Diagnostic Utility of the 23-gene Expression Profile Test for an Atypical Intradermal Melanocytic Proliferation

Abstract

Ancillary tests such as immunohistochemistry (IHC) and gene expression profile (GEP) testing may be needed to arrive at a definitive diagnosis for some atypical melanocytic neoplasms. A 34-year-old male with a family history of melanoma presented with a large, heterogeneous melanocytic lesion on the cheek. Histopathological review of two biopsies revealed an atypical intradermal melanocytic proliferation with spitzoid features without ulceration or regression. Scattered mitotic figures were identified. In addition to performing SOX10 IHC, PRAME and HMB45 staining highlighted weak, patchy positivity that was stronger in superficial, pleomorphic melanocytes (Ki-67, 5–7% mitotic rate). Based on these concerning but ambiguous IHC results and lingering concern for melanoma reiterated by other consulting dermatopathologists, the 23-GEP was requested for both specimens, which both returned a malignant result. The inconclusive histopathological features of malignancy were resolved by 23-GEP testing, facilitating a final diagnosis of malignant melanoma (pT3a, 2.5 mm Breslow depth, Clark’s level IV).

Keywords::

• 23-gene expression profile
• ancillary diagnostic testing
• atypical intradermal melanocytic proliferation
• cutaneous melanoma
• melanoma ex nevus

Author contributions

E Marks and AA Badia were involved in patient care. E Marks, AA Badia, and MS Goldberg conceptualized the study, collected, analyzed and interpreted the data, were involved in the writing and editing of the manuscript, and approved the submission.

Acknowledgments

Presented in part at the American Society of Dermatopathology 59^th Annual Meeting abstracts, 20–23 October 2022.

Financial disclosure

The study was partially supported by Castle Biosciences, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

E Marks has served as a consultant and advisory board member for Castle Biosciences, Inc. AA Badia has no competing financial interests to declare. MS Goldberg is an employee shareholder of Castle Biosciences, Inc. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing disclosure

Writing assistance was provided by JH Rogers and BH Russell who are employee shareholders of Castle Biosciences, Inc.

Informed consent disclosure

This case study was formally exempted from IRB-approval Western IRB (WA, USA). The authors state that they have obtained verbal and written informed consent from the patient/patients for the inclusion of their medical and treatment history within this case report.

Additional information

Funding

The study was partially supported by Castle Biosciences, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.