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Gross examination is the foundation for the pathologic evaluation of all surgical specimens. The rapid identification of cancers is essential for intraoperative assessment and preservation of biomolecules for molecular assays. Key components of the gross examination include the accurate identification of the lesions of interest, correlation with clinical and radiologic findings, assessment of lesion number and size, relationship to surgical margins, documenting the extent of disease spread to the skin and chest wall, and the identification of axillary lymph nodes. Although the importance of gross evaluation is undeniable, current challenges include the difficulty of teaching grossing well and its possible perceived undervaluation compared with microscopic and molecular studies. In the future, new rapid imaging techniques without the need for tissue processing may provide an ideal melding of gross and microscopic pathologic evaluation.

PURPOSE To evaluate the clinical patterns of utilization of OncotypeDX Recurrence Score (RS) in early-stage, hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer (BC) at an academic center with previously established internal reflex testing guidelines. METHODS RS testing in accordance with preexisting reflex criteria and predictors of utilization outside of reflex criteria were retrospectively analyzed for the years 2019-2021 in a quality improvement evaluation. Patients were grouped according to OncotypeDX testing within (cohort A) or outside (cohort B) of predefined criteria which included a cap at age older than 65 years. RESULTS Of 1,687 patients whose tumors had RS testing, 1,087 were in cohort A and 600 in cohort B. In cohort B, nearly half of patients were older than 65 years (n = 279; IQR, 67-72 years). For patients older than 65 years, those with RS testing were younger (median age: 69 v 73 years), with higher grade cancers (G2-3: 84.9% v 54.7%) and were more likely to be treated with chemotherapy (15.4% v 4.1%). Issues for implementation of RS testing in older patients were identified, including potential structural barriers related to the current policy on the reimbursements of genomic tests. CONCLUSION Internal guidelines may facilitate standardized utilization of the RS in early-BC. Our data suggest that clinicians preferred broader utilization of RS across the age spectrum, with therapeutically important consequences. Modifying the current policy for reimbursement of RS testing and in internal reflexive testing criteria for those older than 65 years is warranted.

Superficial angiomyxoma is an uncommon benign mesenchymal neoplasm that usually arises in dermis/subcutis of the extremities or trunk. Some tumors are associated with Carney complex. When arising in breast, these tumors are not well-recognized, mainly due to a lack of uniform nomenclature in the literature. This study therefore aims to improve recognition of angiomyxomas of the breast region. Forty cases were identified: demographics, presence of Carney complex, imaging and histologic features, PRKAR1A expression, and outcomes were evaluated. There were 22 female and 18 male patients (median age 40 years, range: 14 to 72). Most tumors presented as slowly-growing masses (77%). All but one were solitary, and median size was 1.5 cm. Tumors were superficial (dermal/subcutaneous) in 52.5% and deep/parenchymal in 47.5%. Nine involved the nipple-areola complex. All showed characteristic features of superficial angiomyxoma: poorly circumscribed, hypocellular, myxoid neoplasms with lobulated (55%) or infiltrative (45%) architecture, bland spindled fibroblasts, prominent thin-walled vessels, and admixed neutrophils. Tumors involving the nipple-areola complex infiltrated through areolar smooth muscle, and deep/parenchymal tumors showed entrapment of lobules mimicking myxoid fibroadenoma. Mitoses were typically absent, as was significant atypia. Cystic change was common. Two-thirds showed loss of PRKAR1A expression by immunohistochemistry. Two patients had Carney complex (7%). Recurrence after incomplete excision occurred in 1 patient. Angiomyxoma of breast may arise at superficial, nipple-areola or deep/parenchymal locations, where it can be difficult to recognize classic histologic features. Loss of expression of PRKAR1A is not invariable, but may be a helpful diagnostic clue. Recognizing angiomyxoma is important for 2 reasons: first, the recurrence rate is low and therefore wide excision is not essential, and second, it may allow detection of Carney complex in some patients.

Background Outpatient clinics were shifted rapidly to telehealth in Australia during the Coronavirus disease 19 (COVID‐19) pandemic, drastically altering patient care and experience. Aims To investigate patient satisfaction and acceptability of telehealth consultations during the COVID‐19 pandemic. Methods Prospective observation study conducted in two hospital rheumatology outpatient departments (OPD) undertaking telehealth consultations during COVID‐19. A modified version of a validated telehealth evaluation survey was posted to all patients attending the telehealth OPD rheumatology clinics, including balanced 5‐point Likert scales and free‐text responses. Cluster analysis was applied to the Likert‐scale questions, alongside thematic analysis of free‐text responses. Results There were 128 respondents (29% response rate), of which 69.5% were women and the majority (87.5%) was aged 50 years or older. All telehealth consultations were conducted by telephone. Nearly one‐fifth of patients indicated consistent dissatisfaction with telehealth across the range of questions. These patients were older, reported lower educational qualifications and lower health literacy scores and lacked access to the Internet. While many patients found this mode of consultation to be convenient, patients expressed concerns regarding absence of physical examination. A recurrent theme was a desire for a mixed‐model clinic in the future, with flexibility of having both telehealth and face‐to‐face consultations. Conclusions This study offers unique insights into patients' experiences with telehealth, which until the current global pandemic, has been an uncommon mode of consultation delivery in urban areas. This study suggests when defining the place of telehealth in future healthcare delivery, patient perspective and careful patient selection will be key. Disease progression, language and cognitive ability, health literacy, technology access and patient and clinician preference are important considerations when deciding how effectively to embed and integrate telehealth into consultations.

Objectives We compared survival and causes of death in Western Australian (WA) ANCA-associated vasculitis (AAV) and PAN patients with controls and the WA population. Methods In this data linkage study, we identified patients with incident AAV/PAN and age, sex and temporally matched controls 1980–2014 from the WA Rheumatic Disease Epidemiological Registry. Survival analyses and time-varying analyses were performed. Results Six hundred and fourteen patients with incident AAV/PAN were compared with 6672 controls; 229 AAV/PAN patients died over 5277 person-years of follow-up and 1009 controls died over 73835 person-years. Survival was reduced in patients with AAV/PAN compared with matched controls [hazard ratio (HR) 3.5 (95% CI: 3.1, 4.1)], and matched WA population rates [standardized mortality ratio 3.3 (95% CI: 2.9, 3.8)]. Greatest excess mortality in AAV/PAN patients was observed in the first year after diagnosis and remained higher than controls throughout follow-up. Greater excess mortality was observed in patients >60 years at diagnosis. In cause-specific analyses, mortality HR for vasculitis, infection and non-infective respiratory disease were greatest early after diagnosis and remained persistently elevated. The HRs for malignancy and cerebrovascular disease related deaths increased during follow-up, and were constant for ischaemic heart disease related deaths. Conclusion Mortality was increased in AAV/PAN patients compared with controls, with patients older at diagnosis at greater risk. These findings provide mortality risk for AAV/PAN in an Australian population, highlighting key contributors to mortality at different time periods over follow-up and potential areas of focus for reducing mortality.

Breast cancer is the most common malignancy in female patients with Li–Fraumeni syndrome (LFS), a rare autosomal dominant hereditary syndrome characterized by germline TP53 mutations. Recent studies have shown that the majority of these tumors are estrogen receptor (ER) positive with frequent HER2 co-expression. However, the morphologic features of these tumors have not been as well studied as other germline-associated breast cancers. We evaluated the pathologic features of 27 invasive and in situ carcinomas from patients with known germline TP53 mutations collected through the Li–Fraumeni Consortium. Overall, 60% of cases were HER2 positive and 44% showed ER co-expression. Most DCIS was high nuclear grade with central necrosis and associated periductal fibrosis and lymphocytic response. Invasive carcinomas were mostly of ductal type (NOS), modified Scarff–Bloom–Richardson (mSBR) high grade, with marked nuclear atypia and high mitotic rate. Prominent tumor infiltrating lymphocytes, syncytial growth pattern, or pushing borders were not seen in these tumors. High p53 IHC expression was seen in tumors from individuals with germline TP53 missense mutations whereas little or no protein expression (

Objective: To determine beliefs about methotrexate (MTX) in patients with rheumatoid arthritis (RA) in relation to utilized information sources.Methods: RA patients, who were current participants in the Australian national biologic registry, completed an online questionnaire regarding their use and views about MTX (N = 1010). Participants who used MTX were asked about which MTX information sources they consulted, and whether positive or negative views were obtained.The Beliefs about Medicine Questionnaire (BMQ), was used to measure patient beliefs about MTX. Results: The survey response rate was 804/1010 (80%). MTX survey data were analyzed for 742 RA participants (mean age 59 years, 76% female, mean disease duration 19 years) who had used MTX, with 494/742 (67%) reporting current use.Participants consulted multiple information sources (median 3, interquartile range 1-5). Rheumatologists (98%), general practitioners (GPs) (55%), internet searches(39%), educational websites (38%), and pharmacists (37%) were the most common information sources utilized. Positive MTX information was most often obtained from rheumatologists (92%), GPs (66%), and educational websites (56%). Negative information was most often obtained from relatives, social media, internet chat rooms and friends. Information from rheumatologists was the most influential on favorable BMQ MTX-specific scores, whereas information from educational websites also affirmed the need for MTX. Conclusion: RA patients have significant concerns regarding MTX and consult a variety of sources for MTX information. However, the patient perception of this information varies widely. Rheumatologists and educational websites are the most important information sources in terms of a positive influence on the patient's perception of MTX. Refereed/Peer-reviewed

Invasive lobular carcinoma with extracellular mucin (ILCEM) is a rare histologic subtype of breast cancer. Little is known about the pathologic or genomic signatures that distinguish ILCEM from classic invasive lobular carcinoma (ILC) or mucinous carcinoma. We studied 17 breast cancers with lobular morphology and extracellular mucin. Thirteen tumors with sufficient tissue for DNA extraction were analyzed by a next generation sequencing (NGS) assay that interrogates 447 genes for mutations and copy number variations (CNVs). Median patient age was 66 yrs (range: 31-77 yrs). Sixteen patients presented with masses, 7 of which were2 cm. Seven patients had lymph node metastases. The cases of ILCEM were moderately (n = 13) or poorly differentiated (n = 4), frequently exhibiting variant morphology that has not been previously described or emphasized, including grade 3 nuclei (n = 11), diffuse signet ring cells (n = 10), solid growth (n = 4), tumor necrosis (n = 3) or apocrine features (n = 2). All tumors showed absent or reduced membranous E-cadherin expression. Concurrent lobular carcinoma in situ (LCIS) was seen in 11/17 cases, 1 of which was a striking example of signet ring cell LCIS with extracellular mucin. Receptor profiles were ER+/HER2- (n = 15) and ER+/HER2+ (n = 2). With a median follow-up of 83.5 months (range: 3-171 months) in 12 patients with available information, 8 patients had recurrences resulting in 4 cancer-related deaths. The most common CNVs were 16q loss (n = 11) and 1q gain (n = 9). CDH1 gene-level alterations were detected in all but one case, including frameshift (n = 7), nonsense (n = 2), and donor splice site (n = 1) mutations and indels (n = 2). Recurrent mutations were also seen in PIK3CA (n = 3), POLQ (n = 3), TP53 (n = 3), ERBB3 (n = 3), ERBB2 (n = 2), and RUNX1 (n = 2). Genes with recurrent amplifications included GATA3 (n = 4), FOXA1 (n = 3), CCND1 (n = 2). Our data highlights ILCEM as a distinct variant of ILC that often presents with higher-grade and variant morphologic features and is associated with an aggressive clinical course. NGS data support an overall lobular-type molecular profile and reveal potentially targetable alterations in a subset of cases with recurrence.

A successful breast core needle biopsy program provides numerous advantages for patients, radiologists, pathologists, surgeons, biomedical research, and the healthcare system. In order to obtain optimal results, it is essential that multiple healthcare providers and disciplines closely communicate and fully cooperate. The complexity of the process from the detection of a lesion, to biopsy, to ultimate outcome creates many opportunities for error. This chapter is a comprehensive guide for best practices for core needle biopsies. The chapter begins with an explanation of how imaging modalities (mammography, ultrasound, and MRI) detect breast abnormalities and how these findings correlate with pathologic lesions. Types of breast needle biopsies and the resulting specimens are then discussed in conjunction with information necessary to determine radiologic/pathologic correlation by both the radiologist and the pathologist. Recommendations for specimen handling from the removal by the radiologist to the creation of the glass slides by the histotechnologist are included. These topics are followed by optimal practices for identifying, excising, and examining a lesion previously sampled by needle biopsy. Throughout the chapter, commonly seen artifacts and possible pitfalls are discussed and illustrated. The chapter concludes with a review of rare cancer recurrences in needle tracks.

ObjectiveMortality rates for patients with SLE have not been reported in Australia. This study determined the association between a hospitalisation for SLE with mortality.MethodsPopulation-level cohort study of patients with SLE (n=2112; 25 710 person-years) and general population comparators (controls) (n=21, 120; 280 637 person-years) identified from hospital records contained within the WA Rheumatic Disease Epidemiological Registry from 1980 to 2013. SLE was identified by ICD-9-CM: 695.4, 710.0, ICD-10-AM: L93.0, M32.0. Controls were nearest matched (10:1) for age, sex, Aboriginality and temporality. Using longitudinal linked health data, we assessed the association between a hospitalisation for SLE mortality and mortality with univariate and multivariate Cox proportional hazards and competing risks regression models.ResultsAt timezero, patients with SLE were similar in age (43.96 years), with higher representation of females (85.1% vs 83.4%, p=0.038), Aboriginal Australians (7.8% vs 6.0%) and smokers (20.5% vs 13.2%). Before study entry, patients with SLE (mean lookback 9 years) had higher comorbidity accrual (Charlson Comorbidity Index ≥1 item (42.0% vs 20.5%)), especially cardiovascular disease (CVD) (44.7% vs 21.0%) and nephritis (16.4% vs 0.5%), all pConclusionsA hospitalisation for SLE associated with an increased risk of mortality over the 1980–2014 period compared with the general population. The risk was especially high in younger (

PURPOSE The 21-gene recurrence score (RS) is used to identify patients with hormone receptor–positive early-stage breast cancer who may benefit from the addition of chemotherapy to endocrine therapy. We hypothesized that many women with poor prognostic histopathologic grade 3 disease may be offered chemotherapy irrespective of RS results, of whom a subset may not benefit from adjuvant chemotherapy. PATIENTS AND METHODS A total of 30,864 women in the National Cancer Database were diagnosed with pT1c to pT2, pN0 to pN1, grade 3 estrogen receptor–positive, human epidermal growth factor receptor 2–negative invasive breast carcinoma from 2010 to 2015. RS was stratified as low (less than 18), intermediate (18 to 30), and high (31 or more). Overall survival by RS was evaluated by Kaplan-Meier, log-rank, and multivariable proportional hazards, with adjustment for relevant clinical and demographic variables. RESULTS RS testing in grade 3 cancers increased between 2010 and 2015 (pN0, 53% to 72%; pN1, 16% to 36%). Among the 13,558 women with pN0 and the 2,840 with pN1 disease with RS testing, 27.1% and 30.0%, respectively, had low scores (less than 18). The 5-year overall survival rate for patients with a high RS, but not low RS, was significantly higher with chemotherapy ( v no chemotherapy; absolute differences: high RS pN0 = 12.2% and pN1 = 25.5%, both P < .001; low RS pN0 = 2.5%, P = .07; and pN1 = 1.0%, P = .27), findings that were reinforced in multivariable analyses risk adjusted by clinicopathologic characteristics. CONCLUSION Increased use of RS may help to better tailor treatment recommendations by stratifying patients with grade 3 disease into those who will and will not derive survival benefit and should be considered in all patients with estrogen receptor–positive/human epidermal growth factor receptor 2–negative T1c to T2, N0 to N1 disease.

Fibrosis across different organs and tissues is likely to share common pathophysiological mechanisms and pathways. Recently, a polymorphism (rs12979860) near the interferon lambda gene (IFNL3) was shown to be associated with fibrosis in liver across multiple disease etiologies. We determined whether this variant is a risk factor for pulmonary fibrosis (PF) and worsening cutaneous fibrosis in systemic sclerosis (SSc). Caucasian patients with SSc (n = 733) were genotyped to test for association with the presence of PF and worsening of skin fibrosis. Serum IFN-λ3 levels from 200 SSc cases were evaluated. An association of the IFNL3 polymorphism with PF was demonstrated (OR: 1.66 (95% CI: 1.142–2.416, p = 0.008). The IFNL3 variant was not a risk factor for worsening of skin fibrosis. Functionally, IFN-λ3 serum levels were higher among subjects with PF compared to those unaffected (P

Hyperechogenicity in the breast on ultrasound (US) is usually regarded as a benign feature with only rare hyperechoic malignancies reported to date. In this study, we evaluated the pathologic findings on core needle biopsy of hyperechoic lesions and investigated the histologic features in malignancies that give rise to an echogenic pattern. A total of 163 core needle biopsies (CNB) were performed for "hyperechoic" or "echogenic" lesions between 1/1/05 and 7/31/17. Lesions were classified based on the proportion of hyperechoic areas identified. We found that all lesions with a homogenous hyperechoic pattern (>90% hyperechoic) were benign (n = 17), regardless of the type of margins. Malignancies were found in 21% (7/34, six invasive carcinomas and one lymphoma) of heterogenous lesions with ≥50% hyperechoic areas (all with noncircumscribed margins) and in 31% of lesions with

Aims To investigate the utility of fluorine-18-labelled deoxyglucose positron emission tomography (FDG-PET) in routine clinical practice to diagnose and monitor disease activity and treatment response in large vessel vasculitis in a South Australian cohort. Methods We performed a retrospective clinical audit of adult patients who received a FDG-PET at a tertiary referral center between August 2010 and August 2015, where the term "vasculitis" appeared in either the request or report. Results A total of 45 patients met the inclusion criteria. Nine patients (20%) had a positive FDG-PET for large vessel vasculitis. FDG-PET was positive in 3/6 (50%) patients who met the American College of Rheumatology (ACR) criteria for giant cell arteritis or Takayasu's arteritis (TA) on retrospective review. A positive FDG-PET for large vessel inflammation assisted the primary clinician in making the diagnosis of unclassified large vessel vasculitis in six patients. Four of the seven patients who had more than one scan for large vessel vasculitis demonstrated normalized FDG uptake on subsequent scans after a period on glucocorticoid treatment. The remaining three patients persisted in having increased FDG uptake on FDG-PET imaging while on active treatment. Conclusion Fluorine-18-labelled deoxyglucose positron emission tomography has a role in the diagnosis of large vessel vasculitis, particularly in patients with a high suspicion of active large vessel vasculitis who do not meet the ACR criteria. FDG-PET may have a role in monitoring disease activity in selected patients with large vessel vasculitis especially in identifying occult sites of large vessel inflammation or to titrate prednisolone therapy.

Architectural distortion (AD) on mammography is a localized alteration in the uniform texture of the breast characterized by lines radiating from a central point. Radiologic/pathologic correlation is challenging because the types of lesions associated with AD are not well defined and, thus, what signifies a discordant finding requiring excision is less clear. This retrospective case series was performed to elucidate the pathologic lesions associated with AD. Over a 6-year period, 588 core needle biopsies (CNBs) were performed for AD. Thirty-eight percent of the lesions were AD alone (single feature AD) and 62% had additional imaging features (multi-feature AD). Overall, 31% showed invasive carcinoma or ductal carcinoma in situ (DCIS), 37% showed benign lesions likely to correlate with AD, and 32% showed nonspecific benign findings. The invasive carcinomas tended to be low-grade (60%), ER-positive (98%), HER2-negative (98%), and often had lobular features (52%). Ninety-two percent were AJCC pathologic stage group I. Ninety-four cases of benign findings that correlated with AD without atypia underwent excision, and only one was found to have DCIS adjacent to the sclerosing lesion (1%). The remaining cases had benign findings without a clear correlate for AD. Sixty-eight cases without atypia underwent excision, and six multi-feature AD were upgraded to invasive carcinoma (9%). In conclusion, about one-third of CNBs for lesions associated with AD reveal carcinomas that are predominantly invasive, low-grade, ER-positive, HER2-negative, and low stage. Single-feature AD differed from multi-feature AD due to a lower number of carcinomas on CNB (18% vs 39%). For CNBs showing benign lesions on biopsy with a correlate for AD, the finding of malignancy on excision is low (1%). Radiologic/pathologic correlation and decisions to recommend excision will continue to be a challenge after CNB reveals nonspecific findings as some patients with multi-feature AD were found to have undetected invasive carcinomas.

Chronic Rhinosinusitis (CRS) is a multifactorial disease where microorganisms’ innate and adaptive immunity can play a role. This study assessed the total IgG, IgG subclasses, IgE and IgA levels in serum samples from CRS and non-CRS control patients in relation to the disease severity, phenotype, histopathology and comorbidities. Total serum IgG, IgG1, IgG2, IgG3, IgG4 and IgE was determined from 10 non-CRS controls, 10 CRS without nasal polyp (CRSsNP) and 26 CRS with nasal polyp (CRSwNP) patients using ImmunoCap assays. Tissue lysates were analyzed for IgG levels by ELISA. Immunohistochemical analysis was used to measure the expression of IgE and IgG4 in tissue sections. The presence of anti-nuclear antigens (ANAs) against 12 autoantigens in sera and tissue lysates was determined by immunoblot assays. Total serum IgG/IgG1/IgG2 levels were higher in CRS patients vs. controls (p < 0.001), but were not different between CRSwNP and CRSsNP patients (p = 0.57). Serum IgG4/IgE levels were increased in CRSwNP patients compared to controls (p = 0.006), however, this relationship was attenuated by the inclusion of covariates. Serum IgG4 levels were more strongly associated with asthma (p = 0.038, exact median test) and tissue eosinophilia (Spearman’s rank rho = 0.51, p = 0.016) than IgE levels. No systemic ANAs were detected in any of the subjects tested. There was a polyclonal increase in serum immunoglobulins in CRS patients with elevated IgG4/IgE levels in CRSwNP patients having tissue eosinophilia and asthma.

A diagnosis of non-classic lobular carcinoma in situ (NC-LCIS) encompasses a variety of lesions with poorly characterized natural history. We evaluated upgrade rates and factors associated with upgrade to malignancy following a core biopsy diagnosis of NC-LCIS, and its natural history. Upon Institutional Review Board approval, pathology databases were searched for NC-LCIS core biopsy diagnoses (carcinoma in situ [CIS], CIS with ductal and lobular features [CIS/DLF], pleomorphic LCIS [P-LCIS], variant LCIS [V-LCIS], LCIS with necrosis). Cases with available core and excision pathology were included, while cases with concurrent ipsilateral invasive carcinoma (IC), ductal carcinoma in situ (DCIS), and/or atypical ductal hyperplasia were excluded. Overall, 121 NC-LCIS cases were identified from 1998 to 2017. We excluded 46 cases with concurrent cancer; 75 patients with 76 NC-LCIS core biopsy diagnoses followed by excision formed our study cohort. Median age was 56 years (range 41–83), and all imaging findings were classified as Breast Imaging Reporting and Data System 4; calcifications were the most common biopsy indication (80%). Excision yielded malignancy in 27 (36%) patients (IC 17, 63%; DCIS alone 10, 37%). We were unable to identify radiologic or pathologic features predictive of upgrade. Of 49 pure NC-LCIS cases, 15 (31%) had mastectomy, 9 (18%) had excision and radiation, and 25 (51%) had excision alone. At a median follow-up of 58 months (range 1–224), 1/25 (4%) patients with excision alone developed ipsilateral DCIS 14 months later. In this series of NC-LCIS, 36% of cases were upgraded, supporting routine excision. We were unable to identify predictors of upgrade. Among 25 patients with pure NC-LCIS, only one patient developed a future ipsilateral cancer. Further study of the natural history of NC-LCIS is warranted.

Background Gout has an increasing global prevalence. Underutilization of urate-lowering therapy (ULT) is thought to be common, via both suboptimal dosing and poor medication adherence. The aims of this study were to determine the prevalence of self-reported gout and the key predictors of ULT use in those with gout in a representative population survey in South Australia. Methods Data were obtained from the Spring 2015 South Australian Health Omnibus Survey, a multilevel, systematic, survey in a representative population sample involving face-to-face interviews (n = 3005). This study analyzed responses from respondents aged ≥ 25 years (n = 2531) about self-reported gout, ULT use, sociodemographic factors, lifestyle factors, and comorbidities, using survey weighting. Univariate and subsequent adjusted logistic regression analyses on self-reported gout were performed. ULT use was divided into three categories (never use, prior use, and current use) and these data were analyzed using a multinomial logistic regression model. Results Self-reported gout prevalence was 6.8% (95% CI 5.8, 7.9). The mean age of respondents with gout was 64 years (standard deviation 16) and 82% were male. As expected, older age, male gender, lower socioeconomic status (SES), and higher body mass index (BMI) were associated with gout, as were high alcohol consumption, current smoking, other forms of arthritis, and hypertension or hypercholesterolemia medication, after adjustment for sociodemographic variables. Two thirds of respondents with gout reported ULT use (36% current; 29% previous) with only 55% continuing treatment. Predictors of ULT use included male gender, low SES, and concomitant cholesterol-lowering therapy. Respondents with gout with a higher BMI were more likely to remain on ULT. Conclusions Despite gout being a common, potentially disabling joint disease, only 55% of respondents with gout in this study adhered to ULT. Identification of key predictors of ULT use will provide guidance on prescribing strategy in clinical practice and on the quality of gout care in the community. Electronic supplementary material The online version of this article (10.1186/s13075-018-1633-9) contains supplementary material, which is available to authorized users.

Giant cell arteritis is the commonest primary vasculitis of the elderly. However, the prevalence does vary widely between populations with highest incidence amongst Northern Europeans and lowest amongst East Asians. Preliminary studies suggest that clinical manifestations may differ between different populations. Newer diagnostic approaches including ultrasound, MR angiography and PET imaging are under review. While there have been recent advances in the diagnosis of GCA particularly with regard to imaging, there is an urgent need for improvements in methods of diagnosis, treatment and requirement for screening. Glucocorticoid treatment remain the backbone of therapy. However, glucocorticoid therapy is associated with significant adverse effects. Conventional and novel immunosuppressive agents have only demonstrated modest effects in a subgroup of steroid refractory GCA due to the different arms of the immune system at play. However, recently a study of IL-6 blockade demonstrated benefit in GCA. Newer approaches such as fast-track pathways can also result in improvements in consequences of GCA including blindness.

Papillary endothelial hyperplasia (PEH) is a rare non-neoplastic exuberant organizing hematoma that can closely mimic angiosarcoma due to a resemblance to malignant anastomosing blood vessels. It could be particularly difficult to distinguish PEH from angiosarcoma in breast core needle biopsies. We identified all cases of these lesions diagnosed on core needle biopsy in order to identify clinical, radiologic, and pathologic features that could prove helpful to arrive at the correct diagnosis. Four cases of PEH and 4 cases of angiosarcoma were identified. The mean age at diagnosis was 62 for PEH and 33 for primary angiosarcoma. All cases of PEH formed small masses with circumscribed or lobulated margins by imaging (mean size 0.9 cm). In 3 cases, the masses were difficult or impossible to identify after the biopsy. Angiosarcomas presented as larger masses with ill-defined margins (mean size 2.8 cm) that were unchanged in size after biopsy. PEH was surrounded by adipose tissue, whereas angiosarcoma invaded into fibrous stroma and involved lobules. The pseudopapillary structures of PEH were composed mainly of collagen, and thus, additional histologic stains for fibrin were not helpful for diagnosis. The 4 patients with PEH received no further treatment and are alive and disease-free at 2-11 years of follow-up. In contrast, the patients with angiosarcoma underwent mastectomy and chemotherapy or radiation therapy. Two of the patients with angiosarcoma died 3 years after diagnosis and the other 2 patients are alive without disease at 5 and 6 years. Therefore, distinguishing PEH and angiosarcoma is essential for appropriate management. This is the first series to compare these lesions on core needle biopsy and the first to note important clinical, imaging, and histologic differences that aid in making a diagnosis of PEH with confidence on breast core needle biopsy.

Introduction: Non-classic lobular carcinoma in situ (NC-LCIS) is a rare pathologic entity which encompasses a variety of histologic diagnoses. As such its natural history, including upgrade rates to invasive cancer (IC) or ductal carcinoma in situ (DCIS) on excision, is poorly characterized. We sought to evaluate the risk of upgrade to IC or DCIS when NC-LCIS is diagnosed on core biopsy. Methods: After obtaining IRB approval, institutional pathology databases were searched for NC-LCIS core biopsy diagnoses (carcinoma in situ (CIS), carcinoma in situ with ductal and lobular features (CIS/DLF), pleomorphic LCIS (P-LCIS), variant LCIS (V-LCIS), LCIS with necrosis). Cases with a NC-LCIS core biopsy diagnosis and with available pathology results from subsequent surgery were included. Cases with known concurrent ipsilateral IC, DCIS and/or atypical ductal hyperplasia were excluded. Results: 107 cases with NC-LCIS in any pathology report were identified (1998-2016); 44 were excluded due to concurrent ipsilateral IC, the remaining 62 patients with 63 core biopsy diagnoses of NC-LCIS all underwent surgical excision and formed our study cohort. Median age was 56 years (range 43-83); 43 (68%) were postmenopausal. NC-LCIS was diagnosed on core biopsy for mammographic findings in 57 (90%) cases and for MRI findings in 6 (9%). All were BI-RADS 4 lesions; calcifications were the most common biopsy indication (50 (78%)). CIS/DLF was the most common term used for NC-LCIS (28 (44%)), followed by CIS (18 (29%)), V-LCIS (14 (22%)) and P-LCIS (3 (5%)). On core biopsy, 36/44 (82%) of NC-LCIS cases were E-cadherin negative, 38/41 (93%) were ER positive, and 6/34 (18%) were HER2 positive. IC and/or DCIS were diagnosed on subsequent surgery in 22 (33%) of patients, of which 14 (67%) were IC and 8 (18%) had DCIS only. LesionTotalE-cadherin negativeUpgraded, N (%)Invasive cancer, N (%)DCIS only, N (%)CIS188/10 (80%)3 (16%)2 (67%)1 (33%)CIS/DLF2819/23 (83%)12 (43%)7 (58%)5 (42%)P-LCIS31/1 (100%)3 (100%)2 (67%)1 (33%)V-LCIS148/10 (80%)4 (29%)3 (75%)1 (25%) Median IC size was 0.2 cm (0.06-1.1 cm). IC histology was ductal in n=4 (29%), lobular in n=7 (50%), and ductal and lobular in n=3 (21%). Among the 14 invasive lesions, 5 (36%) were grade I, 5 (36%) were grade II and 2(13%) were grade III, (grade was not reported for 2 remaining ICs); 12/14 (86%) were ER positive and 1/14 (7%) was HER2 positive; none had LVI or positive nodes. Among the 42 cases not upgraded, 13 (31%) had mastectomy, 9 (21%) had excision and radiation, 20 had excision only, all had negative margins. At median follow-up of 60 months (1-224 months), 1/20 patients treated with excision only was diagnosed with DCIS, 14 months after surgery for CIS/DLF on core biopsy. Conclusions: In this large series of NC-LCIS diagnosed on core biopsy, the upgrade rate to carcinoma was 33% supporting the recommendation for routine excision of these lesions. The cancers found at excision were all stage I and the majority were grade I or II. At a median follow-up of 60 months only 1/20 patients with pure NC-LCIS treated with excision alone developed a future ipsilateral cancer. Further study of the natural history of these rare lesions is warranted. Citation Format: Nakhlis F, Harrison BT, Lester SC, Hughes KS, Coopey SB, King TA. Evaluating the risk of upgrade to invasive breast cancer and/or DCIS on excision following a diagnosis of non-classic lobular carcinoma in situ [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-22-01.

Eugene Roscioli,1,2 Hubertus PA Jersmann,1,2 Susan Lester,2,3 Arash Badiei,1,2 Andrew Fon,1,2 Peter Zalewski,2,4 Sandra Hodge1,2 1Department of Thoracic Medicine, Royal Adelaide Hospital, 2Department of Medicine, The University of Adelaide, Adelaide, 3Department of Rheumatology, 4Cardiology Unit, The Queen Elizabeth Hospital, Woodville, SA, Australia Abstract: There is now convincing evidence that the airway epithelium drives the pathogenesis of COPD. A major aspect of this is the disease-related reduction in barrier function that is potentiated by dysregulation of tight junction (TJ) protein complexes. However, a significant number of studies using in vitro smoke exposure models have not observed alterations in barrier permeability. We have previously shown that zinc (Zn) is an influential cytoprotective factor for the airway epithelium, and its depletion by cigarette smoke produces disease-related modifications consistent with inflammatory changes in COPD. We hypothesized that Zn deficiency is a significant co-stimulus with cigarette smoke extract (CSE) for potentiating the leaky barrier phenotype exhibited in COPD. We employed an ex vivo model of differentiated human airway epithelium exposed to Zn depletion and CSE to determine the contribution of Zn in maintaining normal epithelial permeability. Western blot analysis demonstrated a significant downregulation of the TJ proteins such as ZO-1 (–1.93-fold, P

Background Glucocorticoids (GCs) are used in ~ 60% of patients with rheumatoid arthritis (RA). Although disease-modifying, they also have significant adverse effects. Understanding factors associated with GC use may help minimise exposure. The aims of the present study were to describe oral GC use in RA; determine any change in use over time; and determine factors associated with oral GC use, commencement or cessation. Methods Adult patients with RA were identified in the Australian Rheumatology Association Database (ARAD), a national Australian registry that collects long-term outcome data from patients with inflammatory arthritis. Patients were categorised by their ARAD date of entry (DOE), with population-averaged logistic regression and transition state analysis used to determine any change in GC use over time. Fixed-effects panel regression was used to examine whether GC current use was associated with pain/arthritis activity/Health Assessment Questionnaire (HAQ) scores or medication use. Transition state analysis was used to assess whether these factors influenced the commencement or cessation of GCs. Results A total of 3699 patients with RA completed a baseline ARAD questionnaire (73% female, mean age 57 years). The probability of GC use decreased over time according to ARAD DOE: September 2001 to March 2005, 55% (95% CI 52–58%); March 2005 to September 2008, 47% (45–49%); September 2008 to March 2012, 42% (39–45%); and March 2012 to October 2015, 39% (34–43%) (p

Purpose: Delays to adjuvant chemotherapy initiation in breast cancer may adversely affect clinical outcomes and patient satisfaction. We previously identified an association between genomic testing (Onco type DX) and delayed chemotherapy initiation. We sought to reduce the interval between surgery and adjuvant chemotherapy initiation by developing standardized criteria and workflows for Onco type DX testing. Methods: Criteria for surgeon-initiated reflex Onco type DX testing, workflows for communication between surgeons and medical oncologists, and a streamlined process for receiving and processing Onco type DX requests in pathology were established by multidisciplinary consensus. Criteria for surgeon-initiated testing included patients ≤ 65 years old with T1cN0 (grade 2 or 3), T2N0 (grade 1 or 2), or T1/T2N1 (grade 1 or 2) breast cancer on final surgical pathology. Medical oncologists could elect to initiate Onco type testing for cases falling outside the criteria. We then examined 720 consecutive patients with breast cancer who underwent Onco type DX testing postoperatively between January 1, 2014 and November 28, 2016 and measured intervals between date of surgery, Onco type DX order date, result received date, and chemotherapy initiation date (if applicable) before and after intervention implementation. Results: The introduction of standardized criteria and workflows reduced time between surgery and Onco type DX ordering, and time from surgery to receipt of result, by 7.3 days ( P < .001) and 6.3 days ( P < .001), respectively. The mean number of days between surgery and initiation of chemotherapy was also reduced by 6.4 days ( P = .004). Conclusion: Developing consensus on Onco type DX testing criteria and implementing streamlined workflows has led to clinically significant reductions in wait times to chemotherapy decision making and initiation.

Objectives Fibromatosis of the breast is an uncommon neoplasm with potential for local recurrence. Treatment has traditionally been surgical excision with current trends toward conservative management. Given the option of observation after diagnosis by core needle biopsy (CNB), we sought to evaluate the accuracy of CNB for diagnosing fibromatosis. Methods We identified a total of 31 cases in which fibromatosis had been diagnosed or included in the differential diagnosis on a CNB, an excision, or both. Morphology and immunohistochemical results were reviewed. Results Aberrant nuclear immunoreactivity for β-catenin and absent staining for CD34 were the most useful studies to diagnose fibromatosis, and one or both were performed in 21 (68%) cases. High molecular weight cytokeratins and p63 were helpful to exclude spindle cell carcinoma. Of 26 cases confirmed as fibromatosis on excision, 22 (85%) were diagnosed as fibromatosis or fibromatosis was favored in the differential diagnosis on CNB. More frequent use of immunohistochemistry would likely have resulted in a greater number of definitive diagnoses. Fibromatosis was rarely mistaken for other nonmalignant stromal lesions, with no cases misdiagnosed as carcinoma. Conclusions CNB can be an accurate method of diagnosing fibromatosis, allowing observation for a select group of patients.

Breast cancer is the most common malignancy in female patients with Li-Fraumeni syndrome (LFS), a rare autosomal dominant hereditary syndrome characterized by germline TP53 mutations. Recent studies have shown that the majority of these tumors are estrogen receptor (ER) positive with frequent HER2 co-expression. However, the morphologic features of these tumors have not been as well studied as other germline-associated breast cancers. We evaluated the pathologic features of 27 invasive and in situ carcinomas from patients with known germline TP53 mutations collected through the Li-Fraumeni Consortium. Overall, 60% of cases were HER2 positive and 44% showed ER co-expression. Most DCIS was high nuclear grade with central necrosis and associated periductal fibrosis and lymphocytic response. Invasive carcinomas were mostly of ductal type (NOS), modified Scarff-Bloom-Richardson (mSBR) high grade, with marked nuclear atypia and high mitotic rate. Prominent tumor infiltrating lymphocytes, syncytial growth pattern, or pushing borders were not seen in these tumors. High p53 IHC expression was seen in tumors from individuals with germline TP53 missense mutations whereas little or no protein expression (1% nuclear expression, null pattern) was seen in tumors from carriers of non-missense mutations. In this study, we report in detail the morphologic features of invasive and in situ carcinomas in LFS. We found that these tumors share features with cancers harboring somatic TP53 mutations but are distinct from BRCA-associated breast cancers.

Staphylococcus aureus is a major human pathogen that causes a wide array of infections ranging in severity from mild skin infections to life-threatening diseases such as sepsis. S. aureus can cause severe inflammation whilst, at the same time, modulating specific innate and humoral immune defense mechanisms. Lipoteichoic acid (LTA) is a component of the cell wall of gram-positive bacteria that is abundantly released by S. aureus. We investigated the dose-dependent effects of LTA on inflammation in airway epithelial cells. Purified S. aureus LTA was applied to airway epithelial (NuLi-1) cells in a range of concentrations, followed by assessment of expression of NFκB p50 and p65/RelA via qPCR, immunofluorescence and western blot. Multiplex analysis of cell culture supernatants was carried out to evaluate cytokine levels. NFκB p50 mRNA varied according to the LTA dose (p = 0.013) whereas NFκB p65/RelA did not (p = 0.90). A dose-dependent increase in NFκB p50 mRNA expression was seen up to 10 μg/ml LTA treatment, before falling at the 100μg/ml treatment. Western blot analysis showed nuclear and cytoplasmic NFκB p50 and cytoplasmic NFκB p65 protein reduced with increasing LTA concentrations. Multiplex analysis demonstrated that cytokine levels increased with LTA dose, but then decreased at the highest LTA dose (100 μg/ml). This study identifies LTA as having a dual dose-dependent effect on immune activation at low dosages and ablation at high dosages, associated with altered expression levels of NFκB. It adds LTA to the extensive repertoire of possible immune modulators produced by S. aureus.

The technique of combining stereotactic targeting of breast lesions with an automated spring-loaded needle biopsy gun reported in 1990 by Steve Parker and colleagues not only ushered in the era of diagnosis almost exclusively by image guided core needle biopsy, but also profoundly changed the practice of pathologists, radiologists, surgeons, and medical oncologists and had major effects on the treatment of women with breast cancer. In this special issue of The Breast Journal celebrating 25 years of publication, it is of value to reflect back on these changes, some expected and some unanticipated, which have occurred over the past three decades and to consider the reasons why core needle biopsies should be considered a milestone in breast pathology.

Introduction. Glucocorticoids (GCs) remain widely used. However, the impact of GCs from the perspective of the patient, rather than of the clinician, remains relatively unexplored. Additionally, no general patient reported outcome measure has been developed to assess the effects of GCs across rheumatological conditions. The aim of this literature review was to identify the adverse effects of systemic GC use that are of importance to patients. Methods. OVID EMBASE, OVID MEDLINE, PsycINFO and CINAHL was searched relating to three concepts: GCs, the patient perspective and adverse effects. A meta-synthesis of the qualitative data was performed separately by two independent researchers before qualitative metasummary was utilized to quantitatively aggregate the findings (combining quantitative and qualitative results), including the derivation of frequency and intensity effect sizes to identify those outcomes most prominently featured across all reviewed articles. Results. The initial search retrieved 1,356 articles, of which 25 (18 quantitative, 7 qualitative) were deemed suitable for quality assessment and data extraction. Four major themes emerged amongst the 71 discrete outcomes: physical symptoms (44), psychological symptoms (18), effect on participation (6) and contextual factors (3). Conclusions. Patients with a broad range of inflammatory diseases and demographic features describe key cross-cutting themes in relation to GCs and their impact on health-related quality of life. This work will inform the development of a core domain set for clinical trials involving GCs and a patient reported outcome to measure impact of GCs from the patient's perspective.

Background: Cataracts and glaucoma are recognised glucocorticoid (GC) adverse effects. However, the impact of GC use, dose and timing on the development of cataracts and glaucoma has not been well quantified. Objectives: 1. To determine the association between GC use and dose and the development of cataract and glaucoma in patients with incident RA, 2. To determine the lag effect of GC dose. Methods: Data were used from the Clinical Practice Research Datalink (CPRD), a large UK primary care database derived from an electronic medical record (Jan 1992- Dec 2017). RA patients were identified using a validated algorithm and only incident patients were included. Parametric log-logistic survival models were used to assess the impact of GC use, dose (prednisolone daily dose equivalent) and lagged dose (at 1, 3, 6 months, 1 & 2 years). A square root transformation of dose was used for the cataract models. Smoking, gender and uveitis were included as covariates in the model and age was used as the timescale. Comorbidities on the causal pathway, such as diabetes and hypertension, were not included. Results were reported as odds ratios (OR) for the cumulative incidence. Results: There were 22607 patients with incident RA (median age 66, IQR 37-84, 68% female), of which 241 had cataracts and 164 had glaucoma on or before baseline. Median duration of follow up was 8.7 years (IQR 1.8-19.8) and 39% were ever GC users during follow up. The incidence rate, per 1000 patient-years was 12.3 (95% CI 11.8, 12.9) for cataracts and 3.1 (95% CI 2.8, 3.4) for glaucoma, and increased with age. Uveitis was an important predictor for both cataracts and glaucoma, and cataracts were more frequent in females. GC use and GC dose were associated with both cataracts and glaucoma (Table 1). In the multivariable lagged dose analysis, GC dose at 1-year prior had the greatest effect size for cataracts (OR 1.26, 95% CI 1.12, 1.42), whereas GC dose at 3-months prior had the greatest effect size for glaucoma (OR 1.06, 95% 1.01, 1.11). Conclusion: The quantification of the risk associated with GCs and the development of cataract and glaucoma is of clinical utility in daily practice. EULAR guidelines recommend patients are informed of the risks and benefits of GC treatment prior to commencement, however the risk of these potential adverse effects had not previously been quantified. This information will allow patients to make better-informed treatment choices in conjunction with their treating doctor. Disclosure of Interests: None declared

Although updated consensus guidelines, and effective therapies, are available for management of gout, suboptimal management remains an issue. Barriers were identified and addressed as part of a dedicated, structured gout clinic. More frequent appointments resulted in a faster rate of serum urate reduction, and the clinic provided the opportunity for the education of both patients and general practitioners in the management of gout.

Background To compare the utility of ESR, CRP and platelets for the diagnosis of GCA. Method A clinical diagnosis of GCA was determined by case-note review of 270 individuals (68% female, mean age 72 years) referred to a central pathology service for a temporal artery biopsy between 2011 and 2014. The highest levels of ESR, CRP and platelets (within 2 weeks of diagnosis) were documented. Evaluation of ESR, CRP and platelets for the diagnosis of GCA were compared using Receiver Operating Characteristic Area Under the Curve (ROC-AUC), and sensitivity/specificity at optimum cut-off values. Results GCA was clinically diagnosed in 139 (67%) patients, with 81 TAB positive. The AUC estimates for ESR, CRP and platelets were comparable (0.65 vs 0.72 vs 0.72, p = 0.08). The estimated optimal cut-off levels were confirmed at 50 mm/hour for ESR, and determined as 20 mg/L for CRP and 300 × 109/L for platelets. Sensitivity estimates for these three tests were comparable (p = 0.45) and ranged between 66% for ESR and 71% for platelets. Specificity estimates were also comparable (p = 0.11) and ranged between 57% for ESR and 68% for CRP. There was only moderate agreement between the three positive tests (agreement 67%, kappa: 0.34), and when considered collectively, CRP and platelet positive tests were independent predictors of GCA (p

Background: Response to neoadjuvant chemotherapy in breast cancer serves as an important prognostic indicator, as patients whose estrogen receptor (ER) negative and/or HER2 positive cancers undergo a pathologic complete response (pCR) have an excellent outcome. Guidelines on classification of treatment response are available, but data is lacking for the rare event where lymph-vascular invasion (LVI) is the only residual disease in the breast. Only one study (Rabban JT et al, Am J Surg Pathol, 2009) has investigated the significance of this pattern of residual disease. These authors reported 6 patients with residual LVI in the breast in the absence of stromal invasion. Five of the patients also had residual disease in lymph nodes. Prognosis was poor with four of the patients dying in less than 4 years and an additional patient dying at 10 years. The aim of our study was to gather more data on this rare pattern of residual disease, with a focus on node negative cases. Design: We retrospectively identified from our pathology database all cases in which LVI was the only residual disease in the breast after neoadjuvant therapy. Results: A total of 16 cases were identified, yielding an incidence of 1.6% of all cancers undergoing neoadjuvant chemotherapy over a 10 year period. All patients were females with a mean age of 54 years (range 40-69 years). Eight cancers initially presented as a palpable breast mass, 4 as vague breast symptoms, 2 as inflammatory carcinoma and 1 was detected on screening mammogram. In twelve cases the axillary lymph nodes were either suspicious by imaging or proven positive by needle biopsy. The mean pre-neoadjuvant tumor size was 2.7cm (range 0.5-8.0cm). Six cancers were negative for hormone receptors and HER2, eight cancers were positive for HER2 and 4 cancers were positive for ER. After neoadjuvant chemotherapy, nine patients had no residual disease in lymph nodes. The remaining seven patients had residual disease in lymph nodes, although minimal in the majority. The mean follow-up was 65 months for the node negative group (range 9-125 months) and 44 months for the node positive group (range 7-102 months). One death occurred in each group (at 12 months and 67 months respectively), two patients are alive with metastatic disease in the node negative group and the remaining 12 patients are alive without disease. Conclusions: Pure residual LVI after neoadjuvant chemotherapy is a rare event. Our findings show that the outcome associated with residual LVI, with or without residual cancer in nodes, might not be as dismal as previously reported, although longer follow-up will be required. The more favorable outcome observed is in contrast to the single study previously published. Although the difference may be due to details in the type of chemotherapy or stage at presentation, it is difficult to compare the 2 groups of patients due to limited information about the earlier cases. More data is needed to draw conclusions on the prognostic significance of this type of residual disease. The lack of a current AJCC/UICC T category for this finding will make identification of these patients difficult in large databases. Citation Format: Guilbert M-C, Lester SC. Lymph-vascular invasion in the absence of stomal invasion after neoadjuvant therapy: A rare pattern of residual carcinoma that lacks an AJCC/UICC T category [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-15.

Background Previous studies of mortality associated with GCA have shown conflicting results. We conducted a systematic review and meta-analysis to determine the mortality risk in GCA patients compared to the general population. Methods We searched for published studies indexed in MEDLINE and EMBASE and the Cochrane database from inception to June 18, 2015 using the terms "giant cell arteritis" and "temporal arteritis" combined with the terms for death, mortality, and survival. A manual search of citations from retrieved articles was also performed. The inclusion criteria were as follows: (1) observational studies of mortality in GCA and (2) comparison of mortality to the general population. Studies published only in abstract form were excluded. Study eligibility and quality (Newcastle–Ottawa scale) were independently assessed by at least two investigators. Random effects meta-analysis of the mortality ratio (MR) was performed by the inverse variance method. Results Out of 435 potentially relevant articles, 64 studies were reviewed, 19 studies were included in the review and 17 studies were included in the meta-analysis. Mortality was not increased in GCA patients ascertained from a population base (MR = 1.03, 95% CI: 0.96–1.10), but was increased in patients ascertained from a hospital setting (MR = 1.61, 95% CI: 1.19–2.19). There was no difference in MR by gender, and two studies provided evidence that mortality was increased in the early years following diagnosis. Conclusion At a population level, long-term mortality is not increased in GCA. However, mortality risk may be increased in some patients, and may vary over time.

Background: Zn (Zn) is an essential trace element with important roles in protein structure and function. Labile Zn is the fraction available for regulatory functions through it loose binding to albumin. As Zn deprivation reduces labile Zn levels and leads to an immune compromised state, we investigated labile Zn levels in the context of systemic autoimmune disease. Methods: Cross sectional case control study in patients with Systemic Lupus Erythematosus (SLE; n= 45), primary Sjogren’s Syndrome (n= 53) and healthy controls (HC; n= 27). Serum labile Zn levels were measured by an in-house assay using the UV-excitable fluorophore zinquin ethyl ester. Associations between labile Zn levels and SLE manifestations were investigated by nonparametric methods. Results: None of the SLE or pSS patients was found to be Zn deficient. Labile Zn levels were significantly higher in SLE (31.7 mcg/dl) than in pSS patients (22.3 mcg/dl) and HC (19.7 mcg/dl) (p

Context.—A review of amended pathology reports provides valuable information regarding defects in the surgical pathology process.Objective.—To review amended breast pathology reports with emphasis placed on interpretative errors and their mechanisms of detection.Design.—All amended pathology reports for breast surgical specimens for a 5-year period at a large academic medical center were retrospectively identified and classified based on an established taxonomy.Results.—Of 12 228 breast pathology reports, 122 amended reports were identified. Most (88 cases; 72%) amendments were due to noninterpretative errors, including 58 report defects, 12 misidentifications, and 3 specimen defects. A few (34 cases; 27.9%) were classified as misinterpretations, including 14 major diagnostic changes (11.5% of all amendments). Among major changes, there were cases of missed microinvasion or small foci of invasion, missed micrometastasis, atypical ductal hyperplasia overcalled as ductal carcinoma in situ, ductal carcinoma in situ involving sclerosing adenosis mistaken for invasive carcinoma, lymphoma mistaken for invasive carcinoma, and amyloidosis misdiagnosed as fat necrosis. Nine major changes were detected at interpretation of receptor studies and were not associated with clinical consequences. Three cases were associated with clinical consequences, and of note, the same pathologist interpreted the corresponding receptor studies.Conclusions.—Review of amended reports was a useful method for identifying error frequencies, types, and methods of detection. Any time that a case is revisited for ancillary studies or other reasons, it is an opportunity for the surgical pathologist to reconsider one's own or another's diagnosis.

INTRODUCTION The aim of this study was to determine whether a single-nucleotide polymorphism (SNP; 1858CT, R620W) in the protein tyrosine phosphatase N22 (PTPN22) gene confers susceptibility to idiopathic inflammatory myopathy (IIM) in South Australian patients with IIM. METHODS Genotyping was performed on stored DNA from 199 patients with histologically confirmed polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM), and then compared with 455 matched controls. Associations with the 8.1 ancestral haplotype (AH), and myositis-specific (MSA) and myositis-associated (MAA) autoantibodies were investigated. RESULTS The PTPN22 R620W minor allele frequency was increased in IIM patients (50 of 398, 12.6%) compared with controls (75 of 910, 8.2%) (odds ratio 1.6, 95% confidence interval 1.1-2.3, P = 0.016). In IIM patients, there was no association between the R620W minor allele and detection of any MSA/MAA (P = 0.70), nor any evidence of epistasis with the 8.1 AH (P = 0.69). CONCLUSIONS The PTPN22 R620W minor allele is associated with susceptibility to IIM in SA patients, independent of the 8.1 AH. Muscle Nerve, 2016 Muscle Nerve 55: 270-273, 2017.

This author accepted manuscript (post print) is made available following a 12 month embargo from the date of publication (26 October 2016) in accordance with the publisher copyright policy.

To determine factors associated with opioid use in rheumatoid arthritis (RA) patients.Adult RA patients (n = 3225, 73% female, mean age 57 years, median follow-up 54 months) were recruited into the Australian Rheumatology Association Database (ARAD) between 2001-2015. A logistic regression examining both within- and between-patient effect sizes for time-varying covariates, and transition-state analysis for covariates associated with opioid commencement or cessation were used to examine determinants of current opioid use.The population-averaged prevalence of any opioid use was 33% (95%CI 32-34), 9% (95% CI 8, 10) for high potency opioid use, and 62% (95% 60, 64) of patients reported opioid ever-use after five years of follow-up. Opioid use was higher in females and decreased with older baseline age. Within-patients opioid use was associated with higher self-reported pain and HAQ scores (p0.001), and NSAID (OR 1.88; 1.67-2.10), oral glucocorticoid (2.23;1.93-2.58), csDMARD (2.08;1.78-2.44) and bDMARD (1.22;1.06-1.40) treatment. Younger baseline age, higher pain scores, HAQ scores and oral GC use were important determinants of change in opioid use, associated with both a higher probability of commencing opioid use, and a lower probability of cessation. Paradoxically, NSAID and DMARD treatments were associated with both a lower probability of commencing opioids, and a lower probability of cessation.There was a high prevalence of opioid use among RA patients, which was associated with pain, function and GC treatment. NSAID, and DMARD treatments obviate the need for opioids in some, but not all, patients.

To retrospectively review the frequency, patterns and intra-abdominal sites of metastatic invasive lobular breast cancer, and to correlate the findings with overall survival. From a pathology database search revealing 327 patients with metastatic lobular breast cancer at our institution from January 2004 through August 2014, imaging was available in 116 patients (age range, 31–87 years, mean age, 55). Simple descriptive statistics were performed to record and tabulate the abdominal metastatic spread. Prognostic significance of abdominal metastases and individual abdominal metastatic sites was studied using the Log-rank test and construction of Kaplan–Meier curves. The most frequent sites of intra-abdominal metastatic invasive lobular breast cancer were peritoneum (55 patients, 47%), followed by liver (37 patients, 32%), bowel (34 patients, 29%), ovary (33 patients, 28%), retroperitoneum (16 patients, 14%), ureter (16 patients, 14%), and lymph nodes (15 patients, 13%). Bowel obstruction was noted in 15 patients (13%) and hydronephrosis in 25 patients (22%). The median abdominal metastasis-free survival was 76 months (interquartile range: 17–191). The overall survival (OS) was 86 months (interquartile range: 49–188). Patients with abdominal metastases had shorter OS. Patients with hepatic metastases had shorter overall survival than those patients without hepatic metastases (p = 0.02, Log-Rank test). Invasive lobular breast cancer has a predilection for metastasizing to both typical (liver) and atypical intra-abdominal sites (peritoneum, GI tract, and adnexa). Presence of intra-abdominal disease and hepatic metastases in patients with ILC negatively affects overall survival.

Objective To determine the relationships between systemic sclerosis (SSc)–related autoantibodies, as well as their clinical associations, in a well-characterized Australian patient cohort. Methods Serum from 505 Australian SSc patients were analyzed with a commercial line immunoassay (EuroLine; Euroimmun) for autoantibodies to centromere proteins CENP-A and CENP-B, RNA polymerase III (RNAP III; epitopes 11 and 155), the 90-kd nucleolar protein NOR-90, fibrillarin, Th/To, PM/Scl-75, PM/Scl-100, Ku, topoisomerase I (topo I), tripartite motif–containing protein 21/Ro 52, and platelet-derived growth factor receptor. Patient subgroups were identified by hierarchical clustering of the first 2 dimensions of a principal components analysis of quantitative autoantibody scores. Results were compared with detailed clinical data. Results A total of 449 of the 505 patients were positive for at least 1 autoantibody by immunoblotting. Heatmap visualization of autoantibody scores, along with principal components analysis clustering, demonstrated strong, mutually exclusive relationships between CENP, RNAP III, and topo I. Five patient clusters were identified: CENP, RNAP III strong, RNAP III weak, topo I, and other. Clinical features associated with CENP, RNAP III, and topo I were consistent with previously published reports concerning limited cutaneous and diffuse cutaneous SSc. A novel finding was the statistical separation of RNAP III into 2 clusters. Patients in the RNAP III strong cluster had an increased risk of gastric antral vascular ectasia, but a lower risk of esophageal dysmotility. Patients in the other cluster were more likely to be male and to have a history of smoking and a history of malignancy, but were less likely to have telangiectasia, Raynaud's phenomenon, and joint contractures. Conclusion Five major autoantibody clusters with specific clinical and serologic associations were identified in Australian SSc patients. Subclassification and disease stratification using autoantibodies may have clinical utility, particularly in early disease.

SummaryInvasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.

Highlights • Recurrence of breast cancer at the site of a prior core needle biopsy after definitive surgery is very rare—only 13 cases have been reported. • The majority are recurrent invasive cancers forming palpable masses in dermis and subcutaneous tissue at the skin puncture site of the core needle biopsy. • Diagnosis can be delayed if a lesion is not initially recognized as being at a needle biopsy site. • We report the first case of needle puncture site recurrence as Paget disease of the epidermis (ductal carcinoma in situ). • It is important to document the site of the skin puncture of a needle biopsy to aid in early detection, and recognition, of needle track recurrences., Introduction Core needle biopsy has become the preferred method of diagnosing breast carcinomas prior to definitive surgery. The possibility of displacing tumor cells into the needle track is a concern. Presentation of case A 38 year old woman was diagnosed with right breast ductal carcinoma in situ (DCIS) with microinvasion by core needle biopsy. Bilateral skin sparing mastectomies with immediate autologous reconstruction were performed. One and a half years later the patient noted erythema and a scaling crust on the skin of the right breast that progressed over several months. Punch biopsy revealed Paget disease restricted to the epidermis. Subsequent comparison to initial clinical photographs confirmed the cancer was associated with the skin puncture site of the needle biopsy. The patient underwent complete excision with skin grafting and remains free of disease three years later. Discussion Only 13 cases of needle track recurrences have been reported. The majority presented as invasive carcinoma forming a subcutaneous mass. In the current case, detection was delayed due to not initially noting that a skin lesion was at the puncture site of the original needle biopsy. This is the only case of recurrence as tumor limited to the epidermis. Conclusion Although recurrence in a needle track occurs very infrequently, clinicians should be aware of this phenomenon and investigate any changes, particularly when occurring at a needle biopsy site. Recording the skin puncture site can aid in early detection of recurrences. Recognition of a recurrence is important for prompt treatment and optimal prognosis.