The impact of 2018 ASCO-CAP HER2 testing guidelines on breast cancer HER2 results. An audit of 2132 consecutive cases evaluated by immunohistochemistry and in situ hybridization.

The 2018 iteration of the ASCO-CAP HER2 testing guidelines proposes significant changes with an emphasis on the integration of concurrent immunohistochemistry (IHC) and in situ hybridization (ISH). We wished to evaluate the impact of these changes on clinical practice. Between Jan 2012 to Feb 2017, 2132 consecutive invasive breast carcinomas were evaluated with IHC and ISH for HER2. The sample tested was the breast primary or axillary nodes in all but 57 (2.7%) distant metastases. For 1824 cases with both dual-probe ISH and IHC results, the ISH subgroup was 1: 299 (16.4%), 2: 19 (1.0%), 1.0%, 3: 6 (0.3%), 4: 48 (2.6%) and 5: 1452 (79.6%). Ultimately 21% of group 2 and 4 cases and 80% of group 4 cases were positive. The change in HER2 status between the 2018 vs 2013 was: amplified in 323 (15.2%) vs 15.5%; not amplified in 1804 (84.6%) vs 82.2%; equivocal in 0 vs 2.3% previously. In 22 of 2127 cases (1.03%) the 2013 and 2018 results were discordant, all in groups 2-4. The discrepant cases included 15 of 331 (4.5%) of 2013 amplified cancers, now negative (all in groups 2 or 3) and 7 of 1796 (0.4%) 2013 nonamplified cases, now positive (all in group 4). Because of routine testing with both IHC and ISH, we found 6 of 1147 (0.52%) IHC negative (0 or 1+) cases were amplified by ISH. Further, 19 of 289 (6.6%) of IHC 3+ cases were nonamplified by ISH, circumstances not covered by these guidelines. In summary at the population level, the 2018 ASCO-CAP guidelines have a 99% agreement with the 2013 results. A major advantage is the abolishment of the clinically problematic equivocal category. Routine performance of both IHC and ISH uncovers a small proportion of cancers whose HER2 status is not addressed by these guidelines.

First human case of fatal Halicephalobus gingivalis meningoencephalitis in Australia.

Halicephalobus gingivalis (previously Micronema deletrix) is a free-living nematode known to cause opportunistic infections, mainly in horses. Human infections are very rare, but all cases described to date involved fatal meningoencephalitis. Here we report the first case of H. gingivalis infection in an Australian human patient, confirmed by nematode morphology and sequencing of ribosomal DNA. The implications of this case are discussed, particularly, the need to evaluate real-time PCR as a diagnostic tool.

Spontaneous self-expulsion of an oesophageal duplication cyst.

A case report of an oesophageal duplication cyst in an adult patient with chronic cough and presenting with a "coughed out lump". This is an unusual presentation highlighting the importance of considering congenital duplication cysts in patients with chronic cough and no obvious respiratory cause.

Extensive orbital inflammation in an anophthalmic socket: is the Bioceramic implant a bystander or a participant?

Purpose: Porous orbital implants are commonly used materials following enucleation or evisceration. Implant-associated inflammation is a rare but serious complication which may necessitate explantation. Observations: We report a case of a patient who developed extensive orbital inflammation six months after implantation of a vicryl (polyglactin 910) mesh-wrapped Bioceramic (aluminum oxide) spherical implant. An orbital biopsy demonstrated an extensive fibroinflammatory reaction with multinucleated giant cells. Removal of the implant resulted in complete resolution of symptoms. Conclusions and importance: We surmise that the Bioceramic implant played a significant contributory role in this patient's orbital inflammation, a complication which has not been described previously.

Lymphoeosinophilic cholecystitis: A rare cause of acalculous cholecystitis in immunocompetent patients - A case report.

INTRODUCTION: Eosinophilic and lymphoeosinophilic cholecystitis are uncommonly encountered causes of acalculous cholecystitis characterised by a clinical presentation of acute cholecystitis with eosinophilic infiltration of the gallbladder. Acalculous cholecystitis is a disease that is traditionally associated with patients who are critically unwell and immunosuppressed. PRESENTATION OF CASE: A fit and well 37-year-old man presented to the emergency department with a 12 -h history of constant upper abdominal pain radiating through to his back. Abdominal examination revealed tenderness in the right upper quadrant with a positive Murphy's sign. An abdominal ultrasound was performed, revealing a thickened gallbladder wall with probe tenderness, but no gallstones. He proceeded to an uneventful emergency laparoscopic cholecystectomy. Histological examination of the gallbladder revealed mucosal and transmural inflammation comprising of lymphocytes and more than 50 % eosinophils. No gallstones were found. A diagnosis of lymphoeosinophilic cholecystitis was made. The patient had improvement in his symptoms and was discharged home. He was well at follow-up. DISCUSSION: There is a small subset of immunocompetent patients who are not critically unwell who present with acalculous cholecystitis. There is significant hesitancy in offering a cholecystectomy to these patients without radiological evidence of gallstones or sludge preoperatively. Cholecystectomy should be offered to these patients if the clinical picture fits acute cholecystitis. CONCLUSION: Eosinophilic and lymphoeosinophilic cholecystitis are important causes of acalculous cholecystitis that can occur in immunocompetent patients. The decision to offer the patient a cholecystectomy should be based on clinical presentation and examination, rather than the absence or presence of gallstones.

CXCR4-CCR7 Heterodimerization Is a Driver of Breast Cancer Progression.

Metastatic breast cancer has one of the highest mortality rates among women in western society. Chemokine receptors CXCR4 and CCR7 have been shown to be linked to the metastatic spread of breast cancer, however, their precise function and underlying molecular pathways leading to the acquisition of the pro-metastatic properties remain poorly understood. We demonstrate here that the CXCR4 and CCR7 receptor ligands, CXCL12 and CCL19, cooperatively bind and selectively elicit synergistic signalling responses in invasive breast cancer cell lines as well as primary mammary human tumour cells. Furthermore, for the first time, we have documented the presence of CXCR4-CCR7 heterodimers in advanced primary mammary mouse and human tumours where number of CXCR4-CCR7 complexes directly correlate with the severity of the disease. The functional significance of the CXCR4-CCR7 association was also demonstrated when their forced heterodimerization led to the acquisition of invasive phenotype in non-metastatic breast cancer cells. Taken together, our data establish the CXCR4-CCR7 receptor complex as a new functional unit, which is responsible for the acquisition of breast cancer cell metastatic phenotype and which may serve as a novel biomarker for invasive mammary tumours.

Cancer Detection in Human Tissue Samples Using a Fiber-Tip pH Probe.

Intraoperative detection of tumorous tissue is an important unresolved issue for cancer surgery. Difficulty in differentiating between tissue types commonly results in the requirement for additional surgeries to excise unremoved cancer tissue or alternatively in the removal of excess amounts of healthy tissue. Although pathologic methods exist to determine tissue type during surgery, these methods can compromise postoperative pathology, have a lag of minutes to hours before the surgeon receives the results of the tissue analysis, and are restricted to excised tissue. In this work, we report the development of an optical fiber probe that could potentially find use as an aid for margin detection during surgery. A fluorophore-doped polymer coating is deposited on the tip of an optical fiber, which can then be used to record the pH by monitoring the emission spectra from this dye. By measuring the tissue pH and comparing with the values from regular tissue, the tissue type can be determined quickly and accurately. The use of a novel lift-and-measure technique allows for these measurements to be performed without influence from the inherent autofluorescence that commonly affects fluorescence-based measurements on biological samples. The probe developed here shows strong potential for use during surgery, as the probe design can be readily adapted to a low-cost portable configuration, which could find use in the operating theater. Use of this probe in surgery either on excised or in vivo tissue has the potential to improve success rates for complete removal of cancers. Cancer Res; 76(23); 6795-801. ©2016 AACR.

Identification of vitamin D3 target genes in human breast cancer tissue.

Multiple epidemiological studies have shown that high vitamin D3 status is strongly associated with improved breast cancer survival. To determine the molecular pathways influenced by 1 alpha, 25-dihydroxyvitamin D3 (1,25D) in breast epithelial cells we isolated RNA from normal human breast and cancer tissues treated with 1,25D in an ex vivo explant system. RNA-Seq revealed 523 genes that were differentially expressed in breast cancer tissues in response to 1,25D treatment, and 127 genes with altered expression in normal breast tissues. GoSeq KEGG pathway analysis revealed 1,25D down-regulated cellular metabolic pathways and enriched pathways involved with intercellular adhesion. The highly 1,25D up-regulated target genes CLMN, SERPINB1, EFTUD1, and KLK6were selected for further analysis and up-regulation by 1,25D was confirmed by qRT-PCR analysis in breast cancer cell lines and in a subset of human clinical samples from normal and cancer breast tissues. Ketoconazole potentiated 1,25D-mediated induction of CLMN, SERPINB1, and KLK6 mRNA through inhibition of 24-hydroxylase (CYP24A1) activity. Elevated expression levels of CLMN, SERPINB1, and KLK6 are associated with prolonged relapse-free survival for breast cancer patients. The major finding of the present study is that exposure of both normal and malignant breast tissue to 1,25D results in changes in cellular adhesion, metabolic pathways and tumor suppressor-like pathways, which support epidemiological data suggesting that adequate vitamin D3 levels may improve breast cancer outcome.

Primary osteosarcoma of the clavicle and the perils of bone biopsy.

We present a rare case of delayed diagnosis of osteosarcoma of the medial clavicle in a young man. He presented following a pathological fracture with a falsely reassuring core and fine-needle aspiration biopsy. The initial biopsy was suggestive of an aneurysmal bone cyst and was therefore treated conservatively without further follow-up. The rapid increase in size over the next 8 months triggered a repeat presentation and subsequent repeat biopsy. The open biopsy confirmed high-grade osteosarcoma and the patient underwent claviculectomy with neoadjuvant chemotherapy.