Use of <scp>PRAME</scp> immunostaining to distinguish early melanoma in situ from benign pigmented conditions

Olds, Hailey; Utz, Sarah; Abrams, Judith; Terrano, David; Mehregan, Darius

doi:10.1111/cup.14212

Cited by 10 publications

(14 citation statements)

References 11 publications

(42 reference statements)

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“…In this study, we assessed PRAME expression in early invasive SSM and DN and went beyond these previous analyses using a standardized computer-assisted procedure to minimize intra- and inter-observer variability [ 29 ]. As DN can have some degree of PRAME reactivity, a clear distinction is even more difficult to determine, and standardized measures are warranted.…”

Section: Discussionmentioning

confidence: 99%

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

Koch

Erdmann

Berking

et al. 2023

IJMS

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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.

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Section: Discussionmentioning

confidence: 99%

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

Koch

Erdmann

Berking

et al. 2023

IJMS

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“…PReferentially expressed Antigen in MElanoma (PRAME) staining may also be useful for margin assessment in this clinical context, although variable staining in solar lentigines and photodamaged skin are potential pitfalls. 12…”

Section: Discussionmentioning

confidence: 99%

Nevus Spilus With Dermatoheliosis: A Histologic Mimicker of Melanoma in Situ at Melanoma Excision Margins

Sheridan

O’Connor

Sitton

et al. 2023

The American Journal of Dermatopathology

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Nevus spilus, or speckled lentiginous nevus, is a relatively common lesion that presents at birth or in early childhood. It consists of a background tan patch, which appears similar to a café au lait macule or lentigo simplex on histology, studded with various types of nevi. Rarely, these nevi can undergo malignant transformation to melanoma. When melanoma develops within a heavily photodamaged nevus spilus, evaluating excision margins may be challenging because the combined histologic features of nevus spilus and severe dermatoheliosis can mimic melanoma in situ. We report a case of an elderly man with extensive sun damage who developed malignant melanoma within an occult nevus spilus, resulting in multiple excisions with false-positive margins.

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“…3 An additional issue arises when evaluating PRAME immunohistochemistry in the context of sun damage as benign skin biopsy specimens with solar elastosis can show increased counts of PRAME+ melanocytes per linear mm of biopsy. 4 We designed a large case-control study to evaluate the accuracy metrics of PRAME immunohistochemistry to distinguish melanocytic pseudonests in lichenoid dermatoses or keratoses from inflamed MIS and identify the optimal interpretation method for evaluating PRAME in that context (PRAME+ melanocytes per linear mm of epidermal basal layer, categorical % of melanocytes staining, clusters of PRAME + melanocytes). As a secondary endpoint, we examined if sundamaged skin with lichenoid inflammation presented increased counts of PRAME+ melanocytes.…”

Section: Introductionmentioning

confidence: 99%

PRAME immunohistochemistry can distinguish melanocytic pseudonests of lichenoid reactions from melanoma in situ

2023

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Background Distinguishing melanocytic pseudonests encountered in lichenoid dermatoses or lichenoid keratoses from melanoma in situ (MIS) with brisk lichenoid inflammation can prove challenging. Methods We designed a case–control study to evaluate the accuracy metrics of PRAME immunohistochemistry to distinguish melanocytic pseudonests in lichenoid dermatoses or keratoses from inflamed MIS. Immunostaining for PRAME was performed on paraffin‐embedded formalin‐fixed diagnostic tissue using a rabbit monoclonal antibody to PRAME (Abcam), with a 1:3200 dilution on a Leica Bond detection system. Results Our search identified 21 cases of melanocytic pseudonests (n = 21, 46%) encountered in lichenoid dermatoses and 24 cases of inflamed MIS (n = 24, 53%). Each method of evaluating PRAME immunohistochemistry (PRAME+ clusters, PRAME % of melanocytes by four categories and PRAME+ melanocyte counts per linear mm of epidermal basal layer) showed statistically significant differences between the MIS and the pseudonest cohorts (respectively, p < 0.001; p < 0.001; and p < 0.001). Receiver operating characteristics analysis for PRAME+ melanocyte counts per linear mm of epidermal basal layer revealed an area under the curve of 0.9 ± 0.05 (95% confidence interval 0.9–1.0). When determining an optimal cut‐off point for the best Youden index [sensitivity (%) + specificity (%) − 100], the cut‐off of 1.0 PRAME+ melanocytes per linear mm showed a sensitivity of 79.2% and specificity of 85.7% (Youden index 0.65) to distinguish MIS from pseudonests. Conclusion PRAME immunohistochemistry may constitute an additional tool for this challenging differential diagnosis.

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Use of PRAME immunostaining to distinguish early melanoma in situ from benign pigmented conditions

Cited by 10 publications

References 11 publications

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

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

Nevus Spilus With Dermatoheliosis: A Histologic Mimicker of Melanoma in Situ at Melanoma Excision Margins

PRAME immunohistochemistry can distinguish melanocytic pseudonests of lichenoid reactions from melanoma in situ

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