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.

Atypical (dysplastic) nevi: outcomes of surgical excision and association with melanoma.

OBJECTIVE: To evaluate the effect of surgical excision, performed after biopsy diagnosis of dysplastic nevus, on final diagnosis, melanoma prevention, and melanoma detection. DESIGN, SETTING, AND PARTICIPANTS: Outcome study using retrospective review conducted in an academic dermatopathology practice (Boston Medical Center Skin Pathology Laboratory) that receives specimens from community and academic practices across the United States. Consecutive patient pathology samples of dysplastic nevi and cutaneous melanomas evaluated between September 1, 1999 and March 1, 2011, and identified using systematized nomenclature of medicine codes were included. MAIN OUTCOMES AND MEASURES: In dysplastic nevi cases, the rate of clinically significant change in diagnosis and the rate of melanoma detection as a result of excision. In melanoma cases, the rate and characteristics of association with dysplastic nevus. RESULTS: Of dysplastic nevi, 196 of 580 (34%) showed a positive biopsy margin, increasing with grade of atypia (P < .001); 127 of 196 with positive biopsy margin received excision (65%), performed more often as grade of atypia increased (P < .001). Two excisions (2 of 127, 1.6%) resulted in a clinically significant change in diagnosis, from biopsy-diagnosed moderately-to-severely dysplastic nevi before excision to melanoma in situ after excision. In melanomas (n = 216), in situ and superficial spreading subtypes were more often associated with dysplastic nevi (20% and 18%, respectively) (P = .002), most often of moderate-to-severe or severe grade. CONCLUSIONS AND RELEVANCE: Excision of biopsy-diagnosed mildly or moderately dysplastic nevi is unlikely to result in a clinically significant change in diagnosis, and risk of transformation to melanoma appears very low. Moderately-to-severely and severely dysplastic nevi are more often associated with melanoma, and excision may be beneficial for melanoma detection or prevention.

Dysplastic nevi.

Dysplastic nevi have been a subject of much debate since their original description in 1978. Although some question the biological potential of dysplastic nevi themselves, several studies have shown that their presence confers substantial risk for melanoma. In addition to predisposing patients to melanoma, dysplastic nevi have been shown to harbor genetic mutations, indicating their position on a continuum between banal nevi and melanomas. Dysplastic nevi are also clinically relevant as mimickers of melanoma, and can be challenging diagnostically. This article reviews the history, epidemiology, biology and genetics, clinical features, histopathologic features, and management guidelines for patients with these lesions.

Eosinophilic dermatosis of hematologic malignancy.

Cutaneous involvement by an eosinophil-rich process (eosinophilic dermatosis) may be encountered in the setting of various hematologic malignancies, including mantle cell lymphoma, acute monocytic leukemia, acute lymphoblastic leukemia, large cell lymphoma, myelofibrosis and chronic lymphocytic leukemia (CLL). Of the various hematologic malignancies, eosinophilic dermatosis has been most frequently described in association with CLL. Published previously as insect bite-like reaction and eosinophilic dermatosis of myeloproliferative disease, this rare dermatitis presents as a pruritic, papular and occasionally vesicular eruption associated with an eosinophil-rich infiltrate histopathologically. Although clinical and histopathologic features are similar to insect bites, affected patients frequently deny a history of insect bites. We report a case of eosinophilic dermatosis of hematologic malignancy in a patient with known history of CLL.

The "dysplastic" nevus.

Dysplastic nevi have become an increasing focus clinically, with evidence that they are associated with a higher risk of developing melanoma. However, there still is contention regarding the significance of dysplastic nevi. This contribution provides an overview of the history, epidemiology, genetics, clinical and histologic features, and procedures for clinical management of dysplastic nevi. Since dysplastic nevi were described originally in 1978, a great deal of research has examined the epidemiology of these lesions and the genetic factors related to the development of dysplastic nevi. However, there is disagreement regarding the clinical management of dysplastic nevi and the histologic definition of dysplastic nevi. Current recommendations include preventative measures, such as sun protection and careful surveillance and biopsies of suspicious lesions as needed. The advent of new technologies, such as computer-vision systems, have the potential to significantly change treatment of dysplastic nevi in the future.

The diagnostic performance of expert dermoscopists vs a computer-vision system on small-diameter melanomas.

OBJECTIVE: To evaluate the performance of dermoscopists in diagnosing small pigmented skin lesions (diameter

Linking transcriptional elongation and messenger RNA export to metastatic breast cancers.

The biochemical pathways that are disrupted in the genesis of sporadic breast cancers remain unclear. Moreover, the present prognosticating markers used to determine the prognosis of node-negative patient leads to probabilistic results, and the eventual clinical course is far from certain. Here we identified the human TREX complex, a multiprotein complex that links transcription elongation to mRNA transport, as culprit of aggressive human breast cancers. We show that whereas p84N5 (called hTREX84) is expressed at very low levels in normal breast epithelial cells, it is highly expressed in breast tumors. Importantly, hTREX84 expression correlates with tumor size and the metastatic state of the tumor progression. Reduction of hTREX84 levels in breast cancer cell lines by small interfering RNA result in inhibition of cellular proliferation and abrogation of mRNA export. These results not only identify hTREX84 as a prognosticator of breast cancer but also delineate human TREX complex as a target for therapeutic drugs against breast cancer.