Microscopic examination of pathology slides is essential to disease diagnosis and biomedical research; however, traditional manual examination of tissue slides is laborious and subjective. Tumor whole-slide image (WSI) scanning is becoming part of routine clinical procedure and produces massive data that capture tumor histological details at high resolution. Furthermore, the rapid development of deep learning algorithms has significantly increased the efficiency and accuracy of pathology image analysis. In light of this progress, digital pathology is fast becoming a powerful tool to assist pathologists. Studying tumor tissue and its surrounding microenvironment provides critical insight into tumor initiation, progression, metastasis, and potential therapeutic targets. Nuclei segmentation and classification are critical to pathology image analysis, especially in characterizing and quantifying the tumor microenvironment (TME). Computational algorithms have been developed for nuclei segmentation and TME quantification within image patches; however, existing algorithms are computationally intensive and time-consuming for WSI analysis. In this study, we present Histology-based Detection using Yolo (HD-Yolo), a new method that significantly accelerates nuclei segmentation and TME quantification. We demonstrate that HD-Yolo outperforms existing methods for WSI analysis in nuclei detection and classification accuracy, as well as computation time.