Dysplastic naevi with moderate to severe histological dysplasia: a risk factor for melanoma

Harvard University, Cambridge, Massachusetts, United States
British Journal of Dermatology (Impact Factor: 4.1). 12/2006; 155(5):988-93. DOI: 10.1111/j.1365-2133.2006.07466.x
Source: PubMed

ABSTRACT The risk of malignant melanoma associated with histologically dysplastic naevi (HDN) has not been defined. While clinically atypical naevi appear to confer an independent risk of melanoma, no study has evaluated the extent to which HDN are predictive of melanoma.
To estimate the risk of melanoma associated with HDN. Secondarily, the risk associated with number of naevi and large naevi is estimated.
We enrolled 80 patients with newly diagnosed melanoma along with 80 spousal controls. After obtaining information on melanoma risk factors and performing a complete cutaneous examination, the most clinically atypical naevus was biopsied in both cases and controls. Histological dysplasia was then assessed independently by 13 dermatopathologists (0, no dysplasia; 1, mild dysplasia; 2, moderate dysplasia; 3, severe dysplasia). The dermatopathologists were blinded as to whether the naevi were from melanoma subjects or controls. Multivariate analyses were performed to determine if there was an independent association between the degree of histological dysplasia in naevi and a personal history of melanoma.
In persons with naevi receiving an average score of > 1 (i.e. naevi considered to have greater than mild histological dysplasia), there was an increased risk of melanoma [odds ratio (OR) 2.60, 95% confidence interval (CI) 0.99-6.86] which persisted after adjustment for confounders (OR 3.99, 95% CI 1.02-15.71). Very few dermatopathologists reliably graded naevi of subjects with melanoma as being more dysplastic than naevi of control subjects. Among the entire group, the interobserver reliability associated with grading histological dysplasia in naevi was poor (weighted kappa 0.28).
HDN do appear to confer an independent risk of melanoma. However, this result may add more to our biological understanding of melanoma risk than to clinical assessment of risk, because HDN assessed by a single pathologist generally cannot be used to assess risk of melanoma. Future studies should be directed at establishing reproducible, predictive criteria for grading naevi.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this work, the effect of cyclic pre-hardening (CPH) and monotonic pre-hardening (MPH), on the Cyclic Stress–Strain Curve (CSSC) and fatigue are considered. New tension-compression tests on two types of 304L alloys used in nuclear power plants are carried out under the following conditions: (i) strain or stress control near endurance limit; (ii) zero or positive mean stress; (iii) virgin, CPH or MPH specimens. Macroscopic results show a detrimental effect of pre-hardening in strain control and a beneficial one in stress control. Some macroscopic considerations are given to explain this result and the effects of an applied mean stress which differ under stress and strain control. Relations between macroscopic results and microstructures at failure are investigated using SEM and TEM. SEM is used for analysis of fatigue striation space.TEM analyses suggest that cyclic pre-hardening mainly promotes wavy slip during subsequent fatigue testing, while monotonous pre-loading favors planar slip. For CPH case it seems that primary cells which are preserved and refined for the most part during fatigue testing, constitute the hard stable structure. After MPH and subsequent fatigue testing, a hard structure is constituted by embedding of three kinds of microstructures, small twins, small cells, crossing twin systems. The formation of a hard structure creates an important internal stress. Observation shows that in pre-hardened specimens, softening arrays as veins and PSBs are frequent under strain control and rather scarce under stress control. It can be so deduced that the increase of fatigue life by pre-hardening in stress control is related to reduced mean free path of mobile dislocations due to internal stress.The obtained results may help to understand some aspects about linear versus non linear fatigue damage accumulation.
    International Journal of Plasticity 12/2011; 27(12):1981-2004. DOI:10.1016/j.ijplas.2011.06.004 · 5.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionAtypical melanocytic nevi are acquired melanocytic lesions that were described for the first time by Clark in studies of melanocytic nevi in patients with melanomas. Today, the use of dermatoscopy has made identification of this type of nevus much easier.
    Actas Dermo-Sifiliográficas 06/2008; 99(5). DOI:10.1016/S0001-7310(08)74697-0
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background There is a perpetuating increase in melanoma and basal cell carcinoma (BCC) incidence in Europe. Few studies are evaluating various risk factors for both tumours.Objectives This pre-planned additional analysis directly compared occupational and past-time ultraviolet exposure behaviour, and examined the effects of sun sensitivity between melanoma and sporadic BCC, and assessed its importance for the two entities.Patients/Methods The study included 503 patients (melanoma, n = 291 and BCC, n = 212), and 329 controls from Germany. In all, 244 (49%) of the cases and 165 (50%) of the controls were male (median age melanoma, 55 years; BCC, 69 years; and controls, 57 years). Selection of important risk factors was performed by backward elimination in a polytomous logistic regression.ResultsWhen directly comparing melanoma and sporadic BCC, actinic elastosis (OR 48.83; 95% CI 17.87, 133.40) and site were associated with a higher risk of melanoma, whereas mountaineering in childhood, sunburn 20 years before diagnosis, farming full time, sunbed use in general, seborrheic keratosis, actinic cheilitis, actinic keratosis and age were associated with a higher risk of sporadic BCC. Gardening 20 years before melanoma, hair colour and solar lentigo were risk factors for both entities. A re-evaluation of the data excluding lentiginous melanoma entities (i.e. acro-lentiginous and lentigo-maligna melanoma) resulted in selection of the same factors. However, compared to controls, atopy evolved as a protective factor for melanoma (OR 0.29; 95% CI 0.15, 0.57) and BCC (OR 0.41; 95% CI 0.17, 0.99), respectively, but was associated with a higher risk of sporadic BCC compared to melanoma.Conclusion The odds for having clinical actinic elastosis was lower in BCC compared to melanoma. In contrast, various factors associated with chronic UV exposure and age had higher odds for sporadic BCC, rather than melanoma. Further research is required to set the context for these findings, especially regarding, atopy in non-lentiginous vs. lentiginous forms of melanoma, and possible molecular pathways involved.
    Journal of the European Academy of Dermatology and Venereology 03/2014; DOI:10.1111/jdv.12488 · 3.11 Impact Factor