Clinical implication of PRAME immunohistochemistry in differentiating melanoma in situ and dysplastic nevus in non-acral nevus-associated melanoma in situ: An institutional experience and meta-analysis.

INTRODUCTION: PReferentially expressed Antigen in MElanoma (PRAME) has shown utility in differentiating benign from malignant melanocytic neoplasms. In this study, we investigated the clinical significance of PRAME expression in dysplastic nevi (DN) and nevus-associated melanoma in situ (MIS). METHODS: We included 172 DN and 38 nevus-associated MIS from our institutional archive. PRAME positive expression was defined as nuclear staining in at least 75% of melanocytes. In addition, relevant studies from PubMed and Web of Science were incorporated into a meta-analysis using the random-effects model to assess PRAME expression in MIS and DN. RESULTS: Our institutional data revealed that 71.1% of nevus-associated MIS cases exhibited positive PRAME expression in the MIS components, whereas all DN components were negative for PRAME. 5.7% of cases diagnosed as DN in our cohort demonstrated diffuse positivity for PRAME. Notably, MIS associated with DN displaying epidermal and dermal components displayed a higher likelihood of PRAME positivity compared to those arising on a background of DN with solely epidermal (junctional) components (84% vs. 46%, p = 0.024). The meta-analysis indicated that the pooled PRAME positivity in MIS and DN was 54.5% and 1.9%, respectively. CONCLUSION: PRAME is a valuable immunohistochemical marker for differentiating MIS from DN, particularly in the context of nevus-associated MIS.

Dysplastic nevus part II: Dysplastic nevi: Molecular/genetic profiles and management.

Dermatologists frequently see patients with clinically atypical nevi and dermatopathologists interpret histologically dysplastic nevi on a near-daily basis, but there is great variability in the definition and management of such lesions. This part of the CME review focuses on information published since the previous comprehensive review (2012), with emphasis on molecular and genetic attributes of histologically dysplastic nevi and clinical management.

Factors associated with suspected nonmelanoma skin cancers, dysplastic nevus, and cutaneous melanoma among first-time SpotMe screening program participants during 2009-2010.

BACKGROUND: There have been no studies of the American Academy of Dermatology's SpotMe skin cancer screening program to collectively analyze and determine the factors associated with suspected basal cell carcinoma (BCC), squamous cell carcinoma (SCC), dysplastic nevus (DN), and cutaneous melanoma (CM) diagnoses. OBJECTIVE: Describe the demographics, risk factors, and access to care profiles associated with suspected diagnoses of BCC, SCC, DN, and CM among first-time SpotMe screenees during 2009-2010. METHODS: We conducted a cross-sectional analysis of data from the SpotMe skin cancer screenings conducted in 2009 and 2010. We performed multivariable logistic regression analysis for each diagnosis, incorporating standard demographic, access to care, and risk factor variables in the models. RESULTS: Men, those without a regular dermatologist, persons reporting recently changing moles, and those with a personal history of melanoma were at increased risk for each of the suspected diagnoses analyzed. Uninsured persons were at increased risk for suspected malignancies (BCC, SCC, and CM). LIMITATIONS: Lack of histologic confirmation for diagnoses and cross-sectional design. CONCLUSION: Among first-time SpotMe participants, suspected diagnoses of BCC, SCC, DN, and CM shared several associated factors, which may be considered when planning outreach and screening for populations at risk for skin cancer.

Differences in nomenclature usage and preference among dermatopathologists for "dysplastic" nevi: A national survey.

BACKGROUND: Ongoing controversy exists regarding terminology used to describe atypical melanocytic nevi. Efforts to standardize nomenclature, including the 1992 NIH consensus conference, have been largely unsuccessful. Significant advances have revealed an increasingly detailed genetic picture of melanocytic neoplasms, including strong evidence for the existence of those with "intermediate" behavior. METHODS: We sent an electronic survey to dermatopathologists (n = 846) to assess trends in nomenclature usage and attitudes toward developing new consensus nomenclature for atypical melanocytic nevi. RESULTS: There were 229 complete responses (27.1% response rate). The most used/preferred nomenclature was "dysplastic nevus" (43%/39%, respectively), followed by the NIH-recommended terminology (28%/26%). Three-tier grading systems were most heavily used/preferred (79%/63%). Dermatopathologists based in New England were most likely to use the NIH terminology; on the other hand, "dysplastic nevus" or "other" were most used elsewhere (p = 0.029). Most (76%) expressed at least "moderate" enthusiasm for developing consensus nomenclature, with 47% "very" or "extremely" enthusiastic. CONCLUSION: Little has changed with the wide variation in terminology for atypical melanocytic nevi. There continues to be no one dominant terminology in use. However, there is enthusiasm for standardization. A new attempt at updated consensus nomenclature may be fruitful.

Optical coherence tomography confirms non-malignant pigmented lesions in phacomatosis pigmentokeratotica using a support vector machine learning algorithm.

INTRODUCTION: Phacomatosis pigmentokeratotica (PPK), an epidermal nevus syndrome, is characterized by the coexistence of nevus spilus and nevus sebaceus. Within the nevus spilus, an extensive range of atypical nevi of different morphologies may manifest. Pigmented lesions may fulfill the ABCDE criteria for melanoma, which may prompt a physician to perform a full-thickness biopsy. MOTIVATION: Excisions result in pain, mental distress, and physical disfigurement. For patients with a significant number of nevi with morphologic atypia, it may not be physically feasible to biopsy a large number of lesions. Optical coherence tomography (OCT) is a non-invasive imaging modality that may be used to visualize non-melanoma and melanoma skin cancers. MATERIALS AND METHOD: In this study, we used OCT to image pigmented lesions with morphologic atypia in a patient with PPK and assessed their quantitative optical properties compared to OCT cases of melanoma. We implement a support vector machine learning algorithm with Gabor wavelet transformation algorithm during post-image processing to extract optical properties and calculate attenuation coefficients. RESULTS: The algorithm was trained and tested to extract and classify textural data. CONCLUSION: We conclude that implementing this post-imaging machine learning algorithm to OCT images of pigmented lesions in PPK has been able to successfully confirm benign optical properties. Additionally, we identified remarkable differences in attenuation coefficient values and tissue optical characteristics, further defining separating benign features of pigmented lesions in PPK from malignant features.

Standardized Computer-Assisted Analysis of PRAME Immunoreactivity in Dysplastic Nevi and Superficial Spreading Melanomas.

PRAME (PReferentially expressed Antigen in MElanoma) is a cancer testis antigen that is frequently expressed in melanoma compared to benign melanocytic proliferations and nevi. However, the interpretation of the intensity and distribution of PRAME immunostaining is not standardized a lot, which makes interpretation difficult. PRAME-stained histological slides of superficial spreading melanomas (SSM) and dysplastic nevi (DN) were digitized and analyzed using the digital pathology and image platform QuPath. t-tests and ROC AUCs were performed with SPSS. A p-value of <0.05 was used for statistical significance, and a ROC AUC score of >0.8 was considered a good result. A cut-off score was defined in an evaluation cohort and subsequently analyzed in an independent validation cohort. In total, 81 PRAME-stained specimens were included. The evaluation cohort included 32 (50%) SSM and 32 (50%) DN, and the mean of PRAME-positive cells/mm2 for the entire lesion was 455.3 (SD 428.2) in SSM and 60.5 (SD 130.1; p < 0.001) in DN. The ROC AUC of PRAME-positive cells of the entire lesion was 0.866, and in the epidermis it was 0.901. The defined cut-off score to distinguish between DN and SSM was 97.67 cells/mm2. In the validation cohort, 16 out of 17 cases (94.1%) were correctly classified by the cut-off score. The computer-aided assessment of PRAME immunostaining is a useful tool in dermatopathology to distinguish between DN and SSM. Lesions with a moderate expression and indifferent morphologic features will remain a challenge for dermatopathologists.

Standardized Computer-Assisted Analysis of 5-hmC Immunoreactivity in Dysplastic Nevi and Superficial Spreading Melanomas.

5-Hydroxymethylcytosine (5-hmC) is an important intermediate of DNA demethylation. Hypomethylation of DNA is frequent in cancer, resulting in deregulation of 5-hmC levels in melanoma. However, the interpretation of the intensity and distribution of 5-hmC immunoreactivity is not very standardized, which makes its interpretation difficult. In this study, 5-hmC-stained histological slides of superficial spreading melanomas (SSM) and dysplastic compound nevi (DN) were digitized and analyzed using the digital pathology and image platform QuPath. Receiver operating characteristic/area under the curve (ROCAUC) and t-tests were performed. A p-value of <0.05 was used for statistical significance, and a ROCAUC score of >0.8 was considered a "good" result. In total, 92 5-hmC-stained specimens were analyzed, including 42 SSM (45.7%) and 50 DN (54.3%). The mean of 5-hmC-positive cells/mm2 for the epidermis and dermo-epidermal junction and the entire lesion differed significantly between DN and SSM (p = 0.002 and p = 0.006, respectively) and showed a trend towards higher immunoreactivity in the dermal component (p = 0.069). The ROCAUC of 5-hmC-positive cells of the epidermis and dermo-epidermal junction was 0.79, for the dermis 0.74, and for the entire lesion 0.76. These results show that the assessment of the epidermal with junctional expression of 5-hmC is slightly superior to dermal immunoreactivity in distinguishing between DN and SSM.

Survey on the Management of Dysplastic Nevus by Dermatologists in the Center-Spain section of the Spanish Academy of Dermatology and Venereology (AEDV). / Encuesta sobre el manejo del nevus displásico por los dermatólogos de la sección Centro de la Academia Española de Dermatología y Venereología (AEDV).

BACKGROUND AND OBJECTIVES: There are no clinical guidelines on the management of dysplastic nevus (DN). The aims of this study were to determine the percentage of dermatologists in the center-Spain section of the Spanish Academy of Dermatology and Venereology (AEDV) who would manage a histologically confirmed DN with a watch-and-wait approach or with wider surgical margins and to investigate whether their attitudes would vary depending on whether or not the patient had a personal and/or family history of melanoma. MATERIAL AND METHODS: We collected data from an anonymous survey sent to 738 dermatologists between June 15 and July 31, 2022. The independent variables were degree of dysplasia (low vs. high), margin status (positive vs. negative), and a personal or family history of melanoma (yes vs. no in both cases). The dependent variables were attitude towards management (watch-and-wait vs. re-excision with a surgical margin of 1 to 4mm or re-excision with a surgical margin of 5 to 10mm). RESULTS: We obtained 86 responses to the questionnaire. When pathology indicated a low-grade DN, 60.5% of dermatologists stated they would obtain a surgical margin of 1 to 4mm if the first margins were positive, and 97.7% would watch and wait if the report described negative margins. For high-grade DNs, 1.2% of dermatologists would watch and wait to manage DN with positive margins; 68.8% would use this approach for negative margins. A family or personal history of melanoma had no influence on most of the dermatologists' attitudes. CONCLUSIONS: Management strategies for DN among dermatologists from the center-Spain section of the AEDV varied, particularly when faced with low-grade DN with positive margins and high-grade DN with negative margins. A family or personal history of melanoma did not influence clinical attitudes in most cases.

Dermoscopic Nevus Patterns Associated with Melanoma Patients.

BACKGROUND: The quantitative and qualitative presence of melanocytic nevi is considered a significant risk factor for melanoma. Little is known whether patients showing any of the recognized global dermoscopic nevus patterns might also be considered at increased risk for the disease. OBJECTIVES: We aimed to investigate the frequency of global dermoscopic patterns of common nevi among melanoma patients and compare them to controls, as well as the dermoscopic patterns of atypical nevi between the groups. METHODS: We included consecutive melanoma patients and age- and sex-matched controls who presented to our Department with at least 10 melanocytic nevi. Total body examination was performed, and all nevi had their dermoscopic pattern described. Global dermoscopic patterns of nevi were compared between groups, as well as atypical nevus patterns. Finally, nevus patterns were stratified by their location and also compared between groups. RESULTS: We included 120 melanoma patients and 120 controls. Melanoma patients presented a larger number of common (p = 0.002) and atypical melanocytic nevi (p < 0.001) and more variability of dermoscopic nevus patterns (p < 0.001). No difference in the global dermatoscopic pattern of common nevi was observed between groups. The complex pattern of atypical nevi was associated with melanoma (OR = 2.87). Melanoma patients also showed more common nevi with a reticular pattern on the back (p = 0.014) and lower limbs (p = 0.041) as well as atypical nevi on the back with reticular pattern (p = 0.01), with reticular-homogeneous pattern (p = 0.001), and with reticular-globular pattern (p = 0.048) than controls. Nevi with multifocal pigmentation were also more frequent among melanoma patients (OR = 2.61). CONCLUSION: Melanoma patients tend to present a higher number of common reticular nevi on the back and lower limbs, as well as atypical nevi with a complex pattern, especially reticular, reticular-homogeneous, and reticular-globular on the back.

Molecular Proof of a Clinical Concept: Expression of Estrogen Alpha-, Beta-Receptors and G Protein-Coupled Estrogen Receptor 1 (GPER) in Histologically Assessed Common Nevi, Dysplastic Nevi and Melanomas.

Background and Objectives: Epidemiologic data show significant differences in melanoma incidence and outcomes between sexes. The role of hormonal receptors in the pathogenesis of melanocytic lesions remains unclear, thus we performed this study aiming to assess estrogen receptors expression in different melanocytic lesions. Materials and Methods: We performed a cross-sectional study that included 73 consecutively excised melanocytic lesions. Estrogen receptor alpha (ERα), beta (ERß), and G-protein coupled estrogen receptor (GPER) expression was analyzed in melanocytes and keratinocytes of common nevi, dysplastic nevi, melanoma, healthy skin margin, and in sebaceous and sweat gland cells. Results: ERß expression was higher in dysplastic nevi margin melanocytes compared to common nevi (p = 0.046) and in dysplastic nevi keratinocytes compared to melanoma keratinocytes (p = 0.021). ERß expression was significantly higher in margin melanocytes compared to melanoma melanocytes (p = 0.009). No difference in ERß expression was shown between melanocytes of three types of lesions. GPER expression was higher in nuclei and cytoplasm of dysplastic nevi (p = 0.02 and p = 0.036 respectively) and at the margin compared to melanoma. GPER expression was lower in sebaceous glands of tissue surrounding common nevi (p = 0.025) compared to dysplastic nevi. GPER expression was higher in skin margin tissue melanocytes (p = 0.016 nuclear, p = 0.029 cytoplasmic) compared to melanoma melanocytes. There were no differences in ERα expression between the melanocytic lesions. Conclusion: Further large-scale studies are warranted to investigate the potential role of ERß and GPER in the pathogenesis of melanocytic lesions.

Matrix metalloproteinases MMP-1, MMP-2, and MMP-13 are overexpressed in primary nodular melanoma.

BACKGROUND: The spread and invasion of malignant melanoma cells involve degradation and reorganization of the extracellular matrix by the activation of several matrix metalloproteinases (MMPs). This study analyzed the expression of MMP-1, MMP-2, and MMP-13 proteins in primary nodular melanoma (NM) and dysplastic nevi (DN) as a significant risk factor for melanoma development. The secondary goal was to analyze the correlation of MMPs protein expression in NM with tumor invasion, BRAF V600 mutation status, and overall survival. METHODS: Immunohistochemistry for MMP-1, MMP-2, and MMP-13 was performed on nodular melanoma (n = 52) and dysplastic nevi (n = 28) on tissue microarray (TMA). BRAF V600 mutation analysis on NM samples was performed by the Sanger sequencing method. RESULTS: A high level of MMPs expression in NM samples (>30%) compared with DN (<8%) was statistically significant (P < 0.001). BRAF V600 mutations were detected in 15 of 39 (38.5%) NM samples. This study revealed an interesting finding that MMP-1 and MMP-13 protein expression in the BRAF V600 mutated melanomas were significantly lower than in the BRAF V600 wild type (P < 0.05). CONCLUSION: Cox analysis revealed that Clark categories, Breslow thickness, and MMP-1 high protein expression are predictive factors for shorter overall survival (P < 0.05).

Is it necessary to perform eye examination for patients with cutaneous atypical nevi?

Regular dermatological examination for patients with dysplastic nevi is indicated. However, the literature on whether those patients should also be examined by ophthalmologists or not regarding a relation between suspicious lesions for ocular melanoma and cutaneous dysplastic nevi is limited. In this study, we aimed to compare the findings of a single ophthalmologic examination between the group of patients with multiple atypical nevi with at least one histopathologically proven dysplastic nevus and another group without atypical nevi. We examined the eyes of 110 patients with multiple atypical nevi with at least one histopathologically proven dysplastic nevus (47 had the diagnosis of dysplastic nevus syndrome type A, B, C, D1 or D2) for any lesion and compared the results with a control group consisted of 110 gender, age and skin-type matched patients without atypical nevi no ocular melanoma was detected in any of the groups. The frequency of the conjunctival nevi, iris nevi, choroidal nevi and conjunctival acquired melanosis were similar in both groups. Iris freckles were detected more frequently in the study group. Conjunctival racial hyperpigmentation was detected more frequently in the control group (P < .05). In this study, any significant difference in the distribution of the ocular lesions with any risk of malignancy in the study and control groups was not observed. However, considering the limitations of the study, there may still be a need of regular ophthalmic examination for the patients with atypical nevi in case of having high risk factors for developing melanoma.

Nuclear and cytoplasmic features in the diagnosis of Clark's nevi.

BACKGROUND: Interpretation of Clark's nevi has generated debate over the years; although criteria have been proposed for grading morphological features of melanocytes, there is still confusion and variability in the assessment of these lesions. METHODS: This is a retrospective observational study conducted on 100 Clark's nevi and 84 melanomas. A single expert dermatopathologist evaluated all blinded and randomized photomicrographs of both the Clark's nevi and melanomas for the presence of 14 cytologic features. Subsequently, a multivariate model was used to obtain sensitivity and specificity. RESULTS: Clark's nevi showed a significantly higher frequency of absent-or-inconspicuous nucleoli over melanoma, whereas mitotic figures, pleomorphism, notching, multiple nucleoli, peppered moth nuclear pattern, flattened adjacent nuclei, prominent nucleoli and vesicular nucleus with rounded nucleoli were found significantly higher in frequency in melanomas. CONCLUSION: Our data suggest that nuclear alterations are of value in the differentiation of atypical nevi from melanoma.

A meta-analysis of nevus-associated melanoma: Prevalence and practical implications.

The reported prevalence of nevus-associated melanoma varies substantially. We performed a systematic review and meta-analysis to determine the incidence and prevalence of this disease; we also performed subanalyses considering age, tumor thickness, and nevus-type classification. In 38 observational cohort and case-control studies, 29.1% of melanomas likely arose from a preexisting nevus and 70.9% de novo. Any given melanoma was 64% less likely to be nevus-associated than de novo (risk ratio 0.36, 95% confidence interval [CI] 0.29-0.44; P < .001; I2 = 99%); nevus-associated melanomas had a lower mean Breslow thickness than de novo melanomas (mean difference -0.39 mm; 95% CI -0.60 to -0.18; P = .0003; I2 = 66%). No significant differences were noted regarding the association of nevus-associated melanomas with nondysplastic nevi or dysplastic nevi (risk ratio 0.77, 95% CI 0.49-1.20; P = .24; I2 = 98%).

Non-invasive tools for the diagnosis of cutaneous melanoma.

BACKGROUND: While the excisional biopsy and histological examination of suspicious lesions remains the current gold standard for diagnosing cutaneous melanoma (CM), there is a demand for more objective and non-invasive examination methods that may support clinicians in their decision when to biopsy or not. METHODS: This review is based on publications and guidelines retrieved by a selective search in PubMed and MEDLINE and focused on non-invasive diagnostic strategies for detecting melanoma. RESULTS: Ten different non-invasive techniques were compared with regard to applicability, status of development, and resources necessary for introduction into clinical routine (dermoscopy, sequential digital dermoscopy, total body photography, computer-aided multispectral digital analysis, electrical impedance spectroscopy, Raman spectroscopy, reflectance confocal microscopy, multiphoton tomography, stepwise two-photon-laser spectroscopy, quantitative dynamic infrared imaging). In an effort to create a classification based on our analyses, we suggest to differentiate i) tools for screening of patients in daily clinical routine, ii) tools for examination of a restricted number of preselected lesions that produce an automated diagnostic score, iii) tools for examination of a restricted number of preselected lesions at specialized centers requiring extensive training, iv) devices at an experimental stage of development. CONCLUSION: None of the discussed examination techniques is able to provide a definite and final diagnosis or to completely replace the histopathological examination. Up to date, the need for fully automated devices offering a complete skin cancer screening has not been satisfied.

Dysplastic (or Atypical) Nevi Showing Moderate or Severe Atypia With Clear Margins on the Shave Removal Specimens Are Most Likely Completely Excised.

BACKGROUND: Dysplastic nevi (DN) are graded by their degree of atypia into 3 categories of mild, moderate, and severe. In many practices, DN with moderate or severe atypia are generally excised regardless of the status of the shave specimen margins. OBJECTIVE: With a new approach toward the margins on the shave removal specimens (SRS), the goal herein is to assess whether the shave removal procedure can sufficiently remove DN with moderate or severe atypia. METHODS: A total of 426 SRS diagnosed with DN showing moderate or severe atypia between January and December 2015 along with their post-shave excision specimens were reviewed. Based on the author's experience, clear or negative margins on the SRS were defined as neoplastic melanocytes confined within >0.2 mm of the lateral and deep specimen margins. The biopsy specimens were accompanied by Melan-A highlighting the subtle neoplastic cells. RESULTS: With a negative predictive value (NPV) of 98.4% (confidence interval: 97.2% to 100%, P < .001), DN showing moderate or severe atypia with clear margins are most likely removed by the shave procedure. CONCLUSION: Routine excision of DN showing moderate or severe atypia with clear margins on SRS is not necessary. Regular surveillance is sufficient.

A nongrading histologic approach to Clark (dysplastic) nevi: A potential to decrease the excision rate.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: 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. CONCLUSION: 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.

Evaluation of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) classification scheme for diagnosis of cutaneous melanocytic neoplasms: Results from the International Melanoma Pathology Study Group.

BACKGROUND: Pathologists use diverse terminology when interpreting melanocytic neoplasms, potentially compromising quality of care. OBJECTIVE: We sought to evaluate the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) scheme, a 5-category classification system for melanocytic lesions. METHODS: Participants (n = 16) of the 2013 International Melanoma Pathology Study Group Workshop provided independent case-level diagnoses and treatment suggestions for 48 melanocytic lesions. Individual diagnoses (including, when necessary, least and most severe diagnoses) were mapped to corresponding MPATH-Dx classes. Interrater agreement and correlation between MPATH-Dx categorization and treatment suggestions were evaluated. RESULTS: Most participants were board-certified dermatopathologists (n = 15), age 50 years or older (n = 12), male (n = 9), based in the United States (n = 11), and primary academic faculty (n = 14). Overall, participants generated 634 case-level diagnoses with treatment suggestions. Mean weighted kappa coefficients for diagnostic agreement after MPATH-Dx mapping (assuming least and most severe diagnoses, when necessary) were 0.70 (95% confidence interval 0.68-0.71) and 0.72 (95% confidence interval 0.71-0.73), respectively, whereas correlation between MPATH-Dx categorization and treatment suggestions was 0.91. LIMITATIONS: This was a small sample size of experienced pathologists in a testing situation. CONCLUSION: Varying diagnostic nomenclature can be classified into a concise hierarchy using the MPATH-Dx scheme. Further research is needed to determine whether this classification system can facilitate diagnostic concordance in general pathology practice and improve patient care.

Immunosuppression is an independent prognostic factor associated with aggressive tumor behavior in cutaneous melanoma.

BACKGROUND: A number of factors other than those identified by the American Joint Committee on Cancer (AJCC) may have prognostic significance in the evaluation of melanoma. OBJECTIVE: We sought to evaluate commonly recorded clinical features potentially associated with aggressive melanoma. METHODS: We conducted a retrospective case-control study. We included patients given a diagnosis of cutaneous melanoma with at least 5 years of follow-up or documented metastases. Patients were divided into nonaggressive and aggressive groups. Univariate and multivariate statistical analyses were performed to evaluate the association of multiple clinical and histologic parameters and metastases. RESULTS: We included 141 patients. Significant prognostic factors in univariate analysis associated with nonaggressive disease included history of dysplastic nevus syndrome and ABCDE criteria. Significant factors in univariate analysis associated with aggressive disease included age and immunosuppression. Only age and immunosuppression remained significant in multivariate analysis when controlled across statistically significant histologic variables from AJCC. LIMITATIONS: The study is retrospective and has a small sample size. CONCLUSION: Older patients and those with a history of immunosuppression may be at higher risk for aggressive disease and should be closely monitored after an initial diagnosis of melanoma.