Few topics in pathology engender as much controversy as the dysplastic nevus. Even its name is not universally accepted. Most investigators use this term to describe a clinically distinct nevus first described in a familial setting of patients with an increased risk of melanoma. Dr. Wallace Clark (of Clark's level fame) noted the distinctive histologic and clinical appearance of these moles. Familial cases were coined B-K mole syndrome (based upon the initials of the surnames of the two of the kindreds) and the FAMMM syndrome (Familial atypical mole/malignant melanoma syndrome). The B-K mole patients were later denoted as part of the dysplastic nevus syndrome.
Terms Used for the Dysplastic Nevus
Nevus with architectural disorder
Nevus with atypical melanocytic hyperplasia
Since the original descriptions, sporadic cases have been described. The latter are estimated to occur in 2-18% of the general population. In comparison to ordinary nevi, they are usually larger with a more variegated appearance. In patients with the dysplastic nevus syndrome, there are many nevi, sometimes 80 or more, many of which are larger than the sporadic cases. In sporadic cases of dysplastic nevi, a Caucasian living in the USA has a 10% lifetime risk of developing melanoma. In patients with familiar melanoma, the risk exceeds 50%.
Although the histologic criteria may appear to be reproducible, some studies have found poor inter- and intra-observer concordance in both the diagnosis and grading of the atypia. Other studies, have found better concordance for the architectural but not the cytologic atypia. Again, if there is any question about the diagnosis, it is best to have a dermatopathologist review the case.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Atypical nevus
Nevus with architectural disorder
Nevus with atypical melanocytic hyperplasia
DISEASE ASSOCIATIONS CHARACTERIZATION HIV INFECTION
Eruptive dysplastic nevi associated with human immunodeficiency virus infection.
Duvic M, Lowe L, Rapini RP, Rodriguez S, Levy ML.
Department of Dermatology, University of Texas Health Science Center, Houston.
Arch Dermatol 1989 Mar;125(3):397-401 Abstract quote
The cutaneous manifestations of the acquired immunodeficiency syndrome include infections and neoplasms resulting from the immunodeficient state.
Seven patients presenting with the symptom of new eruptive nevi with dysplastic histologic findings are described. These patients noted multiple new moles, which occurred in crops and in individuals without the dysplastic nevus syndrome (familial melanomas). This symptom occurred as the patients became symptomatic from their human immunodeficiency virus infection, developing acquired immunodeficiency syndrome or its related complex.
Further confirmation and study of this phenomenon could lead to a better understanding of the pathogenesis of melanocytic dysplasia and its relationship to the immune system.
Cutaneous dysplastic naevi in uveal melanoma patients: markers for prognosis?
Toth-Molnar E, Hammer H, Olah J.
Department of Ophthalmology, Szent-Gyorgyi Albert Medical University, Szeged, Hungary.
Melanoma Res 2000 Feb;10(1):36-9 Abstract quote
We have previously reported that the presence of cutaneous dysplastic naevi is a risk factor for uveal melanoma.
In the present study our goal was to determine the incidence of different histopathological features of uveal melanoma among 91 patients with or without cutaneous dysplastic naevi. Statistical analysis revealed that the presence of cutaneous dysplastic naevi in uveal melanoma patients is associated with an increased incidence of the prognostically worst forms of uveal melanoma (epithelioid or mixed cell type melanomas). The relative risk was 5.97 (95% confidence interval 1.61-22.14).
Our results suggest that the presence of cutaneous dysplastic naevi is not only a risk factor but also a prognostic factor for uveal melanoma.
Primary malignant melanoma of the gallbladder in dysplastic naevus syndrome.
Ricci R, Maggiano N, Martini M, Mule AM, Pierconti F, Capelli A, Larocca LM.
Department of Pathology, Universita Cattolica del Sacro Cuore, Rome, Italy.
Virchows Arch 2001 Feb;438(2):159-65 Abstract quote
A case of gallbladder involvement by malignant melanoma in a 57-year-old woman is reported. The gallbladder, resected for cholelithiasis, harboured a pedunculated polypoid dark mass, which histologically revealed sheets and nests of epithelioid cells with hyperchromatic nuclei in the lamina propria and at the junctional level. These cells were pigmented (with positive reaction with Schmorl's stain and bleaching with peroxide) and showed immunohistochemical positivity for S-100, gp 100 antigen (HMB-45 antibody) and vimentin.
The patient, affected by dysplastic naevus syndrome, had a melanoma in situ excised from the scalp 8 years earlier. The features of the investigated lesion address towards a diagnosis of primary gallbladder melanoma.
Furthermore, this is the first time that the existence of such a controversial entity is sustained by the ultrastructural investigation of melanosomes, demonstrating the presence of two melanocitary populations, a typical one exclusively junctional and an atypical one both at the junctional level and in the lamina propria.
- Dysplastic nevi with an underlying or juxtaposed neurofibroma: does a relationship exist?
Maize Center for Dermatopathology, Charleston, SC, USA.
- J Cutan Pathol. 2007 Nov;34(11):837-43. Abstract quote
Background: Neurofibromas and dysplastic nevi are both common skin disorders found in the general population. The cells in both of these neoplasms are derived from neural crest. There are no published reports of these two lesions occurring in juxtaposition.
Objective: We report, for the first time, three cases of dysplastic nevi in spatial association with a neurofibroma that occurred in unrelated individuals.
Methods and results: Three cases of dysplastic nevi occurring in association with solitary neurofibromas were selected prospectively from the routine accessions from August 1, 2003, to July 31, 2005. In none of the three cases, was a dysplastic nevus suspected by the clinician.
Conclusion: The finding of dysplastic nevi in a spatial relationship to a neurofibroma is not happenstance since they are both of neural crest cell origin and respond to the same growth factors. It is our belief that these lesions are related and may occur together more often than reported.
Eruptive dysplastic naevi following renal transplantation.
Barker JN, MacDonald DM.
Clin Exp Dermatol 1988 Mar;13(2):123-5
PATHOGENESIS CHARACTERIZATION GENERAL
A hypothesis incorporating the histologic characteristics of dysplastic nevi into the normal biological development of melanocytic nevi.
Department of Medicine, University of Utah School of Medicine, Salt Lake City 84132.
Arch Dermatol 1990 Apr;126(4):514-8 Abstract quote
A lentiginous pattern of intraepidermal melanocytic hyperplasia, with mild to moderate, random cytologic atypia, forms the conventional basis for the histologic definition of a dysplastic nevus.
It is proposed here that these changes actually represent the histologic pattern of a nevus in an active phase of radial growth. The lesser degrees of atypia considered by others to be required for the diagnosis are suggested to overlap changes commonly seen in banal nevi and lentigines. This hypothesis allows the parsimonious concept that a nevus, originating as a lentigo, can at the later sequential junctional, compound, or intradermal stages expand peripherally by a resumption or persistence of the lentiginous pattern of proliferation. The random atypia that is seen in such lesions is suggested to be incidental to the proliferative process rather than indicative of dysplasia as conventionally defined.
A familial melanoma-associated phenotype could be accommodated in this model by postulating a heritable defect in mechanisms that control the number or sizes of these hyperplastic lesions.
CDKNA Expression of the tumor suppressor gene product p16 (CDKNA) in benign and malignant melanocytic lesions
J Invest Dermatol 1998;110:932-938
Expression of this major melanoma susceptibility gene is not substantially altered in atypical nevi
Gene-covariate interaction between dysplastic nevi and the CDKN2A gene in American melanoma-prone families.
Goldstein AM, Martinez M, Tucker MA, Demenais F.
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-7236, USA.
Cancer Epidemiol Biomarkers Prev 2000 Sep;9(9):889-94 Abstract quote
The CDKN2A gene has been implicated in cutaneous malignant melanoma pathogenesis. Although CDKN2A mutations confer substantial risk for melanoma, clinicoepidemiological covariates including dysplastic nevi (DN), total nevi, and solar injury also enhance melanoma risk.
To examine the relationship between CDKN2A and these three risk factors, we conducted combined segregation/linkage analysis using the class D regressive logistic model, as implemented in the computer program REGRESS. Genetic and covariate data were collected on 20 American melanoma-prone families, 13 of which had cosegregating CDKN2A mutations. Two types of analyses were conducted. The missing-indicator method used a missing-value indicator, set to 1 for unknown and 0 for known covariate status, and a second variable set to 1 for exposed and 0 for unexposed or unknown. The second method, complete-cases method, coded subjects with missing covariates as unknown for the affection status. The results for both analyses were very similar.
Overall, there was a significant improvement in the likelihood when DN, total nevi or both covariates were added to the base model, which included dominant transmission of the CDKN2A gene and a linear increase of risk with the logarithm of age on the logit scale. In contrast, inclusion of solar injury did not significantly improve the likelihood for the base model. Significant evidence for a gene-covariate interaction was detected between DN and CDKN2A when DN was the only covariate in the model (missing-indicator method or complete-cases method) or when both DN and total nevi were in the model (complete-cases method only). Interestingly, in both methods, the odds ratio (OR) for DN was greater in subjects without mutations (OR, 20.1; 95% confidence interval, 4.8-92.8) versus those with CDKN2A mutations (OR, 3.3; 95% confidence interval, 1.1-10.0; complete-cases method).
The CDKN2A-DN interaction illustrates the complex etiology of melanoma and needs to be confirmed in a larger sample of families.
Comprehensive analysis of 112 melanocytic skin lesions demonstrates microsatellite instability in melanomas and dysplastic nevi, but not in benign nevi.
Hussein MR, Sun M, Tuthill RJ, Roggero E, Monti JA, Sudilovsky EC, Wood GS, Sudilovsky O.
Institute of Pathology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA.
J Cutan Pathol 2001 Aug;28(7):343-50 Abstract quote
INTRODUCTION: the length of DNA repetitive sequences (microsatellite instability (MSI)) represent distinct tumorigenic pathways associated with several familial and sporadic tumors.
MATERIAL AND METHODS: To investigate the prevalence and frequency of MSI in melanocytic lesions, the polymerase chain reaction (PCR)-based microsatellite assay was used to examine formalin-fixed, paraffin-embedded tissues of 30 benign melanocytic nevi, 60 melanocytic dysplastic nevi (MDN), and 22 primary vertical growth phase cutaneous malignant melanomas (CMM). Twenty-four microsatellite markers at the 1p, 2p, 3p, 4q and 9p chromosomal regions were used.
RESULTS: MSI was found at 1p and 9p in MDN and CMM but not in benign melanocytic nevi. The overall prevalence of MSI was 17/60 (28%) in MDN and 7/22 (31%) in CMM. The frequency of MSI ranged from 2/24 (9%) to 4/24 (17%) and was most commonly found at D9S162. There was a statistically significant correlation between degree of atypia and frequency of MSI (p<0.001) in MDN. There were two MSI banding patterns: band shifts and additional bands.
CONCLUSIONS: The data presented revealed the presence of low-frequency MSI (MSI-L) at the 1p and 9p regions in both MDN and CMM. Whether the MSI-L pattern reflects a defect in mismatch repair genes is still to be determined.
MISMATCH REPAIR GENES
Alterations of mismatch repair protein expression in benign melanocytic nevi, melanocytic dysplastic nevi, and cutaneous malignant melanomas.
Hussein MR, Roggero E, Sudilovsky EC, Tuthill RJ, Wood GS, Sudilovsky O.
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Am J Dermatopathol 2001 Aug;23(4):308-14 Abstract quote
Immunoperoxidase-staining methods were used to examine the expression of hMLH1, hMSH2, and hMSH6 mismatch repair (MMR) proteins in 50 melanocytic lesions. Microsatellite instability (MSI), screened previously in these lesions by polymerase chain reaction-based microsatellite assay, showed low-level microsatellite instability (MSI-L) in 11 of 22 melanocytic dysplastic nevi (MDN) and two of nine primary cutaneous malignant melanomas (CMMs) but not in the benign melanocytic nevi (BN).
Mismatch repair proteins were widely expressed in the epidermis and adnexal structures. All lesions showed positive immunoreactivity with a gradual decrease in the MMR staining values during the progression from BN to MDN to CMMs. The average percentage of positively (PP) stained cells for hMLH1, hMSH2, and hMSH6 in BN was 85.50 +/- 1.95, 77.90 +/- 4.50, and 87.11 +/- 1.85, respectively. The PP cell values in CMMs were significantly reduced as compared with BN (75.22 +/- 3.57, p= 0.01; 56.11 +/- 8.73, p= 0.02; 65.22 +/- 6.47, p = 0.0002 for hMLH1, hMSH2, and hMSH6, respectively). No comparable significant difference was found between microsatellite stable and MSI-L lesions (p = 0.173, p = 0.458, and p = 0.385), suggesting a lack of correlation between MMR expression and MMR function. There was a direct correlation between PP cell values of hMSH2 and hMSH6 (R = 0.39, p = 0.008), implying that their expression could be regulated by a common mechanism.
Thus, an important finding of these studies was the reduction of MMR protein levels in CMMs; whether this reflects underlying genetic or epigenetic mechanisms is still to be determined.
VERSICAN Expression of the Proteoglycans Versican and mel-CSPG in Dysplastic Nevi
Malika Touab, PhD,1 Montserrat Arumi-Uría, MD,2 Carlos Barranco, MD,3,4 and Anna Bassols, PhD
Am J Clin Pathol 2003;119:587-593 Abstract quote
Nevi with architectural disorder and cytologic atypia of melanocytes (NAD) (also called dysplastic nevi) have been controversial with regard to their relationship with melanoma risk and to their gradation in 3 degrees of atypia.
Versican and the melanoma-associated proteoglycan (mel-CSPG) are 2 major proteoglycans expressed by malignant melanoma, and they have a role in the regulation of cell adhesion, migration, and differentiation. We evaluated the differences in versican and mel-CSPG expression in nevi, NAD with several degrees of atypia, and primary malignant melanoma. Immunoreactivity for versican was negative in benign melanocytic nevi, positive in NAD (ranging from weakly to intensely positive), and intensely positive in malignant melanoma. Immunostaining for mel-CSPG was negative in benign melanocytic nevi and mild to moderately positive in NAD and melanoma.
Our results suggest that versican expression may be of value for distinguishing NAD from benign melanocytic nevi and for distinguishing severe NAD from mild and moderate NAD.
DNA ploidy and nuclear morphometry for the classification of dysplastic nevi.
Williams RA, Baak JP, Meijer GA, Charlton IG.
Department of Anatomical Pathology, St. Vincent's Hospital, Melbourne, Australia.
Anal Quant Cytol Histol 1999 Oct;21(5):437-44 Abstract quote
OBJECTIVE: To examine the diagnostic value of DNA ploidy and nuclear morphometric features in sporadic dysplastic nevi as compared to those in compound nevi and melanoma.
STUDY DESIGN: DNA ploidy profiles plus seven direct and three derived nuclear features were obtained in a series of 120 melanocytic skin neoplasms (30 dysplastic nevi [DN], 30 melanomas [MM], 60 compound nevi [CN]) and the results compared.
RESULTS: DNA ploidy separated melanomas from benign melanocytic skin neoplasms with 96.5% accuracy in classifying the grouped cases. The derived nuclear shape factor Form PE and nuclear axis ratio were the most successful discriminants separating DN from MM but allowed only 73.3% correct classification of cases. Separation of DN from CN was best achieved using Form PE and mean nuclear area (74.4% correctly classified). Results from compound nevi in subjects < 25 years of age fell between those for DN and MM.
CONCLUSION: Quantitative nuclear cytologic characteristics in sporadic dysplastic nevi span a range seen in common nevi through to those in thin melanomas. Cytologic changes in sporadic dysplastic nevi overlap those seen in other melanocytic skin neoplasms. Therefore, other reproducible morphometric features need to be assessed in order to further refine the histopathologic diagnosis of this entity.
DERMOSCOPY Dermoscopic patterns of benign volar melanocytic lesions in patients with atypical mole syndrome.
Malvehy J, Puig S.
Department of Dermatology, Hospital Clinic, Institut de Investigacions Biomediques August Pi i Sune, Barcelona, Spain.
Arch Dermatol. 2004 May;140(5):538-44. Abstract quote
BACKGROUND: Acral benign melanocytic lesions in white populations, particularly in subjects with atypical mole syndrome, have been poorly characterized until recently. The advent of dermoscopy has enabled more specific diagnoses of these pigmented skin lesions.
OBJECTIVE: To evaluate the clinical and dermoscopic features of benign volar lesions in a group of white patients with atypical mole syndrome.
SETTING: A private medical center specializing in early diagnosis of malignant melanoma and a melanoma unit in a university hospital.
METHODS: Acral melanocytic lesions in 511 patients with atypical mole syndrome were studied using standard clinical assessment and dermoscopy.
RESULTS: Two hundred ten acral melanocytic lesions were observed in 156 of the patients: 165 lesions were present on the soles of 121 patients and 45 lesions on the palms of 35 patients. No acral malignant lesions were detected. We observed the following patterns of lesions: parallel furrow in 111 lesions (52.9%), latticelike in 26 lesions (12.4%), fibrillar or filamentous in 13 lesions (6.2%), and nontypical in 29 lesions (13.8%). In 31 lesions (14.8%), we observed 3 previously undefined patterns: a globular pattern in 11 lesions (5.2%), a homogeneous pattern in 15 lesions (7.1%), and an acral reticular pattern in 5 lesions (2.4%).
CONCLUSIONS: We observed a greater number of benign melanocytic lesions in glabrous skin than expected, probably related to our cohort selection of patients with atypical mole syndrome, although the lesions generally exhibited patterns on dermoscopy similar to those seen in Japanese studies. We defined 3 new benign dermoscopic patterns, which will enable better characterization of acral lesions.
Teaching non-specialist health care professionals how to identify the atypical mole syndrome phenotype: a multinational study.
Bishop JA, Bradburn M, Bergman W, Osterlind A, Pinney E, Rosdahl I, Scerri L, Weichenthal M, Mant D, Breitbart EW, Karlsson P, Altman DG.
ICRF Cancer Medicine Research Unit, St James's University Hospital, Leeds, UK
Br J Dermatol 2000 Feb;142(2):331-7 Abstract quote
The atypical mole syndrome (AMS) phenotype is the strongest known risk factor for cutaneous melanoma but recognition of the phenotype has been claimed to be problematic and to require specialist assessment.
This study determined the ability of previously unskilled doctors and nurses in five countries to recognize the phenotype after brief training. The system used was the AMS scoring system. This incorporates melanocytic naevus counts, clinical atypia of naevi and distribution of naevi. The agreement in scoring between the dermatologist and trained personnel was determined in 986 patients; overall agreement in diagnosis was 94.5% (kappa 0.70, P < 0.0001). The kappa scores in different countries ranged from 0.65 to 0.77 for individual naevus characteristics, indicative of good agreement.
Accurate diagnosis of the atypical mole syndrome phenotype is possible by non-specialists.This has implications for collaborative studies of naevi, for screening and for both primary and secondary prevention of melanoma.
VARIANTS AGMINATED DYSPLASTIC NEVI
Agminated Atypical (Dysplastic) Nevi Case Report and Review of the Literature
Ashfaq A. Marghoob, MD; Robin Blum, BS; Robert Nossa, MD; Klaus J. Busam, MD; Dana Sachs, MD; Allan Halpern, MD
Arch Dermatol. 2001;137:917-920 Abstract quote
Background Patients with the atypical mole syndrome have multiple dysplastic nevi that appear to be randomly distributed on certain preferred anatomical sites such as the upper back. These dysplastic nevi are thought to be acquired melanocytic nevi that begin appearing at puberty. To our knowledge, the presence of agminated atypical (dysplastic) nevi has not been reported.
Observation We describe a patient with the atypical mole syndrome who has more than 100 melanocytic nevi, many of which are clinically atypical and one of which proved to be a melanoma. Among his many melanocytic nevi is a cluster of approximately 50 nevi that are distributed in an area measuring 5 3 cm. The histopathologic features of these nevi are consistent with the diagnosis of "dysplastic nevus."
Conclusions To our knowledge, agminated atypical (dysplastic) nevi have not been described previously. The presence of agminated atypical (dysplastic) nevi in a patient with the atypical mole syndrome can be theorized to arise because of loss of heterozygosity.
Dysplastic nevi of the scalp and forehead in children.
Fernandez M, Raimer SS, Sanchez RL.
Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0783, USA.
Pediatr Dermatol 2001 Jan-Feb;18(1):5-8 Abstract quote
To determine if there is a significant difference in the relative frequency and degree of atypia of sporadic dysplastic nevi from the scalp, face, and neck area in children as compared with nevi from the rest of the body, we reviewed 99 consecutive biopsy specimens of melanocytic nevi from the scalp, face, and neck areas in children less than 18 years of age and compared them with 95 consecutive cases of nevi from other areas of the body in children of the same age.
Large numbers of the nevi biopsied from the scalp (13 of 31; 41.93%) and forehead (2 of 10; 20%) were dysplastic. The number of dysplastic nevi from the neck (1 of 58; 1.72%) was not assessed as very different from the incidence found in other regions of the body, where 7 dysplastic nevi (7.36%) from a total of 95 nevi were found. Of the 13 dysplastic nevi from the scalp, 9 showed minimal atypia and 4 showed moderate atypia. No nevi with severe atypia were found. Many pigmented nevi from the scalp and forehead in children in this study were dysplastic.
This finding points out the importance of examining the scalp of children for the presence of dysplastic nevi. The majority of nevi from the neck were common nevi.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL The histologic criteria has been characterized by the following: HISTOLOGIC DEFINITIONS Description Lentiginous hyperplasia Proliferation of melanocytes singly and within nests along the dermal-epidermal junction. Random cytological atypia
Nuclei equal the size of nuclei of overlying keratinocytes or are larger
Atypia may be graded mild, moderate, or severe
Stromal response Lamellar or concentric fibroplasia of the papillary dermis Variability in nomenclature used for nevi with architectural disorder and cytologic atypia (microscopically dysplastic nevi) by dermatologists and dermatopathologists.
Shapiro M, Chren MM, Levy RM, Elder DE, LeBoit PE, Mihm MC Jr, Margolis DJ, Gimotty PA, Ming ME.
Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
J Cutan Pathol. 2004 Sep;31(8):523-30. Abstract quote
Background: Although a nevus with the microscopic features of a 'dysplastic nevus' is commonly seen, the nomenclature used to describe such a lesion has been thought to be inconsistent. A 1992 National Institutes of Health (NIH) Consensus Conference sought to unify nomenclature and suggested that the term 'nevus with architectural disorder' be used along with a comment on melanocytic atypia.
Methods: We performed a cross-sectional mail survey to determine preferred terminology as well as the level of adherence to the NIH-recommended nomenclature. All 856 active members of the American Society of Dermatopathology (ASDP) and 1100 (13.0%) of the 8471 active members of the American Academy of Dermatology (AAD) were surveyed.
Results: Five hundred and thirty-three ASDP members and 483 AAD members who fulfilled eligibility criteria completed the questionnaire. The term 'dysplastic nevus' was favored by the largest number of responders (favored by 39.1% of ASDP members and 62.3% of AAD members), while the 1992 NIH Consensus Conference-recommended terminology was the second most popular term (25.3% of ASDP and 15.1% of AAD members). Dermatopathologists (OR = 1.9, p = 0.0001) and those who had dual training in dermatology and dermatopathology (OR = 1.6, p = 0.02 for ASDP members; OR = 2.3, p = 0.02 for AAD members) were more likely to adhere to the 1992 NIH Consensus Conference nomenclature.
Conclusions: Despite attempts to unify nomenclature for microscopically dysplastic nevi through the NIH Consensus Conference, wide variation in terminology persists. Shapiro M, Chren M-M, Levy RM, Elder DE, LeBoit PE, Mihm Jr MC, Margolis DJ, Gimotty PA, Ming ME. Variability in nomenclature used for nevi with architectural disorder and cytologic atypia (microscopically dysplastic nevi) by dermatologists and dermatopathologists.
Validity of the histopathological criteria used for diagnosing dysplastic naevi. An interobserver study by the pathology subgroup of the EORTC Malignant Melanoma Cooperative Group.
de Wit PE, van't Hof-Grootenboer B, Ruiter DJ, Bondi R, Brocker EB, Cesarini JP, Hastrup N, Hou-Jensen K, MacKie RM, Scheffer E, et al.
Institute of Pathology, University Hospital Nijmegen, The Netherlands.
Eur J Cancer 1993;29A(6):831-9 Abstract quote
Ten (dermato)pathologists studied 50 cutaneous melanocytic lesions including common naevocellular naevi, dysplastic naevi (DN), melanomas in situ and invasive primary melanomas, with emphasis on the histological criteria of DN.
Using a standardised form, 20 defined histopathological features were scored (semi)quantitatively. Concordance of diagnosis, efficacy and reproducibility of features were investigated. DN were distinguished well from the other entities (mean Po 0.87). Agreement on the degree of atypia of DN was low.
The reproducibility of the scoring was best for the following features: irregular nests, lymphohistiocytic infiltrate, marked junctional proliferation and large nuclei. The overall values of these features to discriminate between DN and non-DN were better than for the other features studied. Using the presence of at least three of the four features as a condition for the diagnosis of DN, values for sensitivity, specificity and positive and negative predictive values were 0.86, 0.91, 0.96 and 0.73, respectively.
On the basis of the results these features seem best suited as histological criteria for the diagnosis of DN.
A multiobserver, population-based analysis of histologic dysplasia in melanocytic nevi.
Piepkorn MW, Barnhill RL, Cannon-Albright LA, Elder DE, Goldgar DE, Lewis CM, Maize JC, Meyer LJ, Rabkin MS, Sagebiel RW, et al.
Department of Internal Medicine (Dermatology), University of Utah School of Medicine, Salt Lake City.
J Am Acad Dermatol 1994 May;30(5 Pt 1):707-14 Abstract quote
BACKGROUND: Nevi that are clinically atypical and histologically dysplastic have been associated with increased melanoma risk. There are few reproducibility studies or population-based studies of nevus histology.
OBJECTIVE: Our purpose was to quantify concordance in histologic diagnosis of melanocytic lesions among a diverse group of pathologists, to assess intraobserver concordance by comparing readings of the same slide as well as of adjacent recuts from the same block, to correlate histology with nevus appearance and melanoma risk, and to estimate the range of prevalence of histologic dysplasia.
METHODS: Histologic slides were prepared from 149 tissue blocks of pigmented lesions from melanoma cases, relatives, and controls. Six dermatopathologists independently evaluated the lesions for histologic dysplasia, without prior agreement on criteria.
RESULTS: According to kappa statistics, intraobserver reproducibility was substantial, and interobserver concordance was fair, despite differences in criteria. The estimated prevalences of histologic dysplasia for the six pathologists ranged from 7% to 32%. Histologic dysplasia was correlated with nevus size for most observers, confounding the observed correlation between nevus appearance and histology.
CONCLUSION: Although experienced dermatopathologists use different diagnostic criteria for histologic dysplasia, their usage is consistent. Histologic changes ascribed to melanocytic dysplasia are prevalent in the white population for all pathologists. The term nevus with histologic dysplasia should be used in preference to dysplastic nevus.
Dysplastic changes in different types of melanocytic nevi. A unifying concept.
Toussaint S, Kamino H.
Department of Dermatology, New York University Medical Center, New York, USA.
J Cutan Pathol 1999 Feb;26(2):84-90 Abstract quote
We observed histopathologic changes previously described in dysplastic melanocytic nevi in association with a dermal component characteristic of other types of melanocytic nevi or overlapping with features of other varieties of nevi.
In order to determine the frequency of these changes, we studied 2,164 cases of compound melanocytic nevi that fulfilled the histopathologic criteria for the diagnosis of compound dysplastic nevus, including architectural pattern, cytologic features, and mesenchymal changes. Of the 2,164 compound dysplastic melanocytic nevi, 1,895 (87.6%) had the histopathologic characteristics previously described for dysplastic nevus, 179 (8.3%) showed a dermal component with a congenital pattern, 67 (3.1%) demonstrated epidermal and dermal characteristics of Spitz's nevus, 8 (0.3%) had features of a combined blue nevus, 13 (0.6%) had a halo phenomenon and 2 (0.1%) showed dermal neuronevus.
By considering these nevi as variants of dysplastic nevi, one may apply a unified conceptual basis for their nomenclature. In order to completely describe the appearance of the nevus, we named them by adding the term "dysplastic", to their main histopathologic subtype.
Accordingly, six different varieties of dysplastic nevi were identified: 1) dysplastic nevus (original); 2) dysplastic nevus with a congenital pattern; 3) dysplastic Spitz's nevus; 4) dysplastic combined blue nevus; 5) dysplastic halo nevus; and 6) dysplastic neuronevus. In summary, we conclude that the histopathologic criteria previously reported for the diagnosis of dysplastic nevi may be found in association with a dermal component characteristic of other types of melanocytic nevi or may have overlapping features with other variants of nevi.
Atypical Histologic Features in Melanocytic nevi
Am J Dermatopathol 2000;22:391-396
253 common, non-dysplastic melanocytic nevi were examined
Six histologic features were identified:
Disordered nested pattern
Dermal lymphocytic infiltrate
This study found atypical histologic features in 72% of nevi, occurring singly or in combination-thus histologic diagnostic criteria for dysplastic nevi may be inappropriate and may not reflect the histologic complexity of the lesions
Critical analysis of histologic criteria for grading atypical (Dysplastic) melanocytic nevi
Am J Clin Pathol 2001;115:194-204
Low concordance in grading atypical (dysplastic) melanocytic nevi (AMN) has been reported, and no systematic evaluation is available
Study of 123 AMN with architectural and cytologic atypia (40 associated with atypical-mole syndrome), classified according to standard criteria by 3 independent observers
Histologic variables included:
Junctional and dermal symmetry
Cohesion and migration of epidermal melanocytes
Inflammatory infiltrate location
AMN (43 junctional and 80 compound) were graded mild (31), moderate (61), and severe (31)
AMN-severe correlated with 3 or more nuclear abnormalities (especially pleomorphism, heterogeneous chromatin, and prominent nucleolus) and absence of regression, mixed junctional pattern, and suprabasilar melanocytes on top of lentiginous hyperplasia.
AMN-severe diagnostic accuracy was 99.5% using these criteria, but only the absence of nuclear pleomorphism differentiated AMN-mild from AMN-moderate
No architectural features distinguishing AMN-mild from AMN-moderate were selected as significant by the discriminant analysis.
AMN from atypical-mole syndrome revealed subtle architectural differences, but none were statistically significant in the discriminant analysis.
Histologic criteria can reliably distinguish AMN-severe but fail to differentiate AMN-mild from AMN-moderate. AMN from atypical-mole syndrome cannot be diagnosed using pathologic criteria alone.
VARIANTS DE NOVO INTRAEPIDERMAL EPITHELIOID MELANOCYTIC DYSPLASIA (DNIEMD)
- De novo intraepidermal epithelioid melanocytic dysplasia as a marker of the atypical mole phenotype - a clinical and pathological study of 75 patients.
Sachdeva M, Frambach GE, Crowson AN, Deng AC, Mihm MC Jr, Magro CM.
College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA.
J Cutan Pathol. 2005 Oct;32(9):622-8 Abstract quote.
Background: We encountered a distinctive pattern of dysplastic intraepidermal melanocytic proliferation, which defies classification as a dysplastic melanocytic nevus, but in which the morphologic features fall short of a diagnosis of melanoma in situ. We designate such lesions as de novo intraepidermal epithelioid melanocytic dysplasia.
Methods: From 75 patients, 82 skin biopsies were encountered that showed this distinctive morphology. Hematoxylin- and eosin-stained histologic sections were studied and the features were correlated with personal and family histories of dysplastic nevi and melanoma.
Results: The diagnosis of de novo melanocytic dysplasia was made in 27 male patients and 48 female patients (mean age: 44 years). The histologic hallmark was a pagetoid (single-cell) array of moderately to severely atypical epithelioid melanocytes within the epidermis. Seventy-three lesions were located on sun-exposed skin and nine on sun-protected skin. In 41 patients, there was an atypical mole phenotype, whereas 20 patients had a prior or subsequent diagnosis of melanoma with five of 16 patients questioned revealing a family history of melanoma.
Conclusions: De novo intraepidermal epithelioid melanocytic dysplasia is a distinct entity associated with an atypical mole phenotype and a personal and/or family history of melanoma.
DYSPLASTIC MELANOCYTIC NEVI OF THE LOWER LEG
Dysplastic Melanocytic Nevi of the Lower Leg: Sex- and Site-Specific Histopathology.
Coras B, Landthaler M, Stolz W, Vogt T.
From the University of Regensburg, Clinic of Dermatology and Allergology, Hospital Munich Schwabing, Munich, Germany.
Am J Dermatopathol. 2010 Jun 9. [Epub ahead of print]
Site-specific histopathology features have been reported for acral, auricular, flexural, and genital melanocytic nevi, however, to the best of our knowledge, site- and sex-specific histology of dysplastic nevi on the lower leg (between knee and ankle) of women (DN-LW) has not been reported.
In this retrospective histopathology study, we compared DN-LW (N = 42) with appropriate control groups of (1) DN of the lower leg of men (N = 20; DN-LM), (2) DN from the back of women (N = 20), (3) common nevi of the lower leg of women (N = 40), and (4) levels 1-2 superficial spreading melanoma of the lower leg of women (N = 20). Compared with dysplastic nevi on the back, DN-LW were smaller in diameter and exhibited a significantly higher score for pagetoid spread (P < 0.05). DN-LW compared with DN-LM showed sex-specific differences with (1) pagetoid spread (P < 0.05), (2) cytologic atypia (P < 0.05), (3) presence of large melanocytes (P < 0.05), and (4) band-like pigmentation in the dermis underlying the nevus (54% in DN-LW vs. 15% in DN-LM).
As with other body sites, the dermatopathologist should be aware that dysplastic nevi occurring on the lower leg in women have site- and sex-specific features. Knowing this profile may lower the risk of misdiagnosing DN-LW and melanoma of the lower leg of women.
Incidental epidermolytic hyperkeratosis and focal acantholytic dyskeratosis in common acquired melanocytic nevi and atypical melanocytic lesions.
Hutcheson AC, Nietert PJ, Maize JC.
J Am Acad Dermatol. 2004 Mar;50(3):388-90. Abstract quote
BACKGROUND: Epidermolytic hyperkeratosis (EH) and focal acantholytic dyskeratosis (FAD) are distinct histologic patterns that have been observed incidentally in a variety of benign and malignant skin lesions, including melanocytic lesions.
OBJECTIVE: Our motivation for this study was to determine whether FAD and/or EH was significantly associated with atypical melanocytic lesions.
METHODS: Skin biopsy specimens of melanocytic lesions diagnosed at our facility over a 3-month period were examined for the occurrence of FAD and EH.
RESULTS: Whereas both FAD and EH are uncommon findings, FAD was statistically increased in atypical melanocytic lesions (P =.0172). EH was not found to differ significantly in common acquired melanocytic nevi vs atypical melanocytic lesions.
CONCLUSIONS: Although both can be found in association with nonneoplastic skin diseases, as well as cutaneous neoplasms, FAD, but not EH, might serve as a marker for melanocytic atypia. Taken together with findings in the literature, FAD might serve as marker for atypical cutaneous proliferations as a whole.
Epidermolytic Hyperkeratosis Associated With Melanocytic Nevi: A report of 53 cases.
Conlin PA, Rapini RP.
Department of Pathology (P.A.C.) and Departments of Dermatology and Pathology (R.P.R.), Texas Tech Medical Center.
Am J Dermatopathol 2002 Feb;24(1):23-5 Abstract quote
Epidermolytic hyperkeratosis (EH) is a unique histopathologic alteration of the skin characterized by hyperkeratosis with perinuclear vacuolization of keratinocytes primarily in the stratum granulosum and the stratum malpighii. It is seen as an incidental finding in a variety of conditions, benign and malignant, as well as sporadic and familial. Recently, it has been reported that EH may be associated with dysplastic nevi (nevus with architectural disorder [NAD]).
Cases of melanocytic nevi with epidermolytic hyperkeratosis were retrieved from the files of a referral dermatopathology laboratory over a 6-year period. We present a series of 53 cases of EH in both ordinary nevi and NAD. Epidermolytic hyperkeratosis identified in association with NAD accounted for 46 cases or 86.8% of the total lesions while ordinary nevi represented 7 or 13.2% of total cases.
Our study confirms that the incidence of EH is higher in association with dysplastic nevi than in ordinary melanocytic nevi and may serve as a marker for NAD, but with lower sensitivity and only moderate specificity.
TREATMENT RELATED CHANGES
Histologic features seen in changing nevi after therapy with an 810 nm pulsed diode laser for hair removal in patients with dysplastic nevi.
Soden CE, Smith K, Skelton H.
Department of Dermatology, University of Alabama, 1720 University Blvd., Birmingham, AL 35294-0009, USA.
Int J Dermatol 2001 Aug;40(8):500-4 Abstract quote
BACKGROUND: The majority of lasers used for hair removal target melanin as the chromophore. In contrast with other cutaneous applications of lasers, lasers used for hair removal must generate a limited, controlled degree of thermal damage to permanently remove hairs.
AIM: To remove excess back hair from two male patients, one with a history of multiple nevi, and prior biopsies showing features of dysplastic nevi, and the other with large nevi greater than 6 mm in diameter and a family history of malignant melanoma.
METHODS: Both patients received monthly treatments with an 810 nm, pulsed, high-power diode laser using a fluence of 20 J/cm2 and 25-30 J/cm2, respectively, and a pulse duration of 30 ms.
RESULTS: Both patients presented 1 month after their last treatment with changing nevi within the treatment areas. Neither patient had clinical inflammation or other alterations suggestive of change in the nevi related to treatment. Thus, the nevi were excised with no mention of the previous laser treatment. The histologic features in all nevi were similar. There was subepidermal blister formation with elongation and disruption of nevus cells. There was homogenization of the collagen within the papillary dermis in all lesions. Only small foci of nevus cells could be identified in the dermis in some of the biopsy specimens. In these biopsy specimens, the dermal stromal matrix homogenization extended into the reticular dermis.
CONCLUSIONS: Laser targeting of nevus cells and surrounding structures may produce clinically atypical nevi in areas previously treated for hair removal. This should be kept in mind, especially in patients with a history of dysplastic nevi or with a personal or family history of malignant melanoma.
CHARACTERIZATION CYCLIN D1
Cyclin D1 expression in dysplastic nevi: an immunohistochemical study.
Ewanowich C, Brynes RK, Medeiros L, McCourty A, Lai R.
Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, Alberta, Canada.
Arch Pathol Lab Med 2001 Feb;125(2):208-10 Abstract quote
OBJECTIVE: We previously surveyed cyclin D1 expression in common acquired nevi, Spitz nevi, and malignant melanomas and reported that benign nevi maintain a zonal pattern of cyclin D1 expression, in contrast with malignant melanomas. Our aim was to extend those observations by examining cyclin D1 expression in dysplastic nevi.
METHODS: Cyclin D1 overexpression in 23 dysplastic nevi was detected by an immunohistochemical technique. The extent of atypia of the nevi was graded as mild, moderate, or severe, using previously established criteria.
RESULTS: Cyclin D1 overexpression in dysplastic nevi maintained a zonal pattern, similar to Spitz nevi. Cyclin D1 overexpression was greatest in the region of the epidermal-dermal junction and was significantly less prominent in the papillary and reticular dermis, suggesting that cyclin D1 expression is under cell control and correlates with maturation of nevus cells. Cyclin D1 overexpression also correlated with cytologic atypia, as dysplastic nevi with moderate or severe cytologic atypia contained a greater percentage of cyclin D1-positive cells than did nevi with mild atypia. Six dysplastic nevi with many cyclin D1--positive cells were assessed by fluorescence in situ hybridization studies using cyclin D1--specific and chromosome 11 centromeric probes. In all cases, there was no evidence of 11q13 translocation, amplification, or trisomy of chromosome 11.
CONCLUSIONS: Cyclin D1 may be involved in the pathogenesis of dysplastic nevi. Cyclin D1 overexpression does not appear to be explained by cyclin D1 locus amplification or translocation in most cases, and it may be a result of other cell abnormalities that up-regulate the protein level of cyclin D1.
DIFFERENTIAL DIAGNOSIS CHARACTERIZATION
Histologic atypia in clinically benign nevi. A prospective study.
Klein LJ, Barr RJ.
Department of Dermatology, University of California, Irvine.
J Am Acad Dermatol 1990 Feb;22(2 Pt 1):275-82 Abstract quote
Histologic features of dysplastic nevi include varying degrees of pattern atypia, cytologic atypia, and host response.
The purpose of this prospective study was to determine the prevalence of these histologic features in benign acquired nevi.
Fifty-eight junctional and compound nevi from 26 volunteer subjects were excised and examined. All nevi met each of the following criteria: 5 mm or less in diameter, symmetric, round or slightly oval, uniform pigmentation, distinct and regular margins, and no erythema.
One or more of the histologic features associated with dysplastic nevi were present in 87.8% of the lesions; two or more were present in 69%; and all three histologic features were found in 29.3%.
These results indicate that histologic features of dysplastic nevi occur in benign common acquired nevi.
Atypical histologic features in melanocytic nevi.
Dermatopathology Section, SM Annunziata Hospital, Florence, Italy.
Am J Dermatopathol 2000 Oct;22(5):391-6 Abstract quote
The atypical histologic features considered to be specific to dysplastic (atypical) nevi have been reported to occur in nevi that are common nevi by all other clinical and histologic features. The distribution and mutual relations among such features in nevi need to be further studied.
Six histologic features (dimension > 5 mm, lentiginous proliferation, disordered nested pattern, melanocytic dyskaryosis, dermal lymphocytic infiltrate, suprabasal melanocytes) were analyzed in 253 melanocytic nevi with different clinical appearances.
Atypical histologic features, found in 72% of nevi, occurred singly or formed numerous and highly variable combinations. Nevi formed a complex histologic spectrum comprising lesions showing a progressively increasing incidence of atypical features rather than two classes (common and dysplastic nevi). To divide the investigated lesions in objectively defined groups, we used a scoring system. In each nevus, a numeric value of 1 was assigned when each of the studied parameters was present and a value of 0 was assigned when each of these parameters was absent; on the basis of the final scores, nevi were divided in six different classes (classes 0-5).
Diagnostic categories such as dysplastic nevi and common nevi seem to be inappropriate, as they do not reflect the real histologic complexity of such lesions.
Correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi.
Annessi G, Cattaruzza MS, Abeni D, Baliva G, Laurenza M, Macchini V, Melchi F, Ruatti P, Puddu P, Faraggiana T.
Department of Dermatology, the Laboratory of Dermatopathology, Istituto Dermopatico dell'Immacolata IRCCS, Rome, Italy.
J Am Acad Dermatol 2001 Jul;45(1):77-85 Abstract quote
BACKGROUND: The validity of clinical and histologic criteria in identifying dysplastic nevi is controversial. Recognition of the dysplastic nevus as a distinct clinicopathologic entity requires demonstration of significant agreement between clinical atypia and histologic dysplasia.
OBJECTIVE: We attempted to determine the correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi and to evaluate the sensitivity and specificity of clinical criteria for dysplastic nevi when compared with histopathologic features.
METHODS: A total of 940 acquired melanocytic nevi 3 mm in diameter or larger were selected by initially choosing clinically unequivocal dysplastic and nondysplastic nevi and then, from these, histologically unequivocal dysplastic and nondysplastic lesions. The level of concordance between clinical atypia and histologic dysplasia was estimated by kappa statistics.
RESULTS: Nevi were classified as clinically dysplastic (n = 499) or nondysplastic (n = 441). On the basis of histologic features, 739 were classified as dysplastic and 201 as nondysplastic. Agreement between clinical atypia and histologic dysplasia was found in 432 nevi, that is, a sensitivity of 58.4% (3-5 mm = 27.2%, >5 mm = 69.8%). Agreement between clinical and histologic criteria on the absence of dysplasia was found in 134 nevi, a specificity of 66.6% (3-5 mm = 92.4%, >5 mm = 47.9%). The kappa value was 0.17 (3-5 mm = 0.14, >5 mm = 0.10).
CONCLUSION: The limited sensitivity and specificity together with the negligible kappa value indicate a poor agreement between clinical and histologic diagnoses of dysplastic nevus. The dysplastic nevus cannot be considered a distinct clinicopathologic entity because histologic dysplasia is found in a range of nevi that may or may not show clinical atypia.
A distinctive melanocytic lesion associated with melanoma-prone dysplastic naevus syndrome: the hybrid naevus.
Schubert C, Parwaresch R, Rudolph P.
Institute of Dermatology and Dermatopathology, Buchholz, Germany.
Virchows Arch 2001 Feb;438(2):166-72 Abstract quote
Clinically and histologically, the concept of dysplastic nevi remains controversial.
To elaborate more precise criteria for the nevi of patients with dysplastic naevus syndrome (DNS), we examined 58 nevi from seven DNS patients who developed one or several malignant melanomas.
Clinical presentation and histomorphology were evaluated, and immunohistochemistry was performed using proliferation marker Ki-S5 and antibody DO-7 to the p53 protein. Sixty nevi from individuals without history of melanoma served as controls. Of the DNS nevi, 21 (36.2%) exhibited no morphological particularities. The remaining 37 nevi presented distinctive histological features consisting of a slight epidermal acanthosis, spitzoid vertically oriented nests of dyscohesive nevus cells, and single-standing atypical melanocytes in the basal cell layer of the epidermis. Immunohistochemical analysis revealed an average proliferation index of 2.5%, which significantly surpassed the mean growth fraction of conventional dysplastic nevi (<1%). No increase in p53 expression was observed. Characteristically, active proliferation was found in junctional single-standing melanocytes with or without nuclear atypia rather than in nest-shaped compounds.
In conclusion, certain moles of patients with DNS possess distinctive features. The newly characterized criteria may provide a basis for the diagnosis of DNS and might help to identify patients at increased risk for malignant melanoma by examination of a single biopsy.
MELANOMA IN SITU (LENTIGO MALIGNA)
- Histologic similarities between lentigo maligna and dysplastic nevus: importance of clinicopathologic distinction.
Farrahi F, Egbert BM, Swetter SM.
Department of Dermatology, Stanford University Medical Center, Stanford, CA, USA.
J Cutan Pathol. 2005 Jul;32(6):405-12. Abstract quote
Background: Lentigo maligna (LM) can histologically simulate dysplastic nevus (DN). Partial biopsy of LM may lead to misdiagnosis.
Methods: One hundred and fourteen cases of LM and LM melanoma (LMM) were diagnosed at the Veterans Affairs Palo Alto Health Care System (1993-2002). Biopsy and excision specimens for 68 in situ and 28 invasive melanomas were classified as having predominant classical LM features, predominant DN-like morphology, or a mixed pattern.
Results: Biopsy specimens demonstrated a predominant classical pattern in 38% (25/65) LM and 36% (10/28) LMM, predominant DN-like features in 43% (28/65) LM and 25% (7/28) LMM, and mixed pattern in 15% (10/65) LM and 29% (8/28) LMM. Most LM and LMM biopsies were partial. Significant DN-like features were present in 51% LM and 57% LMM excision specimens. Median age was 72 years for LM and 73 years for LMM, mean lesion diameters were 1.3 and 1.7 cm for LM and LMM, respectively, and 85% of LM and 75% of LMM cases were located on heavily sun-exposed sites.
Conclusions: Misdiagnosis of LM or LMM as DN could have devastating results. Large pigmented lesions on sun-damaged skin in elderly individuals should warrant consideration of LM/LMM diagnosis, even in the setting of DN-like features histologically. Excisional biopsy may help to avoid misdiagnosis.
MELANOCYTIC NEVI ON THE DISTAL LOWER EXTREMITY (ANKLE) (MNAAF)
- A Subgroup of Melanocytic Nevi on the Distal Lower Extremity (Ankle) Shares Features of Acral Nevi, Dysplastic Nevi, and Melanoma In Situ: A Potential Misdiagnosis of Melanoma In Situ.
Departments of †Pathology ‡Dermatology §Baylor College of Medicine *M. D. Anderson Cancer Center, Houston, TX.
- Am J Surg Pathol. 2007 Jul;31(7):1130-1136. Abstract quote
Melanocytic lesions in certain locations (eg, genital, breast, acral) may have histologic and clinical features simulating melanoma.
Here we describe a group of lesions from the lower distal extremity and analyze their histologic features and possible relation to dysplastic nevi (DN) and melanomas. One hundred fifteen melanocytic lesions from the ankle were retrieved from January 1990 to August 2006 from the files of M. D. Anderson Cancer Center and were classified as benign melanocytic nevi (BN; n=17), DN (n=35), melanomas (MM; n=52), and melanocytic nevi of the ankle with atypical features (MNAAF; ie, cases that did not readily fit in any of the previous categories, n=11).
Data analyzed included clinical (age and sex) and histologic features (circumscription, symmetry, cohesiveness of nests, suprabasal melanocytes, confluence, single-cell proliferation, nuclear chromasia, size, and nucleolar features). Follow-up was collected for all MNAAF. MNAAF differ from the other types of lesions in regard to sex incidence (73% in women). The median age of those patients MNAAF was 47 years (range 29 to 76 y). All MNAAF showed moderate-severe architectural disorder whereas 78% showed only mild-moderate cytologic atypia. No MNAAF cases had recurred after follow-up (4 mo to 13 y).
This study highlights a group of melanocytic lesions located on the ankle that share histologic features with acral nevi, DN, and melanoma. These lesions are more predominant in females and have moderate to severe architectural atypia but only mild-moderate cytologic atypia. After complete excision, follow-up data indicate an apparently benign outcome. Pathologists should be aware of this type of lesions to avoid overdiagnosis of melanoma.
PROGNOSIS AND TREATMENT CHARACTERIZATION RISK OF MELANOMA
Grading of atypia in nevi: correlation with melanoma risk.
Arumi-Uria M, McNutt NS, Finnerty B.
Dermatopathology Division, Department of Pathology, Weill Medical College of Cornell University, New York, New York 10021, USA.
Mod Pathol. 2003 Aug;16(8):764-71. Abstract quote
Nevi with architectural disorder and cytologic atypia of melanocytes (NAD), aka "dysplastic nevi," have varying degrees of histologic abnormalities, which can be considered on a spectrum of grades of atypia. Somewhat controversial and subjective criteria have been developed for grading of NAD into three categories "mild," "moderate," and "severe." Grading involves architectural and cytological features, which often correlate with each other. Architectural criteria were intraepidermal junctional extension beyond any dermal component, complex distortion of rete ridges, and dermal fibrosis. Cytological criteria were based on nuclear size, dispersion of chromatin, prominence of nucleoli, hyperchromasia and variation in nuclear staining. Few tests have been made of the relationship between specific grades of atypia and patient risk for melanoma.
Retrospective review of pathology reports was performed on 20,275 nevi examined between 1989 and 1996. From the total, 6,275 were diagnosed as NAD, which were in 4,481 patients. These patients were divided into those whose worst NAD was mild (2,504), moderate (1,657), or severe (320). Review of accession data revealed that a personal history of melanoma was present in 5.7% of patients with mild, 8.1% with moderate, and 19.7% with severe atypia. The male/female ratios were similar in each group. In the three groups, the mean ages of men were similar and of women were similar, but the mean age of men tended to be 6-11 yrs. older than women in each group. Family histories of melanoma were not considered. The odds ratio as a measure of association between NAD and personal history of melanoma, shows an odds ratio of 4.08 (2.91-5.7) for NAD-severe versus NAD mild, odds ratio 2.81 (2-3.95) for NAD-severe versus NAD-moderate and odds ratio 1.45 (1.13-1.87) for NAD moderate versus NAD-mild.
These data show that the probability of having personal history of melanoma, for any given NAD patient, correlates with the NAD grade. Likewise, the risk of melanoma is greater for persons who tend to make nevi with high grade histological atypia.
Recurrent dysplastic nevus following shave excision.
Duray PH, Livolsi VA.
J Dermatol Surg Oncol 1984 Oct;10(10):811-5 Abstract quote
Distinguishing benign from malignant melanocytic lesions is an on-going challenge for the clinician and the histopathologist. The regrowth of benign melanocytic nevi at the dermoepidermal junction following inadequate excision has been shown to be confused with superficial spreading melanoma. The dysplastic nevus has atypical features in and of itself, which become even more compounded when the lesion recurs in the dermoepidermal junction following inadequate resection by shave excision. The use of Monsel's solution to achieve hemostasis at the biopsy site can itself also produce a clinically irregular area of hyperpigmentation, accompanied by a pathologic pigmented and cellular dermal reaction.
A case of a dysplastic nevus recurring after inadequate shave excision is reported here. The resultant atypia were further compounded by the use of Monsel's solution for hemostasis in the initial excision, which could have led to a mistaken diagnosis of malignant melanoma. The spectrum of dysplastic nevi is reviewed.
TREATMENT Complete excision
Analysis of heterogeneity of atypia within melanocytic nevi.
Barr RJ, Linden KG, Rubinstein G, Cantos KA.
Department of Dermatology, University of California, Irvine, 101 The City Drive, Orange, CA 92868.
Arch Dermatol 2003 Mar;139(3):289-92 Abstract quote
BACKGROUND: Incisional biopsy of clinically atypical nevi continues to be a common practice. Questions can arise as to the adequacy of these partial biopsies.
OBJECTIVE: To determine whether incisional (partial) biopsy specimens may be considered representative of the entire lesion, atypical nevi submitted to our dermatopathology laboratory were examined for the presence or absence of heterogeneity of atypia within the individual nevi.
DESIGN: The study included 250 histologically atypical nevi that were selected consecutively from pigmented lesions that were submitted to our dermatopathology laboratory by community and academic dermatologists for histopathologic analysis. Also, 23 moderately to severely atypical and 25 severely atypical nevi from consecutive submissions were added for statistical reasons. Lesions with both clear and involved margins were used. Lesions were considered homogeneous if the atypia involved the entire lesion or heterogeneous if either the atypia was focal or if different degrees of atypia occurred within the same lesion. Atypia was defined by the usual parameters of architectural and cytologic atypia and host response. Also, the degree of atypia in relationship to heterogeneity and to patient age was determined.
SETTING: The Dermatopathology Laboratory, University of California, Irvine.
MAIN OUTCOME MEASURES: Outcome measures included the percentage of nevi exhibiting heterogeneity of atypia, heterogeneity of atypia in relation to patient age, degree of atypia in relation to patient age, and degree of atypia in relation to the presence of heterogeneity of atypia.
RESULTS: Of the 298 nevi examined, 107 (35.9%) were heterogeneous in atypia and 191 (64.1%) were homogeneous in atypia. There was no significant difference in age between patients with heterogeneous lesions and those with homogeneous lesions. There was a statistically significant correlation between the degree of atypia and patient age. The average age of patients with a lesser degree of atypia was 36.9 years, while the average age of patients with a greater degree of atypia was 44.8 years (P<.005). There was no significant correlation between degree of atypia and heterogeneity of atypia (correlation coefficient, 0.1).
CONCLUSIONS: A clinically significant proportion of atypical nevi exhibited heterogeneity of atypia. Also, there was a significant relationship between the degree of atypia and increasing age (P<.005). Therefore, if a clinically atypical nevus warrants a biopsy, these results give additional support for complete excisional biopsy (which can include shave or punch) to assure adequate histopathologic sampling of the lesion.
Management of dysplastic nevi: A survey of fellows of the American Academy of Dermatology.
Tripp JM, Kopf AW, Marghoob AA, Bart RS.
Ronald O. Perelman Department of Dermatology, New York University School of Medicine New York; Department of Dermatology, State University of New York at Stony Brook Health Sciences Center; and Memorial Sloan-Kettering Cancer Center, New York.
J Am Acad Dermatol 2002 May;46(5 Pt 1):674-82 Abstract quote
BACKGROUND: Opinions concerning the significance of dysplastic nevi and their management vary among dermatologists.
OBJECTIVE: The purpose of this study was to assess how fellows of the American Academy of Dermatology (AAD) perceive and manage dysplastic nevi.
METHODS: Questionnaires were sent to 1216 fellows of the AAD; 456 questionnaires were returned.
RESULTS: Almost all respondents (98%) accept the dysplastic nevus, or atypical mole, as an entity. Seventy-five percent of respondents perform follow-up total cutaneous examinations on all their patients with dysplastic nevi, and another 22% on some of them; 86% usually intend to do total removals when they perform biopsies of dysplastic nevi; 75% use margins of 2 mm or less when removing dysplastic nevi; 49% order baseline total-cutaneous photographs of some or all of their patients with multiple dysplastic nevi, although only 12% do so routinely; 67% prefer to re-excise dysplastic nevi when margins are positive, some using histologic atypia as a criterion; 60% recommend an ophthalmologic examination for at least some of their patients with many dysplastic nevi, although only 3% do so routinely; 12% always recommend cutaneous examinations of blood relatives of their patients with dysplastic nevi and another 81% recommend such examinations for at least some of their patients with dysplastic nevi; 23% use dermoscopy; 99% recommend self-examination; almost 100% recommend sunscreen use and 93%, sun avoidance.
CONCLUSION: Most respondents, in agreement with the literature, accept the concept that patients with dysplastic nevi are at increased risk for melanoma and that methods for prevention and early detection of melanomas are appropriate for these patients.
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