I. History and current status of cardia cancer
The Siewert study group considered that tumors in the cardia area have their own characteristics.
In 1998, the International Society of Gastric Cancer and the International Society of Esophageal Diseases defined pancreatic cancer as adenocarcinoma with a tumor center located in the esophagogastric junction within 5 cm of the proximal/distal cardia. In the year 2000, this classification was slightly changed. Tumors centered within 5 cm proximal or distal to the cardia were designated as adenocarcinoma of the esophagogastric junction. This includes type I adenocarcinoma, which may infiltrate the esophagogastric junction from above; type II, which originates from the esophagogastric junction; and type III adenocarcinoma or subcardia, which infiltrates the esophagogastric junction from below upwards. It has its own characteristics from various aspects such as anatomy, physiology and pathology. Its 5-year survival rate is significantly lower than that of gastric sinus cancer, and its prognosis is poor. The pathological type is mainly adenocarcinoma, with a few adenokeratotic carcinomas and more malignant mucinous carcinomas, and very few squamous cell carcinomas originating from above the esophagogastric junction.
Cardia cancer is one of the common malignant tumors, and its pathomorphology, biological behavior and surgical approach have been studied extensively. With the rapid development of cell biology, molecular biology and bioengineering technology in recent years, especially the application of immunohistochemistry technology, the research of cardia cancer has been more profoundly developed. This article only summarizes and discusses the research on the pathomorphology and biological behavior of pancreatic cancer, to understand the relationship between these molecular changes and the biological behavior of pancreatic cancer, to further guide the early clinical diagnosis and the selection of therapeutic measures, to improve the survival rate of patients, and to achieve the ultimate goal of curing pancreatic cancer.
Pathomorphology of pancreatic cancer
(A) Pathological characteristics of early pancreatic cancer
Early pancreatic cancer refers to the cancerous tissue limited to the mucosal layer or submucosal layer, regardless of whether there is lymph node metastasis or not.
1.The general types of early cardia cancer
At present, our country divides early cardia cancer into the following three types.
(1) Depressed type: the mucosa of the lesion area is depressed, with erosion and occasionally superficial ulcer formation, and the demarcation with normal tissue is not obvious.
(2) Elevated type: The mucosa of the lesion area shows a slightly irregular elevation with a rough, granular surface, which is hard to touch and occasionally forms nodular or polyp-like protrusions.
(3) Flat type: Except for slightly rough mucosa in the lesion area, there is usually no abnormality seen by the naked eye, and the thickness of the lesion is similar to that of normal mucosa in the cut surface.
2.Histological types of early pancreatic cancer
Early pancreatic cancer is superficial cancer, which refers to mucosal cancer where the infiltration of cancer stops at the submucosa. According to the infiltration depth of cancer tissue, early cardia cancer can be divided into mucosal cancer and submucosal cancer. Mucosal cancer refers to cancer infiltration confined to the intramucosal layer, also called intramucosal cancer (carcinoma in situ); submucosal cancer refers to cancer infiltration that has reached the submucosal layer.
(B) Pathological characteristics of middle and advanced cardia cancer (progressive cardia cancer)
1.Middle and advanced pancreatic cancer sarcoid type
(1) International staging
Currently, the internationally widely used staging method proposed by Bormann (1926) classifies pancreatic cancer into four types.
(1) Confined ulcer type: the tumor ulcer is deeper, the edge is elevated, the swelling is more confined, the surrounding infiltration is not obvious, and the cut surface is clearer.
(2) Bulging type: the tumor grows mainly into the gastric cavity, forming a highly convex mass with a larger size, cauliflower and tumor-like nodular polyps. There are ulcers of different depths on its surface, and the cut surface boundary is clearer.
(3) Infiltrative ulcer type: The tumor grows infiltratively into the cardia canal and forms deeper ulcers, the surrounding mucosa is contracted radially, and the cut surface boundary is not clear. (4) Diffuse infiltrative type
The cancerous tissue grows infiltratively in the stomach wall, the infiltrated stomach wall thickens and hardens, the wrinkled wall disappears, the mucosa flattens, sometimes accompanied by shallow ulcers, and if the whole stomach is involved, it forms the so-called leather capsule-like stomach.
(2) Domestic typing
At present, there are three types of mid- to late-stage cardia cancer in China.
(1) Infiltrative cardia cancer: smaller in size, mostly riding at the junction, with only shallow erosions or shallow ulcers on the surface. On the section, the tumor mainly infiltrates beyond the muscular layer, and the esophagus and stomach wall are uniformly thickened.
(2) Cauliflower type cardia cancer: it mainly grows into the gastric lumen and forms a highly convex larger mass. On the cross-section, most of the cancer is inside the muscular layer, and the edges are more distinct in the longitudinal section. This type of pancreatic cancer is mostly located below the junction of esophagus and stomach, with a few riding at the junction.
(3) Ulcerated pancreatic cancer: large ulcers are formed, mostly located below the junction.
2.Histological types of middle and late stage cardia cancer
Unlike early-stage pancreatic cancer, cancerous tissues have invaded into the muscular layer, plasma membrane layer or extra-plasma membrane of gastric wall, regardless of the size of the cancer foci or the presence of metastasis, all are called mid-advanced pancreatic cancer. At present, there is no special histological classification for pancreatic cancer, but all refer to the classification of gastric cancer. According to WHO histological classification of gastric cancer, this classification is also mostly used in China at present. The main characteristics of each type are as follows.
(1) Ductal adenocarcinoma (differentiated adenocarcinoma): Cancer cells form an obvious ductal cavity, which varies in size and shape. Some of them have very small lumen and are called adenoid adenocarcinoma. This type of adenocarcinoma is also a highly differentiated adenocarcinoma, and the cancer cells are well differentiated, columnar or rectangular in shape, neatly arranged, and clearly polarized. Among tubular adenocarcinomas, some are more differentiated and some are less differentiated, so there are highly differentiated tubular adenocarcinomas and moderately differentiated tubular adenocarcinomas.
(2) Papillary adenocarcinoma: The cancer cells form irregular luminal spaces, and the cancer cells form branched papillae protruding into the luminal spaces, which have fibrous axes in their branched papillae, but sometimes they are pseudopapillary, i.e. papillae without fibrous axes. The cancer cells are columnar or hypocolumnar, with enlarged and malformed nuclei, and the cells maintain a certain polarity, which are well differentiated adenocarcinomas. Sometimes mixed with images of tubular adenocarcinoma, it is called papillary tubular adenocarcinoma.
(3) Mucinous adenocarcinoma: This type of adenocarcinoma also forms a glandular cavity, characterized by cancer cells that can secrete a large amount of mucus to accumulate in the glandular cavity, so the cavity often expands or is squeezed and ruptured and infiltrates the interstitium to form a mucus lake. The cancer cells are mostly columnar in shape, lightly stained due to the production of large amounts of mucus in the cytoplasm, and are lightly basophilic. It is common to see patches of cancer cells shed into the glandular lumen or mucus lake. Sometimes, single shed cancer cells become spherical or ring-like due to surface tension. This type of gastric cancer contains a large amount of mucus in the tissue, which is translucent and jelly-like in the specimen, so it is also called “jelly-like cancer” or “mucus cancer”.
(4) Indolent cell carcinoma or mucinous cell carcinoma: The cells of this type of gastric cancer are mostly scattered infiltrating and do not form obvious cancer nests. The cancer cells can produce a large amount of mucus but do not secrete it outside the cells, thus the cancer cells are spherical in shape.
(5) Hypodifferentiated adenocarcinoma: Adenocarcinoma with inconspicuous glandular duct structure or almost no glandular duct-like structure (solid carcinoma) with great conformational variation, including medullary carcinoma of the stomach and hard carcinoma.
(6) Undifferentiated carcinoma: solid carcinoma that does not form glandular-like structures, with small cancer cells, large, densely stained nuclei and many nuclear fission images, constituting different degrees of lamellae or striae.
(7) Rare types of gastric cancer: including gastric adenosquamous carcinoma, squamous cell carcinoma, hepatocellular adenocarcinoma, mural cell-like adenocarcinoma, choriocapillary epithelial carcinoma and carcinoid tumor.
(1) Squamous carcinoma: squamous carcinoma presenting various degrees of differentiation, and the foci must be surrounded by gastric mucosa.
Adenosquamous carcinoma: It refers to a carcinoma with both adenocarcinoma and squamous carcinoma components, and the amount of both components is almost equal. If the adenocarcinoma contains only a small amount of squamous chemistry, then it should be diagnosed as adenosquamous carcinoma.
(3) Carcinoid tumor: It is a neuroendocrine tumor. Carcinoid tumors are composed of interconnected cords or bands, sometimes in daisy-like or adenoidal rows. Carcinoid cells are round, ovoid or columnar in shape and uniform in size. The nucleus is round and vacuolated, with occasional odd nuclei, usually without nuclear division, and the cytoplasm often contains eosinophilic granules. The interstitium is a small amount of fibrous tissue rich in blood vessels, usually without necrosis and inflammatory cell infiltration.
Mural cell carcinoma: generally solid growth, rich cytoplasm with a large number of eosinophilic granules, positive phosphotungstic hematoxylin and solid blue staining; immunohistochemistry is positive for antibodies against mural cells, which is helpful for diagnosis.
⑤ Hepatocellular adenocarcinoma: tumor cells with adenoid and hepatocyte-like differentiation characteristics, both of which are mixed. The tumor is usually nodular or mass-like in appearance.
(6) Choriocapillary epithelial carcinoma: Its morphology is similar to that of uterine choriocarcinoma; a few cases are often associated with adenocarcinoma component. Immunohistochemistry shows positive HCG.
(iii) Ultrastructural study of pancreatic cancer
The ultrastructure of pancreatic cancer is mostly referred to gastric cancer. In addition to the above pathological histological types, gastric adenocarcinoma is further classified into gastric type gastric cancer and intestinal type gastric cancer and mural cell adenocarcinoma according to its histogenesis and secretion of mucus by using electron microscopy, combined with immunohistochemical staining or HE staining. In the case of adenocarcinoma, mucinous adenocarcinoma, undifferentiated adenocarcinoma and other gastric cancers, there are cells with neuroendocrine cell differentiation phenotype, i.e., tumor cells with bi-directional differentiation characteristics.