Rare Hematology News

Disease Profile

Digestive System Melanoma

Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.


US Estimated

Europe Estimated

Age of onset





Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.


Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

Melanoma of the gastrointestinal tract; Melanoma of the GI tract; Malignant melanoma of the gastrointestinal tract;


Rare Cancers


Digestive system melanoma refers to a melanoma starting in the stomach, intestines, salivary glands, mouth, esophagus, liver, pancreas, gallbladder, or rectum. Melanoma is a disease in which malignant (cancer) cells form in the melanocytes. Melanocytes are commonly found in the skin and are the cells that give the skin color. While it is not uncommon for melanomas to start in the skin and later spread to other parts of the body (metastasize), melanomas originating in the gastrointestinal tract are rare. The most frequently reported site is in the esophagus and anorectum.[1] Symptoms of a digestive system melanoma may be nonspecific, including blood in the stool, stomach pain, vomiting, diarrhea, weight loss and anemia (low red blood cell count).[2] The cause of digestive system melanoma is not well understood. Some researchers theorize that it may have originated from an undetected primary tumor.[1][2] Treatment may include surgical excision of the gastrointestinal tract involved, chemotherapy, and immunotherapy.[2]


Symptoms of digestive system melanoma can vary from person to person. Symptoms tend to be non-specific including: nausea, vomiting, stomachache, fatigue, hemorrhage (broken blood vessels), blood in stool, and anemia (low red blood cell count).[1][3][4][2]


The cause of digestive system melanoma is currently unknown. Theories include:[1][3][4][2]

  • The cancer originated from a undetectable primary tumor that spontaneously (naturally) regressed on its own
  • The cancer originated from a primary tumor that is so small it can not be detected using standard clinical and laboratory investigations
  • Early melanocyte cells (not usually found in the digestive system) lost their way during the development of the baby in the womb, and that these misplaced cells later became cancerous


A variety of imaging tests may be involved in the initial detection of the tumor, including: video capsule endoscopy, ultrasound, PET scan, and CT scan.[3][4][2] The tumor is confirmed by surgical resection. Careful study of tissue samples from the tumor under a microscope will show the same immunohistochemical characteristics of skin melanomas.[3] Once this has been established, the following are proposed diagnostic criteria for primary melanoma of the small intestine:[2]

I. The identification of a single solitary melanoma in the mucosa of the digestive system

II. The presence of other melanoma in the surrounding areas of the digestive system 

III. The absence of cutaneous melanoma or other atypical skin tumors in the melanocytes


Treatment of digestive system melanoma is dependent on the spread of the cancer and where it is located. Treatment might include surgery to remove the tumor and portion of the gastrointestinal tract involved, chemotherapy, and immunotherapy.[2] 

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.


Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • The National Cancer Institute provides the most current information on cancer for patients, health professionals, and the general public.

        In-Depth Information

        • PubMed is a searchable database of medical literature and lists journal articles that discuss Digestive System Melanoma. Click on the link to view a sample search on this topic.


          1. Letovanec I, Vionnet M, Bouzourene H. . Primary appendiceal melanoma: Fiction or reality?. Human Pathol. 2004 May;
          2. Andreas V. Hadjinicolaou,corresponding author1 Christopher Hadjittofi, Panagiotis G. Athanasopoulos, Rahul Shah,Aftab A. Ala. Primary small bowel melanomas: fact or myth?. Ann Transl Med. Mar 2016; 4(6):113. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828744/.
          3. Atmatzidis KS et al.,. Primary malignant melanoma of the small intestine: Report of a case. Surg Today. 2002;
          4. Lagoudianakis EE et al.,. Primary gastric melanoma: A case report. World J. Gastroenterology. 2006 July 21;

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