Development of a cost-effective diagnostic algorithm incorporating transcription factor immunohistochemistry in the evaluation of pituitary tumours.

PURPOSE: To determine the utility of the 2022 WHO Classification of pituitary tumours in routine clinical practice and to develop an optimal diagnostic algorithm for evaluation of tumour type in a real-world setting. METHODS: Retrospective evaluation of pituitary tumour immunohistochemistry (IHC), operatively managed at St Vincent's Hospital Sydney, between 2019 and 2021. Routine IHC comprised evaluation of transcription factors [steroidogenic factor 1 (SF1), T-box transcription factor 19 (TPIT) and pituitary-specific positive transcription factor (PIT1)] and anterior pituitary hormones. Three tiered algorithms were tested, in which hormone IHC was performed selectively based on the initial transcription factor results. These were applied retrospectively and compared with current practice 'gold standard' comprising all transcription factor and hormone IHC. Diagnostic accuracy and cost were evaluated for each. RESULTS: There were 113 tumours included in the analysis. All three algorithms resulted in 100% concordance with the 'gold standard' in the characterisation of tumour lineage. While all three were associated with relative cost reduction, Algorithm #3, which omitted hormone IHC in the setting of positive SF1 or TPIT and performed IHC for growth hormone, prolactin and thyroid stimulating hormone only in the setting of PIT1 positivity, was the most cost-efficient. Additionally, there were 12/113 tumours with no distinct cell lineage. CONCLUSION: A diagnostic algorithm omitting hormone IHC except in cases of PIT1 positivity is an accurate and cost-effective approach to diagnose the type of pituitary tumour. A significant subgroup of pituitary tumours with no distinct cell lineage, frequently plurihormonal, remains difficult to classify with the new WHO criteria and requires further evaluation.

Digital vs traditional: Are diagnostic accuracy rates similar for glass slides vs whole slide images in a non-gynaecological external quality assurance setting?

INTRODUCTION: The Royal College of Pathologists of Australasia Quality Assurance Programs introduced virtual microscopy cases into its cytopathology non-gynaecological programme after a short pilot phase, to address the challenges of providing a purely glass slide-based external quality assurance programme to multiple participants both locally and internationally. The use of whole slide image (WSI) cases has facilitated a more robust programme in relation to standardised material and statistical analysis, with access to a wider variety of specimen types and diagnostic entities. METHOD: Diagnostic accuracy rates on 56 WSI were assessed against the reference diagnosis. A portion (12) of these WSI slides had been used in glass slide format in previous external quality assurance surveys, and the results of these were compared to the responses received as glass slide cases. RESULTS: Overall diagnostic accuracy for the 56 WSI cases was acceptable in comparison to the reference diagnosis. When these 12 cases were analysed individually, for seven of the 12 cases, virtual format was found to be not inferior to glass slides for diagnostic accuracy. For one case, accuracy using WSI for diagnosis was superior to glass format. CONCLUSION: Diagnostic accuracy, using WSI for cases in our external quality assurance programme is acceptable. As the use of digital microscopy in a large scale external quality assurance programme offers extensive advantages over a glass slide-based format, our results encourage future comparison of diagnostic accuracy for virtual compared to glass slide format at a point in time where pathologists are becoming increasingly familiar with virtual microscopy in everyday practice.

Characteristics of macrolide responders in persistent post-surgical rhinosinusitis.

INTRODUCTION: The anti-inflammatory effects of long term low dose macrolide therapy have shown benefit in the management of diffuse panbronchiolitis. Dramatic responses to macrolide in the upper airway are seen but our understanding of the patient phenotype predisposing to macrolide response in chronic rhinosinusitis (CRS) is poor. METHODS: A case control study was performed in a tertiary level rhinology practice of consecutive chronic rhinosinusitis patients placed on a 3-month low dose macrolide therapy after failing at least 3 months of corticosteroid irrigation therapy post-endoscopic sinus surgery. Patients were defined as a macrolide responder when having near normal endoscopy after a 3-month period of clarithromycin treatment. Patient characteristics of smoking, asthma, atopy status, revision surgery, symptom severity (SNOT-22) along with biomarkers from serum and tissue histopathology results were compared between groups. RESULTS: Of twenty-eight consecutive macrolide treated patients, 19 responders were compared to 9 non-responders. The groups were similar in age, female gender, non-smoking, asthma, and atopy. Macrolide response was associated with a lack of tissue eosinophilia (more than 10/HPF) and lower serum eosinophilia. Neutrophil expression was similar in tissue and serum. Squamous metaplasia was overexpressed in non-responders. CONCLUSION: Low tissue and serum eosinophilia, and absence of tissue squamous metaplasia may predict a CRS phenotype suitable to a trial of long-term macrolide therapy when surgery and topical therapy has failed.

Osteitic bone: a surrogate marker of eosinophilia in chronic rhinosinusitis.

BACKGROUND: Causes of osteitis in chronic rhinosinusitis (CRS) other than previous surgery are poorly defined. Patients with eosinophilic CRS (ECRS) have more severe disease and poorer outcomes despite repeated surgery. Associations between osteitis and markers of ECRS are not well described. METHODS: A cross-sectional study of CRS patients undergoing sinus surgery was conducted. Osteitis was scored radiologically using previously published measures. Associations between osteitis and histopathology, symptoms, endoscopy, CT mucosal score and seromarkers were analyzed. RESULTS: Eighty-eight patients were assessed of whom forty-five had osteitis. Patients undergoing revision surgery recorded higher osteitis scores. Patients with mucosal eosinophilia had higher osteitis score than those without. Patients with osteitis had higher serum eosinophil. Similar relationships were also found in primary surgery. Osteitis was associated with endoscopic and radiologic, but not symptomatic disease severity. CONCLUSIONS: Osteitis is associated with tissue and serum eosinophilia in both patients with and without prior surgery. Patients with these features may benefit from post-operative corticosteroid therapy to prevent osteitis.

From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal.

The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.

Role of cyclins D1 and D3 in vestibular schwannoma.

BACKGROUND: Vestibular schwannomas in younger patients have been observed to be larger in size and grow more quickly. OBJECTIVE: This study aimed to evaluate the expression of three important cell cycle proteins, cyclin D1, cyclin D3 and Ki-67, in vestibular schwannoma patients separated into two age groups: ≤ 40 years or > 40 years. METHOD: Immunohistochemical detection of cyclin D1, cyclin D3 and Ki-67 was undertaken in 180 surgically resected vestibular schwannomas. RESULTS: The proliferation index of vestibular schwannomas was statistically higher in the ≤ 40 years age group compared to that in the > 40 years age group (mean of 4.52 vs 3.27, respectively; p = 0.01). Overexpression of cyclin D1 and cyclin D3 was found in 68 per cent and 44 per cent of tumours, respectively. CONCLUSION: There was an increased Ki-67 proliferation index in the younger age group that appears to correlate with clinical behaviour. Vestibular schwannomas in both age groups show increased expression of cyclin D1 and cyclin D3.

In vivo studies with dimethyldithiocarbamate, a possible new antimicrobial for use against Aspergillus fumigatus in poultry.

Dimethyldithiocarbamate (DmDTC), the carbamate analogue, was tested for therapeutic efficacy in a series of in vivo challenge trials using 5- and 10-week-old white leghorn chickens. Challenge organisms were Pasteurella multocida X-73, Escherichia coli O1:K1, and Aspergillus fumigatus. Birds were evaluated for survival rates, lesion scores, and the rate at which the bacteria or mold could be reisolated following challenge. Results showed DmDTC to be ineffective against P. multocida and E. coli at the treatment levels and in the form used in these trials, but DmDTC significantly reduced lesion scores and inhibited the rate of isolation of A. fumigatus compared with untreated infected birds.