Aggressive Neuroendocrine Tumors of the Colon and Rectum

High Grade Large and Small Cell Neuroendocrine Tumors of the Colon

doctor discussing medical chart with male patient
What are aggressive (high grade) neuroendocrine tumors of the colon and rectum?. Hero Images/Getty Images

If you or a loved one have been diagnosed with an aggressive or high grade neuroendocrine tumor of the colon or rectum you're probably feeling frightened as well as confused. Aggressive neuroendocrine tumors are less common than some of the other colon cancers. In addition, they are commonly misdiagnosed and it is important to be your own advocate if you have one of these tumors. What do we know about these cancers, how are they treated, and what is the prognosis?

What are Neuroendocrine Tumors of the Colon and Rectum?

Neuroendocrine tumors are tumors which begin in neuroendocrine cells. They may occur in the digestive tract, the lungs, or the brain. In the digestive tract they may involve the stomach, the pancreas, the small intestine, colon, and rectum.

In the colon and rectum, neuroendocrine tumors account for two percent or less of of colorectal cancers. Unfortunately, unlike some other types of colon cancer, the prognosis has not changed much in recent years with colon cancer screening.

Neuroendocrine tumors have been increasing, with a 5-fold increase noted from 1973 to 2004 and a continued increase since that time. It is uncertain why this is happening at this time.

Aggressive (High Grade) vs. Indolent Neuroendocrine Tumors

Neuroendocrine tumors are first divided into two basic categories based on the aggressiveness of the tumors.

  • High grade large cell and small cell neuroendocrine tumors are aggressive. These tumors tend to grow rapidly and invade other tissues
  • Carcinoid tumors of the colon are considered indolent. They tend to be slower growing and less invasive than large cell and small cell neuroendocrine tumors.

It is important to differentiate aggressive and indolent tumors as the optimal treatments and well as prognosis differ considerably.

Aggressive (High Grade) Large Cell and Small Cell Neuroendocrine Tumors

High grade or aggressive neuroendocrine tumors are divided into large cell and small cell tumors, which differ based on the appearance of the cells under a microscope.

Both types of cancer are considered highly "undifferentiated" which essentially means that the cells appear very primitive relative to normal neuroendocrine cells and behave very aggressively. In the past it was thought that large cell tumors were more common, yet a 2016 study found that 89 percent of the tumors were small cell neuroendocrine tumors.

In some ways, high grade neuroendocrine tumors are similar to small cell lung cancer, and often respond to similar treatments, but are less likely to be associated with smoking than small cell lung cancers and are less likely to have metastases to bones and the brain.

Some studies have found that the tumors occur more commonly on the right side of the colon (ascending colon) whereas a recent study found that the most common location for these tumors was the rectum and sigmoid colon.

Colon cancer creening hasn't led to a significant increase in the prognosis of these tumors, though in one study, 30 percent of tumors were found to be associated with adenomas.

The majority of tumors (64 percent) are stage 4 or metastatic at the time of diagnosis.

Symptoms of Aggressive Neuroendocrine Tumors

Symptoms of neuroendocrine tumors of the colon may include changes in bowel habits, such as diarrhea, abdominal pain, and both an elevated or decreased blood glucose level.

Since these tumors are often found in the later stages, symptoms of advanced cancer such as unintentional weight loss are commonly found.

Ensuring the Proper Diagnosis of Neuroendocrine Tumors

Research shows that aggressive neuroendocrine tumors are often initially misdiagnosed as carcinoid tumors. That's an unfortunate mistake since carcinoids grow slowly and seldom spread. If you've been told you have a carcinoid tumor, make sure an experienced pathologist agrees with your diagnosis. Doing so will require that you ask your doctor some key questions:

  1. Has a pathologist participated in the final read of my tumor specimen?
  1. Is the pathologist experienced in differentiating between aggressive and indolent neuroendocrine tumors?
  2. Did the pathologist express any doubts about my diagnosis?

If the answers aren't yes, yes, and no (or real close to that), your medical team has more work to do before providing you with a definitive diagnosis.

Treatments for Aggressive Neuroendocrine Tumors of the Colon and Rectum

There are not currently any standard treatments for aggressive neuroendocrine tumors of the colon and rectum. The treatment will, however, depend on the stage of the tumor. If one of these tumors is found in the early stages, a combination of surgery, radiation therapy, and chemotherapy may be considered.

For advanced stage high-grade neuroendocrine tumors, chemotherapy is the treatment of choice and can result in longer survival. Chemotherapy regimens are similar to those used to treat small cell lung cancer, usually involving platinum drugs such as Platinol (cisplatin) or Paraplatin (carboplatin.)

Research involving genomic profiling of these tumors offers hope that, in the future, targeted therapies may become available to treat the disease.

Prognosis of Aggressive Neuroendocrine Tumors

Aggressive neuroendocrine tumors are usually diagnosed at more advanced stages, a circumstance that generally results in a poor prognosis. The only treatment which has thus far shown to improve survival is chemotherapy.

At the current time, median survival (the length of time after which half of people have died and half are still living) is 13 to 15 months, with a 2-year survival rate of 23 percent and a 5-year survival of only eight percent.

Coping with Aggressive Neuroendocrine Tumors

Being diagnosed with a high grade neuroendocrine tumor is not only frightening, but can be very confusing as the condition is not very common. The prognosis of the tumor has, unfortunately not changed significantly in recent years, but advances in treatments, such as the advent of targeted therapies and immunotherapy, offers hope that new treatments will be available in the new future.

Talk to your doctor about the option of clinical trials which are evaluating these new treatments. Be your own advocate in your cancer care and ask questions. Ask for help from your loved ones and allow them to help you. In addition, many people find it helpful to reach out to the online support communities. Though aggressive neuroendocrine tumors are uncommon and it's unlikely that you have a support group for this in your community, the internet allows you to get in touch with others facing the same thing you are around the world.

Sources:

Conte, B., George, B., Overman, M. et al. High-Grade Neuroendocrine Colorectal Carcinomas: A Retrospective Study of 100 Patients. Clinical Colorectal Cancer. 2016. 15(2):e1-7.

Hammond, W., Crozier, J., Nakhleh, R., and K. Mody. Genomic Profiling of High-Grade Large-Cell Neuroendocrine Carcinoma of the Colon. Journal of Gastrointestinal Oncology. 2016. 7(2):E22-4.

Shafgat, J., Ali, S., Salhab, M., and A. Oszewski. Survival of Patients with Neuroendocrine Carcinoma of the Colon and Rectum: A Population-Based Analysis. Diseases of the Colon and Rectum. 2015. 58(3):294-303.

Smith, J., Reidy, D., Goodman, K., Shia, J., and G. Nash. A Retrospective Review of 126 High-Grade Neuroendocrine Carcinomas of the Colon and Rectum. Annals of Surgical Oncology. 2014. 21(9):2956-62.

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