Reviewed: 11/17/2017
Initial question
Which classification is best to use?
Recommendation
Standardized classification is important for determining prognostic factors and results of treatment, and therefore important in determining policy and information for the individual patient. The working group recommends aligning with the internationally proposed cutaneous classification of Krengel et al. [Krengel 2013 JAAD,www.nevus.org/CMN-classification]. This is easy to apply in the consulting room, you only need a measuring tape.
The working group recommends to classify each patient with CMN once according to this classification, based on theontreated status and the number of satellite nevi in the first year of life (if known). Only in the case of clear morphological changes (spontaneous, not due to treatment) should the classification be adjusted accordingly. This change must be stated in the classification.
For the classification of CMN, you can fill in the form in 'Protocol classification CMN' (with the related products) and then scan it in the file. An example of then noting the full classification in the status:
“Krengel 2013 classification: untreated status, age 1 year: L1, hip+thigh, S1, C0, R1, H1, N0.”
In addition, the maximum diameter of the CMN in length and width in centimeters is noted, for example: “maximum size 12x10cm”
Considerations
The working group is of the opinion that the proposed classification of Krengel et al. is easily applicable in the consulting room and provides an accurate phenotyping of CMN. All you need for this is a measuring tape (possibly printable in actual size from the internet). The working group also considers it important to join this classification internationally in order to obtain more clarity in the future about prognostic factors and results of treatment for CMN.
With this classification, across sectionalcutaneous classification can be obtained: the classification is quite static, so in principle it only needs to be noted once. Only if major phenotypic changes occur in the spontaneous course (e.g. becoming larger due to 'colouring in' a light background spot, or morphological changes whereby a category is moved up in the classification) should the classification be adjusted accordingly. To estimate the risk of complications, it is important to note the 'untreated' status, and if this is unknown, to state that it concerns a 'treated' status. Furthermore, the number of satellite nevi in the first year of life is used, if known. In addition to this classification, the working group considers it important that the actual size of the CMN is also noted (maximum diameter in length and width, in cm). See it 'Protocol classification CMN' with the related products, this form can be added to the status and possibly scanned.
Regarding the division into solitary vs multiple CMN; the working group has also found that there appears to be an increased risk of complications, especially in the group with multiple CMN (melanoma, NCM). Multiple CMN is defined as a "mother nevus" with satellite nevi or only multiple smaller CMN without "mother nevus". Risk phenotypes identified in this guideline are CMN >20cm PAS with satellites or ≥3 CMN 1.5~20cm PAS with or without multiple smaller nevi [see the module ‘Melanoom CMN' in 'Neurocutane melanocytose (NCM)’]. The working group considers this classification sufficiently included in the Krengel classification: size and number of satellite nevi ('S') are classified (S0 if solitary CMN, S1-S3 if multiple), with a separate phenotype for multiple medium-sized CMN (≥3 mMCMN), In addition, additional classification of cutaneous features remains desirable.
More and more insights have recently been gained into the origin and molecular signature of CMN (including postzygotic NRAS/BRAF mutation). It is possible that the classification of CMN will (also) be based on genetics in the future.
substantiation
Background
Classification of CMN is important for clear communication between doctors, the correct interpretation and comparison of studies (prognostic factors, treatment results) and thus the ability to determine policy and information for the individual patient.
Conclusions
Level 3 | Many different classification systems have been used in the CMN literature to date, mainly based on size of the CMN alone, and whether or not related to expected size in adulthood. C Hall 2004 |
Level 4 | It is often unclear in the literature which classification has been applied, which leads to ambiguity in the interpretation of the literature (e.g. prognostic factors, treatment results) D Working group opinion |
Level 3 | Consensus was reached among some international experts on a new, more complete classification of cutaneous features in CMN. The following characteristics are included in this classification: largest diameter in projected adult size (PAS), localisation, number of satellite nevi and four morphological characteristics (colour heterogeneity, surface roughness, hypertrichosis, nodules). This classification was recently tested for practical applicability in a study. C Price 2015, Krengel 2013 |
Level 3 | There are authors who propose a main division in number of CMN: one versus multiple CMN regardless of size, based on the risk of complications. C Magana 2015, Kinsler 2011 |
Summary literature
Scientific basis
A systematic search was performed (see the search strategy). Various classification systems for CMN have been used in the literature [Zaal 2004]. Classifications based on size alone are most commonly used: based on largest diameter, surface area in square centimeters, percentage of body surface area, or possibility of primary excision. Different authors have often proposed different cut-off points.* Apart from size, hardly any other aspects were included in classifications. Ruiz-Maldonado were the only ones to include satellite nevi in the classification [Ruiz-Maldonado 2004], but none of the classifications also included morphological features of CMN, such as the surface, hairiness, etc. The application of many different classifications in the literature, often with not clearly indicated which one was used, creates uncertainty in the interpretation of the literature (e.g. prognostic factors, treatment results).
Recently (2013) an international team of experts developed a 'consensus-based' international classification based on the need for a standardized and more complete cutaneous classification of CMN [Krengel 2013]. For the classification of size, the largest diameter in 'projected adult size' (PAS) has been chosen. Based on diagrams developed by the authors, it can be determined at any age. Size is divided into multiple subcategories, with a separate subtype for multiple medium-sized CMNs that may or may not include multiple smaller CMNs. Localization, number of satellite nevi ('S') and four morphological features of CMN were also included, namely color heterogeneity ('C'), backostity/wrinkling of the surface ('R'), presence of hypertrichosis ('H'). , presence of dermal or subcutaneous nodules ('N'). See fig. 1.
Applicability studies showed rapid, accurate and detailed phenotyping of patients with a good inter-observer agreement [Price 2015, Krengel 2013]. However, in practice it sometimes turned out to be difficult to determine the size when patients had undergone surgery, categorizing the morphology was sometimes difficult and the number of satellite nevi in the first year of life was often unknown.
Furthermore, Magaña and Kinsler propose a division into two main types of CMN: namely a single CMN (Type I) vs. multiple CMN (Type II) regardless of size [Magaña 2015, Kinsler 2011]. In particular, patients with multiple CMN would be at risk for developing complications in CMN.
*The most commonly used classification of size is that of Kopf et al. [Kopf 1979], based on the expected largest diameter in adulthood. They classified CMN as follows: small CMN <1.5 cm PAS, medium CMN 1.5 to 19.9 cm PAS, and large CMN greater than or equal to 20 cm in adulthood. Giant CMN were often classified as larger than 40 or 50 cm PAS [Zaal 2004]. Ruiz-Maldonado et al. proposed multiple subcategories and pushed the cutoff for large and giant CMN to 10 and 20 cm PAS, respectively. The projected adult size has not been taken into account in all studies. Another commonly used size classification is that of Pers et al. [Pers 1963]. They classified a nevus as giant CMN if it was at least 2x palm size (2% body surface area, BSA), or 1x CMN on the head or neck. This cut-off point has also been used by others for large (instead of giant) CMN.
fig. 1: Proposed international classification Krengel et al.[source: Krengel 2013,www.nevus.org/CMN-classification]
References
Kinsler V. Satellite lesions in congenital melanocytic nevi--time for a change of name. Pediatr Dermatol. 2011;28(2):212-3.
Kopf AW, Bart RS, Hennessey P. Congenital nevocytic nevi and malignant melanomas. J Am Acad Dermatol. 1979;1(2):123-30.
K[ PubMed ] [ Cross Ref ] Rengel S, Scope A, Dusza SW, Vonthein R, Marghoob AA. New recommendations for the categorization of cutaneous features of congenital melanocytic nevi. J Am Acad Dermatol. 2013;68(3):441-51.
Magana M, Sanchez-Romero E, Magana P, Beck-Magana A, Magana-Lozano M. Congenital melanocytic nevus: two clinicopathological forms. Am J Dermatopathol. 2015;37(1):31-7.
Pers M. Nevus pigmentosus giganticus.. Ugekr Laeger. 1963(125):6139.
Price HN, O'Haver J, Marghoob A, Badger K, Etchevers H, Krengel S. Practical application of the new classification scheme for congenital melanocytic nevi. Pediatr Dermatol. 2015;32(1):23-7.
Ruiz-Maldonado R. Measuring congenital melanocytic nevi. Pediatr Dermatol. 2004;21(2):178-9.
Zaal LH, Mooi WJ, Sillevis Smitt JH, van der Horst CM. Classification of congenital melanocytic naevi and malignant transformation: a review of the literature. Br J Plast Surg. 2004;57(8):707-19.
Accountability
Authorization date and validity
Last reviewed: 17-11-2017
Last authorized: 17-11-2017
A guideline only has expressiveness if maintenance takes place on a continuous basis, based on systematic monitoring of both the medical scientific literature and practical data and comments provided by users of the guideline. It has been agreed for this guideline to evaluate the literature once a year to monitor new developments. In case of essential developments, it can be decided to convene an entire guideline working group and to make interim electronic amendments and to distribute these among the various professional groups. To keep the guideline 'alive', modular revision is possible, whereby only part or parts of the guideline can be revised.
Initiative and authorization
Initiative:
- Dutch Society for Dermatology and Venereology
Authorized by:
- Dutch Society for Dermatology and Venereology
- Dutch Pediatric Association
- Dutch Society for Neurology
- Dutch Society for Pathology
- Dutch Society for Plastic Surgery
- Nurses and Carers in the Netherlands
- Dutch Society for Pediatric Neurology
General data
The guideline development was financed from the Quality Funds for Medical Specialists (SKMS).
Purpose and target group
Goal
This guideline is a document with recommendations to support daily practice in the management of patients with congenital melanocytic nevi (CMN) and their immediate environment. The guideline is based on the results of scientific research and subsequent opinion-forming by experts aimed at establishing good medical practice. The financing of this guideline has come about with funds that the NVDV has released from its SKMS programme.
Target audience
The guideline is intended for members of the medical and paramedical professions, which at least include: dermatologists, plastic surgeons, pathologists, paediatricians, neurologists, general practitioners, nurses and skin therapists. A GP brochure has also been developed in collaboration between patient association NNN and the VSOP.
Composition working group
A multidisciplinary working group was set up to develop the guideline, consisting of representatives from the disciplines involved in CMN. When compiling the working group, an attempt was made to take into account the geographical spread of the working group members and to ensure that academic and non-academic working group members are equally represented. The working group members acted independently and none of the working group members received favors for the purpose of influencing the guideline.
Working group members | Association |
Prof.dr. Suzanne Pasmans (chairman) | Dutch Society for Dermatology and Venereology (NVDV) |
drs. Céline Eggen (secretary) | PhD candidate in pediatric dermatology Erasmus MC (NVDV) |
Prof.dr. Wilma Bergman | Dutch Society for Dermatology and Venereology (NVDV) |
Dr. Nicole Kukutsch | Dutch Society for Dermatology and Venereology (NVDV) |
Dr. Albert Wolkerstorfer | Dutch Society for Dermatology and Venereology (NVDV) |
Dr. Simone Stadhouders-Keet | Dutch Society for Dermatology and Venereology (NVDV) |
Dr. Marianne Crijns | Dutch Society for Dermatology and Venereology (NVDV) |
Drs. Annelies Lommerts | Dutch Society for Dermatology and Venereology (NVDV) |
Prof. Dr. Chantal van der Horst | Dutch Society for Plastic Surgery (NVPC) |
Dr. Corstiaan Breugem | Dutch Society for Plastic Surgery (NVPC) |
Prof.dr. Walter Beautiful | Dutch Society for Pathology (NVP) |
Dr. Hanneke Rijk-van Gent | Dutch Pediatric Association (NVK) |
Prof. dr. Michel Willemsen | Dutch Society for Neurology (NVN) and Dutch Society for Pediatric Neurology (NVKN) |
Mr. Anja Ebus | Nurses and Carers Netherlands Nursing Specialist (V&VN VS) and V&VN Dermatology. |
Mrs. Marjolein van Kessel | Nevus Network Netherlands (NNN) |
Drs. Joep Wijnand and drs. Michéle Hennekam also contributed to this guideline.
Input patient perspective
Since the start of the guideline process, the patient association Nevus Netwerk Nederland (NNN) has been very involved in the development of this guideline, by delegating a board member to the working group. In this capacity, they have been involved throughout the entire guideline process, through active participation during working group meetings, and by putting forward bottlenecks that are of great importance from a patient perspective, as well as sharing ongoing initiatives in the field. Nevus Netwerk Nederland has also given its approval to the content of the directive.
Method development
Evidence based
Implementation
In the various phases of the development of the draft guideline, the implementation of the guideline and the actual feasibility of the recommendations have been taken into account as much as possible. The guideline is published on the website of the NVDV, the website of the guideline database, and is also distributed among all professional groups involved in CMN. A summary of the guideline will also be published and attention will be paid to it in various specific specialist journals. In addition, the guideline is brought to the attention of the relevant patient association. The guideline is housed in skinhuis.nl (from the NVDV) and linked to the personal health file of Patient1 in skinhuis.nl for people with a skin disorder and the professionals involved.
Method
The guideline congenital melanocytic nevi is a completely new guideline. The melanoma guideline (approved on 13.08.2012) already refers to the CMN guideline that is being developed. The guideline working group was started in the autumn of 2011, but has been suspended several times in between, partly because of a different prioritization on the NVDV's guideline agenda.
In the first meeting(s), the bottlenecks and wishes regarding the subject of CMN were inventoried within the working group. Based on this, the working group formulated key questions stated in the guideline. At the start of the process, a survey was also conducted among dermatologists and plastic surgeons in the Netherlands to make an inventory of the current policy regarding CMN. The objectives of this survey were to record the starting situation in order to arrive at a guideline that is in line with the workplace, and to identify additional bottlenecks.
The initial questions were elaborated into PICO search questions at the office of the Dutch Association for Dermatology and Venereology (NVDV). Useful literature was collected through systematic searches and reference checking. The secretary of the guideline and students, together with the working group members, assessed the literature on content and quality. Subsequently, texts were written in which the assessed literature was incorporated. These texts, based on the evidence tables with the processed literature, were discussed during a two-day meeting and provided with nuances and recommendations. After further discussion within the entire guideline working group, the text was fine-tuned.
The final text was presented to all scientific associations involved in September 2016. People were given the opportunity to comment on the guideline via the websites of the associations involved. The comments have been incorporated into the final version of the guideline.
Scientific evidence
The recommendations in this guideline are, as far as possible, based on evidence from published scientific research.
Relevant articles were searched through a systematic, exploratory search in Pubmed, covering the topic of congenital melanocytic nevi (from 1987 to November 2014, languages Dutch, English, French, German). For specific clinical questions, an additional systematic search was performed with more specific search terms for the relevant question, and in additional databases (such as Embase, CENTRAL, Cochrane library, etc.). The search was also repeated more recently for some key questions and passages (2014~2016). See also the search strategy.
The searches were constructed using the PICO system. This means that a search question has been formulated for each initial question, using the following structure as much as possible: Patient-Intervention-Control-Outcome. The search questions have the P as a common part, the other parts of the PICO are formulated on the basis of the initial question. Most of the search criteria depend on the initial question.
In general, the following search and selection criteria have been drawn up:
Taal | English, Dutch, German, French |
Population | Congenital melanocytic nevi (in all synonyms), all sizes, all ages (excluding acquired melanocytic nevi, or if it was not specified whether the nevi were congenital) |
level of evidence | Literature selection according to pyramid of evidence (EBRO method). Due to the often lack of good quality studies (randomized or prospective), there is no restriction on the fundamental design of the study |
size of the studies | In general, no limit has been set here, because for most clinical questions only case series with a few patients are available. Case reports and case series with <5 patients were, however, excluded from several clinical questions, because they give an even greater selection bias and therefore a possibly too distorted picture of reality. |
The full text of the references selected on the basis of title and/or abstract was requested. Subsequently, further selection was made on the basis of full-text articles and articles without information about the relevant clinical question were excluded. The remaining articles were assessed full-text for quality and content.
During the search, no (foreign) guidelines on this subject were identified, but a few relevant and reliable learning articles, in which relevant literature on the subject of CMN in its entirety has been brought together in a thorough manner. These articles partly form the basis for the single guideline texts [Alikhan 2012, Ibrahimi 2012, Viana 2013], supplemented with other relevant literature.
fig. 1: Pyramid of Scientific Evidence
Method of literature review
The guideline has been developed according to the EBRO method (Evidence-based Guideline Development). An 'evidence table' of the relevant articles has been drawn up for each sub-topic, in which the literature is summarized and assessed for quality. The description and assessment of the articles can be found in the various modules under the heading 'scientific substantiation', and the literature is then summarized in 'conclusions'. The quality of the articles and the level of relevant evidence were graded according to the EBRO method, using the classification in Table 1.
In addition, the GRADE method (Grading of Recommendations Assessment, Development and Evaluation) was chosen for the assessment of clinical question 12, in which the available evidence is 'pooled' for each outcome measure and assessed for the quality of the evidence, see table 2. The application of GRADE for this guideline was difficult because there are only observational studies, no comparative studies, and the studies are very heterogeneous in terms of patient and nevus characteristics. This method was therefore only applied to treatment modalities where pooling of results was possible according to the working group.
Table 1: EBRO method; A. level of claims according to EBRO; B. Classification of methodological quality of individual studies
A.
level | Conclusion based on |
1 | Level A1 examination or at least 2 level A2 examinations conducted independently of each other |
2 | 1 level A2 study or at least 2 level B studies conducted independently of each other |
3 | 1 level B or C examination |
4 | Expert opinion |
B.
Quality | Intervention | Diagnostic accuracy research | Harm / side effects*, etiology, prognosis |
A1 | Systematic review of at least two independently conducted A2 level studies | ||
A2 | Randomized double-blind comparative clinical trial of good quality of sufficient size | Study against a reference test (a “gold standard”) with predefined cut-off values and independent assessment of test and gold standard results, on a sufficiently large series of consecutive patients who all had the index and reference test | Prospective cohort study of sufficient size and follow-up, with adequate control for confounding and sufficient exclusion of selective follow-up. |
B | Comparative research, but not with all the characteristics as mentioned under A2 (this also includes case-control research, cohort research) | Research against a reference test, but not with all the characteristics mentioned under A2 | Prospective cohort study, but not with all characteristics as mentioned under A2 or retrospective cohort study or case-control study |
C | Non-comparative study | ||
D | Expert opinion | ||
* This classification only applies in situations where controlled trials are not possible for ethical or other reasons. If they are possible, the classification applies to interventions.
Table 2: GRADE method; A. GRADE level of evidence; C. method of assessing level of evidence per outcome measure
A.
GRADE Working Group grades of quality of evidence | |
High | We are very confident that the true effect lies close to that of the estimate of the effect |
Moderate | We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different |
Low | Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect |
Very low | We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect |
B.
Starting point of assessing quality of evidence | |
RCT’s | Start as ‘high quality’ |
Observational studies | Start as ‘low quality’ |
For each outcome measure across the studies, possibly downgrade one or two levels of quality of evidence (1-5) or upgrade (6-8) | |
1. | risk of bias |
2. | inconsistency |
3. | indirectness |
4. | imprecision |
5. | publication bias |
6. | large effect |
7. | plausible confounding |
8. | dose response gradient |
Development of the recommendations
In addition to the scientific evidence, other aspects are often important in arriving at a recommendation, for example: patient preferences, availability of special techniques or expertise, organizational aspects, social consequences or costs. These aspects are discussed after the conclusion(s) under 'other considerations'. In this, the conclusion based on the literature is placed in the context of daily practice and the advantages and disadvantages of the various policy options are weighed up. The ultimately formulated recommendation is the result of the available evidence in combination with these considerations from expert opinion. Following this procedure and drafting the guideline in this format aims to increase the transparency of the guideline.
fig. 2: Schematic representation of methodology of evidence-based guideline development
Innovation
The field of congenital melanocytic nevi is in flux. On the one hand, the molecular signature of CMN is gradually being unraveled, which provides important new starting points for new (genetic) diagnostics and (non-surgical) therapies. In addition, over the years there has been a shift from invasive and aggressive treatment to remove as much nevus tissue as possible in the context of an allegedly high risk of melanoma, to less aggressive and more superficial or partial intervention with a greater eye for the cosmetic result. Furthermore, in the past, only retrospective research has often been carried out with a high risk of bias. Some prospective studies have now been published on melanoma risk, but not yet on therapy in CMN.
Advice for research
Overall, well-conducted studies on CMN are lacking. Often only case series and case reports have been published, with a high risk of bias. This is somehow inherent to the subject, in which larger CMN in particular are rare, and CMN also differ to a large extent between individuals. Reliable research is particularly lacking in the field of therapies. Almost all authors measure different or non-validated outcome measures, and 'patient-important outcomes', such as quality of life, patient satisfaction, but also safety, are hardly studied. In the studies on melanoma risk, studies in adult patients and smaller CMN, and studies with longer follow-up duration (>10 years) are lacking. This also applies to studies into the risk of NCM, in which many different definitions of NCM have also been used.
Research on CMN should consist of prospective studies, with accurate and standardized recording of patient characteristics, and validated and standardized recording of outcomes, over a long period of time. With regard to treatment, more attention must also be paid to outcomes and safety that are important to the patient. In the field of melanoma risk, this has already been taken up internationally by setting up (national) prospective registries in various countries. The working group plans to set up such a registry in the Netherlands in the near future (via skinhuis.nl from the NVDV), which will also include the outcomes of therapies. It will later be linked to international registries.
In addition, more and better research is needed into diagnostic modalities in CMN, such as dermatoscopy and MRI, and diagnostic techniques to detect melanoma in CMN and to distinguish it from benign nevus tissue or proliferations.
Legal significance of guidelines
Guidelines are not legal requirements, but scientifically based and widely supported insights and recommendations that care providers should comply with in order to provide high-quality care. Since guidelines are based on 'average patients', healthcare providers can deviate from the recommendations in the guideline in individual cases if necessary. Deviating from guidelines is sometimes even necessary if the patient's situation requires it. However, if there is a deliberate deviation from the guideline, this must be substantiated, documented and, where necessary, discussed with the patient.
Search accountability
Searches are available on request. To do this, please contact theGuidelines database.
Attachments
- Relevant for patients
- Instructions for self-examination (to give)
- Summary Congenital Melanocytic Nevi (CMN)
- Background and definitions
- General introduction
- Explanation of laser modalities
- To apply
- Instructions for the medical photographer
- Quality of life questionnaires
- Protocol classification CMN
- Consulting room protocol