Spread and metastasis of cancerous tumors are two interrelated and distinct concepts. Proliferation means local invasion or distant metastasis of tumor, which can be connected with the tumor body or far away from the main body, while metastasis is that tumor cells leave the main body and form a kind of tumor with the same type as the primary tumor in distant organs or tissues, which is a main form of tumor proliferation. I. The main ways of tumor proliferation: 1. Direct spread of tumor cells: this is the basic condition of tumor proliferation, which is usually seen that tumor cells directly invade outward from the tumor mother body, often spreading uninterruptedly along the pathways of tissue interstitial space, lymphatic vessels, blood vessels, body cavities or cerebral spinal cord cavities to reach the distant parts. However, it remains connected to the main body of the tumor. Local direct invasion of tumor cells is an inevitable stage in the growth process of malignant tumors, but its spreading potential can be very different for different types of tumors, which is determined by many factors. Thus, some tumors are dominated by local infiltration and metastasis does not play a major role. On the contrary, some tumors are dominated by extensive metastasis. For example, in cervical cancer, its clinical characteristic is local spread, tumor cells along the tissue gap, directly to the cervix or the body of the uterus outside the expansion, in the process of tumor invasion, the local connective tissue hyperplasia, the tumor local diffuse infiltration, often form frozen pelvis, the substance for the tumor direct infiltration of the results. As far as cervical cancer is concerned, the main clinical problem is local invasion, and metastasis is not the main problem. For example, we found that there were not many organ metastasis (lung and colon metastasis each accounted for 15.8%) and lymph node metastasis in 19 cases of cervical cancer in autopsy, and the main cause of patient’s death is the complications caused by tumor infiltration, which would be half the result with half the effort if the clinical can deal with the local treatment of cervical cancer well. Another example is esophageal cancer, in which the tumor invades deeply along the tissue gap, even destroys the esophageal wall and spreads to the surrounding area, which directly involves the neighboring organs, leading to various complications and even the death of the patient as a result. In non-surgically treated esophageal cancer, the tumor metastasis is not extensive, and the main causes of patient’s death are esophageal aortic leakage caused by local infiltration of the tumor, esophageal aortic leakage, esophageal (bronchial) tracheal leakage, and mediastinitis caused by perforation of the esophageal cancer, and so on. In conclusion, through the literature reports and our material analysis, it is evident that the main problems of esophageal cancer are also local rather than systemic, and for esophageal cancer, complications caused by direct infiltration of the tumor are the main cause of death in patients with esophageal cancer, while metastasis does not occupy an important position. Direct infiltration of tumor, besides infiltrating along the looser tissues such as muscular space, fascial space, etc., it can also expand directly along lymphatic vessels. For example, in primary lung cancer, when the cancer cells involve lymphatic vessels, it displays white striped mesh structure in the dirty layer of pleura (or lung membrane), which is called carcinomatous lymphadenitis or carcinomatous transformation of lymphatic vessels by some people. Sometimes malignant melanoma of the foot, involving the lymphatic vessels of the lower extremities, may extend in lines from the soles of the feet to the groin. Microscopically, the tumor cells can be seen to grow along the lymphatic vessels in a “columnar” fashion. Sometimes the tumor may extend continuously and uninterruptedly along the perineural or perivascular lymphatic space. This kind of expansion of lymphatic vessels or lymphatic space can sometimes involve a very wide area, such as the so-called inflammatory breast cancer, which is essentially a local inflammation of lymphatic tumor embolus, resulting in redness, swelling, heat and pain, and even the formation of orange peel-like. In addition, the direct spread of tumor can also expand along the venous cavity, such as liver cancer can form portal vein, splenic vein tumor embolus, or enter into the superior vena cava along the hepatic vein over the right atrium, thus the tumor embolus dislodges and leads to the metastasis of organs. 2. Lymphatic channel metastasis: this is the main way of cancer spreading. The lymphatic vessels of each organ are like a network, communicating with each other and having their own characteristics, and the distribution of lymphatic vessels of each organ is not uniform. In the luminal organs (such as the esophagus, stomach, intestines, etc.), although the distribution of lymphatic vessels of each organ is available in each layer, the distribution of lymphatic vessels of the subplasma membrane and the plasma membrane layer is most extensive, therefore, when the cancer invades into the subplasma membrane, muscularis ossificans, or the plasma membrane layer of the wall of the esophagus, the metastasis of lymph nodes is also very extensive. Therefore, when the cancer invades into the subplasma, muscle or plasma layer of the esophageal wall, the lymph node metastasis is often extensive. On the contrary, lymph node metastasis is rarely found in intramucosal cancer or carcinoma in situ. In lymphatic metastasis, cancer must first involve local lymphatic vessels, and the direction of lymphatic drainage varies from organ to organ. For example, the lymphatic drainage of lungs mainly goes to the lymph nodes in hilar area, and the lymphatic drainage of breast mainly goes to the lymph nodes in axilla or internal mammary vein area, therefore, it is very important for clinicians to understand the distribution of lymphatic ducts and drainage direction of each organ, and for example, in the same case of male reproductive organs, the lymphatic drainage of penis mainly flows into inguinal lymph nodes, and that of testes is in the direction of retroperitoneal lymph nodes. Thus, penile cancer firstly metastasizes to inguinal lymph nodes, while testicular malignant tumor firstly metastasizes to retroperitoneal lymph nodes. The proliferation and metastasis of lymphatic tracts are affected by many factors, and the clinical stage (early stage, middle stage and late stage) is one of the most important factors of lymphatic tract metastasis. For example, there is a great difference in lymph node metastasis between surgically resected cancer specimens and autopsy specimens of the same cancer. For example, in our 849 surgically resected esophageal cancer specimens, lymph node metastasis accounted for 42.l%, whereas in 41 esophageal cancer autopsy specimens by the same authors, lymph node metastasis accounted for 63.3%, and in 26 cases of gastric cancer autopsy, all the cases had extensive lymph node metastasis. Lymphatic tract metastasis of carcinoma firstly involves regional draining lymph nodes. For example, among 854 cases of gastric cancer that we resected in the department of surgery, perigastric lymph nodes (first station lymph nodes) metastasized in 556 cases (accounting for 65.l%), while second station lymph nodes such as splenic area metastasized in only 37 cases (accounting for 4.3%), which indicates that metastasis of carcinoma is firstly to lymph nodes near the tumor, and then second station lymph nodes metastasis is found later. However, there are exceptions. In a few cases, the tumor occurred jumping metastasis, and when the tumor cells entered the thoracic duct along the lymphatic vessels, they could enter the blood circulation at the confluence of the left internal jugular vein and subclavian vein, and bloodway metastasis occurred. 3.Bloodway metastasis: this is the most common way of metastasis of sarcoma, such as osteosarcoma, lung metastasis can occur at a very early stage. However, in epithelial cancer, bloodway metastasis usually occurs in middle and late stages. When tumor cells invade into blood vessels (generally into small veins or capillaries, arteries are more difficult to invade), they can travel along the bloodstream to various organs of the whole body, and bloodway metastasis occurs. In bloodway metastasis of tumor, tumor cells usually invade capillaries or small veins first, sometimes form tumor embolus first, and then the tumor cells are dislodged and run along the direction of blood flow in the venous system. For example, gastrointestinal tumors firstly involve upper and lower mesenteric veins, and then enter into portal vein, and liver metastasis occurs. Thus, in the middle and late stages of gastrointestinal cancers, liver is often the first organ to be metastasized, and in the case of metastatic tumors in the liver, the tumor cells can be detached, and enter into the inferior vena cava along the hepatic vein, and then enter into the lungs through the heart, and then pulmonary metastasis occurs. As for soft tissue sarcoma of trunk or limbs, tumor cells often enter the venous system of body circulation and directly drain into the lungs, resulting in early lung metastasis. Numerous data show that soft tissue sarcoma is the earliest to develop lung metastasis, and the site of its tumor occurrence as well as the direction of blood flow is one of the reasons. Another important pathway of bloodway metastasis is through the spinal venous system, which is the third group of blood circulation system different from the body circulation or pulmonary circulation. It is characterized by the absence of venous valves, located in the vicinity of the vertebral canal and the thoracic and abdominal spine. When the posterior mediastinum or retroperitoneal tumors are squeezed (or when the thoracic or abdominal pressure increases), the tumor cells can pass through the vertebral venous system without passing through the lungs, but directly enter the spine or the cranial cavity to metastasize; therefore, the clinical tendency is to see the patients with vertebral or cerebral metastatic tumors and not to see metastatic foci of lungs, which is the reason for this. Bloodway metastasis is the main metastatic pathway in the early stage of sarcoma, such as osteosarcoma, rhabdomyosarcoma and so on, one of the main reasons is that the tumor blood vessels are very rich, and most of the walls of the blood sinus itself is composed of tumor cells, thus it is easy to be shed into the blood stream, and there is a pulmonary metastasis, and as a result, in the metastatic foci in the lungs, the tumor cells are shed into the body circulation, and metastatic foci in other organs or tissues are formed. However, in clinical work, the appearance of bloodway metastasis of middle and late stage cancer is often seen, and sometimes it is very extensive, therefore, bloodway metastasis of cancer should not be neglected. For example, in our analysis of 400 complete autopsies of carcinomas, we very carefully and routinely used bilateral neck, axillary fossa, mediastinum, retroperitoneum, mesentery and inguinal lymph nodes as well as organs in the whole body, and found that in addition to extensive lymph node metastasis, the rate of organ metastasis (most of which was through the blood tract) was also very high, and the frequency of organ hematological metastasis in the order of the lungs and the liver were each 162 cases (each accounting for 40.5%), which indicated that blood tract metastasis of cancer was more frequent in lungs and liver than in other organs. This indicated that the bloodway metastasis of cancer was most frequent in lung or liver. It was followed by adrenal gland in 79 cases (19.8%). There were 60 cases of pancreas (15.0%), 56 cases of bone (14.0%), 49 cases of spleen (12.3%), 46 cases of kidney (11.5%), 46 cases of septum (11.5%), 10.3% of large intestinal wall, 37 cases of small intestinal wall (9.3%), and other metastatic organs in the order of gastric wall, peritoneum, thyroid gland, pleura, subcutaneous, body, esophagus, etc. Among 400 cases of autopsy. In 400 cases of autopsy, except 65 cases of malignant lymphoma, there were only 14 cases of soft tissue and bone tumors (3.5%), and the vast majority of them were cancers, which indicated that the hematogenous metastasis of cancer should not be neglected. 4. Cultivation metastasis: this is a common way of cancer metastasis, especially gastrointestinal cancer. When the cancer cells break through the gastrointestinal wall, the cancer cells fall off and seem to “scatter seeds”, planting on the surface of peritoneum or mesentery, forming corn-like or nodular, sometimes accompanied by the proliferation of connective tissues, forming “discus-like” lumps. This kind of implantation metastasis can also be seen in the pleural cavity, pericardial cavity or subspideral cavity, but it is relatively rare. In addition, ovarian actinic adenoma or appendiceal actinic cyst, although the morphology is benign, once ruptured, can be planted in the abdominal cavity in the form of locally malignant peritoneal pseudo-taxinic fluid tumors, which is also known as implantation metastasis, this kind of patients, can cause ascites, intestinal adhesions, and finally cause intestinal obstruction, which is life-threatening. 5, Epithelial surface implantation metastasis, which is a controversial issue, some people think that upper lip cancer can also be implanted in the lower back. In clinic, patients with metastatic cell carcinoma of renal benefit, long at the same time or successively occurred metastatic cell carcinoma of ureter or bladder skin, some people think that it is planted, some people think that it is the spread of cancer lymphatics, but most scholars think that they are multicenter occurring at present. Factors affecting tumor proliferation and metastasis It is well known that many factors affect the proliferation and metastasis of malignant tumors. 1. Biological characteristics of tumor cells: In experimental research, cancer or sarcoma can sometimes be clearly determined as high metastatic group and low metastatic group, but in clinic, although the metastatic potentials of various tumors are different, due to the influence of the organism, they are not the same as those of other tumors. s metastatic potential is different, it is difficult to determine a certain tumor as high metastatic or low metastatic because of the different immune status (or other factors) of the organism itself. Thus, the degree of metastasis of two individual tumors of the same type and with similar degree of differentiation can be very different. In the literature reports with our experience, there are also different results. For example, we used DNA graphic phase analysis technology and found that the ploidy of esophageal invasive carcinoma and esophageal carcinoma in situ had a large difference, and the number of aneuploid was significantly higher in invasive carcinoma than carcinoma in situ. Most authors believe that PCNA or P53, which are cell proliferation-associated antigens, have a clear relationship with metastasis of carcinoma tumors, but there are also conclusions to the contrary. 2.Histological origin and histological type of carcinoma: It is a well-known fact that carcinoma is dominated by lymphatic tract metastasis, and sarcoma is dominated by hematogenous tract metastasis, but this is an early manifestation of carcinoma or sarcoma. For example, when we analyzed 967 cases of surgically resected gastric carcinoma, at that time, lymph node metastasis in the periphery of the stomach accounted for 65.5%, and hematogenous tract metastasis was only 2.8%. However, in the autopsy of 26 cases of gastric carcinoma in our case, except for the extensive metastasis of the lymph nodes, organ metastasis (bloodway metastasis) was as high as %. As for sarcoma, we rarely saw lymph node metastasis in surgical specimens, such as osteosarcoma, although we also saw inguinal lymph node metastasis, the earliest metastasis we saw was lung metastasis. There is a clear relationship between the histologic type of carcinoma and metastasis. For example, we cited cases of lung cancer autopsy, of which 26 cases of small cell carcinoma, 12 cases of squamous carcinoma, 11 cases of adenocarcinoma, the degree of metastasis extensive in the order of small cell carcinoma I “adenocarcinoma I “squamous carcinoma. In the same way, we performed bladder cancer autopsy in 5 cases, and the lymph node metastasis and organ metastasis were not much, indicating that urinary tract metastatic cell carcinoma was not extensive. The metastasis was not extensive. Another example is that we additionally performed 57 lung cancer autopsies and 56 cases of primary and secondary carcinoma autopsies, the number of both autopsies was almost equal, the former had 123 lymph node metastases (times) and 194 organ metastases (times), while liver cancer had 78 lymph node metastases (times) and organ metastases. It can be seen that the metastasis of lung cancer is much more extensive than that of liver cancer. The above materials indicate that, in addition to the histological type of tumor metastasis, there is also a clear relationship between the status of blood or lymphatic channels of organs. 3. Degree of tumor infiltration: there is a clear relationship between the extent of tumor involvement and the survival time of patients. This phenomenon is prominent in digestive or respiratory tract tumors. For example, in our analysis of 967 cases of surgically resected gastric cancer, we found that the depth of cancer infiltration was positively correlated with lymph node metastasis. The lymph node metastasis was 41.9% when the cancer invaded the superficial muscular layer, 58.7% when it invaded the deep muscular layer, 63.0% when it invaded the plasma membrane layer, and 74.0% when it invaded the extra-plasma membrane, which may be related to the abundance of lymphatic vessels. 4.Tumor differentiation degree: this is also a complicated issue with different opinions, for example, we classified invasive ductal carcinoma into 3 grades with reference to Bloom’s and Richacdson’s grading standard in 826 cases of radical mastectomy breast cancer specimens that had been followed up for more than five years after surgery. Among them, grade 1 lymph node metastasis accounted for 41.4%, grade 2 was 48.8%, and grade 3 was 66.7%. In addition to the present material confirming a definite relationship between breast cancer grade and patient survival, there is also a definite relationship between grade (degree of cancer cell differentiation) and lymph node metastasis. However, in the literature, there are also different conclusions on grading and prognosis III. Frequency of metastasis of major carcinomas: According to the guidance of Prof. Hou Baozhang, we adopted a special anatomical approach to tumors, i.e., in addition to the careful examination and sampling of all organs (except the brain), we routinely excised the bilateral cervical, bi-axillary, bi-inguinal, mediastinal, mesenteric, and peritoneal lymph nodes, which were numbered separately. All were taken for microscopic examination. For lymph nodes in other areas (e.g., hepatoportal, splenic portal, etc.), only enlarged lymph nodes were sampled. Otherwise, they were not sampled. For bone tissues, those clinically suspected of metastasis were sampled. Conclusion: 1. The metastasis of cancer is regular. Generally speaking, carcinoma in situ (or intraepithelial carcinoma) does not metastasize, and metastasis occurs when the tumor grows infiltratively to adjacent tissues, so it can be said that tumor infiltration is the forerunner of metastasis, and metastasis is the precursor of metastasis. Tumor infiltration is the forerunner or necessary way of metastasis. Therefore, it can be said that tumor infiltration is the precursor or the necessary way of metastasis. 2. Cancer (carcinoma) metastasizes along the lymphatic channel, firstly involves the lymph nodes near the tumor (the first station), and then metastasizes to the lymph nodes in the distant region. This is an early phenomenon of clinical cancer, but in the middle – late stage of cancer, bloodway metastasis cannot be ignored. In sarcoma, bloodstream metastasis is the main pathway. However, lymph node metastasis has also been seen to occur in many sarcomas. For example, in our autopsy, lymph node metastasis was found in osteosarcoma, malignant fibrous group, rhabdomyosarcoma and so on. 3.Metastasis is one of the main reasons for patient’s death, but some carcinomas, such as cervical cancer, bladder cancer, esophageal cancer, etc., are not widely metastasized, but mainly localized infiltration, so if these carcinomas are well handled locally, it will be half the result with half the effort. 4. The phenomenon of “target site” of metastatic foci of primary tumors: it means that some specific primary tumors have their site-specific target organs, which are always invaded by metastatic tumors firstly, such as small-cell lung cancer and melanoma preferentially metastasize to the brain, which may be related to the fact that these two kinds of tumors and host tissues have neuroendocrine properties. Gastrointestinal tract tumors firstly involve upper and lower mesenteric veins, and then enter into portal vein, and liver metastasis occurs; metastatic tumors in other parts of the body enter into lungs through vena cava and heart, and lung metastasis and brain metastasis occur. 5.Hematogenous pulmonary metastasis: early metastatic nodules are mostly located between bronchial vascular bundles of lung lobules and the edge of lobules, and a few nodules can be close to the above structures, in the position where tumor embolus stays. Cancer lymphadenitis: it manifests as linear or cord-like shadows radiating from the hilum to the lung field, interlobular septal lines, terminal bronchial vascular granular shadows, etc. It is most commonly seen in lung cancer, gastric cancer, cervical cancer, breast cancer and pancreatic cancer. In lung cancer and other malignant tumors with lung metastasis, carcinomatous lymphangitis is often an important mechanism for the formation of pleural fluid, and the appearance of pleural fluid is one of the signs suggesting carcinomatous lymphangitis. Unilateral carcinomatous lymphangitis is mostly caused by lung cancer. Bilateral adrenal enlargement or mass can be identified as metastasis, while unilateral adenoma should be excluded from the diagnosis. 20% of non-small cell lung cancer patients have adrenal mass at the time of definitive diagnosis, and 2/3 of them are asymptomatic adrenal adenoma. Some adrenal adenomas also have FDG uptake, which is often low, equal to or lower than that of the liver, while metastases often have high uptake. 8.Mucinous adenocarcinoma liver metastasis, containing more mucus, will be like a cyst with irregular cyst wall, which needs to be strengthened to identify.