Overview of Carcinoid Tumors
The term carcinoid was coined in the early 20th century when Oberndorfer used the term “karzinoid” in 1907 to describe a group of slow-growing, low-grade malignant tumors that were subsequently discovered to originate from the gastrointestinal tract, the silver-loving Lieberkuhn’s gland. In 1953, Lembeck discovered that these tumor cells could secrete 5-hydroxytryptamine, and in 1969, Pearse discovered that these cells had the ability to take up amine precursors and decarboxylate, and subsequently, due to the development and application of immunohistochemical techniques, it was discovered that carcinoid cells could produce many peptide and amine hormones, thus questioning the nomenclature and classification of carcinoid tumors. Kloppel et al. suggested that the term “neuroendocrine tumor” should be used instead of “carcinoid tumor” and the following principles should be followed in its classification: (i) the primary site of the tumor; (ii) the growth behavior of the tumor (benign, less malignant, malignant, etc.), in which the size of most tumors has a clear relationship with the prognosis of the disease. Some tumors produce a lot of hormones and show clinical symptoms, which is called functional, while others have few hormone-related symptoms and are called non-functional. Yan Zu, Department of Oncology, Affiliated Hospital of Qinghai University
Carcinoid tumor is relatively rare, accounting for 0105 to 012 % of all malignant tumors and 014 to 118 % of gastrointestinal tract tumors, and its incidence rate is 113/100,000 according to foreign statistics, but the actual incidence rate may far exceed the statistics. It can occur at any age. The age of onset of appendiceal carcinoid tumor is relatively young, 30 years old on average, while the age of onset of carcinoid tumors in other parts of the body is about 50 years old on average. With the exception of appendiceal carcinoid tumors, most carcinoid tumors occur more frequently in men, and more than 90% of carcinoid tumors occur in the gastrointestinal tract, primarily in the appendix, terminal ileum, and rectum. The appendix, ileum and rectum accounted for more than 90% of all carcinoid tumors in the gastrointestinal tract, with a few occurring in the colon, stomach, duodenum, Mckel’s diverticulum, bile duct, pancreatic duct, gonads, lung and bronchus, etc. Orloff collected 3,000 cases of carcinoid tumors in the gastrointestinal tract, of which 47% were appendix carcinoid tumors, 3013% were small intestine carcinoid tumors and 12% were rectum carcinoid tumors; Yu Hong Shao et al. According to the analysis of 412 cases of gastrointestinal tract carcinoid tumors, rectal carcinoid tumors accounted for 64.1%, appendiceal carcinoid tumors accounted for 12.1%, and small intestinal carcinoid tumors accounted for 2.2%. The prevalence of carcinoid tumors may vary among different ethnic groups. In Japan, more carcinoid tumors occurred in the stomach, duodenum and colon than in Europe and the United States, but fewer carcinoid tumors occurred in the small intestine, which may be related to the different distribution of chromophores in the organs of Japanese and European Americans.
Pathological features of carcinoid tumors.
Typical carcinoid tumors of the gastrointestinal tract are usually small yellow or gray submucosal nodular masses, single or multiple, with intact mucosal surface, and varying in shape, including nodular, polyp-like or annular. In some cases, ulcers may form on the surface of the tumor, resembling adenocarcinoma, and often invade the muscular layer and plasma layer. Some patients may have carcinoid tumors of multiple origins. Ileal carcinoid tumors are often multiple, small, < 3.5 cm in diameter, mostly around 1.5 cm. Carcinoid cells originate from intestinal chromophores (also known as kulchitsky cells) in the APUD cell system, which originate from the embryonic neural crest and are mainly distributed in all gastrointestinal tracts except the esophagus, mainly in the duodenum, distal ileum and appendix in the small intestine, and diffusely in the large intestine, producing a variety of peptidomimetic hormones. Carcinoid cells are square, columnar, polygonal or round under the microscope. The nuclei were uniform, with few nuclear fission phases, and the cell pulp contained eosinophilic granules. According to electron microscopy, the morphology and histochemistry of intracytoplasmic granules in various carcinoid tracts of the gastrointestinal tract were different. Small intestine carcinoma cells contained large and polymorphic granules, which were silver staining positive and therefore silver-friendly. The granules of gastric carcinoma cells are round in shape, and the silver staining reaction is positive only when an exogenous reducing agent is added, so they are silver-loving. The granules of rectal carcinoid tumor cells are large, round, uniform, and negative for silver and silverophilic staining, so they are non-reactive.
Williams classified carcinoid tumors of foregut, midgut and hindgut origin according to embryogenesis and blood supply. Carcinoid tumors in the foregut (respiratory tract, stomach, duodenum, and jejunum) produce many hormones, but the amount is small, so there are few clinical symptoms; carcinoid tumors in the midgut (ileum, appendix, and ascending colon) mainly secrete 5-hydroxytryptamine, which exceeds the degradation capacity of the liver, especially in the presence of liver metastases, and often show symptoms of carcinoid syndrome; carcinoid tumors in the hindgut (descending colon and rectum) secrete many peptides. The carcinoid cells in the hindgut (descending colon and rectum) can secrete a variety of peptides, such as growth inhibitors, enkephalins, and P substances, which rarely show carcinoid syndrome.
Metastatic pathways.
The metastasis rate of small intestine carcinoid tumor is 30 %, and 38 % for colon. Malignant carcinoid tumors of the duodenum and stomach are less common than those of the small intestine. The metastatic route of carcinoid tumor can be direct infiltration and growth, penetrate the plasma membrane to the surrounding tissues, or lymphatic metastasis or hematogenous metastasis. Direct hematogenous metastasis without local lymph node metastasis has been reported occasionally. Other rare metastatic sites have been reported: ovary, epididymis, skin, bone marrow, retroperitoneum, orbit, adrenal gland, spleen, pancreas, kidney, thyroid, bladder, prostate, and cervix. Metastasis to the breast has also been reported, and its clinical signs are very similar to those of the primary breast cancer.
Current status of research.
Currently, most studies on carcinoid tumors have focused on their neuroendocrine cell markers, such as NSE, Chomogranin A, Synaptophysin, etc., and the secretion of peptide hormones such as 5-hydroxytryptamine. It is now generally accepted that carcinoid tumors represent a group of tumors rather than a single pathological process. Therefore, a large number of studies have focused on the neuroendocrine hormones of carcinoid tumors, but little research has been reported on the proliferation and invasiveness of carcinoid tumors. The relationship between the malignancy of carcinoid tumor and its proliferation, proto-oncogene and oncogene, and its invasiveness and clinical relationship needs to be studied in depth.
Gastrointestinal carcinoid tumor is also a kind of cancer, but it is a slow-growing and less malignant tumor. These cancers are rare, accounting for only 0.05%-0.2% of all malignant tumors, and can occur in the digestive, respiratory, genitourinary systems, thymus, thyroid, skin and other parts of the body. According to statistics, carcinoid tract cancer accounts for 67.5% of all carcinoid tumors and 0.4%-1.8% of all malignant tumors in the digestive tract. Gastrointestinal tract carcinoid tumors can occur in any part of the esophagus to the rectal canal, and the most frequent parts are appendix, small intestine, colon, rectum and stomach in order of prevalence. The malignancy of carcinoid tumor is determined by the size of the tumor, the depth of tumor infiltration and whether there is metastasis. If the tumor is 2 cm in diameter and the local tumor infiltrates into the muscular layer and plasma membrane of the gastrointestinal tract, metastasis can reach 85%. Tumor cells may metastasize via lymphatic vessels to the associated lymph nodes, mesentery, liver, and the whole body. Carcinoid tumor can occur at any age, from 10 days after birth to 92 years old, with 40-60 years old being the most common.
Early symptoms of GI carcinoid tract
1. Skin flushing
This is the earliest warning signal, which starts with flushing of skin, with a short duration, usually only 5-10 minutes per attack, starting from face, neck and chest, then extending to other parts of the body, showing deep red color, then turning into greenish purple, and finally pale white, which is the characteristic tricolor change. This is the characteristic trichromatic change. This skin manifestation is called carcinoid syndrome, which is caused by the secretion of serotonin, i.e. 5-chromogel, histogel, and other gums and skin-like substances by carcinoid cells with strong biological activity.
2. Abdominal pain and diarrhea
Diarrhea is usually seen after meals or early in the morning, mostly intermittent in the early stage, but in severe cases, it can reach 20-30 times a day, and can be accompanied by malnutrition and imbalance of water and electrolyte balance.
(1) Colorectal carcinoma usually presents with abdominal discomfort, abdominal pain, change in stool habit, blood in stool, and eventually intestinal obstruction.
(2) Appendiceal carcinoma often presents with pain and pressure in the right lower abdomen similar to acute appendicitis.
(3) Small intestine carcinoid tumors usually do not have obvious warning signs, but may show abdominal pain, diarrhea, abdominal masses, and in some cases, intestinal obstruction, and duodenal carcinoid tumors occurring in Vater’s jugular abdomen may show obstructive yellow distemper.
(4) Gastric carcinoid tumor is characterized by upper abdominal discomfort, vague pain, sometimes burning sensation, nausea, vomiting and vomiting blood, similar to gastric stain.
Diagnosis of digestive tract test
The presence of carcinoid tumor is suggested by skin flushing, diarrhea, abdominal pain and other manifestations. Increased serotonin levels in blood (normal value 0.57-1.71umol/L) and increased urinary excretion of 5-tool of acetic acid (normal value 24-hour urinary excretion) are measured.