Most patients may have more contact with doctors in clinical departments (such as internal medicine, surgery, gynecology, pediatrics, etc.) and generally have little understanding of pathology or feel mystified by it. Here is a small introduction to pathology to help you understand it. What does pathology do? Pathology is an independent medical discipline, which can be subdivided into orthopedic pathology, gynecologic pathology, gastrointestinal pathology, neuropathology, oral pathology, urologic pathology, and more than ten specialized pathology subspecialties. Pathologists mainly help to identify lesions in clinical practice, especially to distinguish benign and malignant tumors. However, pathology only observes the benignity and malignancy of the patient’s lesions from a certain perspective, and sometimes there are “blind spots” which are not comprehensive. How is pathology done? The clinician cuts or punctures a small part or all of the tumor or other lesions (called: specimen), and submits it to the pathology department together with the description of the disease (pathology application form), and the pathology technician makes a conventional paraffin section of the specimen (first soak the tumor in paraffin, then use a special slicer to make a thin to transparent film, and then paste it onto a glass slide for staining. The pathologist observes the section with a microscope, refers to the basic conditions of the patient described in the application form, and analyzes it comprehensively. The pathology is then provided to the clinician for reference in a written report. The whole process takes at least 72 hours. In case of difficult pathology problems (about 20%), it may take 1 to several weeks for further special staining, immunohistochemistry, consultation and discussion, etc. for careful analysis. What is “frozen” intraoperative pathology? Intraoperative “frozen” pathology is a rapid intraoperative pathology diagnostic method. The advantage is that it is quick (the diagnosis is usually made in about 30 minutes after the specimen is received). However, the most fatal disadvantage of ‘frozen diagnosis’ is that it is less accurate and can only be used by the surgeon for preliminary reference. Even after freezing, the remaining specimens will have to be routinely paraffin-sectioned again for precise pathological diagnosis. If the frozen diagnosis is inconsistent with the subsequent routine diagnosis, the paraffin section diagnosis should generally prevail. How is the “gold standard” regarded? Pathological diagnosis is called the gold standard of medical diagnosis and treatment, but this gold standard must have prerequisites. If the entire lesion is cut down and submitted to the pathology department, the pathology has the highest accuracy (close to 100%) in identifying benign and malignant. If only a portion of the lesion is excised or aspirated by puncture, the pathology is less accurate. In general, the less cut down, the less accurate it is. In the case of tumors, for example, even the same tumor is often heterogeneous: there may be parts that are highly malignant, parts that are less malignant, and parts that have no malignant cells at all. There are malignant cells that appear benign (likened to a wolf in sheep’s clothing) and benign cells that appear malignant. After endoscopy and puncture to obtain specimens, it is advantageous to have little damage to the patient’s flesh, but it is less accurate for pathology than cutting off a piece of tissue. It needs to be understood that any diagnostic method in medicine has limitations and cannot be seen as absolutely reliable. “The same is true for pathological diagnosis. Why are there difficult cases of pathological diagnosis? Some diseases have common or similar morphology (i.e. “homomorphic heteropathy”), such as round cell tumor, spindle cell tumor, pleomorphic cell tumor, small cell malignant tumor, etc. They are actually not the same independent disease, but they are difficult to distinguish in pathological sections because of “homomorphism”. However, they are difficult to distinguish in pathological sections because of their “isomorphism”, and must be analyzed by more pathological techniques such as immunohistochemistry and molecular pathology testing. For example, the differential diagnosis of “small cell malignancy” can include small cell carcinoma, lymphoma, embryonal rhabdomyosarcoma, neuroblastoma, primitive neuroectodermal tumor/Ewing sarcoma, and so on. All these limitations can be narrowed by subjective and objective efforts, but it is not objective to make it disappear completely. Both clinical and pathological aspects should be highly alert to this.