Pathology of Challenging Melanocytic Neoplasms: Diagnosis and Management

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  1. Article Tools
  2. Genomic Landscape of Spitzoid Neoplasms Impacting Patient Management
  3. Atlas of Diagnostically Challenging Melanocytic Neoplasms
  4. Table of contents

There is little or no pagetoid spread pattern. Epidermal changes include acanthosis, hypergranulosis, and hyperkeratosis. The intradermal pattern displays maturation, with single-file or single-unit arrays descending to the base. Eosinophilic Kamino bodies frequently are found along the dermoepidermal interface. Kamino bodies are globular clusters that represent apoptotic degenerative melanocytes Figure 4. They stain positive with both periodic acid-Schiff and trichrome stains. At the dermal base, there is no mitosis, no pushing deep margins, and lack of significant pleomorphism. Little or no melanin is present.

The atypical Spitz nevus is difficult to formally define. Instead, it is loosely defined.

An atypical Spitz nevus shares histologic features with the classic Spitz nevus, but it may have one or more atypical features, which can be characteristic of malignancy. Histologically, there can be one or more of the following features: pleomorphism; increased cellularity; loss of cellular cohesion; epidermal pagetoid spread; minimal epidermal changes; absence of Kamino bodies; lack of maturation in the intradermal pattern; high-grade nuclear atypia; high basal mitotic rate; pushing deep margins into the dermal base or subcutis; and nests variable in size, shape, and orientation.

The behavior of any atypical Spitz nevus is unpredictable. There are case reports of metastasizing and malignant lesions with Spitz-like characteristics causing fatal outcomes. They point out that many of these case reports of melanomas with Spitz-like features do not fit the diagnosis of the Spitz nevus. In general, the more features an atypical Spitz nevus shares with melanoma, the greater the risk for malignant behavior. In , Spatz et al 12 proposed formal and specific criteria for determining the risk for malignant behavior in atypical Spitz nevi in children. In the retrospective study, atypical features were used to define atypical Spitz nevi and grade their risk for metastasis.

The 5 major factors were age, size, presence of ulceration, involvement of subcutaneous fat, and mitotic activity. Positive risk factors that increased the grade included age greater than 10 years, diameter greater than The higher the grade, the higher the risk for malignancy and metastasis. Within the subset of diagnostically challenging cases, For diagnostically challenging cases initially diagnosed as indeterminate, definitive diagnoses increased by A diagnosis of indeterminate was indicated for 82 cases post-testing, while a definitive diagnosis of benign was indicated in 89 cases and a definitive diagnosis of malignant in 47 cases.

Overall, this corresponds to a The changes were primarily diagnostic downgrades from indeterminate to benign , with benign diagnoses increasing Malignant diagnoses increased This reduction in indeterminate diagnoses along with an increase in confidence for benign or malignant diagnoses resulted in an overall decrease in the number of diagnostically challenging cases identified within the total population after testing.

Similar reductions in indeterminate diagnoses were observed for each of the 3 major subtypes in the diagnostically challenging subset: atypical junctional melanocytic proliferations The accompanying increases in benign and malignant diagnoses for atypical junctional melanocytic proliferations Among the diagnostically challenging cases that received a benign test result, 5. Treatment recommendations were revised in These trends were also observed for the three major subtypes in the subset of diagnostically challenging cases.

Overall changes in treatment for atypical junctional melanocytic proliferations The proportion of treatment recommendations that were changed to align with the test result was also similar for each of the major subtypes relative to all diagnostically challenging cases.

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Figure 3 shows an example of an atypical Spitz tumor that was given a final diagnosis of benign nevus after receiving a benign test result. Molecular diagnostics are increasingly utilized to achieve a more objective and reproducible diagnosis of melanocytic lesions.

Risk of Melanoma

Molecular diagnostics are anticipated to offer their maximum clinical utility in ambiguous or diagnostically challenging melanocytic lesions, when the dermatopathologist is unable to confidently provide a definitive diagnosis. The present study demonstrated within a prospective cohort of diagnostically challenging melanocytic lesions that the MDS impacts diagnoses and treatment recommendations among dermatopathologists. Similar results were observed among the 3 major subtypes included in the diagnostically challenging subset: atypical junctional melanocytic proliferations, dysplastic nevi, and atypical Spitz tumors.

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Genomic Landscape of Spitzoid Neoplasms Impacting Patient Management

Previous studies suggest that the impact of adjunctive diagnostic tests on diagnosis and treatment recommendations may vary based on lesion subtype. This is not an unexpected result given that the gene expression signature is an adjunctive, rather than absolute, diagnostic tool. It is likely that in the limited number of cases where the modified treatment recommendation did not align with the test result the ordering physician observed features independent of the test score that provided greater significance in rendering a final treatment decision than the test result did.

Key stakeholders in the healthcare system, including regulatory agencies, clinical guideline panels, third-party payers, physicians and patients, are increasingly seeking evidence of the clinical utility of diagnostic tests in order to support standard use of such tests in clinical practice. Integration of this test into the pathologic diagnosis of melanocytic lesions has the potential to contribute to more definitive diagnoses and optimized clinical care in the treatment of melanocytic lesions.

We would like to thank Kirstin Roundy for assistance with figure preparation, editing, and formatting the manuscript for submission. You may be trying to access this site from a secured browser on the server. Please enable scripts and reload this page. Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent.

Atlas of Diagnostically Challenging Melanocytic Neoplasms

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Please try after some time. Abstract 1 Introduction 2 Methods 3 Results 3. Back to Top Article Outline. Table 1. Table 2. Figure 1. Table 3. Table 4. Figure 2. Figure 3. Figure 4. American Cancer Society. What are the key statistics about melanoma skin cancer? Accessed January 21, Cited Here What are the survival rates for melanoma skin cancer by stage? Am J Surg Pathol ; — Discordance in the histopathologic diagnosis of melanoma at a melanoma referral center. J Am Acad Dermatol ; — J Pathol ; — PubMed CrossRef. Elder DE, Xu X. The approach to the patient with a difficult melanocytic lesion.

Pathology ; — Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. Hum Pathol ; — Ferrara G, Misciali C, Brenn T, et al The impact of molecular morphology techniques on the expert diagnosis in melanocytic skin neoplasms. Int J Surg Pathol ; — Am J Pathol ; — Bauer J, Bastian BC. Distinguishing melanocytic nevi from melanoma by DNA copy number changes: comparative genomic hybridization as a research and diagnostic tool.


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