Hereditary diffuse gastric cancer (HDGC) is a rare type of adenocarcinoma (cancer arising from mucus-producing glands in organs) that forms in the lining of the stomach. It is also known as isolated cell-type carcinoma, or signet ring carcinoma, due to an unusually large cytoplasmic vacuoles that push the nucleus to the edge of the cell, forming a signet-ring shape. This type of cancer thickens the lining of the stomach; however, it does not form a distinct mass.
Familial cancer syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased risk of cancer as the result of inherited genetic mutattions in certain cancer-related genes. They can affect both adults and children, however they generally develop in people at a younger age than normal. While familial cancer syndromes are not classified as cancer, they are equally as severe and can be life-threatening as they are associated with the development of various tumours throughout the body. Having a familial cancer syndrome does not guarantee the development of cancer, however the risk of developing cancer is higher than those who do not have a familial cancer syndrome. The familial cancer syndrome that causes a predisposition to HDGC is called hereditary diffuse gastric cancer syndrome.
HDGC is a genetic condition that is generally diagnosed before the age of 40. However, it can develop at any age. While this disease has a higher incidence in males, women who has a family history of HDGC have a higher risk of developing a related condition called lobular breast cancer.
Treatment
If HDGC is detected, it will be staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you.
Cancers can be staged using the TNM staging system:
- T (tumour) indicates the size and depth of the tumour.
- N (nodes) indicates whether the cancer has spread to nearby lymph nodes.
- M (metastasis) indicates whether the cancer has spread to other parts of the body.
This system can also be used in combination with a numerical value, from stage 0-IV:
- Stage 0: this stage describes cancer cells in the place of origin (or ‘in situ’) that have not spread to nearby tissue.
- Stage I: cancer cells have begun to spread to nearby tissue. It is not deeply embedded into nearby tissue and had not spread to lymph nodes. This stage is also known as early-stage cancer.
- Stage II: cancer cells have grown deeper into nearby tissue. Lymph nodes may or may not be affected. This is also known as localised cancer.
- Stage III: the cancer has become larger and has grown deeper into nearby tissue. Lymph nodes are generally affected at this stage. This is also known as localised cancer.
- Stage IV: the cancer has spread to other tissues and organs in the body. This is also known as advanced or metastatic cancer.
Cancers can also be graded based on the rate of growth and how likely they are to spread:
- Grade I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.
- Grade II: cancer cells present as abnormal and grow faster than grade-I tumours. This is also known as an intermediate-grade tumour.
- Grade III: cancer cells present as very abnormal and grow quickly. This is also known as a high-grade tumour.
Once your tumour has been staged and graded, your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment is dependent on several factors, including location, stage of disease and overall health.
Treatment options for HDGC may include:
- Surgery (usually a partial or total gastrectomy – removal of the stomach).
- Chemotherapy.
- Radiation therapy.
- Clinical trials.
- Palliative care.
For more information on the treatment options, please refer to the Rare Cancers Australia Treatment Options page.
Risk factors
HDGC is a genetic condition, which is associated with the following risk factors:
- A mutation of the cadherin-1 (CDH1) gene.
- A mutation of the alpha catenin (CTNNA1) gene.
- Family history of HDGC or CDH1/CTNNA1 mutations.
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Early symptoms
HDGC is very difficult to diagnose. The symptoms of HDGC often appear asymptomatic or with vague symptoms in the early stages of the disease. As the cancer progresses, some of the following symptoms may appear:
- Abdominal pain.
- Nausea and/or vomiting.
- Unexplainable weigh loss/loss of appetite.
- Difficulties swallowing.
The CDH1 and CTNNA1 genes are not only associated with HDGC, but also colorectal cancer and lobular breast cancer. As such, other symptoms relating to these conditions may be present.
Not everyone with the symptoms above will have cancer, but see your GP if you are concerned.
Diagnosis/diagnosing
If your doctor suspects you have a HDGC, they may order the following tests to confirm the diagnosis and refer you to a specialist for treatment.
Genetic testing
In addition to guiding treatment, genetic testing can be used to help diagnose certain conditions. HDGC is associated with mutations with the CDH1 and CTNNA1 genes, which are both classified as protein-encoding tumour suppressor genes. These changes can lead to cell abnormalities and, in extreme cases, cancer. Your doctor may perform genetic testing to better understand your condition.
Physical examination
Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.
Imaging & blood tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), and/or positron emission tomography (PET scan), depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and looks for signs of metastasis. Additionally, a blood test may be taken to assess your overall health and help guide treatment decisions.
Endoscopy & biopsy
An endoscopy is a surgical procedure that involves inserting a long, flexible tube with a light and small camera through oesophagus and into the stomach. You will be given a sedative or anaesthetic throughout the procedure. You will be asked to fast for several hours prior to the procedure. An endoscopy is often done as a day surgery. Your doctor will discuss the risks and any possible complications prior to the procedure.
Throughout the procedure, your doctor may also perform an endoscopic ultrasound to guide the needle during a biopsy, or to check for signs of cancer metastasis.
If any abnormalities are observed, your doctor will remove a small tissue sample for analysis.
Prognosis (Certain factors affect the prognosis and treatment options)
Unfortunately, the prognosis for this disease remains poor. While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on the rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, early-stage HDGCs have a better prognosis and survival rates. However, if the cancer is advanced and has spread, the prognosis may not be as good and there may be a higher risk of cancer recurrence. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.