Pathologic diagnosis is the “gold standard” for most diagnoses, especially in determining benign and malignant tumors. After a patient has undergone a puncture biopsy of a lung or lymph node, or a biopsy taken during surgery, the doctor sends the tissue for pathology.
While we are always anxious to find out sooner if it is a tumor, benign or malignant, it often takes 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’s how the process works and why it takes “days” from the time the material is taken to the time the pathology report is issued.
What is the process from biopsy to report?
What is the process from biopsy to report?
In general, there are two processes: “technical processing” and “physician reading” from lung cancer tissue biopsy and retrieval to the official pathology report.
Technical processing
Technical processing
When the pathologist receives the patient specimen, he/she has to do two examinations: first, “macroscopic examination”, which is to observe the appearance, color, size, shape, texture, etc. of the tissue sent to him/her with the naked eye; second, “microscopic examination”, which is to look at the subtle tissue structure and cell morphology under the microscope. The second is “microscopic examination”, which is to look at the subtle tissue structure and cell morphology under the microscope, first of all, the tissue specimen needs to be made into a “readable” pathology section. This is a very complex process, 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 a few hours, and staining alone has nearly 20 procedures, so it usually takes 2~3 days to complete.
The main specific steps of filming are as follows:
- Fixation.
- Fixation. 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 contained, most commonly formalin. For adequate fixation, the fixation time is usually as little as a few hours and as long as 1 to 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
There are usually two levels of “reading”: diagnosis by the junior physician and review and revision by the senior physician, and in difficult cases, consultation among senior physicians to reach a final diagnosis. Only after the diagnosis is confirmed can the appropriate person issue a report. When you see this, you should be able to understand why it takes so long to issue a report, right?
Sometimes additional special tests are needed
Of course, this is only for specimens that can be diagnosed 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 the tissue cells (adenocarcinoma, squamous carcinoma, etc.) and accurate determination of the tissue origin (e.g., lung origin, liver origin, etc.), which requires immunohistochemistry.
How it works is that any cell can secrete a specific protein as an “identifier” for the cell, 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. When a known antibody (equivalent to a “decoy”) is applied to a tissue cell, it binds to a specific protein (i.e., antigen) and reacts with a color developer, allowing the physician to determine the origin of the tissue or type of cell. If immunohistochemistry is added, it will take another 3 business days or so for the report to come back.
Sometimes, routine immunohistochemistry is not enough to determine the source of the tissue and additional specific immunohistochemical reactions are needed, or even a consultation with pathologists from multiple hospitals, to reach a conclusion. The time required in such cases is much longer.
Pathology can be “faulty”
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In some cases, even if a tissue biopsy is taken, it is not always possible to get a “definitive” pathology report. This is because the tumor biopsy is usually obtained from a “small specimen” (about 1 mm in diameter, rather than a large tumor obtained from surgery), and the amount of tumor tissue or cells is small and 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 needed. When this happens, please understand this and ask your family to cooperate with your doctor to complete the tests needed for a more accurate diagnosis.
It is therefore important to allow sufficient time for the diagnostic pathologist to make a diagnosis and interpretation. We need to be patient in order to get a quality pathology report for a more appropriate diagnosis.
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Co-reviewed by: Guangdong Provincial People’s Hospital Guangdong Provincial People’s Hospital Lung Cancer Institute Dr. Tu Haiyan, Associate Chief Physician Dr. Sun Yueli Dr. Zhang Mingfeng