscopic features of regression.     

(17) Histopathology of giant congenital melanocytic naevi: implications for treatment

Giant hairy naevi pose not only cosmetic problems, but also therapeutic difficulties because of the increased risk of malignant melanoma. Prophylactic full thickness excision and grafting have previously been recommended for such lesions, but because of the large size this is not always practical. Following observations that in the neonatal period, naevus cells are superficial (predominantly in the papillary dermis) and only later migrate into reticular dermis, some authors have suggested that dermabrasion or shaving of the naevi must be performed soon after birth, as an alternative therapy. We studied 26 children with giant congenital melanocytic naevi to assess: (i) the histological progression with age; (ii) correlation of clinical and histological appearance; and (iii) results of shaving in the treatment of these naevi.
Initial biopsies revealed that naevus cells often occupy the entire dermis, even in the neonatal period, and not infrequently involve the subcutis. Melanocytes showed little organization into nests.
Follow-up biopsies of all naevi showed no change in histological pattern or progression in depth with age, despite changes in clinical appearance.
Post-shaving biopsies revealed that although the epidermis and sometimes the papillary dermis were removed, all the deeper dermal, subcutaneous and fascial components of the naevi remained.
In conclusion our data suggest that: (i) many congenital melanocytic naevi already show deep dermal involvement in the neonatal period; this does not support the hypothesis that naevus cells migrate into the dermis during infancy; (ii) there is no change in naevus depth with age; (iii) shaving does not remove all the naevus cells, and should only be considered as a cosmetic procedure, Three cases showed regeneration of melanocytes following shaving, similar to what is described as the 'pseudomelanoma' phenomenon.     

A study of the value of the seven-point checklist in distinguishing benign pigmented lesions from melanoma

A seven-point scoring system has been adopted by the Cancer Research Campaign to help non-dermatologists recognize melanoma (MM). Its value is reviewed in the light of increasing referrals of pigmented lesions. One-hundred and ninety-five patients (M:F, 43:152; mean age = 43 years, s.d. = 19) were asked whether their lesions possessed the seven points before diagnosis. The dermatologist assessed the signs. Six patients were unable to comply and some had multiple lesions; thus, 216 lesions were fully assessed by patient and dermatologist, and six by the dermatologist alone. Histology was obtained where appropriate. There were eight MMs, 95 naevi, 80 seborrhoeic warts, three dysplastic naevi, and 36 other lesions. Seven of the eight MMs were diagnosed clinically; the other was biopsied because of suspicious features and was a nodular MM. Four lesions suspected to be MMs proved benign. The predictive value (PV) of a clinical diagnosis of MM was 64% and of non-MM was 99%. Using accepted cutpoints for the seven-point system (refer if score greater than or equal to 3) patients' scores gave a PV for MM of 7% and for non-MM of 99%. Two MMs scored less than three. Dermatologists' scores gave a PV for MM of 8% and for non-MM of 99%. One MM scored less than 3. Univariate analyses showed that enlargement (P less than 0.05), dermatologists' assessments of an irregular margin (P less than 0.001), size (P less than 0.05) and pigmentary irregularity (P less than 0.05), and patients' assessments of size (P less than 0.05) were statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Proliferative activity of cutaneous melanocytic neoplasms defined by a proliferating cell nuclear antigen labelling index

Summary To evaluate the proliferative activity of benign, borderline and malignant cutaneous melanocytic neoplasms, 30 cases of malignant melanoma (MM) and 41 cases of naevi were studied by immunostaining using a monoclonal antibody against proliferating cell nuclear antigen (PCNA). PCNA is a nuclear antigen expressed in the late G1 and S phase and serves as a marker of proliferating cells. Invasive MM and MM in situ showed much higher PCNA positivity rates than melanocytic naevi (invasive MM, 18.0%; MM in situ, 11.3%; ordinary melanocytic naevi, 2.6%). The PCNA positivity rate did not increase significantly with the thickness of MM. Among ordinary melanocytic naevi, junctional naevi had a higher PCNA positivity rate than compound or intradermal naevi. Mean PCNA positivity rates for Spitz's naevi and sporadic dysplastic naevi were within the range for ordinary melanocytic naevi, indicating the benign nature of both types of naevus. Contrary to some previous studies, MM in situ showed high proliferative activity, indicating that cells of MM in situ are actively proliferating. This study clearly demonstrates that MM and various types of naevi can be separated according to differences in proliferative activity defined by the PCNA labeling index.This work was presented in part at the 14th International Pigment Cell Conference, Kobe, Japan, October 31–November 4, 1990     

Dermoscopy,reflectance confocal microscopy and histopathology of an amelanotic melanoma from an individual heterozygous for MC1R and tyrosinase variant alleles

We present a case of an amelanotic nodular melanoma occurring in a 26‐year‐old woman who carried a heterozygous (melancortin‐1‐receptor) MC1R 160R/W and tyrosinase (TYR) 402R/Q genotype and had a dark hair phenotype. We present dermoscopic, reflectance confocal microscopy (RCM) and histopathological images of the melanoma. We discuss the relationship between MC1R red hair colour (RHC) variants, TYR variants, phenotype and melanoma development. We also discuss the merits of RCM as an additional diagnostic aid for equivocal melanocytic lesions.     

Expression of c-kit (CD117) in Spitz nevus and malignant melanoma

BACKGROUND: CD117, the receptor for kit-ligand, which is a growth factor for melanocyte migration and proliferation, has shown differential staining in various benign and malignant melanocytic lesions. The purpose of this study is to compare CD117 immunohistological staining in Spitz nevus versus malignant melanoma, to determine whether CD117 can aid in the diagnosis of these two lesions. METHODS: CD-117 immunohistological staining was performed in 22 clinically and pathologically diagnosed pigmented lesions including 9 cases of Spitz nevus, 10 cases of primary MM and 3 cases of metastatic melanoma. RESULTS: There was no significant difference in CD117 staining in either epidermis or dermis between Spitz nevi and primary melanomas. However staining of metastatic melanomas is less than dermal staining of primary MM and Spitz nevus. CONCLUSIONS: CD117 is unlikely a useful diagnostic tool in differentiating Spitz nevus from primary MM. On the other hand, CD 117 may be useful in differentiating metastatic melanoma from primary melanoma in patients who had a history of melanoma and who present with new dermal lesions.     

Computer description of colours in dermoscopic melanocytic lesion images reproducing clinical assessment

BACKGROUND: The assessment of colours is essential for the diagnosis of malignant melanoma (MM), both for pattern analysis on dermoscopic images, and when employing semiquantitative methods. OBJECTIVES: To develop a computer program for colour assessment in MM images mimicking the human perception of lesion colours, and to compare the automatic colour evaluation with one performed by human observers. METHODS: A colour palette comprising six colour groups (black, dark brown, light brown, blue-grey, red and white) was created by selecting single colour components inside melanocytic lesion images acquired by means of a digital videomicroscope, and was implemented in the image analysis program. Subsequently, colours were assessed by the computer program on 331 melanocytic lesion images composing our image database, and the results were compared with the evaluation of lesion colours performed by the clinician. RESULTS: The black, white and blue-grey colours were more frequently found in MMs than in naevi, both by the clinicians and by the computer. In MM images we observed 4.27 +/- 1.14 colours (mean + or - SD) per lesion, as opposed to 3.22 +/- 0.68 in naevi. The correlation between clinical and computer evaluation of the colours was very good, with a value of 0.781 for overall assessment. CONCLUSIONS: This innovative method for automatic colour evaluation, reproducing clinical assessment of melanocytic lesion colours, may provide numerical parameters to be employed for computer-aided diagnosis of MM.     

Expression of the neuronal isoform of nitric oxide synthase (nNOS) and its inhibitor, protein inhibitor of nNOS, in pigment cell lesions of the skin

Nitric oxide (NO) is involved in many physiological processes. In cancer, low levels of NO are thought to enhance tumour progression and metastasis. NO is generated from arginine by NO synthase (NOS); the Ca2+-dependent neuronal isoform or nNOS (expressed by neurones and inhibited by the protein inhibitor of nNOS, PIN), is also expressed by cultured normal melanocytes and by all malignant melanoma (MM) cell lines. We studied the expression of nNOS and PIN in paraffin sections of 177 and 58 pigment cell lesions, respectively, using immunohistochemistry; the activity of the necessary cofactor NADPH was studied in 26 frozen cases. Normal melanocytes in situ lacked nNOS and PIN expression, but were NADPH +. Almost half of common acquired benign naevi expressed nNOS; however, halo naevi and congenital naevi expressed nNOS very frequently. Dysplastic naevi and MM showed variable nNOS immunoreactivity in 72% and 83% of cases, respectively. Early (Clark I and Clark II) MM displayed nNOS staining most frequently, and all MM with an invasive radial growth phase expressed nNOS in the papillary dermis. In contrast, only 67% of metastatic MM were nNOS +. PIN was coexpressed with nNOS in 40 of 58 lesions. NADPH activity was present in all nNOS + naevi, but in two malignant cases, NADPH activity was not accompanied by nNOS expression. We conclude that nNOS expression is induced de novo in benign and malignant pigment cell lesions which have all the requirements (NADPH, PIN) necessary for the production and modulation of NO. We postulate that the frequent expression of nNOS in the junctional part of dysplastic naevi may be responsible for their particular histological features. NO generated by the neoplastic dermal cells in the invasive radial growth phase may contribute to the increased number of blood vessels in the papillary dermis.     

MIB-1 monoclonal antibody to determine proliferative activity of Ki-67 antigen as an adjunct to the histopathologic differential diagnosis of Spitz nevi

BACKGROUND: The histopathologic differential diagnosis of Spitz nevus (SN) from malignant melanoma (MM) may be difficult. OBJECTIVE: Our purpose was to determine the staining pattern and usefulness of MIB-1 antibody, which recognizes Ki-67 antigen in formalin-fixed, paraffin-embedded tissue, as an adjunct to the histopathologic differential diagnosis of SN. METHODS: Twenty-five compound SNs, 27 MMs, and 26 compound nondysplastic melanocytic nevi (MNs) were immunostained with the MIB-1 antibody. RESULTS: The mean counts of MIB-1--stained tumor cells of the epidermal and dermal components, both alone and together, were significantly lower in SNs and MNs than in MMs (P <.0001). The dermal counts showed the best discriminating power. In addition, the mean dermal/epidermal count ratios for MIB-1 in SNs and MNs (0.25 and 0.23, respectively) were significantly lower than the corresponding ratio (0.94) in MMs (P <.0001). CONCLUSION: MIB-1-stained tumor cell counts, especially of the dermal component, and dermal/epidermal MIB-1 count ratios may be helpful as an adjunct to the histopathologic differential diagnosis of SN.     

Nevus associated malignant melanomas--diagnostic validation and prognosis

The diagnosis and prognosis of naevus-associated malignant melanomas are examined in the present study. For this purpose, 581 cases of primary malignant melanoma seen in the University Department of Dermatology, Berlin Steglitz, were histologically investigated for naevus association. A naevocytic association was proven in 135 (23%) of the malignant melanoma biopsies. Naevocytic malignant melanomas were found at a significantly higher rate (P less than 0.01) in patients under 50 years of age. The 5-year survival rate for naevocytic melanomas was not significantly different from that for other malignant melanoma types: around 80% in both groups. An immunohistological evaluation of the diagnosis of naevus-associated melanoma was also performed on the basis of specimens from 89 melanocytic lesions. The use of HMB-45 for diagnosis of melanocytic tumours made it possible to differentiate resting dermal naevus cells from malignant melanoma infiltrates in paraffin sections in the present study, thus simplifying the diagnosis of naevus-associated malignant melanomas. However, dysplastic naevi, junctional naevi and juvenile melanomas are also stained by HMB-45, which means that malignant melanomas associated with junctional melanocytic naevi still cannot be reliably identified even today.     

The prevalence of melanocytic naevi among schoolchildren in South Hungary

Background Malignant melanoma is an increasing public health problem worldwide; accordingly, identification of the constitutional and environmental factors which contribute to the development of the disease, and hence identification of the individuals at high risk of melanoma, is an indispensable step in all primary prevention efforts. Objectives This paper aims to assess the prevalence of different pigmented lesions among schoolchildren and to investigate their relationship with phenotypic pigmentary characteristics, sun exposure and other factors. Patients/methods A cross‐sectional study was performed in two secondary schools in Szeged, Hungary. A total of 1320 schoolchildren, aged 14 to 18 years, underwent a whole‐body skin examination. A standardized questionnaire was used to collect data on phenotypic, sun exposure and other variables. Results One to 10 common melanocytic naevi were found in 27% of the participants, and the naevus numbers were in the range of 10–100 in 67%; 5.4% of them had more than 100 common melanocytic naevi. The prevalence of clinically atypical naevi was 24.3%. Statistically significant associations were found between the number of pigmented lesions and gender, hair colour, eye colour, skin phototype, a history of severe painful sunburns and a family history of a large number of melanocytic naevi. Conclusion Our study population displayed a markedly high prevalence of clinically atypical melanocytic naevi. Moreover, a considerable proportion of the investigated individuals had multiple common melanocytic naevi. Since the presence of a large number of melanocytic naevi is a strong predictor for future melanoma development, health educational programmes on melanoma prevention should be aimed at young age groups.     

Expression of matrilysin (matrix metalloproteinase-7) in primary cutaneous and metastatic melanoma

BACKGROUND: Matrilysin (MMP-7), a member of the matrix metalloproteinase (MMP) family of proteins, is expressed in various types of malignant tumours. There have been no previous studies of the correlation between matrilysin expression and melanoma. OBJECTIVES: Protein expression of matrilysin was evaluated in human cutaneous melanomas, metastatic melanomas, acquired common melanocytic naevi and Spitz naevi, and the data were corrected with the clinicopathological factors. METHODS: We retrospectively investigated 18 primary melanomas, 15 metastatic melanomas, 10 common melanocytic naevi and five Spitz naevi samples at our clinic using immunohistochemistry (IHC). Both promatrilysin and active matrilysin were found in the melanoma tissue extracts by Western immunoblotting. In situ hybridization demonstrated that melanoma cells selectively express matrilysin mRNA. RESULTS: Of the melanoma samples, 29 of 33 (87 x 9%) were positive for matrilysin, including 14 of 18 (77 x 8%) primary cutaneous melanomas and 15 of 15 (100%) metastatic melanomas. In contrast, matrilysin was not expressed in common naevi or Spitz naevi. The matrilysin IHC staining score in primary melanomas was associated with the presence of metastases, tumour thickness and TNM staging (P=0 x 001, 0 x 025 and 0 x 021, respectively). The 5-year overall survival was 26.3% for matrilysin-positive cases and 100% for matrilysin-negative cases among melanoma specimen. CONCLUSIONS: We found matrilysin expression in primary melanomas and in metastatic melanomas. We further demonstrated that the matrilysin IHC staining score was associated with invasive depth of primary melanoma lesions and metastases. Our observations indicate that matrilysin may be associated with melanoma progression, and may enhance melanoma tumour cell invasion. Therefore, matrilysin may be potentially valuable as a prognostic indicator to predict the clinical behaviour of melanoma.     

Surveillance of patients at high risk for cutaneous malignant melanoma using digital dermoscopy

BACKGROUND: Dermoscopy has improved the sensitivity and specificity of clinical diagnosis of melanoma from 60% to over 90%. However, in order not to miss melanoma a certain percentage of suspicious but benign lesions has to be excised. OBJECTIVES: To evaluate the dermoscopic changes and the rates of excision in benign melanocytic naevi and cutaneous malignant melanoma in long-term follow-up of high-risk patients using digital dermoscopy. METHODS: Digital dermoscopic images of 2015 atypical melanocytic naevi in 196 high-risk patients were analysed retrospectively. Among others, the following data were collected for each naevus: changes in surface area, overall architecture, dermoscopic patterns and distribution of pigmentation. All tumours suspicious for melanoma or showing asymmetrical changes were excised. RESULTS: During a median follow-up time of 25 months 128 (6.4%) of all naevi showed changes in size or architecture. Eighty-six per cent of all changes in patients who attended more than one visit were observed at the first follow-up visit. Thirty-three lesions showing changes were excised and two melanomas in situ and 31 melanocytic naevi were diagnosed. CONCLUSIONS: Follow-up examinations using digital dermoscopy revealed unchanged morphology in the large majority of melanocytic naevi. Excisions were only performed in cases of asymmetrical growth, asymmetrical changes of pigmentation, or development of dermoscopic features indicative of melanoma. The ratio of 33 lesions excised in order to identify two melanomas in situ seems reasonable and may be further reduced in future.     

Ipilimumab induces simultaneous regression of melanocytic naevi and melanoma metastases

Ipilimumab blocks cytotoxic T‐lymphocyte‐associated antigen (CTLA)‐4, potentiating the antimelanoma T‐cell host response. Ipilimumab has been shown to improve overall survival in patients with previously treated metastatic melanoma. CTLA‐4 antibodies generate immune responses to the melanoma‐associated antigens Melan‐A, NY‐ESO‐1 and glycoprotein (gp)100 in metastatic melanoma. Digital epiluminescence microscopy (DELM) is a noninvasive method permitting the monitoring of the morphology of melanocytic lesions over time. A 50‐year‐old man with metastatic melanoma received four ipilimumab injections after failure of dacarbazine chemotherapy. Positron emission tomography revealed regression of pulmonary metastases, and simultaneously, DELM showed regression of several melanocytic naevi. On histological examination of the regressing naevi, prominent CD8+, CD4+ and CD45R0 lichenoid lymphohistiocytic infiltrates were seen, whereas nonregressing naevi were almost free of inflammatory infiltrate. Expression of melanoma‐associated antigens in benign melanocytic naevi may explain the induction of naevus regression by ipilimumab. DELM could represent a valuable noninvasive method to monitor ipilimumab efficacy.