Fiona Bonar - Academia.edu (original) (raw)

Papers by Fiona Bonar

In this study we used the Illumina Infinium Methylation array to investigate in a cohort of match... more In this study we used the Illumina Infinium Methylation array to investigate in a cohort of matched archival human tissue samples (n = 32) from 14 individuals with soft tissue sarcomas if genome-wide methylation changes occur during metastatic and recurrent (Met/Rec) disease. A range of sarcoma types were selected for this study: leiomyosarcoma (LMS), myxofibrosarcoma (MFS), rhabdomyosarcoma (RMS) and synovial sarcoma (SS). We identified differential methylation in all Met/Rec matched samples, demonstrating that epigenomic differences develop during the clonal evolution of sarcomas. Differentially methylated regions and genes were detected, not been previously implicated in sarcoma progression, including at PTPRN2 and DAXX in LMS, WT1-AS and TNXB in SS, VENTX and NTRK3 in pleomorphic RMS and MEST and the C14MC / miR-379/miR-656 in MFS. Our overall findings indicate the presence of objective epigenetic differences across primary and Met/Rec human tissue samples not previously reported.

Histopathology

AIMS MDM2 gene amplification, usually detected by fluorescence in situ hybridization (FISH), is t... more AIMS MDM2 gene amplification, usually detected by fluorescence in situ hybridization (FISH), is the key driving event in atypical lipomatous tumours/well-differentiated liposarcomas (ALT/WDL). We sought to determine the concordance between the histopathological findings and MDM2 FISH in the diagnosis of ALT/WDL and to identify the histological features of MDM2 amplified tumours lacking classic atypia. METHODS AND RESULTS We performed a retrospective analysis of all mature lipomatous lesions subjected to MDM2 FISH analysis at our institution. MDM2 FISH analysis was performed on 439 mature lipomatous lesions: 364 (82.9%) were negative and 75 (17%) were positive. In 17/75 (22.6%) ALT/WDLs, cytological atypia was not identified on initial histological assessment, thus favouring lipoma. On review, these cases shared common histological features consisting of a very low number of relatively small stromal cells within the tumour lobules, with mildly coarse chromatin and oval shaped nuclei, admixed with unremarkable adipocytes in a tumour background devoid of fibroconnective septa, areas of fibrosis or blood vessels. These cells matched the cells displaying MDM2 amplification by FISH. In contrast, 13 cases (3.5%) regarded as suspicious for ALT/WDL based on histology, lacked MDM2 amplification and were reclassified following the FISH findings. CONCLUSIONS We conclude that a subset of lipoma-like ALT/WDL is not associated with any of the features typically described in ALT/WDL. Our study also identified that tumours >10cm are more likely to be ALT/WDL, however a history of recurrence or concerning clinical/radiological features was not significantly associated with classification as ALT/WDL.

Skeletal Radiology

Members of the International Skeletal Society compiled a glossary of terms for musculoskeletal ra... more Members of the International Skeletal Society compiled a glossary of terms for musculoskeletal radiology. The authors also represent national radiology or pathology societies in Asia, Australia, Europe, and the USA. We provide brief descriptions of musculoskeletal structures, disease processes, and syndromes and address their imaging features. Given the abundance of musculoskeletal disorders and derangements, we chose to omit most terms relating to neoplasm, spine, intervention, and pediatrics. Consensus agreement was obtained from 19 musculoskeletal radiology societies worldwide.

Pathology

Peutz-Jeghers polyposis syndrome is characterised by pigmented melanotic lesions, hamartomatous g... more Peutz-Jeghers polyposis syndrome is characterised by pigmented melanotic lesions, hamartomatous gastrointestinal polyps and increased risk of multiple cancers, including those of the female genital tract. The genetic defect is autosomal dominant, affecting the STK11 gene, which normally functions as a tumour suppressor. We report the case of a 48-year-old female who presented with dysfunctional uterine bleeding who was found to have a cervical mass, which on resection was diagnosed as minimal deviation adenocarcinoma (adenoma malignum). In addition, there was extensive local involvement and ovarian metastases, with associated concurrent ovarian sex cord tumour with annular tubules.

We assessed the frequency of programmed death-ligand 1 (PD-L1) expression by immunohistochemistry... more We assessed the frequency of programmed death-ligand 1 (PD-L1) expression by immunohistochemistry (IHC) in a cohort of 522 sarcomas from 457 patients, incuding a subset of 46 patients with 63 matched samples from local recurrence or metastases with primary tumours and/or metachronous metastases. We also investigated the correlation of PD-L1 with the presence and degree of tumour-infiltrating lymphocytes (TILs) in a subset of cases. IHC was performed using the PD-L1 SP263 companion kit (VENTANA) on tissue microarrays from an archival cohort. Evaluation of PD-L1 and TILs was performed on full sections for a subset of 23 cases. Fisher’s exact and Mann Whitney test were used to establish significance (P <0.05). PD-L1 positive expression (≥1%) was identified in 31% of undifferentiated pleomorphic sarcomas, 29% of angiosarcomas, 26% of rhabdomyosarcomas, 18% of myxofibrosarcomas, 11% of leiomyosarcomas and 10% of dedifferentiated liposarcomas. Negative expression was present in all aty...

Leukemia & Lymphoma

A 29-year-old female presented with 12months of polyuria, polydipsia, nausea, headaches and worse... more A 29-year-old female presented with 12months of polyuria, polydipsia, nausea, headaches and worsening left hip pain, beginning 7months into her first pregnancy. Galactorrhea persisted after cessation of breastfeeding. Neurological examination including visual fields and extraocular movements was normal. There were no palpable masses, hepatosplenomegaly or lymphadenopathy. Skin was unremarkable although she reported an intermittent blistering rash on her hands. Endocrinological testing revealed diabetes insipidus (DI), hyperprolactinemia and hypogonadotropic hypogonadism. Thyroid function, growth hormone, cortisol, ACTH and short synacthen tests were normal. There was mild normocytic anemia (10.2 g/dL). Biochemistry, renal and liver functions were unremarkable. Treatment was initiated with desmopressin and a combined contraceptive pill. Magnetic resonance imaging (MRI) of the brain demonstrated a 24 22 25mm dural-based lesion eroding through the left frontal bone with central low T1, high T2 signal and peripheral enhancement. The pituitary stalk was thickened and short with absence of the posterior bright spot but no pituitary adenoma. Staging computed tomography (CT) demonstrated a 40 30 20mm lucent lesion in the left ilium. The skull lesion and adherent dura were excised and repaired with a titanium mesh cranioplasty. Histopathological examination showed features of Langerhans cell histiocytosis (LCH) with a proliferation of histiocytic cells with characteristic bean-shaped nuclei and amphophilic cytoplasm amongst an inflammatory background including prominent eosinophils and necrosis. Expression of CD68, S100 and CD1a confirmed the diagnosis. Multinucleated Langerhans cells and foamy histiocytes were not seen. Monthly zoledronic acid infusions were given for 2 years. Six months later she developed right hip pain. Xray and CT showed a right femoral lytic lesion with sclerotic borders, and sclerosis of the left ilium. Positron emission tomography (PET) scan showed increased glucose metabolism (SUV 24.8) in the right femur and anterior left ilium. Internal fixation of the right femur was performed, with histology again typical of LCH. The left iliac lesions were treated with radiofrequency ablation. Despite these measures, PET scan one year later demonstrated progression in the right femoral neck, left ilium and possibly in the vicinity of the left frontal craniectomy. The patient underwent right proximal femur resection and reconstruction. There was a pathological fracture through the subcapital region where a 30 35mm tan soft tissue lesion replaced bone. Surrounding sclerosis was noted. Microscopically, heterogeneous populations of histiocytic cells were seen, all expressing CD68 and CD163 but with variable co-expression of S100, CD1a and Langerin, reflecting a mixed histiocytosis. Characteristic features of LCH predominated (Figure 1(a)). However, in addition there were clusters of cells which had abundant foamy cytoplasm and xanthogranulomatous features. Some were multinucleated and in some there was a wreath-like arrangement of nuclei resembling Touton giant cells of Juvenile Xanthogranuloma (JXG). All expressed CD68 and CD163 and many expressed S100 and weak Langerin, suggestive of dendritic differentiation (Figure 1(b,c)). Similar sheets of foamy histiocytes were present elsewhere expressing CD68 and CD163 but negative for Langerin, CD1a and S100, features characteristic of phagocytic-type histiocytes. There were intermingled cells with abundant pink cytoplasm and intracytoplasmic lymphocytes consistent with emperipolesis. These cells coexpressed CD68, CD163 and S100 but not Langerin and CD1a, a constellation characteristic of Rosai-Dorfman histiocytes (Figure 1(d)). Within the osseous component, particularly in the macroscopically sclerotic region, sheets of largely

Journal of Clinical Oncology

3060 Background: Sarcomas represent 1015% of cancers in adolescent and young adult (AYA) patient... more 3060 Background: Sarcomas represent 1015% of cancers in adolescent and young adult (AYA) patients, and survival for those with metastatic disease or after relapse is poor. Immunotherapy with checkpoint inhibition has improved outcomes in multiple tumour types, but there are limited data on the efficacy of immunotherapy in advanced sarcomas, particularly within the AYA population. Methods: We retrospectively reviewed AYA patients with advanced bone and soft tissue sarcoma who received self-funded pembrolizumab at Chris OBrien Lifehouse and Childrens Hospital Westmead. Initial response was evaluated after cycle three or four using RECIST v1.1 criteria. Results: Fourteen AYA patients with sarcoma received pembrolizumab 2mg/kg IV every 3 weeks from May 2015 to December 2016. Median age was 24 (14 35), male to female was 7:7, ECOG PS was 0 1 in 6 patients, 2 in 6 patients and 3 4 in 2 patients. Malignancy type included three patients with osteosarcoma (OS), five patients with Ew...

Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association, 2018

To examine the histologic properties of supercritical carbon dioxide (sCO)-sterilized bone allogr... more To examine the histologic properties of supercritical carbon dioxide (sCO)-sterilized bone allograft for tunnel grafting and determine in vivo graft quality, as well as graft incorporation and remodeling, in 2-stage revision anterior cruciate ligament (ACL) surgery. Histologic evaluation was performed in 12 subjects undergoing 2-stage revision ACL reconstruction. In the first stage, the femoral and tibial tunnels were debrided, tunnel dimensions were measured, and tunnels were grafted with sCO-sterilized bone allograft. In the second stage, revision ACL reconstruction was performed and bone biopsy specimens were taken from the tibia. Tissue, bone, and graft volumes were measured, and histomorphometric analysis was performed. The mean time between the 2 stages was 8.8 months (range, 5.6-21.3 months). In the second stage, bone graft material was easily identified by its necrotic appearance comprising mature lamellar bone devoid of osteocyte nuclei within osteocyte lacunae. In all tiss...

ANZ Journal of Surgery

1. Davidovic LB, Vasic DM, Colic MI. Inferior mesenteric artery aneurysm: case report and review ... more 1. Davidovic LB, Vasic DM, Colic MI. Inferior mesenteric artery aneurysm: case report and review of the literature. Asian J. Surg. 2003; 26: 176–9. 2. Edogawa S, Shibuya T, Kurose K, Sasaki K, Tomita H. Inferior mesenteric artery aneurysm: case report and literature review. Ann. Vasc. Dis. 2013; 6: 98–101. 3. Suzuki K, Tanaka N, Ebine T, Momma T. Pelvic congenital arteriovenous malformation diagnosed by transrectal ultrasonography: a case report. Can. Urol. Assoc. J. 2012; 6: 61–3. 4. Nakad G, AbiChedid G, Osman R. Endovascular treatment of major abdominal arteriovenous fistulas: a systematic review. Vasc. Endovascular Surg. 2014; 48: 388–95. Djordje Radak,*† MD, PhD Milorad Sevkovic,* MD Vladimir Kecmanovic,‡ MD Slobodan Tanaskovic,*† MD *Vascular Surgery Clinic, ‘Dedinje’ Cardiovascular Institute, Belgrade, Serbia, †Faculty of Medicine, University of Belgrade, Belgrade, Serbia and ‡Clinic for Radiology, ‘Dedinje’ Cardiovascular Institute, Belgrade, Serbia

Histopathology, Jan 6, 2016

Recurrent EWSR1 gene rearrangements characterise a select group of bone and soft tissue tumours. ... more Recurrent EWSR1 gene rearrangements characterise a select group of bone and soft tissue tumours. In our routine diagnostic practice with fluorescence in situ hybridisation (FISH), we have occasionally observed EWSR1 gene rearrangements in tumours not classically associated with EWSR1 translocations. This study aimed to review our institutional experience of this phenomenon and also to highlight the occurrence of unusual EWSR1 FISH signals (i.e. 5' centromeric region or 3' telomeric region signals) that do not fulfill the published diagnostic criteria for rearrangements. Using an EWSR1 break-apart probe, we performed FISH assays on formalin-fixed paraffin embedded tissue sections from 135 bone and soft tissue specimens as part of their routine diagnostic workup. EWSR1 gene rearrangements were identified in 51% of cases, 56% of which also showed an abnormal FISH signal pattern (in addition to classically rearranged signals). However, atypical FISH signals were present in 45% o...

Pathology, 2015

Angiomatoid fibrous histiocytoma is a rare mesenchymal neoplasm of intermediate malignant potenti... more Angiomatoid fibrous histiocytoma is a rare mesenchymal neoplasm of intermediate malignant potential which occurs predominantly in the extremities of children and young adults. Local recurrence occurs in 2–12% of cases. The rate of local metastasis, defined as a second nodule in the same extremity or within loco regional lymph nodes, ranges from 1–5%, and is related to the depth of invasion, presence of infiltrative margins, and anatomical site. The average time between surgery and local metastasis is 1–2 years. Distant metastasis has been reported but is rare. We present a case of a 24 year old male who presented with a mass in his right forearm. An initial biopsy and subsequent wide excision of a red-brown mass, confined to the dermis and subcutis, was submitted. Histology showed typical features of an angiomatoid fibrous histiocytoma including solid sheets of histiocytoid and spindle cells, areas of haemorrhage and cystic change, a prominent lymphoid component at the periphery, and a fibrous pseudocapsule. Immunohistochemical staining for desmin, CD99, and CD68 were positive. FISH studies showed positive EWSR1 (22q12) rearrangement. Despite complete excision and the tumour's superficial location, the patient represented with local metastasis to the right epitrochlear lymph node and three right axillary lymph nodes five months after initial surgery. Angiomatoid fibrous histiocytoma shows three characteristic translocations that it shares with several other tumours that appear and behave quite differently. EWSR1-CREB1 is the most frequent gene fusion identified. EWSR1-ATF1 and FUS-ATF1 rearrangements are also described. The type of gene fusion does not appear to correlate with clinical behaviour, nor does the presence of pleomorphism. Evaluation for the characteristic translocations should always be interpreted in conjunction with morphologic features and tumour immunoprofile to avoid misdiagnosis of this rare tumour.

Skeletal Radiology, 2013

The retention of foreign bodies after surgery is rare, but carries significant morbidity and mort... more The retention of foreign bodies after surgery is rare, but carries significant morbidity and mortality as well as financial and legal implications. Such retained items cause a foreign-body reaction, which in the case of cotton-based materials are called gossypibomas. We present the case of an 84-year-old woman with a pseudotumor secondary to a retained dressing gauze roll, presenting 5 months after resection of a gluteal sarcoma, which had raised concerns of local recurrence. We also outline the imaging modalities that may assist in diagnosis of a retained foreign body, and suggest the MRI &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;row of dots&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; sign as a useful radiological feature associated with gossypiboma. Awareness of the imaging appearances of retained foreign bodies allows the inclusion of this possibility in differential diagnosis of a mass in patients with a surgical history.

The Journal of Arthroplasty, 2013

Foot & Ankle International, 1999

The results of 79 high resolution ultrasound examinations of the forefoot that were performed for... more The results of 79 high resolution ultrasound examinations of the forefoot that were performed for suspected Morton's metatarsalgia were retrospectively assessed. Scans were only obtained if the pain was poorly localized or if there were atypical features that made the clinical diagnosis uncertain. Ultrasound detected 92 hypoechoic intermetatarsal web space masses in 63 patients. Surgery was performed on 23 web spaces in 22 patients where the response to nonsurgical management had been poor. The surgical specimens were retrieved and reviewed by a pathologist in 21 cases. The histopathology in 20 of 21 operated cases was that of Morton's neuroma; however, prominent mucoid degeneration was also found to involve the adjacent loose fibroadipose tissues in 19 of 20 neuroma specimens. Ultrasound was sensitive in the detection of web space abnormality (sensitivity, 0.95), but could not clearly separate Morton's neuroma from associated mass-like mucoid degeneration in the adjacen...

… : The Journal of …, 1997

Anterior cruciate ligament (ACL) reconstruction using four-strand hamstring graft with round-head... more Anterior cruciate ligament (ACL) reconstruction using four-strand hamstring graft with round-headed, cannulated, interference (RCI) screw fixation requires osteointegration of the tendon graft. This report describes the histology at the bone-tendon junction of two specimens retrieved from patients undergoing revision surgery after traumatic mid-substance ACL graft rupture at 6 and 10 weeks after initial reconstruction. Revision was performed at 12 and 15 weeks. Integration of the graft was evident by observation of collagen fiber continuity between bone and tendon. This histology plus the low incidence of early graft failure suggest that free tendon autograft attached to bone by RCI screw allows adequate osteointegration between 6 and 15 weeks after surgery.