Systemic Workup for High-Risk Cutaneous Malignancies

Educational Objectives

The goal of this program is to improve the systemic workup for high-risk cutaneous malignancies. After hearing and assimilating this program, the clinician will be better able to:

1. Diagnose micrometastatic disease in regional lymph nodes of patients with invasive melanoma.
2. Explain the role of baseline imaging and laboratory tests in managing high-risk cutaneous malignancies.

Summary

Clinical evaluation: for patients newly diagnosed with invasive melanoma (IM), high-risk squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC), a detailed history and a full-body skin examination with particular attention to the primary site should be performed; one should look for in-transit and satellite metastasis and examine the regional and distant lymph node basins as these can significantly upstage the tumor and change clinical management; an extensive metastatic workup is not essential for patients at lower risk

Sentinel lymph node biopsy (SLNB): it is the most sensitive and specific staging test for IM and MCC to assess micrometastatic disease in the regional lymph nodes; SLNB in melanoma — SLNB is not routinely recommended for stage 1A or T1a melanoma (can be considered for stage 1B melanoma); specific adverse features, ie, younger age of diagnosis, the head and neck location, a high mitotic index, and lymphovascular invasion, even in a T1a melanoma (Breslow depth ≥ 0.5 mm), may have a slightly higher risk for a positive SLNB; SLNB should be considered for melanoma grades T2a, T2b, or higher (likelihood of being positive is >10%); clinical scenarios where SLNB may not be recommended in melanoma — patient specific comorbidities, patient preference, and pure desmoplastic melanoma; SLNB is recommended for only mixed desmoplastic melanoma

SLNB in high-risk SCC: SLNB can be considered for Brigham and Women’s Hospital (BWH) T2b and T3 tumors; Tremblay-Abel et al (2021) found 5.4% SLNB positivity in BWH T2b tumors

SLNB in MCC: SLNB should be recommended for all clinically node-negative patients; truncal location, presence of tumor infiltrating lymphocytes, and lymphovascular invasion are predictors of a positive test

Imaging: the National Comprehensive Cancer Network (NCCN) guidelines recommend that for stage 0, 1, and 2 melanoma, baseline imaging is not required unless there are specific signs or symptoms or it is needed for possible surgical planning; for patients with equivocal, indiscriminate, or palpable lymphadenopathy, direct examination of the lymph node, often using ultrasonography with fine-needle aspiration (FNA) or core needle biopsy (CNB), is recommended; ultrasonography or ultrasonography-guided FNA is one of the best staging and surveillance imaging tools, specifically for lymph node metastasis in melanoma

Imaging in clinical stage 3 and 4 melanoma: baseline whole body imaging, ie, positron emission tomography (PET)-computed tomography (CT), or whole body CT is recommended for clinical stage 3 disease; in specific high-risk patients, baseline central nervous system (CNS) imaging to screen for asymptomatic CNS metastasis is recommended; for stage 4 disease, baseline whole body imaging and CNS imaging should be performed

Imaging in high-risk SCC: in a study by Maher et al (2020), imaging detected subclinical disease in 21% of patients that led to altered management in ≈25% of patients; in BWH T2b and T3 tumors, patients without any baseline imaging were twice as likely to develop a poor prognosis (Ruiz et al [2017]); it is recommended to consider baseline imaging (with primary site plus lymphatic node basins) for BWH T2b and T3 tumors; CT with contrast is commonly used for SCC; for concerning lymph nodes, imaging and tissue diagnosis, often with ultrasonography-guided FNA or a CNB is recommended

Imaging in MCC: the NCCN guidelines recommend performing baseline imaging in most patients as metastatic disease can occur in 20% of asymptomatic patients; whole body fluorodeoxyglucose PET or CT can be performed; baseline imaging is helpful for staging, to assess for any metastases, and to rule out skin metastasis from a noncutaneous source

Laboratory tests: lactate dehydrogenase is an independent predictor of poor outcome in patients with melanoma; it is a nonspecific marker of tumor burden and is used to upstage the M category of the American Joint Committee on Cancer-8 guidelines; genomic testing, eg, for BRAF mutation or KIT mutation may aid in deciding targeted therapies for melanoma; testing for the presence of Merkel cell polyomavirus (MCPyV) DNA is essential as MCPyV-negative MCC patients have a higher tumor burden and mutational burden; the antibodies to the virus help to track tumor response to therapeutics and recurrence

Readings

Knispel S, Gassenmaier M, Menzies AM, et al. Outcome of melanoma patients with elevated LDH treated with first-line targeted therapy or PD-1-based immune checkpoint inhibition. Eur J Cancer. 2021;148:61-75. doi:10.1016/j.ejca.2021.01.034; Maher JM, Schmults CD, Murad F, et al. Detection of subclinical disease with baseline and surveillance imaging in high-risk cutaneous squamous cell carcinomas. J Am Acad Dermatol. 2020;82(4):920-926. doi:10.1016/j.jaad.2019.10.067; Ruiz ES, Karia PS, Morgan FC, et al. The positive impact of radiologic imaging on high-stage cutaneous squamous cell carcinoma management. J Am Acad Dermatol. 2017;76(2):217-225. doi:10.1016/j.jaad.2016.08.051; Tremblay-Abel V, Poulin MA, Blouin MM, et al. Sentinel lymph node biopsy in high-risk cutaneous squamous cell carcinoma: analysis of a large size retrospective series. Dermatol Surg. 2021;47(7):908-913. doi:10.1097/DSS.0000000000003085; Wong SL, Faries MB, Kennedy EB, et al. Sentinel lymph node biopsy and management of regional lymph nodes in melanoma: American society of clinical oncology and society of surgical oncology clinical practice guideline update. J Clin Oncol. 2018;36(4):399-413. doi:10.1200/JCO.2017.75.7724.

Disclosures

For this programm, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Fronek was recorded at the Melanoma and Cutaneous Oncology Symposium, held January 25-26, 2025, in Coronado, CA, and presented by Scripps. For information on upcoming CME activities from this presenter, please visit scripps.org. Audio Digest thanks the speakers and Scripps for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.50 CE contact hours.

Lecture ID:

ON160803

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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