Review of axillary lesions, emphasising some distinctive imaging and pathology findings.

The axilla is often included on mammography, ultrasound (US), CT and MRI. Axillary masses can arise from any of the tissue components present in this region including breast parenchyma. Aetiologies include: lymphadenopathy due to inflammation, malignancy and degenerative causes; soft tissue tumours such as haemangioma, lymphangioma, peripheral nerve sheath tumours and lipomas; post-surgical complications such as seroma, lymphocoele and haematoma; lesions arising in accessory breast tissue such as fibroadenoma and carcinoma. Some of these entities have distinctive imaging appearances knowledge of which can be helpful in suggesting the correct diagnosis.

Inflammatory breast disease: A pictorial essay with radiological-pathological correlation.

Inflammatory conditions of the breast are an important group of diseases that can mimic breast carcinoma on clinical and radiological grounds. This pictorial essay presents the radiological and pathological features of some of these entities.

Malignant hyperechoic breast lesions at ultrasound: A pictorial essay.

Malignant breast lesions are typically hypoechoic at sonography. However, a small subgroup of hyperechoic malignant breast lesions is encountered in clinical practice. We present a pictorial essay of a number of different hyperechoic breast malignancies with mammographic, sonographic and histopathologic correlation. Suspicious sonographic features in a hyperechoic lesion include inhomogeneity in echogenic pattern, an irregular margin, posterior acoustic shadowing and internal vascularity. A hyperechoic lesion at ultrasound does not discount the need to undertake histological assessment of a mammographically suspicious lesion.

Screen-detected breast carcinoma with macroscopic dystrophic calcification: A pictorial essay with radiolological pathological correlation.

Breast calcifications are among the most common abnormal radiographic findings detected at screening mammography. This essay illustrates the clinico-pathological features of nine screen-detected breast carcinomas, which had benign-appearing macrocalcifications, as a radiographically dominant presenting feature. We aimed to demonstrate that benign-appearing calcifications within a breast lesion are not diagnostic of a benign process if the other imaging characteristics of the lesion are suspicious of malignancy.

Review of ultrasound appearance in inflammatory breast cancer: A pictorial essay.

Inflammatory breast cancer (IBC) is a rare malignancy accounting for 1-2% of breast cancers. It has an aggressive clinical presentation and poor prognosis. The sonographic findings in 41 patients with a clinical diagnosis of IBC and biopsy-proven breast malignancy are presented in this study. The most common finding was the presence of skin thickening (92%). Multiple small anechoic spaces within the dermis, correlating with the presence of dermal lymphatic invasion by tumour emboli on histopathology were noted in approximately one-third of cases. Other sonographic findings included single or multiple masses, parenchymal oedema, axillary lymphadenopathy, echogenic foci consistent with microcalcifications and increased vascularity.

Clinical and imaging features of male breast disease, with pathological correlation: a pictorial essay.

The majority of male breast diseases are benign. The most common is gynaecomastia. Although it is rare, the most critical diagnosis is a malignancy. Radiologists are generally less familiar with breast disease in males compared with females. This pictorial review will highlight the ultrasonographic, mammographic and pathological features of a spectrum of benign and malignant male breast diseases. This includes gynaecomastia, fat necrosis, lipoma, epidermoid cyst, subareolar abscess, chronic inflammation, melanoma and ductal carcinoma.

Nipple discharge in a screening programme: imaging findings with pathological correlation.

BreastScreen Australia provides free mammographic screening for asymptomatic women over the age of 40, targeting women aged 50-69. Occasionally women will present to screening programmes with a history of nipple discharge, which is uncommonly associated with significant underlying breast disease. Seventy-six women with a history of nipple discharge were recalled to BreastScreen Western Australia assessment centres from 2004 to 2008, of whom 72 were recalled primarily for their symptoms. Thirty-six of these patients had pathology investigations, including 18 nipple discharge smears, 17 fine needle aspirations, 11 core biopsies and eight surgical biopsies or therapeutic resections. The biopsies found 11 intraduct papillomas and one invasive ductal carcinoma with ductal carcinoma in situ. Fourteen patients had imaging findings consistent with benign mammary duct ectasia. Our findings confirm that the presentation of nipple discharge in a screening programme is uncommonly associated with significant breast disease, and present representative cases of the radiological findings with pathological correlation of benign and malignant causes including mammary duct ectasia, intraduct papillomas, multiple papillomas, invasive ductal carcinoma and ductal carcinoma in situ.

Audit of paired anal cytology and histopathology outcomes in patients referred to a public sexual health clinic.

BACKGROUND: The level of agreement between anal cytology and histopathology is not clear with only a few studies evaluating the reliability of anal specimen reporting. Australian data in relation to this are limited. METHODS: The results of paired anal cytology and histopathology specimens received between 2002 and 2008 from patients who were referred within the sexual health clinic were retrieved from the anatomical pathology database. A total of 248 paired samples from 154 (21 females, 133 males) participants were extracted. Concurrent high risk human papilloma virus (hrHPV) DNA assay and HIV status for the study group were also collected. Data were tabulated according to reported grade of squamous abnormality based on the Bethesda system. Using the biopsy result as the gold standard the specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) for cytology were calculated and the association between grade of abnormality, HIV status and hrHPV infection estimated. RESULTS: Concordance between cytology and histology showed that in 204 (85%) paired samples both tests were categorised as abnormal (Kappa statistic 0.73, P = 0.013). The cytology result showed a sensitivity of 96%, specificity 14%, PPV 89% and NPV 31% when compared with histopathology. HrHPV assay was positive in 192 (80%) samples. High-grade squamous abnormalities were reported in biopsy specimens from 60% (n = 42/67) of HIV-positive subjects and 25% (n = 22/87) of HIV-negative subjects. HIV-positive individuals were more likely to be hrHPV positive, odds ratio (OR) 6.21 [95% confidence interval (CI) 2.69 to 14.34], when compared with HIV-negative subjects. CONCLUSION: Anal cytology is highly sensitive for the detection of abnormal squamous cells. While cytology has low specificity for predicting the grade of abnormality compared with biopsy outcome, its application as a screening method in asymptomatic at risk populations warrants further study.

Interferon-induced thyroid dysfunction in chronic hepatitis C.

BACKGROUND: Treatment of chronic hepatitis C with interferon is known to be associated with thyroid dysfunction (TD) in 5-14% of patients. We studied the incidence, types, outcome and risk factors predictive of thyroid dysfunction. METHODS: A retrospective analysis was performed on all patients treated with interferon alpha (IFN) or pegylated interferon alpha (PEG-IFN) +/- ribavirin (RBV), who developed abnormal thyroid function tests (TFTs). These cases were compared with treatment-matched controls to identify factors predictive of thyroid dysfunction. Statistical methods consisted of: chi(2) test, Fischer's exact test, Welch's t-test, and multivariate analysis. RESULTS: From a total of 511 patients, 45 cases with TD were identified (8.8%). Pegylated interferon alpha was associated with higher rates of TD than IFN (14.1% vs 6.0%, P = 0.0029). Female sex (OR 5.6, 95% CI 1.1-7) and Asian ethnicity (OR 2.7, 95% CI 1.4-22) were independent predictors of developing TD. Cytology was obtained in 13 patients: benign follicular pattern (8); thyroiditis (3); and normal (2). Thyroid peroxidase (TPO) antibodies (P = 0.004) and earlier onset of dysfunction (P = 0.03) were associated with need for treatment. Sixteen patients had persistent TD by the end of the follow-up period, predicted by female sex, non-Asian ethnicity, prior history of TD and TPO antibodies. CONCLUSIONS: Pegylated interferon alpha, female sex and Asian ethnicity are independent risk factors for TD. Thyroid peroxidase antibodies and earlier TD within the course of IFN are associated with the requirement for treatment. Thyroid function tests should be monitored during and after IFN-based therapy. The most common cytological finding is a benign follicular pattern.

Multiple papillomas of the breast: is current management adequate?

Multiple papillomas (MP) are subject to debate in terms of their clinical and pathological significance and management. To date the ideal management is still not well established. The Royal Perth Hospital Multidisciplinary Breast Service has prospectively accrued clinical and pathological data on over 9000 patients since 1994. The database was interrogated and all pathology reports retrospectively reviewed. A total of 23 cases with the diagnosis of MP were retrieved from the database between 1994 and 2004. Of these 23 cases, 13 (56.5%) were diagnosed by core biopsy, nine (39.1%) on excision biopsy, and one (4.4%) on a mastectomy specimen. The average age of patients was 56.4 years (range 44-74 years). The average duration of follow up is 4.1 years (range 1-10 years). In our series a close association with malignancy was noted for MP, which was also associated with a spectrum of proliferative breast disease. Contemporary guidelines should be developed for this controversial condition. We recommend that all patients with MP, especially when associated with atypia, undergo wide excision of the lesion with clear margins of at least 10mm and that these patients be monitored closely with annual imaging.

SLIRP, a small SRA binding protein, is a nuclear receptor corepressor.

Steroid receptor RNA activator (SRA), the only known RNA coactivator, augments transactivation by nuclear receptors (NRs). We identified SLIRP (SRA stem-loop interacting RNA binding protein) binding to a functional substructure of SRA, STR7. SLIRP is expressed in normal and tumor tissues, contains an RNA recognition motif (RRM), represses NR transactivation in a SRA- and RRM-dependent manner, augments the effect of Tamoxifen, and modulates association of SRC-1 with SRA. SHARP, a RRM-containing corepressor, also binds STR7, augmenting repression with SLIRP. SLIRP colocalizes with SKIP (Chr14q24.3), another NR coregulator, and reduces SKIP-potentiated NR signaling. SLIRP is recruited to endogenous promoters (pS2 and metallothionein), the latter in a SRA-dependent manner, while NCoR promoter recruitment is dependent on SLIRP. The majority of the endogenous SLIRP resides in the mitochondria. Our data demonstrate that SLIRP modulates NR transactivation, suggest it may regulate mitochondrial function, and provide mechanistic insight into interactions between SRA, SLIRP, SRC-1, and NCoR.

Mitochondrial DNA depletion and morphologic changes in adipocytes associated with nucleoside reverse transcriptase inhibitor therapy.

BACKGROUND: Nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy provides sufficient conditions for progressive subcutaneous fat wasting in HIV-infected patients. As NRTI-induced host toxicity is proposed to involve cellular mitochondrial DNA (mtDNA) depletion, determinants of cellular mtDNA copy number and mitochondrial mass in adipocyte samples from NRTI-treated HIV-infected patients and antiretroviral-naive controls were investigated. Adipose tissue morphology was also assessed. METHODS: Subcutaneous fat samples were obtained from NRTI-treated, HIV-infected patients (n = 21), antiretroviral therapy-naive HIV-infected controls (n = 11), and HIV-seronegative controls (n = 6). Non-adipocytes were removed by collagenase digestion. Adipocyte mtDNA copies/cell was measured using a real time PCR-based assay, and adipocyte mitochondrial protein content was also measured. Light and electron microscopy were performed on tissue samples. FINDINGS: Adipocyte mtDNA copies/cell values were similar (P = 0.56) in HIV seronegative and HIV-infected control groups. NRTI treatment was associated with reduced adipocyte mtDNA copies/cell, representing mean mtDNA depletion in NRTI-treated individuals of 77.7% compared with the mean value for the HIV-infected control group (P < 0001). Additionally, significant differences were found in adipocyte mtDNA copies/cell between patients receiving stavudine (n = 12, mean mtDNA depletion 87.1%) and zidovudine (n = 9, mean mtDNA depletion 52.1%) (P < 0.001). Adipocyte mitochondrial mass was increased in the stavudine group only (mean increase 289%, P < 0.01). INTERPRETATION: NRTI therapy is associated with mtDNA depletion and mitochondrial proliferation in adipocytes, consistent with the hypothesis that NRTI-induced mtDNA depletion contributes to the pathogenesis of subcutaneous fat wasting. Morphologic assessment also supports a role for NRTI therapy in inducing adipocyte metabolic dysfunction and cell death.

Histologic analysis of liver tissue following hepatic arterial infusion of ferromagnetic particles in a rabbit tumour model.

It is possible to arterially embolize liver tumours in small animal models with ferromagnetic particles that generate hysteretic heating on exposure to an alternating magnetic field. The aim of this study was to determine the response of hepatic tissue to arterial infusion of ferromagnetic particles. Eight rabbits containing hepatic VX2 carcinomas received a hepatic arterial infusion of ferromagnetic particles suspended in lipiodol. Four rabbits were sacrificed after 60 min to determine the acute tissue response, and the other four rabbits were sacrificed after 14 days to determine the longer-term tissue response. The tumour, normal hepatic parenchyma (NHP), lungs and gallbladder of each subject were examined using light microscopy, and chemically analysed for iron concentration. Large aggregates of particles embolized within the tumour vasculature. There was only a sparse distribution of particles in the NHP, with no acute tissue response. The tumour to NHP iron concentration ratio was 4.9. Particles also lodged in blood vessels of the gallbladder wall. Two weeks after infusion there were isolated foci of necrosis in the NHP, and macrophages were associated with particle aggregates, which were also observed within multinucleated giant cells. There was no evidence that particles embolized in the lungs. Hepatic arterial infusion of ferromagnetic particles suspended in lipiodol resulted in excellent tumour targeting with no acute tissue reaction in the NHP, and no evidence of pulmonary embolization. After 14 days there was evidence of phagocytosis of the particles in NHP, but not in the tumour tissue. However, the suspension caused multiple foci of infarction in NHP, probably due to occlusion of larger arteries.

An evidence-based specialist breast nurse role in practice: a multicentre implementation study.

The objective of this study was to examine the feasibility, implementation, acceptability and impact of an evidence-based specialist breast care nurse (SBN) model of care in Australia. Primary data were collected from four diverse Australian breast cancer treatment centres over a 12-month period. The design was a multicentre demonstration project. Information about the provision of care and patient needs was collected through prospective logs. Structured interviews were conducted with women who received the SBN intervention (N = 167) and with a control group of women treated prior to the intervention period (N = 133). Health professionals (N = 47) were interviewed about their experience of the SBN. Almost all women had contact with an SBN at five scheduled consultations and 67% of women in the intervention group requested at least one additional consultation with the SBN. Women in the intervention group were more likely to receive hospital fact sheets and to be told about and participate in clinical trials. Ninety-eight per cent of women reported that the availability of an SBN would affect their choice of hospital, with 48% indicating that they would recommend only a hospital with a SBN available. Health professionals reported that SBNs improved continuity of care, information and support for the women, and resulted in more appropriate referrals and use of the time of other members of the team. In conclusion, the SBN model is feasible and acceptable within diverse Australian treatment centres; there is evidence that some aspects of care were improved by the SBN.