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Cancer of unknown primary origin (CUP) had a poor prognosis, determined by clinico-histological characteristics, partly due to the lack of insights on its biology. We screened tumour DNA from 87 patients with CUP for CTNNB1 (coding exons 2,3,4,5), MET (coding exon 18), PIK3CA (coding exons 9,20), KRAS (coding exons 1,2), BRAF (coding exon 15) gene mutations by using dd-sequencing and evaluated their impact on prognosis. Mutated gene incidences in the 87 CUP cases were: KRAS 11 (12.6 %), BRAF 5 (5.7 %), PIK3CA 8 (9 %), MET 6 (6.7 %) and CTNNB1 18 (20.7 %). Several mutations in the KRAS gene were not the commonly encountered mutations in other solid tumours. Activating mutations were observed in 10.2 % in KRAS, 4.5 % in BRAF, 6.6 % in PIK3CA, 4.5 % in MET, and 19.5 % in CTNNB1. Activating mutations in PIK3CA coding exon 9 were inversely correlated with MET coding exon 18 activating mutations (p = 0.036). MET activating mutations were prognostic for poor Progression-Free Survival (median PFS 5 vs 9 months, p = 0.009) and Overall Survival (median OS 7 vs 20 months, p = 0.005). The complex profile of either CTNNB1 or MET mutations also had an adverse prognostic significance (median OS 11 vs 21 months, p = 0.015). No other gene mutation exhibited prognostic significance. In multivariate analysis, poor performance status, male gender, visceral disease and adenocarcinoma histology, but not gene mutations, were independently associated with poor patient outcome. CTNNB1 gene mutations are frequent, and along with MET mutations have an adverse prognostic effect in patients with CUP. © 2014, Springer Science+Business Media Dordrecht. 31 7 761 769

Merkel cell nodal carcinoma of unknown primary (MCCUP) is a rare neuroendocrine tumour with distinct clinical and biological behaviour. We conducted a review of retrospective data extracted from 90 patients focusing on the management and outcome of this disease. We also compared life expectancy of these patients with the outcome of patients with known Merkel primaries and with neuroendocrine cancers of unidentifiable primary. There is a limited body of data for this type of malignancy, however, patients with Merkel cell nodal carcinoma of unknown primary site, seem to have better survival when treated aggressively than patients with cutaneous Merkel tumours of the same stage and equal survival with patients with low-grade neuroendocrine tumour of unknown origin. The lack of prospective trials, and the inadequate data, hamper the management of these tumours. Establishment of treatment guidelines is urgently needed. © 2014 Elsevier Ireland Ltd. 94 1 116 121

Background: Coexistence of an adrenocortical carcinoma and pregnancy is extremely rare with only 25 described cases so far, and has a poor prognosis. Case Report: We report the case of a 28-year-old patient with adrenocortical carcinoma initially presenting with Cushing's syndrome and pre-eclampsia in the 22nd week of gestation, treated in our department. She underwent adrenalectomy, but eventually died from metastatic disease. We focus on existing treatment options and concerns for this rare malignancy during pregnancy. Conclusion: Early diagnosis and surgery are the cornerstones for better outcome. Copyright © 2012 S. Karger AG, Basel. 35 9 517 519

Purpose: Introduction of cyclin-dependent inhibitors was a milestone in therapeutics for patients with estrogen receptor+/HER2− metastatic breast cancer. Despite the wide use of such agents and remarkable improvement of survival rates, drug-related adverse events are not yet fully characterized. We describe vitiligo-like lesions as a new adverse event occurring in patients with advanced breast cancer treated with cyclin-dependent inhibitors. Methods: We performed an international retrospective study including patients with advanced breast cancer who developed vitiligo-like lesions during treatment with cyclin-dependent kinases 4 and 6 inhibitors, in the period January 2018–December 2019. Patients > 18 years, both males and females, were recruited at six Dermatology Departments located in Italy (3), France (1) and Greece (2). We evaluated epidemiological and clinical characteristics, impact on quality of life and outcome of vitiligo-like lesions in patients treated with cyclin-dependent 4 and 6 inhibitors. The percentage of skin involved by vitiligo-like lesions was assessed using the Body Surface Area (BSA) score. Changes in patients’ quality of life were investigated through the evaluation of the Dermatology Life Quality Index (DLQI) questionnaire. Results: Sixteen women (median age: 62.5 years; range 40–79 years) treated with cyclin-dependent kinases 4 and 6 inhibitors for advanced breast cancer presented with vitiligo-like lesions during follow-up visits. Cutaneous lesions consisted of white, irregular macules and patches located mainly on sun-exposed areas in 11/16 patients or diffuse to the entire body surface in 5/16. Cutaneous lesions clearly impaired the quality of life of patients tested (DLQI ≥ 10). Conclusions: We present for the first time, to our knowledge, a case series of vitiligo-like lesions developing in patients with advanced breast cancer treated with cyclin-dependent kinases 4 and 6 inhibitors. We showed that such lesions further impair the patients’ quality of life and their treatment is challenging.

Background The aim of this prospective study was to identify the most clinically relevant hypercoagulability biomarkers in lung adenocarcinoma patients for elaboration of an improved risk assessment model (RAM) for venous thromboembolism (VTE). Subjects, Materials, and Methods One hundred fifty ambulatory patients with lung adenocarcinoma were prospectively enrolled. Thrombin generation, procoagulant phospholipid-dependent clotting time (Procoag-PPL), tissue factor activity (TFa), factor VIIa (FVIIa), factor V (FV), antithrombin, D-Dimers, P-selectin, and heparanase levels were assessed in platelet-poor plasma at inclusion (baseline) and at the end of the third chemotherapy cycle (third chemotherapy). Cox regression analysis was used to identify independent VTE predictors. Results At baseline, patients had significantly attenuated thrombin generation, shorter Procoag-PPL, higher levels of TFa, D-Dimers, and heparanase, and lower levels of FVIIa and P-selectin, compared with controls. A significant increase in Procoag-PPL, FV, and FVIIa and a decrease of P-selectin levels were observed between baseline and third chemotherapy. Hospitalization within the last 3 months prior to assessment, time since cancer diagnosis less than 6 months, mean rate index (MRI) of thrombin generation, and Procoag-PPL were independently associated with symptomatic VTE. Accordingly, a prediction model including Procoag-PPL and MRI showed significant discriminating capacity (area under the curve: 0.84). Conclusion Ambulatory patients with lung adenocarcinoma may display pronounced blood hypercoagulability due to decreased Procoag-PPL, increased endothelial cell activation, and increased degradation of fibrin. Incorporation of Procoag-PPL and MRI of thrombin generation may improve the accuracy of a VTE-RAM in the above setting. Implications for Practice The prospective ROADMAP-CAT study identified two biomarkers of hypercoagulability, the procoagulant phospholipid-dependent clotting time (Procoag-PPL) and the mean rate index (MRI) of the propagation phase of thrombin generation assessed with the Calibrated Automated Thrombinoscope, as being clinically relevant for the classification of ambulatory patients with lung adenocarcinoma receiving a maximum of one cycle of chemotherapy into high and intermediate/low risk for venous thromboembolism. Measurement of Procoag-PPL and MRI within 1 month after the administration of the first chemotherapy cycle provides significant accuracy of the assessment. Association of the Procoag-PPL and MRI with the clinical risk assessment model for cancer-associated thrombosis in ambulatory patients with solid tumors (COMPASS-CAT RAM) further improved its accuracy.