Capsular synovial metaplasia mimicking silicone leak of a breast prosthesis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Synovial metaplasia around a prosthesis and in particular around silicone breast implants has been noted by various investigators, but has unknown clinical significance. We report on a patient where a large amount of synovial fluid mimicked rupture of an implant. We believe this to be an unusual clinical presentation of this phenomenon. Review of the English language literature failed to identify a comparable case.</p> <p>Case presentation</p> <p>A 25-year-old woman had undergone bilateral breast augmentation for cosmetic reasons. One implant was subsequently subjected to two attempts at expansion to correct asymmetry. The patient was later found to have a large quantity of viscous fluid around the port of that same prosthesis. Histological assessment of the implant had consequently confirmed capsular synovial metaplasia. This had initially caused the suspicion of a silicone 'bleed' from the implant and had resulted in an unnecessary explantation.</p> <p>Conclusion</p> <p>Capsular synovial metaplasia should be ruled out before the removal of breast implants where a leak is suspected. Manipulation and expansion of an implant may be risk factors for the development of synovial metaplasia.</p

Lymphangiogenesis and lymph node metastasis in breast cancer

<p>Abstract</p> <p>Introduction</p> <p>There have been few studies on lymphangiogenesis in the past due to the lack of specific lymphatic endothelial markers, and lymphatic-specific growth factors. Recently, these limitations have been relieved by the discovery of a small number of potential lymphatic-specific markers. The relationship between lymphangiogenesis and regional or distant metastasis has not previously been investigated in humans. Using these lymphatic markers, it is possible to explore the relationship between lymphangiogenesis and tumour metastasis. This study indirectly quantified lymphangiogenesis by measuring mRNA expression of all seven lymphatic markers described above in breast cancers and correlated these markers with lymphatic involvement and survival.</p> <p>The cDNA from 153 frozen archived breast samples were analysed with Q-PCR for all seven lymphangiogenic markers. This was correlated with various prognostic factors as well as patient survival.</p> <p>Results</p> <p>There was significantly greater expression of all 7 markers in malignant compared to benign breast tissue. In addition, there was greater expression in lymph node positive/grade 3 tumours when compared to lymph node negative/grade 1 tumours. In 5 of the markers, there was a greater expression in poor NPI prognostic tumours when compared to favourable prognostic tumours which was not statistically significant. There was no association between recurrence risk and lymphangiogenic marker expression.</p> <p>Conclusion</p> <p>In summary, the findings from this study show that lymphangiogenesis, measured by specific lymphatic marker expression, is higher in breast cancers than in normal breast tissue. Secondly, breast cancers which have metastasised to the regional lymphatics show higher expression compared to those which have not, although the individual differences for all five markers were not statistically significant.</p

HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer

BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse

A Nationwide Cross-Sectional Survey of UK Breast Surgeons’ Views on the Management of Ductal Carcinoma In Situ

Background. There is wide variation in the management of Ductal Carcinoma In Situ (DCIS) nationwide. We aimed to investigate whether the attitudes of surgeons towards different aspects of DCIS treatment varied by seniority of surgeon or by geographical region within the UK. Materials and Methods. A nationwide online survey targeted at UK breast surgeons was undertaken. The anonymous survey contained questions regarding demographics of respondents and specific questions regarding DCIS management that were identified as areas of uncertainty during a systematic search of the literature. Results. Responses from 80 surgeons were obtained. Approximately 57% were male and the majority were consultant or specialist registrar. Approximately 63% of participants were based in district general hospitals with all training deaneries represented. Surgeons’ views on the prognosis and management of DCIS varied geographically across the UK and terminology for DCIS varied with surgeon seniority. Surgeons’ views particularly differed from national guidance on indications for SLNB, tamoxifen, and follow-up practice. Conclusion. Our survey reaffirms that, irrespective of national guidelines and attempts at uniformity, there continues to be a wide variety of views amongst breast surgeons regarding the ideal management of DCIS. However, by quantifying this variation, it may be possible to take it into account when examining long-term trends in nationwide treatment data

Prognostic value of rho GTPases and rho guanine nucleotide dissociation inhibitors in human breast cancers

PURPOSE: Rho family members are small GTPases that are known to regulate malignant transformation and motility of cancer cells. The activities of Rhos are regulated by molecules such as guanine nucleotide dissociation inhibitors (GDIs). This study determined the levels of expression and the distribution of Rho-A, -B, -C, and -G, and Rho-6, -7, and -8, as well as Rho-GDI-beta, and Rho-GDI-gamma, in breast cancer and assessed their prognostic value. EXPERIMENTAL DESIGN: The distribution and location of Rhos and RhoGDIs were assessed using immunohistochemical staining of frozen sections. The levels of transcripts of these molecules were determined using a real-time quantitative PCR. Levels of expression were analyzed against nodal involvement and distant metastasis, grade, and survival over a 6-year follow-up period. RESULTS: The levels of Rho-C, Rho-6, and Rho-G were significantly higher in breast cancer tissues (n = 120) than in background normal tissues (n = 32). However, the level of Rho-A and -B and rho-7 and -8 was found to be similar in tumor and normal tissues. Immunohistochemical staining revealed the high level of staining of Rho-C protein in tumor cells. The levels of Rho-GDI-gamma transcripts were found to be significantly lower in tumor tissues than in normal tissues (P < 0.05 and P < 0.001, respectively). Node-positive tumors have significantly higher levels of Rho-C and Rho-G, and lower levels of Rho-GDI and Rho-GDI-gamma transcripts, than do node-negative tumors. Significantly higher levels of Rho-C and Rho-G were seen in patients who died of breast cancer than in those who remained disease free. Patients with recurrent disease, with metastasis or who died of breast cancer, also exhibited higher levels of Rho-6 but lower levels of Rho-GDI-gamma. Higher-grade tumors were also associated with low levels of Rho-GDI and Rho-GDI-gamma. CONCLUSIONS: Raised levels of Rho-C, Rho-G and Rho-6 and reduced expression of Rho-GDI and -GDI-gamma in breast tumor tissues are correlated with the nodal involvement and metastasis. This suggests that the expression of Rhos and Rho-GDIs in breast cancer is unbalanced and that this disturbance has clinical significance in breast cancer