Digestive system tumors can either be benign (non-cancerous) or malignant (cancerous). There are certain tumors that are classified as atypical (uncertain or unspecified behavior) meaning that some behave in a benign manner, or some behave in a malignant manner. A majority of the tumors diagnosed via lab studies (biopsy) are benign.

Tumors of the digestive system may involve the anatomical regions of esophagus, stomach, small intestine and ampulla, appendix, colon and rectum, liver and intrahepatic bile ducts, gallbladder and extrahepatic bile ducts, pancreas, and the anal canal.

The World Health Organization (WHO) is an authoritative body that compiles, prepares, and publishes histological and molecular classification of tumors, via their Blue Books, based on research inputs from experts worldwide. These reference books chiefly aid in global cancer research, provide gold standards for tumor diagnosis, and help in treating cancer patients.

According to the WHO Classification of Digestive System Tumors (2019), 5th Ed., Vol. 1, benign and malignant tumors of the digestive system are classified in the following manner:

Tumors of the esophagus:

Tumors of the esophagus

Epithelial tumors

• Benign epithelial tumors and precursors
  • Esophageal squamous papilloma
  • Barrett dysplasia
  • Esophageal squamous dysplasia
• Malignant epithelial tumors
  • Adenocarcinoma of the esophagus and esophagogastric junction NOS
  • Esophageal adenoid cystic carcinoma
  • Esophageal adenosquamous and mucoepidermoid carcinomas
  • Esophageal squamous cell carcinoma NOS
  • Esophageal undifferentiated carcinoma
  • Esophageal neuroendocrine neoplasms

Tumors of the stomach:

Tumors of the stomach

Gastritis and metaplasia: precursors of gastric neoplasms

Epithelial tumors

• Benign epithelial tumors and precursors
  • Fundic gland polyps
  • Gastric hyperplastic polyps
  • Gastric dysplasia
  • Intestinal-type gastric adenoma
  • Foveolar-type adenoma
  • Gastric pyloric gland adenoma
  • Oxyntic gland adenoma
• Malignant epithelial tumors
  • Gastric adenocarcinoma
  • Gastric squamous cell carcinoma
  • Gastric adenosquamous carcinoma
  • Gastric undifferentiated carcinoma
  • Gastroblastoma
  • Gastric neuroendocrine neoplasms

Tumors of the small intestine and ampulla:

Tumors of the small intestine and ampulla

Epithelial tumors

• Benign epithelial tumors and precursors
  • Non-ampullary adenoma
  • Ampullary adenoma
• Malignant epithelial tumors
  • Non-ampullary adenocarcinoma
  • Ampullary adenocarcinoma
  • Small intestinal and ampullary neuroendocrine neoplasms

Tumors of the appendix:

Tumors of the appendix

Epithelial tumors

• Appendiceal serrated lesions and polyps
• Appendiceal mucinous neoplasm
• Appendiceal adenocarcinoma
• Appendiceal goblet cell adenocarcinoma
• Appendiceal neuroendocrine neoplasms

Tumors of the colon and rectum:

Tumors of the colon and rectum

Epithelial tumors

• Benign epithelial tumors and precursors
  • Colorectal serrated lesions and polyps
  • Conventional colorectal adenoma
  • Inflammatory bowel disease-associated dysplasia of the colorectum
• Malignant epithelial tumors
  • Colorectal adenocarcinoma
  • Colorectal neuroendocrine neoplasms

Tumors of the anal canal:

Tumors of the anal canal

Epithelial tumors

• Benign epithelial tumors and precursors
  • Inflammatory cloacogenic polyp
  • Anal condyloma
  • Anal squamous dysplasia (intraepithelial neoplasia)
• Malignant epithelial tumors
  • Anal squamous cell carcinoma
  • Anal adenocarcinoma
  • Anal neuroendocrine neoplasms

Tumors of the liver and intrahepatic bile ducts:

Tumors of the liver and intrahepatic bile ducts

Epithelial tumors

• Benign hepatocellular tumors
  • Focal nodular hyperplasia of the liver
  • Hepatocellular adenoma
• Malignant hepatocellular tumors and precursors
  • Hepatocellular carcinoma
  • Hepatoblastoma
• Benign biliary tumors and precursors
  • Bile duct adenoma
  • Biliary adenofibroma
  • Biliary intraepithelial neoplasia
  • Intraductal papillary neoplasm of the bile ducts
  • Mucinous cystic neoplasm of the liver and biliary system
• Malignant biliary tumors
  • Intrahepatic cholangiocarcinoma
• Combined hepatocellular-cholangiocarcinoma and undifferentiated primary liver carcinoma
• Hepatic neuroendocrine neoplasms

Tumors of the gallbladder and extrahepatic bile ducts:

Tumors of the gallbladder and extrahepatic bile ducts

Epithelial tumors

• Benign epithelial tumors and precursors
  • Pyloric gland adenoma of the gallbladder
  • Biliary intraepithelial neoplasia
  • Intracholecystic papillary neoplasm (formerly Intracystic / intraductal papillary neoplasm)
  • Intraductal papillary neoplasm of the bile ducts
• Malignant epithelial tumors
  • Carcinoma of the gallbladder
  • Carcinoma of the extrahepatic bile ducts
  • Neuroendocrine neoplasms of the gallbladder and bile ducts

Tumors of the pancreas:

Tumors of the pancreas

Epithelial tumors

• Benign epithelial tumors and precursors
  • Acinar cystic transformation of the pancreas
  • Serous neoplasms of the pancreas
  • Pancreatic intraepithelial neoplasia
  • Pancreatic intraductal papillary mucinous neoplasm
  • Pancreatic intraductal oncocytic papillary neoplasm
  • Pancreatic intraductal tubulopapillary neoplasm
  • Pancreatic mucinous cystic neoplasm
• Malignant epithelial tumors
  • Pancreatic ductal adenocarcinoma
  • Pancreatic acinar cell carcinoma
  • Pancreatoblastoma
  • Solid pseudopapillary neoplasm of the pancreas
• Pancreatic neuroendocrine neoplasms
  • Pancreatic neuroendocrine neoplasms: Introduction
  • Non-functioning pancreatic neuroendocrine tumors
• Functioning pancreatic neuroendocrine tumors
  • Insulinoma
  • Gastrinoma
  • VIPoma
  • Glucagonoma
  • Somatostatinoma
  • ACTH-producing neuroendocrine tumor
  • Serotonin-producing neuroendocrine tumor
• Pancreatic neuroendocrine carcinoma
• Pancreatic MiNENs

Hematolymphoid tumors of the digestive system:

Hematolymphoid tumors of the digestive system

Hematolymphoid tumors

• Site-specific hematolymphoid tumors
  • Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) involving the digestive tract
  • Duodenal-type follicular lymphoma
  • Enteropathy-associated T-cell lymphoma: It is a T-cell non-Hodgkin’s lymphoma of the gastrointestinal tract. It is a rare and aggressive malignancy of T-cell lymphocytes arising in the intestines. It is noted in middle-aged and older adults
  • Monomorphic epitheliotropic intestinal T-cell lymphoma
  • Intestinal T-cell lymphoma NOS
  • Indolent T-cell lymphoproliferative disorder of the GI tract
  • Hepatosplenic T-cell lymphoma: It is an extremely rare and aggressive type of ‘extranodal lymphoma’ observed in the spleen, liver, and bone marrow. It is most commonly seen in adolescents  and young adults
  • EBV+ inflammatory follicular dendritic cell sarcoma of the digestive tract
• Hematolymphoid tumors occurring with some frequency in the digestive system
  • Diffuse large B-cell lymphoma
  • Follicular lymphoma: Gastrointestinal Follicular Lymphoma (GI-FL) is a rare type of B-cell non-Hodgkin’s lymphoma that generally affects older adults. It is typically a low-grade malignancy lymphoma
  • Mantle cell lymphoma
  • Burkitt lymphoma
  • Plasmablastic lymphoma
  • Posttransplant lymphoproliferative disorders
  • Extranodal NK/T-cell lymphoma
  • Systemic mastocytosis
  • Langerhans cell histiocytosis: It is a rare, complicated, and non-heritable genetic disorder that can result in tumor formation in many different body parts. The disorder typically affects very young children
  • Follicular dendritic cell sarcoma
  • Histiocytic sarcoma

Mesenchymal tumors of the digestive system:

Mesenchymal tumors of the digestive system

Mesenchymal tumors

• Gastrointestinal stromal tumor
  • Gastrointestinal stromal tumor: It is a type of tumor that occurs in the gastrointestinal tract. The most common location of this tumor is the stomach, or the small intestine. The tumor usually forms in adults
• Adipose tissue and (myo)fibroblastic tumors
  • Inflammatory myofibroblastic tumor
  • Desmoid fibromatosis
  • Solitary fibrous tumor
  • Lipoma
  • Inflammatory fibroid polyp
  • Plexiform fibromyxoma
• Smooth muscle and skeletal muscle tumors
  • Leiomyoma
  • Leiomyosarcoma
  • Rhabdomyosarcoma
• Vascular and perivascular tumors
  • Hemangioma
  • Epithelioid hemangioendothelioma (prev Vascular Tumors in Liver)
  • Kaposi sarcoma
  • Angiosarcoma
  • Glomus tumor
  • Lymphangioma and lymphangiomatosis
• Neural tumors
  • Schwannoma
  • Granular cell tumor
  • Perineurioma: Gastrointestinal (GI) Tract Perineurioma is a rare tumor that affects middle-aged and older women. It usually occurs in the left colon (large intestine) and rectum. The tumor usually occurs in adult women
  • Ganglioneuroma and ganglioneuromatosis
• Tumors of uncertain differentiation
  • PEComa, including angiomyolipoma
  • Mesenchymal hamartoma of the liver
  • Calcifying nested stromal-epithelial tumor of the liver
  • Synovial sarcoma
  • Gastrointestinal clear cell sarcoma / malignant gastrointestinal neuroectodermal tumor
  • Embryonal sarcoma of the liver

Other tumors of the digestive system:

• Other tumors of the digestive system
  • Mucosal melanoma of the digestive system
  • Germ cell tumors of the digestive system
  • Digestive system metastases

Genetic tumor syndromes of the digestive system:

Genetic tumor syndromes of the digestive system

Genetics

• Genetic tumor syndromes of the digestive system
  • Lynch syndrome: It is an inherited syndrome wherein there are increased malignancy of the gastrointestinal tract, particularly in the colon and rectum. The average age of colon cancer diagnosis in those with Lynch Syndrome is 44 years
  • Familial adenomatous polyposis 1
  • GAPPS and other fundic gland polyposes
  • Other adenomatous polyposes
  • Serrated polyposis
  • Hereditary diffuse gastric cancer
  • Familial pancreatic cancer
  • Juvenile polyposis syndrome: It is a disorder characterized by multiple hamartomatous benign growths or polyps, usually in large intestines. It is a rare congenital disorder with symptom onset in the second decade
  • Peutz-Jeghers syndrome: It is a rare autosomal dominant condition that increases one’s susceptibility to developing polyps and certain malignancy types; polyp formation is observed into adolescence and young adulthood
  • Cowden syndrome: It is an inherited condition that is characterized primarily by multiple, noncancerous growths, known as hamartomas, on various parts of the body. It is known to present symptoms during early adulthood
  • Other genetic tumor syndromes

Additional digestive system tumor articles (on DoveMed) that are not part of WHO Classification of Digestive System Tumors:

Digestive System Melanoma: It refers to a melanoma starting in the stomach, intestines, salivary glands, mouth, esophagus, liver, pancreas, gallbladder, or rectum. It is a rare condition that may affect individuals of all ages.

Rosai-Dorfman Disease of Digestive System: It is an extremely rare extranodal form of Rosai-Dorfman disease, wherein along-with involvement of the lymph nodes, the gastrointestinal tract including the liver, spleen, gallbladder, and pancreas is also affected. It is a very rare condition that may affect children and adults.