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Background: Tumor-positive sentinel lymph node (SLN) biopsy results in a risk of non sentinel node metastases in micro-and macro-metastases ranging from 20 to 50%, respectively. Therefore, most patients underwent unnecessary axillary lymph node dissections. We have previously developed a mathematical model for predicting patient-specific risk of non sentinel node (NSN) metastases based on 2460 patients. The study reports the results of the validation phase where a total of 1945 patients were enrolled, aimed at identifying a tool that gives the possibility to the surgeon to choose intraoperatively whether to perform or not axillary lymph node dissection (ALND). Methods: The following parameters were recorded: Clinical: hospital, age, medical record number; Bio pathological: Tumor (T) size stratified in quartiles, grading (G), histologic type, lymphatic/vascular invasion (LVI), ER-PR status, Ki 67, molecular classification (Luminal A, Luminal B, HER-2 Like, Triple negative); Sentinel and non-sentinel node related: Number of NSNs removed, number of positive NSNs, cytokeratin 19 (CK19) mRNA copy number of positive sentinel nodes stratified in quartiles. A total of 1945 patients were included in the database. All patient data were provided by the authors of this paper. Results: The discrimination of the model quantified with the area under the receiver operating characteristics (ROC) curve (AUC), was 0.65 and 0.71 in the validation and retrospective phase, respectively. The calibration determines the distance between predicted outcome and actual outcome. The mean difference between predicted/observed was 2.3 and 6.3% in the retrospective and in the validation phase, respectively. The two values are quite similar and as a result we can conclude that the nomogram effectiveness was validated. Moreover, the ROC curve identified in the risk category of 31% of positive NSNs, the best compromise between false negative and positive rates i.e. when ALND is unnecessary (< 31%) or recommended (> 31%). Conclusions: The results of the study confirm that OSNA nomogram may help surgeons make an intraoperative decision on whether to perform ALND or not in case of positive sentinel nodes, and the patient to accept this decision based on a reliable estimation on the true percentage of NSN involvement. The use of this nomogram achieves two main gools: 1) the choice of the right treatment during the operation, 2) to avoid for the patient a second surgery procedure.

A complementary DNA (cDNA) library was constructed from a human malignant mesothelioma (MM) cell line and a cDNA fragment encoding for a cytoplasmic mesothelial protein recognized by the polyclonal antibody AMAD-1 was then cloned and expressed in Escherichia coli. The purified recombinant protein was used to raise a novel antibody, named AMAD-2, in rabbits. This antibody reacted with normal mesothelium and most MM (15 of 17) on paraffin sections and featured a cytoplasmic labeling. Conversely, AMAD-2 immunostaining of normal and tumor tissues from body sites other than serosal membranes was limited with respect to the proportion of positive specimens and usually less conspicuous than in MM. AMAD-2 immunoreactivity was subsequently compared with staining for HBME-1, another newly marketed antimesothelial monoclonal antibody, concerning the ability to distinguish pleural MM from metastatic pleural tumors of epithelial type. A granular cytoplasmic immunoreactivity for AMAD-2 was present in 50% or more of tumor cells in all 84 MM, regardless of histological type, but also in 3 (7%) of 42 pleural metastases, albeit only focally. HBME-1 was shown in 63 of 66 epithelial MM and in the epithelial component of all 8 mixed MM, with a prevailingly membranous pattern, usually homogeneous and strong, whereas none of the 10 sarcomatous MM was positive. HBME-1 was also expressed in 6 (14%) of 42 pleural metastases in a cytoplasmic or membranous pattern. Compared with HBME-1, AMAD-2 showed a higher degree of specificity and sensitivity for MM. AMAD-2 still proved to be superior to HBME-1, also when sarcomatoid MM were excluded from the assessment. This finding supports the view that AMAD-2 is an antibody highly, although not entirely, specific for the mesothelial lineage, whereas HBME-1 is probably a cell marker more closely related to the epithelial differentiation of MM. Therefore, AMAD-2 is preferable as a positive tissue marker to be incorporated in the optimal immunohistochemical panel for the diagnosis of MM.

HCV-RNA was examined in serum and liver tissue obtained from 8 hepatitis B surface antigen (HBsAg) negative patients with liver nodules ranging in size from 2 to 11 cm. Histological examination of ultrasound-guided fine needle biopsies revealed the presence of hepatocellular carcinoma (HCC) in six patients (5 of whom were anti-HCV positive), cholangiocarcinoma in 1 patient (anti-HCV positive) and dysplastic regenerative nodule in 1 patient (anti-HCV negative). The HCCs were surrounded by cirrhosis (3 cases), chronic active hepatitis (CAH) ( n = 2) and post hepatitic fibrosis ( n =1), the cholangiocarcinoma by CAH and the regenerative nodule by cirrhotic liver. Total and replicative intermediate HCV-RNA was analyzed by reverse-transcription-nested PCR of the 5'-untranslated region. The five patients with HCC had HCV-RNA in serum, in tumorous and surrounding liver tissues. The viral nucleic acid was also detected in the cirrhotic tissue surrounding the cholangiocarcinoma but not in the tumor. Two out of 5 HCC patients had replicative intermediate RNA (negative strand) in tumorous tissue, 4 in nontumorous tissue and 3 in serum. These results demonstrate that fine needle biopsy can provide sufficient material for both histological examination and HCV-RNA determination and suggest the existence of continuous viral replication during the carcinogenic process.

Melorheostosis is a rare congenital disease, some 300 cases have been reported in the literature. The main purpose of this case report is twofold: (1) to present an unusual case of melorheostosis of the right hand, beginning in infancy, with serial radiographic studies to show the gradual progression of the disease; and (2) to present the first case with the development of "aggressive" fibromatosis (desmoid tumor) of the adjacent soft tissues, associated with melorheostosis.