Ms. Chen, 45, was holding a pathology consultation sheet and wanted to request an accurate pathological diagnosis. It turns out that Ms. Chen, who visited the clinic last year for a head and neck lump, was diagnosed with a nodular goiter with adenoma formation after ultrasound and fine needle aspiration examination. After some tests, the diagnosis changed from “benign” to “malignant” and was diagnosed as a subtype of papillary thyroid cancer. Nodules and calcifications are not all “bad” Once the word “nodules” appears in the ultrasound diagnostic report, people’s hearts will be pulled up. But in fact, according to incomplete statistics, benign lesions account for about 55% of the nodule population. The most common benign lesions are Hashimoto’s nodules, nodular goiter, and follicular adenoma, which are caused by the “malfunction” of the autoimmune system, and are mostly presented as nodules in ultrasound images. Generally speaking, these benign lesions do not require surgery and can be treated by taking thyroid tablets to relieve and control symptoms, and by adhering to regular follow-up visits every 3-6 months. However, it is important to note that if the thyroid nodule-like growth is rapid, causing the adenoma or nodule to grow in size and affect the patient’s appearance or compress the airway, the doctor may still recommend surgical removal. The gold standard for clinical diagnosis of benign and malignant thyroid nodules is pathological diagnosis. The only way to obtain pathological tissue is through fine needle aspiration. Clinically, patients with calcifications detected by ultrasound and with high suspicion of malignancy on palpation by the attending physician require a cytologic pathology to determine the benignity of the nodule. Calcification is not the same as malignancy; benign lesions may also show signs of calcification. During the puncture session, the physician, under the guidance of ultrasound, takes a targeted sample of relevant tissue through a fine needle in the area of highly suspected calcification sites, and then performs a cytopathological diagnosis, which can reach a positive diagnostic rate of about 90%. Uncovering well-disguised nodules with surgical pathology In clinical practice, cytology aspiration diagnosis can also result in false negative results, and there are two main types of causes for false negatives. The first is due to the limited experience of the physician and the level of the puncture technique, resulting in a situation where the lesion is seen but not detected. The other reason is that some thyroid cancer cells are good at camouflage. Papillary thyroid cancer accounts for about 80% of all thyroid cancers, and it is a tumor with a good prognosis. In the pathological diagnosis, papillary thyroid cancer has a papillary morphological structure, which can be diagnosed more directly by “morphological appearance” under the microscope. However, follicular papillary thyroid cancer, a subtype of papillary thyroid cancer, is a “bad guy” disguised as a thyroid nodule and is always misdiagnosed as a benign lesion in clinical pathology. The anonymity of follicular papillary thyroid cancer is that this type of thyroid cancer has no obvious papillary structure under the microscope and is often misdiagnosed as a nodular goiter with adenoma formation. The diagnosis of follicular papillary thyroid cancer is made by microscopic observation of the tumor cells by the physician. Of course, in some cases, fine needle aspiration to obtain tissue samples for pathologic diagnosis does not yield a positive diagnosis. The main reason for this is that the sample size of fine needle aspiration is small. The coverage is not wide enough to reflect the whole picture of tumor cells, and it is more difficult to make an accurate diagnosis. Therefore, we suggest that it is better for these patients to obtain the lesion tissue through surgery and make paraffin pathology report to give accurate diagnosis. Immunohistochemical testing is a diagnostic tool Here, we have to say that with the advancement of pathological diagnostic techniques, the combination of HE diagnosis and immunohistochemistry is a diagnostic tool that can unmask those nodules that are good at camouflage. In addition to the conventional morphological diagnosis under the microscope, the immunohistochemical examination of the tissue specimen can reveal the true nature of the nodule in most cases. Once the nodule is a “bad thing”, the tumor cells themselves will produce certain proteins that can be interpreted as an antigen, and when specific antibodies are added, the two will combine to show a positive signal that can be determined microscopically by immunohistochemistry. For example, follicular papillary thyroid cancer has three relatively specific antigens, and if they show positive, combined with the morphological diagnosis under HE microscopy, a final and precise diagnosis can be made.