The role of TERT promoter mutations in differentiating recurrent nevi from recurrent melanomas: A retrospective, case-control study.

BACKGROUND: Repigmentation at previous biopsy sites pose a significant diagnostic dilemma given clinical and histologic similarities between recurrent nevi and locally recurrent melanoma. Though common in melanoma, the role of TERT promoter mutations (TPMs) in recurrent nevi is unknown. OBJECTIVE: We investigated the role of TPMs in recurrent nevi and whether the presence of hotspot TPM distinguishes recurrent nevi from locally recurrent melanoma. We also characterized clinical and histologic features differentiating these lesions. METHODS: We analyzed 11 locally recurrent melanomas, 17 recurrent nevi, and melanoma and nevus controls to determine TPM status. We also assessed clinical and histologic features of the recurrent groups. RESULTS: Hotspot TPMs were more common in recurrent melanomas than recurrent nevi (P = .008). Recurrent melanomas were more likely to have solar elastosis (P = .0047), multilayering of melanocytes in the epidermis (P = .0221), adnexal involvement (P = .0069), and epidermal consumption (P = .0204). Recurrent nevi had intra-epidermal atypia limited to the area above the scar (P < .0001) and occurred earlier after the original biopsy (P < .0008). Solar elastosis, months to recurrence, and hotspot TPMs were independently associated with recurrent melanoma in multivariate analysis. LIMITATIONS: This was a retrospective study. CONCLUSION: Hotspot TPMs are significantly more frequent in recurrent melanomas and could serve as a diagnostic clue in histologically ambiguous cases.

Histomorphologic spectrum of germline-related and sporadic BAP1-inactivated melanocytic tumors.

BACKGROUND: BRCA1-associated protein 1 (BAP1)-inactivated melanocytic tumors (BIMTs) are often the earliest sign of the BAP1 tumor predisposition syndrome. Identification of BIMTs and selection of patients for germline testing affect the lives of patients with germline BAP1 mutations. OBJECTIVE: To describe the spectrum of histomorphologic findings in BAP1-inactivated melanocytic lesions to improve their recognition. We determined the frequency of sporadic versus germline cases in our cohort, assessing whether any features were statistically linked to germline status. METHODS: Histomorphologic features of BAP1-inactivated melanocytic lesions were analyzed by comparing cases with germline mutations with those with unknown or negative status. Available clinical follow-up data were reported. RESULTS: The histomorphologic spectrum of BAP1-inactivated melanocytic lesions is broad; it includes cases with spitzoid cytomorphology (69%), smaller epithelioid cells without spitzoid features (31%), and rhabdoid cytologic features (58%). BIMTs from patients with germline mutations were statistically more likely to have an extensive junctional component of BAP1-inactivated melanocytes (P = .0177). All 11 patients with suspected or confirmed germline mutations had a history of cutaneous melanoma or multiple BIMTs. LIMITATIONS: The unknown germline status of 77 patients. CONCLUSION: Approximately 12% of patients with BIMTs have germline mutations. Extensive junctional involvement in a BIMT and a personal history of melanoma or previous BIMT may be additional indications for germline testing.

The diagnostic value and histologic correlate of distinct patterns of shiny white streaks for the diagnosis of melanoma: A retrospective, case-control study.

BACKGROUND: Shiny white streaks (SWSs) are best visualized with polarized dermoscopy and correlate with dermal fibroplasia histopathologically. SWSs have been described at higher frequencies in melanomas than in benign nevi. OBJECTIVE: We assessed the diagnostic value of different patterns of SWSs and their histologic correlate in melanocytic lesions. METHODS: Polarized dermoscopic images of 1507 histopathologically diagnosed melanocytic neoplasms were analyzed for presence and pattern of SWSs. Histology was also reviewed for correlation. RESULTS: Among 1507 melanocytic neoplasms, SWSs were observed in 31 of 144 melanomas (22%) and 22 of 1363 benign neoplasms (1.6%) (P < .001). The sensitivity and specificity of SWSs for melanoma were 22% and 98%, respectively. Diffuse SWSs exhibited the greatest diagnostic value for melanoma, with sensitivity of 11.8% and specificity of 99.5%. Focal central and peripheral SWSs were comparable in diagnostic significance. The presence of SWSs was highly uncommon in dysplastic nevi, whereas in certain benign subgroups of nevi such as Spitz nevi and atypical genital special site nevi, SWSs were not uncommon. Diffuse SWSs correlated with greater breadth of deep fibroplasia than focal SWSs (P = .009), and SWSs correlated with greater Breslow depth among melanomas (P = .007). LIMITATIONS: This study was retrospective. CONCLUSION: Polarized dermoscopy is a valuable diagnostic tool in the identification of SWSs, a feature that is highly specific for melanoma.

Incorporation of dermoscopy improves inter-observer agreement among dermatopathologists in histologic assessment of melanocytic neoplasms.

Histopathologic assessment of melanocytic neoplasms is the current gold standard of diagnosis. However, there are well recognized limitations including inter-observer diagnostic discordance. This study aimed to determine if integrating dermoscopy with histopathology of melanocytic neoplasms impacts diagnosis and improves inter-observer agreement. We conducted a prospective cohort study in a pigmented lesion clinic. Consecutive melanocytic lesions were identified for biopsy based on atypical gross or dermoscopic features. Standardized immunohistochemistry and levels were ordered on each specimen. The cases were randomized. Three dermatopathologists blinded to the clinical impression assessed each lesion. The cases were then re-randomized and re-assessed with addition of gross clinical and dermoscopic images. Inter-rater reliability (IRR) using Fleiss' kappa statistic revealed an increase from 0.447 without to 0.496 with dermoscopy amongst all dermatopathologists. The kappa increased from 0.495 before to 0.511 with dermoscopy in separating high-grade atypia or melanoma from moderate atypia or less. In 16 of 136 cases, at least 2 of 3 dermatopathologists favored a diagnosis of melanoma only after dermoscopy. In total, the consensus grade of atypia changed in 24.3% (33/ 136) of cases thereby representing changes to excisional margins and patient follow up. This study is limited by the cohort size. Dermoscopy significantly impacts diagnosis and improves identification of early melanomas in high risk populations and improves inter-observer agreement.

Childhood lichen planus: demographics of a U.S. population.

Lichen planus is an inflammatory dermatosis of unknown origin that is relatively uncommon in children. Demographic data for lichen planus of children in the United States are lacking, with most large case reports originating from India, Kuwait, Mexico, and the United Kingdom. We hypothesized that a greater proportion of our pediatric lichen planus patients were African American, an observation not previously documented. A retrospective chart review was performed to investigate characteristics of our pediatric lichen planus patients. The ethnicity of the lichen planus patients was compared with the data for our general patient population. The proportion of African American patients in each group was compared using the chi-squared test. We report 36 children (female to male ratio 2:1) who presented with lichen planus to the pediatric dermatology clinic at Children's Hospital of Wisconsin. Twenty-six (72%) of these patients were African American (OR 9.63, p < 0.0001). A personal or family history of autoimmune disease was present in six (17%) patients. Although there has been no reported racial predominance of lichen planus, we observed lichen planus to occur more commonly in African American children. Interestingly, the incidence of autoimmune disease was higher than has previously been reported. Future studies will confirm or refute these observations and advance our understanding of potential genetic or environmental risk factors for the development of lichen planus.