Pathological diagnosis is the “gold standard” for most diseases, especially for benign and malignant tumors. After a patient undergoes a puncture biopsy of the lung or lymph nodes, or a biopsy taken during surgery, the doctor sends the obtained tissue for pathological testing.
Although we are always anxious to know whether it is a tumor, benign or malignant, we often have to wait at least 3 to 5 days before the report is available. It may be difficult for you to understand why you have to wait so long. Here we will talk about the process from biopsy to pathology report, and why it takes “several days”.
What is the process from biopsy collection to report?
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Generally speaking, from the time a lung cancer tissue is biopsied and retrieved to the time a formal pathology report is issued, there are two processes: “technical processing” and “physician reading”.
Technical processing
When a pathologist receives a patient specimen, he or she has to do two examinations: first, “macroscopic examination,” which is mainly to observe with the naked eye the appearance, color, size, shape, texture, etc. of the tissue sent to him or her; second, “microscopic examination,” which is to look at the fine tissue structure and cell morphology under a microscope. Cellular morphology, the first need to make the tissue specimen can be “read” pathological section. This process is very complicated, which includes a series of tedious steps such as fixation, extraction, dehydration, wax immersion, embedding, sectioning, staining, sealing, etc. Each step takes an hour or even several hours, and there are nearly 20 procedures for staining alone, thus it usually takes 2~3 days to complete.
The main specific steps of sectioning are as follows.
- Fixing. Fixation is the process of placing the specimen in a chemical reagent to preserve the tissue, cellular morphology, structure, and composition of the various substances it contains, most commonly formalin. For adequate fixation, the fixation time is usually as little as a few hours and as long as 1-2 days.
- Taking, dehydration, transparency, and wax immersion. After fixation, a representative part of the lesion is taken for filming, which is called “picking” and can be done in half a day to a day. This is followed by secondary fixation to prevent poor fixation of larger tissues. Afterwards, the water is replaced with a dehydrating agent, and the dehydrating agent is replaced with a transparent agent, which is called “dehydration” and “transparency”. Finally, wax is injected into the cells. It takes about 12 hours to go from “dehydration” to “wax immersion”.
- Embedding
- Embedding, sectioning, staining, and sealing. Next, the wax-impregnated tissue is placed in a mold and formed into a block, then 3-4 micron sections are cut out, the best ones are baked and firmly adhered to the slides. After slicing, the different cellular components need to be stained in different colors before they can be observed under the microscope, a step that takes 1 to 2 hours. After the staining is completed, the specimen can be stored for a long time by applying a drop of neutral gum on the section and covering it with a coverslip. These four steps usually take one working day, and once completed, the slides are ready to be read.
Physician reading
The “reading” is usually done at two levels: diagnosis by the junior physician and review and correction by the senior physician, and in difficult cases, consultation among senior physicians to arrive at a final diagnosis. Only after the diagnosis is confirmed can the corresponding personnel issue a report. Seeing this, you should understand why it takes so long to issue a report, right?
Sometimes additional special tests are needed
Of course, the above is only for those specimens for which the diagnosis can be given directly. In many cases, the doctor can only get preliminary pathological results from ordinary staining, such as non-small cell lung cancer (NSCLC), and cannot make precise typing of tissue cells (adenocarcinoma, squamous carcinoma, etc.) and accurate determination of tissue origin (e.g., lung origin, liver origin, etc.), and then immunohistochemistry is needed.
The principle of immunohistochemistry is that any cell can secrete specific proteins as cellular “identifiers” and when a known antibody (equivalent to a “decoy”) is applied to a tissue cell, it can bind to the specific protein (i.e., antigen) and react with it by When a known antibody (equivalent to a “decoy”) is applied to a tissue cell, it binds to a specific protein (i.e., antigen) to produce a reaction that is revealed by a chromogen, which allows the physician to determine the origin of the tissue or type of cell. If immunohistochemistry is added, it takes another 3 business days or so for the report to be ready.
Sometimes, routine immunohistochemistry is not enough to determine the origin of the tissue, and additional special immunohistochemistry reactions are needed, or even a consultation with pathologists from multiple hospitals is required to reach a conclusion. The time required in such cases is much longer.Pathology can also be “faulty”
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In some cases, even after a tissue biopsy is taken, a definitive pathology report may not be available. This is because, in general, tumor punctures are obtained from “small specimens” (about 1 mm in diameter, rather than a large tumor obtained from surgery), and the small amount of tumor tissue or cells does not support a completely reliable conclusion. Even if the sample size obtained by puncture is not so small, sometimes the sample taken does not always contain detectable tumor tissue or cells due to the heterogeneous distribution of tumor cells or necrosis of the tumor tissue. Therefore, it is difficult to guarantee that a single puncture biopsy will give a definitive pathological answer.
If your doctor has a high suspicion of lung cancer and the results of one puncture do not show evidence of tumor, a second puncture may be required. When this happens, we ask you and your family to understand this and to cooperate with your doctor to complete the required tests for a more accurate diagnosis.
Therefore, we need to allow sufficient time for the diagnostic pathologist to make diagnosis and interpretation. We need to be patient in order to get a high quality pathology diagnosis report for more appropriate treatment.
Co-reviewed by: Guangdong Provincial People’s Hospital Guangdong Provincial People’s Hospital Lung Cancer Research Institute Dr. Haiyan Tu, Deputy Chief Physician Dr. Yue-Li Sun, Dr. Ming-Feng Zhang