Clinicopathologic gene expression profiling in lieu of sentinel lymph node biopsy: A case report in an uninsured patient with melanoma

Introduction

Cutaneous melanoma is among the most aggressive forms of skin cancer, with an estimated 325,000 new cases and 57,000 deaths worldwide in 2020.^1,2 Its global incidence is rising—projected to reach 510,000 new cases and 96,000 deaths annually by 2040.³ While incidence has steadily increased at an average annual rate of 1.13%, global mortality and disability-adjusted life years rates have declined, reflecting advances in melanoma management.⁴

Accurate staging guides treatment decisions, improving survival outcomes. For patients with intermediate-thickness melanomas, sentinel lymph node biopsy (SLNB) remains the standard procedure for assessing regional nodal metastasis.^5,6 According to current National Comprehensive Cancer Network (NCCN) guidelines, SLNB should be discussed and offered to patients whose risk of nodal involvement exceeds 10%, corresponding to pathologic stage T2a melanomas.⁶

While SLNB provides critical prognostic information, its availability is often limited in underserved populations due to cost, lack of insurance, geographic barriers to surgical oncology centers, and other socioeconomic barriers.¹ These access gaps highlight the need for accessible, noninvasive risk stratification tools to guide melanoma staging.

The clinicopathologic and gene expression profiling (CP-GEP) test—a validated gene expression profiling assay that integrates clinicopathologic features—offers an evidence-based method to identify patients at low risk for sentinel lymph node metastasis, thereby supporting risk-adapted clinical judgment and potentially reducing reliance on invasive procedures.⁷ This case report illustrates the application of the CP-GEP test in a patient with pathologic stage T2a melanoma for whom SLNB was not feasible due to financial and access-related barriers and emphasizes how molecular risk stratification tools can serve as a practical solution to mitigate access-related disparities in melanoma care.

Case report

A 75-year-old Hispanic male with a history of hypertension presented to a volunteer health clinic for a routine skin examination. The patient had a progressively enlarging new pigmented lesion on his right arm. The lesion measured 1.2 cm in diameter, appeared asymmetrical, had irregular borders, and demonstrated variegated pigmentation in shades of brown and black (Fig 1).

Fig 1.

Clinical image of the 1.2 cm lesion on the right arm, displaying asymmetry, irregular borders, and variegated pigmentation—features suspicious for cutaneous melanoma.

Dermoscopy revealed an irregular pigment network and the presence of a blue-white veil (Fig 2).

Fig 2.

Dermoscopic image revealing an irregular pigment network and the presence of blue-white veil. The lesion measures approximately 7 mm in diameter based on the dermoscopic scale.

A deep shave biopsy was performed. Histopathological evaluation demonstrated nests of atypical melanocytes within the epidermis and extending into the dermis. Immunohistochemical studies demonstrated SOX-10 positivity, confirming a melanocytic lesion. HMB-45 stained diffusely throughout the lesion, PRAME was positive in 100% of lesional cells, and the Ki-67 proliferative index was increased. Although P16 expression was retained, the combined findings supported a diagnosis of cutaneous melanoma (Fig 3).

Fig 3.

Histopathologic image (H&E stain, ×100 magnification) showing nests of atypical melanocytes extending into the dermis. Findings are consistent with pathologic stage T2a cutaneous melanoma (Breslow depth 1.1 mm, nonulcerated).

The Breslow depth was 1.1 mm, and the tumor was classified as pathologic stage T2a. There was no clinical evidence of regional lymphadenopathy. The patient denied systemic symptoms, including fatigue, weight loss, abdominal pain, appetite changes, chest pain, or shortness of breath.

Per the American Society of Clinical Oncology, Society of Surgical Oncology, and NCCN guidelines, SLNB was indicated for staging due to the >10% risk of nodal metastasis associated with pathologic stage T2a melanoma.^1,5,6 However, lack of insurance and limited access to surgical oncology limited his care.

To support risk stratification and clinical decision-making, the CP-GEP test was pursued through a patient assistance program at no cost to the patient. Results stratified the patient as low risk, obviating the need for SLNB and enabling a shared decision to proceed with wide local excision alone.

The patient underwent wide local excision with 1 cm radial margins. The defect was closed with layered sutures, and margins were clear. Without SLNB, the patient began surveillance with skin and lymph node examinations every 3 months and is completing the Appetite change, Tiredness, Lymph node enlargement, Abdominal pain, Shortness of breath questionnaire, a validated symptom-based tool for early detection of melanoma recurrence, which stands for appetite change, tiredness, lymph node enlargement, abdominal pain, and shortness of breath, offering structured, noninvasive follow-up suited to his risk and circumstances.

Discussion

Melanoma care requires addressing systemic barriers. Uninsured, isolated, and underserved patients often face delays in diagnosis and treatment, worsening outcomes.⁸ SLNB remains the standard for pathologic staging in intermediate-thickness melanomas, guiding prognosis and eligibility for adjuvant therapy, as emphasized by American Society of Clinical Oncology and Society of Surgical Oncology.¹ However, SLNB necessitates specialized surgical expertise, insurance coverage, and patient consent for an invasive procedure—resources that are frequently inaccessible to vulnerable populations.⁸ These disparities underscore the need for innovative strategies and policy interventions to ensure equitable delivery of melanoma care.

This case brings to focus an evolving solution. The CP-GEP assay offers a molecular lens through which nodal risk might be assessed without surgery.⁹ By synthesizing gene expression with traditional clinicopathologic features, it achieves a high negative predictive value—accurately identifying patients who are unlikely to benefit from SLNB. For this patient, the test not only substituted a surgical staging procedure but reshaped the care pathway entirely: reducing the procedural risks associated with SLNB—such as edema, seroma formation, infection, and scarring—while respecting socioeconomic constraints and maintaining concordance with NCCN recommendations.⁶

Beyond staging, GEP testing may also redefine follow-up. Recent evidence suggests that GEP-classified low-risk patients enjoy favorable recurrence-free and melanoma-specific survival—even without nodal sampling.⁷ This challenges the notion that SLNB is the sole gateway to safe surveillance and introduces a precision-medicine framework for long-term monitoring in low-resource settings. However, current NCCN and American Academy of Dermatology guidelines still consider GEP investigational and recommend its use primarily within clinical trials or multidisciplinary discussions.5, 6, 7

Cost and access are central to the use of GEP in melanoma care. While CP-GEP does not yet have standardized US reimbursement pricing, comparable assays such as the 31-GEP assay is reimbursed by Medicare at approximately $7200 per test, whereas SLNB often exceeds $10,000 to $15,000 when operative and facility fees are included.¹⁰ Unlike SLNB, GEP is performed once at diagnosis to guide staging decisions and is not used for ongoing surveillance, which remains based on clinical and nodal examinations. In our patient, after 1 year of follow-up with quarterly full-body skin and nodal examinations supplemented by the Appetite change, Tiredness, Lymph node enlargement, Abdominal pain, Shortness of breath questionnaire, he has remained negative for recurrence; however, prospective long-term outcome data for GEP-guided melanoma management are still limited.¹⁰ Access is inconsistent: insurance coverage is variable, and uninsured patients must often rely on restrictive manufacturer-led patient assistance programs. Without access to such programs, however, affordability remains severely limited, as the several-thousand-dollar test cost is prohibitive for most uninsured patients, and coverage across payers is inconsistent. Broader adoption must be grounded in ongoing prospective research, real-world outcome data, and consensus on how these results should influence therapy and follow-up.

If we are to embrace these tools, we must also ensure they do not widen existing gaps. Patient assistance programs, like the one accessed in this case, are an essential stopgap—but policy solutions will be needed to make access the rule, not the exception.

For patients like this—caught between clinical need and systemic constraint—GEP testing represents more than a test. It’s a pivot point: a chance to rethink what risk-adapted, resource-conscious melanoma care can look like.

This report is limited by its single-patient design, which precludes generalizability; gene expression profiling remains investigational, and access is inconsistent across insurers.⁸

Conflicts of interest

None disclosed.