What is tumor morphology?

(A), the general shape and structure of the tumor

(1) Macromorphology of tumor

Visually, tumors have various forms, which can reflect the benign and malignant of tumors to some extent.

1) Number and size of tumors: The number and size of tumors vary. More than one, sometimes more than one. The size of a tumor is related to its nature (benign or malignant), growth time and location. Tumors that grow on the body surface or in a larger body cavity can sometimes grow very large, while tumors that grow in a closed narrow cavity are generally smaller. Patients with particularly large tumors usually grow slowly and are mostly benign; Malignant tumors grow rapidly, which can bring adverse consequences in a short time, so they often don't grow up.

2) Tumor morphology: There are many kinds of tumors, including polypoid (exogenous growth), papillary (exogenous growth), nodular (expansive growth), lobulated (expansive growth), cystic (expansive growth), invasive mass (invasive growth), diffuse hypertrophy (exogenous with invasive growth) and ulcer with invasive growth. Morphological differences are closely related to its location, tissue source, growth mode and benign or malignant tumor.

3) Color of tumor: Generally, the section of tumor is grayish white or grayish red, depending on the amount of bleeding, the amount of bleeding, degeneration and necrosis. Some tumors will show different colors because they contain pigments. So we can infer what kind of tumor it is according to its color. For example, lipoma is yellow, malignant melanoma is black, and hemangioma is red or crimson.

4) The hardness of tumor: It is related to the type of tumor, the ratio of tumor substance to stroma, whether there is degeneration or necrosis. Tumors with more parenchyma than stroma are generally soft; On the contrary, tumors with more stroma than parenchyma are generally harder. Tumor tissue is soft when necrosis occurs and hard when calcification or ossification occurs. Lipoma is soft, osteoma is hard.

(2) the tissue structure of the tumor

The tissue structure of tumor is varied, but all the tissue components of tumor can be divided into two parts: parenchyma and stroma.

1) tumor parenchyma: tumor parenchyma is the general name of tumor cells and the main component of tumor. It determines the biological characteristics of tumors and the particularity of each tumor. Usually, the tissue source of various tumors is identified according to their substantive morphology, and the classification, naming and histological diagnosis of tumors are carried out, and the benign and malignant degree of tumors is determined according to their differentiation and maturity and dysplasia.

2) Tumor stroma: The stroma of tumor has no specificity and plays a role in supporting and nourishing tumor parenchyma. It is generally composed of connective tissue and blood vessels, and sometimes there are lymphatic vessels in the stroma. Usually, tumors with rapid growth are rich in interstitial blood vessels and less in connective tissue; There are fewer interstitial vessels in slow-growing tumors. In addition, tumors are often infiltrated by monocytes such as lymphocytes, which is the body's immune response to tumor tissue. In addition, fibroblasts and myofibroblasts can also be seen in tumor connective tissue. Myofibroblasts have the dual characteristics of fibroblasts and smooth muscle cells, which can not only produce collagen fibers, but also have contraction function, which may limit the infiltration of tumor cells. The proliferation of these cells can explain the intestinal stiffness and stenosis caused by nipple invagination of breast cancer, esophageal cancer and intestinal cancer.

(2) the specificity of tumor

No matter in cell morphology and tissue structure, tumor tissue is different from the normal tissue of its origin, and this difference is called atypical. Atypical is the morphological manifestation of abnormal differentiation of tumor. Small heteromorphism means high degree of differentiation, while large heteromorphism means low degree of differentiation. Distinguishing the size of this dysplasia is the main histological basis for diagnosing tumors and determining their benign and malignant. The atypia of benign tumor cells is not obvious, and it is generally similar to its source tissue. Malignant tumors often have obvious atypia.

Malignant tumor composed of undifferentiated cells is also called anaplastic tumor. Anaplastic refers to the lack of differentiation of malignant tumor cells, which is obviously atypical. Anaplastic tumors have obvious pleomorphism, and the size and morphology of tumor cells are very different, so it is often impossible to determine their tissue sources. Anaplastic tumors are usually highly malignant.

1, atypical tumor cells

Benign tumor cells have almost no atypia and are usually similar to normal cells from which they are derived. Malignant tumor cells are often highly atypical, showing the following characteristics:

(1) The pleomorphism of tumor cells means that the shape and size of tumor cells are inconsistent. Malignant tumor cells are generally larger than normal cells, and sometimes tumor giant cells can be seen. However, a few poorly differentiated tumors have small, round and uniform tumor cells.

(2) Polymorphism of tumor nuclei

Tumor nuclei are larger than normal nuclei, and their size, shape and staining are also different. And there may be binuclear, megakaryon, multinuclear, exotic nuclei and dark nuclei (due to the increase of DNA in the nuclei). Chromatin is coarsened and unevenly distributed, and often accumulates under the nuclear membrane, which makes the nuclear membrane appear hypertrophy. The increase of mitotic images, especially when asymmetric, multipolar, frustrated and other pathological mitoses appear, is of diagnostic significance to malignant tumors. The abnormal nuclear changes of malignant tumor cells are mostly related to polyploid or non-integer ploidy of chromosomes.

(3) Cytoplasmic changes of tumor cells: Due to the increase of nucleosomes in cytoplasm, most of them are basophilic. Tumor cells produce abnormal secretions or metabolites (such as hormones, mucus, protein, pigments, etc. ), so they have different characteristics.

(4) Heterogeneity of tumor cell ultrastructure: Generally speaking, the ultrastructure of benign tumor is basically similar to the tissue from which it originated. Malignant tumor cells show different atypia according to their differentiation degree. Generally speaking, malignant tumor cells are usually absolutely or relatively obviously enlarged, and the nuclear membrane may be invaginated or protruded, making the nuclear morphology irregular or even forming a single nucleus. Cytoplasmic organelles are usually reduced in number, stunted or abnormal in shape. Cell connection is often reduced, which is beneficial to tumor infiltration and growth.

2. Heterogeneity of tumor tissue structure

The heterogeneity of tumor tissue structure refers to the difference in spatial arrangement between tumor tissue and normal tissue (including polarity, organ-like structure and its relationship with stroma). The atypia of benign tumor cells is not obvious, but the arrangement is different from that of normal tissues. The diagnosis depends on the atypical tissue structure, such as uterine leiomyoma. The tissue structure of malignant tumor is obviously atypical, and the arrangement of tumor cells is more disordered, losing its normal arrangement structure, hierarchy or polar orientation, such as fibrosarcoma and adenocarcinoma.

(3) the growth and spread of tumor

Local infiltration and distant metastasis are the most important characteristics of malignant tumors and the main cause of death.

1. Tumors are formed by the continuous proliferation of transformed cells.

The natural growth history of typical malignant tumors can be divided into several stages:

Malignant transformation of A cells → clonal proliferation of transformed cells → local infiltration → distant metastasis.

In this process, the inherent characteristics of malignant transformed cells (such as tumor growth fraction) and the host's response to tumor cells and their products (such as tumor angiogenesis) all affect the growth and evolution of tumors.

(l) tumor growth kinetics. The growth rate of tumor is related to the following three factors:

1) tumor cell doubling time: the cell cycle of tumor population is also divided into G0, G 1, S, G2 and M stages. The doubling time of most malignant tumor cells is not faster than normal cells, but similar or slower than normal cells.

2) Growth fraction: refers to the proportion of cells in the proliferative phase (S phase +G2 phase) in the tumor cell population. In the initial stage of malignant transformation, the growth fraction is high, but with the continuous growth of tumors, most tumor cells are in G0 stage, even if the tumors grow rapidly, only 20% of them are.

3) Growth and loss of tumor cells: insufficient nutrition supply, necrosis and shedding, anti-tumor reaction of the body and other factors will make tumor cells lose, and the generation and loss of tumor cells will affect whether the tumor can grow progressively and its growth rate.

The growth rate of tumor depends on the growth fraction and the ratio of tumor cell formation and loss, but has little to do with doubling time. At present, almost all chemotherapy drugs are aimed at cells in the proliferative phase. Therefore, tumors with high growth fraction (such as highly malignant lymphoma) are particularly sensitive to chemotherapy. Common solid tumors (such as colon cancer) are not sensitive to chemotherapy because of their low growth fraction.

(2) Tumor angiogenesis. Inducing angiogenesis is one of the prerequisites for the growth, invasion and metastasis of malignant tumors. Tumor cells themselves and inflammatory cells (mainly macrophages) infiltrating into tumor tissues and their surroundings can produce a class of angiogenic factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (B-FGF). These angiogenic factors promote vascular endothelial cell division and capillary bud growth. New capillaries not only provide nutrition for tumor growth, but also provide favorable conditions for tumor metastasis.

(3) The evolution and heterogeneity of tumor. The phenomenon that malignant tumors become more and more aggressive in the process of growth is called tumor evolution, including accelerated growth, infiltration of surrounding tissues and distant metastasis. The appearance of these biological phenomena is related to the heterogeneity of tumors. Tumor heterogeneity refers to the process that a cloned tumor cell forms subclones with different invasion ability, growth rate, response to hormones and sensitivity to anticancer drugs. Because of these differences, subclones adapted to survival, growth, infiltration and metastasis were preserved during tumor growth.

2. Growth mode and spread of tumor

(1) Growth rate of tumor: The growth rate of various tumors varies greatly, mainly depending on the differentiation and maturity of tumor cells. Benign tumors grow slowly, malignant tumors grow rapidly, and the growth rate of benign tumors suddenly increases when they become malignant.

(2) Tumor growth mode: Tumors can be expansive growth, exogenous growth and invasive growth.

1) Expansive growth: It is the growth mode of most benign tumors. Tumors grow slowly, do not invade the surrounding tissues, and are often nodular, with complete capsule and obvious boundary with the surrounding tissues. They mainly squeeze or block the surrounding organs and tissues. There is no obvious damage to the structure and function of general organs. Because of its clear boundary with surrounding tissues, it is easy to be surgically removed and not easy to recur after resection.

2) Exogenous growth: Tumors that occur on the body surface, the surface of body cavity or the surface of pipeline organs (such as digestive tract and urogenital tract) often grow to the surface, forming protruding papillary, polypoid and cauliflower tumors. Both benign and malignant tumors can grow outward. However, while the malignant tumor grows exogenously, its basal part also grows infiltratively. Because of the fast growth speed and insufficient blood supply, the exogenously growing malignant tumor is easy to necrosis and fall off, forming a malignant ulcer with uneven bottom and protruding edges.

3) Invasive growth: it is the growth mode of most malignant tumors. Because of the rapid growth of tumors, they invade the interstitial spaces, lymphatic vessels and blood vessels around them. For example, the roots of trees grow into the soil and infiltrate and destroy the surrounding tissues. Tumors often have no capsule or incomplete capsule, and the boundary with the surrounding tissues is not obvious. At the time of clinical palpation, the tumor was fixed. In order to prevent recurrence, the resection range is larger than that seen by naked eyes, because there may be tumor cells infiltrating in these parts.

3. The spread of tumor

This is the main feature of malignant tumor. Invasive growth of malignant tumors can not only grow and spread in the primary site (direct spread), but also spread to other parts of the body (metastasis) through various channels.

(1) Direct diffusion: Tumor cells infiltrate along stroma, lymphatic vessels, blood vessels or nerve bundles, destroy adjacent normal tissues and organs, and continue to grow, which is called direct diffusion. For example, advanced cervical cancer can spread to the rectum and bladder, and advanced breast cancer can pass through the pectoral muscle and chest cavity and even reach the lungs.

(2) Metastasis: Tumor cells invade lymphatic vessels, blood vessels and body cavities from the primary site, migrate to other places and continue to grow, forming the same type of tumor as the primary tumor. This process is called transfer. Benign tumors do not metastasize, only malignant tumors metastasize. Common transfer routes are as follows:

1) Lymphatic metastasis: Epithelial malignant tumors mostly metastasize through lymphatic channels;

2) Blood metastasis: all kinds of malignant tumors can occur, especially sarcoidosis, renal cancer, liver cancer, thyroid follicular cancer and choriocarcinoma;

3) Implantable metastasis: cancer common in abdominal organs.

4. Invasion and metastasis mechanism of malignant tumor.

(l) local infiltration. The emergence of subclones of tumor cells with strong infiltration ability and the formation of blood vessels in tumor play an important role in local infiltration of tumor.

Steps of local infiltration:

1) Cell adhesion molecules mediate the decrease of tumor cell adhesion;

2) Tumor cells are closely attached to the basement membrane; 3) Degradation of extracellular matrix. After 4 ~ 8 hours of close contact between cancer cells and basement membrane, the main components of extracellular matrix, such as LN, FN, proteoglycan and collagen fiber, can be dissolved by proteolytic enzymes secreted by cancer cells, resulting in local defect of basement membrane.

4) Cancer cells pass through the dissolved basement membrane defect with amoeba movement. After the cancer cells pass through the basement membrane, the above steps are repeated to dissolve the interstitial connective tissue and move in the stroma. When it reaches the blood vessel wall, it passes through the basement membrane of the blood vessel and enters the blood vessel in the same way.

(2) blood diffusion. After a single cancer cell enters a blood vessel, it is generally destroyed by immune cells of the body, but the tumor cell mass with platelet aggregation is not easy to be destroyed, and it can pass through the vascular endothelium and basement membrane through the above-mentioned ways to form a new metastatic focus.

The occurrence of metastasis is not random, but has obvious organ tendency. The location and organ distribution of blood metastasis have special affinity in some tumors, such as lung cancer, adrenal gland and brain, thyroid cancer, renal cancer and prostate cancer, breast cancer, etc., and often metastasize to liver, lung and bone. The reason for this phenomenon is not clear, which may be that there are ligands on the vascular endothelium of these organs, which can specifically bind to adhesion molecules on the surface of cancer cells entering the blood circulation, or because these organs can release chemicals that attract cancer cells.

5. Classification and staging of tumors: generally only used for malignant tumors.

Tumor classification: Grade I differentiation is good, belonging to low-grade malignancy; Grade ⅱ is moderately differentiated and moderately malignant; Grade ⅲ differentiation is poor and the degree of malignancy is high.

Tumor staging: TNM staging system is generally used. According to the size, infiltration depth and scope of the primary tumor, and whether adjacent organs are involved, whether there is lymph node metastasis, whether there is blood-borne or other distant metastasis, the course of tumor development is determined sooner or later.