[Melanocytoma, an intermediate entity between nevus and melanoma: implications of the WHO classification of melanocytic skin tumours]. / Melanocytoom, intermediair tussen naevus en melanoom.

The WHO classification of melanocytic skin tumours published in 2018 describes a new classification with nine different pathways based on molecular driver mutations, localization, clinical context and solar damage. The dichotomous concept of benign (nevus) versus malignant (melanoma) is replaced by a gradual concept starting with a benign nevus with progression into low to high grade intermediate melanocytic lesions, called melanocytoma, and ending at melanoma. The current European recommendation is (re-)excision with 2-5mm margin of low grade melanocytoma and with 5-10mm margin of high grade melanocytoma. Low grade melanocytoma needs no follow-up. For high grade melanocytoma a follow-up for at least 5 years every 6 months is recommended. Routine sentinel node procedure is not indicated. If diagnosis melanoma cannot be ruled out the lesions have to be treated as melanoma. Correct classification of a melanocytoma is a diagnostic challenge, but of high importance for therapeutic choices and prognosis.

Anti-plasminogen antibodies compromise fibrinolysis and associate with renal histology in ANCA-associated vasculitis.

Antibodies recognizing plasminogen, a key component of the fibrinolytic system, associate with venous thrombotic events in PR3-ANCA vasculitis. Here, we investigated the prevalence and function of anti-plasminogen antibodies in independent UK and Dutch cohorts of patients with ANCA-associated vasculitis (AAV). We screened Ig isolated from patients (AAV-IgG) and healthy controls by ELISA. Eighteen of 74 (24%) UK and 10/38 (26%) Dutch patients with AAV had anti-plasminogen antibodies compared with 0/50 and 1/61 (2%) of controls. We detected anti-plasminogen antibodies in both PR3-ANCA- and MPO-ANCA-positive patients. In addition, we identified anti-tissue plasminogen activator (tPA) antibodies in 13/74 (18%) patients, and these antibodies were more common among patients with anti-plasminogen antibodies (P = 0.011). Eighteen of 74 AAV-IgG (but no control IgG) retarded fibrinolysis in vitro, and this associated with anti-plasminogen and/or anti-tPA antibody positivity. Only 4/18 AAV-IgG retarded fibrinolysis without harboring these antibodies; dual-positive samples retarded fibrinolysis to the greatest extent. Patients with anti-plasminogen antibodies had significantly higher percentages of glomeruli with fibrinoid necrosis (P < 0.05) and cellular crescents (P < 0.001) and had more severely reduced renal function than patients without these antibodies. In conclusion, anti-plasminogen and anti-tPA antibodies occur in AAV and associate with functional inhibition of fibrinolysis in vitro. Seropositivity for anti-plasminogen antibodies correlates with hallmark renal histologic lesions and reduced renal function. Conceivably, therapies that enhance fibrinolysis might benefit a subset of AAV patients.

Discriminating basal cell carcinoma from its surrounding tissue by Raman spectroscopy.

The objective of this in vitro study was to explore the applicability of Raman spectroscopy to distinguish basal cell carcinoma from its surrounding noncancerous tissue; therefore, identifying possibilities for the development of an in vivo diagnostic technique for tumor border demarcation. Raman spectra were obtained in a two-dimensional grid from unstained frozen sections of 15 basal cell carcinoma specimens. Pseudo-color Raman images were generated by multivariate statistical analysis and clustering analysis of spectra and compared with histopathology. In this way a direct link between histologically identifiable skin layers and structures and their Raman spectra was made. A tissue classification model was developed, which discriminates between basal cell carcinoma and surrounding nontumorous tissue, based on Raman spectra. The logistic regression model, shows a 100% sensitivity and 93% selectivity for basal cell carcinoma. The Raman spectra were, furthermore, used to obtain information about the differences in molecular composition between different skin layers and structures. An interesting finding was that in four samples of nodular basal cell carcinoma, the collagen signal contribution in spectra of dermis close to a basal cell carcinoma, was markedly reduced. The study demonstrates the sensitivity of Raman spectroscopy to biochemical changes in tissue accompanying malignancy, resulting in a high accuracy when discriminating between basal cell carcinoma and noncancerous tissue.