The diagnoses of pancreatic neuroendocrine tumors are often delayed as a result of paucity of specific symptoms.
Emmanuel Enabulele
In our previous outing on dealing with the lesions affecting the anatomical area referred to as the foregut, we had tried to briefly discuss cancer of the pancreas. We had concentrated on the cancer derived from the enzyme producing cells of the pancreas known as the exocrine portion of the pancreatic gland. This cancer, we recounted, is often referred to as adenocarcinoma as a result of their glandular appearance on microscopy. Today, we intend to mention a rare type of pancreatic tumors often referred to as neuroendocrine neoplasm. These are tumors that arise from the endocrine or hormone producing and the nervous system within the pancreas.
Pancreatic neuroendocrine tumors are not as common as the adenocarcinoma and constitute about two per cent of the cancers afflicting the pancreas. In my journey so far as a clinician, I have only encountered one case. The abdominal swelling was very obvious and low blood sugar level or hypoglycemic spells were so frequent then that the diagnosis of an INSULINOMA was very easy to come by. The old man didn’t even give us time to figure out what the treatment modality would be before throwing in the towel. Severe infection and hypoglycemic coma took him away.
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In terms of prevalence, the great majority of these neuroendocrine tumors are benign while some are malignant meaning that they have the ability to spread to other organs. In practice, they are classified based on their grade of malignancy and level of cellular differentiation. For the uninitiated when the word differentiation is used in oncology reference is being made to how well the cancer cell looks like the cell of its origin. A well-differentiated tumor cell means that it looks almost like the cell of origin and a poorly differentiated means that there is no semblance with the progenitor cell. In extreme case the cancer cell may be completely unrecognisable and primitive in which case it is described as being ANAPASTIC. These types of carcinomas are very virulent.
Secondly, theses tumors can be classified as functional or non-functional. Functional tumors are commonly identified and classified by the hormone most strongly secreted and expressed. In this regard, we have insulinoma, which occurs with concurrent elevation of insulin and related peptide
in the blood. The hallmark of this is the lowering of blood sugar level in the blood known as hypoglycemia. Gastrinoma is the tumor derived from gastrin secreting cells in the pancreas. This hormone is responsible for the production and expression of hydrochloric acid from the antral cells in the stomach.
Glucagon is a hormone produced by the alpha cells in the pancreas. The function of this hormone is to increase the level of blood sugar in the blood. It does this through a process known as gluconeogenesis where glucose is produced from protein and amino acids and also through lipolysis which is the breakdown of fat to sugars. A tumor arising from these cells is known as Glucagonoma. Obviously, the symptoms of this condition would include high level of glucagon in the blood, decreased blood level of amino acids and predisposition to diabetes mellitus.
Somatostatinoma is a malignant tumor arising from the delta cell of the pancreas that produces Somatostatin. This hormones function is to inhibit the activities of pancreatic and gastrointestinal hormones. Because of this, high level of this hormone in the blood would lead to the decrease in activity of insulin and diabetes. And as a result of its effect on Cholecyctokinin, emptying of bile into the duodenum would be adversely affected resulting in the formation of gallstones or Cholelithiasis. This also would result in the passage of fatty stool known as steatorrhoea due to poor emulsification of fat by bile acids. Due to the inhibition of gastrin by high level of Somatostatin, production of hydrochloric acid in the stomach would be impaired, a condition known as achlorhydria with its digestive challenges.
VIPoma is a pancreatic neuroendocrine, which secretes Vasoactive Intestinal Peptide. This substance increases intestinal motility leading to chronic watery diarrhoea, dehydration, hypokalemia or low level of potassium in the blood and achlorhydria. The combination of this symptom complex and its clinical manifestation is often referred to as Pancreatic Cholera Syndrome. This condition carries a poor prognosis or clinical outlook. Other hormones that are also affected by the activities of Somatostatin include the growth hormone and thyroid-stimulating hormone; both produced in the anterior pituitary gland in the brain. There others for want of space we may not be able to be listed here.
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You must have noticed the three-letter suffix – oma – in the tumors mentioned above. For the uninitiated, in the study of oncology the suffix is used to describe a swelling with the source, substance produced or the cellular type preceding it. This is applicable to virtually all tumors. For example, if we had wanted to include adrenocorticotropic hormone ACTH as one the pancreatic neuroendocrine tumor we have designated it ACTHoma!
In terms of symptoms, pancreatic neuroendocrine tumors do not present with any specific clinical picture. Notwithstanding symptoms like abdominal or back pains mainly referred may be present though non-specific. Having loose stools, indigestion and signs of jaundice may all be present when the tumor is huge. This is usually the consequence of pressure and obstructive effects. It must be stated that more than two thirds of neuroendocrine tumors are non functional and therefore do not secrete hormones. Having so stated, it must be born in mind that most neuroendocrine tumors have elevated tumor marker in the blood. This then may be highly suggestive of the presence of the cancer.
The diagnoses of pancreatic neuroendocrine tumors are often delayed as a result of paucity of specific symptoms. At the time of diagnosis after a high index of suspicion measurements of hormones including pancreatic polypeptides, gastrin, proinsulin, insulin, glucagon and vasoactive intestinal peptide are usually carried out to enhance diagnosis. Computerised tomography and Magnetic Resonance Imaging is usually employed to determine the location of the tumor and size. This could be useful in staging the tumor, which is graded from l to IV. This is important in determining whether there is a need to proceed with a needle aspiration in order to ascertain the state of differentiation and treatment options.
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The treatment options in the management of neuroendocrine neoplasm are varied and so many that cannot be accommodated here. There is a general principle involved which includes managing the symptoms, surgery for respectable or rather operable tumors and chemotherapy. Radiotherapy with radio nucleotide therapies are all included in this arsenal. The application of SOMATOSTATIN analog has also been found to be useful. The list is long.