Irrfan Khan diagnosed with neuroendocrine tumor

Dr K K Aggarwal, Recipient of Padma Shri

New Delhi, March 16, 2018: A short while back, actor Irrfan Khan released a statement and revealed that he has neuroendocrine tumor.

As we have no other specific information aside from the diagnosed condition, here is an overview on neuroendocrine tumors.

• Neuroendocrine tumors (NETs) are abnormal growths that begin in the neuroendocrine cells, which are distributed widely throughout the body. While some clinical and pathologic features of NETs are unique to the site of origin, other characteristics are shared, regardless of site of origin. NETs are also sometimes referred to as carcinoid tumors.
• NETs are rare neoplasms, but the incidence is increasing. Most NETs are slow proliferating and clinically silent, and so are often diagnosed at a stage with advanced disease.
• Many NETs first appear in the lungs or the gastrointestinal tract, including the stomach, pancreas, appendix, intestines, colon and rectum. NETs may also appear in the thymus, thyroid gland, adrenal gland and pituitary gland.
• NETs may be benign or malignant. Although NETs comprise less than 2% of GI malignancies, these tumors are actually more prevalent than stomach and pancreatic cancers combined.
• Symptoms of NETs depend on the tumor location and whether it is functional or nonfunctional.
• Functioning NETs are defined based upon the presence of clinical symptoms due to excess hormone secretion by the tumor. Functioning (hormone-secreting) pancreatic NETs are classified according to the predominant hormone they secrete and the resulting clinical syndrome (eg, insulinoma, gastrinoma, glucagonoma, VIPoma, somatostatinoma.
• Nonfunctional NETs do not secrete hormones and symptoms due to them are caused by the tumor’s growth.
• NETs are often asymptomatic in the early stage. When present, symptoms appear similar to those caused by other common conditions. Therefore, NETs are at times misdiagnosed as irritable bowel syndrome (IBS). But abdominal discomfort in IBS is usually relieved by going to the bathroom.
• NENs arising in the digestive tract may be grouped into two major categories: well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs).
• Proliferative rate, as assessed by mitotic count and Ki-67 labeling index, is of prognostic significance in well-differentiated NETs, independent of tumor stage. A grading scheme endorsed by the World Health Organization (WHO) and the American Joint Committee on Cancer (AJCC) for NETs of the pancreas and tubular gastrointestinal tract classifies well-differentiated NETs into low and intermediate grades based on the proliferative rate.
• Poorly differentiated NECs are often associated with a rapid clinical course, while well-differentiated NETs of the digestive system generally have a much better prognosis. However, well-differentiated NETs are not a homogeneous group, and there is a spectrum of aggressiveness. The biologic behavior of well-differentiated NETs cannot be predicted based on morphology alone.
• To accurately grade the tumor and provide better guidance for chemotherapy, it may be necessary to assess the tumor’s proliferative rate by both mitotic count and Ki-67 labeling index.
• NETs can present in several different ways:

o As a result of the carcinoid syndrome: Chronic flushing and/or diarrhea are the typical manifestations of the carcinoid syndrome, which is the result of secretion of serotonin and other vasoactive substances into the systemic circulation. The carcinoid syndrome is primarily associated with metastatic tumors originating in the midgut (distal small intestine and proximal colon). In contrast, hindgut (distal colorectal) and foregut (gastroduodenal, lung) NETs uncommonly produce the carcinoid syndrome.)

o As a result of tumor growth: Small bowel NETs may cause chronic/recurrent abdominal pain, occasionally leading to bowel obstruction. Metastatic tumors in the liver can cause right upper quadrant pain, hepatomegaly, and early satiety.

o As an incidental finding: Many NETs are discovered during endoscopic or radiographic procedures planned for other purposes; this is especially true of carcinoids of the stomach and rectum.

• The presence of the carcinoid syndrome may be suspected when a patient has suggestive symptoms, such as otherwise unexplained diarrhea or flushing. However, other diagnoses must be considered.
• The differential diagnosis of flushing, for example, includes physiologic events, drugs, and a number of diseases other than the carcinoid syndrome. Moreover, other neuroendocrine tumor types can cause severe chronic diarrhea
• A useful initial diagnostic test for the carcinoid syndrome is to measure 24-hour urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), which is the end product of serotonin metabolism. This test has a sensitivity of over 90% and specificity of 90% for the carcinoid syndrome.
• False positive results may be induced by the ingestion of certain drugs (acetaminophen, coumaric acid, guaifenisin, mephenisin, phenobarbital, reserpine, acetanilid, ephedrine, methamphetamine, nicotine, phentolamine, phenmetrazine, caffeine, flourouracil, melphalan, methocarbamol, phenacetin, mesalamine) and tryptophan-rich foods such as avocados, pineapples, bananas, kiwi fruit, plums, eggplants, walnuts, hickory nuts, pecans, tomatoes, plantains, and butternut. These foods should be avoided for three days prior to urine collection
• Measurement of urinary 5-HIAA excretion is generally not useful in foregut (gastroduodenal, lung) neuroendocrine tumors, which often lack aromatic amino acid decarboxylase. In such a situation, imaging studies are done to search for a carcinoid tumor.
• NETs may spread to other parts of the body, most commonly to the liver, peritoneal cavity or bone. At the time of diagnosis, more than 50 percent of NETs have already spread to other parts of the body.
• Once the biochemical diagnosis of the carcinoid syndrome is confirmed, usually by an elevated 24-hour excretion of 5-HIAA, the tumor must be localized. Two techniques, standard cross-sectional imaging and diagnostic imaging with radiolabeled somatostatin analogs, have a complementary role in tumor localization.
• The primary treatment goal for patients with NETs should be curative (i.e., complete resection of tumor), with symptom control and the limitation of tumor progression as secondary goals.
• Surgery to remove the primary malignancy and/or local lymph nodes is the only possible curative approach and so represents the traditional first-line therapy. Somatostatin analogs are the mainstay of therapy for the alleviation of symptoms of so-called functioning tumors.