Cecily Metcalf

Reduction of mitochondrial DNA content and respiratory chain activity occurs in adipocytes within 6-12 months of commencing nucleoside reverse transcriptase inhibitor therapy

Mitochondrial enzyme activity was assessed in adipocytes from seven patients initiating nucleoside reverse transcriptase inhibitor (NRTI) regimens. After 6-12 months of therapy, adipocytes from six patients demonstrated cytochrome C oxidase (COX) activity reduced from baseline, correlating positively with mitochondrial DNA levels, concomitant with evidence of cellular toxicity. Three patients also showed reduced expression of COX subunit I. This is the first study to demonstrate that NRTI-associated mtDNA depletion in adipocytes impacts functionally on mitochondrial respiratory proteins in vivo.

Loss of heterozygosity on chromosome 2q: possibly a poor prognostic factor in head and neck cancer.

Loss of heterozygosity (LOH) correlates with inactivated tumor suppressor genes. The aim of this study was to see if LOH on chromosomes 2q, 3p, 5q, 9p, and 17p correlated with survival in early squamous cell carcinoma of the head and neck (SCCHN).

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.

Male breast ductal carcinoma in situ.

A 35-year-old male presented to his local general practitioner with breast discomfort and nipple discharge. His symptoms had begun 5 months prior to his ultimate surgery. He noticed a degree of swelling in the left breast region and a blood stained discharge from one duct. There was no history of trauma or infection in the region. He had no significant past medical or drug history. His mother had died at 45 years from breast cancer. A maternal aunt had also been diagnosed with breast cancer aged 56. A maternal cousin was diagnosed and undergoing treatment for breast cancer aged 37. There was no history of breast cancer affecting the maternal or paternal grandfather. The patient was unmarried with no children (Fig. 1). On examination he had a slight diffuse swelling of the breast and haemoserous nipple discharge from one duct. There was no associated axillary lymphadenopathy or any concerning features in the other breast. Cytological examination of the discharge showed papillary aggregates of epithelial cells exhibiting mild disorganization and moderate anisonucleosis with red cells and macrophages, findings suggestive of an intraduct papilloma. A microdochectomy was performed. The pathology revealed an intraduct proliferation of tumour cells filling multiple dilated ducts (Fig. 2). The cells were intermediate in size with mildly pleomorphic nuclei and scant to moderate amounts of cytoplasm (Fig. 2). The predominant pattern was a solid papillary proliferation with compressed epithelium and fibrovascular cores. A smaller component was largely solid with very occasional glands. A few aggregates of foam cells occurred within the tumour. In some ducts, an accumulation of proteinaceous material often associated with blood was seen.

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.

EGFR mutation testing in NSCLC: Patterns of care and outcomes in Western Australia

Aims:  This study evaluated the EGFR mutation status, administration of gefitinib or erlotinib and outcomes of patients assessed for EGFR mutations since the commencement of testing in Western Australia.

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.

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.