Department Wide Validation in Digital Pathology-Experience from an Academic Teaching Hospital Using the UK Royal College of Pathologists' Guidance.

AIM: we describe our experience of validating departmental pathologists for digital pathology reporting, based on the UK Royal College of Pathologists (RCPath) "Best Practice Recommendations for Implementing Digital Pathology (DP)," at a large academic teaching hospital that scans 100% of its surgical workload. We focus on Stage 2 of validation (prospective experience) prior to full validation sign-off. METHODS AND RESULTS: twenty histopathologists completed Stage 1 of the validation process and subsequently completed Stage 2 validation, prospectively reporting a total of 3777 cases covering eight specialities. All cases were initially viewed on digital whole slide images (WSI) with relevant parameters checked on glass slides, and discordances were reconciled before the case was signed out. Pathologists kept an electronic log of the cases, the preferred reporting modality used, and their experiences. At the end of each validation, a summary was compiled and reviewed with a mentor. This was submitted to the DP Steering Group who assessed the scope of cases and experience before sign-off for full validation. A total of 1.3% (49/3777) of the cases had a discordance between WSI and glass slides. A total of 61% (30/49) of the discordances were categorised as a minor error in a supplementary parameter without clinical impact. The most common reasons for diagnostic discordances across specialities included identification and grading of dysplasia, assessment of tumour invasion, identification of small prognostic or diagnostic objects, interpretation of immunohistochemistry/special stains, and mitotic count assessment. Pathologists showed similar mean diagnostic confidences (on Likert scale from 0 to 7) with a mean of 6.8 on digital and 6.9 on glass slide reporting. CONCLUSION: we describe one of the first real-world experiences of a department-wide effort to implement, validate, and roll out digital pathology reporting by applying the RCPath Recommendations for Implementing DP. We have shown a very low rate of discordance between WSI and glass slides.

RFID analysis of the complexity of cellular pathology workflow-An opportunity for digital pathology.

Digital pathology (DP) offers potential for time efficiency gains over an analog workflow however, to date, evidence supporting this claim is relatively lacking. Studies available concentrate on specific workflow points such as diagnostic reporting time, rather than overall efficiencies in slide logistics that might be expected. This is in part a result of the complexity and variation in analog working, and the challenge therefore in capturing this. We have utilized RFID technology to conduct a novel study capturing the movement of diagnostic cases within the analog pathway in a large teaching hospital setting, thus providing benchmark data for potential efficiency gains with DP. This technology overcomes the need to manually record data items and has facilitated the capture of both the physical journey of a case and the time associated with relevant components of the analog pathway predicted to be redundant in the digital setting. RFID tracking of 1,173 surgical pathology cases and over 30 staff in an analog cellular pathology workflow illustrates the complexity of the physical movement of slides within the department, which impacts on case traceability within the system. Detailed analysis of over 400 case journeys highlights redundant periods created by batching of slides at workflow points, including potentially 2-3 h for a case to become available for reporting after release from the lab, and variable lag-times prior to collection for reporting, and provides an illustration of patterns of lab and pathologist working within the analog setting. This study supports the challenge in evidencing efficiency gains to be anticipated with DP in the context of the variation and complexity of the analog pathway, but also evidences the efficiency gains that may be expected through a greater understanding of patterns of working and movement of cases. Such data may benefit other departments building a business case for DP.

Digital Pathology Transformation in a Supraregional Germ Cell Tumour Network.

BACKGROUND: In this article we share our experience of creating a digital pathology (DP) supraregional germ cell tumour service, including full digitisation of the central laboratory. METHODS: DP infrastructure (Philips) was deployed across our hospital network to allow full central digitisation with partial digitisation of two peripheral sites in the supraregional testis germ cell tumour network. We used a survey-based approach to capture the quantitative and qualitative experiences of the multidisciplinary teams involved. RESULTS: The deployment enabled case sharing for the purposes of diagnostic reporting, second opinion, and supraregional review. DP was seen as a positive step forward for the departments involved, and for the wider germ cell tumour network, and was completed without significant issues. Whilst there were challenges, the transition to DP was regarded as worthwhile, and examples of benefits to patients are already recognised. CONCLUSION: Pathology networks, including highly specialised services, such as in this study, are ideally suited to be digitised. We highlight many of the benefits but also the challenges that must be overcome for such clinical transformation. Overall, from the survey, the change was seen as universally positive for our service and highlights the importance of engagement of the whole team to achieve success.

Role of digital pathology in diagnostic histopathology in the response to COVID-19: results from a survey of experience in a UK tertiary referral hospital.

The COVID-19 pandemic has challenged our diagnostic services at a time when many histopathology departments already faced a diminishing workforce and increasing workload. Digital pathology (DP) has been hailed as a potential solution to at least some of the challenges faced. We present a survey of pathologists within a UK National Health Service cellular pathology department with access to DP, in which we ascertain the role of DP in clinical services during this current pandemic and explore challenges encountered. This survey indicates an increase in uptake of diagnostic DP during this period, with increased remote access. Half of respondents agreed that DP had facilitated maintenance of diagnostic practice. While challenges have been encountered, these are remediable, and none have impacted on the uptake of DP during this period. We conclude that in our institution, DP has demonstrated current and future potential to increase resilience in diagnostic practice and have highlighted some of the challenges that need to be considered.

On the Edge of a Digital Pathology Transformation: Views from a Cellular Pathology Laboratory Focus Group.

INTRODUCTION: Digital pathology has the potential to revolutionize the way clinical diagnoses are made while improving safety and quality. With a few notable exceptions in the UK, few National Health Service (NHS) departments have deployed digital pathology platforms. Thus, in the next few years, many departments are anticipated to undergo the transition to digital pathology. In this period of transition, capturing attitudes and experiences can elucidate issues to be addressed and foster collaboration between NHS Trusts. This study aims to qualitatively ascertain the benefits and challenges of transitioning to digital pathology from the perspectives of pathologists and biomedical scientists in a department about to undergo the transition from diagnostic reporting via traditional microscopy to digital pathology. METHODS: A focus group discussion was held in the setting of a large NHS teaching hospital's cellular pathology department which was on the brink of transitioning to digital pathology. A set of open questions were developed and posed to a group of pathologists and biomedical scientists in a focus group setting. Notes of the discussion were made along with an audio recording with permission. The discussion was subsequently turned into a series of topic headings and analyzed using content analysis. RESULTS: Identified benefits of digital pathology included enhanced collaboration, teaching, cost savings, research, growth of specialty, multidisciplinary teams, and patient-centered care. Barriers to transitioning to digital pathology included standardization, validation, national implementation, storage and backups, training, logistical implementation, cost-effectiveness, privacy, and legality. CONCLUSION: Many benefits of digital pathology were identified, but key barriers need to be addressed in order to fully implement digital pathology on a trust and national level.

Exfoliative cytology for diagnosing basal cell carcinoma and other skin cancers in adults.

BACKGROUND: Early accurate detection of all skin cancer types is essential to guide appropriate management, reduce morbidity and improve survival. Basal cell carcinoma (BCC) is usually localised to the skin but has potential to infiltrate and damage surrounding tissue, while cutaneous squamous cell carcinoma (cSCC) and melanoma have a much higher potential to metastasise and ultimately lead to death. Exfoliative cytology is a non-invasive test that uses the Tzanck smear technique to identify disease by examining the structure of cells obtained from scraped samples. This simple procedure is a less invasive diagnostic test than a skin biopsy, and for BCC it has the potential to provide an immediate diagnosis that avoids an additional clinic visit to receive skin biopsy results. This may benefit patients scheduled for either Mohs micrographic surgery or non-surgical treatments such as radiotherapy. A cytology scrape can never give the same information as a skin biopsy, however, so it is important to better understand in which skin cancer situations it may be helpful. OBJECTIVES: To determine the diagnostic accuracy of exfoliative cytology for detecting basal cell carcinoma (BCC) in adults, and to compare its accuracy with that of standard diagnostic practice (visual inspection with or without dermoscopy). Secondary objectives were: to determine the diagnostic accuracy of exfoliative cytology for detecting cSCC, invasive melanoma and atypical intraepidermal melanocytic variants, and any other skin cancer; and for each of these secondary conditions to compare the accuracy of exfoliative cytology with visual inspection with or without dermoscopy in direct test comparisons; and to determine the effect of observer experience. SEARCH METHODS: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We also studied the reference lists of published systematic review articles. SELECTION CRITERIA: Studies evaluating exfoliative cytology in adults with lesions suspicious for BCC, cSCC or melanoma, compared with a reference standard of histological confirmation. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Where possible we estimated summary sensitivities and specificities using the bivariate hierarchical model. MAIN RESULTS: We synthesised the results of nine studies contributing a total of 1655 lesions to our analysis, including 1120 BCCs (14 datasets), 41 cSCCs (amongst 401 lesions in 2 datasets), and 10 melanomas (amongst 200 lesions in 1 dataset). Three of these datasets (one each for BCC, melanoma and any malignant condition) were derived from one study that also performed a direct comparison with dermoscopy. Studies were of moderate to poor quality, providing inadequate descriptions of participant selection, thresholds used to make cytological and histological diagnoses, and blinding. Reporting of participants' prior referral pathways was particularly poor, as were descriptions of the cytodiagnostic criteria used to make diagnoses. No studies evaluated the use of exfoliative cytology as a primary diagnostic test for detecting BCC or other skin cancers in lesions suspicious for skin cancer. Pooled data from seven studies using standard cytomorphological criteria (but various stain methods) to detect BCC in participants with a high clinical suspicion of BCC estimated the sensitivity and specificity of exfoliative cytology as 97.5% (95% CI 94.5% to 98.9%) and 90.1% (95% CI 81.1% to 95.1%). respectively. When applied to a hypothetical population of 1000 clinically suspected BCC lesions with a median observed BCC prevalence of 86%, exfoliative cytology would miss 21 BCCs and would lead to 14 false positive diagnoses of BCC. No false positive cases were histologically confirmed to be melanoma. Insufficient data are available to make summary statements regarding the accuracy of exfoliative cytology to detect melanoma or cSCC, or its accuracy compared to dermoscopy. AUTHORS' CONCLUSIONS: The utility of exfoliative cytology for the primary diagnosis of skin cancer is unknown, as all included studies focused on the use of this technique for confirming strongly suspected clinical diagnoses. For the confirmation of BCC in lesions with a high clinical suspicion, there is evidence of high sensitivity and specificity. Since decisions to treat low-risk BCCs are unlikely in practice to require diagnostic confirmation given that clinical suspicion is already high, exfoliative cytology might be most useful for cases of BCC where the treatments being contemplated require a tissue diagnosis (e.g. radiotherapy). The small number of included studies, poor reporting and varying methodological quality prevent us from drawing strong conclusions to guide clinical practice. Despite insufficient data on the use of cytology for cSCC or melanoma, it is unlikely that cytology would be useful in these scenarios since preservation of the architecture of the whole lesion that would be available from a biopsy provides crucial diagnostic information. Given the paucity of good quality data, appropriately designed prospective comparative studies may be required to evaluate both the diagnostic value of exfoliative cytology by comparison to dermoscopy, and its confirmatory value in adequately reported populations with a high probability of BCC scheduled for further treatment requiring a tissue diagnosis.

Histopathological assessment of metastasis.

In spite of advances in the fields of immunohistochemistry and molecular biology, in clinical practice much of the assessment of metastases still relies on light microscopy using conventional histological stains. This is not so much a reflection of a reluctance by histopathologists to adopt new techniques, but more an indication that for most malignancies an enormous amount of useful prognostic data can be gained from relatively unsophisticated assessment of tissues, and that many of the strongest studies of prognostic factors in malignancy predate the era of molecular diagnostics. Although it is undoubtedly true that newer techniques have added prognostic information in the assessment of many tumors, and many, such as the measurement of estrogen receptor status in breast cancer, could be considered routine, a skilled assessment of the morphology of the tissues still provides the fundamental basis of assessing prognosis in the vast majority of cases.

One in four patients with follicular thyroid cytology (THY3) has a thyroid carcinoma.

BACKGROUND: Fine-needle aspiration (FNA) biopsy is the cornerstone of assessment of thyroid nodules. Cytological criteria for benign (THY2) and malignant (THY5) aspirates are well established and reliable. When cytology suggests a follicular neoplasm (THY3), only formal histological assessment can differentiate between benign and malignant lesions. The objective of this study was to determine the factors predictive of malignancy in thyroid nodules when cytological assessment is restricted to euthyroid patients living in an area without endemic goiter who undergo routine diagnostic lobectomy once the FNA raises the suspicion of a follicular neoplasm. METHOD: Retrospective review of histological and clinical data in a cohort of patients with a palpable thyroid nodule and THY3 cytology. RESULTS: Between January 2000 and December 2007, 1981 patients (346 males and 1635 females) underwent 2809 thyroid FNAs. There were 201 THY3 reports (9%). Histology demonstrated thyroid carcinomas in 57 patients (31 follicular carcinomas, 11 Hurthle cell carcinomas, 11 papillary carcinomas, 1 medullary thyroid carcinoma, 1 poorly differentiated thyroid cancer, 1 lymphoma, and 1 metastatic renal carcinoma). Benign tumors were found in 144 patients with follicular adenomas (n = 76), Hurthle cell adenomas (n = 33), multinodular goiter (n = 13), adenomatoid nodules (n = 15), colloid nodules (n = 4), and thyroiditis (n = 3). THY3 cytology was more predictive of malignancy in men (13/34 male symbol vs. 44/167 female symbol, p < 0.001, chi(2) test). The risk for malignancy was 1:4 for the entire group and 1:3 for patients under 30 years and over 60 years. About 17/46 nodules over 40 mm in diameter were carcinomas, compared with only 35/140 in nodules under 40 mm (p < 0.01, chi2 test). CONCLUSION: One in four patients with cytological features of a follicular neoplasm has a thyroid carcinoma. A large nodule (>4 cm) with THY3 cytology has a high likelihood of being a cancer, and arguably such patients could be offered total thyroidectomy rather than diagnostic lobectomy.

Routine preoperative (123)I-MIBG scintigraphy for patients with phaeochromocytoma is not necessary.

BACKGROUND: Functional imaging using (123)I-meta-iodo-benzyl-guanetidine (MIBG) scintigraphy has alleged 100% specificity for phaeochromocytoma (PHAEO). Its benefit in patients with biochemical diagnosis of PHAEO is arguable when cross-sectional radiology can demonstrate the side-size of the adrenal tumours. MATERIALS AND METHODS: This is a retrospective review of clinical notes of patients undergoing adrenalectomy for PHAEO in a University centre. RESULTS: Between January 2000 and December 2007, adrenalectomy for PHAEO was performed on 66 patients (28 M and 38 F, aged 24-82 years). Diagnosis was demonstrated by raised 24-h urine catecholamines (n = 14) or metanephrines (n = 52). The side and size of adrenal tumours were demonstrated on computed tomography (n = 58) and/or magnetic resonance imaging (n = 20) scans. MIBG scans were performed in 38 patients. Four of these patients were found to have non-adrenal pathology (haemangioblastomas, haemangioma, a bronchogenic cyst and an angiomyolipoma); hence, the positive predictive value of MIBG scan was 90%. In a further five patients, MIBG raised the suspicion of local metastatic disease but this was not confirmed on operative findings and no recurrence was detected in these patients during 6-92-month follow-up. This led to an overall rate of false-positive rate of 23%. CONCLUSION: MIBG scintigraphy adds little to the routine preoperative management of patients with suspected PHAEO. Its use should be limited to the small minority of patients with negative cross-sectional imaging and those with recurrent or metastatic disease.

Negative imaging studies for primary hyperparathyroidism are unavoidable: correlation of sestamibi and high-resolution ultrasound scanning with histological analysis in 150 patients.

BACKGROUND: Preoperative localization studies with Tc99m-sestamibi have become an integral step in the preoperative assessment of patients with primary hyperparathyroidism (PHPT). This enables scan-directed minimally invasive parathyroidectomy (MIP) to be the preferred treatment for PHPT in many units. This study aimed to identify factors that lead to negative imaging studies in patients with PHPT. METHODS: Over a 3-year period consecutive unselected patients with PHPT underwent Tc99m-sestamibi scanning and high-resolution ultrasound (US) scanning by the same radiologist. When localization studies were concordant, patients underwent MIP. Those patients with negative imaging studies underwent bilateral neck exploration. Histology slides were independently reviewed and the proportion of chief cells and oxyphil cells within each adenoma was estimated. RESULTS: One hundred and fifty-eight patients underwent localization studies (38 men and 120 women, aged 61.8 +/- 15.2 years). Sestamibi scans were negative in 52 (32%) and positive in 106 (68%) patients. There was a higher incidence of hyperplasia in the group of patients with negative sestamibi scans (4 out of 52 vs. 4 out of 103, P < 0.05, chi2 test). In patients with negative sestamibi scans the majority of adenomas were formed predominantly from chief cells (26 out of 36) while the majority of patients with adenomas composed predominantly of oxyphil cells had positive scans (21 out of 23) (P < 0.05, chi2 test). The weight of parathyroid adenomas was higher when sestamibi scans were positive (median: 1,180 vs. 517 mg, P < 0.05, Student's t-test). CONCLUSION: Successful preoperative localization of parathyroid adenomas using Tc99m-sestamibi scanning is influenced by the cytological predominance of individual tumors. Negative scans might therefore be unavoidable in a subgroup of patients.

Traditional and established indicators of prognosis and treatment success.

The outcome of breast cancer in an individual patient can be predicted by assessing a range of factors relating to the particular cancer. This assessment can be used to select treatments that are most likely to be successful, and to avoid futile or unnecessarily aggressive procedures. Histopathological examination provides information on most of these factors. The most useful prognostic indicators in standard use are currently tumor stage, tumor grade, completeness of surgical excision, and estogen receptor status.