The difficulty with measuring the largest melanoma tumour diameter in sentinel lymph nodes.

Identification of sentinel node (SN) metastases can set the adjuvant systemic therapy indication for stage III melanoma patients. For stage IIIA patients, a 1.0 mm threshold for the largest SN tumour diameter is used. Therefore, uniform reproducible measurement of its size is crucial. At present, the number of deposits or their microanatomical sites are not part of the inclusion criteria for adjuvant treatment. The goal of the current study was to show examples of the difficulty of measuring SN melanoma tumour diameter and teach how it should be measured. Histopathological slides of SN-positive melanoma patients were retrieved using the Dutch Pathology Registry (PALGA). Fourteen samples with the largest SN metastasis around 1.0 mm were uploaded via tele-pathology and digitally measured by 12 pathologists to reflect current practice of measurements in challenging cases. Recommendations as educational examples were provided. Microanatomical location of melanoma metastases was 1 subcapsular, 2 parenchymal and 11 combined. The smallest and largest difference in measurements were 0.24 mm and 4.81 mm, respectively. 11/14 cases (78.6%) showed no agreement regarding the 1.0 mm cut-off. The median discrepancy for cases ≤5 deposits was 0.5 mm (range 0.24-0.60, n=3) and 2.51 mm (range 0.71-4.81, n=11) for cases with ≥6 deposits. Disconcordance in measuring SN tumour burden is correlated with the number of deposits. Awareness of this discordance in challenging cases, for example, cases with multiple small deposits, is important for clinical management. Illustrating cases to reduce differences in size measurement are provided.

High discordance rate in assessing sentinel node positivity in cutaneous melanoma: Expert review may reduce unjustified adjuvant treatment.

INTRODUCTION: Identification of sentinel node (SN) metastases can set the adjuvant systemic therapy indication for patients with stage III melanoma. Studies re-evaluating the diagnosis of initially positive SN biopsies are scarce. MATERIALS AND METHODS: Dutch patients with melanoma who underwent SN biopsy between 2003 and 2014 were selected from PALGA, the Dutch Pathology Registry. Histopathological slides of SN-positive patients were retrieved for review. A random sample was reassessed by an expert melanoma pathologist. Recurrence-free survival (RFS) of patients who were misclassified (false-positive) was compared with those with a true positive SN status. For comparison, a group of SN-negative patients was included. Multivariable logistic analysis was performed to assess clinicopathological characteristics associated with misclassification of SN status. RESULTS: Diagnosis was downgraded from melanoma metastasis to nodal nevus in 38 of the 322 reviewed patients (11.8%). Considering the inclusion criteria of phase III adjuvant trials, at least 4.3% of patients would have falsely qualified for adjuvant therapy. In multivariable analysis, patients with a low SN tumour burden and subcapsular SN tumour location had a significantly higher chance of being misclassified. The five-year RFS of the 38 downgraded patients was 86.7% (95% confidence interval [CI] = 72.6-96.6), similar to the 85.9% (95% CI = 84.9-86.8, p = 0.18) for 6413 SN-negative patients and better than the 53.2% (95% CI = 47.2-59.9, p = 0.009) of 284 patients who were truly SN positive upon review. CONCLUSION: More than 10% of originally positive SN biopsies of patients with melanoma concern misclassified nodal nevi. We advocate that when adjuvant treatment is considered in patients with stage III melanoma, SN biopsies should be reassessed by an expert melanoma pathologist.

Desmoplastic melanoma: The role of pure and mixed subtype in sentinel lymph node biopsy and survival.

BACKGROUND: Desmoplastic melanoma (DM) is an uncommon type of melanoma. Two histological subtypes of DM can be distinguished: pure and mixed (PDM and MDM). We hypothesized that discrimination between these subtypes is associated with sentinel lymph node biopsy (SLNB) status and survival. METHODS: Clinicopathological data from PALGA, the Dutch Pathology Register were retrieved from patients diagnosed with DM in The Netherlands between 2000 and 2014. Clinical and pathological variables were extracted from pathology text files, including pure or mixed desmoplastic morphology. A Cox proportional hazard model was performed for overall and recurrence-free survival (OS and RFS). RESULTS: A total of 239 patients with DM were included, representing 0.4% of all primary cutaneous melanoma in The Netherlands. A total of 114 PDM and 125 MDM patients were identified. MDM was significantly associated with positive SLNB status (P = .035). In multivariable analysis, age (HR 1.10, 95% CI 1.07-1.14, P < .001) and ulceration (HR 1.98, 95% CI 1.05-3.75, P = .036) were significant predictors for OS. For RFS, mixed subtype (HR 2.72 95% CI 1.07-6.89, P = .035), male gender (HR 2.54, 95% CI 1.03-6.27, P = .043), and Breslow thickness (HR 1.13 per mm, 95% CI 1.05-1.21, P = .001) were significant predictors. CONCLUSION: MDM is significantly associated with a positive SLNB status. Mixed subtype is significantly correlated with RFS, but not with OS. The distinction between pure and mixed desmoplastic subtype therefore seems to be of clinical importance.