Correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi

doi:10.1067/mjd.2001.114580

Journal of the American Academy of Dermatology

Volume 45, Issue 1, July 2001, Pages 77-85

https://doi.org/10.1067/mjd.2001.114580 Get rights and content

Abstract

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 κ 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 κ value was 0.17 (3-5 mm = 0.14, >5 mm = 0.10). Conclusion: The limited sensitivity and specificity together with the negligible κ 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. (J Am Acad Dermatol 2001;45:77-85.)

Section snippets

Terminology

In the present study the terms hereafter listed have been defined as follows:

•
Clinically dysplastic nevus, nevus with clinical atypia, or atypical mole2, 4, 6, 7, 9, 16, 22, 25, 26: Acquired melanocytic nevus with a macular component in association with at least 3 of the following attributes: (1) asymmetry, (2) variegation of color (haphazard mixture of tan, dark brown, and pink colors), (3) erythema, (4) irregular borders, (5) indistinct margins that tend to fade into the adjacent normal skin
•

Results

The 940 melanocytic nevi were excised from 898 patients (512 females, 386 males; age range 19 to 72 years, average age 33 years). A total of 570 nevi were located on the trunk and 370 on the limbs; 499 (53%) nevi were judged clinically to be dysplastic and 441 (47%) nondysplastic. For the purpose of the study, the lesions were arbitrarily subdivided into 2 groups on the basis of clinical diameter: group A, 3 to 5 mm (290 cases); group B, >5 mm (650 cases). In group A, 61 (21%) nevi were

Discussion

Although there is some controversy,45, 46 the dysplastic nevus is at present regarded to be a distinct clinicopathologic entity by many authors.4, 5, 28, 47 This concept is grounded primarily in the assumption that there are reliable criteria to identify dysplastic nevi both clinically and histologically.22, 26, 27, 29, 31, 33, 34, 35, 36 Moreover, various studies have ascertained a significant correlation between clinical atypia and histologic dysplasia.26, 37, 48 The present clinicopathologic

Acknowledgements

We thank Anna Luisa Bucci, Luciana Martini, and Leonilde Sposato for technical assistance and Dr Giovanna Zambruno for helpful discussion.

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The question of whether there is a correlation between clinical and histologic atypia also has been investigated. In one study, clinical dermatologists categorized nevi as “clinically dysplastic or nondysplastic,” and dermatopathologists were then asked to identify whether there was evidence of histologic “dysplasia” in the biopsied lesions.57 The study demonstrated poor sensitivity, specificity, and statistical agreement between clinical atypia and histologic dysplasia.
Since the late 1970s, the diagnosis and management of dysplastic nevi have been areas fraught with controversy in the fields of dermatology and dermatopathology. Diagnostic uncertainty and lack of standardized nomenclature continue to propagate confusion among clinicians, dermatopathologists, and patients. In part I of this CME review article, we summarize the historical context that gave rise to the debate surrounding dysplastic nevi and review key features for diagnosis, classification, and management, as well as epidemiology. We discuss essentials of clinical criteria, dermoscopic features, histopathologic features, and the diagnostic utility of total body photography and reflectance confocal microscopy in evaluating dysplastic nevi, with emphasis on information available since the last comprehensive review a decade ago.
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Approximately 20% of the cases assigned to the excision group were not captured as excision specimens. As histologic atypia may not correlate with clinical atypia,10 some of these cases may represent those cases that the clinicians decided to monitor rather than excising them. Alternatively, they were excised and sent to a different laboratory.
Despite a lack of evidence that dysplastic nevi are precursors to melanoma, a large proportion of dermatologists continue to treat them as such. Emerging data suggest that histologic grading approach may result in many unnecessary excisions.
Using a nongrading approach to diagnosis of Clark/dysplastic nevi, the current study sought to define and determine the diagnostic uncertainty rate, and to report on the results of re-excisions of such lesions.
All melanocytic nevi submitted to an academic dermatopathology laboratory between January 1, 2007, and December 31, 2013, were categorized. The number of Clark nevi recommended for re-excision divided by the total number of Clark nevi was taken to be the diagnostic uncertainty rate.
This nongrading approach resulted in an excision recommendation/diagnostic uncertainty rate of 11.1%. In 2% of the excised specimens, the diagnosis was changed to melanoma.
The study was performed at a single institution, and assigned diagnoses could not be verified other than by the diagnosing dermatopathologists. Lesions that were not submitted as re-excision specimens could have altered the results had they been available for evaluation.
Compared with previously reported excision rates, the current study shows that the nongrading approach to Clark nevi results in a lower excision rate while still maintaining a low rate of change in diagnosis similar to the grading approach.
Dysplastic nevus: Fact and fiction
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The term “dysplastic nevus” (DN) implies that this nevus exists as a distinct and defined entity of potential detriment to its host. We examine the current data, which suggest that this entity exists as histologically and possibly genetically different from common nevus, with some overlapping features. Studies show that a melanoma associated with a nevus is just as likely to arise in a common nevus as in DN. Furthermore, there is no evidence that a histologically defined DN evolves into a melanoma or that the presence of 1 or more DN on an individual patient confers any increased melanoma risk. We suggest that the term “dysplastic nevus” be abandoned so that the focus can shift to confirmed and relevant indicators of melanoma risk, including high nevus counts and large nevus size.
The dysplastic nevus: From historical perspective to management in the modern era: Part II. Molecular aspects and clinical management
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Nevertheless, DN share some histologic features of nondysplastic or “common” nevi (CN), including the presence of neoplastic nests of melanocytes, and features of melanoma such as cytologic atypia and dermal inflammatory response.1 The benign lesions (DN and CN) cannot be distinguished from each other based on clinical examination alone,2,3 and DN often have some clinical features associated with melanoma, such as an irregular border and the asymmetric distribution of pigmentation.4,5 Given these considerations, this review will focus on studies based on lesions that have been defined histologically.
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The overall concordance between clinical and histologic atypia was fair, as the presence of macularity and color variegation correlated somewhat with higher grades of histological atypia. Similarly, Annessi et al65 found very poor correlation between nevi that were clinically atypical and histologically dysplastic. In this study, 940 acquired nevi were clinically assessed by five dermatologists, and then blindly examined histologically by a single experienced dermatopathologist.
Since its description in the 1970s, the dysplastic nevus has been a source of confusion, and whether it represents a precursor to melanoma remains a controversial subject. Although a Consensus Conference in 1992 recommended that the term “dysplastic nevus” no longer be used, the histologic diagnosis continues to present a therapeutic quandary for dermatologists and other physicians, and there remains significant variation in clinical management. In part I of this continuing medical education review, we will discuss the historical origins of the term, the evidence for its distinct histologic basis, and its clinical significance.
In vivo confocal microscopy for detection and grading of dysplastic nevi: A pilot study
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Dysplastic nevi are thought to be precursors of melanoma during a stepwise process. However, this concept is still controversial and precise correlation between clinical and histopathologic features is lacking. In vivo confocal microscopy represents a noninvasive imaging technique producing horizontal sections at nearly histopathologic resolution.
We sought to determine whether specific histologic features in dysplastic nevi have reliable correlates on confocal microscopy and to develop an in vivo microscopic grading system.
Sixty melanocytic lesions with equivocal dermatoscopic aspects, corresponding to 19 nondysplastic nevi, 27 dysplastic nevi, and 14 melanomas, were analyzed by confocal microscopy and histopathology, using the Duke grading criteria.
All architectural and cytologic features of the Duke grading score had significant reflectance confocal microscopy correlates. Confocally, dysplastic nevi were characterized by a ringed pattern, in association with a meshwork pattern in a large proportion of cases, along with atypical junctional cells in the center of the lesion, and irregular junctional nests with short interconnections. A simplified algorithm was developed to distinguish dysplastic nevi from melanoma and nondysplastic nevi. The contemporary presence of cytologic atypia and of atypical junctional nests (irregular, with short interconnections, and/or with nonhomogeneous cellularity) was suggestive of histologic dysplasia, whereas a widespread pagetoid infiltration, widespread cytologic atypia at the junction, and nonedged papillae suggested melanoma diagnosis.
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^☆: Reprint requests: Giorgio Annessi, MD, Laboratorio di Dermatopatologia, Istituto Dermopatico dell'Immacolata, Via Monti di Creta 104, 00167 Roma, Italy.

^☆☆: J Am Acad Dermatol 2001;45:77-85

View full text

ReportsCorrelation between clinical atypia and histologic dysplasia in acquired melanocytic nevi☆,☆☆

Abstract

Section snippets

Terminology

Results

Discussion

Acknowledgements

Hum Pathol

J Am Acad Dermatol

Prev Med

J Invest Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

Hum Pathol

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

Hum Pathol

J Am Acad Dermatol

Current status of the dysplastic melanocytic nevus

J Cutan Pathol

The early and intermediate precursor lesions of tumor progression in the melanocytic system: common acquired nevi and atypical (dysplastic) nevi

Semin Diagn Pathol

Origin of familial malignant melanomas from heritable melanocytic lesions: “the B-K mole syndrome.”

Arch Dermatol

Dysplastic nevus syndrome: a phenotypic association of sporadic melanoma

Cancer

The dysplastic nevus syndrome: our definition

Am J Dermatopathol

Acquired precursors of cutaneous malignant melanoma: the familial dysplastic nevus syndrome

N Engl J Med

High risk of malignant melanoma in melanoma-prone families with dysplastic nevi

Ann Intern Med

Demographic study of clinically atypical (dysplastic) nevi in patients with melanoma and comparison subjects

Cancer Res

Acquired melanocytic nevi and melanoma: the dysplastic nevus syndrome

Reports
Correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi☆,☆☆