What are the characteristics of breast cancers misclassified as benign by quantitative ultrasound shear wave elastography?

OBJECTIVES: Shear wave elastography (SWE) is a promising adjunct to greyscale ultrasound in differentiating benign from malignant breast masses. The purpose of this study was to characterise breast cancers which are not stiff on quantitative SWE, to elucidate potential sources of error in clinical application of SWE to evaluation of breast masses. METHODS: Three hundred and two consecutive patients examined by SWE who underwent immediate surgery for breast cancer were included. Characteristics of 280 lesions with suspicious SWE values (mean stiffness >50 kPa) were compared with 22 lesions with benign SWE values (<50 kPa). Statistical significance of the differences was assessed using non-parametric goodness-of-fit tests. RESULTS: Pure ductal carcinoma in situ (DCIS) masses were more often soft on SWE than masses representing invasive breast cancer. Invasive cancers that were soft were more frequently: histological grade 1, tubular subtype, ≤10 mm invasive size and detected at screening mammography. No significant differences were found with respect to the presence of invasive lobular cancer, vascular invasion, hormone and HER-2 receptor status. Lymph node positivity was less common in soft cancers. CONCLUSION: Malignant breast masses classified as benign by quantitative SWE tend to have better prognostic features than those correctly classified as malignant. KEY POINTS: • Over 90 % of cancers assessable with ultrasound have a mean stiffness >50 kPa. • 'Soft' invasive cancers are frequently small (≤10 mm), low grade and screen-detected. • Pure DCIS masses are more often soft than invasive cancers (>40 %). • Large symptomatic masses are better evaluated with SWE than small clinically occult lesions. • When assessing small lesions, 'softness' should not raise the threshold for biopsy.

Direct comparison of Neuroform and Enterprise stents in the treatment of wide-necked intracranial aneurysms.

AIM: To compare the complications and outcomes of Neuroform and Enterprise stents in the treatment of unruptured wide-necked aneurysms. MATERIALS AND METHODS: Under the auspices of the institutional review board, a review of a prospectively collected patient log identified 130 patients who underwent elective stent-assisted coil embolization of a wide-necked aneurysm, including 53 patients treated with an Enterprise stent and 77 patients treated with a Neuroform stent. Immediate and long-term clinical and radiographic outcomes were recorded for all patients. All patient data were handled in accordance with Health Insurance Portability and Accountability Act of 1996 (HIPAA) regulations. RESULTS: The technical success rate was 94%. Overall morbidity was 15% with Enterprise stents and 3% with Neuroform stents (p = 0.020). However, the type of stent used was not predictive of clinical outcomes as measured by the modified Rankin scale. In a multivariate analysis, the use of a Neuroform stent was one of the predictors of retreatment (p = 0.034). CONCLUSION: Multivariate analyses identified the use of Neuroform stents as an independent predictor of the need for retreatment and the use of Enterprise stents as an independent predictor of morbidity. However, the type of stent was not predictive of clinical outcome as measured by the modified Rankin scale.

Pattern of brain metastatic disease according to HER-2 and ER receptor status in breast cancer patients.

AIMS: To document the type, location, extent, and complications of brain metastases in patients with breast cancer and identify associations with oestrogen receptor (ER) negative and human epidermal growth factor receptor 2 (HER-2) receptor expression. MATERIALS AND METHODS: Breast cancer patients with known brain metastases were included in this retrospective study, if cross-sectional imaging of the brain [computed tomography (CT)] was available to review and HER-2 and ER status was known. Two neuroradiologists, who were blinded to the receptor status, separately and for each patient, documented on a proforma the location, number, and dimensions of the deposits and the presence or absence of hydrocephalus. Adjudication was sought where there was discrepancy between the two reports. ER status, HER-2 receptor status, and patient age were also documented. The results were analysed using two-sided Fisher's exact tests with Lancaster's mid-P correction and associations were sought between the tumour characteristics and the pattern of brain disease. RESULTS: Sixty patients were included in the study. There was an association between young age (<40 years) and HER-2 positivity [10 of 24 (41.7%) versus three of 36 (8.3%); p = 0.002]. In ER-negative women, HER-2 positivity was found to be associated with a larger number (six or more) of metastases [11 of 18 (61%) versus nine of 25 (36%); p = 0.049], more brain stem metastases [11 of 18 (61%) versus three of 26 (11.5%); p = 0.035], more frequent occurrence of hydrocephalus [7 of 12 (36.8%) versus three of 26 (11.5%); p = 0.049], and a higher incidence of occipital metastases [12 of 18 (66.7%) versus eight of 26 (30.8%); p = 0.029]. CONCLUSION: ER-negative HER-2-positive women are more likely to present with a larger number of lesions, more brain stem/occipital metastases, and hydrocephalus, which may predispose them to unfavourable outcomes following treatment.

Histology of Convergent Probing Appendages in Mormyridae.

Mormyridae is an early diverging family of Teleostean fishes that produce an electric field for navigation and communication using an electric organ. This clade has a diverse array of soft-tissue rostral appendages, such as the chin-swelling, the Schnauzenorgan, and the tubesnout combined with a Schnauzenorgan, that have evolved multiple times. Here we assess if macroscopically convergent, soft-tissue rostral appendages are also histologically convergent. Further, we investigate how the histology of these appendages can inform their function. We sampled independent gains of the chin-swelling and Schnauzenorgan to understand similarities and differences in their anatomies. We show that macroscopically convergent rostral appendages are also convergent at a histological level, and different types of rostral appendages share a similar anatomy; that said, minor differences likely relate to their specific functions. Based on a comparison of the skeletal muscle distribution and the differing attachment shapes of each appendage to the dentary, we conclude that the Schnauzenorgan is capable of a wider range of movements than the chin swelling. Furthermore, the anatomy suggests that these soft-tissue rostral appendages likely function as electrosensory foveas (i.e., an appendage that focuses a sensory system). Lastly, these histological data support the hypothesis that the chin swelling may be a precursor to the Schnauzenorgan.

ResumenMormyridae es una de las primeras familias divergentes de peces teleósteos que producen un campo eléctrico para la navegación y la comunicación mediante un órgano eléctrico. Este clado tiene una variedad diversa de apéndices rostrales de tejidos blandos, como el mentón hinchado, el Schnauzenorgan y el hocico tubular combinado con un Schnauzenorgan, que han evolucionado varias veces. Aquí evaluamos si los apéndices rostrales de tejido blando macroscópicamente convergentes también son histológicamente convergentes. Además, investigamos cómo la histología de estos apéndices puede informar sus funciones. Tomamos muestras de ganancias independientes del mentón hinchado y del Schnauzenorgan para comprender las similitudes y diferencias en sus anatomías. Mostramos que los apéndices rostrales macroscópicamente convergentes también lo son a nivel histológico, y diferentes tipos de apéndices rostrales comparten una anatomía similar; dicho esto, es probable que las diferencias menores se relacionen con sus funciones específicas. Con base en una comparación de la distribución del músculo esquelético y las diferentes formas de unión de cada apéndice al dentario, concluimos que el Schnauzenorgan es capaz de realizar una gama más amplia de movimientos que el mentón hinchado. Además, la anatomía sugiere que estos apéndices rostrales de tejido blando probablemente funcionen como fóveas electrosensoriales (es decir, un apéndice que enfoca un sistema sensorial). Por último, estos datos histológicos apoyan la hipótesis de que el mentón hinchado puede ser un precursor del Schnauzenorgan.

Topographical analysis of telomere length and correlation with genomic instability in whole mount prostatectomies.

BACKGROUND: Many critical events in prostatic carcinogenesis appear to relate to the emergence of genomic instability. Characteristic genomic abnormalities such as 8p loss, 8q gain, trisomy 7, and PTEN microdeletions may provide selective advantages to increase neoplastic transformation. Evidence suggests that telomere dysfunction is a plausible mechanism for some of these abnormalities on the basis of the break-fusion-bridge cycle that can lead to manifestations of genomic instability. METHODS: In this study, we correlate telomere length measured by quantitative FISH in various prostatic histologies with markers of genomic instability and immunohistochemical measures of proliferation and oxidative stress. RESULTS: We find that telomere shortening is correlated with abnormalities on chromosome 8, but not with trisomy 7 or abnormalities of the PTEN locus. There are associations with C-MYC aberrations in stroma with greater proximity to cancer and a correlation between telomere length in a number of prostatic histologies and the adjacent stroma, suggesting the importance of microenvironmental effects on telomere maintenance in the prostate. This finding was also supported by the finding of the correlation between telomere attrition and the levels of oxidative stress as measured by malondialdehyde staining in HPIN lesions close to cancer. CONCLUSIONS: Telomere attrition in the prostate gland is associated with particular genomic aberrations that contribute to the genomic instability characteristic of prostatic carcinogenesis. Correlations between various histologies and adjacent stroma telomere length suggest it is also may reveal microenvironmental effects within the prostate gland. Oxidative stress may contribute to telomere attrition in HPIN close to cancer.

miRNA profiling in metastatic renal cell carcinoma reveals a tumour-suppressor effect for miR-215.

BACKGROUND: Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Metastatic RCC is difficult to treat. The 5-year survival rate for metastatic RCC is ≤10%. Recently, microRNAs (miRNAs) have been shown to have a role in cancer metastasis and potential as prognostic biomarkers in cancer. METHOD: We performed a miRNA microarray to identify a miRNA signature characteristic of metastatic compared with primary RCCs. We validated our results by quantitative real-time PCR. We performed experimental and bioinformatic analyses to explore the involvement of miR-215 in RCC progression and metastasis. RESULTS: We identified 65 miRNAs that were significantly altered in metastatic compared with primary RCCs. We validated our results by examining the expression of miR-10b, miR-126, miR-196a, miR-204 and miR-215, in two independent cohorts of patients. We showed that overexpression of miR-215 decreased cellular migration and invasion in an RCC cell line model. In addition, through gene expression profiling, we identified direct and indirect targets of miR-215 that can contribute to tumour metastasis. CONCLUSION: Our analysis showed that miRNAs are altered in metastatic RCCs and can contribute to kidney cancer metastasis through different biological processes. Dysregulated miRNAs represent potential prognostic biomarkers and may have therapeutic applications in kidney cancer.

Concurrent stenting of multiple cerebrovascular stenotic lesions: technical note.

INTRODUCTION: Until recently, the treatment of intracranial atherosclerosis has remained limited. Due to advances in endovascular technology and technique, angioplasty and stenting has become an accepted treatment for medically-refractory intracranial atherosclerosis. Patients with intracranial atherosclerosis frequently have multiple lesions, however, the clinical significance of each individual lesion is not always evident. In these instances the treating physician must decide which lesions should be managed conservatively, and which should be treated. TECHNIQUE: Emphasizing decision-making, we describe a patient in whom 3 separate atherosclerotic lesions in the same vascular territory underwent endovascular treatment in one treatment session. Each of the lesions was treated with angioplasty and stent placement. CONCLUSION: This may be a relatively safe and efficacious technique that allows for the treatment of multiple lesions without the risks associated with multiple cerebral angiograms.

Sonographic correlations with the new molecular classification of invasive breast cancer.

Ultrasound is a useful adjunct to mammography for the characterisation and biopsy of solid breast lesions. Protein expression profiling of breast cancer has identified specific subgroups with potential clinical, biological and therapeutic implications. The aim of this study was to determine the ultrasound correlates of these novel molecular classes of invasive breast cancer. The ultrasound findings in 358 patients with operable breast cancer were correlated with the previously described protein expression classes identified by our group using immunohistochemical (IHC) assessment of a large series of breast cancer cases in which 25 proteins of known relevance in breast cancer were assessed, including hormone receptors, HER2 status, basal and luminal markers, p53 and e-cadherin. The proportion of occult lesions was not significantly different in the two groups. Significant differences were noted between the two groups expressing luminal epithelial markers and hormone receptors (1 and 2), including a greater proportion of ill-defined, irregular and distally attenuating tumours in group 2. Tumours characterised by c-erbB2/MUC1 expression, with weak hormone receptor positivity (group 3) were also more likely to be ill defined. Tumours expressing basal markers (group 5) were less likely to have an echogenic halo. The ultrasound features of breast cancer show areas of significant correlation with molecular classes of invasive breast cancer identified by IHC analysis. The biological reasons for these findings and their implications regarding imaging protocols require further study and may enable improved detection of these lesions.

Predictive value of needle core biopsy diagnoses of lesions of uncertain malignant potential (B3) in abnormalities detected by mammographic screening.

AIMS: Breast needle core biopsy (NCB) is now a commonplace diagnostic procedure in breast cancer screening, providing accurate diagnoses of both benign and malignant lesions. However, NCB may result in the borderline diagnoses of lesion of uncertain malignant potential (B3) or suspicious of malignancy (B4). The aim was to study a large series of B3 cases from population-based screening subjects in order to evaluate positive predictive values (PPVs) for malignancy. METHODS AND RESULTS: The results of 523 NCBs of women screened over a 7-year period (1999-2006) in the East Midlands region, UK, with a B3 diagnosis who underwent surgical excision, were reviewed and compared with the final excision histology. Five percent of NCBs were reported as B3. The most frequent histological subtypes were atypical intraductal epithelial proliferation (AIDEP) and radial scar/complex sclerosing lesion (RS/CSL). Final excision histology was benign in 417 (80%) and malignant in 106 (20%) subjects (60 ductal carcinoma in situ and 46 invasive carcinoma). Lesion-specific PPVs were as follows: AIDEP 32%; lobular neoplasia (LN) 30%; RS/CSL with AIDEP or LN 24%; RS/CSL without atypia 9%; papillary lesion with AIDEP or LN 36%; and papillary lesion without atypia 4%. Five of the 32 fibroepithelial lesions with cellular stroma were phyllodes tumours (four benign and one borderline). None of the five mucinous lesions on NCB was malignant. CONCLUSIONS: Our results show that approximately one-fifth of NCB of screen-detected breast lesions classified as B3 are malignant on excision, and the likelihood of malignancy varies substantially between different histological subtypes.

The significance of lobular neoplasia on needle core biopsy of the breast.

The management of a core biopsy diagnosis of lobular neoplasia is controversial. Detailed radiological-pathological review of 47 patients with cores showing classical lobular neoplasia was performed (patients with pleomorphic lobular carcinoma in situ (LCIS) or associated risk lesions were considered separately). Immediate surgical excision in 25 patients showed invasive carcinoma in 7, ductal carcinoma in situ (DCIS) in 1 and pleomorphic LCIS in 1; radiological-pathological review showed that the core biopsy missed a mass in 5, missed calcification in 2 and that calcification appeared adequately sampled in 2. Nineteen patients had follow-up of at least 2 years. Four patients developed malignancy at the site of the core biopsy (invasive carcinoma in three, DCIS in one); one carcinoma was mammographically occult, one patient had dense original mammograms and two had calcifications apparently adequately sampled by the core. In conclusion, most carcinomas identified at the site of core biopsy showing lobular neoplasia were the result of the core missing the radiological lesion, emphasising the importance of multidisciplinary review and investigation of any discordance. Some carcinomas were found after apparently adequate core biopsy, raising the question of whether excision biopsy should be considered after all core biopsy diagnoses of lobular neoplasia.

Can computerised tomography replace bone scintigraphy in detecting bone metastases from breast cancer? A prospective study.

BACKGROUND: The aim of this study was to determine whether bone scans (BS) can be avoided if pelvis was included in CT thorax and abdomen to detect bony metastases from breast cancer. MATERIALS AND METHODS: Results of 77 pairs of CT (thorax, abdomen, and pelvis) and BS in newly diagnosed patients with metastatic breast cancer (MBC) were compared prospectively for 12 months. Both scans were blindly assessed by experienced radiologists and discussed at multidisciplinary team meetings regarding the diagnosis of bone metastases. RESULTS: CT detected metastatic bone lesions in 43 (98%) of 44 patients with bone metastases. The remaining patient had a solitary, asymptomatic bony metastasis in shaft of femur. BS was positive in all patients with bone metastases. There were 11 cases of false positive findings on BS. CONCLUSION: Our findings suggest routine BS of patients presenting with MBC is not required if CT (thorax, abdomen, and pelvis) is performed.

Primary cutaneous mucormycosis in a lung transplant recipient: case report and concise review of the literature.

Mucormycosis (zygomycosis) is an invasive, opportunistic fungal infection caused by organisms of the class Zygomycetes. Immunocompromised individuals, including both solid organ and hematopoietic stem cell transplant recipients, are preferentially affected. Among solid organ transplant (SOT) recipients, the sinuses, with or without involvement of the orbits and cerebrum, are the most common sites of disease, although the pulmonary allograft appears to be targeted following lung transplantation. Here, we describe the unique case of a lung transplant recipient who developed multifocal cutaneous mucormycosis without involvement of the pulmonary allograft, and review the published literature regarding incidence, treatment, and prognosis of primary cutaneous mucormycosis following SOT.

Peritoneal keratin granulomas complicating endometrial carcinoma: a report of two cases and review of the literature.

Squamous differentiation in endometrial adenocarcinoma is common. Rarely, it may be complicated by peritoneal keratin granulomas. Keratin granulomas accompanied by viable adenocarcinoma cells are regarded as conventional metastatic foci. However, the significance of keratin granulomas without accompanying viable adenocarcinoma cells is difficult to ascertain. Only a small number of cases with significant follow up are documented in the literature. We present two cases of peritoneal keratin granulomas, review the literature and discuss the significance of these lesions.

The mammographic correlations of a new immunohistochemical classification of invasive breast cancer.

AIM: Recent protein expression profiling of breast cancer has identified specific subtypes with clinical, biological, and therapeutic implications. The aim of this study was to identify the mammographic correlates of these novel molecular classes of invasive breast cancer. MATERIALS AND METHODS: The mammographic findings of 415 patients with operable breast cancer were correlated with the previously described protein expression classes identified by our group using immunohistochemical (IHC) assessment of a large series of breast cancer cases prepared as tissue microarrays (TMAs). Twenty-five proteins of known relevance in breast cancer were assessed, including hormone receptors, HER-2 status, basal and luminal markers, p53 expression, and E-cadherin. RESULTS: The mammographic background pattern and proportion of lesions that were mammographically occult were similar in all groups. Groups characterized by luminal and hormone receptor positivity had significantly more spiculate lesions at mammography. Groups characterized by HER-2 overexpression, basal characteristics, and E-cadherin positivity had a significantly higher proportion of ill-defined masses. These findings were independent of histological grade. CONCLUSION: The mammographic features of breast cancer show significant correlation with molecular classes of invasive breast cancer identified by protein expression IHC analysis. The biological reasons for the findings and implications of these regarding imaging protocols require further study and may provide mechanisms for improvement of detection of these lesions.

The influence of basal phenotype on the metastatic pattern of breast cancer.

AIMS: To assess whether basal phenotype influences the metastatic pattern and survival in patients with metastatic breast cancer. MATERIALS AND METHODS: The basal phenotype status of a well-characterised series of consecutive primary operable breast cancers (1868 cases) was ascertained using the basal cytokeratin markers CK5/6 and CK14. Follow-up data, including time, site and pattern of distant metastasis and post-metastasis survival, were available for 113 women with basal phenotype cancers and they were compared with 178 matching cases from women in the non-basal phenotype group. RESULTS: Patients with basal phenotype were more likely to present with intrapulmonary (25/48, [52%] vs 15/64, [23%]; P=0.0009) and/or brain metastases (20/113, [18%] vs 3/178, [2%]; P<0.0001) than non-basal phenotype patients. Patients with non-basal phenotype were more likely to present with bone metastases in the absence of visceral disease (48/102, [47%] vs 14/62, [23%]; P=0.0017) than patients with basal phenotype. There was no significant difference in the frequency of pleural or liver metastases between both groups. Basal phenotype was also associated with a shorter median survival with metastatic disease (10.1 months vs 25 months, P<0.001). The multivariate analysis, including other established prognostic variables in breast cancer, showed that basal phenotype is an independent poor prognostic factor. CONCLUSION: Intrapulmonary and brain metastases are seen more frequently at metastatic presentation in basal phenotype breast cancer patients, and the basal phenotype is associated with a poorer survival after metastatic presentation. Assessment of basal cytokeratin expression status may provide valuable prognostic information relevant to breast cancer patients' management.

Transorbital puncture for the treatment of cavernous sinus dural arteriovenous fistulas.

This report describes a series of patients for whom dural arteriovenous fistulae (DAVFs) of the cavernous sinus were successfully embolized using a percutaneous, transorbital technique to directly cannulate the cavernous sinus. A vascular access needle and catheter are percutaneously advanced along the inferolateral aspect of the orbit to access the cavernous sinus via the superior orbital fissure. Safe and effective embolization is achieved without the need for a surgical cut-down.

How relevant is breast cancer screening in the Asia/Pacific region?

Nationwide breast cancer screening with mammography is well-established in many western countries. Many studies have shown its benefit in mortality reduction. However, breast cancer screening in Asia has been slow to implement, as it was perceived that the breast cancer incidence was low and the parenchyma of Asian women was difficult to assess mammographically. With changing disease patterns, breast cancer is now one of the most common cancers amongst women in Asia. Breast cancer screening has become an important and relevant health problem. However, apart from biological differences between western and Asian women, cultural and economic considerations need to be addressed. This paper looks at the various issues pertaining to the feasibility and relevance of population-based screening in the Asia/Pacific region.

Basal phenotype: a powerful prognostic factor in small screen-detected invasive breast cancer with long-term follow-up.

OBJECTIVE: To assess the frequency and prognostic significance of a basal phenotype in a group of women with screen-detected invasive breast cancers with long-term follow-up and to focus particularly on women with small ( < 15 mm) breast cancers. METHODS: The study group was derived by finding women common to a consecutive series of 1944 invasive breast cancers diagnosed in Nottingham between 1986 and 1998 with a known basal phenotype status and a prospectively collected database of all screen-detected breast cancers. In total, 356 women constituted the study group. Pathological and radiological features were recorded. Basal cell markers used were CK5/6 (cloneD5/16134) and CK14 (clone LL002). Tumours were classified as of basal phenotype if > or = 10% staining was seen with either marker. RESULTS: Of all screen-detected lesions, 43 (12%) had a basal immunophenotype and 313 (88%) were non-basal. There were 15 (35%) and 40 (13%) breast cancer deaths in the basal group and nonbasal groups, respectively ( P = 0.0006). On univariate analysis, nodal stage, histological grade, lympho-vascular invasion (LVI) status, invasive size and basal phenotype had prognostic significance. On multivariate analysis, basal phenotype, LVI and nodal stage maintain prognostic significance. Of the 189 women with < 15 mm lesions, eight of 20 (40%) of the basal group and eight of 169 (5%) of the non-basal group died of breast cancer ( P < 0.0001). On multivariate analysis, basal phenotype was the only factor to maintain independent prognostic significance. CONCLUSIONS: Basal phenotype is a powerful prognostic factor for women with small screen-detected invasive breast cancer.