Soh S.-B.,Anatomical Pathology |
Pham A.,Anatomical Pathology |
O'Hehir R.E.,Monash University |
Cherk M.,Nuclear Medicine Alfred |
And 3 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013
A 42-year-old woman presented with a rapidly enlarging right-sided thyroid mass and underwent hemithyroidectomy. Riedel's thyroiditis was only diagnosed upon surgical decompression of the right carotid artery 2 years later. She became more symptomatic as Riedel's thyroiditis progressed, and mediastinal fibrosclerosis developed over the next 12 months. Oral prednisolone failed to improve her condition, and she was commenced on tamoxifen. Despite initial improvement, her symptoms recurred 2 years later, mainly arising from compression of the trachea and esophagus at the thoracic inlet. Fluorodeoxyglucose positron emission tomographic scan showed locally advanced active invasive fibrosclerosis in the neck and mediastinum. An elevated activin-A level of 218 pg/mL was consistent with active inflammation. IgG subtypes (including IgG4) were normal. Two courses of iv methylprednisolone were given but only produced transient improvement. Subsequently, the patient received 3 doses of iv rituximab at monthly intervals and had prompt sustained symptomatic improvement. Activin-A level decreased to 122 pg/mL 10 months after rituximab therapy. Fluorodeoxyglucose positron emission tomographic scan 6 weeks after therapy showed reduction in inflammation. A further scan at 10 months demonstrated ongoing response to rituximab. This is a case of refractory Riedel's thyroiditis with symptomatic, biochemical, and radiological improvement that has persisted 14 months after rituximab. The likelihood and duration of response to rituximab in Riedel's thyroiditis requires further study. Copyright © 2013 by The Endocrine Society.
Gill A.J.,Royal North Shore Hospital |
Gill A.J.,University of Sydney |
Benn D.E.,University of Sydney |
Chou A.,Royal North Shore Hospital |
And 7 more authors.
Human Pathology | Year: 2010
Up to 30% of pheochromocytomas and paragangliomas are associated with germline RET, Von Hippel-Lindau (VHL), neurofibromatosis type I (NF1), and succinate dehydrogenase subunits (SDHB, SDHC, and SDHD) mutations. Genetic testing allows familial counseling and identifies subjects at high risk of malignancy (SDHB mutations) or significant multiorgan disease (RET, VHL, or NF1). However, conventional genetic testing for all loci is burdensome and costly. We performed immunohistochemistry for SDHB on 58 tumors with known SDH mutation status. We defined positive as granular cytoplasmic staining (a mitochondrial pattern), weak diffuse as a cytoplasmic blush lacking definite granularity, and negative as completely absent staining in the presence of an internal positive control. All 12 SDH mutated tumors (6 SDHB, 5 SDHD, and 1 SDHC) showed weak diffuse or negative staining. Nine of 10 tumors with known mutations of VHL, RET, or NF1 showed positive staining. One VHL associated tumor showed weak diffuse staining. Of 36 tumors without germline mutations, 34 showed positive staining. One paraganglioma with no known SDH mutation but clinical features suggesting familial disease was negative, and one showed weak diffuse staining. We also performed immunohistochemistry for SDHB on 143 consecutive unselected tumors of which 21 were weak diffuse or negative. As SDH mutations are virtually always germline, we conclude that approximately 15% of all pheochromocytomas or paragangliomas are associated with germline SDH mutation and that immunohistochemistry can be used to triage genetic testing. Completely absent staining is more commonly found with SDHB mutation, whereas weak diffuse staining often occurs with SDHD mutation. Crown Copyright © 2010.
Al-Odat I.,University of Technology, Sydney |
Al-Odat I.,Kolling Institute |
Chen H.,University of Technology, Sydney |
Chan Y.L.,University of Technology, Sydney |
And 5 more authors.
PLoS ONE | Year: 2014
This study aimed to investigate whether maternal cigarette smoke exposure can disrupt fetal kidney development by changing the expression of growth and transcription factors essential for renal development, and thereafter predispose the offspring to chronic kidney disease later in life. Female Balb/c mice (6 weeks) were exposed either to cigarette smoke or air under identical conditions, 6 weeks prior to mating, during gestation and during lactation. Male offspring were sacrificed at three time points, postnatal day (P)1, P20 (weaning age), and 13 weeks (mature age). Blood, urine, and kidneys were collected for analysis. At P1, the developmental genes fibroblast growth factor 2, glial cell-line derived neurotrophic factor and paired box 2 were upregulated at mRNA and protein levels; whilst fibroblast growth factor (FGF) 7 and FGF10 were downregulated. At P20, mRNA expression of FGF2, FGF10 and Wingless-type 4 was upregulated by maternal smoke exposure. These changes were normalised in adulthood. Nephron development was delayed, with fewer nephron numbers from P1 persisted to adulthood; while glomerular volume was increased at P20 but reduced in adulthood. Pro-inflammatory marker monocyte chemoatractant protein 1 (MCP1) was increased in the kidney by maternal smoke exposure. These changes were accompanied by an increased albumin/creatinine ratio in adulthood, suggesting reduced renal dysfunction. In conclusion maternal cigarette smoke exposure prior to and during pregnancy, as well as lactation leads to significant renal underdevelopment and functional abnormalities in adulthood. This study confirms the hypothesis that maternal smoking predisposes offspring to chronic kidney disorders. © 2014 Al-Odat et al.
Assi K.,University of British Columbia |
Bergstrom K.,Child and Family Research Institute |
Vallance B.,Child and Family Research Institute |
Owen D.,Anatomical Pathology |
Salh B.,University of British Columbia
BMC Gastroenterology | Year: 2013
Background: Integrin-linked kinase (ILK) is a serine-threonine kinase that transduces extracellular matrix-related cues into intracellular signals, with fundamental roles in cell motility, development and cancer. Recently ILK been shown to have an important role in bacterial epithelial cell attachment, through ILK-bacterial OspE binding. Here we report on the role of epithelial derived ILK in response to Citrobacter rodentium infection. Methods: C. rodentium was administered to both control and intestinal epithelial cell ILK knockout mice. Histological inflammatory scores were assessed, and cytokines measured by ELISA as well as RT-PCR, in mouse colons. Bacterial colonization was determined by plating homogenates onto MacConkey agar, and immunofluorescence microscopy performed using anti-LPS and anti-Tir antibodies. Results: ILK-ko mice exhibited reduced weight loss at 15 days post-infection (p < 0.01) and demonstrated reduced histological inflammatory scores (p < 0.01), reduced CCL2 and pro-inflammatory cytokines. This was not due to reduced colonization, but was associated with an altered pattern of C. rodentium bacterial migration. Attenuated fibronectin expression was found in the ILK-ko mice. C. rodentium exposure was shown to increase ILK expression in cell lines, and in murine epithelium in vivo. In ILK-ko mice reduced activation of ser473Akt and reduced crypt proliferation, together with reduced cyclin D1 expression were observed. Conclusions: ILK influences the host response to C. rodentium -induced infection, independently of reduced colonization in the ILK knockout mice. The reduced inflammation and dramatically attenuated hyperplastic cryptal response to infection in this group, are at least in part the result of, the reduction in CCL2 and cyclin D1 expression respectively. © 2013 Kiran et al.; licensee BioMed Central Ltd.
PubMed | QIMR Berghofer Medical Research Institute, Queensland Medical Laboratory and Anatomical Pathology
Type: Journal Article | Journal: The Journal of investigative dermatology | Year: 2016
Cutaneous melanomas arise through causal pathways involving interplay between exposure to UV radiation and host factors, resulting in characteristic patterns of driver mutations in BRAF, NRAS, and other genes. To gain clearer insights into the factors contributing to somatic mutation genotypes in melanoma, we collected clinical and epidemiologic data, performed skin examinations, and collected saliva and tumor samples from a community-based series of 414 patients aged 18 to 79, newly diagnosed with cutaneous melanoma. We assessed constitutional DNA for nine common polymorphisms in melanocortin-1 receptor gene (MC1R). Tumor DNA was assessed for somatic mutations in 25 different genes. We observed mutually exclusive mutations in BRAF(V600E) (26%), BRAF(V600K) (8%), BRAF(other) (5%), and NRAS (9%). Compared to patients with BRAF wild-type melanomas, those with BRAF(V600E) mutants were significantly younger, had more nevi but fewer actinic keratoses, were more likely to report a family history of melanoma, and had tumors that were more likely to harbor neval remnants. BRAF(V600K) mutations were also associated with high nevus counts. Both BRAF(V600K) and NRAS mutants were associated with older age but not with high sun exposure. We also found no association between MC1R status and any somatic mutations in this community sample of cutaneous melanomas, contrary to earlier reports.
Day T.,John Hunter Hospital |
Scurry J.,Anatomical Pathology
Journal of Lower Genital Tract Disease | Year: 2014
OBJECTIVE: To report a case of isolated vulvar pityriasis versicolor in a 24-year-old healthy woman. MATERIALS AND METHODS: A 24-year-old woman presented with variable color change on the vulva of 8 months in duration. RESULTS: Areas of tan and white skin were observed on the mons pubis. The pubic hair had been shaved. Initially, the paler areas were deemed abnormal suggesting vitiligo, but the biopsy showed normal skin including normal numbers of melanocytes. Subsequently, biopsy of the tan area showed pityriasis versicolor. She was successfully treated with topical 2% ketoconazole, with gradual fading of lesions. CONCLUSIONS: With increased body awareness and the current popularity of pubic hair removal, young women may consult clinicians about color changes on the vulva. Clinicians should be aware that vulvar pityriasis versicolor may occur in healthy women with no other skin involvement. © 2014, American Society for Colposcopy and Cervical Pathology.
Brokenshire C.,University of Newcastle |
Pagano R.,Royal Womens Hospital |
Scurry J.,Anatomical Pathology
Journal of Lower Genital Tract Disease | Year: 2014
OBJECTIVE: This study aimed to determine whether histology can predict response to vestibulectomy in the management of provoked vestibulodynia. MATERIALS AND METHODS: Inflammatory cell, mast cell, and nerve fiber counts were determined in prospectively collected vulvar vestibulectomy specimens from 30 women treated surgically for provoked vestibulodynia. RESULTS: Twenty-three subjects (77%) had a complete early response to surgery. At 3 years of follow-up, this had increased to 28 (93%), with a 29th showing some improvement. No subject had gotten worse after surgery or in the 3 years of follow-up. When comparing patients with an early complete response with those patients who still had symptoms, no difference in lymphocyte counts (27.6 vs. 37.8 per mm), mast cell counts (110.4 vs. 97.8 per mm), or stromal nerve fiber counts (16.4 vs. 16.4 per mm) was found. CONCLUSIONS: Vestibulectomy is a very effective treatment option in women with provoked vestibulodynia who have had failed conservative treatment. Histology is unable to predict which patients will respond to surgery. © 2014, American Society for Colposcopy and Cervical Pathology.
Iacopetta B.,University of Western Australia |
Grieu F.,Anatomical Pathology |
Amanuel B.,Anatomical Pathology
Asia-Pacific Journal of Clinical Oncology | Year: 2010
Approximately 20 percent of right-sided colon cancers and 5 percent of left-sided colon and rectal cancers have a deficient DNA mismatch repair system. This results in the widespread accumulation of mutations to nucleotide repeats, some of which occur within the coding regions of cancer-related genes such as TGFΒRII and BAX. A standardized definition for microsatellite instability (MSI) based on the presence of deletions to mononucleotide repeats is gaining widespread acceptance in both research and the clinic. Colorectal cancer (CRC) with MSI are characterized histologically by an abundance of tumor-infiltrating lymphocytes, poor differentiation and a signet ring or mucinous phenotype. In younger patients these tumors usually develop along the chromosomal instability pathway, in which case the mismatch repair genes are inactivated by germline mutation, somatic mutation and loss of heterozygosity. In older patients MSI CRC usually develops against a background of widespread hypermethylation that includes methylation-induced silencing of the mismatch repair gene MLH1. The overall biological and clinical phenotype of MSI CRC that arise in these two pathways is likely to be different and may account for some of the discordant results reported in the literature relating to the clinical properties of these tumors. The available evidence indicates that MSI is unlikely to be a clinically useful marker for the prognostic stratification of early-stage CRC. The predictive value of MSI for response to 5-fluorouracil-based chemotherapy remains controversial, while for other agents the predictive value is difficult to assess because they are used in combination regimens. The MSI phenotype is being actively investigated for novel therapeutic approaches based on the principle of synthetic lethality. Finally, the MSI status of CRC is an extremely useful marker for population-based screening programs that aim to identify individuals and families with the hereditary cancer condition known as Lynch syndrome. © 2010 Blackwell Publishing Asia Pty Ltd.
Yeo J.,Anatomical Pathology |
Winhoven S.,Skin Center |
Tallon B.,Pathlab Bay of Plenty
Journal of Cutaneous Pathology | Year: 2013
Porokeratosis ptychotropica represents a rare and under-recognized variant of porokeratosis. There are also alternative descriptions for this disorder in the literature. Since its original description in 1995, additional characteristic features have been showed in case reports published in the literature. These cumulative reports, although still limited in numbers, have helped to further shape and define this entity. A case report and review of published literature on this unusual entity are presented. The specific combination of clinical, morphological and histopathological characteristics that can facilitate recognition of the disorder is discussed. There has been a call for uniformity in terminology and a suggestion for alternative terminology has been made. However, we discuss why the earlier term, porokeratosis ptychotropica, is still preferred. © 2013 John Wiley & Sons A/S.
Yin J.,Anatomical Pathology |
Lloydd R.,Anatomical Pathology
New Zealand Journal of Medical Laboratory Science | Year: 2014
Melanoma is infamous for its ability to mimic other tumours and metastasise anywhere within the body. Our case, a 67-year-old male patient, presented with an enlarged right axillary lymph node. Fine needle aspiration was performed. Cytological slides showed a rare morphologic variant: mixed spindle cells with nuclear grooves and epithelioid/plasmacytoid cells without macronucleoli. Immunostaining was performed on cell block sections. Tumour cells demonstrated S-100 and Melan-A, and melanoma was diagnosed. Morphologic variants of melanoma can pose a significant challenge to cytological diagnosis, which often requires supplementation using immunocytochemical stains. © 2014 The authors.