Mammary Paget's disease occurring after mastectomy

BACKGROUND: Mammary Paget's disease and extramammary Paget's disease are neoplastic conditions, in which there is intraepithelial (usually intraepidermal) infiltration by neoplastic cells showing glandular differentiation. Mammary Paget's disease occurs exclusively on the nipple/areola complex from where it may spread to the surrounding skin. CASE PRESENTATION: We here describe a case of Paget's disease occurring on the thoracic wall site of a previous simple mastectomy, and also briefly summarise the most important aspects leading to a diagnosis of mammary Paget's disease. CONCLUSION: To the best of our knowledge, this is the first reported case of mammary Paget's disease occurring after mastectomy. The absence of the nipple/areola complex obviously raised some questions concerning whether it was mammary or extra-mammary Paget's disease, and how it could occur in the absence of the nipple/areola complex

Expression of proliferating cell nuclear antigen, Ki-67 antigen, estrogen receptor protein, and tumor suppressor p53 gene in cytologic samples of breast cancer: an immunochemical study with clinical, pathobiological, and histologic correlations

Sixty-six unselected breast cancers were analyzed in cytologic smears and histologic sections for the expression of Ki-67, proliferating cell nuclear antigen (PCNA), estrogen receptor protein (ERP), and p53 protein using a standard immunochemical method. The results, expressed as both positive cases and labelling index (LI), were compared with clinical and pathobiological variables. Ki-67 and PCNA immunostaining was seen in all cases, whereas ERP was detectable in 46/63 cases and p53 protein in 20/66 cases. The expression of these markers was generally lower in cytology than in histology, though the differences were not statistically significant. PCNA-LI and Ki-67-LI were closely correlated (P < 0.001), the mean PCNA:Ki-67 ratio being 0.92 +/- 0.57. Occasional discrepancies, however, were found. PCNA and Ki-67 expression was associated with an increase in histologic grade and a decrease in ERP content of tumors, whereas p53 was statistically associated with no clinical or pathobiological variables. The data suggest that proliferative activity and oncogene overexpression may be reliably evaluated in breast cancer by FNA cytology, though PCNA is not a suitable indicator for cell proliferation. The results do not resolve the issue as to whether immunostaining for p53 protein constitutes a dedifferentiation product of the tumor, or is a fundamental aspect of the malignant progression. Survival studies in a larger series of tumors are thus needed to elucidate this point

Peritoneal cytology does not increase the prognostic information provided by TNM in gastric cancer.

Background: This study aimed at verifying whether peritoneal cytology could improve the prognostic information provided by TNM staging in gastric cancer patients. Method: The presence of free peritoneal tumor cells was investigated in 168 patients who underwent curative resection for gastric cancer from January 1992 to July 2002 in Verona, Italy. The influence of peritoneal cytology on survival was evaluated by a Cox regression model, controlling for potential confounders. Results: Twenty-three patients (14%) had positive peritoneal cytology. Patients with positive lavage were more likely to present serosal infiltration (100 vs. 46%) and nodal metastases (91 vs. 67%; P < 0.001). Positive lavage was associated with a very poor prognosis: 3-year survival was only 9% (95% CI 2-27%) when peritoneal cancer cells had been detected, whereas survival reached 50% (95% CI 42-59%) in patients with a negative cytology. In multivariate survival analysis, peritoneal cytology was an independent predictor of mortality when controlling for sex, age, site, histology, and nodal metastases, but not when adjusting also for depth of tumor invasion (RR of positive versus negative = 1.2, 95% CI 0.7-2.0). Similarly, the influence of peritoneal cytology on survival was no longer significant when univariate analysis was restricted to T3/T4 patients (RR = 1.5, 0.9-2.5). Conclusions: Positive peritoneal cytology was a marker of poor prognosis in gastric cancer patients. Nevertheless, peritoneal lavage did not increase the prognostic information already provided by the TNM staging system in this Italian series

Ectopic expression of PLC-β2 in non-invasive breast tumor cells plays a protective role against malignant progression and is correlated with the deregulation of miR-146a

Cells in non-invasive breast lesions are widely believed to possess molecular alterations that render them either susceptible or refractory to the acquisition of invasive capability. One such alteration could be the ectopic expression of the β2 isoform of phosphoinositide-dependent phospholipase C (PLC-β2), known to counteract the effects of hypoxia in low-invasive breast tumor-derived cells. Here, we studied the correlation between PLC-β2 levels and the propensity of non-invasive breast tumor cells to acquire malignant features. Using archival FFPE samples and DCIS-derived cells, we demonstrate that PLC-β2 is up-regulated in DCIS and that its forced down-modulation induces an epithelial-to-mesenchymal shift, expression of the cancer stem cell marker CD133, and the acquisition of invasive properties. The ectopic expression of PLC-β2 in non-transformed and DCIS-derived cells is, to some extent, dependent on the de-regulation of miR-146a, a tumor suppressor miRNA in invasive breast cancer. Interestingly, an inverse relationship between the two molecules, indicative of a role of miR-146a in targeting PLC-β2, was not detected in primary DCIS from patients who developed a second invasive breast neoplasia. This suggests that alterations of the PLC-β2/miR-146a relationship in DCIS may constitute a molecular risk factor for the appearance of new breast lesions. Since neither traditional classification systems nor molecular characterizations are able to predict the malignant potential of DCIS, as is possible for invasive ductal carcinoma (IDC), we propose that the assessment of the PLC-β2/miR-146a levels at diagnosis could be beneficial for identifying whether DCIS patients may have either a low or high propensity for invasive recurrence

Levels of miR-126 and miR-218 are elevated in ductal carcinoma in situ (DCIS) and inhibit malignant potential of DCIS derived cells

A substantial number of ductal carcinoma in situ (DCIS) detected by mammography never progress to invasive ductal carcinoma (IDC) and current approaches fail to identify low-risk patients not at need of adjuvant therapies. We aimed to identify the key miRNAs protecting DCIS from malignant evolution, that may constitute markers for non-invasive lesions. We studied 100 archived DCIS samples, including pure DCIS, DCIS with adjacent IDC and pure DCIS from patients with subsequent IDC in contralateral breast or no recurrence. A DCIS derived cell line was used for molecular and cellular studies. A genome wide study revealed that pure DCIS has higher miR-126 and miR-218 expression than DCIS with adjacent IDC lesions or than IDC. The down-regulation of miR-126 and miR-218 promoted invasiveness in vitro and, in patients with pure DCIS, was associated with later onset of IDC. Survival studies of independent cohorts indicated that both miRNAs play a protective role in IDC. The clinical findings are in agreement with the miRNAs' roles in cell adhesion, differentiation and proliferation. We propose that miR-126 and miR-218 have a protective role in DCIS and represent novel biomarkers for the risk assessment in women with early detection of breast cancer

Morphological parameters of lobular in situ neoplasia in stereotactic11-gauge vacuum-assisted needle core biopsy do not predict the presence of malignancy on subsequent surgical excision

Aims: The management of lobular in situ neoplasia (LN) when diagnosed on core biopsy remains a controversial issue. The present study aimed to investigate the association between morphological parameters of LN on vacuum-assisted needle core biopsy (VANCB) and the presence of malignancy (ductal carcinoma in situ, pleomorphic lobular carcinoma in situ, or invasive carcinoma) at surgical excision (SE). Methods and results: The study included 14 pathology departments in Italy. Available slides from 859 cases of VANCB reporting an original diagnosis of flat epithelial atypia, atypical ductal hyperplasia or LN, all with subsequent surgical excision, were reviewed. Overall, 286 cases of LN, pure or associated with other lesions, were identified, and a malignant outcome was reported at excision for 51 cases (17.8%). Among the 149 cases of pure LN, an increased risk of malignancy emerged in women in mammographic categories R4-R5 as compared with those in categories R2-R3 (OR 2.46; P = 0.048). In the series, a statistically significant decreased malignancy risk emerged among cases without determinant microcalcifications (P = 0.04). Conclusions: Our results suggest that the diagnosis of pure LN on VANCB warrants follow-up excision, because clinicopathological parameters do not allow the prediction of which cases will present carcinoma at surgical excision. © 2013 John Wiley and Sons Ltd