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What Is A Low-Grade Neuroendocrine Tumor & Are Neuroendocrine Tumors Always Cancerous?

The neuroendocrine cells are known to be originated from neural crest cells which are found in the embryo during the development. Neuroendocrine tumors are those which arise from the neural and hormone-producing cells of the tissue.

The most commonly and strongly associated cancer syndrome with neuroendocrine tumors in multiple endocrine neoplasia type 1. It is usually associated with other tumors including pituitary and parathyroid glands. Other syndromes related to NET’s are von Hippel Lindau syndrome, neurofibromatosis type 1, tuberous sclerosis, etc.

What Is A Low-Grade Neuroendocrine Tumor?

What Is A Low-Grade Neuroendocrine Tumor?

The origin of the neuroendocrine tumors is seen in various body tissues and organs like pancreas, intestines, appendix, breast, pituitary gland, thyroid gland, parathyroid gland, lungs, bronchus, genitourinary tract, peripheral nervous system, skin, etc. Usually, these tumors are metastatic with poor prognosis and also have systemic symptoms due to extra hormones production. But not all of the neuroendocrine tumors are metastatic; some are of low grade and are not life-threatening. Continuous monitoring and medical therapy are required to control the hormonal symptoms, keep the tumor size in check and to prevent the neuroendocrine tumor turning into metastatic cancer.[1]

For grading of the neuroendocrine tumors, various different tumor markers are used. For gastrointestinal and pancreatic neuroendocrine tumors, mitotic index and ki67 tumor markers are used because these tumor markers give reliable results. Mitotic index is a measure of a number of multiplications in-unit high power field of the microscope. Ki67 is a tumor marker which characterizes the multiplication factor of tumor cells per unit time. Grade 1 is described as a low-grade tumor with good differentiation of the tumor cells. Ki67 and mitotic index are low in grade 1 tumors.

For neuroendocrine tumors of lungs and thymus, mitotic index and necrosis are used as tumor markers for grading. Mitotic index of less than < 2 mitoses/10 high power field (HPF) and no necrosis is diagnosed as a low-grade neuroendocrine tumor. For bronchial neuroendocrine tumors, the criteria used is less than < 10 mitoses/10 HPF for diagnosing it as a low-grade neuroendocrine tumor[1].

The size usually less than a few centimeters or microscopic size corresponds to the low-grade tumors. The cells having well-differentiated matrix along with low nucleocytoplasmic ratio and lacking anaplastic features are commonly found in low-grade neuroendocrine tumors. Low-grade tumors are also characterized by lymph nodes sparing, very low or nil local spread, no hematogenous or lymphatic spread, encapsulation, absence of exogenous tissue at the site, etc.

Are Neuroendocrine Tumors Always Cancerous?

Neuroendocrine tumors are commonly cancerous but not always. These can also present as benign growths in the respective tissues or organs where neuroendocrine cells are present. Benign neuroendocrine tumors have cells featuring differentiation and large nucleus and less cytoplasm. For example, insulinoma which is a pancreatic neuroendocrine tumor is common of benign origin and surgical resection can provide complete treatment from the tumor. One of the most common benign neuroendocrine tumors to be found is ganglioneuroma. The neuroendocrine tumors detected in early age are having more chances to get converted into a benign tumor such as ganglioneuroma upon treatment.[1]


Although the majority of the neuroendocrine tumors are malignant it would be incorrect to say that these tumors are always malignant. Various benign forms of these tumors have been detected and treated successfully. Sometimes the treatment is also associated with the conversion of a malignant neuroendocrine tumor into a benign one like ganglioneuroma.

Various associations and authorities have given their classifications of the grading of neuroendocrine tumors and are followed accordingly in different countries. Usually, the mitotic index and Ki67 tumor markers are the responsible tests for grading because these markers are providing the important factor of multiplication and the malignant potential of the neuroendocrine cells. Conversion of malignant into benign have the possibility to occur if the tumor is presented in early-stage and treatment is started immediately.


Also Read:

Pramod Kerkar, M.D., FFARCSI, DA
Pramod Kerkar, M.D., FFARCSI, DA
Written, Edited or Reviewed By: Pramod Kerkar, M.D., FFARCSI, DA Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:October 8, 2021

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