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Biomarker assessment of breast cancer tumor samples is part of the routine workflow of pathology laboratories. International guidelines have recently been updated, with special regards to the pre-analytical steps that are critical for the quality of immunohistochemical and in situ hybridization procedures, whatever the biomarker analyzed. Fixation and specimen handling protocols must be standardized, validated and carefully tracked. Cooperation and training of the personnel involved in the specimen workflow (e.g. radiologists, surgeons, nurses, technicians and pathologists) are of paramount importance. The GEFPICS' update of the recommendations herein details and comments the different steps of the pre-analytical process. Application of these guidelines and participation to quality insurance programs are mandatory to ensure the correct evaluation of oncotheranostic biomarkers.

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International guidelines on HER2 determination in breast cancer have just been updated by the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP), on the basis of more than ten-year practice, results of clinical trials and concordance studies. The GEFPICS group, composed of expert pathologists in breast cancer, herein presents these recommendations, adapted to the French routine practice. These guidelines highlight the possible diagnosis difficulties with regards to HER2 status determination, such as intra-tumor heterogeneity, special histological subtypes and biomarker re-evaluation during metastatic relapse. Pre-analytical issues and updated scoring criteria (especially for equivocal cases) are detailed, in order to decrease the occurrence of false negative cases. In the era of personalized medicine, pathologists are more than ever involved in the quality of oncotheranostic biomarker evaluation.

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PURPOSE: To analyze dose-volume histogram parameters and pathologic response after preoperative high-dose-rate brachytherapy (HDRB) for high-risk early stage cervical cancers (ESCCs). METHODS AND MATERIALS: From June 2007 to December 2011, 32 patients with a histologically proven invasive cervical cancer with high risk of local recurrence (size >2cm, adenocarcinoma type, perineural and/or lymphovascular invasion) underwent a preoperative HDRB, which delivered a total dose of 39Gy in nine fractions over 5 days. All the patients underwent hysterectomy after HDRB. RESULTS: With a median clinical target volume of 50cc (minimum-maximum, 42-74), the median V100 was 49cc (minimum-maximum, 42-50). Median D90 was 45Gy (equivalent dose at 2Gy per fraction, 56Gyαß10). Median D2cc was 34Gy, 31Gy, 28Gy, and 38Gyαß3 for bladder, rectum, sigmoid, and vagina, respectively. Twenty-eight patients (88.5%) achieved a complete histologic response after surgery, whereas for the 4 remaining patients, residual tumor cells (3 patients) and gross residual disease (1 patient) were observed in the pathologic specimen. With a median followup of 24 months (minimum-maximum, 5-48), no local recurrence was observed; 1 patient died of intercurrent cause. Early toxicity occurred within the 30 days after HDRB (Common Terminology Criteria for Adverse Events v3.0) was G1 diarrhea for 15 patients (47%) and G1 urinary frequency or urgency for 13 patients (40.6%). No G2-G3 toxicities were noticed. CONCLUSIONS: Preoperative HDRB for high-risk ESCCs represents a well-tolerated procedure, which leads to a high rate of postoperative pathologic response. Dose-volume histogram parameters were at least equivalent to those obtained with a low-dose-rate procedure. Long-term results will help to analyze the place of preoperative brachytherapy in the management of high-risk ESCCs.

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Solitary fibrous tumor (SFT), usually described in the pleura, is exceedingly rare in the prostate. We report a 60-year-old man with prostatic SFT revealed by obstructive urinary symptoms, and detected by ultrasonography. Computed tomography (CT) and magnetic resonance imaging suggested a prostatic origin. CT-guided tumor biopsy diagnosed a SFT. A cystoprostatectomy was performed. Pathologic examination showed a 15-cm tumor arising from the prostate and showing histological criteria suggestive of aggressiveness. The surgical resection margins were tumor-free. The patient was then regularly monitored and is still alive in complete remission, 28 months after surgery. In conclusion, we report a new exceptional case of prostatic SFT. We review the literature and discuss the challenging issues of misdiagnosis, prognosis and treatment.

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INTRODUCTION: Focal therapy of prostate cancer is gaining more and more interest. One of the drawbacks of focal therapy of prostate cancer is the problem of correct identification of prostate cancer lesions. The aim of the study was to evaluate the ability of real-time elastography to correctly identify the prostate cancer index lesion. MATERIALS AND METHODS: In 32 patients, real-time elastography was performed the day before prostatectomy. During the examination, the location of the main lesion suspicious for prostate cancer was prospectively recorded. Moreover, the results of the randomized multicore biopsies were also used to predict the location of the index lesion. The preoperative elastography results, the biopsy results, and a combined use of elastography and biopsy results were then compared with the pathological results to calculate the diagnostic values for correct index lesion identification. RESULTS: When using real-time elastography alone to identify the prostate cancer index lesion, sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 58.8, 43.3, 54.1, 48.1, and 51.6%, respectively. Data from randomized biopsies alone achieved 67.8, 48.4, 56.8, 60.0, and 58.1%, respectively. The combination of elastography and biopsy data increased the values to, respectively, 84.9, 48.4, 61.9, 75.0, and 66.1%. CONCLUSION: In this study, real-time elastography alone did not allow to identify the prostate cancer index lesion with satisfactory reliability. The combination of real-time elastography and data from randomized 12 core biopsies allows promising ability to correctly identify the prostate cancer index lesion.

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BACKGROUND: Cystic pancreatic endocrine tumors (PETs) are rare neoplasms with a preoperative diagnostic challenge. The aim of this study was to evaluate the preoperative diagnostic strategy for these tumors and to assess the clinical and pathologic characteristics. METHODS: Six cases of cystic PET were retrospectively enrolled. Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) was performed in 4 cases. All cytomorphologic data from conventional smears, ThinPrep preparations, and cell block preparations were reported in detail. RESULTS: There were 3 male and 3 female patients with a mean age of 52.3 years. Tumor size ranged from 10 mm to 60 mm (mean, 29.8 mm). EUS-FNAB contributed to an accurate diagnosis in all cases. Cytologically, loosely cohesive aggregates and single cells were predominant. Cells were small and typically plasmacytoid, with occasional cytoplasmic vacuolization. Nuclei were round or oval, uniform, with finely and evenly distributed chromatin. Immunocytochemistry confirmed the endocrine differentiation. Histologic findings were typical for endocrine proliferation. All tumors were well differentiated. CONCLUSIONS: Cystic PET is an unusual finding that presents diagnostic challenges for both endoscopists and cytologists. EUS-FNAB with the Thinprep preparation technique and cell block material were found to be helpful in improving diagnostic accuracy. Immunocytochemical staining with endocrine markers confirmed the diagnosis.

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Although the follicular variant of papillary thyroid carcinoma (FVPTC) has been classified as a papillary cancer based on nuclear features, its follicular growth pattern and potential for hematogenous spread are more characteristic of follicular carcinoma. To gain insight into the biologic nature of FVPTC, we compared genetic alterations characteristic of papillary and follicular thyroid carcinomas in 24 FVPTCs and 26 classic PTC (CPTCs). In FVPTCs, we observed ras mutation in 6 of 24 cases (25%), BRAF mutation in 1 of 13 cases (7.6%), and ret rearrangement in 5 of 12 cases (41.7%). In CPTCs, we found ras mutation in no case, BRAF mutation in 3 of 10 cases (30%), and ret rearrangement in 5 of 11 cases (45%). One FVPTC exhibited simultaneous ras mutation and ret/PTC1 rearrangement, and one CPTC harbored simultaneous BRAF mutation and ret/PTC3 rearrangement. Based on these findings, we concluded that ras mutation correlates with follicular differentiation of thyroid tumors whereas ret activation is associated with papillary nuclei but not with papillary architecture. ret activation is not exclusive of ras or BRAF mutation, whereas ras and BRAF mutations are mutually exclusive. The implications of these results for follicular and papillary carcinogenesis are discussed.

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We report a case of signet ring cell carcinoma of the pancreas. This rare variant of ductal adenocarcinoma is composed exclusively of signet ring neoplastic cells in a mucinous stroma. Altogether, clinical, radiological and immunohistochemical data supported the pancreatic origin of the tumor.

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