What are the other Names for this Condition? (Also known as/Synonyms)

• Carcinoma of the Colon and Rectum, Signet Ring-Cell Carcinoma type
• Colorectal Signet Ring-Cell Carcinoma
• SRCC of Colon and Rectum

What is Signet Ring-Cell Carcinoma of Colon and Rectum? (Definition/Background Information)

• Colorectal carcinoma (CRC) is a common carcinoma of the colon and rectum, typically observed in men and women worldwide. There are many types of colorectal carcinomas, but colorectal adenocarcinomas constitute the most common type (over 90% of them)
• They may be described as epithelial cancers of the large intestine/colon and rectum, meaning that it develops in the intestinal/rectal wall lining and spreads to involve other layers and sites
• Signet Ring-Cell Carcinoma (SRCC) of Colon and Rectum is a rare histological subtype of colorectal adenocarcinoma. They constitute less than 1% of all colorectal adenocarcinomas and are known to be highly-aggressive tumors
• The tumor is diagnosed under a microscope, on examination of the cancer cells by a pathologist. The subtype is denoted based on the predominant histologic pattern observed (over 50% signet ring cell areas are noted)
• The cause of Signet Ring-Cell Carcinoma of Colon and Rectum is generally unknown. It is believed to be associated with genetic defects and certain food and lifestyle factors. A lack of physical exercise and high-calorie diet is linked to this cancer type
• The signs and symptoms may include abdominal pain, bleeding from the rectum, fatigue, and weight loss. Complications, such as tumor metastasis to distant sites, are known to occur
• The mainstay of treatment is surgical excision of the tumor, during the early stages. However, in many cases a combination of treatment measures that include surgery, chemotherapy, and radiation therapy may be necessitated
• The prognosis of Signet Ring-Cell Carcinoma of Colon and Rectum is generally poor in many cases, since the tumor is diagnosed during the advanced stages (after it has metastasized to the lymph nodes and various organs)

Who gets Signet Ring-Cell Carcinoma of Colon and Rectum? (Age and Sex Distribution)

• Signet Ring-Cell Carcinoma of Colon and Rectum is a rare malignancy. Only about 1 in 100 colorectal adenocarcinomas are SRCCs
• It is generally seen in adults around 40 years of age. The tumor is seen in younger age groups than conventional carcinoma, but older adults are affected too
• When children and/or young adults are affected, the tumors may be seen in the background of a predisposing (genetic) factor
• Both males and females are affected, although more number of cases are observed in males
• All races and ethnic groups are at risk for the condition
• In general, a higher number of cases of colorectal carcinoma are reported from certain well-developed regions of the world such as Australia and New Zealand, Japan, USA and Canada, and European countries. Parts of Africa, India, Pakistan, and other underdeveloped/developing geographical regions report a much lower incidence

What are the Risk Factors for Signet Ring-Cell Carcinoma of Colon and Rectum? (Predisposing Factors)

The following factors are known to increase the risk for Signet Ring-Cell Carcinoma of Colon and Rectum:

• Aging: The greater the age, the higher is the risk
• Presence of a genetic disorder (such as Lynch syndrome, polyposis syndrome, etc.)
• Chronic inflammatory bowel disorders such as Crohn’s disease, ulcerative colitis, and schistosomiasis (caused by the pathogen Schistosoma mansoni)
• Consuming a high calorie diet and leading a sedentary lifestyle
• Meat consumption (including animal fat)
• Presence of premalignant lesions including adenomatous colon polyps and serrated colon polyps
• Alcohol consumption
• Obesity
• Radiation therapy to the pelvic region for cancer
• Procedure for bladder cancer treatment called ureterosigmoidostomy
• Smoking tobacco may increase the risk

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Signet Ring-Cell Carcinoma of Colon and Rectum? (Etiology)

The cause of development of Signet Ring-Cell Carcinoma of Colon and Rectum is generally unknown.

• Research scientists believe that the cause of the condition is mostly due to genetic mutations, influenced by factors that include food and lifestyle habits such as high-fat, high-calorie diet and sedentary lifestyle
• Genetic factors: Some tumors show high-levels of microsatellite instability (MSI-H), which is a type of genetic defect that indicates a low-grade tumor. When no MSI-H seen, the tumor is usually highly-aggressive. Some tumors show mutations on KRAS gene

What are the Sign and Symptoms of Signet Ring-Cell Carcinoma of Colon and Rectum?

In some cases, Signet Ring-Cell Carcinoma of Colon and Rectum is detected while conducting diagnostic imaging tests for other medical conditions, since no symptoms may be observed. Reports indicate that most tumors are detected at higher stages, when tumor metastasis has already taken place.

In others, the signs and symptoms of Colorectal Signet Ring-Cell Carcinoma may include:

• Typically, a single mass like a polyp is noted; ulceration of the tumor is common, especially when it is large
• It can cause narrowing of the colon
• The tumor may invade the intestinal submucosal surface
• Tumors that are confined to the surface are rarely associated with lymph node metastasis
• Passing of fresh blood in stool (hematochezia) and anemia is observed, if bleeding from the tumor is observed
• Change in bowel habits; increased episodes of constipation may be noted, due to stool being obstructed by the tumor mass
• Severe constipation can cause enlarged intestine (abdominal distention) and abdominal pain
• Sometimes, perforation of the intestinal walls may occur
• Fever, unintended weight loss and fatigue/tiredness
• Signs and symptoms of any underlying genetic disorder, if present, may be noted

Location of the cancer:

• Most tumors are located either in the right or left side of the large intestine, but rarely in the rectum
• The location depends on the type of genetic defect observed
• The symptoms may vary based on location of tumor in the colon (whether tumor is to the right or left side)

How is Signet Ring-Cell Carcinoma of Colon and Rectum Diagnosed?

A diagnosis of Signet Ring-Cell Carcinoma of Colon and Rectum may be undertaken using the following tests and exams:

• Complete evaluation of family (medical) history, along with a thorough physical examination
• Stool sample analysis
• Screening colonoscopy: Signet Ring-Cell Carcinoma of Colon and Rectum may be diagnosed during colonoscopies. A colonoscopy is a test that allows the physician to look at the inner lining of the colon and rectum. A typical colonoscopy involves using a thin, flexible tube (called a colonoscope), with an attached video camera, to view the colon and rectum
• Lower gastrointestinal series, which are a combination of analysis methods, combining X-rays and barium to visualize the intestinal region
• Imaging studies, such as MRI scan, transrectal ultrasound scan (TRUS), scintigraphy, and PET scan, may be performed to detect tumor invasion and metastasis
• Tissue biopsy of the tumor:
  • A tissue biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
  • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
  • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies to assist in the diagnosis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Signet Ring-Cell Carcinoma of Colon and Rectum?

Some potential complications of Signet Ring-Cell Carcinoma of Colon and Rectum include:

• Emotional and psychological stress due to cancer diagnosis
• Intussusception: When one part of the intestine pushes itself into another part of the intestine, causing obstruction of the bowel necessitating surgical correction
• Metastasis to local and regional sites: Frequently, the spread of tumor to the lymph nodes, ovary, peritoneum, and sometimes to the liver, is observed
• Recurrence of the tumor after treatment, especially due to partial surgical removal
• Anastomotic leak; leakage of GI tract contents following surgical procedures, which can result in severe infection and even sepsis
• Side effects due to cancer therapy

How is Signet Ring-Cell Carcinoma of Colon and Rectum Treated?

The treatment of colorectal cancer may depend upon a consideration of the following set of factors:

• The histological subtype of the cancer
• Stage of the cancer
• Size and location of the tumor
• Severity of the signs and symptoms
• Age of the individual
• Overall health status of the individual
• The treatment preferences of the individual

The staging system most often used for colorectal cancer is the American Joint Committee on Cancer (AJCC) TNM system, which is based on 3 key pieces of information:

• The extent (size) of the tumor (T): How far has the cancer grown into the wall of the colon or rectum?
• The spread to nearby lymph nodes (N): Has the cancer spread to nearby lymph nodes?
• The spread (metastasis) to distant sites (M): Has the cancer spread to distant lymph nodes or distant organs such as the liver or lungs?

Numbers or letters after T, N, and M provide more details about each of these factors. Higher numbers mean the cancer is more advanced. Once a person’s T, N, and M categories have been determined, this information is combined in a process called stage grouping to assign an overall stage.

Stage 0: Tis, N0, M0

• The cancer is in its earliest stage. This stage is also known as carcinoma in situ or intramucosal carcinoma (Tis)
• It has not grown beyond the inner layer (mucosa) of the colon or rectum

Stage I: T1 or T2, N0, M0

• The cancer has grown through the muscularis mucosa into the submucosa (T1), and it may also have grown into the muscularis propria (T2)
• It has not spread to nearby lymph nodes (N0) or to distant sites (M0)

Stage IIA: T3, N0, M0

• The cancer has grown into the outermost layers of the colon or rectum but has not gone through them (T3)
• It has not reached nearby organs. It has not spread to nearby lymph nodes (N0) or to distant sites (M0)

Stage IIB: T4a, N0, M0

• The cancer has grown through the wall of the colon or rectum but has not grown into other nearby tissues or organs (T4a)
• It has not yet spread to nearby lymph nodes (N0) or to distant sites (M0)

Stage IIC: T4b, N0, M0

• The cancer has grown through the wall of the colon or rectum and is attached to or has grown into other nearby tissues or organs (T4b)
• It has not yet spread to nearby lymph nodes (N0) or to distant sites (M0)

Stage IIIA:

T1 or T2, N1/N1c, M0

• The cancer has grown through the mucosa into the submucosa (T1), and it may also have grown into the muscularis propria (T2)
• It has spread to 1 to 3 nearby lymph nodes (N1) or into areas of fat near the lymph nodes but not the nodes themselves (N1c)
• It has not spread to distant sites (M0)

‘OR’

T1, N2a, M0

• The cancer has grown through the mucosa into the submucosa (T1)
• It has spread to 4 to 6 nearby lymph nodes (N2a)
• It has not spread to distant sites (M0)

Stage IIIB:

T3 or T4a, N1/N1c, M0

• The cancer has grown into the outermost layers of the colon or rectum (T3) or through the visceral peritoneum (T4a) but has not reached nearby organs
• It has spread to 1 to 3 nearby lymph nodes (N1a or N1b) or into areas of fat near the lymph nodes but not the nodes themselves (N1c)
• It has not spread to distant sites (M0)

‘OR’

T2 or T3, N2a, M0

• The cancer has grown into the muscularis propria (T2) or into the outermost layers of the colon or rectum (T3)
• It has spread to 4 to 6 nearby lymph nodes (N2a)
• It has not spread to distant sites (M0)

‘OR’

T1 or T2 N2b, M0

• The cancer has grown through the mucosa into the submucosa (T1), and it may also have grown into the muscularis propria (T2)
• It has spread to 7 or more nearby lymph nodes (N2b)
• It has not spread to distant sites (M0)

Stage IIIC:

T4a, N2a, M0

• The cancer has grown through the wall of the colon or rectum (including the visceral peritoneum) but has not reached nearby organs (T4a)
• It has spread to 4 to 6 nearby lymph nodes (N2a)
• It has not spread to distant sites (M0)

‘OR’

T3 or T4a, N2b, M0

• The cancer has grown into the outermost layers of the colon or rectum (T3) or through the visceral peritoneum (T4a) but has not reached nearby organs
• It has spread to 7 or more nearby lymph nodes (N2b)
• It has not spread to distant sites (M0)

‘OR’

T4b, N1 or N2, M0

• The cancer has grown through the wall of the colon or rectum and is attached to or has grown into other nearby tissues or organs (T4b)
• It has spread to at least one nearby lymph node or into areas of fat near the lymph nodes (N1 or N2)
• It has not spread to distant sites (M0)

Stage IVA: Any T, Any N, M1a

• The cancer may or may not have grown through the wall of the colon or rectum (Any T)
• It might or might not have spread to nearby lymph nodes. (Any N)
• It has spread to 1 distant organ (such as the liver or lung) or distant set of lymph nodes, but not to distant parts of the peritoneum (the lining of the abdominal cavity) (M1a)

Stage IVB: Any T, Any N, M1b

• The cancer might or might not have grown through the wall of the colon or rectum (Any T)
• It might or might not have spread to nearby lymph nodes (Any N)
• It has spread to more than 1 distant organ (such as the liver or lung) or distant set of lymph nodes, but not to distant parts of the peritoneum (the lining of the abdominal cavity) (M1b)

Stage IVC: Any T, Any N, M1c

• The cancer might or might not have grown through the wall of the colon or rectum (Any T)
• It might or might not have spread to nearby lymph nodes (Any N)
• It has spread to distant parts of the peritoneum (the lining of the abdominal cavity), and may or may not have spread to distant organs or lymph nodes (M1c)

The system described above uses the pathologic stage (also called the surgical stage), which is determined by examining tissue removed during an operation. This is also known as surgical staging. This is likely to be more accurate than clinical staging, which takes into account the results of a physical exam, biopsies, and imaging tests, done before surgery.

(Source: Colorectal Cancer Stages, January 2018, provided by the National Cancer Institute at the National Institutes of Health; U.S. Department of Health and Human Services)

Signet Ring-Cell Carcinoma of Colon and Rectum may be treated in the following manner:

• Surgery is performed in most cases, unless tumors are small and superficially located
• In case of lymph node metastasis, surgery is followed by chemotherapy and/or radiation therapy (adjuvant therapy)
• In case of rectal carcinoma, chemotherapy and/or radiation therapy, to shrink tumor before surgery, may be provided (neoadjuvant therapy)

The treatment measures include the following:

• Surgical removal of the entire tumor may be the preferred method of treatment
• In case of cancer spread to local and distant region, ablation and embolization techniques may be used
  • In ablation, the cancer is destroyed without surgically removing them using high-energy radio waves (called radiofrequency ablation), injecting the tumor with ethanol (called ethanol/alcohol ablation), or by using extremely cold temperatures to freeze them using a probe (called cryotherapy)
  • In embolization, the blood flow to the tumor is minimized or obstructed through techniques termed as arterial embolization, chemoembolization, or radioembolization
• Chemotherapy: This approach uses a combination of drugs to kill the cancerous cells and can be used in patients, for all stages of the tumor
  • There can be severe side effects including fatigue, nausea, hair loss, anemia, high risk of infection, and drug-specific reactions
  • Chemotherapy can be administered as a pill, liquid, shot, or intravenously
• Radiation: Radiation therapy is the use of high-energy radiation waves to kill cancer cells, by destroying their DNA
  • This treatment modality may be used in combination with chemotherapy
  • The radiation may be administered by a machine placed outside the body, or by placing a radioactive material inside the body
  • The side effects of radiation therapy include nausea, vomiting, fatigue, pain, risk of cancer later in life, and risk of heart disease
  • Radiation can damage healthy cells in addition to cancer cells, causing further complications
• Supportive treatment: Steroids, blood transfusions, anti-nausea medications, and antibiotics, may be used as supportive therapy. In combination with other treatment measures, these can help combat the symptoms of immunodeficiency
• Undertaking treatment of underlying inflammatory bowel diseases/genetic disorders, as necessary
• Targeted drug therapy: Specific medications are administered periodically to stop tumor growth, particularly for advanced stages. The medications that are given intravenously include Bevacizumab, Ramucirumab, Ziv-aflibercept, Cetuximab, and Panitumumab
• Immunotherapy: A patient’s immune system is activated to combat the cancer in this kind of therapy

Regular observation and periodic checkups to monitor the condition is strongly recommended following treatment.

How can Signet Ring-Cell Carcinoma of Colon and Rectum be Prevented?

Presently, there are no specific methods or guidelines to prevent the formation of Signet Ring-Cell Carcinoma of Colon and Rectum. However, if it is associated with a genetic disorder, the following points may be considered:

• Genetic counseling and testing: If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Regular health check-ups might help those individuals with a history of the condition in the immediate family and help diagnose the tumor early

In general, the factors that can help prevent or reduce incidence of colorectal adenocarcinoma (according to studies) include:

• It is important to undergo routine colonoscopy screenings as one gets older (over the age of 45-50 years), to ensure that no colonic tumors or polyps develop
• Consuming a diet that is rich in whole grains, vegetables, and fruits
• Taking foods rich in vitamin D and calcium
• Physical activities and regular exercising
• In women, estrogen replacement treatment
• Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs)
• Taking early and appropriate treatment for inflammatory bowel diseases, if any
• In order to avoid a relapse, or be prepared for a recurrence, the entire diagnosis, treatment process, drugs administered, etc. should be well-documented and follow-up measures initiated

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory. Often several years of active vigilance are crucial and necessary.

What is the Prognosis of Signet Ring-Cell Carcinoma of Colon and Rectum? (Outcomes/Resolutions)

• The prognosis of Signet Ring-Cell Carcinoma of Colon and Rectum is generally poor, in a majority of cases, since it is a highly-malignant tumor; overall 5-year survival is around 12% or less. The prognosis is typically much worse than conventional colorectal adenocarcinomas
• A poor prognosis is dictated by advanced stage, surgical resection with positive margins (indicating that the some cancer cells are left behind following surgery), and tumors causing obstruction of the colon
• In general, the prognosis depends upon a set of several factors, which include: 
  • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Individuals with bulky disease have a poorer prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical resectability of the tumor (meaning, if the tumor can be removed completely) - it is a rare option
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
  • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
  • Progression of the condition makes the outcome worse (progressive Signet Ring-Cell Carcinoma of Colon and Rectum)
• The combination chemotherapy drugs used, may have some severe side effects (such as cardio-toxicity). This chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Tolerance to the chemotherapy sessions is a positive influencing factor

An early diagnosis and prompt treatment of Colorectal Signet Ring-Cell Carcinoma generally yields better outcomes than a late diagnosis and delayed treatment.

Additional and Relevant Useful Information for Signet Ring-Cell Carcinoma of Colon and Rectum:

The following article link will help you understand other cancers and benign tumors:

http://www.dovemed.com/diseases-conditions/cancer/