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Sarcomas are mesenchymal malignant tumors with poor prognosis and limited treatment options. Hippo pathway is a recently discovered pathway normally involved in organ development and wound healing. Hippo signaling is often altered in solid tumors. The molecular elements of Hippo signaling include MST1/2 and LATS1/2 kinases which phosphorylate and regulate the activity of YAP and TAZ co-transcriptional activators. Hippo pathway cross-talks with several molecular pathways with known oncogenic function. In sarcomas Hippo signaling plays a pivotal role in tumorigenesis, evolution and resistance in chemotherapy regimens. Targeting Hippo pathway could potentially improve prognosis and outcome of sarcoma patients.

Abstract This review attempts to outline the alternative measures and interventions used in bloodless surgery in the field of gynecologic oncology and demonstrate their effectiveness. Nowadays, as increasingly more patients are expressing their fears concerning the potential risks accompanying allogenic transfusion of blood products, putting the theory of bloodless surgery into practice seems to gaining greater acceptance. An increasing number of institutions appear to be successfully adopting approaches that minimize blood usage for all patients treated for gynecologic malignancies. Preoperative, intraoperative and postoperative measures are required, such as optimization of red blood cell mass, adequate preoperative plan and invasive hemostatic procedures, assisting anesthetic techniques, individualization of anemia tolerance, autologous blood donation, normovolemic hemodilution, intraoperative cell salvage and pharmacologic agents for controlling blood loss. An individualised management plan of experienced personnel adopting a multidisciplinary team approach should be available to establish non-blood management strategies, and not only on demand of the patient, in the field of gynecologic oncology with the use of drugs, devices and surgical-medical techniques.

Abstract Background Gestational Trophoblastic Neoplasia (GTN) is a pathologic entity that can affect any pregnancy and develop long after the termination of the pregnancy. Its course can be complicated by metastases to distant sites such as the lung, brain, liver, kidney and vagina. The therapeutic approach of this condition includes both surgical intervention and chemotherapy. The prognosis depends on many prognostic factors that determine the stage of the disease. Case Report We present a woman with GTN and retroperitoneal metastatic disease who came to our department and was diagnosed as having high risk metastatic GTN. Accordingly she received chemotherapy as primary treatment but unfortunately developed massive bleeding after the first course of chemotherapy, was operated in an attempt to control bleeding but finally succumbed. Conclusion This case demonstrates that GTN, while usually curable, can be a deadly disease requiring improved diagnostic, treatment modalities and chemotherapeutic agents. The gynaecologist should be aware of all possible metastatic sites of GTN and the patient immediately referred to a specialist center for further assessment and treatment.

Abstract Background Elevated Hsp90 expression has been documented in breast ductal carcinomas, whereas decreased Hsp90 expression has been reported in precursor lobular lesions. This study aims to assess Hsp90 expression in infiltrative lobular carcinomas of the breast. Methods Tissue specimens were taken from 32 patients with infiltrative lobular carcinoma. Immunohistochemical assessment of Hsp90 was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. Concerning Hsp90 assessment: i) the percentage of positive cells and ii) the intensity were separately analyzed. Subsequently, the Allred score was adopted and calculated. The intensity was treated as an ordinal variable-score (0: negative, low: 1, moderate: 2, high: 3). Statistical analysis followed. Results All infiltrative lobular carcinoma foci mainly presented with a positive cytoplasmic immunoreaction for Hsp90. Compared to the adjacent normal ducts and lobules, infiltrative lobular carcinoma exhibited a statistically significant decrease in Hsp90 expression, both in terms of Hsp90 positive cells (%) and Allred score (74.2 ± 11.2 vs. 59.1 ± 14.2 p = 0.0001; 7.00 ± 0.95 vs. 6.22 ± 1.01, p = 0.007, Wilcoxon matched-pairs signed-ranks test). Concerning the intensity of Hsp90 immunostaining only a marginal decrease was noted (2.16 ± 0.68 vs. 1.84 ± 0.63, p = 0.087, Wilcoxon matched-pairs signed-ranks test). Conclusion ILC lesions seem to exhibit decreased Hsp90 expression, a finding contrary to what might have been expected, given that high Hsp90 expression is a trait of invasive ductal carcinomas.

Abstract Background Hsp90 (heat shock protein90) is a chaperone protein essential for preserving and regulating the function of various cellular proteins. Elevated Hsp90 expression seems to be a trait of breast cancer and may be an integral part of the coping mechanisms that cancer cells exhibit vis-à-vis stress. This manuscript tries to examine the immunohistochemical expression of Hsp90 all along the continuum of breast ductal lesions encompassing ductal hyperplasia without atypia (DHWithoutA), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). Methods Tissue specimens were taken from 30 patients with DHWithoutA, 31 patients with ADH, 51 with DCIS and 51 with IDC. Immunohistochemical assessment of Hsp90 was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. Concerning Hsp90 assessment the percentage of positive cells and the intensity were separately analyzed. Subsequently, the Allred score was calculated. Post hoc analysis on the correlations between Hsp90 Allred score and possible predictors (grade, nodal status, tumor size, ER Allred score, PR Allred score, c-erbB-2 status and triple negative status) was conducted in IDC. Results Hsp90 exhibited mainly cytoplasmic immunoreactivity. Hsp90 Allred score exhibited an increasing trend along the continuum of breast ductal lesions (Spearman's rho = 0.169, p = 0.031). Compared to the adjacent normal ducts and lobules, no statistically significant differences were noted in DHwithoutA, ADH and DCIS. Hsp90 expression (intensity, positive cells, Allred score) was higher in IDC, compared to the adjacent normal tissue. Higher Hsp90 expression was observed in grade 2/3 IDCs (borderline association) and tumors of larger size. At the univariable analysis, higher Hsp90 expression was associated with higher ER Allred score, PR Allred score and c-erbB-2 positivity in IDC. Triple-negative IDCs exhibited significantly lower Hsp90 expression. The multivariable logistic regression model revealed that between the three markers, solely ER Allred score and c-erbB-2 positivity were independently associated with higher Hsp90 expression in IDC. Conclusion The above point to significant variability in Hsp90 expression with significant implications upon the effectiveness and limitations of anti-Hsp90 drugs.

Abstract Background To evaluate whether the volume of blood suctioned during vacuum-assisted breast biopsy (VABB) is associated with hematoma formation and progression, patient's age and histology of the lesion. Findings 177 women underwent VABB according to standardized protocol. The volume of blood suctioned and hematoma formation were noted at the end of the procedure, as did the subsequent development and progression of hematoma. First- and second-order logistic regression was performed, where appropriate. Cases with hematoma presented with greater volume of blood suctioned (63.8 ± 44.7 cc vs. 17.2 ± 32.9 cc; p < 0.001, Mann-Whitney-Wilcoxon test for independent samples, MWW); the likelihood of hematoma formation was increasing till a volume equal to 82.6 cc, at which the second-order approach predicts a maximum. The volume of blood suctioned was positively associated with the duration of the procedure (Spearman's rho = 0.417, p < 0.001); accordingly, hematoma formation was also positively associated with the latter (p = 0.004, MWW). The volume of blood suctioned was not associated with patients' age, menopausal status and histopathological diagnosis. Conclusion The likelihood of hematoma is increasing along with increasing amount of blood suctioned, reaching a plateau approximately at 80 cc of blood lost.

Abstract Background Neurofibromatosis Type 1(NF-1) has autosomal dominant inheritance with complete penetrance, variable expression and a high rate of new mutation. Pheochromocytoma occurs in 0.1%-5.7% of patients with NF-1. Case presentation We present the case of a 37-year-old patient with laparoscopically resected pheochromocytoma. He was investigated for hypertension, flushing and ectopic heart beat. Abdominal CT and MRI revealed a mass measuring 8 × 4 cm in the right adrenal gland. The diagnosis of pheochromocytoma was confirmed by elevated 24-hour urine levels of VMA, metanephrines and catecholamines as well as positive MIBG scan. The patient presented with classic clinical features of NF-1, which was confirmed by pathologic evaluation of an excised skin nodule. The patient underwent laparoscopic right adrenalectomy through a transabdominal approach and was discharged on the second postoperative day, being normotensive. The patient is normotensive without antihypertensive therapy 11 years after the procedure. Conclusion Nowadays in the era of laparoscopy, patients with pheochromocytoma reach the operating theatre easier than in the past. Despite, the feasibility and oncological efficacy of the laparoscopic approach to the adrenals, continued long term follow-up is needed to establish the minimally invasive technique as the preferred approach. Furthermore, these patients should be further investigated for other neoplasias and stigmata of other neurocutaneous syndromes, taking into account the association of the familial pheochromo-cytoma with other familial basis inherited diseases.

Abstract Background The impact of Vacuum-assisted breast biopsy (VABB, 11-Gauge) upon Health-related Quality of Life (HRQoL) remains an open field. This study aims to: i) assess short-term (4 days after VABB) responses in terms of HRQoL after VABB, ii) evaluate long-term (18 months after VABB) responses, if any, and iii) examine whether these responses are modified by a variety of possible predictors (anthropometric, sociodemographic, lifestyle habits, breast-related parameters, reproductive history, VABB-related features and complications, seasonality). Methods This study included 102 eligible patients undergoing VABB and having benign lesions. A variable number of cores (24-96 cores) has been excised. HRQoL was assessed by EQ-5D and SF-36® questionnaires: i) in the morning of the VABB procedure day (baseline measurement), ii) four days after VABB (early post-biopsy measurement) and iii) 18 months after VABB (late post-biopsy measurement). Statistical analysis comprised two steps: i. evaluation of differences in EQ-5D/SF-36 dimensions and calculated scores (baseline versus early post-biopsy measurement and baseline versus late post-biopsy measurement) and ii. assessment of predictors through multivariate linear, logistic, ordinal logistic regression, as appropriate. Results At baseline patients presented with considerable anxiety (EQ-5D anxiety/depression dimension, EQ-5D TTO/VAS indices, SF-36 Mental Health dimension). At the early post-biopsy measurement women exhibited deterioration in Usual Activities (EQ-5D) and Role Functioning-Physical dimensions. At the late measurement women exhibited pain (EQ-5D pain/discomfort and SF-36 Bodily Pain), deterioration in Physical Functioning (SF-36 PF) and overall SF-36 Physical Component Scale (PCS). Mastalgia, older age and lower income emerged as significant predictors for baseline anxiety, whereas seasonality modified early activities-related responses. Pain seemed idiosyncratic. Conclusions The HRQoL profile of patients suggests that VABB exerts effects prior to its performance at a psychological level, immediately after its performance at a functioning-physical level and entails long-term effects associated with pain.

Abstract Background Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9) is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL) during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity. Methods The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays. Results Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p < 0.003, NGAL: p < 0.008 MMP-9/NGAL: p < 0.01). Significant correlations were observed between MMP-9 and NGAL serum levels and breast disease severity score (r = 0.229, p < 0.006 and r = 0.206, p < 0.01, respectively), whereas a non-significant correlation was found for their complex. MMP-9, NGAL and their complex MMP-9/NGAL levels were not correlated with either Body Mass Index (BMI) or age of patients. Conclusion These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.

Abstract Background Breast ductal endoscopy is a relatively new diagnostic method with ever growing importance in the work-up of patients with bloody nipple discharge. The ability to perform ductal endoscopy is very important and useful for breast fellows. Learning curve in breast ductal endoscopy remains a terra incognita, since no systematic studies have addressed this topic. The purpose of this study is to determine the point (number of procedures during training) beyond which ductal endoscopy is successfully performed. Findings Ten breast fellows received training in our Breast Unit. For the training process, an ex vivo model was adopted. Fellows were trained on 20 surgical specimens derived from modified radical mastectomy for breast cancer. The target of the education program was to acquire proficiency in performing ductoscopy. The achievement of four consecutively successful ductal endoscopies was determined as the point beyond which proficiency had been achieved. The number of procedures needed for the achievement of proficiency as defined above ranged between 9 and 17 procedures. The median value was 13 procedures; i.e. 50% of trainees had achieved proficiency at the 13th procedure or earlier. Conclusion These pilot findings point to approximately 13 procedures as a point beyond which ductal endoscopy is successfully performed; studies on a larger number of fellows are nevertheless needed. Further research, focusing on the learning curves of different training models of ductal endoscopy, seems desirable.

Abstract Uterine sarcomas are a rare group of neoplasms with aggressive clinical course and poor prognosis. They are classified into four main histological subtypes in order of decreasing incidence: carcinosarcomas, leiomyosarcomas, endometrial stromal sarcomas and "other" sarcomas. The pathological subtype demands a tailored approach. Surgical resection is regarded as the mainstay of treatment. Total abdominal hysterectomy and bilateral salpingo-oophorectomy represents the standard treatment of uterine sarcomas. Pelvic and para-aortic lymph node dissection in carcinosarcomas is recommended, given their high incidence of lymph node metastases, and may have a role in endometrial stromal sarcomas. Adjuvant radiation therapy has historically been of little survival value, but it appears to improve local control and may delay recurrence. Regarding adjuvant chemotherapy, there is little evidence in the literature supporting its use except for carcinosarcomas. However, more trials are needed to address these issues, especially, their sequential application. Patients with uterine sarcomas should be referred to large academic centers for participation in clinical trials.

Abstract Background Heat shock protein 90 (Hsp90) overexpression has been implicated in breast carcinogenesis, with putative prognostic and therapeutic implications. The purpose of this study is to evaluate the immunohistochemical expression of Hsp90 and to examine whether Hsp90 expression is associated with estrogen receptor alpha (ER-alpha) and beta (ER-beta) immunostaining in lobular neoplasia (LN) of the breast. Methods Tissue specimens were taken from 44 patients with LN. Immunohistochemical assessment of Hsp90, ER-alpha and ER-beta was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. As far as Hsp90 evaluation is concerned: i) the percentage of positive cells, and ii) the intensity was separately analyzed. Additionally, the Allred score was adopted and calculated. Accordingly, Allred score was separately evaluated for ER-alpha and ER-beta. The intensity was treated as an ordinal variable-score (0: negative, low: 1, moderate: 2, high: 3). Statistical analysis followed. Results Hsp90 immunoreactivity was mainly cytoplasmic in both the epithelial cells of normal breast (ducts and lobules) and LN. Some epithelial cells of LN also showed nuclear staining, but all the LN foci mainly disclosed a positive cytoplasmic immunoreaction for Hsp90. In addition, rare intralobular inflammatory cells showed a slight immunoreaction. The percentage of Hsp90 positive cells in the LN areas was equal to 67.1 ± 12.2%, whereas the respective percentage in the normal adjacent breast tissue was 69.1 ± 11.6%; the difference was not statistically significant. The intensity score of Hsp90 staining was 1.82 ± 0.72 in LN foci, while in the normal adjacent tissue the intensity score was 2.14 ± 0.64. This difference was statistically significant (p = 0.029, Wilcoxon matched-pairs signed-ranks test). The Hsp90 Allred score was 6.46 ± 1.14 in the LN foci, significantly lower than in the normal adjacent tissue (6.91 ± 0.92, p = 0.049, Wilcoxon matched-pairs signed-ranks test). Within the LN foci, the Hsp90 Allred score was neither associated with ER-alpha, nor with ER-beta percentage. Conclusion Hsp90 was lower in LN foci both at the level of intensity and Allred score, a finding contrary to what might have been expected, given that high Hsp90 expression is detected in invasive breast carcinomas. Hsp90 deregulation does not seem to be a major event in LN pathogenesis.

Abstract Introduction Vacuum-assisted breast biopsy is a minimally invasive technique that has been used increasingly in the treatment of mammographically detected, non-palpable breast lesions. Clip placement at the biopsy site is standard practice after vacuum-assisted breast biopsy. Case presentation We present the case of a 62-year-old woman with suspicious microcalcifications in her left breast. The patient was informed about vacuum-assisted breast biopsy, including clip placement. During the course of taking the patient's history, she communicated excellently, her demeanor was normal, she disclosed no intake of psychiatric medication and had not been diagnosed with any psychiatric disorders. Subsequently, the patient underwent vacuum-assisted breast biopsy (11 G) under local anesthesia. A clip was placed at the biopsy site. The pathological diagnosis was of sclerosing adenosis. At the 6-month mammographic follow-up, the radiologist mentioned the existence of the metallic clip in her breast. Subsequently, the woman presented complaining about "being spied [upon] by an implanted clip in [her] breast" and repeatedly requested the removal of the clip. The patient was referred to the specialized psychiatrist of our breast unit for evaluation. The Mental State Examination found that systematized paranoid ideas of persecutory type dominated her daily routines. At the time, she believed that the implanted clip was one of several pieces of equipment being used to keep her under surveillance, the other equipment being her telephone, cameras and television. Quite surprisingly, she had never had a consultation with a mental health professional. The patient appeared depressed and her insight into her condition was impaired. The prevalent diagnosis was schizotypal disorder, whereas the differential diagnosis comprised delusional disorder of persecutory type, affective disorder with psychotic features or comorbid delusional disorder with major depression. Conclusion This is the first report of a psychiatric disorder being brought to the fore using a vacuum-assisted breast biopsy clip. Vacuum-assisted breast biopsy, and breast biopsy in general, represent a significant experience, encompassing anxiety and pain; it may thus aggravate psychiatric conditions. Apart from these well-established factors, other aspects, such as the clip, may occasionally become significant. In a modern breast unit, the evaluation of patients should be multidisciplinary. A psychiatrist may be needed for optimal management of anxiety-related issues, as well as for the detection of psychiatric disorders.

Abstract Introduction Vacuum-assisted breast biopsy is a minimally invasive technique used increasingly for the assessment of mammographically detected, non-palpable breast lesions. The effectiveness of vacuum-assisted breast biopsy has been demonstrated on lesions both with and without microcalcifications. Given that the position of the lesion represents a major factor in stereotactic vacuum-assisted breast biopsy, targeting lesions in close proximity to the skin (superficial lesions) has been described as a problematic issue. Case presentation A 53-year-old woman presented with a newly developed, non-palpable lesion in her left breast. The lesion consisted of widely spread microcalcifications located approximately 5 mm from the skin. The lesion was isoechoic on ultrasound examination. Vacuum-assisted breast biopsy was scheduled (on the Fischer's table, using 11-gauge probes, under local anaesthesia). The vacuum-assisted breast biopsy probe was inserted antidiametrically into the breast, the probe reached the lesion and effort was made to excise the microcalcifications. As only a small proportion of the microcalcifications were excised an accurate diagnosis could not be expected. However, with the probe having entered the breast antidiametrically, the probe tip underlying the skin could be palpated. Following the palpation of the tip, the exact point was marked by a pen, the probe was removed and the patient was transferred to the surgery room to have the remaining lesion removed by a spindle-form excision under local anaesthesia. The mammogram of the removed specimen confirmed the total excision of the suspicious microcalcifications. Conclusion Isoechoic superficial lesions can be localized with a hook-wire and open breast biopsy under general or local anaesthesia can be performed. However, vacuum-assisted breast biopsy might offer an alternative solution and serve as an alternative approach to localize the lesion. The clinical significance of the present exploratory effort remains to be assessed in the future.

Abstract Introduction Breast lymphoma, either as a manifestation of primary extranodal disease or as secondary involvement, is a rare malignancy, and its diagnosis, prognosis, and treatment have not been clearly defined. On the other hand, Vacuum-assisted breast biopsy (VABB) is a minimally invasive technique with ever-growing use for the diagnosis of mammographically detected, non-palpable breast lesions. Case presentation A symptom-free, 56-year-old woman presented with a non-palpable BI-RADS 4B lesion without microcalcifications. She had a positive family history for breast cancer and a history of atypical ductal hyperplasia in the ipsilateral breast four years ago. She reported having been treated for non-Hodgkin lymphoma 12 years ago. With the suspicion of breast cancer, mammographically guided VABB with 11-gauge probe (on the stereotactic Fisher's table) was performed. VABB made the diagnosis of a non-Hodgkin, grade II, B-cell germinal-center lymphoma. VABB yielded enough tissue for immunohistochemistry/WHO classification. Conclusion This is the first case in the literature demonstrating the successful diagnosis of breast lymphoma by VABB, irrespectively of the level of clinical suspicion. It should be stressed that VABB was able to yield enough tissue for WHO classification. In general, lymphoma should never be omitted in the differential diagnosis, since no pathognomonic radiologic findings exist for its diagnosis.

Abstract Background Breast cancer is usually associated with metastases to lungs, bones and liver. Breast carcinoma metastasizing to the gallbladder is very rare. Case presentation A 59-year-old woman presented with bilateral synchronous breast lesions. A palpable, retroareolar solid lesion of diameter equal to 5 cm was present in the right breast, and a newly developed, non-palpable lesion with microcalcifications (diameter equal to 0.7 cm) was present in the upper outer quadrant of the left breast. Modified radical mastectomy was performed on the right breast and lumpectomy after hook-wire localization was performed on the left breast, combined with lymph node dissection in both sides. The pathological examination revealed invasive lobular carcinoma grade II in the right breast and invasive ductal carcinoma grade I in the left breast. Chemotherapy, radiation therapy, trastuzumab and letrozole were appropriately administered. At her 18-month follow-up, the patient was free of symptoms; the imaging tests (chest CT, abdominal U/S, bone scan), biochemical tests, blood cell count and tumor markers were also normal. At the 20th month after surgery however, the patient developed symptoms of cholecystitis and underwent cholecystectomy. The histopathological examination revealed metastasis of the lobular carcinoma to the gallbladder. Conclusion This extremely rare case confirms on a single patient the results of large series having demonstrated the preferential metastasis of lobular breast cancer to the gallbladder. Symptoms of cholecystitis should not be neglected in such patients, as they might indicate metastasis to the gallbladder.

Abstract Background Vacuum-Assisted Breast Biopsy (VABB) is effective for the preoperative diagnosis of non-palpable mammographic solid lesions. The main disadvantage is underestimation, which might render the management of atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) difficult. This study aims to develop and assess a modified way of performing VABB. Patients and methods A total of 107 women with non-palpable mammographic breast solid tumors BI-RADS 3 and 4 underwent VABB with 11G, on the stereotactic Fischer's table. 54 women were allocated to the recommended protocol and 24 cores were obtained according to the consensus meeting in Nordesterdt (1 offset-main target in the middle of the lesion and one offset inside). 53 women were randomly allocated to the extended protocol and 96 cores were excised (one offset-main target in the middle of the lesion and 7 peripheral offsets). A preoperative diagnosis was established. Women with a preoperative diagnosis of precursor/preinvasive/invasive lesion underwent open surgery. A second pathologist, blind to the preoperative results and to the protocol made the postoperative diagnosis. The percentage of the surface excised via VABB was retrospectively calculated on the mammogram. The discrepancy between preoperative and postoperative diagnoses along with the protocol adopted and the volume removed were evaluated by Fisher's exact test and Mann-Whitney-Wilcoxon test, respectively. Results Irrespectively of the protocol adopted, 82.2% of the lesions were benign. 14.0% of the lesions were malignancies (5.1% of BI-RADS 3, 5.3% of BI-RADS 4A, 25% of BI-RADS 4B, and 83.3% of BI-RADS 4C lesions). 3.7% of the biopsies were precursor lesions. There was no evidence of underestimation in either protocols. In the standard protocol, the preoperative/postoperative diagnoses were identical. In the extended protocol, the postoperative diagnosis was less severe than the preoperative in 55.5% of cases (55.5% vs. 0%, p = 0.029), and preoperative ADH was totally removed. The phenomenon of discrepancy between diagnoses was associated with larger volume removed (8.20 ± 1.10 vs. 3.32 ± 3.50 cm3, p = 0.037) and higher removed percentage of the lesion (97.83 ± 4.86% vs. 74.34 ± 23.43%, p = 0.024) Conclusion The extended protocol seems to totally excise precursor lesions, with minimal underestimation. This might possibly point to a modified management of ADH lesions.

Abstract Precursors and preinvasive lesions of the breast include atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and lobular neoplasia (LN). There is a significant debate regarding the classification, diagnosis, prognosis and management of these lesions. This review article describes the current theories regarding the pathogenesis and molecular evolution of these lesions. It reviews the implication of a variety of molecules in the continuum of breast lesions: estrogen receptors (ER-alpha and ER-beta), c-erb-B2 (Her2/neu), p53, Ki-67, bcl-2, E-cadherin, transforming growth factor-beta (TGF-beta), p27 (Kip1), p16 (INK4a), p21 (Waf1), vascular endothelial growth factor (VEGF). With respect to the aforementioned molecules, this article reviews their pathophysiological importance, and puts the stress on whether they confer additional risk for invasive breast cancer or not. This knowledge has the potential to be of importance in the therapeutic decisions presenting in the common clinical practice.

Abstract Background To evaluate imprint cytology in the context of specimens with microcalcifications derived from Vacuum-Assisted Breast Biopsy (VABB). Patients and methods A total of 93 women with microcalcifications BI-RADS 3 and 4 underwent VABB and imprint samples were examined. VABB was performed on Fischer's table using 11-gauge Mammotome vacuum probes. A mammogram of the cores after the procedure confirmed the excision of microcalcifications. For the application of imprint cytology, the cores with microcalcifications confirmed by mammogram were gently rolled against glass microscope slides and thus imprint smears were made. For rapid preliminary diagnosis Diff-Quick stain, modified Papanicolaou stain and May Grunwald Giemsa were used. Afterwards, the core was dipped into a CytoRich Red Collection fluid for a few seconds in order to obtain samples with the use of the specimen wash. After the completion of cytological procedures, the core was prepared for routine histological study. The pathologist was blind to the preliminary cytological results. The cytological and pathological diagnoses were comparatively evaluated. Results According to the pathological examination, 73 lesions were benign, 15 lesions were carcinomas (12 ductal carcinomas in situ, 3 invasive ductal carcinomas), and 5 lesions were precursor: 3 cases of atypical ductal hyperplasia (ADH) and 2 cases of lobular neoplasia (LN). The observed sensitivity and specificity of the cytological imprints for cancer were 100% (one-sided, 97.5% CI: 78.2%–100%). Only one case of ADH could be detected by imprint cytology. Neither of the two LN cases was detected by the imprints. The imprints were uninformative in 11 out of 93 cases (11.8%). There was no uninformative case among women with malignancy. Conclusion Imprint cytology provides a rapid, accurate preliminary diagnosis in a few minutes. This method might contribute to the diagnosis of early breast cancer and possibly attenuates patients' anxiety.

Background/Aim: The molecular classification of breast cancer has enabled targeted therapy for specific molecular subtypes. Nestin, which has been studied for its role in oncogenesis, could contribute to this direction. This study aimed to investigate the differences between serum nestin levels and molecular profiling, as well as histopathological tumor types, in women who underwent surgery for breast cancer. Patients and Methods: Women who underwent surgery for breast cancer at the Breast Unit of the 1st Propaedeutic Department of Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens were prospectively included. Patients’ demographic data were recorded and serum nestin levels were measured. Molecular biomarker analysis was performed, as well as histopathologic assessment. Results: Seventy patients were included in the analysis. Among patients with breast cancer, 93% were estrogen receptor (ER) positive, 91% were progesterone receptor (PR) positive, and 43% were human epidermal growth factor receptor 2 (HER2) positive. Ki67 was expressed in 16% of patients and p53 was expressed in 32% of patients. Invasive ductal carcinoma was diagnosed in 80% of patients, with 44% of tumors classified as T1 and 46% as T2. Additionally, 43% were G1 and 56% were N0, while 34% were N1. No statistically significant difference was observed between serum nestin levels and ER, PR, HER2, Ki67, and p53 expression. Furthermore, no difference was observed between serum nestin levels and breast cancer histological type, size, N-stage, and grading. Conclusion: The diagnostic and prognostic role of circulating nestin for breast cancer was not confirmed and no correlation with immunohistochemistry results was observed. Thus, the necessity of larger prospective studies is enhanced. [ABSTRACT FROM AUTHOR]