LESS: Label-efficient Multi-scale Learning for Cytological Whole Slide Image Screening

In computational pathology, multiple instance learning (MIL) is widely used to circumvent the computational impasse in giga-pixel whole slide image (WSI) analysis. It usually consists of two stages: patch-level feature extraction and slide-level aggregation. Recently, pretrained models or self-supervised learning have been used to extract patch features, but they suffer from low effectiveness or inefficiency due to overlooking the task-specific supervision provided by slide labels. Here we propose a weakly-supervised Label-Efficient WSI Screening method, dubbed LESS, for cytological WSI analysis with only slide-level labels, which can be effectively applied to small datasets. First, we suggest using variational positive-unlabeled (VPU) learning to uncover hidden labels of both benign and malignant patches. We provide appropriate supervision by using slide-level labels to improve the learning of patch-level features. Next, we take into account the sparse and random arrangement of cells in cytological WSIs. To address this, we propose a strategy to crop patches at multiple scales and utilize a cross-attention vision transformer (CrossViT) to combine information from different scales for WSI classification. The combination of our two steps achieves task-alignment, improving effectiveness and efficiency. We validate the proposed label-efficient method on a urine cytology WSI dataset encompassing 130 samples (13,000 patches) and FNAC 2019 dataset with 212 samples (21,200 patches). The experiment shows that the proposed LESS reaches 84.79%, 85.43%, 91.79% and 78.30% on a urine cytology WSI dataset, and 96.88%, 96.86%, 98.95%, 97.06% on FNAC 2019 dataset in terms of accuracy, AUC, sensitivity and specificity. It outperforms state-of-the-art MIL methods on pathology WSIs and realizes automatic cytological WSI cancer screening.Comment: This paper was submitted to Medical Image Analysis. It is under revie

Radial Basis Function Artificial Neural Network for the Investigation of Thyroid Cytological Lesions

Objective. This study investigates the potential of an artificial intelligence (AI) methodology, the radial basis function (RBF) artificial neural network (ANN), in the evaluation of thyroid lesions. Study Design. The study was performed on 447 patients who had both cytological and histological evaluation in agreement. Cytological specimens were prepared using liquid-based cytology, and the histological result was based on subsequent surgical samples. Each specimen was digitized; on these images, nuclear morphology features were measured by the use of an image analysis system. The extracted measurements (41,324 nuclei) were separated into two sets: the training set that was used to create the RBF ANN and the test set that was used to evaluate the RBF performance. The system aimed to predict the histological status as benign or malignant. Results. The RBF ANN obtained in the training set has sensitivity 82.5%, specificity 94.6%, and overall accuracy 90.3%, while in the test set, these indices were 81.4%, 90.0%, and 86.9%, respectively. Algorithm was used to classify patients on the basis of the RBF ANN, the overall sensitivity was 95.0%, the specificity was 95.5%, and no statistically significant difference was observed. Conclusion. AI techniques and especially ANNs, only in the recent years, have been studied extensively. The proposed approach is promising to avoid misdiagnoses and assists the everyday practice of the cytopathology. The major drawback in this approach is the automation of a procedure to accurately detect and measure cell nuclei from the digitized images

Risk Stratification of Thyroid Nodule: From Ultrasound Features to TIRADS

Since the 1990s, ultrasound (US) has played a major role in the assessment of thyroid nodules and their risk of malignancy. Over the last decade, the most eminent international societies have published US-based systems for the risk stratification of thyroid lesions, namely, Thyroid Imaging Reporting And Data Systems (TIRADSs). The introduction of TIRADSs into clinical practice has significantly increased the diagnostic power of US to a level approaching that of fine-needle aspiration cytology (FNAC). At present, we are probably approaching a new era in which US could be the primary tool to diagnose thyroid cancer. However, before using US in this new dominant role, we need further proof. This Special Issue, which includes reviews and original articles, aims to pave the way for the future in the field of thyroid US. Highly experienced thyroidologists focused on US are asked to contribute to achieve this goal

A study of palpable breast lumps with emphasis on early detection of malignancy using a modified triple test

INTRODUCTION: Breast lumps are one of the common problems encountered in women. These lumps are frequently seen in younger to middle aged women and often they go undetected for various reasons. These lumps have different etiologic causes and can be either benign of malignant. Early recognition of malignancy plays a vital role for improving survival. The need of the hour is a system to detect malignancy earlier and minimize the time needed for the detection of malignant lumps. OBJECTIVE: This study is done to determine the clinical characteristics of palpable breast lumps and with the objective of detecting malignancy earlier in patients presenting with palpable breast lumps using a modified triple test. MATERIALS AND METHODS: This is a Prospective observational study done in the department of General Surgery, Coimbatore Medical College Hospital, Coimbatore from July 2016 to June 2017.103 patients were included in this study after application of inclusion and exclusion criteria. Inclusion Criteria: 1. Female patients with age of > 20 years with palpable Breast lump. 2. Patient willing for lump excision. Exclusion Criteria: 1. Patients who are below 20 years, 2. Male patients, 3. Female patients with advanced disease which makes the diagnosis obvious, 4. Patients not willing for lump excision. Each patient underwent a modified triple test comprising of a detailed Clinical examination, Ultrasonography of breast and Fine Needle aspiration. All the patients finally underwent surgery for their condition and the results of the modified triple test as analyzed individually and collectively and were compared to histopathological diagnosis. DISCUSSION: Our study was an observational study and 103 patients were subjected to the study. In our study breast lumps were commonly seen in the age group of 31 to 40 years (45.6%) and least commonly seen after the age of 60 years, this is similar to the distribution seen in other studies. Younger aged women have more educationstandards and awareness that lead them to present earlier in the course of disease. About 59.2% of all the patients had symptoms for 4 to 9 months which was similar to that seen in few studies but some studies reported shorter duration of symptoms of mean of 3 months (Afsar A Bhatti et al 2010). Pain over the lump was an important symptom and 60% of patients with painless lumps had malignancy on histopathological examination (30 out of 50) in contrast to 15 % of the patients with painful breast lumps (8 out 53).Similar findings were also seen in a study conducted by Kaire innos et al (BMC public health 2013) and the usual mode of presentation of malignancy was a painless palpable lump. Of the clinical examination findings nipple discharge was also found to be an important finding. Of the patients with nipple discharge 77 % (17 out of 22) were found to have malignancy on final histopathological diagnosis, so nipple discharge might serve as an important clue to the diagnosis of malignancy, but many studies have shown that nipple discharge is usually benign and 10 to 15% of the patients with nipple discharge tend to have malignancy. (Van Zee K J et al Cancer 1998), probably study with a larger sample size would iron out the skewed results seen in our study. In our study the upper outer quadrant was commonly involved with tumor (45.6%) this was also consistent with the findings with a study done by Khemka et al., Hussain et al., and Khoda et al (JMS 2015).It has been demonstrated that the upper outer quadrant of the breast has more amount of epithelial tissue compared to other quadrants leading to more incidence of tumors. Axillary lymph node involvement was seen in 20.4 % (21 out of 103) of patients presenting with breast lumps and out of the patients who had axillary nodes 90%(19 out of 21) had biopsy proven malignancy, so axillary node involvement is a strong predictor that the tumor is malignant, this has also been recorded by Voss M et al (J Surg Oncol. 1999). It has been concluded in the study that patients with stage 3 breast cancer have a higher incidence of axillary metastasis and well differentiated tumors tend to metastasize slowly. So axillary involvement may be a pointer towards advanced or fast growing malignancy and should prompt immediate attention. When the clinical examination findings were examined as a whole clinical examination had sensitivity of 86.34 % and specificity of 91% for the detection of malignancy. Positive predictive value of Clinical examination was 85% and Negative predictive value was 92.19%. On analysis of various studies, it has been shown that sensitivity of the Clinical breast examination ranges from 21% to as high as 100% and the specificity ranges from 50% to 97.8%. In the present study, the high sensitivity could be because only patients with confirmed palpable lumps were included for the study. Our results are in concordance with many studies. ULTRASONOGRAPHY OF BREAST: The triple test used mammography as one of its components and mammogram had a sensitivity of 87% for malignancy detection. Crystal et al (2003), Susan k et al (2005), Corsetti et al (2006) and Sahiner et al (2007) had supported the use of USG in young patients with dense breast tissues and ultrasound was found to have a sensitivity of 89% in detecting symptomatic and palpable breast abnormalities. Though relatively a fresh modality ultrasound has gained widespread popularity due to easy availability of the equipment, it is less expensive and is non invasive and can provide accurate information in tumors more than 2mm. Both USG and mammography have their inherent advantages and disadvantages that have been discussed in literature. But in the current scenario USG has gained the acceptance among the medical fraternity and is included in the screening for malignant lesions of breast as a part of the modified triple test and its results are adequately validated by many studies. In our study 33 out of 103 patients had ultrasound findings suggestive of malignancy; out of them all had biopsy proven malignancy. Ultrasound had a sensitivity of 86.84% and specificity of 100% for the detection of malignancy, Positive predictive value for detection of malignancy was 100%, Negative predictive value to rule out malignancy was 92.86%. These findings when compared to available literature shows good correlation and in a study done by Khoda et al, USG sensitivity was 91.6%, specificity was 100%, positive predictive value was 100%, negative predictive value was 97.3%, Similarly in a study done by Pande et al sensitivity, specificity, positive predictive value and negative predictive value for ultrasonography were 95%, 94.1%, 95.5%, and 93.7%, respectively. Another study by Jan et al also yielded similar results. A sensitivity of 86.84 % means 13.16 malignant lesions would be missed out of 100 malignant lesions, so the diagnosis of a benign lump always does not mean that it is benign and it would need a combination of tests to confirm it, but nonetheless USG of the breast is a valuable and easy tool for the detection of malignancy. FINE NEEDLE ASPIRATION CYTOLOGY: In our study Fine Needle aspiration classified, 60 patients out of 103 (58.2%) as having benign breast disease, whereas 35 patients (34%) were diagnosed to have malignant disease. 8 (7.8%) patients had inconclusive reports. All patients with FNAC report suggestive of malignancy were biopsy proven to have carcinoma. But 1 out of 60 patients (1.6%) who were reported to have benign disease had malignant disease. Sensitivity and specificity of Fine Needle Aspiration Cytology to detect malignancy were 92.10% and 100% respectively. Positive predictive value was 100% and Negative predictive value was 95.58%. FNAC RESULTS IN VARIOUS STUDIES The results of our study are comparable to various studies and the values closely resemble the results seen by Mohamed et al. So the results indicate that FNAC as an independent variable has adequate diagnostic power and this is further enhanced by combination with other 2 tests. THE MODIFIED TRIPLE TEST ANALYSIS: Using modified triple test 37 patients (36%) had features suggestive of malignant disease and 66 patients (64%) were suspected to have benign breast disease. All of the 37 patients suspected to have malignancy on Modified Triple Test were biopsy proven to have malignant breast disease, where as 1 out of 66 (1.5%) patients assigned to have benign disease on Modified Triple Test turned out to be malignant. The sensitivity of modified triple test for the detection of malignancy was 97.36% and the specificity for the detection of malignancy was 100%.The positive predictive value of the Modified triple test was 100% and the Negative predictive value was 98.4%. This comparison shows that our results were comparable to the results seen in many studies and it has shown that the modified triple test can be used as a valuable clinical test for the detection of malignant lumps and it helps us to plan the surgical treatment earlier, accurately and helps us save time needed for a definitive diagnosis. CONCLUSION: Breast cancer is the foremost cause of cancer related death in young females; hence early detection of breast cancer carries much importance. The modified triple test in our study was an accurate predictor of malignancy, all of the patients who were suspected to have malignancy by Modified triple test had malignancy on histological analysis and specificity was 100%, that proved it as a best initial test for diagnosis of malignancy preoperatively. The results of the modified test in our study are as accurate as histological diagnosis. Of the three components of the modified triple test FNAC and Ultrasound of breast had 100% specificity for the diagnosis of malignant lumps. The modified triple test can be done in an outpatient clinic and the patients are not exposed to ionizing radiation. So it is a suitable diagnostic modality for breast lumps in young women of childbearing age. It has been shown that Ultrasound is as accurate as mammography in detection and differentiation of palpable breast lumps and it can also aid in guiding the site for FNAC and biopsy. Of the three components of the modified triple test FNAC was the most accurate modality. Three components of the modified triple test complemented each other and when done with experienced clinicians and Radiologists can reduce the time lag for the detection of malignancy and help us to institute early definitive treatment

IMAGE UNDERSTANDING OF MOLAR PREGNANCY BASED ON ANOMALIES DETECTION

Cancer occurs when normal cells grow and multiply without normal control. As the cells multiply, they form an area of abnormal cells, known as a tumour. Many tumours exhibit abnormal chromosomal segregation at cell division. These anomalies play an important role in detecting molar pregnancy cancer. Molar pregnancy, also known as hydatidiform mole, can be categorised into partial (PHM) and complete (CHM) mole, persistent gestational trophoblastic and choriocarcinoma. Hydatidiform moles are most commonly found in women under the age of 17 or over the age of 35. Hydatidiform moles can be detected by morphological and histopathological examination. Even experienced pathologists cannot easily classify between complete and partial hydatidiform moles. However, the distinction between complete and partial hydatidiform moles is important in order to recommend the appropriate treatment method. Therefore, research into molar pregnancy image analysis and understanding is critical. The hypothesis of this research project is that an anomaly detection approach to analyse molar pregnancy images can improve image analysis and classification of normal PHM and CHM villi. The primary aim of this research project is to develop a novel method, based on anomaly detection, to identify and classify anomalous villi in molar pregnancy stained images. The novel method is developed to simulate expert pathologists’ approach in diagnosis of anomalous villi. The knowledge and heuristics elicited from two expert pathologists are combined with the morphological domain knowledge of molar pregnancy, to develop a heuristic multi-neural network architecture designed to classify the villi into their appropriated anomalous types. This study confirmed that a single feature cannot give enough discriminative power for villi classification. Whereas expert pathologists consider the size and shape before textural features, this thesis demonstrated that the textural feature has a higher discriminative power than size and shape. The first heuristic-based multi-neural network, which was based on 15 elicited features, achieved an improved average accuracy of 81.2%, compared to the traditional multi-layer perceptron (80.5%); however, the recall of CHM villi class was still low (64.3%). Two further textural features, which were elicited and added to the second heuristic-based multi-neural network, have improved the average accuracy from 81.2% to 86.1% and the recall of CHM villi class from 64.3% to 73.5%. The precision of the multi-neural network II has also increased from 82.7% to 89.5% for normal villi class, from 81.3% to 84.7% for PHM villi class and from 80.8% to 86% for CHM villi class. To support pathologists to visualise the results of the segmentation, a software tool, Hydatidiform Mole Analysis Tool (HYMAT), was developed compiling the morphological and pathological data for each villus analysis

Goiter

The thyroid gland is a commonly diseased endocrine organ of human body. The disorders affecting the thyroid gland are varied but are very much amenable to treatment. The enlargement of the thyroid is termed goiter. It can affect the whole gland or only part of it. The disease is perplexing but in-depth knowledge of the pathophysiology helps in elucidating causes and thereby treating the disease. In this book, the diffuse and nodular goiter has been addressed as well as the functional abnormalities of the gland and its implications on the body are discussed in various chapters. The relevant updated information is included. To address a few of these current issues and recent updated information, authors have put in a lot of effort to organize the book