Global and mitosis-specific interobserver variation in mitotic count scoring and implications for malignant melanoma staging

AIMS Staging is the gold standard for predicting malignant melanoma outcome but changes in its criteria over time indicate ongoing evolution. One notable recent change from the 8 edition of the AJCC staging manual was removal of mitotic count. We explore the extent that this feature is limited by interobserver error in order to find ways to improve its fitness for use should it be revisited in future staging versions. METHODS AND RESULTS In a cohort of 476 patients with melanoma ≤ 1.0 mm, a mitotic count of 0 vs 1 was significant for metastasis-free survival, but not melanoma-specific or overall survival. In 10 melanomas that were 0.9 to 1.0 mm thick, the mitotic count intra-class correlation coefficient for histopathologists was 0.58 (moderate agreement). Uniquely, we also assessed agreement for specific putative mitotic figures, identifying precise reasons why specific mitotic figures qualified for scoring or elimination. A kappa score was 0.54 (moderate agreement). We also gathered data on other staging features. Breslow thickness had an intraclass correlation coefficient of 0.41 (moderate agreement) and there was a systematic difference between histopathologists across cases (p = 0.04). Every case had a range that crossed the AJCC8 0.8 mm pT1a/pT1b staging boundary. Ulceration was only identified in 2 out the 10 cases. For ulceration, kappa agreement score was 0.31 (fair). CONCLUSION This study supports the removal of mitotic count from staging but shows that its scoring is substantially affected by interobserver variation, suggesting that more prescriptive guidelines might have a beneficial impact on its prognostic value

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Oncogene-Expressing Senescent Melanocytes Up-Regulate MHC Class II, a Candidate Melanoma Suppressor Function

Work in the lab of PDA was funded by CRUK program C10652/A16566, AI by Kay Kendall Leukemia Fund KKL1101, EM by the Medical research Council grants MR/K021095/1, MR/N023625/1

A case of ectopic cilia in nail-patella syndrome.

Both ectopic cilia and nail-patella syndrome (NPS) are rare entities. To our knowledge we report the first case of the two anomalies coexisting in one patient. We present the case of a 2-year-old girl, with no other ophthalmic complication of NPS, who had an excellent cosmetic outcome and no lesion recurrence following surgical excision of ectopic cilia