Background: Recent clinical studies have suggested that denosumab is associated with tumor response and reduced surgical morbidity in patients with giant-cell tumor of bone (GCTB). We therefore evaluated the recurrence-free survival rate of patients who had GCTB in an extremity and were treated with surgery and denosumab, to determine the influence of denosumab and clinical factors on the risk of local recurrence. Methods: We retrospectively reviewed the medical records of 408 patients treated for GCTB in an extremity in a single institution from 1990 through 2013. Two hundred and forty-seven patients underwent curettage (intralesional surgery) with a high-speed burr, and 161 underwent resection. Phenol adjuvant was used in 221 of the 247 patients who had curettage. We also reviewed the medical records of 30 patients treated surgically (25 with curettage and 5 with resection) and with denosumab from 2010 through 2013 and compared their clinical results with 378 historical control subjects. The overall minimum duration of follow-up was 24 months. Results: The local recurrence rates were 60% (15) of 25 patients treated with curettage and denosumab and 16% (36) of 222 patients treated with curettage alone. The joint preservation rates were 80% (20) of 25 patients treated with curettage and denosumab and 94% (209) of 222 patients treated with curettage alone. Univariate and multivariable analyses showed that denosumab was the only independent factor associated with a poor prognosis when recurrence-free survival and joint preservation were considered. The overall median duration of follow-up was 85.6 months (interquartile range, 54.3 to 125.1 months). Viable tumor was present in all 30 specimens from patients treated with denosumab. Conclusions: There was a higher rate of recurrence in the cohort exposed to denosumab. Because there were substantial differences in the cohorts and randomization was not applied, however, causation could not be evaluated. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

The Turin Proposal algorithm defines poorly differentiated carcinoma on the basis of the presence of solid/trabecular/insular growth pattern, absence of conventional nuclear features of papillary carcinoma, and the presence of at least one of the following features: convoluted nuclei, mitotic activity ≥3/10 HPF, or tumor necrosis. IMP3 appears to have diagnostic and prognostic value in many solid tumors, including thyroid carcinomas. We examined a series of follicular-cell carcinomas with prominent solid patterns diagnosed at Mayo Clinic (56 cases) (Rochester, MN, USA) and at the University of Turin (96 cases) (Northern Italy) to validate the Turin consensus criteria defining poorly differentiated carcinoma of the thyroid and to evaluate the prevalence and prognostic behavior of this tumor. On this series, we analyzed the expression of conventional markers by immunohistochemistry and we investigated the expression of IMP3 by both immunohistochemistry and qRT-PCR. The prevalence of poorly differentiated carcinoma among the USA cases was 1.8% (56/3128) and that in the cases of Northern Italy was 6.7% (96/1442). Tumor characteristics were similar in the cases from the USA and from Italy except for extensive vascular invasion and a prevalent insular growth pattern (lower the former, higher the latter in the Italian series). In univariate analysis, the risk of death was higher for age ≥45, tumors ≥4 cm, and IMP3 positivity. Multivariate analysis showed that the risk of death from poorly differentiated carcinoma was higher for age ≥45. The Turin consensus criteria can reliably select poorly differentiated carcinomas. Tumors from the USA and from Italy showed similar overall survival, although the prevalence of poorly differentiated carcinoma was higher in Northern Italy. Expression of IMP3 appears to be an adverse prognostic factor for poorly differentiated thyroid carcinoma.

BACKGROUND.: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumor, mostly affecting elderly individuals. The histogenesis of this rare tumor as well as its prognostic criteria are a matter of dispute.METHODS.: An immunohistochemical analysis of markers of proliferation (Ki‐67/MIB‐1), neuroendocrine differentiation (chromogranin A and synaptophysin), and basal cell differentiation (p63) was performed in a series of 47 cases of MCC. The significance of pathologic data and of immunoreactivity with different markers was evaluated using the chi‐square test. Survival curves were calculated using the Kaplan‐Meyer method. The survival difference was estimated using the Wilcoxon or Mantel‐Cox test.RESULTS.: Immunohistochemical evidence of neuroendocrine differentiation and immunopositivity for cytokeratin 20 were observed in all cases, whereas positivity for p63 was detected in approximately half of the cases (25 of 47 cases; 53.2%). Cases that were positive for p63 demonstrated a more aggressive clinical course than those that were negative (Z value of 2.93;P= .0003; hazards ratio of 22.22).CONCLUSIONS.: Data from the current study indicate that p63 expression is associated with a worse prognosis in patients with MCC and represents a new independent marker of clinical evolution. Cancer 2007. © 2007 American Cancer Society.

Objective and design: A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods: The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results: In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions: Our data confirmed the validity of Trouillas’ score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.