Margin control of lentigo maligna with SOX10-frozen section immunostaining: A case series.

Mohs micrographic surgery is associated with an improved overall survival rate in patients with melanoma of the head and neck.1 However, visualizing melanocytes on frozen sections may be challenging. Although permanent section analyses are commonly performed, they require multi-day procedures. To overcome this situation, melanocyte-specific immunostains on frozen tissue such as MART-1 have been tested.2 However, this marker can lead to false-positive margins, particularly in chronically sun-damaged skin.3 SOX10 has been widely used as a nuclear marker of melanoma, and shown to be both highly sensitive and specific,4 with promising results in frozen sections.5 However, its performance in fresh–frozen section margin control techniques (FSMCT) has not been previously evaluated in patients with lentigo maligna (LM). Our objective was to evaluate the sensitivity and specificity of SOX10 on FSMCT samples of LM of the head, compared with paraffin-embedded SOX10 immunostaining. Biopsy-proven LM patients who consulted the Dermatology Department of a tertiary Hospital (September 2021–June 2022), were included in a prospective study and treated with an FSMCT (‘Spaghetti technique’).6 Each sample was first processed into frozen sections, stained with H&E and SOX10 (12-min protocol, reference K47040-005, Novodiax Inc.) and finally evaluated by a single dermatopathologist. Samples were then thawed, fixed in formalin for paraffin sections, H&E, SOX10 staining (clone SP267, Roche) and evaluated by the same pathologist. Samples were dichotomously classified as positive (melanoma) and negative (actinic melanocytic hyperplasia or no lesion detected). Twenty patients, 11 males and 9 females, were included in this study. The median age was 68 years (range: 40–88) (Table 1). A total of 153 SOX10-frozen tissue slides were evaluated. Positivity for SOX10 was observed in 47 slides, while 105 were negative. One slide was not assessable due to technical problems (non-represented epidermis). The time needed to stain a case with SOX10 depended on the size of the samples (average 2 cm per sample) and their number. On average, a case of 8–10 fragments was processed in 120 min, from the time the sample was received in the laboratory until the pathologist performed the diagnosis. SOX10-stained frozen sections detected LM with a sensitivity of 94% and a specificity of 100% when compared with conventional analysis (paraffin-embedded sections) (gold standard) (Figure 1). The positive predictive value (PPV) was 100% and the negative predictive value (NPV) was 97.2%. False-negative results with SOX10-frozen sections were obtained in three patients (2.8% tissue specimens); a close follow-up was carried out and no recurrence was observed. SOX10 has shown a sensitivity approaching 100% for melanoma in formalin-fixed tissue.5 Our study revealed that SOX10 reliably detects LM in FSMCT, allowing, in the majority of cases, the entire surgical procedure (FSCMT, debulking and reconstruction) to be carried out on the same day, avoiding multi-day procedures and potentially reducing costs. Our study has several limitations. It was performed in a single centre with a limited number of patients. On the other hand, the slides were not blindly assessed. In conclusion, SOX10 immunostaining in frozen tissue shows high sensitivity and specificity for the detection of LM, while reducing the inconveniences of multi-day procedures associated with conventional staged margin control techniques. The research at the Melanoma Unit in Hospital Clinic Barcelona is partially financed by the AGAUR 2017_SGR_1134. None. None of the authors state any conflict of interest. This study was approved by the IRB of our institution (HCB/2018/0872).