We present a 65-year-old woman who developed a diffuse pruritic papular eruption after receiving induction chemotherapy with daunorubicin and cytarabine for newly diagnosed acute myelomonocytic leukemia. The rash improved clinically with triamcinolone treatment and chemotherapy was allowed to continue. This case adds to the growing literature of transient acantholytic dermatosis development in the setting of anti-cancer therapy and emphasizes the importance of clinicopathologic correlation in cutaneous eruptions in cancer patients.

We present a case of SCALP syndrome, which was diagnosed in a male infant with the characteristic findings of sebaceous nevi, central nervous system malformations, aplasia cutis congenita, limbal dermoid, and giant congenital melanocytic nevi, or pigmented nevi. We identified a germline compound heterozygous DOCK6 mutation and a somatic mosaic NRAS Q61R mutation in the giant congenital melanocytic nevus. This report will increase clinician awareness of SCALP syndrome and augment the literature in characterizing this rare syndrome, including its genetic background.

Early diagnosis of melanoma is critical for improved survival as melanoma is the deadliest of the common forms of skin cancer. The gold standard for the diagnosis of melanoma is a biopsy followed by histopathological analysis. Melanocytic nevi, which are very common benign neoplasms of the melanocytes, are often biopsied because they are mimics and precursor for melanoma. Annually, 4.5 million pigmented lesions are biopsied in the United States. A subset of melanoma is difficult to distinguish from melanocytic nevi, resulting in diagnostic errors and worsened patient outcomes. Therefore, improved diagnostic tests, including the utilization of novel biomarkers, are being developed to improve clinical and histological diagnostic accuracy of melanoma. Moreover, non-invasive tests prior to surgical biopsy have been introduced, including an adhesive patch-based assay that tests the expression of melanoma biomarkers PRAME and noncoding long RNA LINC00518. Our prior work identified that S100A8, a member of the calcium-binding S100 family, is differentially expressed in melanomas versus nevi4 . Specifically, S100A8 is expressed by the keratinocyte microenvironment of melanomas but not nevi. S100A8 is a melanoma biomarker of interest for an adhesive patch-based assay, because it is expressed in the epidermis, the most superficial layer of the skin.

Background

S100A8 is a melanoma biomarker expressed in the melanoma-associated epidermal keratinocytes, but its diagnostic utility has not been compared with other biomarkers, including PRAME.

Objectives

To compare the utility of S100A8 and PRAME immunohistochemistry (IHC) in the differential diagnosis of melanoma and naevi in a case-control study.

Methods

A previously described cohort of 209 melanomas (case samples) and naevi (control samples) dual-immunostained for S100A8 and PRAME were included. For S100A8, previously reported scores indicating the proportion of tumour-associated epidermis stained (0 = indeterminate; 1 = 0-4%; 2 = 5-25%; 3 = 26-50%; 4 = 51-75%; 5 = > 75%) were utilized. PRAME IHC was reviewed by at least two reviewers and a consensus score assigned, with score indicating the proportion of tumour stained (0 = indeterminate; 1 = 0%; 2 = 1-50%; 3 = > 50%). A positive test was defined as > 50% staining.

Results

The area under the receiver operating characteristic curves for S100A8 (0.833) and PRAME (0.874) were not significantly different from each other (P = 0.22). The diagnostic sensitivity and specificity were 42.4% [95% confidence interval (CI) 32.6-52.8%] and 98.2% (95% CI 93.6-99.8%) for S100A8, and 79.8% (95% CI 70.5-87.2%) and 87.3% (95% CI 79.6-92.9%) for PRAME, respectively. A combined test requiring both S100A8 and PRAME IHC positivity had a sensitivity of 39.4% (95% CI 29.7-49.7%) and specificity of 99.1% (95% CI 95.0-100.0%).

Conclusions

S100A8 and PRAME have utility in the diagnostic workup of melanoma, with S100A8 being more specific and PRAME being more sensitive when using this threshold. Our findings suggest that these two immunohistochemical markers may favourably complement one another to improve the detection of melanoma.