Pathological Image Classification Research Articles

CINNAMON-GUI: Revolutionizing Pap Smear Analysis with CNN-Based Digital Pathology Image Classification

Background Medical imaging has seen significant advancements through machine learning, particularly convolutional neural networks (CNNs). These technologies have transformed the analysis of pathological images, enhancing the accuracy of diagnosing and classifying cellular anomalies. Digital pathology methodologies, including image analysis, have improved cervical cancer diagnostics. However, existing commercial platforms are often costly and restrictive, limiting customization and scalability. Methods CINNAMON-GUI is an open-source digital pathology tool based on CNNs for classifying Pap smear images. Transitioning to a Shiny app in Python, it offers enhanced user interface and interactivity. The application supports dynamic web interactions, advanced features for image analysis, and state-of-the-art CNN models tailored for digital pathology. Key features include intuitive UI components, real-time image and plot generation, memory-efficient data handling, and robust training capabilities with customizable CNN architectures. The tool also integrates with Labelme for defining regions of interest and allows testing on external biospecimens. Results Model A (seed 42, 100 epochs) and Model B (same architecture with adjusted augmentation parameters) were compared. Model A stabilized with training accuracy around 0.88 and validation accuracy around 0.913. Model B showed improved performance with training accuracy around 0.91 and validation accuracy around 0.95. Feature mapping highlighted critical morphological aspects, improving classification accuracy. Model B reduced misclassification errors significantly compared to Model A. Conclusions CINNAMON-GUI demonstrates the potential of an open-source platform in digital pathology, providing transparency and collaborative opportunities. The tool enhances diagnostic accuracy through feature map analysis and optimized CNN training. Future development aims to extend its application to other cancer types, leveraging its dynamic and user-friendly interface for broader use in diagnostics.

Dual-Channel Prototype Network for Few-Shot Pathology Image Classification.

In the field of pathology, the scarcity of certain diseases and the difficulty of annotating images hinder the development of large, high-quality datasets, which in turn affects the advancement of deep learning-assisted diagnostics. Few-shot learning has demonstrated unique advantages in modeling tasks with limited data, yet explorations of this method in the field of pathology remain in the early stages. To address this issue, we present a dual-channel prototype network (DCPN), a novel few-shot learning approach for efficiently classifying pathology images with limited data. The DCPN leverages self-supervised learning to extend the pyramid vision transformer (PVT) to few-shot classification tasks and combines it with a convolutional neural network to construct a dual-channel network for extracting multi-scale, high-precision pathological features, thereby substantially enhancing the generalizability of prototype representations. Additionally, we design a soft voting classifier based on multi-scale features to further augment the discriminative power of the model in complex pathology image classification tasks. We constructed three few-shot classification tasks with varying degrees of domain shift using three publicly available pathological datasets-CRCTP, NCTCRC, and LC25000-to emulate real-world clinical scenarios. The results demonstrated that the DCPN outperformed the prototypical network across all metrics, achieving the highest accuracies in same-domain tasks-70.86% for 1-shot, 82.57% for 5-shot, and 85.2% for 10-shot setups-corresponding to improvements of 5.51%, 5.72%, and 6.81%, respectively, over the prototypical network. Notably, in the same-domain 10-shot setting, the accuracy of the DCPN (85.2%) surpassed that of the PVT-based supervised learning model (85.15%), confirming its potential to diagnose rare diseases within few-shot learning frameworks.

Contrastive Learning Joint Regularization for Pathological Image Classification with Noisy Labels

The annotation of pathological images often introduces label noise, which can lead to overfitting and notably degrade performance. Recent studies have attempted to address this by filtering samples based on the memorization effects of DNNs. However, these methods often require prior knowledge of the noise rate or a small, clean validation subset, which is extremely difficult to obtain in real medical diagnosis processes. To reduce the effect of noisy labels, we propose a novel training strategy that enhances noise robustness without prior conditions. Specifically, our approach includes self-supervised regularization to encourage the model to focus more on the intrinsic connections between images rather than relying solely on labels. Additionally, we employ a historical prediction penalty module to ensure consistency between successive predictions, thereby slowing down the model’s shift from memorizing clean labels to memorizing noisy labels. Furthermore, we design an adaptive separation module to perform implicit sample selection and flip the labels of noisy samples identified by this module and mitigate the impact of noisy labels. Comprehensive evaluations of synthetic and real pathological datasets with varied noise levels confirm that our method outperforms state-of-the-art methods. Notably, our noise handling process does not require any prior conditions. Our method achieves highly competitive performance in low-noise scenarios which aligns with current pathological image noise situations, showcasing its potential for practical clinical applications.

Convolutional neural network with parallel convolution scale attention module and ResCBAM for breast histology image classification

Breast cancer is the most common cause of female morbidity and death worldwide. Compared with other cancers, early detection of breast cancer is more helpful to improve the prognosis of patients. In order to achieve early diagnosis and treatment, clinical treatment requires rapid and accurate diagnosis. Therefore, the development of an automatic detection system for breast cancer suitable for patient imaging is of great significance for assisting clinical treatment. Accurate classification of pathological images plays a key role in computer-aided medical diagnosis and prognosis. However, in the automatic recognition and classification methods of breast cancer pathological images, the scale information, the loss of image information caused by insufficient feature fusion, and the enormous structure of the model may lead to inaccurate or inefficient classification. To minimize the impact, we proposed a lightweight PCSAM-ResCBAM model based on two-stage convolutional neural network. The model included a Parallel Convolution Scale Attention Module network (PCSAM-Net) and a Residual Convolutional Block Attention Module network (ResCBAM-Net). The first-level convolutional network was built through a 4-layer PCSAM module to achieve prediction and classification of patches extracted from images. To optimize the network's ability to represent global features of images, we proposed a tiled feature fusion method to fuse patch features from the same image, and proposed a residual convolutional attention module. Based on the above, the second-level convolutional network was constructed to achieve predictive classification of images. We evaluated the performance of our proposed model on the ICIAR2018 dataset and the BreakHis dataset, respectively. Furthermore, through model ablation studies, we found that scale attention and dilated convolution play an important role in improving model performance. Our proposed model outperforms the existing state-of-the-art models on 200 × and 400 × magnification datasets with a maximum accuracy of 98.74 %.

A dual data stream hybrid neural network for classifying pathological images of lung adenocarcinoma

Lung cancer has seriously threatened human health due to its high lethality and morbidity. Lung adenocarcinoma, in particular, is one of the most common subtypes of lung cancer. Pathological diagnosis is regarded as the gold standard for cancer diagnosis. However, the traditional manual screening of lung cancer pathology images is time consuming and error prone. Computer-aided diagnostic systems have emerged to solve this problem. Current research methods are unable to fully exploit the beneficial features inherent within patches, and they are characterized by high model complexity and significant computational effort. In this study, a deep learning framework called Multi-Scale Network (MSNet) is proposed for the automatic detection of lung adenocarcinoma pathology images. MSNet is designed to efficiently harness the valuable features within data patches, while simultaneously reducing model complexity, computational demands, and storage space requirements. The MSNet framework employs a dual data stream input method. In this input method, MSNet combines Swin Transformer and MLP-Mixer models to address global information between patches and the local information within each patch. Subsequently, MSNet uses the Multilayer Perceptron (MLP) module to fuse local and global features and perform classification to output the final detection results. In addition, a dataset of lung adenocarcinoma pathology images containing three categories is created for training and testing the MSNet framework. Experimental results show that the diagnostic accuracy of MSNet for lung adenocarcinoma pathology images is 96.55 %. In summary, MSNet has high classification performance and shows effectiveness and potential in the classification of lung adenocarcinoma pathology images.

ProDiv: Prototype-driven consistent pseudo-bag division for whole-slide image classification

Background and ObjectivePathology image classification is one of the most essential auxiliary processes in cancer diagnosis. To overcome the problem of inadequate Whole-Slide Image (WSI) samples with weak labels, pseudo-bag-based multiple instance learning (MIL) methods have attracted wide attention in pathology image classification. In this type of method, the division scheme of pseudo-bags is usually a primary factor affecting classification performance. In order to improve the division of WSI pseudo-bags on existing random/clustering approaches, this paper proposes a new Prototype-driven Division (ProDiv) scheme for the pseudo-bag-based MIL classification framework on pathology images. MethodsThis scheme first designs an attention-based method to generate a bag prototype for each slide. On this basis, it further groups WSI patch instances into a series of instance clusters according to the feature similarities between the prototype and patches. Finally, pseudo-bags are obtained by randomly combining the non-overlapping patch instances of different instance clusters. Moreover, the design scheme of our ProDiv considers practicality, and it could be smoothly assembled with almost all the MIL-based WSI classification methods in recent years. ResultsEmpirical results show that our ProDiv, when integrated with several existing methods, can deliver classification AUC improvements of up to 7.3% and 10.3%, respectively on two public WSI datasets. ConclusionsProDiv could almost always bring obvious performance improvements to compared MIL models on typical metrics, which suggests the effectiveness of our scheme. Experimental visualization also visually interprets the correctness of the proposed ProDiv.

Renal Pathological Image Classification Based on Contrastive and Transfer Learning

Following recent advancements in medical laboratory technology, the analysis of high-resolution renal pathological images has become increasingly important in the diagnosis and prognosis prediction of chronic nephritis. In particular, deep learning has been widely applied to computer-aided diagnosis, with an increasing number of models being used for the analysis of renal pathological images. The diversity of renal pathological images and the imbalance between data acquisition and annotation have placed a significant burden on pathologists trying to perform reliable and timely analysis. Transfer learning based on contrastive pretraining is emerging as a viable solution to this dilemma. By incorporating unlabeled positive pretraining images and a small number of labeled target images, a transfer learning model is proposed for high-accuracy renal pathological image classification tasks. The pretraining dataset used in this study includes 5000 mouse kidney pathological images from the Open TG-GATEs pathological image dataset (produced by the Toxicogenomics Informatics Project of the National Institutes of Biomedical Innovation, Health, and Nutrition in Japan). The transfer training dataset comprises 313 human immunoglobulin A (IgA) chronic nephritis images collected at Fukushima Medical University Hospital. The self-supervised contrastive learning algorithm “Bootstrap Your Own Latent” was adopted for pretraining a residual-network (ResNet)-50 backbone network to extract glomerulus feature expressions from the mouse kidney pathological images. The self-supervised pretrained weights were then used for transfer training on the labeled images of human IgA chronic nephritis pathology, culminating in a binary classification model for supervised learning. In four cross-validation experiments, the proposed model achieved an average classification accuracy of 92.2%, surpassing the 86.8% accuracy of the original RenNet-50 model. In conclusion, this approach successfully applied transfer learning through mouse renal pathological images to achieve high classification performance with human IgA renal pathological images.

DeepTree: Pathological Image Classification Through Imitating Tree-Like Strategies of Pathologists.

Digitization of pathological slides has promoted the research of computer-aided diagnosis, in which artificial intelligence analysis of pathological images deserves attention. Appropriate deep learning techniques in natural images have been extended to computational pathology. Still, they seldom take into account prior knowledge in pathology, especially the analysis process of lesion morphology by pathologists. Inspired by the diagnosis decision of pathologists, we design a novel deep learning architecture based on tree-like strategies called DeepTree. It imitates pathological diagnosis methods, designed as a binary tree structure, to conditionally learn the correlation between tissue morphology, and optimizes branches to finetune the performance further. To validate and benchmark DeepTree, we build a dataset of frozen lung cancer tissues and design experiments on a public dataset of breast tumor subtypes and our dataset. Results show that the deep learning architecture based on tree-like strategies makes the pathological image classification more accurate, transparent, and convincing. Simultaneously, prior knowledge based on diagnostic strategies yields superior representation ability compared to alternative methods. Our proposed methodology helps improve the trust of pathologists in artificial intelligence analysis and promotes the practical clinical application of pathology-assisted diagnosis.

Breast Tumor Tissue Image Classification Using Single-Task Meta Learning with Auxiliary Network.

Breast cancer has a high mortality rate among cancers. If the type of breast tumor can be correctly diagnosed at an early stage, the survival rate of the patients will be greatly improved. Considering the actual clinical needs, the classification model of breast pathology images needs to have the ability to make a correct classification, even in facing image data with different characteristics. The existing convolutional neural network (CNN)-based models for the classification of breast tumor pathology images lack the requisite generalization capability to maintain high accuracy when confronted with pathology images of varied characteristics. Consequently, this study introduces a new classification model, STMLAN (Single-Task Meta Learning with Auxiliary Network), which integrates Meta Learning and an auxiliary network. Single-Task Meta Learning was proposed to endow the model with generalization ability, and the auxiliary network was used to enhance the feature characteristics of breast pathology images. The experimental results demonstrate that the STMLAN model proposed in this study improves accuracy by at least 1.85% in challenging multi-classification tasks compared to the existing methods. Furthermore, the Silhouette Score corresponding to the features learned by the model has increased by 31.85%, reflecting that the proposed model can learn more discriminative features, and the generalization ability of the overall model is also improved.

Global attention based GNN with Bayesian collaborative learning for glomerular lesion recognition

Background:Glomerular lesions reflect the onset and progression of renal disease. Pathological diagnoses are widely regarded as the definitive method for recognizing these lesions, as the deviations in histopathological structures closely correlate with impairments in renal function. Methods:Deep learning plays a crucial role in streamlining the laborious, challenging, and subjective task of recognizing glomerular lesions by pathologists. However, the current methods treat pathology images as data in regular Euclidean space, limiting their ability to efficiently represent the complex local features and global connections. In response to this challenge, this paper proposes a graph neural network (GNN) that utilizes global attention pooling (GAP) to more effectively extract high-level semantic features from glomerular images. The model incorporates Bayesian collaborative learning (BCL), enhancing node feature fine-tuning and fusion during training. In addition, this paper adds a soft classification head to mitigate the semantic ambiguity associated with a purely hard classification. Results:This paper conducted extensive experiments on four glomerular datasets, comprising a total of 491 whole slide images (WSIs) and 9030 images. The results demonstrate that the proposed model achieves impressive F1 scores of 81.37%, 90.12%, 87.72%, and 98.68% on four private datasets for glomerular lesion recognition. These scores surpass the performance of the other models used for comparison. Furthermore, this paper employed a publicly available BReAst Carcinoma Subtyping (BRACS) dataset with an 85.61% F1 score to further prove the superiority of the proposed model. Conclusion:The proposed model not only facilitates precise recognition of glomerular lesions but also serves as a potent tool for diagnosing kidney diseases effectively. Furthermore, the framework and training methodology of the GNN can be adeptly applied to address various pathology image classification challenges.

Semi-Path: An interactive semi-supervised learning framework for gigapixel pathology image analysis

The efficacy of supervised deep learning in medical image analyses, particularly in pathology, is hindered by the necessity for extensive manual annotations. Annotating images at the gigapixel level manually proves to be a highly labor-intensive and time-consuming task. Semi-supervised learning (SSL) has emerged as a promising approach that leverages unlabeled data to reduce labeling efforts. In this work, we introduce Semi-Path, a practical SSL framework enhanced with active learning (AL) for gigapixel pathology tasks. Unlike existing methods that treat SSL and AL as independent components where AL incurs significant computational complexity to SSL, we propose a deep fusion of SSL and AL into a unified framework. Our framework introduces Informative Active Annotation (IAA) that employs a SSL-AL iterative structure to effectively extract knowledge from unlabeled pathology data. This structure significantly minimizes labeling efforts and computational complexity. Then, we propose Adaptive Pseudo-Labeling (APL) to address heterogeneity in class distribution, and prediction difficulty that are often observed in real-world pathology tasks. We evaluate Semi-Path on pathology image classification and segmentation tasks over three datasets that include WSIs from breast, colorectal, and brain tissues. The experimental results demonstrate the consistent superiority of Semi-Path over state-of-the-art methods.

Research on breast cancer pathological image classification method based on wavelet transform and YOLOv8.

Breast cancer is one of the cancers with high morbidity and mortality in the world, which is a serious threat to the health of women. With the development of deep learning, the recognition about computer-aided diagnosis technology is getting higher and higher. And the traditional data feature extraction technology has been gradually replaced by the feature extraction technology based on convolutional neural network which helps to realize the automatic recognition and classification of pathological images. In this paper, a novel method based on deep learning and wavelet transform is proposed to classify the pathological images of breast cancer. Firstly, the image flip technique is used to expand the data set, then the two-level wavelet decomposition and reconfiguration technology is used to sharpen and enhance the pathological images. Secondly, the processed data set is divided into the training set and the test set according to 8:2 and 7:3, and the YOLOv8 network model is selected to perform the eight classification tasks of breast cancer pathological images. Finally, the classification accuracy of the proposed method is compared with the classification accuracy obtained by YOLOv8 for the original BreaKHis dataset, and it is found that the algorithm can improve the classification accuracy of images with different magnifications, which proves the effectiveness of combining two-level wavelet decomposition and reconfiguration with YOLOv8 network model.

Exploiting Geometric Features via Hierarchical Graph Pyramid Transformer for Cancer Diagnosis Using Histopathological Images.

Cancer is widely recognized as the primary cause of mortality worldwide, and pathology analysis plays a pivotal role in achieving accurate cancer diagnosis. The intricate representation of features in histopathological images encompasses abundant information crucial for disease diagnosis, regarding cell appearance, tumor microenvironment, and geometric characteristics. However, recent deep learning methods have not adequately exploited geometric features for pathological image classification due to the absence of effective descriptors that can capture both cell distribution and gathering patterns, which often serve as potent indicators. In this paper, inspired by clinical practice, a Hierarchical Graph Pyramid Transformer (HGPT) is proposed to guide pathological image classification by effectively exploiting a geometric representation of tissue distribution which was ignored by existing state-of-the-art methods. First, a graph representation is constructed according to morphological feature of input pathological image and learn geometric representation through the proposed multi-head graph aggregator. Then, the image and its graph representation are feed into the transformer encoder layer to model long-range dependency. Finally, a locality feature enhancement block is designed to enhance the 2D local representation of feature embedding, which is not well explored in the existing vision transformers. An extensive experimental study is conducted on Kather-5K, MHIST, NCT-CRC-HE, and GasHisSDB for binary or multi-category classification of multiple cancer types. Results demonstrated that our method is capable of consistently reaching superior classification outcomes for histopathological images, which provide an effective diagnostic tool for malignant tumors in clinical practice.

A prediction model based on digital breast pathology image information.

The workload of breast cancer pathological diagnosis is very heavy. The purpose of this study is to establish a nomogram model based on pathological images to predict the benign and malignant nature of breast diseases and to validate its predictive performance. In retrospect, a total of 2,723 H&E-stained pathological images were collected from 1,474 patients at Qingdao Central Hospital between 2019 and 2022. The dataset consisted of 509 benign tumor images (adenosis and fibroadenoma) and 2,214 malignant tumor images (infiltrating ductal carcinoma). The images were divided into a training set (1,907) and a validation set (816). Python3.7 was used to extract the values of the R channel, G channel, B channel, and one-dimensional information entropy from all images. Multivariable logistic regression was used to select variables and establish the breast tissue pathological image prediction model. The R channel value, B channel value, and one-dimensional information entropy of the images were identified as independent predictive factors for the classification of benign and malignant pathological images (P < 0.05). The area under the curve (AUC) of the nomogram model in the training set was 0.889 (95% CI: 0.869, 0.909), and the AUC in the validation set was 0.838 (95% CI: 0.7980.877). The calibration curve results showed that the calibration curve of this nomogram model was close to the ideal curve. The decision curve results indicated that the predictive model curve had a high value for auxiliary diagnosis. The nomogram model for the prediction of benign and malignant breast diseases based on pathological images demonstrates good predictive performance. This model can assist in the diagnosis of breast tissue pathological images.

Classification of breast pathological images based on multiscale information interaction and fusion

Classification of breast pathological images based on multiscale information interaction and fusion

Spatially-constrained and -unconstrained bi-graph interaction network for multi-organ pathology image classification.

In computational pathology, graphs have shown to be promising for pathology image analysis. There exist various graph structures that can discover differing features of pathology images. However, the combination and interaction between differing graph structures have not been fully studied and utilized for pathology image analysis. In this study, we propose a parallel, bi-graph neural network, designated as SCUBa-Net, equipped with both graph convolutional networks and Transformers, that processes a pathology image as two distinct graphs, including a spatially-constrained graph and a spatially-unconstrained graph. For efficient and effective graph learning, we introduce two inter-graph interaction blocks and an intra-graph interaction block. The inter-graph interaction blocks learn the node-to-node interactions within each graph. The intra-graph interaction block learns the graph-to-graph interactions at both global- and local-levels with the help of the virtual nodes that collect and summarize the information from the entire graphs. SCUBa-Net is systematically evaluated on four multi-organ datasets, including colorectal, prostate, gastric, and bladder cancers. The experimental results demonstrate the effectiveness of SCUBa-Net in comparison to the state-of-the-art convolutional neural networks, Transformer, and graph neural networks.

Reversed domain adaptation for nuclei segmentation-based pathological image classification

Despite the fact that digital pathology has provided a new paradigm for modern medicine, the insufficiency of annotations for training remains a significant challenge. Due to the weak generalization abilities of deep-learning models, their performance is notably constrained in domains without sufficient annotations. Our research aims to enhance the model’s generalization ability through domain adaptation, increasing the prediction ability for the target domain data while only using the source domain labels for training. To further enhance classification performance, we introduce nuclei segmentation to provide the classifier with more diagnostically valuable nuclei information. In contrast to the general domain adaptation that generates source-like results in the target domain, we propose a reversed domain adaptation strategy that generates target-like results in the source domain, enabling the classification model to be more robust to inaccurate segmentation results. The proposed reversed unsupervised domain adaptation can effectively reduce the disparities in nuclei segmentation between the source and target domains without any target domain labels, leading to improved image classification performance in the target domain. The whole framework is designed in a unified manner so that the segmentation and classification modules can be trained jointly. Extensive experiments demonstrate that the proposed method significantly improves the classification performance in the target domain and outperforms existing general domain adaptation methods.

An improved multi-scale gradient generative adversarial network for enhancing classification of colorectal cancer histological images.

Deep learning-based solutions for histological image classification have gained attention in recent years due to their potential for objective evaluation of histological images. However, these methods often require a large number of expert annotations, which are both time-consuming and labor-intensive to obtain. Several scholars have proposed generative models to augment labeled data, but these often result in label uncertainty due to incomplete learning of the data distribution. To alleviate these issues, a method called InceptionV3-SMSG-GAN has been proposed to enhance classification performance by generating high-quality images. Specifically, images synthesized by Multi-Scale Gradients Generative Adversarial Network (MSG-GAN) are selectively added to the training set through a selection mechanism utilizing a trained model to choose generated images with higher class probabilities. The selection mechanism filters the synthetic images that contain ambiguous category information, thus alleviating label uncertainty. Experimental results show that compared with the baseline method which uses InceptionV3, the proposed method can significantly improve the performance of pathological image classification from 86.87% to 89.54% for overall accuracy. Additionally, the quality of generated images is evaluated quantitatively using various commonly used evaluation metrics. The proposed InceptionV3-SMSG-GAN method exhibited good classification ability, where histological image could be divided into nine categories. Future work could focus on further refining the image generation and selection processes to optimize classification performance.

Content-based image retrieval for medical diagnosis using fuzzy clustering and deep learning

Brain tumors are one of the most threatening causes of death worldwide. Neuroradiologists widely use Magnetic Resonance Imaging as a golden standard non-invasive imaging method for diagnosing Glioma grades. Brain tumor diagnosis based on radiology images is tedious and highly subjective to intra and inter-observer variability; it adversely affects therapeutic planning. Better medical treatment can be provided relating to similar past cases if relevant images are retrieved from an extensive medical image database. Content-Based Image Retrieval systems are potent image tools for dealing with such massive datasets. In a CBIR system, accurate classification and retrieval of similar pathological images can be effectively automated by utilising Convolutional Neural Network-based feature extraction methods. This paper presents a Content-Based Medical Image Retrieval pipeline on a medical domain using the CNN model for feature extraction and the clustering method used to index the feature map database. The proposed system applies a Multi-level Gain-based feature selection to reduce the dimensionality of the feature vectors obtained from the pre-trained CNN models. The experiment follows five-fold cross-validation on BraTS 2018 and 2020 datasets. The proposed system achieves state-of-the-art MRI brain image retrieval performance with a mean Average Precision and Precision@10 of 98.15% and 97.62%, respectively. The results prove the proposed method’s effectiveness and validate its clinical application.

CCF-GNN: A Unified Model Aggregating Appearance, Microenvironment, and Topology for Pathology Image Classification.

Pathology images contain rich information of cell appearance, microenvironment, and topology features for cancer analysis and diagnosis. Among such features, topology becomes increasingly important in analysis for cancer immunotherapy. By analyzing geometric and hierarchically structured cell distribution topology, oncologists can identify densely-packed and cancer-relevant cell communities (CCs) for making decisions. Compared to commonly-used pixel-level Convolution Neural Network (CNN) features and cell-instance-level Graph Neural Network (GNN) features, CC topology features are at a higher level of granularity and geometry. However, topological features have not been well exploited by recent deep learning (DL) methods for pathology image classification due to lack of effective topological descriptors for cell distribution and gathering patterns. In this paper, inspired by clinical practice, we analyze and classify pathology images by comprehensively learning cell appearance, microenvironment, and topology in a fine-to-coarse manner. To describe and exploit topology, we design Cell Community Forest (CCF), a novel graph that represents the hierarchical formulation process of big-sparse CCs from small-dense CCs. Using CCF as a new geometric topological descriptor of tumor cells in pathology images, we propose CCF-GNN, a GNN model that successively aggregates heterogeneous features (e.g., appearance, microenvironment) from cell-instance-level, cell-community-level, into image-level for pathology image classification. Extensive cross-validation experiments show that our method significantly outperforms alternative methods on H&E-stained and immunofluorescence images for disease grading tasks with multiple cancer types. Our proposed CCF-GNN establishes a new topological data analysis (TDA) based method, which facilitates integrating multi-level heterogeneous features of point clouds (e.g., for cells) into a unified DL framework.