Influence of surgical margins on the outcome of breast cancer patients: a retrospective analysis.

OBJECTIVE: Breast-conserving surgery has become the preferred treatment for early breast cancer. Yet the question of what constitutes a 'safe margin', in terms of impact on patient outcome, remains unanswered. Our aim was to address this knowledge gap by determining the prevalence of positive and narrow margins after breast-conserving surgery, and evaluating how margin status impacted local recurrence and overall survival. MATERIALS AND METHODS: We collected data about all women who underwent breast-conserving cancer surgery in our department between 2002 and 2011, focusing on patient and tumor characteristics, the distance from the tumor to the surgical margin, therapies administered, and outcome (measured in terms of local recurrence and overall survival). Data were analyzed by R (version 3.0.1), considering p < 0.05 as significant. Multivariate analyses were also performed. RESULTS: Of 1,192 women who received breast-conserving surgery, 264 were considered for widening; 111 of these patients had positive margins and 153 narrow (where narrow was defined as less than 5 mm). Widening was performed for 38 % of these patients (99/264) and mastectomy for 27 % (70/264), while 36 % (95/264) had no further surgery and were simply followed-up. Our multivariate analysis confirmed that local tumor recurrence and overall survival were not significantly influenced by margin status, either at initial surgery, or (for those patients with initially positive margins) at secondary margin-widening surgery. However, the following were found to be significantly correlated with local recurrence: tumor multifocality, high expression of Ki-67/Mib-1, comedo-like necrosis, and non-axillary lymph node positivity (p < 0.05). CONCLUSIONS: We found the status of resection margins and the management of infiltrated or narrow margins to have no significant influence on local tumor recurrence rates or on overall patient survival. Instead, biological factors connected with tumor aggressiveness seem to play the most important role in breast cancer prognosis, independent of surgical radicality.

Nine years of experience with the sentinel lymph node biopsy in a single Italian center: a retrospective analysis of 1,050 cases.

BACKGROUND: This study aims to determine the prevalence and predictive factors for recurrence after sentinel lymph node biopsy (SLNB) and for sentinel lymph node positivity by SLNB in our population. METHODS: We followed up all SLNBs performed between 2002 and 2010 and analyzed data by R (version2.10.1), considering p < 0.05 significant. RESULTS: Among 1,050 patients with SLNB, 23% (245/1050) underwent secondary axillary dissection (CALND). Axillary recurrence prevalence among patients with negative SLNB was 1% (6/805) at a mean follow-up of 54 months (±14), and 1.7% (95% CI 0.2-3.1%) after 6 years of follow-up, as all recurrences developed between the 3rd and the 6th years of follow-up. By multivariate analysis, axillary recurrence results correlated with large tumor size, high number of excised nodes, lymphovascular invasion, high grading, multifocality, Her-2 positivity, intraductal histology, and comedo-like necrosis. Moreover, SLNB positivity results correlated with young age, large tumor size, high number of excised nodes, negative history for second primary malignancies, lymphovascular invasion, and high grading. CONCLUSIONS: Cancer characteristics represent important predictive factors for SLNB positivity, as well as for axillary recurrence in patients with negative SLNB, independently, by surgical and nonsurgical treatment. Therefore, cancer biological behavior and the patient's hormonal profile should be evaluated with care to better tailor the follow-up of women with breast cancer.

Reproducibility in the diagnosis of needle core biopsies of non-palpable breast lesions: an international study using virtual slides published on the world-wide web.

AIMS: To conduct an internet-based study using virtual slides (VS) of sterotactic core biopsy specimens of non-palpable breast lesions in order to evaluate interobserver reproducibility between pathologists. METHODS AND RESULTS: A total of 18 breast lesions, determined to be histologically complex by two pathologists, were selected. Digitized VSs were then created using QuickTime Virtual Reality technology (Apple, Cupertino, CA, USA) and posted on the world-wide web. In all, 10 pathologists completed the evaluations of 18 VSs using the five diagnostic categories (B1-B5) from the European guidelines for quality assurance in breast cancer screening and diagnosis. Their results were compared with those of every other participating pathologist, and were then individually compared with the results of a highly experienced breast pathologist (referee). Of the 18 cases, 10 (56%) were classified by the referee as borderline (B3 and B4). Comparisons with reference values showed a less than satisfactory level of reproducibility (median kappa(w) = 0.60). As regards interobserver reproducibility, results showed that, in general, the level of agreement was not satisfactory (median kappa(w) = 0.53). CONCLUSIONS: Overall, the findings are comparable to those quality control studies using circulating slides when analysis is done on borderline cases.

Primary cutaneous nevoid melanoma with Homer-wright rosettes: a hitherto unrecognized variant with immunohistochemical and ultrastructural study.

We report a case of cutaneous nevoid melanoma manifesting as a growing and pruritic pigmented lesion of the back in a 43-year-old woman. The lesion measured 1.2 cm in its largest dimension. The salient microscopic features were discrete dermal nests of palisading tumor cells and a central fibrillary tangled core. Other features were microscopically consistent with melanoma: irregular tumor cell nesting associated with upward migration of melanocytes and consumption of the epidermal component, lack of maturation, expansile growth pattern, and a tendency to confluence of the dermal nests. No prominent mitotic activity was recognized. Breslow thickness was 1.3 mm. Tumor cells were positive for HMB45, Melan A, tyrosinase, and S100 protein. The MIB-1/ki-67 proliferative index was 2%. Histologic examination of a biopsy sample from the axillary sentinel lymph node was positive for small foci of melanocytic cells measuring 0.04 mm in their largest dimension.

[Recurrent multifocal cancer lesions in a patient on hemodialysis after kidney pancreas transplant failure]. / Lesioni neoplastiche multifocali e recidivanti in un paziente in emodialisi dopo fallimento di trapianto combinato rene-pancreas.

Cancer is an important cause of mortality in patients on hemodialysis and kidney transplant recipients. Immunodepression and the genotoxic action of uremia are critical pathogenic agents. A 59-year-old man, ex-smoker, who had been on hemodialysis for seven months because of uremic degeneration of diabetic nephropathy, underwent a combined kidney-pancreas transplant in 1991, complicated by slow-resolution CMV infection. In 1993, after kidney graft failure due to chronic rejection, hemodialysis treatment was restarted with good pancreatic function. Steroid therapy was interrupted and azathioprine and cyclosporine immunosuppressive therapy maintained. In September 2007 the patient was diagnosed with two neoplasms of the oral mucosa: a well-differentiated squamous carcinoma and a spinocellular carcinoma associated with field cancerization. The tumors were resected, followed by laser treatment. Histological examination revealed squamous cell carcinoma without lymph node involvement. Azathioprine was interrupted. In January 2008 adjuvant radiotherapy to the surgical areas of the oral mucosa and neck was started. In February a verrucous nevus on the patient's chest turned out to be a spinocellular carcinoma in situ. In May 2008 recurrence of keratinizing squamous carcinoma of the oral mucosa was found, this time with nodal involvement. Cyclosporine administration was interrupted and after consultation with the oncology committee it was decided to continue with supportive therapy only, until the patient's death in August 2008.

Intraoperative examination for suspected prostatic carcinoma: frozen sections in "marginal" (cadaveric) transplant donors.

Elderly patients are a potential source of additional organ supply for transplantation. Unfortunately, with increasing age, the chance is greater that an apparently healthy aged man will be carrying a silent prostatic carcinoma. Therefore, in order to maximize safety, intraoperatory evaluation of the prostatic gland may be required to rule out adenocarcinoma. We evaluated 14 prostatic tissue specimens obtained from "marginal" donors and examined by intraoperatory frozen sections. These were positive for carcinoma in three cases and negative in 11. Examination of permanent sections from snap-frozen tissue revealed three additional cases that were unrecognized on the initial frozen sections. The inaccuracy of the method could be explained by the difficulty, caused by freezing, of discriminating benign from malignant gland and by technical artifacts. Snap-freezing artifacts also compromised the evaluation of tumor invasion into the extraprostatic fat in 2 cases. Because of the architectural distortion, frozen sections were also ineffective in the recognition of Gleason pattern in all cases. Examination of prostatic frozen sections may be useful if the pathologist is asked to recognize only larger tumors. The estimation of small volume tumors, extracapsular extension, as well as Gleason pattern assessment suffers from an irreducible bias.

Eosinophil-rich squamous carcinoma of the oral cavity: a study of 13 cases and delineation of a possible new microscopic entity.

We report 13 cases of squamous cell carcinoma (SCC) of the oral cavity characterized by a prominent eosinophilic infiltration of the stroma. All patients were adults, 10 men and 3 women (aged 54 to 92 years; median, 71 years). They presented with tumors of the gingiva (5 cases), tongue (3 cases), palatine tonsil (2 cases), palate (2 cases), and mucosal aspect of lip (1 case). Metastatic involvement of regional lymph nodes was seen in 5 cases. The metastatic foci were associated with heavy eosinophilia as well. No patient had an abnormal eosinophil count in blood. Microscopically, the clusters of eosinophils were characteristically noticed in intimate admixture with the advancing edge of squamous carcinoma, either as nests or small tumor cords. The pattern of eosinophilic infiltration was comparable, regardless of tumor site or grade. Data from our series indicate that SCC with a reactive inflammatory infiltrate rich in eosinophils is consistently associated with stromal invasion. This observation may be useful in dealing with small tissue fragments where subepithelial stromal invasion cannot be easily assessed by conventional criteria. In addition, our data seem to confirm that eosinophil-rich SCC, although associated with metastatic involvement of cervical lymph node, seems to pursue a less aggressive course if compared with ordinary SCC.

Tumour-infiltrating lymphocytes, programmed death ligand 1 and cyclooxygenase-2 expression in skin melanoma of elderly patients: clinicopathological correlations.

Age is an important prognostic factor in melanoma; notably, elderly patients tend to present with advanced stage skin melanoma (SM) and worse outcome. Moreover, SM is an immunogenic cancer, and its interaction with the aging immune system could have an effect on biologic behaviour of this disease. Tumour-infiltrating lymphocytes (TILs) could represent the host response in SM; it has been shown that higher grade of TILs is associated with better survival. Moreover, programmed death ligand 1 (PD-L1) and cyclooxygenase-2 (COX-2) are potential markers of host immune response and inflammation. We retrospectively reviewed 113 consecutive cases of early-stage SM that occurred in patients aged greater than or equal to 65 years at the time of diagnosis, followed between January 2010 and March 2014 at the University and General Hospital of Udine, Italy. The aim of this study was to evaluate TILs grade, PD-L1 expression on TILs and tumour expression of PD-L1 and COX-2 and their prognostic value in elderly patients with early SM. A better disease-free survival as well as melanoma-specific survival (MSS) was significantly associated with TILs [hazard ratios (HR): 0.41, 95% confidence interval (CI): 0.20-0.84, P=0.02 and HR: 0.37, 95% CI: 0.17-0.82, P=0.01, respectively]. PD-L1 positivity on TILs was associated with a better MSS (HR: 0.41, 95% CI: 0.17-0.97, P=0.04). Moreover, among patients with TILs, those showing COX-2 positivity on tumour cells and no PD-L1 expression on TILs had a worse disease-free survival and MSS (HR: 5.18, 95% CI: 1.33-20.23, P=0.018; HR: 6.21, 95% CI: 1.20-32.24, P=0.03; respectively). Immune and inflammatory markers deserve further investigation in aging patients with melanoma.

Applicability of two different validated models to predict axillary non-sentinel lymph node status by sentinel node biopsy in a single Italian center.

BACKGROUND: The necessity of complete axillary lymph node dissection (CALND) after sentinel lymph node biopsy (SLNB) for women with sentinel lymph node metastases is a matter of debate because non-sentinel lymph nodes after CALND contain no further metastases in about 50 % of cases. Our study aims to determine the applicability in our setting of two different validated nomograms to predict axillary lymph node status after SLNB. METHODS: We collected data about all women who underwent SLNB in our Department of Surgery from 2007 to 2010, focusing on tumor, patient, and breast characteristics. Data was analyzed by R (version 2.15.2); p < 0.05 was considered significant. RESULTS: Among 511 women who underwent SLNB, 126 received CALND due to sentinel lymph node metastasis, and 73.0 % of these had no further metastatic non-sentinel lymph node. The area under the receiver operating characteristic (ROC) curves for the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and the Tenon score were 78.5 % (95 % CI 70.1-86.8 %) and 77.0 % (95 % CI 67.9-86.0 %) (p = 0.678), respectively. CONCLUSIONS: Both the MSKCC nomogram and the Tenon score were predictive for the axillary non-sentinel lymph node status by SLNB. The MSKCC nomogram was the more accurate of the two and the Tenon score was the easier one to apply.

Synchronous and metachronous breast malignancies: a cross-sectional retrospective study and review of the literature.

OBJECTIVE: There is increasing interest in patients with metachronous (MBC) and synchronous breast cancer (SBC). The objective of this study was to evaluate the occurrence and outcome of MBCs and SBCs. METHODS: A retrospective study on women operated in our department for breast cancer between 2002 and 2005 was carried out. Patients were divided into three groups: women with MBC, SBC, and unilateral breast cancer (UBC). Moreover, we performed a meta-analysis of the English literature about multiple breast cancers between 2000 and 2011 taking into consideration their prevalence and overall survival (OS). RESULTS: We identified 584 breast cancer patients: 16 women (3%) presented SBC and 40 MBC (7%, second cancer after 72-month follow-up IQR 40-145). Although the meta-analysis showed significant OS differences between MBC or SBC and UBC, we did not observe any significant OS difference among the three groups of our population. Anyway, we found a significant worse disease-free survival in MBC than UBC and a significant higher prevalence of radical surgery in MBC and SBC than UBC. CONCLUSIONS: Despite the low prevalence of MBC and SBC, the presence of a long time risk of MBC confirms the crucial role of ipsi- and contralateral mammographies in the postoperative follow-up.

Prevalence and risk factors of intraoperative identification failure of sentinel lymph nodes in patients affected by breast cancer.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) has progressively replaced complete axillary lymph node dissection in the evaluation of breast cancer patients with clinically node-negative disease. Our study investigates the rate of and risk factors involved in sentinel node identification failure. MATERIALS AND METHODS: We collected data on SLNBs performed during 2002-2010, focusing on tumor, patient, and breast characteristics, radioactivity parameters, and operators' experience. Data were analyzed by R (v2.14.2), considering significance at P values lower than 0.05. RESULTS: Among 1050 women who underwent an SLNB, the rate of identification failure was 2% (23/1050), which, on bivariate analysis, was seen to be significantly influenced (P<0.05) by the preoperative and intraoperative low radiotracer uptake (axilla/lesion radiotracer uptake ratio<1%), low level of experience of the specialist in nuclear medicine, luminal A subtype, and radiotracer uptake localization in internal mammary lymph nodes. On multivariate analysis, significant risk factors for sentinel node identification failure were found to be: axilla/lesion radiotracer uptake ratio less than 1%, radiotracer uptake localization in internal mammary lymph nodes, and luminal A subtype. Considering only the preoperative variables in our multivariate analysis, axilla/lesion radiotracer uptake ratio less than 1%, negative lymph node scintiscan, and radiotracer uptake localization in internal mammary lymph nodes had an area under the curve (receiver operating characteristic curve) of 96% (95% confidence interval 92-100%). Further, we built a nomogram based on these simple parameters for counseling the patient about the probability of not finding the sentinel lymph node during the surgical procedure. CONCLUSION: The relatively low prevalence of SLNB failure (2%) is indicative of the accuracy of the procedure when performed by experienced surgeons. The sentinel node identification failure in our population seemed to be related to biological tumor factors (luminal A subtype) and probably to physiological or pathological variations in the lymphatic drainage (axilla/lesion radiotracer uptake ratio<1% and radiotracer uptake localization in internal mammary lymph nodes).

Intrathoracic rhabdoid carcinoma: a clinicopathological, immunohistochemical, and ultrastructural study of 6 cases.

We evaluated the clinicopathological spectrum of intrathoracic rhabdoid carcinoma, including its immunophenotype and ultrastructural features. Our series included 6 cases arising from the lung (4 cases) and the anterior mediastinum (2 cases). The patients were 4 men and 1 woman aged between 40 and 63 years (median, 53 years). Microscopically, all of the lesions were composed of loosely cohesive, large, atypical polygonal cells, with glassy cytoplasms and eccentric nuclei. Chromatin texture was finely granular or open. On immunohistochemical stain, the neoplastic cells were positive for vimentin in all cases, positive for vimentin, keratins and/or epithelial membrane antigen in all cases, and negative for other antigens. In 1 case, neoplastic cells were also positive for CD34. Electron microscopic study showed prominent perinuclear whorls of densely packed intermediate filaments or mitochondria. All patients were treated with combined chemotherapy and radiotherapy. One patient died 8 months after the diagnosis was made. Of the remaining patients, 3 are alive with evidence of disease progression, including brain metastases. We concluded that rhabdoid neoplasms arising in the thoracic cavity are aggressive tumors of epithelial lineage and should be categorized as true "rhabdoid carcinomas" instead of being ambiguously designated as "intrathoracic rhabdoid tumors" or "carcinomas with rhabdoid phenotype."